MRM 01-2011_def:Layout 1

Transcript

Associazione Scientifica Interdisciplinare
per lo Studio delle Malattie Respiratorie
1
M u ltid is c ip lin a ry R e s p ira to ry M e d ic in e
Poste Italiane Spa - Spedizione in Abbonamento Postale - D.L. 353/2003 (convertito in L. 27/02/2004 n. 46) art. 1 comma 1, DCB MILANO
Annesi-Maesano I
Does urban asthma exist? How climatic changes and urban
air pollution intervene on asthma and respiratory allergy
Esiste l’asma urbano? In che modo le modificazioni climatiche
e l’inquinamento urbano intervengono sull’asma e sulle patologie
respiratorie allergiche
Abul Y, Karakurt S, Bostanci K, Yuksel M, Eryuksel E, Evman S, Celikel T
Spontaneous pneumothorax and ozone levels: is there a relation?
C’è un rapporto tra pneumotorace spontaneo e livelli di ozono?
Zaric B, Perin B, Ilic A, Kopitovic I, Matijasevic J, Andrijevic L, Secen N, Stanic J,
Bijelovic M, Kosjerina Z, Antonic M
Clinical trials in advanced stage lung cancer:
a survey of patients’ opinion about their treatment
Trial clinici nel tumore del polmone in stadio avanzato:
un’analisi dell’opinione dei pazienti riguardo al trattamento
D’Amato G
Effects of climatic changes and urban air pollution
on the rising trends of respiratory allergy and asthma
Effetti delle modificazioni climatiche e dell’inquinamento urbano
sul trend in incremento delle patologie respiratorie allergiche
e dell'asma
Matthys H
Fit for high altitude: are hypoxic challenge tests useful?
Idoneità all’alta montagna: i test all’ipossia sono davvero utili?
Indexed and Abstracted in: Science Citation Index Expanded (SciSearch®),
Journal Citation Reports/Science Edition, and Scopus Elsevier Bibliographic
Databases
anno 6 - n. 1 - Reg.Trib. Novara n.120 dell’11/11/2005
ISSN 1828-695X
Multidisciplinary Respiratory Medicine
vol. 6 n.1/february 2011:1-70
6
volume
number
february 2011
MRM 01-2011_def:Layout 1 23/02/11 11:32 Pagina 1
MULTIDISCIPLINARY RESPIRATORY MEDICINE
OFFICIAL SCIENTIFIC JOURNAL OF AIMAR
An Italian scientific journal of AIMAR dedicated to the advancement of knowledge in all
fields of respiratory medicine. MRM publishes - in English and Italian - original articles,
new methodological approaches, reviews, points of view, editorials, states of the art,
position papers and congress proceedings.
Editors
Fernando De Benedetto, Chieti
Claudio F. Donner, Borgomanero (NO)
Claudio M. Sanguinetti, Roma
Multidisciplinary
Respiratory
Medicine
Editorial Board
Coordinator: Mario Polverino, (SA)
Sabina Antoniu, Iasi, Romania
Alberto Braghiroli, Veruno (NO)
Mauro Carone, Cassano Murge (BA)
Lucio Casali, Terni
Mario Cazzola, Roma
Stefano Centanni, Milano
George Cremona, Milano
Roberto Dal Negro, Bussolengo (VR)
Filippo De Marinis, Roma
Francesco Ioli, Veruno (NO)
Giovanni Paolo Ligia, Cagliari
Rasmi Magadle, Hadera, Israel
Riccardo Pela, Ascoli Piceno
Luca Richeldi, Modena
Roberto Torchio, Torino
International Advisory Board
Isabella Annesi-Maesano, Paris, France
Antonio Anzueto, San Antonio, TX, USA
Peter J. Barnes, London, UK
Panagiotis Behrakis, Athens, Greece
Peter M.A. Calverley, Liverpool, UK
Richard Casaburi, Los Angeles, CA, USA
Bartolome Celli, Boston, MA, USA
Alexander Chuchalin, Moscow, Russia
Ronald Dahl, Aarhus, Denmark
Roger Goldstein, Toronto, Canada
Peter Howard, Sheffield, UK
Günseli Kilinç, Istanbul, Turkey
Marc Miravitlles, Barcelona, Spain
David J. Pierson, Seattle, WA, USA
Stephen I. Rennard, Omaha, NE,USA
Josep Roca, Barcelona, Spain
Nikolaos Siafakas, Heraklion, Crete, Greece
Samy Suissa, Montreal, Canada
Martin Tobin, Maywood, IL, USA
Jadwicha Wedzicha, London, UK
Emiel Wouters, Maastricht, The Netherlands
Jan Zielinski, Warsaw, Poland
Richard ZuWallack, Hartford, CT, USA
AIMAR Scientific Committee
Coordinator: Luigi Allegra (MI)
Allergology and Environmental Medicine: Gennaro D’Amato (NA)
Cardiac Surgery: Mario Viganò (PV)
Cardiology: Nazzareno Galié (BO), Alessandro Palmarini (MI)
Endocrinology: Aldo Pinchera (PI)
Epidemiology: Fernando Romano (RM)
Formation and Quality: Maurizio Capelli (BO), Piera Poletti (PD)
Gastroenterology: Gabriele Bianchi Porro (MI), Lucio Capurso (RM)
General Medicine: Claudio Cricelli (FI)
Geriatrics: Emanuele Tupputi (BA), Stefano M. Zuccaro (RM)
Imaging: Alessandro Carriero (NO), Francesco Schiavon (BL)
Immunology: Giuseppe Montrucchio (TO)
Infectivology: Ercole Concia (VR)
Intensive Care: Marco Ranieri (TO)
Internal Medicine: Roberto Corinaldesi (BO)
Microbiology: Giancarlo Schito (GE)
Neurology: Luigi Ferini Strambi (MI)
Occupational Medicine: Plinio Carta (CA), Giacomo Muzi (PG)
Oncology: Filippo De Marinis (RM), Cesare Gridelli (AV)
Otolaryngology: Michele De Benedetto (LE), Desiderio Passali (SI)
Pediatrics: Angelo Barbato (PD), Fernando M. De Benedictis (AN)
Pharmacology: Ilario Viano (VC)
Pneumology: Francesco Blasi (MI), Lucio Casali (TR), Mario Cazzola (RM),
Giuseppe U. Di Maria (CT), Giuseppe Girbino (ME), Carlo Grassi (MI), Dario Olivieri (PR),
Pier Luigi Paggiaro (PI), Paolo Palange (RM), Riccardo Pela (AP),
Mario Polverino (SA).
Relationships with Patients’ Organizations: Fausta Franchi (RM)
Thoracic Surgery: Francesco Sartori (PD)
Editorial Office Manager
Stefano Nardini, Vittorio Veneto (TV)
Managing Editor
Gianfranco Sevieri, Viareggio (LU)
Editorial Office
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Tel +39 0322 846549
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[email protected]
Editorial Supervision
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Marketing & Advertising
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Giorgio Maggiani
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MRM
1
Spontaneous pneumothorax
Pneumotorace spontaneo
6
Heinrich Matthys
Patient, doctor, disease, and informed consent
Il paziente, il medico, la malattia e il consenso informato
8
Riccardo Pela
Does urban asthma exist? How climatic changes and urban
air pollution intervene on asthma and respiratory allergy
Esiste l’asma urbano? In che modo le modificazioni climatiche
e l’inquinamento urbano intervengono sull’asma
e sulle patologie respiratorie allergiche
INDICE / INDEX
Editorials / Editoriali
10
Isabella Annesi-Maesano
The lung at high altitude
Il polmone in alta quota
14
Annalisa Cogo
Original Articles / Articoli Originali
Spontaneous pneumothorax and ozone levels: is there a relation?
C’è un rapporto tra pneumotorace spontaneo e livelli di ozono?
16
Yasin Abul, Sait Karakurt, Korkut Bostanci, Mustafa Yuksel, Emel Eryuksel, Serdar Evman,
Turgay Celikel
Clinical trials in advanced stage lung cancer: a survey
of patients’ opinion about their treatment
Trial clinici nel tumore del polmone in stadio avanzato: un’analisi
dell’opinione dei pazienti riguardo al trattamento
20
Bojan Zaric, Branislav Perin, Aleksandra Ilic, Ivan Kopitovic, Jovan Matijasevic, Ljiljana Andrijevic,
Nevena Secen, Jelena Stanic, Milorad Bijelovic, Zdravko Kosjerina, Milan Antonic
Reviews / Rassegne
Effects of climatic changes and urban air pollution on the rising
trends of respiratory allergy and asthma
Effetti delle modificazioni climatiche e dell’inquinamento urbano
sul trend in incremento delle patologie respiratorie allergiche e dell'asma
28
Gennaro D’Amato
Fit for high altitude: are hypoxic challenge tests useful?
Idoneità all’alta montagna: i test all’ipossia sono davvero utili?
38
Heinrich Matthys
MRM
3
Congress report / Resoconto congressuale
Time for physicians to be aware of molecular genetic testing
Report from the 3rd Viareggio Health Festival
È tempo per i medici di essere consapevoli delle possibilità della genetica
molecolare. Resoconto dal III Festival della Salute di Viareggio
47
Cecilia Nardini
RUBRICHE
ATP corner
L'Unione Nazionale Asmatici (UNA). Mission e prospettive
National Union of Asthmatics (UNA). Mission and future prospects
50
Roberto W. Dal Negro
Capitolo Italiano dell'American College of Chest Physicians (ACCP)
Italian Chapter of the American College of Chest Physicians (ACCP)
52
Stefano Picciolo
AIMAR Newsletter
54
From the CFC Bulletin
56
L'Angolo della Cultura (non solo Medicina...)
The gender debate in medicine
Il dibattito sul genere nella medicina
59
Flavia Franconi, Anna Maria Moretti
Women in the history of medicine
Le donne nella storia della medicina
60
Corrado Petrocelli
Il tonfo della sterlina: la “Cool Britannia” è al capolinea?
The slump of the British pound: is British ‘cool’ at an end?
64
Francesco Iodice
67
Meeting Calendar
Avviso
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4 MRM
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Interdisciplinare per lo Studio
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Editorial / Editoriale
Spontaneous pneumothorax
Pneumotorace spontaneo
Heinrich Matthys
Medical Director emeritus, University Hospital, Freiburg, Germany
Pneumothorax is defined as the presence of air in
the pleural space due to: a) communication between alveolar spaces and pleura; b) direct or indirect exchange of air between the atmosphere and
the pleural space; or c) the presence of gas producing organisms in the pleural space.
From the clinical and etiological standpoint the
pneumothorax is classified as: primary spontaneous pneumothorax if occurring without obvious
reason or apparent lung disease, secondary spontaneous pneumothorax if due to a well known underlying lung or systemic disease, or as traumatic
pneumothorax if it is the result of iatrogenic or noniatrogenic blunt and/or penetrating chest interventions and injuries.
Primary spontaneous pneumothorax (PSP) is therefore defined as the presence of air in the pleural
space without apparent underlying lung disease or
trauma. The pathogenesis of PSP is not the same for
all events. Most authors believe that the communication of air between the alveolar spaces and the
pleura is due to a rupture of subpleural blebs or bullae [1].
Although most children [2] and adults (3] present
blebs or bullae, it is unclear how often this pathology is responsible for the leakage of air from the
alveolar into the pleural space [4].
During thoracoscopy or surgery often there are other lesions present, such as inflammatory elastofibrotic layers with increased porosity and areas of
disrupted mesothelial cells at the visceral pleura, allowing air leakage into the pleural space [5,6].
Bullectomy has a recurrence rate of up to 20%
without pleurodesis, which may be explained by
factors like peripheral airway inflammation due to
noxious agents, e.g. tobacco smoke [7], or exposure
to high levels of ozone as discussed by Abul et al.
in this issue of Multidisciplinary Respiratory
Medicine (pp. 16-19). Hereditary factors [8],
anatomical abnormalities of the bronchial tree,
ischemia at the apices of the lungs [9], low body
+ Heinrich Matthys
Department of Pneumology, University Hospital Freiburg,
Hochrüttestr. 17, D-79117, Freiburg, Germany
email: [email protected]
Multidisciplinary Respiratory Medicine 2011; 6(1): 6-7
6 MRM
mass index due to anorexia and other causes of
food restriction [10], Marfan syndrome [11] as well
as increased aluminium plasma concentrations [12]
may also lead to abnormal connective tissue formations (fibrillopathies) predisposing for the occurrence of PSP [13].
Secondary spontaneous pneumothorax (SSP) is defined as the presence of air in the pleural space as a
consequence of clinically apparent underlying lung
disease without iatrogenic or other external blunt
(barotraumata, etc.) or penetrating chest injuries.
Frequent or typical causes of SSP are:
- chronic airway and alveolar diseases: e.g. severe
asthma, cystic fibrosis, emphysema, bullae and
cysts;
- infectious lung diseases: e.g. pneumonia
(Pneumocystis carinii), TB, lung abscess leading to
pneumothorax with pleural empyema;
- interstitial lung diseases: e.g. idiopathic fibrosing
alveolitis, sarcoidosis, histiocytosis X, lymphangioleiomyomatosis;
- systemic connective tissue diseases: e.g. rheumatoid arthritis, ankylosing spondylitis, scleroderma,
Marfan- and Ehlers Danlos-syndrome;
- malignant lung and chest diseases: e.g. bronchial
cancer, sarcoma.
SSP has a higher recurrence rate than PSP, up to
80% in cystic fibrosis.
The age-adjusted incidence of PSP is 7.4-18 cases
per 100,000 population each year in males and 1.26 in females and it occurs typically at rest. A 2nd
World War study showed no difference of incidence between royal air force pilots and army soldiers. Therefore, avoiding physical stress and exercise should not be recommended. In contrast loud
music as an atmospheric pressure change may be a
risk factor for PSP [14]. Tension pneumothorax in
PSP is rare. The outpatient treatment for the first
event consists in introducing a small chest tube with
a one-way valve (Matthys Drain®) followed by pleurodesis in patients at risk for recurrent PSP [15].
1. Bradley M, Willams C, Walshaw MJ. The value of routine
expiratory chest films in the diagnosis of pneumothorax.
Arch Emerg Med 1991;8:115-116.
2. Guimaraes CV, Donnely LF, Warner BW. CT findings for
blebs and bullae in children with spontaneous pneumothorax and comparison with findings in normal age-matched
controls. Pediatr Radiol 2007;37:879-884.
3. Amjadi K, Alvarez GG, Vanderhelst E, Velkeniers B, Lam M,
Noppen M. The prevalence of blebs and bullae among
young healthy adults: a thoracoscopic investigation. Chest
2007;132:1140-1145.
4. Noppen M. Con: Blebs are not the cause of primary spontaneous pneumothorax. J Bronchol 2002;9:319-325.
5. Masshoff W, Höfer W. Zur Pathologie des sogenannten
idiopathischen Spontanpneumothorax. Dtsch Med
Wochenschr 1973;98:801-805.
6. Radomsky J, Becker HP, Hartel W. Pleuraporosität beim
idiopathischen Spontanpneumothorax. Pneumologie
1989;43:250-253.
7. Bense L, Lewander R, Eklund G, Hedenstierna G, Wiman
LG. Nonsmoking, non-alpha 1-antitrypsin deficiencyinduced emphysema in nonsmokers with healed spontaneous pneumothorax, identified by computed tomography
of the lungs. Chest 1993;103:433-438.
8. Morrison PJ, Lowry RC, Nevin NC. Familial primary sponta-
9.
10.
11.
12.
13.
14.
15.
neous pneumothorax consistent with true autosomal dominat inheritance. Thorax 1998;53:151-152.
Withers JN, Fishback ME, Kiehl PV, Hannon JL.
Spontaneous pneumothorax. Suggested etiology and comparison of treatment methods. Am J Surg 1964;108:772776.
Coxson HO, Chan IH, Mayo JR, Hlynsky J, Nakano Y,
Birmingham CL. Early emphysema in patients with anorexia
nervosa. Am J Respir Crit Care Med 2004;170:748-752.
Neptune ER, Frischmeyer PA, Arking DE, Myers L, Bunton
TE, Gayraud B, Ramirez F, Sakai LY, Dietz HC.
Dysregulation of TGF-beta activation contributes to pathogenesis in Marfan syndrome. Nat Genet 2003;33:407-411.
Leo F, Venissac N, Drici MD, Mouroux J. Aluminium and
spontaneous pneumothorax. A suggestive but unconfirmed
hypothesis. Interact Cardiovasc Thorac Surg 2005;4:21-22.
Loeys BL, Matthys DM, De Paepe AM. Genetic fibrillinopathies: new insights in molecular diagnosis and clinical management. Acta Clin Belg 2003;58:3-11.
Noppen M, Verbanck S, Harvey J, Van Herreweghe R, W,
Vincken W, Paiva M. Music: a new cause of primary spontaneous pneumothorax. Thorax 2004;59:722-724.
Matthys H. Emergency management of pneumothorax – a
case report and guidelines. Multidisciplinary Respiratory
Medicine 2006;3:64-66.
H Matthys
Editorial - Editoriale
References
MRM
7
Patient, doctor, disease, and informed
consent
Il paziente, il medico, la malattia e il consenso
informato
Riccardo Pela
UOC di Pneumologia, Ospedale “C. e G. Mazzoni”, Ascoli Piceno, Italy
Lung cancer is the 10th ranking cause of death in the
world: its incidence has reached a steady state in
the male gender while it is still increasing in females. Even if data are now available on lung cancer screening with low-dose spiral computerized
tomography (CT), still today the diagnosis is often
late, due to underestimation and late appearance of
specific symptoms. Hence, in the great majority of
cases (stages IIIB and IV) the only possible option is
a definitive chemotherapy with a platin doublet,
alone or with bevacizumab, or other target drugs.
Unfortunately, the results are not satisfying, either
for overall survival or for progression free survival.
So, performing new clinical trials is essential.
Taking into account the prognosis of locally advanced or metastatic lung cancer, the utility of
chemotherapy is discussed more often with the patient’s relatives than with the patient him/herself.
But survival and quality of life (QoL) are significantly better in patients treated with chemotherapy than
in those who receive the best supportive care but
not chemotherapy.
In this respect it has been demonstrated that the patient is more agreeable to chemotherapy than are
the relatives and even the doctor, if the expected results are in terms of survival or quality of life [1]:
• 57% of patients opt for chemotherapy if the oneyear-survival is at least 10%
• 68% of patients opt for chemotherapy if the QoL
is ameliorated
• the majority of patients opt for chemotherapy if a
median survival of at least 4.5 months is expected.
So, a real informed consent is of paramount importance in order to obtain the patient’s cooperation
+ Riccardo Pela
UOC di Pneumologia, Ospedale “C. e G. Mazzoni”
Via degli Iris 1, 63100 Ascoli Piceno, Italia
8 MRM
for the therapeutic plan. The informed participation
of the patient – in the sense of understanding the disease, its therapy and the interaction between the two
- is necessary for the patient to be able to deal with a
critical period of his/her life. This task is even more
important in the case of enrolment in clinical trials.
The study by Zaric et al. in this issue [2] carried out
a survey on the perception of lung cancer patients
undergoing experimental treatments. The authors
argue that “the patients participating in clinical trials contribute not only to their own and future patients’ treatment benefits, but also to the benefits of
medicine and the science itself” and they ask the
question: “physicians are aware of this fact, but are
the patients aware of the same fact, too?”.
In this respect, 59 patients with advanced lung cancer, previously treated and enrolled in a clinical
therapeutic trial, filled in a questionnaire with 20
items. The patients were asked about their knowledge of their own disease (type, stage) and the kind
of therapy (previously and currently received),
about the information received on the trial results,
and about the utility of the experimental trial itself
and the quality of treatment.
All the patients were familiar with the nature of
their disease, and the majority of them knew their
lung cancer stage. A significant number of patients
knew what kind of chemotherapy they received.
Almost all patients knew that they were participating in a clinical trial and they believed that the
chemotherapy given in the clinical trial would give
them a better chance for survival.
The fact that 8.5% of the patients (more often the
less educated ones) did not read the entire informed
consent form (ICF) is an alarming finding, because
formed consent, in particular in the presence of
less educated patients.
• Do not hide from the patients their real condition.
• Do not inform only the relatives, but make sure
also the patients are informed.
The results of the study by Zaric et al. strengthen the
fact that an honest attitude ameliorates the relationship between patients and doctor, providing the patient with the knowledge to understand their disease, its actual state, the type and purpose of the
treatment, and helping them to cope with a very difficult period of their life.
R Pela
the ICFs provide more detailed information about
the trial than an investigator can give during the interview with a patient. This suggests that doctors
should pay more attention when they provide information to less educated patients. Giving clear information, maintaining the patient's hope for the future, permits to obtain the confidence and the collaboration of the patient.
Some practical suggestions for physicians that can
be derived are:
• When informing the patient take into account
their educational level and do not use only the in-
References
1. Brundage MD, Feldman-Stewart D, Cosby R, Gregg R,
Dixon P, Youssef Y, Mackillop WJ. Cancer patients’ attitudes
toward treatment options for advanced non-small cell lung
cancer: implications for patient education and decision
support. Patient Educ Couns 2001;45:149-157.
2. Zaric B, Perin B, Ilic A, Kopitovic I, Matijasevic J, Andrijevic
L, Secen N, Stanic J, Bijelovic M, Kosjerina Z, Antonic M.
Clinical trials in advanced stage lung cancer: a survey of
patients’ opinion about their treatment. Multidisciplinary
Respiratory Medicine 2011;6:20-27.
MRM
9
Does urban asthma exist?
How climatic changes and urban air pollution
intervene on asthma and respiratory allergy
Esiste l’asma urbano?
In che modo le modificazioni climatiche e
l’inquinamento urbano intervengono sull’asma e sulle
patologie respiratorie allergiche
Isabella Annesi-Maesano1,2
1
INSERM, U 707: EPAR, Paris, France
Université Pierre et Marie Curie, Paris 6, Medical School Saint-Antoine, UMR S 707: EPAR, Paris, France
2
In his important article [1], Gennaro D’Amato provides elements that contribute to reply to two burning questions of the present time. How bad is the
fact of living in a city for asthma and, more generally, for respiratory allergy? And to what extent does
climate change worsen asthma in individuals living
in cities? The two questions are strictly related.
How bad is living in a city for asthma?
Several investigations have indicated that individuals living in cities have a higher risk of suffering from
asthma and allergies compared to those living in the
countryside, this being due to several factors. Besides
the fact that individual susceptibility varies between
urban and rural settings, there are environmental factors that are typical of living in a city.
First of all, as perfectly indicated by D’Amato in his
article, urban air pollution is composed of gases
and particles. Whereas industrial pollution has decreased in recent decades, at least in industrialized
countries, air pollution related to traffic is rising or
remaining at the same level (www.eea.org). Gases
and particulate matter have been shown by experimental and epidemiological studies to be involved
in respiratory adverse effects. At the population lev-
el, not only can short-term exposure to elevated
concentrations of urban air pollutants exacerbate
pre-existing asthma and allergic rhinitis but also
long-term exposure to these pollutants can be responsible for adverse effects, including asthma and
the development of allergies [2]. Most investigations reporting long-term effects of air pollution
have considered exposure to background air pollution as assessed by monitoring stations, which provide an under-estimation of the real exposure to
these pollutants. Fewer studies have considered a
more robust assessment of the individual’s exposure
to air pollution so avoiding miss-classification of exposure. Among them, very recently, is the French 6
Cities study in which long-term average exposure to
major urban air pollutants, including benzene,
volatile organic compounds (VOCs), sulfur dioxide
(SO2), particles with an aerodynamic diameter of 10
µm or less (PM10), nitrogen dioxide (NO2), nitrogen
oxides (NOx), and carbon monoxide (CO), was assessed using a dispersion model capable of capturing small-scale variations in 6,683 children. These
children underwent clinical examinations, including lung function and skin prick tests, and their parents completed questionnaires on asthma and aller-
+ Isabella Annesi-Maesano
INSERM, U 707: EPAR, Paris, France
EPAR UMR-S 707 INSERM & UPMC Paris6, Medical School Saint-Antoine Bureaux 803-4-6, 8ème étage 27,
rue Chaligny 75571, Paris CEDEX 12, France
10 MRM
gree of severity of asthma and how well it responds
to medication. Their interaction is complex and not
fully understood. Indeed, in developing countries
children and their families still preserve some protective factors of the traditional lifestyle which exert
their influence, despite the fact the children are exposed to many environmental factors including air
pollution, and this could protect them from asthma.
This phenomenon has been discussed in the frame
of the Hygiene Hypothesis [5]. Of note, in this respect, a difference could exist according to whether
asthma is allergic or not, but this aspect has been
little investigated.
I Annesi-Maesano
Editorial – Editoriale
gic diseases [3]. Children constitute a good model
because they do not commute. In this study, we
found associations between long-term exposure to
urban air pollution, and asthma and allergies including skin prick test positivity after taking into account potential confounders like passive smoking,
familial history of asthma and allergies, type of diet,
etc. Among the 4,907 children who had lived at
their current address for at least the past 3 years,
each incremental increase in the average interquartile range for benzene (1.1 µg/m3), SO2 (5 µg/m3),
PM10 (10.5 µg/m3), and CO (199 µg/m3) was associated with an increased risk for lifetime asthma, with
adjusted odds ratios (ORs) of 1.25, 1.26, 1.28, 1.21,
respectively. Each incremental increase in PM10 levels was also associated with an increased risk for allergic rhinitis (OR = 1.20) and sensitization to
pollen (OR = 1.35). Among the 2,213 children who
had lived at their current address since birth, each
incremental increase in the interquartile range for
benzene and PM10 was associated with a respective
1.30- and 1.40-fold increased risk for lifetime asthma, while each incremental increase in average
VOCs and PM10 was associated with a respective
1.30- and 1.20-fold increased risk for sensitization
to pollen. As reported in D’Amato’s article, pollens
are particularly sensitive to pollution effects. In addition, various studies suggest that there is an interaction between air pollutants and pollen allergens
that exacerbates atopy and respiratory symptoms
[4]. The links between chemical and biological pollutants and asthma and allergies in children living
in polluted areas are confirmed, although for less
pollutants, by prospective birth cohorts. All together
these results corroborate an emerging body of evidence that traffic-related air pollution could induce
asthma and allergies.
However, air pollution is not the only culprit for
asthma and allergies in individuals living in the
cities. Other urban factors associated with asthma
include: passive smoking, high exposure to cockroaches or other pests, damp, indoor air pollution,
poor ventilation, inadequate heating or faulty air
conditioning, air-borne viral infections, overcrowding, stress and violence as well as, for low social
classes of some countries, inadequate access to
health care. These “stressors” have been identified
thanks to epidemiological investigations among
which the study of inner-city asthma in the USA
showing that children living in inner cities suffered
more from asthma and related diseases than other
children from the same city. These other factors are
essential to explain why worldwide the geographical distributions of air pollution and asthma and allergies do not match with the lowest prevalence of
asthma in megalopolis of developing countries
where the level of air pollution is very high and the
highest prevalence in English-speaking countries,
like Australia, New Zealand or UK, in spite of the
fact that the levels of air pollution are not exaggerated there (Figure 1). Indeed, asthma is a multifactorial condition caused by several environmental
and genetic factors. These factors influence the de-
How much can climate change worsen urban asthma?
The year 2010 was the warmest recorded on Earth
since the first “rélevé” in 1880, ex aequo with
2005, as reported by two U.S. agencies (NOAA and
NASA). 2010 was the 34th consecutive year that
global temperatures ranged above the average of
the 20th century according to the National Climatic
Data Center (NCDC), an organization dependent
on the National Oceanic and Atmospheric
Administration. Last year, the temperature at the
earth's surface was about 0.62 degrees Celsius
above the average of the century. The rise of mercury on Earth coincides with a major change in the
warm ocean current El Niño in the Pacific that affects global temperatures and precipitation. Despite
a summer season shorter than normal in 2010 during which the ice cap melted, the Arctic surface witnessed the third lowest amount of ice since 1979,
after 2007 and 2008. Antarctic sea ice has reached
its eighth lowest annual maximum in March and in
September the size of the ice has increased rapidly,
reaching its third largest area on record. These results show that the climate continues to reflect the
influence of greenhouse gas emissions. This is evidence of global warming and climate change.
D’Amato’s article reports with precision that various data indicate that climate change and global
warming act on both individual health, including
allergic and respiratory diseases, as well as on risk
factors for such diseases like temperature, humidity,
chemical and biological air pollutants [6-7].
Climate change will affect individuals with pre-existing respiratory disease [6]. In addition, climate
change is expected to alter the concentration and
distribution of pollutants in the atmosphere.
Climate change will be responsible for an overall
increase in ozone concentrations in high-income
countries. Ozone is a powerful oxidant that has
been associated with reduced lung function, exacerbation of chronic respiratory diseases, and increases in respiratory hospital admissions and mortality in both Europe and the USA. Desertification
and a higher frequency of forest fires may increase
transboundary transport of particles, which will
have significant public health consequences.
Climate change has also an impact on living organisms, including plants and fungi [7]. Over the last
three decades, studies have shown changes in production, dispersion and allergen content of pollen
MRM
11
and spores, which may be region- and species-specific. These changes may have been influenced by
urban air pollutants interacting directly with pollen,
which suggests an increasing effect of aeroallergens, pollens, mold, house dust mites, on allergic
patients over this period, which may also imply a
greater likelihood of the development of an allergic
respiratory disease in sensitized subjects and exacerbation of symptoms in pre-existing asthmatic patients. However, contrary to what is the case for air
pollution, the scientific community lacks sufficient
data to allow it to investigate the repercussions of
climate change on the environment as well as on
individuals. Ecological but not semi-individual
analyses have been conducted so far. Hence, predictions for the future are uncertain.
In summary: living in a town is bad for asthma because of urban air pollution but also because of other urban factors like overcrowding, indoor air pollution in confined dwellings including passive
smoking, and inadequate heating, and the situation
should result worsened by climate change although
data are few in this respect. Thereafter, and this is
very relevant, D’Amato’s article raises the hypothesis according to which there exists “urban asthma”,
a specific phenotype for asthma in individuals living in cities, and intimately related to climate
change in the long term. This urban asthma phenotype will pay the price for wrong actions taken by
mankind in its fight against global warming.
Because of its features, urban asthma is not only a
clinical variant of asthma characterized by an inflammatory response of cells and airways after exposure to chemical and biological air pollutants
and toxicants but a social condition affecting the
less affluent individuals in high income countries
and for which the main factor responsible is poverty
with its manifold facets encountered in the cities.
Further and specifically designed studies are needed to better understand the urban phenotype of
asthma. These investigations have to be multidisciplinary to catch the multifaceted aspects of urban
FIGURE 1: WORLDWIDE DISTRIBUTIONS OF PARTICULATE MATTER POLLUTION AND ASTHMA PREVALENCE
Asthma prevalence
***
: < 5%
*** : ≥ 20%
Level of pollution
(World Bank 2010)
1 weak
2
3
4
5 high
***
***
***
Ranking of concentrations of particulate matter (PM10) in 3,200 cities hosting more than 100,000 inhabitants as mapped by the World
Bank.
Asthma prevalence as assessed by the International Study of asthma and allergies in childhood. Phase III.
References
1. D’Amato G. Effects of climatic changes and urban air pollution on the rising trends of respiratory allergy and asthma.
Multidisciplinary Respiratory Medicine 2011;6:28-37.
2. Holguin F. Traffic, outdoor air pollution, and asthma.
Immunol Allergy Clin North Am 2008;28:577-588.
3. Pénard-Morand C, Raherison C, Charpin D, Kopferschmitt
C, Lavaud F, Caillaud D, Annesi-Maesano I. Long-term
exposure to close-proximity air pollution and asthma and
allergies in urban children. Eur Respir J 2010;36:33-40.
12 MRM
4. Huynh BT, Tual S, Turbelin C, Pelat C, Cecchi L, D'Amato
G, Blanchon T, Annesi-Maesano I. Short-term effects of airborne pollens on asthma attacks as seen by general practitioners in the Greater Paris area, 2003-2007. Prim Care
Respir J 2010;19:254-259.
5. Matricardi PM. 99th Dahlem conference on infection,
inflammation and chronic inflammatory disorders: controversial aspects of the 'hygiene hypothesis'. Clin Exp
Immunol 2010;160:98-105.
7. Cecchi L, D'Amato G, Ayres JG, Galan C, Forastiere F,
Forsberg B, Gerritsen J, Nunes C, Behrendt H, Akdis C, Dahl
R, Annesi-Maesano I. Projections of the effects of climate
change on allergic asthma: the contribution of aerobiology.
Allergy 2010;65:1073-1081.
I Annesi-Maesano
Editorial – Editoriale
6. Ayres JG, Forsberg B, Annesi-Maesano I, Dey R, Ebi KL, Helms
PJ, Medina-Ramón M, Windt M, Forastiere F; Environment
and Health Committee of the European Respiratory Society.
Climate change and respiratory disease: European Respiratory
Society position statement. Eur Respir J 2009;34:295-302.
MRM
13
The lung at high altitude
Il polmone in alta quota
Annalisa Cogo
Clinica Pneumologica e Centro Studi Biomedici Applicati allo Sport, Università di Ferrara, Ferrara, Italy
The lung is the interface between the environment
and the metabolic mechanisms of the body, and
plays a pivotal role in exposure to high altitude. In
fact, high altitude is a challenge for the human body
due to the progressive reduction of barometric pressure and subsequent reduction of oxygen pressure,
leading to a series of important physiologic responses that enable individuals to tolerate hypoxia and
secure the oxygen supply to tissues. These compensatory responses are known as the acclimatization
process. Most of the adaptations are observed from
2000 m a.s.l. and they become progressively more
evident with increasing altitude, from near sea level
through to moderate and extreme altitude.
A new classification of altitude levels based on the
effects on performance and well-being has been recently proposed [1]: the decrease in partial pressure
of oxygen reduces maximal oxygen uptake and impairs "aerobic" performance by reducing maximal
aerobic power. Submaximal exercise performance
is also impaired at altitude. When the acclimatization is not adequate, hypoxia triggers maladaptive
responses that lead to various forms of high altitude
illness or acute mountain sickness (AMS), characterized by headache plus gastrointestinal symptoms
(anorexia, nausea) and sleep disturbances. AMS is
present in 10-30% of subjects at altitudes between
2500 and 3000 m a.s.l. and is usually due to a fast
ascent. It is well defined by the short phrase: “Too
fast, too high”. Less frequent, but much more serious, consequences are high-altitude cerebral edema (HACE), and high-altitude pulmonary edema
(HAPE).
The lung response to acute altitude exposure is
mainly hyperventilation which, together with elevated heart rate, aims at achieving an adequate supply of oxygen to the tissues. At rest, ventilation increases by firstly increasing the tidal volume, at
least up to 3500 m. Above this altitude, also the
breathing rate significantly increases. Besides the
compensatory response, other mechanisms affect
lung physiology during hypoxic exposure: the increase of pulmonary artery pressure and endothelial
permeability which can explain the extravascular
lung fluid accumulation described in many papers
[2]. It must be underlined that the interstitial fluid
accumulation which affects a large part of climbers
at high altitude should be considered a para-physiological mechanism and does not predict subsequent
pulmonary edema [3].
The role of the lung in the acute exposure to altitude
was first described by Angelo Mosso, physiologist at
the University of Torino, at the end of the 19th century. He very well pointed out the changes in ventilation and the reduction of lung volumes consistent
with the extravascular fluid accumulation in the
pulmonary interstitium [4].
However, mountain climate is characterized not
only by the progressive reduction of barometric and
inspiratory oxygen pressure, but also by other
changes that can variably affect respiratory function
and bronchial hyperresponsiveness: progressive reduction of air density, humidity, temperature,
aeroallergens, and outdoor pollution. The lower
density of air reduces respiratory resistances and increases inspiratory and expiratory flows; this fact
explains the improvement of some parameters of
the forced exhalation curve observed at altitude.
The reduced temperature and the reduced humidity
cause hyperventilation of dry and cold air, especially during exercise; this fact could induce an asthma
attack, especially in subjects suffering from exercise
induced bronchospasm. The reduction or even the
absence of some aeroallergens (i.e. dermatophagoides) and outdoor pollution reduces the airway inflammation. Mountain climate can therefore
variably affect the respiratory system.
An increasing number of people travel each year to
high altitude for leisure, sport and even work purposes. Because of the critical role played by the respiratory system in the adaptive and maladaptive responses, patients with underlying lung disease may
+ Annalisa Cogo
Clinica Pneumologica e Centro Studi Biomedici Applicati allo Sport, Università di Ferrara
Via Savonarola 9, 44121 Ferrara, Italia
14 MRM
a gas exchange defect impairing the oxygen supply
at altitude? The severity of the disease and the altitude to which the patient will go are critical points,
but the first rule is that the disease must be in a stable state.
The physician, after a careful examination of the patient, must take into account the level of hypoxia
(i.e. the altitude), the duration of exposure to hypoxic conditions, and the exercise intensity [5,6].
Heinrich Matthys in his paper in this issue [7] describes all these points, and provides physicians
with valuable recommendations for management of
respiratory patients prior to and during a sojourn at
high altitude.
A Cogo
be at increased risk for complications in this environment and warrant careful evaluation before a sojourn to higher altitudes. Given the high prevalence
of chronic respiratory diseases such as asthma and
COPD in the general population, it is to be expected that many patients will ask their physicians
about the safety of travel to altitude. This fact highlights the importance for physicians to have a good
understanding of the high-altitude environment, the
compensatory mechanisms of the body and high altitude illness. Advice for respiratory patients must
be founded on an adequate knowledge of the altitude environment and the underlying disease. Is the
patient at risk of an asthma attack? Can the patient
adequately increase the ventilation? Has the patient
References
1. Bärtsch P, Saltin B. General introduction to altitude adaptation and mountain sickness. Scand J Med Sci Sports
2008;18(Suppl 1):1-10.
2. Cremona G, Asnaghi R, Baderna P, Brunetto A, Brutsaert T,
Cavallaro C, Clark TM, Cogo A, Donis R, Lanfranchi P, Luks
A, Novello N, Panzetta S, Perini L, Putnam M, Spagnolatti L,
Wagner H, Wagner PD. Pulmonary extravascular fluid
accumulation in recreational climbers: a prospective study.
Lancet 2002;359:303-309.
3. Senn O, Clarenbach CF, Fischler M, Thalmann R, BrunnerLa Rocca H, Egger P, Maggiorini M, Bloch KE. Do changes
4.
5.
6.
7.
in lung function predict high-altitude pulmonary edema at
an early stage? Med Sci Sports Exerc 2006;38:1565-1570.
Mosso A. Fisiologia dell’uomo sulle Alpi. Milano: Treves, 1893.
Cogo A, Fiorenzano G. Bronchial asthma: advice for
patients traveling to high altitude. High Alt Med Biol
2009;10:117-121.
Stream JO, Luks AM, Grissom CK. Lung disease at high altitude. Expert Rev Respir Med 2009;3:635-650.
Matthys H. Fit for altitude exposure: are hypoxic challenge
tests useful? Multidisciplinary Respiratory Medicine
2011;6:38-46.
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15
Original Article / Articolo Originale
Spontaneous pneumothorax and ozone levels:
is there a relation?
C’è un rapporto tra pneumotorace spontaneo
e livelli di ozono?
Yasin Abul¹, Sait Karakurt², Korkut Bostanci³, Mustafa Yuksel3, Emel Eryuksel4, Serdar Evman³,
Turgay Celikel²
1
Ministry of Health Bismil Government Hospital, Pulmonary Medicine Clinics, Diyarbakir, Turkey
Marmara University, Faculty of Medicine, Department of Pulmonary and Critical Care, Istanbul, Turkey
3
Marmara University, Faculty of Medicine, Department of Thoracic Surgery, Istanbul, Turkey
4
Ministry of Health Yedikule Chest Diseases and Thoracic Surgery Research and Education Hospital, Critical Care
Unit, Istanbul, Turkey
2
ABSTRACT
Study objectives: Although links between meteorological conditions and spontaneous pneumothorax (SP) have been proposed, the reports are controversial. In this study ozone levels, which are known to have some adverse effects on lung
tissues, were investigated as a potential triggering factor of
SP. At present there is not sufficient information about the
effects of ozone on SP.
Methods: Of a total 79 pneumothorax patients recruited for
the study, 21 secondary pneumothorax cases were excluded.
In the remaining 58 SP patients, meteorological data at the
time of SP occurrence were recorded.
Results: The number of SP patients was higher in spring than
in the other seasons (p < 0.05). There was an association
between the SP frequency and the average ozone level at different seasons (F 3,52 = 19.45, p = 0.001). The average ozone
level was higher in spring (363 ± 25 Dobson) than during the
other seasons (autumn 296 ± 18 Dobson; summer 321 ± 26
Dobson; winter 324 ± 32 Dobson) (p = 0.001). There was a
positive correlation between SP frequency and the average
ozone values for each season (r = 0.301, p = 0.024). There was
no significant correlation between the severity of SP and
ozone level (r = 0.236, p = 0.16).
Conclusions: The number of SP patients increases in spring
when ozone levels are highest. Ozone is known to affect alveolar cells and cause interstitial edema. Ozone causes damage
to the lung interstitium by way of oxidative stress. Rupture of
unrecognized underlying blebs/bullae has been proposed as a
cause of SP. Increased levels of ozone may be a triggering factor for these ruptures.
RIASSUNTO
Obiettivi: Sebbene siano state proposte possibili connessioni
tra le condizioni meteorologiche e lo pneumotorace spontaneo
(SP), i risultati sono ad oggi contoversi. In questo studio i livelli
di ozono, del quale sono noti gli effetti dannosi per le strutture
polmonari, sono stati oggetto di valutazione come possibili fattori causali nel SP. Al momento attuale le informazioni sugli effetti dell’ozono sul SP non sono sufficienti.
Metodi: Su un totale di 79 pazienti con pneumotorace reclutati
per lo studio ne sono stati esclusi 21 perché lo pneumotorace
era secondario. Nei rimanenti 58 pazienti con SP sono stati registrati i dati meteorologici alla data dell’evento.
Risultati: Il numero dei pazienti con SP era maggiore in primavera
rispetto alle altre stagioni (p < 0,05). Si è rilevata un’associazione
tra la frequenza di SP e i livelli medi di ozono nelle varie stagioni
(F 3,52 = 19,45; p = 0,001). Il livello medio di ozono era maggiore
in primavera (363 ± 25 Dobson) rispetto alle altre stagioni (autunno 296 ± 18 Dobson; estate 321 ± 26 Dobson; inverno 324 ±
32 Dobson) (p = 0,001). Si è rilevata una correlazione positiva tra
frequenza di SP e valori medi di ozono in ogni stagione (r = 0,301,
p = 0,024), mentre non vi erano correlazioni significative tra la
gravità del SP ed i livelli di ozono (r = 0,236, p = 0,16).
Conclusioni: Il numero di pazienti con SP aumenta in primavera
quando i livelli di ozono sono massimi. È risaputo che l’ozono
provoca danni sulle cellule dell’alveolo polmonare e causa edema interstiziale, danneggiando l’interstizio polmonare mediante stress ossidativo. La rottura di bolle e bollicine di cui il paziente è portatore inconsapevole è il meccanismo abitualmente attribuito come causa del SP: i maggiori livelli di ozono potrebbero essere un fattore scatenante di queste rotture.
Keywords: Ozone, seasonality, spontaneous pneumothorax.
Parole chiave: Ozono, pneumotorace spontaneo, stagionalità.
+ Yasin Abul
Ministry of Health Bismil Government Hospital, Pulmonary Medicine Clinics, Diyarbakir, Turkey
Ataturk M. Tantavi C. No:52/7 Umraniye-Istanbul, Turkey
Data di arrivo del testo: 30/06/2010 – Accettato dopo revisione: 22/07/2010
16 MRM
Primary spontaneous pneumothorax (SP) is a disease that occurs without a precipitating event in patients with no known lung diseases. In fact, most
SPs are usually thought to result from rupture of unrecognized blebs or bullae [1-2]. Triggering factors
causing rupture of blebs or bullae have not been determined. The proposed factors for the rupture of
blebs or bullae are disequilibrium between pressure
in the blebs/bullae and pressure in the surroundings
[3]. SP has differing geographical incidences. The
reason for these differences are unknown [4].
Certain climate changes, including atmospheric
pressure, humidity, temperature and seasonal variations have been studied as a potential cause of SP
occurrence [5-7]. However, the results of these
studies are controversial and have consistently
failed to show an association [3,8]. Additional studies are necessary to evaluate the possible triggering
factors of SP which may be caused by the rupture of
blebs or bullae. The possible impact of changes in
ozone level on the occurrence of SP has not been
studied before. Similarity between electron microscopic findings of ozone effects on lung tissue and
electron microscopic findings of SP encourage us to
expect an association between ozone concentration and the occurrence and severity of pneumothorax [9-10]. We aimed to evaluate the association
between the occurrence of SP and ozone levels.
Such an association may help us to understand the
mechanism of SP and the potential triggering factors
causing rupture of blebs or bullae which may be the
actual cause of SP.
METHODS AND MATERIALS
A total of 79 consecutive pneumothorax patients
who were admitted to emergency outpatient clinics
of Marmara University Hospital were included in
the study. We subsequently excluded 21 secondary
pneumothorax patients; the remaining 58 SP patients were investigated. Meteorological data and
ozone levels, recorded at the date and time of the
SP occurence at that latitude and longitude, were
obtained from a website of the Total Ozone
Mapping Spectrometer, Ozone Processing TeamNASA/GSFC Code 613.3. Pearson’s χ2, analysis of
variance, the t-test and the Pearson correlation coefficient were used as the statistical measures.
RESULTS
The female/male ratio was 7/51 while mean age
was 39 ± 30 years for females and 35 ± 17 years for
males. Demographic characteristics and risk factors
including smoking did not differ significantly in patients presenting in different seasons (Table I). The
number of SP patients was higher in spring than in
other seasons (spring n = 25, summer n = 12, autumn = 12, winter = 9; p < 0.05). Numbers of SP patients were higher in March (n = 6), April (n = 11),
May (n = 8) (p < 0.05) than in any of the other
months. There was an association between the frequency of SP incidence and the average ozone level
for the different seasons (F 3,52 = 19.45, p = 0.001).
As Figure 1 shows, the average ozone level was
higher in spring (363 ± 25 Dobson) than in the other seasons (autumn, 296 ± 18 Dobson; summer,
321 ± 26 Dobson; winter, 324 ± 32 Dobson) (p =
0.001). There was a positive correlation between SP
frequency and the average ozone values for the seasons (r = 0.301, p = 0.024). There was no significant
correlation between the severity of SP and ozone
levels (r = 0.236, p = 0.16).
DISCUSSION
This is the first study examining the effects of ozone
levels on spontaneous pneumothorax occurrences.
Some previous studies have proposed that seasonality and especially atmospheric pressure may be precipitating factors for SP. Bense and Scott et al. had
previously shown the link between SP and changes
in atmospheric pressure [5,11]. However, more recent studies in different regions have failed to show
an association between SP and climate changes
[12-14]. Recently, the first large nationwide population based study did not support the premise that
seasonality is a precipitating factor for SP [8]. In all
these studies, humidity, atmospheric pressure
changes and temperatures were under consideration in relation to the spontaneous pneumothorax
occurrences. Many studies have demonstrated no
association of changes in atmospheric pressure in
different regions and SP. Also with regard to SP and
variations in ambient temperature, some studies
have revealed no relationships. The results from
these studies are controversial, but they have consistently failed to show a significant association.
The most important finding of our study was the increased number of patients with SP during periods
of high ozone levels. The increased SP frequency
may be due to the oxidative stress effect of ozone.
Ozone is known to cause damage to the lung interstitium by way of oxidative stress [15]. Ozone has
also been known as a protoplasmic poison causing
damage to lung tissue during lung exposure to chlorine [16]. Studies of the noxious effects of ozone on
lung tissues are limited but it is known that ozone
can cause damage in lung tissue. Previously, acute
ozone exposure has been shown to decrease lung
volume per unit of distending pressure. This effect
may be potentially caused by a change of lung tissue elasticity or by changes in surface tension forces
of the alveoli [10]. The lungs are constantly exposed
to oxidants which are present in the air inhaled. The
oxidants in inhaled air include cigarette smoke and
ozone, or those released from inflammatory leukocytes. These oxidants, including ozone, cause direct
damage to the lung interstitium. These oxidative
stressors have been shown to contribute to the
pathogenesis of SP in some studies [15]. An increase in interstitial mass and a proliferation of epithelial cells has been reported as a response to pulmonary stress and insult including exposure to
Y Abul, S Karakurt, K Bostanci, M Yuksel, E Eryuksel, S Evman, T Celikel
Spontaneous pneumothorax and ozone levels – Pneumotorace spontaneo e livelli di ozono
INTRODUCTION
MRM
17
Multidisciplinary Respiratory Medicine 2011:6(1):16-19
TABLE I: CHARACTERISTICS AND RISK FACTORS FOR SPONTANEOUS PNEUMOTHORAX (SP) IN PATIENTS ACCORDING
TO SEASONS*
Characteristics
Spring (n = 25)
Summer (n = 12)
Autumn (n =12)
Winter (n = 9)
p
Male/Female
21/4
11/1
11/1
8/1
0.87
Age (years)
40 ± 20
31 ± 15
30 ± 18
34 ± 18
0.43
18/7
10/2
7/5
7/2
0.56
13
4
8
3
4
5
5
3
4
6
0
3
0.28
Smoking History +/Severity of SP
Moderate
Severe
Undefined**
*Data are presented as mean ± SD or absolute numbers.
**SP patients who did not have chest X-rays because of emergency conditions.
ozone [9]. By way of these effects on lung tissue, increased levels of ozone in the inhaled air may contribute to the pathogenesis and occurrence of SP.
The other important finding of our study was the increased SP frequency in the spring. There was also
a positive correlation between SP frequency and average ozone values for the seasons. The average
ozone value was higher in spring, and in spring
there was an increased SP frequency. In the literature there is no consensus regarding the causes of
the apparent increase in the rate of SP. There is also
no agreement about factors causing the occurrence
of SP. Some studies have proposed that changes in
atmospheric pressure cause alterations of the volume of air-holding lung cysts, and that this may
cause weakening of the walls [3]. However, both
weakening of the walls due to atmospheric changes
and contributions from other seasonal factors in-
FIGURE 1: NUMBER OF SPONTANEOUS PNEUMOTHORAX
PATIENTS AND OZONE LEVEL ACCORDING TO SEASONS
25 (43.1%), Spring
12 (20.7%), Summer
12(20.7), Autumn
9 (15.5), Winter
Limitations
The first limitation is the small sample size of the
study. A larger sample would have provided more
precise information about the effect of ozone level
on the occurrence and severity of SP. A second limitation is that this study is an uncontrolled retrospective study that could have a recall bias.
390
Ozone level (Dobson)
370
350
330
CONCLUSIONS
310
We found a higher incidence of SP in the spring
months when the ozone levels were highest. There
was a positive correlation between SP frequency
and average ozone values for the seasons in our
study. A high level of ozone may be involved in the
pathogenesis of SP. Larger population-based studies
in addition to the animal studies for effect of ozone
level on SP should be carried out to assess this
relationship.
290
270
250
0
10
20
Number of patients with spontaneous
pneumothorax
18 MRM
cluding temperature, humidity and storms as an explanation for the occurrence of SP do not provide
strong explanations for the SP occurrence from the
point of view of pathophysiology.
In our study, we found that SP was more often seen
in high ozone levels. Ozone itself is known to have
some destructive effects on lung tissue. This has
been shown by both biochemical studies and by
electron microscopical studies [10,15,17]. It is also
interesting that similar ultrastructural changes are
seen in lungs both in response to acute ozone exposure and in the occurrence of spontaneous pneumothorax. These changes include proliferation of epithelial cells and an increase in the intersitial mass and
edema [9-10]. As certain climatic parameters have
shown weak and controversial associations with the
incidence of SP, there is a need to invesitigate possible
other associations. From our findings and from the potential pathophysiological mechanisms of ozone acting on lung tissue, a high level of ozone may be a precipitating factor in the alteration of lung tissue elasticity and may also be a factor in the rupture of
blebs/bullae in SP. In our study a high level of ozone
in the spring may explain the more frequent occurrence of SP in this season.
30
CONFLICT OF INTEREST STATEMENT: None of the authors has
any conflict of interest to declare in relation to the subject
matter of this manuscript.
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2. Sahn SA, Heffner JE. Spontaneous pneumothorax. N Engl J
Med 2000;342:868-874.
3. Smit HJ, Devillé WL, Schramel FM, Schreurs JM, Sutedja
TG, Postmus PE. Atmospheric pressure changes and outdoor temperature changes in relation to spontaneous pneumothorax. Chest 1999;116:676-681.
4. Light R. Pleural Diseases. 4th ed. Philadelphia: Lippincott,
Williams and Wilkins, 2001.
5. Bense L. Spontaneous pneumothorax related to falls in
atmospheric pressure. Eur J Respir Dis 1984;65:544-546.
6. Ozenne G, Poignie P, Lemercier JP, Nouvet G, Grancher G.
Meteorological conditions and spontaneous pneumothorax.
Retrospective study of 165 cases in the Rouen area. Rev
Pneumol Clin 1984;40:27-33.
7. Alifano M, Forti Parri SN, Bonfanti B, Arab WA, Passini A,
Boaron M, Roche N. Atmospheric pressure influences the
risk of pneumothorax: beware of the storm! Chest
2007;131:1877-1882.
8. Chen CH, Kou YR, Chen CS, Lin HC. Seasonal variation in
the incidence of spontaneous pneumothorax and its association with climate: a nationwide population-based study.
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9. Tueller EE, Crise NR, Belton JC, McLaughlin RF Jr.
Idiopathic spontaneous pneumothorax. Electron micro-
scopic study. Chest 1977;71:419-421.
10. Boatman ES, Frank R. Morphologic and ultrastructural
changes in the lungs of animals during acute exposure to
ozone. Chest 1974;65(Suppl):9S-11S.
11. Scott GC, Berger R, McKean HE. The role of atmospheric
pressure variation in the development of spontaneous pneumothoraces. Am Rev Respir Dis 1989;139:659-662.
12. Ayed AK, Bazerbashi S, Ben-Nakhi M, Chandrasekran C,
Sukumar M, Al-Rowayeh A, Al-Othman M. Risk factors of
spontaneous pneumothorax in Kuwait. Med Princ Pract
2006;15:338-342.
13. Bulajich B, Subotich D, Mandarich D, Kljajich RV, Gajich
M. Influence of atmospheric pressure, outdoor temperature,
and weather phases on the onset of spontaneous pneumothorax. Ann Epidemiol 2005;15:185-190.
14. Suarez-Varel MM, Martinez-Selva MI, Llopis-Gonzalez A,
Martinez-Jimeno JL, Plaza-Valia P. Spontaneous pneumothorax related with climatic characteristics in the Valencia
area (Spain). Eur J Epidemiol 2000;16:193-198.
15. Tabakoglu E, Ciftci S, Hatipoglu ON, Altiay G, Caglar T.
Levels of superoxide dismutase and malondialdehyde in
primary spontaneous pneumothorax. Mediators Inflamm
2004;13:209-210.
16. Banyai AL. Paper. Chest 1974;66:540.
17. Alpert SM, Gardner DE, Hurst DJ, Lewis TR, Coffin DL.
Effects of exposure to ozone on defensive mechanisms of
the lung. J Appl Physiol 1971;31:247-252.
Y Abul, S Karakurt, K Bostanci, M Yuksel, E Eryuksel, S Evman, T Celikel
Spontaneous pneumothorax and ozone levels – Pneumotorace spontaneo e livelli di ozono
ACKNOWLEDGEMENT
The authors would like to thank Prof. RW Guillery from University
of Oxford for the English correction of the manuscript.
MRM
19
Original Article / Articolo Originale
Clinical trials in advanced stage lung cancer:
a survey of patients’ opinion about their
treatment
Trial clinici nel tumore del polmone in stadio
avanzato: un’analisi dell’opinione dei pazienti
riguardo al trattamento
Bojan Zaric1, Branislav Perin1, Aleksandra Ilic1, Ivan Kopitovic1, Jovan Matijasevic1,
Ljiljana Andrijevic2, Nevena Secen1, Jelena Stanic1, Milorad Bijelovic3, Zdravko Kosjerina1,
Milan Antonic1
1
Institute for Pulmonary Diseases of Vojvodina, Clinic for Pulmonary Oncology, Faculty of Medicine, University
of Novi Sad, Serbia
2
Institute for Oncology of Vojvodina, Faculty of Medicine, University of Novi Sad, Serbia
3
Institute for Pulmonary Diseases of Vojvodina, Clinic for Thoracic Surgery, Faculty of Medicine, University of Novi
Sad, Serbia
ABSTRACT
Background: The major aim of this study was to investigate
what patients with advanced stage lung cancer, enrolled in a
clinical trial, thought about their treatment. We also wanted
to investigate if there exist any characteristics that could
influence patients’ opinion about the clinical trial.
Patients and methods: Over the period from June 2008 to June
2009, 59 eligible patients were enrolled in this study. The
major inclusion criteria were: participation in a clinical trial,
previously treated advanced stage lung cancer, and good performance status (ECOG 0-2). All patients were asked to
answer a questionnaire designed to investigate their impressions about participation in a clinical trial. The questionnaire
was deposited in a sealed box which was opened at the end of
the study. We investigated a possible influence of age, gender,
education, lung cancer stage, chemotherapy line and tumor
type on the patients' opinion about some aspects of the clinical trial.
Results: The majority of the patients were aware they were
participating in the clinical trial and a significant number of
them were very satisfied with the treatment. Of the investigated factors, only the level of education had a statistically
significant influence on some of the questions raised in the
questionnaire.
Conclusions: Patients participating in clinical trials are satisfied with their treatment, ready to proceed with it and would
recommend it to other patients. It depends mainly on health
professionals to maintain this level of confidence and justify
their trust.
Keywords: Chemotherapy, clinical investigation, clinical trial,
lung cancer, non small cell lung cancer (NSCLC), small cell
lung cancer (SCLC).
RIASSUNTO
Razionale: Lo scopo principale di questo studio era valutare
ciò che pensano i pazienti con un tumore polmonare in stadio
avanzato arruolati in un trial clinico riguardo al trattamento
cui sono sottoposti. Desideravamo inoltre valutare se esistesse qualche caratteristica dei pazienti in grado di influenzare la
loro opinione sui trial clinici.
Pazienti e metodi: Nel periodo tra giugno 2008 e giugno 2009
sono stati inclusi in questo studio 59 pazienti. I principali criteri di inclusione erano la partecipazione ad un trial clinico,
essere già stati trattati per un tumore polmonare in stadio
avanzato ed avere una buona condizione generale (punteggio
0-2 alla scala Eastern Cooperative Oncology Group). A tutti i
pazienti è stato richiesto di compilare un questionario dise-
+ Bojan Zaric
Institute for Pulmonary Diseases of Vojvodina, Clinic for Pulmonary Oncology
Institutski put 4, 21204 Sremska Kamenica, Serbia
Data di arrivo del testo: 02/08/2010 – Accettato per la pubblicazione: 06/09/2010
20 MRM
Parole chiave: Chemioterapia, studio clinico, tumore polmonare, tumore polmonare non a piccole cellule (NSCLC), tumore polmonare a piccole cellule (SCLC), valutazione clinica.
INTRODUCTION
Lung cancer still remains one of the deadliest cancer types in the world. Both the incidence and mortality are still high, equally among male and female
patients, in practically all parts of the world. Lung
cancer is still a leading cause of cancer related mortality, with an overall 5-year survival < 20% in
Europe and USA. The estimated number of new
cases of lung cancer in USA for 2009 is 219,440.
The estimated number of deaths in USA for 2009 is
even more discouraging: 159,390 [1-4].
Many prevention and political measures, such as
prohibition of smoking in public places or the banning of cigarette commercials, might contribute to a
decrease in morbidity and mortality. However,
these measures need time to show their true potential. In the past decade, we have observed a drop in
morbidity (mostly in squamous cell lung cancer)
due to the public measures and increased public
awareness, but mortality still remains alarmingly
high [5-8].
The introduction of novel chemotherapeutic agents,
the development of targeted therapy, the combination of standard chemotherapy with molecular targeted therapy, and combinations with various radiotherapy regimens, might result in a better survival of
lung cancer patients. Indeed, some clinical trials
with novel targeted therapy agents, or their combinations with chemotherapy, have shown a significant improvement in the disease free survival, or
even the overall survival. On the other hand, we
should always be cautious about the results of clinical studies and wait for more data, or meta-analyses before implementing these results in the clinical
practice [4,9-12]. Nevertheless, in the light of the
current situation regarding lung cancer mortality, it
is true that the most appropriate treatment for a patient is his/her inclusion in a clinical trial.
Practically all cancer societies, dealing with the
problem of lung cancer, recommend treatment in a
clinical trial setting [12-16].
However, in the hunt for a better survival and better
results, with a substantial number of patients in
clinical trials, what do we actually know about our
patients’ thoughts and feelings? What do they themselves know about their own condition and the
treatment itself? The regulations and rules for the
clinical trials are strict and defined, and all physicians investigating the treatment of lung cancer adhere to these rules and regulations [14-18]. But still,
what do patients think and know about it? Many patients receive therapeutic benefits from participating
in clinical trials, even moreso than they are aware,
and in some cases these benefits exceed those that
standard care could provide. However, the patients
participating in clinical trials contribute not only to
their own and future patients' treatment benefits,
but also to the benefits of medicine and to science
itself. The physicians are aware of this fact, but are
the patients aware of the same fact, too?
The major aim of the study we conducted was to investigate what patients knew and thought about
their disease, about the options for their current and
future treatment, as well as about the clinical trial
they participated in. We wanted to investigate how
satisfied they were with the treatment in the clinical
trial (this is why we included only previously treated patients), and what they thought and knew about
the novel chemotherapy they were treated with. We
designed a short questionnaire in order to obtain
the answers to some of these questions. The secondary aim of the study was to investigate the influence
of age, gender, education, lung cancer type and
stage, chemotherapy duration and chemotherapy
line on the patients’ opinion about the disease,
treatment, and clinical trial.
PATIENTS AND METHODS
This was a prospective trial conducted at the Clinic
for Pulmonary Oncology of the Institute for
Pulmonary Diseases of Vojvodina, Serbia. The study
was carried out over a 1-year period, from July 2008
to July 2009, and it was approved by the institutional review and ethical board. All the patients who
agreed to participate in the study and answer the
questionnaire were informed about the study and
signed the informed consent form.
Of 86 patients who at the time participated in clinical trials on administration of novel chemotherapeutic agents, 59 met all the inclusion criteria and
were eligible for the study. The inclusion criteria
were: current participation in a phase II or III clinical trial on non-small cell lung cancer (NSCLC) or
small cell lung cancer (SCLC), the treatment including targeted molecular therapy, chemotherapy or
their combination, advanced stage (IIIB, IV) NSCLC
or extensive SCLC, second or third line chemotherapy, good performance status graded by Eastern
Cooperative Oncology Group (ECOG) 0-2, and
willingness to participate in the study. The exclusion
criteria were: the first line chemotherapy, stage I –
IIIA NSCLC, limited SCLC, current or concurrent
radiotherapy, ECOG ≥ 3, inability or refusal to par-
B Zaric, B Perin, A Ilic, I Kopitovic, J Matijasevic, L Andrijevic, N Secen, J Stanic, M Bijelovic, Z Kosjerina, M Antonic
Lung cancer trials and patient opinion – L’opinione dei pazienti sui trial per il tumore polmonare
gnato per valutare le loro impressioni sulla partecipazione al
trial clinico. Il questionario era depositato in un contenitore
sigillato che veniva poi aperto al termine dello studio.
Abbiamo ricercato una possibile influenza di età, sesso, scolarità, stadiazione del tumore polmonare, tipologia di chemioterapia e di tumore sull’opinione del paziente riguardo alcuni
aspetti del trial clinico.
Risultati: La maggioranza dei pazienti era consapevole di partecipare ad un trial clinico ed una quota significativa di loro
era molto soddisfatta del trattamento. Tra i fattori oggetto di
questa ricerca solo il livello di scolarità dimostrava un’influenza statisticamente significativa su alcuni dei punti toccati dal questionario.
Conclusioni: I pazienti che partecipano a trial clinici sono soddisfatti del loro trattamento, desiderosi di continuarlo e disposti a raccomandarlo ad altri pazienti. Dipende soprattutto
dai professionisti della salute mantenere questo livello di fiducia e giustificare questo credito.
MRM
21
ticipate in the study.
A specially designed questionnaire (Figure 1) was
given to each patient enrolled. The patients were
asked to answer the questionnaire after the third
course of the second or third line chemotherapy
regimen. All of the patients had sufficient time to
answer the questions and to place the question-
naires in the “answer box”. The “answer box” was a
sealed carton container placed in the main hall of
the clinic, enabling the patients to keep their privacy and anonymity after completing the questionnaire. This approach provided privacy to the patients, and ensured true and honest answers. It was
explained to the patients that they should write their
FIGURE 1: AD-HOC QUESTIONNAIRE TO INVESTIGATE PATIENTS’ IMPRESSIONS ABOUT PARTICIPATION IN A CLINICAL TRIAL
QUESTIONNAIRE
The main purpose of this investigation is explained to you in the informed consent form you read and signed. If you wish, you can answer
the questions in this questionnaire. Answer the questions by simply circling the answer you think is appropriate. When you finish, please
put the questionnaire in the answer box located in the main lobby of the clinic.
Thank you for your participation.
1. Are you familiar with the nature of the disease you suffer from?
a) Yes b) No c) I am not sure
2. Do you know the type of lung cancer you suffer from?
3. Do you know what kind of chemotherapy for lung cancer you have so far received?
4. Are you aware in what stage your condition (lung cancer) currently is?
5. Have you received your previous chemotherapy in a regional hospital or at the Institute for Pulmonary Diseases
of Vojvodina (IPBV)?
a) Regional hospital
b) IPBV
c) I am not sure
6. Do you understand that you are participating in the clinical trial with novel chemotherapy or targeted therapy drug?
7. Do you understand what a clinical trial is?
8. Have you read the entire Informed Consent Form (ICF) your physician gave you before you entered the clinical trial?
a)Yes b) No c) I am not sure
9. How satisfied are you with the information about the clinical trial you obtained from your physician or from the ICF?
a) Very satisfied
b) Satisfied
c) Not satisfied
d) I am not sure
10. Do you think that during the clinical trial period you will need additional information about the study treatment?
11. Do you think that by participating in a clinical trial you have a better chance for surviving the lung cancer?
12. Do you think that chemotherapy given within the clinical trial is better than the chemotherapy patients usually get?
13. Are you aware of the fact that you might not be treated with the investigational product in the clinical trial you are currently
participating?
14. Do you think the investigational product (chemotherapy) given in the clinical trial you are currently participating in has fewer side
effects than the chemotherapy you were previously treated with?
15. Do you think that the medical personnel (physicians and nurses) conducting this clinical trial have sufficient knowledge and training?
16. Do you think the physicians and nurses are more easily accessible to you because you are participaring in the clinical trial?
17. Do you think that your treatment within the clinical trial is better than the treatment of patients who are not participating
in clinical trials?
18. How would you assess your treatment in the clinical trial so far?
a) Excellent
b) Very good
c) Good
d) Neither good nor bad
e) Bad
19. If there were an opportunity to join another clinical trial, after you finish the current one, would you join?
20. Would you recommend to other patients to join the clinical trial you have been participating in?
22 MRM
RESULTS
Fifty-nine patients were included in this study. The
average age of the patients was 56 ± 10 years (range
36-73). The average chemotherapy duration was 11
± 4 months (range 3-19). There were 48 (81.4%)
male patients and 11 (18.6%) females included in
this study. Most patients (n = 32, 54.2%) had squamous cell lung cancer diagnosed; small cell lung
cancer was diagnosed in 16 (27.1%) patients, and
adenocarcinoma in 11 (18.6%) patients. The majority of the patients (30/59, 50.8%) had an advanced
stage IV NSCLC. Thirteen patients (22%) had stage
IIIB NSCLC. Extensive SCLC was investigated in 16
patients (27.2%). There were 17 patients (28.8%)
enrolled in phase II clinical trials versus 42 (71.2%)
in phase III clinical trials. The majority of the patients (32 or 54.2%) were high school graduates; 16
(27.1%) patients had a university degree, while 11
patients (18.6%) had elementary school education.
An overview of the questions, and frequency and
percentage of the answers is presented in Table I.
The questions marked with an asterisk are explained further in the text. It is clear from the table
that all the patients who participated in both clinical trials and our study were familiar with the nature
of their disease. A significant number of patients
knew the type of lung cancer they suffered from.
There was also a significant number of patients who
knew what kind of chemotherapy they received prior to the enrollment in the clinical trial. The majority of the patients were aware of their current lung
cancer stage. Question 5 addressed the place or institution where the patients received previous
chemotherapy. Most patients were previously treated in our institution (44/59 or 74.6%); 14 (23.7%)
patients were treated in the regional hospital, while
one patient did not know where he was treated.
Almost all patients (58/59 or 98.3%) knew that they
were participating in a clinical trial; the remaining
patient responded that he did not know he was participating in a clinical study. The large majority of
patients (47/59 or 79.7%) said they understood
what “a clinical trial” was, but 12 patients (20.3%)
were not sure what “a clinical trial” means. One of
the most interesting results shows that 5 patients
(8.5%) did not read the entire informed consent
form (ICF). However, a significant number of patients (54/59 or 91.5%) had read the entire ICF.
Question 9 addressed the level of satisfaction with
the information about the treatment within the clinical trial. Forty-three patients (72.9%) were very satisfied with the information given by the investigators or provided in the ICF and 16 patients were satisfied. There were no patients who were not satisfied or who were unable to answer question 9.
Practically equal numbers of patients thought they
would/would not require additional information
during the clinical trial period, i.e. 47.5% and
49.2% of the patients, respectively.
One of the most important findings obtained in the
study was the opinion of patients that the
chemotherapy given in the clinical trial would give
them a better chance for survival. A significant
number of patients (93.2%) thought they had a better chance of survival in the clinical trial, and 6.8%
of the patients were not sure about it. There was also a large number of patients who answered that
chemotherapy given in the clinical trial was better
than the therapy used previously. Forty-eight patients (81.4%) thought that chemotherapy in the
clinical trial was better than the “usual” chemotherapy, 2 patients thought it was not better, while 9 patients (15.3%) were not sure. A majority of patients
(98.3%) understood that during the clinical trial
they might not receive the investigational product.
There were 38 patients (64.4%) who thought that
chemotherapy given in the clinical trial had fewer
side effects, 16 who thought the contrary (that
chemotherapy given in the clinical trial did not have
fewer side effects), and 5 (8.5%) who were not sure.
There were 57/59 (96.6%) patients who thought
that the medical personnel conducting the clinical
trial had sufficient knowledge and skills. This shows
that a majority of patients believe that their doctors
and nurses are adequately trained. All the patients
enrolled in the study expressed the opinion that the
physicians and nurses were more easily accessible
to them because they participated in the study. A
significant number of patients (57/59 or 96.6%) believed the treatment within a clinical trial was better
than the treatment given to patients not included in
trials. Two remaining patients were not sure about
this issue. A majority of the patients (89.8%) graded
their overall treatment in the clinical trial as excellent. Five patients (8.5%) assessed their treatment as
very good, while one patient assessed it as good.
There were no patients who assessed their treatment
as “neither good nor bad” or “bad”. Interestingly,
88.1% of the patients answered that they would
participate in future clinical trials when they finished the treatment in the current one. This means
that a significant number of patients would like to
continue the treatment within the clinical trial. On
the other hand, two patients (3.4%) would not any
more participate in clinical trials, while 5 patients
(8.5%) were not sure about it. The majority of patients (56/59 or 94.9%) would recommend the clin-
initials and date of birth in order to enable obtaining other relevant data from their medical charts
needed for evaluation of the results to be performed
later.
Descriptive statistics were generated for all study
variables, including the mean and standard deviation for continuous variables and relative frequencies for categorical variables.
The variables concerning ’the patients’ satisfaction’
were treated as the data in nominal category. In order to compare these answers according to gender,
cancer type, cancer stage, education level of patients and line of chemotherapy, we used Pearson’s
χ2 test with p < 0.05 as a significant level of probability. All statistical analyses were performed using
the SPSS for Windows, version 11.5 (SPSS Inc.,
Chicago, IL) software.
MRM
23
TABLE I: PATIENTS’ RESPONSES PER RESPONSE CATEGORY (NUMBER AND %) TO EACH ITEM OF THE
QUESTIONNAIRE
Question
Answers
Yes
n/%
No
n/%
I am not sure
n/%
1. Are you familiar with the nature
of disease you suffer from?
59/100
0/0
0/0
2. Do you know the type of lung cancer
you suffer from?
50/84.7
0/0
9/15.3
3. Do you know what kind of chemotherapy
for lung cancer you received so far?
58/98.3
0/0
1/1.7
4. Are you aware at what stage
your condition (lung cancer) currently is?
44/74.6
1/1.7
14/23.7
58/98.3
0/0
1/1.7
5. Have you received your previous chemotherapy
in a regional hospital or at the Institute for Pulmonary
Diseases of Vojvodina (IPBV)?*
6. Do you understand that you are participating
in a clinical trial with novel chemotherapy
or a targeted therapy drug?
7. Do you understand what a clinical trial is?
47/79.7
0/0
12/20.3
8. Have you read the entire Informed
Consent Form (ICF) your physician gave
before you entered the clinical trial?
54/91.5
5/8.5
0/0
10. Do you think that during the clinical trial
period you will need additional information
about the study treatment?
28/47.5
29/49.2
2/3.4
11. Do you think that by participating in a clinical
trial you have a better chance for surviving
the lung cancer?
55/93.2
0/0
4/6.8
12. Do you think that chemotherapy given within
the clinical trial is better than the chemotherapy
patients usually get?
48/81.4
2/3.4
9/15.3
13. Are you aware of the fact that you might
not be treated with the investigational product
in the clinical trial you are currently participating?
58/98.3
0/0
1/1.7
16/27.1
5/8.5
1/1.7
1/1.7
16. Do you think that physicians and nurses are more
59/100
easily accessible to you because you are participating
in the clinical trial?
0/0
0/0
17. Do you think that your treatment within the clinical
trial is better than the treatment of patients who
are not participating in clinical trials?
57/96.6
0/0
2/3.4
52/88.1
2/3.4
5/8.5
20. Would you recommend to other patients
56/94.9
to join the clinical trial you have been participating in?
1/1.7
2/3.4
9. How satisfied are you with the information about
the clinical trial you obtained from your physician
or from the ICF?*
14. Do you think that the investigational product
38/64.4
(chemotherapy) given in the clinical trial you are
currently participating in has fewer side effects than
the chemotherapy you were previously treated with?
15. Do you think that medical personnel
(physicians and nurses) conducting this clinical trial
have sufficient knowledge and training?
57/96.6
18. How would you assess your treatment
in the clinical trial so far?*
19. If there would be an opportunity to join another
clinical trial, after you finish the current one,
would you join?
Answers on questions marked with asterisk are explained in the text.
Questions are consecutively stated in Figure 1.
24 MRM
DISCUSSION
The findings of this study reveal that the majority of
the patients included in the study had an advanced
stage NSCLC, primarily the squamous cell lung cancer. This is due to the fact that squamous cell lung
cancer is the most prevalent type of lung cancer in
our country, but selection bias also played a significant role: most of the studies from which our patients were drawn were examining chemotherapy in
squamous cell lung cancer. That is the main reason
why the distribution of lung cancer types does not
correlate with the general distribution of lung cancer types in most published studies. Lung cancer is
usually diagnosed in its late or advanced stage; in
our country almost 80% of patients with NSCLC are
diagnosed with an advanced stage lung cancer. The
majority of patients with SCLC are also diagnosed
in an extensive disease stage. In most countries
there are no clear screening programs for lung cancer. The same is true for Serbia, but here we are also
facing low public health awareness. The political
measures for prevention of lung cancer are still in
their infancy in Serbia, as in many developing
countries, and it is too early to expect the results until in the next few years.
Our patients were asked to answer the questionnaire after the third cycle of the clinical trial
chemotherapy regimen in order to be able to compare their previous experience with the current one.
The patients included in this study were receiving
second or third line chemotherapy within the clinical trial in which they were participating, so they already had substantial experience with chemotherapy. The results show that most patients know
the true nature of their disease and even the type of
lung cancer they suffer from, suggesting that patients are well informed about their condition and
disease. A frank approach to a patient, giving
him/her a thorough explanation of the disease characteristics and the treatment, is a cornerstone for
gaining the patient's trust. It can also create a relationship in which it is easier to explain to the patient
the significance of participation in the clinical trial,
if the patient qualifies for it. This is particularly important in low income countries where clinical trial
therapy, even for control groups, is a big step forward with respect to the therapy patients would
usually get. We often have the situation that the
physicians are highly interested in the clinical trial,
not from the financial standpoint, but because it is
the only way for patients to be treated as recommended by the guidelines. This is probably one of
the reasons why we are often among the sites with
the highest enrollment in many clinical trials.
The adequate approach to the patient with lung
cancer can also be observed through a significant
number of the patients who knew what type of
chemotherapy they received prior to the enrollment
in the clinical trial. However, this may be related to
the fact that the majority of the patients received
that therapy in our institution where the institutional
policy is to explain to patients what kind of therapy
they will receive. One of the most important results
showed that the majority of the patients knew that
they were participating in the clinical trial, except
for one patient. One of the reasons might be insufficient engagement of the physician or inability to
completely understand the informed consent form
(ICF). The ICF is usually too robust for a patient to
read it completely, and without significant help
from the physician the patient can hardly understand all that is written in the document. Whatever
the reason for that one negative answer is, it stands
as a warning. We must pay due attention to all patients in clinical trials all the time they are under our
treatment. The fact that 8.5% of the patients did not
read the entire ICF represents also an alarming finding. As stated before, ICFs usually provide more detailed information about the trial than an investigator can give during the interview with a patient. The
multivariate analysis showed that a significant number of the patients with a university degree read the
entire ICF. This suggests we should pay more attention to less educated patients, especially when providing information and ICF documentation. On the
other hand, the scientific management and study
protocol teams should pay more attention to the
concept of the ICF, taking into consideration its
length and the patients' ability to understand what
is written. Too extensive ICFs exceeding a certain
ical trial treatment to other patients. One of the patients would not recommend it, while two were not
sure about it.
Several factors that could potentially influence the
patients' answers were evaluated in the multivariate
analysis, including age, gender, lung cancer type,
current lung cancer stage, chemotherapy line, patients' education level, and duration of chemotherapy treatment. However, only one factor proved influential on the patient’s answers on specific questions: and that factor was the patients' education
level. A statistically significant higher number of patients (p = 0.008) with university education knew
the exact type of lung cancer they suffered from
compared to patients with high or elementary
school level of education. There was also a statistically significant number of patients with a university degree (p < 0.001) who knew the exact stage of
their disease, a significant number of them
(p = 0.004) understood what the “clinical trial” was.
There was also a significant number of patients with
university degree who had read the entire informed
consent form (p = 0.02) and a significant number of
them thought that they would require additional information regarding the trial (p = 0.001). On the
other hand, there was a statistically significant number of patients with high school education level
who believed that the investigational product given
in the chemotherapy trial caused less side effects
(p = 0.04). There was also a statistically significant
number of patients with a lower education level
than university degree (high school) who would join
another clinical trial after completion of the current
one (p = 0.01).
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number of pages, with complicated explanations
and medical terms are usually not understandable
for the patient. No matter how a patient may be motivated to read the entire document, 20 pages of text
are a bit too much. One factor is also very important - the translation from English to native languages. These translations are usually made by professional translators and not medical professionals,
leading to a literary translation which is sometimes
hard to understand even for physicians.
The overall satisfaction with the level of information
provided was significantly high in our group, suggesting that our study teams provided sufficient and
relevant information. We tried to avoid potential biases by providing a level of anonymity to the patients who dispatched their answers in a sealed carton box placed in the clinic lobby. We also explained to the patients that the sincerity of their answers was of major importance, and that whatever
answers they gave, it would not have any influence
on their further treatment. The level of education influenced the requirement of the patients for additional information although the number of patients
who answered that they would require additional
information and those who answered that they
wouldn't was practically equal. This is related to the
fact that more educated patients expect a more detailed update on their condition. The patients' belief
and trust in the treatment is also reflected by a significant number of patients who answered that they
believed that chemotherapy given in the clinical trial is better than the “usual” chemotherapy. The answer might be biased by an excessive explanation
of the advantages for participation in the clinical trial given by the physician. However there were two
patients with university degree who gave a negative
answer, and 9 patients who were not sure, and they
represent almost 20% of the patients included in
the study. These results suggest that the possible bias
could be minimal, and that the patients really believed the trial chemotherapy was better. The important issue is that chemotherapy given in the clinical
trial protocol in developing countries is more advanced, from the medical point of view, and patients are able to recognize this fact.
It is very important that a significant majority of the
patients know that they might not receive the investigational product during the trial. That shows that
the patients are aware of the study design, its benefits and pitfalls and they still want to participate,
even though they have the opportunity to withdraw
from the trial whenever they want. Still, they are satisfied with the treatment and consider their physicians as trustworthy, well educated and knowledgeable. The patients enrolled in the clinical trial think
that because of their participation in the trial, nurses
and physicians are more easily accessible to them.
This might be true - it is a fact that more time and
special care is provided to the patients in the clinical trial. It is sometimes required by the protocol of
the trial itself (to perform more examinations or
more detailed examinations, more lab tests, to
check the patients' condition several times a day).
All this creates an impression of special care received, so the patients usually feel more comfortable and more appreciated. This might be also one
of the reasons why the majority of the patients expressed the opinion that their treatment was better
than the treatment of the patients not included in
the trial. A significant number of our patients qualified their overall treatment in the clinical trial as excellent. This is a direct consequence of the number
and quality of provided services. Certainly, the
quality and engagement of the sponsors who provided travel reimbursement and refreshments could
play a significant role in such assessment of the
treatment. On the other hand, the fact is that the
combination of drugs in the clinical trials in advanced stage lung cancer nowadays includes targeted therapy alone or in combination with
chemotherapy. This results in fewer side effects and
better clinical improvement compared to standard
chemotherapy available in developing countries.
The patients can observe and feel the improvement
and they usually feel satisfied with the treatment.
The physicians are eager to monitor the patients
more carefully, ready to dedicate more time and attention to them in order to detect a result of the
treatment and record the patients' current condition. The physician’s interest is generated on one
side by scientific and, on the other, by financial reasons. But, no matter what generates it, a higher
physicians’ vigilance results in better care for the
patients and this is what matters most. This of course
is the case in developing countries; the situation in
more developed economies could be substantially
different.
The overall success of the treatment in the clinical
trials in our study is testified by the fact that a statistically significant number of patients would join another trial after they finish the current one, and a
significant majority of the patients would recommend the treatment in clinical trials to other patients. That should be one of the goals of clinical trials in advanced lung cancer. The majority of the
published guidelines suggest that the best treatment
for patients with advanced stage lung cancer is in a
clinical trial. But if one patient recommends the trial to another, the trial itself gains popularity and importance among the patients. There is no better motivation for a patient to join a trial than the recommendation of a friend or a fellow patient. We encountered situations in which a significant number
of patients were interested in joining the study because they had heard about it form other patients.
However, this implies a huge responsibility for the
physicians: a very selective choice of the trials with
special concern for a full ethical discolsure of the
study, taking of course into consideration the medical justification.
A major disadvantage of this study is that the questionnaire was developed by our own study team
that included medical physicians and non-medical
staff (pulmonologists and medical oncologists, nurses, statisticians and IT engineers). The questionnaire
did not undergo all the testing phases in concor-
CONCLUSION
Clinical trials in advanced stage lung cancer are
currently the best option for the treatment of patients with that condition. Our study showed that
the patients included in several clinical trials have a
very positive attitude toward the current trial and
clinical trials in general. The overall satisfaction
with the treatment was very high, suggesting that
the patients think they received the best possible
care, and probably they think so because they are
enrolled in a clinical trial. The patients' confidence
and trust in their physicians and nurses is very firm
and the majority of patients completely trusted their
physicians. The major conclusion of this study
could be that not only do the physicians have high
hopes from the trials, but that patients understand
what the trial is and have high hopes too. This study
showed that the patients would recommend the trial to other patients, proving that they are aware of
the fact that they could, with their opinion and experience, help others, too.
The only factor identified in this study that possibly
influences the patients’ opinion about the treatment
is the level of education. We should adjust our approach to each individual patient with a special
concern about the level of education. Our recommendation to study teams and protocol writers
would be to pay special attention to the ICF, its
length and amount of information provided by it. In
conclusion, our patients do believe in clinical trials
and they do believe in us. It is difficult to say how
much effort we must additionally invest to obtain
better results and longer survival of patients with
lung cancer. One thing is sure: we must give our
best to justify the confidence and the hope our patients place in us.
ACKNOWLEDGEMENT
The authors would like to express their gratitude for the statistical management of the data to Zoran Potic and Marijela
Potic.
CONFLICT OF INTEREST STATEMENT: None of the authors has
any conflict of interest to declare in relation to the subject
matter of this manuscript.
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dance with the guidelines for questionnaires in clinical trials. However, our intent was to make a survey of the patients’ opinion, not to measure their
satisfaction, because that would require a fully developed and tested questionnaire, which is not
available in that form. With the form of the questionnaire we created, we tried to minimize the biases and maximize the quality of the answers used for
the analysis.
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Review / Rassegna*
Effects of climatic changes and urban air
pollution on the rising trends of respiratory
allergy and asthma
Effetti delle modificazioni climatiche e
dell’inquinamento urbano sul trend in incremento
delle patologie respiratorie allergiche e dell'asma
Gennaro D’Amato
1
Division of Pneumology and Allergology Department of Respiratory Diseases, High Speciality Hospital
“A. Cardarelli”, Naples, Italy
2
Chairman ERS-EAACI joint task force on “Climate changes, air pollution and respiratory diseases”
3
Chairman WAO committee on “Climate changes and Allergy”
ABSTRACT
Over the past two decades there has been increasing interest
in studies regarding effects on human health of climate
changes and urban air pollution. Climate change induced by
anthropogenic warming of the earth’s atmosphere is a daunting problem and there are several observations about the role
of urbanization, with its high levels of vehicle emissions and
other pollutants, and westernized lifestyle with respect to
the rising frequency of respiratory allergic diseases observed
in most industrialized countries.
There is also evidence that asthmatic subjects are at
increased risk of developing exacerbations of bronchial
obstruction with exposure to gaseous (ozone, nitrogen dioxide, sulfur dioxide) and particulate inhalable components of
air pollution.
A change in the genetic predisposition is an unlikely cause of
the increasing frequency in allergic diseases because genetic
changes in a population require several generations.
Consequently, environmental factors such as climate change
and indoor and outdoor air pollution may contribute to
explain the increasing frequency of respiratory allergy and
asthma. Since concentrations of airborne allergens and air
pollutants are frequently increased contemporaneously, an
enhanced IgE-mediated response to aeroallergens and
enhanced airway inflammation could account for the increasing frequency of allergic respiratory diseases and bronchial
asthma.
Scientific societies such as the European Academy of Allergy
and Clinical Immunology, European Respiratory Society and
the World Allergy Organization have set up committees and
task forces to produce documents to focalize attention on
this topic, calling for prevention measures.
Keywords: Air pollution, airway hyperreactivity, bronchial
asthma, pollen allergy, respiratory allergy, thunderstormassociated asthma, urban air pollution.
RIASSUNTO
Nelle ultime due decadi si è registrato un crescente interesse
sugli effetti delle modificazioni climatiche e dell’inquinamento urbano sulla salute dell’uomo. Le modificazioni climatiche
indotte dal riscaldamento globale dell’atmosfera terrestre su
base antropica rappresentano un problema pressante e si sono moltiplicate le osservazioni sul ruolo dell’urbanizzazione,
con i suoi elevati livelli di emissioni di veicoli e di altri inquinanti, e dello stile di vita occidentale sulla sempre maggior
frequenza di malattie respiratorie su base allergica nei paesi a
più elevato tasso di industrializzazione.
+ Gennaro D’Amato
Division of Pneumology and Allergology Department of Respiratory Diseases, High Speciality Hospital “A. Cardarelli”
Via Rione Sirignano 10, 80121 Napoli, Italy
*This review is based on the work carried out by the European Academy of Allergy and Clinical Immunology and European
Respiratory Society in the EAACI-ERS Joint Task Force on “Climate changes, air pollution and respiratory diseases” and on the
work carried out by the World Allergy Organization (WAO) Committee “Climate changes and Allergy”.
Data di arrivo del testo: 27/07/2010 – Accettato per la pubblicazione: 08/09/2010
28 MRM
Parole chiave: Allergia ai pollini, allergie respiratorie, asma
bronchiale, asma associata ai temporali, inquinamento dell’aria, inquinamento urbano, iperreattività bronchiale.
INTRODUCTION
Evidence suggests that allergic respiratory diseases
such as rhinitis and bronchial asthma have become
more common worldwide over the past three
decades [1-4]; in parallel, in the past few years,
much etiological and pathogenic research has been
carried out in an attempt to determine the causes of
this rising frequency and significant improvements
have been made in our knowledge concerning the
effects of air pollution on human health. Several
studies have shown the adverse effects of ambient
air pollution on respiratory health [5-9] and scientific societies such as the European Academy of
Allergy and Clinical Immunology, European
Respiratory Society and World Allergy Organization
have organized committees and task forces to produce documents on this issue [10-12].
About climate change it is now widely accepted
that the earth’s temperature is increasing, as confirmed by warming of the oceans, rising sea levels,
glaciers melting, sea ice retreating in the Arctic and
diminished snow cover in the Northern
Hemisphere. Moreover, changes are also occurring
in the amount, intensity, frequency and type of precipitation as well as the increase of extreme weather events, like heat waves, droughts, floods and hurricanes. The Working Group I to the 4th Assessment
Report of the Intergovernmental Panel on Climate
Change (IPCC) states “most of the observed increase
in globally averaged temperatures since the mid20th century is very likely due to the observed increase in anthropogenic greenhouse gas concentrations” [13]. However, observational evidence indicates that recent regional changes in climate, particularly temperature increases, have already affected
a diverse set of physical and biological systems in
many parts of the world [10,11,13].
Exposure to air pollution enhances the airway response to inhaled allergens in susceptible subjects.
Indeed, in most industrialized countries people
who live in urban areas tend to be more affected by
allergic respiratory diseases than those in rural areas
[14,15].
An individual’s response to air pollution depends
on the source and components of the pollution, as
well as on climatic agents. Indeed, some air pollution-related episodes of asthma exacerbation are
due to climatic factors that favour the accumulation
of air pollutants at ground level [7,11] and some
cities are continuously affected by black smog
caused by motor vehicles. There is evidence that
living near high traffic roads is associated with deterioration of respiratory health. Road traffic with its
gaseous and particulate emissions is currently, and
likely to remain for several years, the main contributor to air pollution in most urban areas [512,16,17].
Air pollution is associated with many signs of asthma exacerbation, e.g. increased bronchial hyperresponsiveness, increased medication use, and increased visits to emergency departments and hospital admissions [16-19]. Time series data show that
traffic-related air pollution in urban areas has adverse effects on mortality from respiratory and cardiovascular disease [20-29].
The most abundant components of air pollution in
urban areas with high levels of vehicle traffic are inhalable particulate matter (PM), nitrogen dioxide
and ozone. The effects of air pollutants on lung
function depend on the type of pollutant and its environmental concentration, the duration of exposure and the total ventilation of exposed persons.
Aeroallergens, such as those derived from pollens
and fungal spores in outdoor atmosphere, are able
to induce bronchial obstruction in predisposed subjects and pollen allergy is widely used to study the
interrelationship between air pollution and respiratory allergy in atopic subjects [27,30-33].
Airborne pollen grains, plant debris of very small
size [31] and pollen grains ruptured during thunderstorms [32-36] can cause allergic respiratory symptoms in predisposed subjects. They also interact
with other airborne contaminants in producing
these effects.
There is a hypothesis that air pollutants promote airway sensitization by inducing changes in the allergenic content of airborne particles carrying allergens [29-33,37]. There is also evidence that airway
mucosal damage and impaired mucociliary clearance induced by air pollution may facilitate the
penetration and access of inhaled allergens to the
cells of the immune system [29-33,37-40].
However, patients affected by asthma frequently experience rhinitis and thus they breathe through the
mouth, bypassing the nasal function and so facilitating the penetration of pollutants and aeroallergens
into the lower airways [40-42].
G D’Amato
Climate change, air pollution, and respiratory health – Cambiamenti climatici, inquinamento e patologie respiratorie
Vi è inoltre evidenza che gli asmatici sono a maggior rischio
di sviluppo di riacutizzazioni dell’ostruzione bronchiale con
l’esposizione alle componenti dell’inquinamento atmosferico
di tipo gassoso (ozono, biossido di azoto, biossido di zolfo) e
particolato. È improbabile che possa essere chiamata in causa
una modificazione della predisposizione genetica per giustificare l’aumentata incidenza di malattie allergiche, perché le
modificazioni genetiche richiedono diverse generazioni per
esprimersi. Sono quindi i fattori ambientali come le modificazioni climatiche, l’inquinamento dell’ambiente esterno e domestico a potere spiegare almeno in parte la maggiore frequenza di malattie respiratorie su base allergica e di asma.
Poiché le concentrazioni di allergeni inalati e di inquinamento
atmosferico vanno spesso di pari passo, una maggior risposta
IgE-mediata agli aeroallergeni ed una maggior flogosi delle
vie aeree può dar conto della maggior frequenza di forme allergiche respiratorie e di asma bronchiale.
Le società scientifiche come la European Academy of Allergy
and Clinical Immunology, la European Respiratory Society e la
World Allergy Organization hanno organizzato comitati e task
force per produrre documenti che mettono a fuoco questa
materia, raccomandando misure di tipo preventivo.
Air pollution of urban areas
The most abundant pollutants in the atmosphere of
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urban areas are ozone, nitrogen dioxide and respirable PM. Sulphur dioxide is an addition of industrial areas. Aeroallergens are carried and delivered
by fungal spores or by plant-derived particles (pollens, components of paucimicronic diameter and of
vegetal nature, e.g. soybean dust, ricinus, etc.).
Ozone
Ozone is the main component of photochemical
oxidants and “Summer smog”, and probably accounts for up to 90% of total oxidant levels in cities
that enjoy a mild sunny climate such as those of the
Mediterranean area, California, etc. Ozone is generated at ground level by photochemical reactions
involving ultraviolet radiations on atmospheric mixtures of nitrogen dioxide and hydrocarbons deriving
from vehicle emissions. Safety standards for ozone
levels are frequently exceeded in southern Europe,
in particular in Mediterranean countries. About 4060% of inhaled ozone is absorbed in the nasal airways, while the remainder reaches the lower airways and it can affect both the upper and lower respiratory tract.
Inhalation of high concentrations of ozone induces
deterioration in lung function and increased airway
reactivity to nonspecific and specific bronchoconstrictor agents and is related to an increased risk of
asthma exhacerbation in asthmatic patients [4352]. Increased atmospheric concentrations of
ozone and nitrogen dioxide have been linked to increases in respiratory morbidity and in hospital admissions for asthma in children and adults [43-52].
Ozone exposure has also been reported to have a
priming effect on allergen induced responses as
well as an intrinsic inflammatory effect in the airways of allergic asthmatics [49-52]. Ozone produces an increase in intracellular reactive oxygen
species and in epithelial cell permeability, which
could facilitate penetration of inhaled allergens and
toxins in the airways, so inducing an increased release of inflammatory mediators (interleukin [IL]-1,
IL-6, IL-8, tumor necrosis factor [TNF]-alpha, etc.).
Vagaggini et al. [51] showed that ozone’s more dramatic effect in asthmatic subjects is most likely a result of existing chronic inflammation in the lower
airways [51].
As the primary mechanism for ozone-induced
decrements in FEV1, a neurally-mediated inhibition
of inspiratory effort involving C-fibres rather than
bronchoconstriction has been proposed [45,52].
Because ozone-induced airway inflammation may
last several days and ozone-related asthma exacerbations often occur several days after exposure, it
seems feasible that ozone-induced enhancement of
pre-existing airway inflammation enhances susceptibility to obstructive symptoms and asthma exacerbations.
It has long been hypothesized that ozone and other
pollutants may increase the susceptibility of allergic
individuals to antigens to which they are sensitized,
and there are animal studies to support such an effect [49-52]. It has been reported that ozone is associated with an increased risk of asthma develop-
ment among children in California playing outdoor
sports. Thus, air pollution and outdoor exercise
could contribute to the development of asthma in
children by increasing airway inflammation and airway responsiveness [53].
Nitrogen dioxide
Like ozone, nitrogen dioxide is an oxidant pollutant, although it is less chemically reactive and thus
probably less potent. Nitrogen dioxide (NO2) is a
precursor of photochemical smog, is found in outdoor air in urban and industrial regions and, in conjunction with sunlight and hydrocarbons, results in
the production of ozone. Automobile exhaust is the
most significant source of outdoor NO2, although
power plants and other sources that burn fossil fuels
also release NO2 into the environment. The most
significant exposure to NO2 occurs indoors in conjunction with the use of gas cooking stoves and
kerosene space heaters. Most ambient NO2 is generated by the burning of fossil-derived fuels.
Outdoor levels of NO2 are not usually associated
with notable changes in bronchial function in asthmatic patients. Controlled exposure studies of subjects with asthma have produced inconsistent results regarding the ability of NO2 to enhance nonspecific airway responsiveness with some evidence
of a subgroup with increased sensitivity [54-56].
Results of epidemiologic studies suggest that exposure to NO2 is associated with increased prevalence
of asthma and rhinitis and with acute decrements in
lung function in asthmatic subjects [57-60].
Sulphur dioxide
Sulphur dioxide is released into the atmosphere primarily as a result of industrial combustion of highsulphur-containing coal and oil. It is primarily generated from the burning of sulphur-containing fossil
fuel and it has been demonstrated to induce acute
bronchoconstriction in asthmatic subjects at concentrations well below those required to induce this
response in healthy subjects [61-63]. In contrast to
ozone, the bronchoconstrictor effect of inhaled sulfur dioxide in individuals with asthma occurs after
extremely brief periods of exposure, especially with
oral breathing and high ventilatory rates, as in exercise [64-65]. Significant responses are observed
within 2 minutes, maximal response is seen within
5 to 10 minutes. There can also be spontaneous recovery (30 minutes after challenge) and a refractory
period of up to 4 hours, whereas repeated exposure
to low levels of sulfur dioxide results in tolerance to
subsequent exposure. Pharmacologic studies suggest that the effect is a cholinergically-mediated
neural mechanism. Moreover, sulfur dioxide exposure enhances responses to other environmental
agents that exacerbate bronchospasm.
Particulate matter
Particulate matter (PM) is the most serious air pollution problem in many cities and towns and it appears to be the component of air pollution most
consistently associated with adverse health effects.
Diesel exhaust particulate
Diesel exhaust particulate (DEP) accounts for most
of the airborne particulate matter (up to 90%) in the
atmosphere of the world’s largest cities [76]. It is
characterized by a carbonaceous core in which
18,000 different high-molecular-weight organic
compounds are adsorbed. DEP presents a large
number of particles, about 100 times more particles
per mile than petrol engines of equivalent power.
Although diesel engines emit far less carbon dioxide than petrol engines, they emit over 10 times
more nitrogen dioxide, aldehydes and respirable
particulate matter than unleaded petrol engines and
over 100 times more than engines fitted with catalytic converters [77]. DEP exerts its effect by way
of specific activities of chemical agents, i.e. polyaromatic hydrocarbons. The particles are deposited on the mucosa of the airways, and by virtue of
their hydrophobic nature, the aromatic hydrocarbons allow them to diffuse easily through cell membranes and bind to a cytosolic receptor complex.
Through the subsequent nuclear action, aromatic
hydrocarbons can modify the growth and the differentiation programmes of cells [77-78].
Acute exposure to diesel exhaust causes irritation of
the nose and eyes, headache, lung function
changes, respiratory changes, fatigue and nausea,
while chronic exposure is associated with cough,
sputum production and lung function decrements
[77,79-84]. Experimental studies have shown that
DEP causes respiratory symptoms and is able to
modify the immune response in predisposed animals and humans [77,79-81]. In this context DEP
seems to exert an adjuvant immunological effect on
IgE synthesis in atopic subjects thereby influencing
sensitization to airborne allergens. Rudell et al. [84]
showed that healthy volunteers exposed to DEP had
a greater number of alveolar macrophages, neutrophils and T lymphocytes in BAL than did controls. Other studies confirmed the effects favouring
airway inflammation and demonstrated an atopyenhancing effect of diesel exhaust [81-84]. DiazSanchez et al. [81-82] studied the effect of DEP on
antigen in ragweed-sensitive subjects challenged
(nasal provocation test) with DEP, the major ragweed allergen (Amb a 1) and a combination of DEP
and Amb a 1. Provocation with ragweed led to an
increase in both total and ragweed-specific IgE in
nasal lavage fluid measured 18 hours, 4 days and 8
days post-challenge. The DEP challenge increased
the concentration of ragweed-specific IgE 16-fold
versus concentrations observed after challenge with
ragweed alone. The same authors showed that combined exhaust particulate and ragweed allergen
challenge markedly enhances human in vivo nasal
ragweed-specific IgE and skews cytokine production to a T-helper cell 2-type pattern [82]. All these
results indicate that DEP plays a role in the enhanced allergic inflammatory response [77,79-84].
Regarding the DEP-related allergic respiratory disease, DEP can adsorb aeroallergens released by
pollen grains and can prolong the retention of the
allergen so as to provide for an enhanced IgE-mediated response [85]. The data on DEP are of particular interest in view of the increasing percentage of
new cars with diesel engines in industrialized countries. Diesel-powered cars are usually promoted as
being environmentally friendly because they produce up to 25% less carbon dioxide, which is a major contributor to global warming. The new diesel
cars with new filters appear to reduce the production of PM at risk for exposed subjects.
G D’Amato
In other words, PM is a major component of urban
air pollution. It is a mixture of solid and liquid particles of different origin, size and composition
among which pollen grains and other vegetable particles carrying allergens and mold spores. Inhalable
PM that can reach the lower airways is measured as
PM10 (less than 10 µm in aerodynamic diameter)
and PM2.5 (less than 2.5 µms) [66-69]. Human lung
parenchyma retains PM2.5, while particles larger
than 5 µm and < 10 µm only reach the proximal airways where they are eliminated by mucociliary
clearance if the airway mucosa is intact [66-69]. In
many geographical areas particulate air pollution is
significantly associated with enhanced mortality
from respiratory and cardiovascular diseases, exacerbation of allergic asthma, chronic bronchitis, respiratory tract infection and hospital admissions [2029]. The World Health Organization estimates that
inhalation of particulate matter is responsible for
500,000 excess deaths each year worldwide [1].
Seaton et al. [70] hypothesized that fine particulate
matter found in urban areas, by penetrating deep into airways, is able to induce alveolar inflammation
which is responsible for variation in blood coagulability and release of mediators favouring acute
episodes of respiratory and cardiovascular diseases.This observation has been validated by recent
studies [26-28].
To try to find an explanation for the acute respiratory effects associated with inhalable particulate matter, the same authors [71] suggested that transition
metals in the particles damage airways thereby generating free radicals. In particular, iron, which generates hydroxyl radicals, seems to be responsible for
the adverse respiratory effects [72]. Other transition
metals (chromium, cobalt, copper, manganese,
nickel, titanium, vanadium and zinc) derived from
various urban or combustion source samples have
also been correlated to radical activation and lung
injury in animal experiments [73-75].
Plant-derived allergens
Respiratory allergy induced by antigens released by
pollen grains is very common [86]. For instance, between 8% and 35% of young adults in countries of
the European Community have IgE serum antibodies to grass pollen allergens [87]. The cost of pollen
allergy in terms of impaired work fitness, sick leave,
physician visits and drug prescriptions is very high.
Subjects living in urban areas tend to be more affected by plant-derived respiratory disorders than
those living in rural areas [14,15]. Ishizaki et al.
[88] observed that respiratory allergy was more
MRM
31
prevalent in subjects living near busy roads than in
subjects living in areas with higher atmospheric
concentrations of pollen allergens but with less traffic. Various studies suggest that there is an interaction between air pollutants and allergens that exacerbates the development of atopy and the respiratory symptoms of allergic disease. These results
should be interpreted with caution because they
can be affected by several factors that were not examined. In a time-series study Brunekreef et al. [27]
found a strong association between the day-to-day
variation in pollen concentrations and deaths due
to cardiovascular disease, chronic obstructive pulmonary disease, and pneumonia.
To prevent pollen allergy, an ideal (but hardly feasible approach) is to minimize the risk of contact with
these agents by moving to a non-risk area on the basis of pollen-calendars. Pollen grains are the primary carriers of pollen allergens, which explains
why the symptoms typical of hay fever are located
in the eyes, nose and nasopharynx. Differently, allergic asthma in pollen-sensitive patients is an enigma because intact pollen grains, which measure
over 10 µm in diameter, are too large to enter the
lower airways [31-33,89]. Moreover, in many instances peak asthma symptom scores differ temporally from peak pollen counts, and early morning
symptoms sometimes precede later peaks in the
daily pollen cycle. The etiology of pollen asthma
and the discordance between pollen count and
bronchial symptoms was partially explained with
the identification of pollen allergens in microaerosol suspensions smaller than pollen grains [89],
which could be present in atmosphere before the
start and after the end of the season, so prolonging
the respiratory symptoms of sensitized patients. By
virtue of their small size, these paucimicronic particles can reach the peripheral airways with inhaled
air, so inducing asthma in sensitized subjects. Thus,
parts of an organism (in this case of vegetal nature)
other than pollen grains or spores contain significant allergen concentrations that are readily disseminated via an airborne route. These allergenic
paucimicronic particles act only as carriers for the
protein agent with antigenic property that causes
symptoms. Allergens have been detected in the
leaves and stems of allergenic plants [9,32]. They
may result from elution of allergens from pollen
grains with their later dispersion in microdroplets.
It is important also to note that, starting with pollen,
the interest in smaller airborne allergenic units now
embraces a variety of agents (e.g. house dust,
arthropod emanations, and animal allergens) of undefined or variable particle size [9,32]. The advent
of high speed impingers, which are very efficient in
collecting small aerosols on filters, has given impetus to the study of a variety of environmental agents,
and antigenic activity has been identified in both
micronic and submicronic fractions.
Thunderstorm-associated asthma in pollinosis
patients
Suphioglu et al. [90] and Knox et al. [85] found that
32 MRM
under wet conditions or during thunderstorms
pollen grains may, after rupture by osmotic shock,
release part of their content, including respirable,
allergen-carrying starch granules (0.5-2.5 µm) into
the atmosphere. ‘Thunderstorm-associated asthma’
was recognized over 15 years ago in Britain by
Packe and Ayres [91], who described an association
between a thunderstorm and an asthma outbreak
with 26 asthmatic subjects treated in Birmingham
Hospital in 36 hours compared with 2-3 cases in
the same time interval in the days preceding the
thunderstorm. Other asthma outbreaks during thunderstorms have been described in Melbourne,
Australia [92,93]. Also, this phenomenon was followed by a rapid increase in hospital or general
practitioner visits for asthma. No unusual levels of
air pollution were noted at the time of these epidemics but there was a strong association with grass
pollen. Grass pollens after rupture by osmotic shock
during thunderstorms release large amounts of
paucimicronic allergenic particles, i.e. cytoplasmatic
starch granules containing grass allergens. Because
of their very small size, starch granules can penetrate the lower airways and induce the appearance
of bronchial allergic symptoms. Other thunderstorm-associated asthma outbreaks have been reported: in London on the night between 24 and 25
June 1994 [94], in Wagga Wagga, Australia on 30
October 1997 [95], and in Naples on June 4 2004
[9,71,96]. The asthma outbreak of London was the
largest episode, with about 100 emergency visits to
several hospitals of London and southwest England.
Interestingly, in the London outbreak several patients examined, who were not known to be asthmatics or were affected only by seasonal rhinitis,
experienced an asthma attack. This explains why
grass induces mainly allergic rhinitis in sensitized
atopic subjects. In fact, being more than 30 µm, intact grass pollen grains can only reach the lower airways after rupture.
During the episode of thunderstorm-associated
asthma registered in Naples on 4 June 2004 (between 1.30 and 2.00 am), 6 adults (3 women and 3
men aged between 38 and 60 years) and a girl of 11
had attacks of severe bronchial asthma, which was
nearly fatal in one case. All patients received treatment in emergency departments and one was admitted to an intensive care unit for very severe
bronchial obstruction and acute respiratory insufficiency. However, also without outbreaks, frequently
pollinosis patients experience a deterioration of
their symptoms when thunderstorms or strong rains
start.
Plant derived carriers of aeroallergens
Among vegetal small particles carrying allergens
are the so-called Ubish bodies, paucimicronic
spheroidal structures which develop in the anthers
of higher plants [30,32,33,97,98]. Their function is
unknown. They generally occur in large numbers,
are usually only a few micrometers in diameter and
can contain allergens. Ubish bodies may be involved in the dispersal of pollen and their size is op-
Other aeroallergens responsible for epidemic
asthma in urban areas
Soybean dust could be responsible for outbreaks of
severe asthma that were first attributed to urban air
pollution. Examples are asthma epidemics in cities
with large industrial port facilities such as
Barcelona. From 1981 to 1987, 26 outbreaks of
asthma with 11 deaths occurred in Barcelona without any apparent relation to air pollution [99-103].
The causal agent was subsequently found to be soybean dust released into the air during unloading of
cargo into a harbour silo that was not equipped
with a dust-control device. Antò and colleagues
demonstrated that about 74% of epidemic cases
had specific IgE antibodies versus a commercial
soybean antigen in comparison with 4.6% of controls [99,101]. In addition, using the assays of urban
aerosols collected with high-volume samplers and
the RAST inhibition technique these authors
showed highly significant differences in the atmospheric content of soybean antigens between days
marked by the asthma epidemic and days free of an
excess of asthma crisis. The strong association between airborne soybean dust and asthma outbreaks
was reinforced by the results of studies showing
high airborne concentrations on epidemic days and
low values on nonepidemic days.
All these studies showed that asthma outbreaks
were a “point-source” epidemic. Protective measures (i.e. cargo unloading after filters were fitted to
the grain elevators) dramatically reduced airborne
allergen levels of soybean dust and asthma-related
visits to the emergency room [101]. The IgE serum
levels in exposed subjects also progressively decreased.
In Naples, more than 100 patients were admitted to
hospital for asthma on a single day in December
1993 [102]. This asthma outbreak coincided with
the unloading of a cargo of soybean. Interestingly,
neither in the Barcelona nor in the Naples outbreaks were there cases of severe asthma attacks in
children.
When the asthma epidemic which occurred in New
Orleans in 1969 [103,104] was reexamined [105],
it was found that the number of asthma attacks was
higher on days when ships carrying soybean were
anchored in the harbour. Attacks were also higher
in concomitance with air stagnation and with winds
carrying particles from two grain elevators. No association was observed between asthma attacks and
the presence of ships carrying wheat or corn.
Air pollution, climate changes and pollen-related
respiratory allergy
We still have much to learn about the effects of other climatic factors that seem to be important for
asthma, e.g. wind speed and transition of cold
fronts. It is well known that inhalation of cold air reduces lung function in asthmatics thus favouring
bronchoconstriction. Moreover, exercise in polluted
areas results in greater deposition of air pollutants,
including allergen-carrying allergens, in the lower
airways. Exercise increases oral breathing, total
ventilation and inertial impaction of inhaled particles in the airways. The role of climatic factors (e.g.
barometric pressure, temperature and humidity) in
triggering and/or exacerbating respiratory allergic
symptoms in predisposed subjects is still poorly understood and asthma attacks have been linked with
both low and high atmospheric pressure. More
studies are required to clarify the role of weather in
morbidity and mortality for respiratory allergy.
There is also the thorny question as to how increasing levels of greenhouse gases and concomitant climate changes will influence the frequency and
severity of pollen-induced respiratory allergy. A variety of direct and indirect evidence suggests that
climate changes may affect pollen release and consequently pollen-related asthma [9,11,12]. Climate
variations are likely to influence vegetation with
consequent changes in growth, reproductive cycle,
etc. as well as in the production of allergenic pollen
(seasonal period and intensity) with a greater proliferation of weed species. Climate changes vary from
region to region: some areas will be subject to increases in ultraviolet radiation and or rainfall frequency and other areas to reductions.
In Italy in the 20 years from 1981 to 2000 the average mean temperature has increased by about
0.6°C: this warming is accompanied by an average
reduction of 15% in rainfall, and the rain is concentrated is a shorter period causing more violent rainstorms [106]. How are allergenic plants responding
to these changes? The increased temperature in
winter and spring has brought about early pollination, and the increased summer temperature has resulted in a prolonging of the pollination of herbaceous, allergenic plants. Pollen seasons, and therefore seasonal allergic symptoms, tend to be longer
in warmer years. The prolonging of autumn could
prolong the presence of fungal spores in the atmosphere. Due to the ‘urban climate effect’ (heating
caused by high building density and soil sealing),
pollination can occur 2-4 days earlier in urban than
in rural areas.
Vegetation reacts with air pollution over a wide
G D’Amato
timal for penetration into lower airways.
Besides providing an explanation for bronchial
asthma symptoms in pollinosis patients, a practical
offshoot of these studies is that the traditional
“pollen count” may be misleading as an index of
outdoor allergen exposure in particular situations.
In fact, the pollen count technique consists of examination of pollen grains collected in volumetric
“pollen traps” under the microscope and the definition of their concentration per cubic meter of air,
whereas immunochemical methods are required to
identify the allergens carried by airborne microparticulate matter such as starch granules and Ubish
bodies [33,97]. In an attempt to establish correlations with clinical symptoms and to estimate the
different risks for asthma and hay fever in pollinosis
subjects it would be interesting to quantify atmospheric variations in these biological aerosols and in
their allergenic activity.
MRM
33
range of environmental conditions and pollutant
concentrations. Several factors influence the interaction, including type of air pollutant, plant species,
nutrient balance, soil conditions and climatic factors. At low levels of exposure for a given species
and pollutant, no significant effect is observed.
However, as the exposure level increases, there
may be biochemical alterations of the plants [107110]. Plants can absorb pollutants through the
leaves or through the root system. In the latter case,
deposition of air pollutants on soils can alter the nutrient content of soil in the proximity of the plant
thus leading to indirect or secondary effects of air
pollutants on vegetation. Metabolic variations affect
the plant’s structural integrity and there are probably changes in the pollen proteins, including those
acting as allergens.
Air pollution can influence the plant allergenic content, and by affecting plant growth it can affect both
the amount of pollen produced and the amount of
allergenic proteins contained in pollen grains. The
pollen of plants stressed by air pollution express enhanced levels of allergenic proteins [109]. Pollen
grains collected from roadsides with heavy traffic
and from other areas with high levels of air pollution are covered with large numbers of microparticulates (usually less than 5 µm in diameter) and there
is a hypothesis that interaction between air pollution components and pollen allergens alters the
antigenicity of pollen allergens.
CONCLUSIONS
Both the prevalence and severity of respiratory allergic diseases such as rhinitis and bronchial asthma have increased in recent years and indoor and
outdoor air pollution and climate changes are im-
plicated in this increasing frequency. Increasing
production of CO2 with climate changes, urbanization with its high levels of vehicle emissions and
westernized lifestyle parallel the increase in respiratory allergy in most industrialized countries. People
living in urban areas tend to be more affected by the
disease, than those living in rural areas. In atopic
subjects, exposure to air pollution increases airway
responsiveness to aeroallergens. Pollen grains, seem
to be a useful model to study the interrelationship
between air pollution and respiratory allergic diseases, and in atmosphere and in the airways an interaction has been observed between pollen allergens and air pollution [106-110]. By adhering to
the surface of pollen grains, components of air pollution could modify their antigenic properties.
However, the airway mucosal damage and the impaired mucociliary clearance induced by air pollution may facilitate the penetration and the access of
inhaled allergens to the cells of the immune system,
and so promote airway sensitization. Consequently
an increased IgE-mediated response to aeroallergens and enhanced airway inflammation favoured
by air pollution could account for the increasing
prevalence of allergic respiratory diseases in urban
areas. Among the measures for reducing air pollution and its effects are:
- reducing the private traffic in towns by promoting
public transportation;
- controlling vehicle emissions;
- planting in urban areas non-allergenic trees such
as pinaceae, palmaceae and ulmaceae, avoiding
cupressaceae, betulaceae and oleaceae [11,86].
CONFLICT OF INTEREST STATEMENT: The author has no conflict of interest to declare in relation to the subject matter of
this manuscript.
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Review / Rassegna
Fit for high altitude: are hypoxic challenge
tests useful?
Idoneità all’alta montagna: i test all’ipossia
sono davvero utili?
Heinrich Matthys
Medical Director emeritus, University Hospital Freiburg, Freiburg, Germany
ABSTRACT
Altitude travel results in acute variations of barometric pressure, which induce different degrees of hypoxia, changing the
gas contents in body tissues and cavities. Non ventilated air
containing cavities may induce barotraumas of the lung
(pneumothorax), sinuses and middle ear, with pain, vertigo
and hearing loss. Commercial air planes keep their cabin pressure at an equivalent altitude of about 2,500 m. This leads to
an increased respiratory drive which may also result in symptoms of emotional hyperventilation. In patients with preexisting respiratory pathology due to lung, cardiovascular,
pleural, thoracic neuromuscular or obesity-related diseases
(i.e. obstructive sleep apnea) an additional hypoxic stress
may induce respiratory pump and/or heart failure. Clinical
pre-altitude assessment must be disease-specific and it
includes spirometry, pulsoximetry, ECG, pulmonary and systemic hypertension assessment. In patients with abnormal
values we need, in addition, measurements of hemoglobin,
pH, base excess, PaO2, and PaCO2 to evaluate whether O2- and
CO2-transport is sufficient.
Instead of the hypoxia altitude simulation test (HAST), which
is not without danger for patients with respiratory insufficiency, we prefer primarily a hyperoxic challenge. The supplementation of normobaric O2 gives us information on the
acute reversibility of the arterial hypoxemia and the reduction of ventilation and pulmonary hypertension, as well as
about the efficiency of the additional O2-flow needed during
altitude exposure. For difficult judgements the performance
of the test in a hypobaric chamber with and without supplemental O2-breathing remains the gold standard. The increasing numbers of drugs to treat acute pulmonary hypertension
due to altitude exposure (acetazolamide, dexamethasone,
nifedipine, sildenafil) or to other etiologies (anticoagulants,
prostanoids, phosphodiesterase-5-inhibitors, endothelin
receptor antagonists) including mechanical aids to reduce
periodical or insufficient ventilation during altitude exposure
(added dead space, continuous or bilevel positive airway pres-
sure, non-invasive ventilation) call for further randomized
controlled trials of combined applications.
Keywords: Altitude exposure, drug therapy, hypoxic and
hyperoxic challenge tests, mechanical aids for insufficient
ventilation, pulmonary hypertension.
RIASSUNTO
Portarsi in alta quota implica variazioni in acuto della pressione barometrica che comportano vari gradi di ipossia, modificazioni nel contenuto di gas nei tessuti corporei e nelle cavità.
L’aria non ventilata contenuta nelle cavità può indurre barotraumi del polmone (pneumotorace), dei seni paranasali e
dell’orecchio medio, con possibile dolore, vertigine e perdita
dell’udito. Gli aerei commerciali pressurizzano le loro cabine
ad un equivalente di circa 2.500 m di altitudine. Questo comporta un aumento del drive respiratorio che può giungere a
dare gli stessi sintomi dell’iperventilazione su base emotiva.
Nei pazienti con patologie respiratorie preesistenti, con malattie polmonari, cardiovascolari, pleuriche, neuromuscolari
toraciche o correlate all’obesità (es.: apnee ostruttive nel sonno) lo stress ipossico supplementare può portare all’insufficienza respiratoria o cardiaca.
La valutazione clinica prima dell’esposizione alla quota deve
perciò essere specifica per la patologia ed includere spirometria, pulsossimetria, ECG, valutazione della pressione arteriosa sistemica e polmonare. Nei pazienti con valori anormali si
rendono necessarie ulteriori valutazioni di emoglobina, pH,
eccesso di basi, PaO2, e PaCO2 per valutare se il trasporto di O2
e di CO2 sia sufficiente.
Piuttosto che il test di simulazione dell’ipossia da alta quota
(HAST), che non è privo di pericoli per i pazienti in insufficienza respiratoria, preferiamo in prima battuta un test iperossico. Infatti il supplemento di O2 in normobaria ci fornisce le
informazioni sulla reversibilità acuta dell’ipossiemia arteriosa
e sulla riduzione di ventilazione e pressione arteriosa polmonare, così come sull’efficienza del supplemento di O2 necessa-
+ Heinrich Matthys
Department of Pneumology, University Hospital Freiburg
Hochrüttestr. 17, D-79117, Freiburg, Germany
Data di arrivo del testo: 13/12/2010 - Accettato per la pubblicazione: 12/01/2011
38 MRM
Parole chiave: Alta quota, farmacoterapia, ipertensione polmonare, test all’ipossia e all’iperossia, ventilatori polmonari.
INTRODUCTION
Altitude exposure became an increasingly common
phenomenon during the 20th century due to the popularity of various sporting activities (skiing, mountaineering, trekking) and greater availability of transport facilities (air planes, cars, trains, cable cars).
It is the purpose of this article to focus on the possible dangers during acute altitude exposure of normal subjects and patients suffering in particular
from respiratory disorders. To be able to advise on
health issues and the risk of possible accidents, the
physician should not only know the patient’s current medical condition but also the duration and the
type of the intended altitude exposure with its specific hazards [1]. We distinguish illnesses due to
rapid barometric pressure changes according to
whether they occur under conditions of acute, subacute or chronic altitude exposure and whether they
occur in normal subjects or patients with pre-existing lung and/or respiratory pump diseases (Figure 1).
ACUTE ALTITUDE-RELATED ILLNESSES
Acute altitude exposure
A sudden cabin pressure loss of commercial air
planes at altitudes above 5,000-6,000 m or a rapid
ascent to this altitude breathing air under ambient
pressure can lead to decompression illness similar
to that recognised in diving accidents. Acute hypoxic exposure (balloon rides) may induce signs of
emotional hyperventilation, problems to speak, to
calculate followed by dizziness, nausea and vomiting, but also uncritical euphoria. This situation can
be simulated in hypobaric chambers to demonstrate
the danger of altitude hypoxia to pilots and to study
patients at risk with or without O2 breathing [2-5].
Acute mountain sickness (AMS)
AMS affects 10-40% of lowlanders ascending to
moderate altitudes above 2,500 m and 60% of subjects who reach altitudes of 4,000-5,000 m within a
few hours. Physical fitness does not protect against
any high altitude related illnesses. The incidence of
H Matthys
Altitude exposure and hypoxic challenge tests – Esposizione all’alta quota e test all’ipossia
rio durante l’esposizione in alta quota. In caso di risultato inconclusivo la ripetizione del test con e senza O2 in camera
ipobarica rimane il gold standard.
Il crescente numero di farmaci per il trattamento dell’ipertensione polmonare acuta da alta quota (acetazolamide, desametasone, nifedipina, sildenafil) e da altre eziologie (anticoagulanti, prostanoidi, inibitori della fosfodiesterasi-5, antagonisti dei recettori per l’endotelina), compresi i supporti meccanici per ridurre la ventilazione a carattere periodico o insufficiente durante l’esposizione all’alta quota (spazio morto,
pressione positiva continua o bilevel, ventilazione non invasiva) richiedono decisamente un maggior numero di studi controllati e randomizzati sulle loro azioni combinate.
FIGURE 1: REDUCTION OF O2- AND N2-PARTIAL PRESSURES IN INSPIRED AIR AT BTPS CONDITIONS (100% SATURATED
WATER VAPOUR PRESSURE DEPENDS ONLY ON TEMPERATURE) WITH INCREASING ALTITUDE EXPOSURE (DECREASING
BAROMETRIC PRESSURE)
m Alt.
Tracheal inspired air
10,000
Water vapour
5,000
Air travel induces hypoxia including
de- and recompression of gas in body
tissues and air containig cavities.
P (kPa)
Altitude diseases due to hypoxia can be compensated by O2-breathing and/or travelling in pressurized cabins.
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39
AMS depends on ascent rate, whether the journey is
made by climbing or travelling by plane (La Paz,
Bolivia airport is at 4,100 m), car or train (the
Chinese Tibet railway reaches 5,000 m).
The AMS-symptoms start generally 6-12 hours after
arrival at altitude with headaches (in mild to moderate cases with good response to analgesics), loss
of appetite, nausea, vomiting, fatigue, insomnia and
weakness. The Lake Louise scoring system allows
the severity of AMS to be graded (see Table 1) [6].
The heel-to-toe walking test is an additional check
of objective neurological signs such as ataxia. Mild
to moderate AMS disappears within 1-2 days with
ongoing acclimatisation. The development of somnolence and cognitive defects are signs of high altitude cerebral edema (HACE), which may result in
progressive unconsciousness, coma and death within 1-3 days due to herniation of the brain. It requires
adequate treatment whenever possible by immediate descent to lower altitude. The rapid response of
symptoms (headache with no response to analgesics, low grade fever, dizziness, ataxia, altered
consciousness, confusion, impaired mentation,
drowsiness, stupor, coma) to oxygen and steroids
are consistent with the patho-mechanism of a vasogenic edema [7].
High altitude pulmonary edema (HAPE)
HAPE develops at altitudes above 2,500 m. It is a
high-permeability pulmonary edema caused by elevated pulmonary capillary pressures due to alveolar
hypoxia [8]. It may affect primarily only one lung.
The initial onset is usually at night and not related
to the frequently observed periodic breathing at altitude, which is a major cause of poor sleep quality.
This so-called Cheyne-Stokes breathing is common
in normal subjects at altitude and disappears, like
AMS, during the first three nights. Chronic periodic
breathing has also been observed above 4,500 m
lasting for weeks.
Recent studies showed that HAPE is more frequent
in subjects with patent foramen ovale (PFO) who
develop at altitude an increasing right to left shunt
due to the hypoxic pulmonary vasoconstriction. In
general the mean O2-saturation at normal barometric pressures is lower in subjects who developed
HAPE at altitude compared to HAPE-resistant
climbers. It is not clear whether closure of PFO prevents HAPE in these patients.
The symptoms of HAPE are dry cough, decreased
exercise performance, dyspnea at rest, orthopnea,
cyanosis, tachypnea (> 25 breaths/min), tachycardia
(> 100 beats/min), low grade fever, crackles on pulmonary auscultation and ultimately hemoptysis and
death.
Prevention of altitude related illness
A slow and gradual ascent with sufficient time and
a recreational sleep before ascent is the best strategy for successful acclimatisation. Also the sleeping
altitude prior to higher exposures and the individual
susceptibility is important. To prevent altitude-related sickness, not more than a 500 m increase of
40 MRM
sleeping altitude per day above 2,500 m is recommended, albeit there is little evidence to support
this. For a safe ascent, the general recommendation
is: climb high, sleep low, avoid doing more physical
exercise than needed. If this is not possible for logistic or other reasons a prophylactic pharmacological
treatment to prevent symptoms of AMS, periodic
breathing and non-recreational sleep is recommended: acetazolamide (Diamox®) 125 mg the
evening before ascent above 2,500 m and later
twice daily for a stay of some days. Possible side effects are gastrointestinal symptoms and paresthesias. Dexamethasone 4 mg can be taken the
evening before ascent and later twice daily, especially in patients with a history of asthma and for
prevention of HACE and HAPE. In subjects with a
history of HAPE, 30-40 mg of slow release nifedipine may be given in addition. Mountaineers with severe sleep disordered breathing at altitude improve
their nocturnal sleep quality by using benzodiazepines and/or a fitted mask with a dead space of
500 ml [9].
Management of manifest high altitude diseases
Mild and moderate AMS: Rest, avoidance of exertion, acclimatisation, analgesia, antiemetics, and
azetazolamide 250 mg twice daily until descent are
recommended. Treatment of periodic breathing and
sleep disturbances is also primarily with acetazolamide which stabilizes nocturnal O2-saturation, reduces awakenings and hence improves sleep quality. In addition benzodiazepines taken before sleeping (Tenazepam® 10 mg) result in a significant decrease of periodic breathing without reduction of
next-day reaction time, wakefulness, cognition and
AMS-symptoms. Immediate descent is generally not
indicated in mild forms of AMS.
Severe AMS and HACE: Immediate descent below
2,500 m is recommended. If available, O2 with or
without pressure bag should be administered. Drug
therapy consists of acetazolamide 125 mg twice
daily, or dexamethasone 8 mg and later 4 mg every
6 hours.
HAPE and/or HACE: O2 breathing in- or outside a
pressure bag, and 10-20 mg slow release nifedipine
and 8 mg dexamethsone every 6 hours are recommended [10]. Against headaches and pulmonary hypertension, sildenafil should be administered
(Revatio®, Viagra®) as a vasodilator [11]. Immediate
descent below 2,500 m is recommended whenever
possible. In all cases, dehydration is a risk and it is
important to ensure a careful control of fluid balance.
SUBACUTE AND CHRONIC MOUNTAIN SICKNESS
(CMS)
Some persons do not acclimatize to altitudes of
2,500-5,000 m. In these patients AMS-symptoms
and sleep disturbances due to periodic breathing
persist. Other subjects apparently well adapted to
these altitudes for many months or years develop
CMS, also called Monge’s disease, characterized by
excessive production of red cells (with the risk of
ALTITUDE EXPOSURE WITH PRE-EXISTING
RESPIRATORY DISEASES
Diseases of the lung and/or respiratory pump affect
the O2 and CO2 transport which is further impaired
by altitude exposure. Prophylactic recommendations and measures require disease-specific evaluation of these patients prior to high altitude travel.
The British Thoracic Society (BTS) recommendations give detailed advice for doctors dealing with
patients suffering from respiratory disorders who are
planning air travel. Two billion passengers currently
fly worldwide each year on commercial planes,
about 5% having problems [13,14].
Flying with no or partial compensation of the environmental barometric pressures at cruising altitudes
should be known in advance as well as the intended and final altitude of the travel (landing place).
Previous episodes of complications (the need for
supplemental oxygen, pulmonary hypertension,
asthma attacks, emotional hyperventilation, thrombo-embolic and cardiac diseases), decompression
and recompression symptoms during altitude travel
(difficulties in ventilating the middle ear and the sinuses), previous pneumothorax, obstructive and restrictive ventilatory defects and other causes of respiratory impairment should be carefully evaluated
(lung function tests and pulse oximetry) during the
medical consultation.
The BTS-guidelines recommend the hypoxic altitude simulation test (HAST) breathing 15% FiO2 under normobaric conditions in patients with respiratory insufficiency, if they present at sea level with a
SaO2 below 92% (PaO2 67-73 mm Hg) and/or additional risk factors (hypercapnia, FEV1 < 50% pred,
cardiac disease), if a hypobaric chamber exposition
(the ideal test) is not possible, which gives also information on possible barotraumata. We prefer in
these patients to administer first supplemental O2
(primum nihil nocere) and to control the possibility
to reach normal values of blood gases under normobaric conditions (Figures 2 and 3), if necessary in
the sleep laboratory, to exclude critical hypoventilation at higher O2-flows and the need for non invasive ventilation. A one night supplemental O2 challenge test provides also more meaningful information than the HAST about the long term adaptation
FIGURE 2: POLYSOMNOGRAPHY OF A COPD PATIENT
BREATHING 2 L/MIN NASAL AIR AT NIGHT
Sleep Stage
Awake
REM
I
II
III+IV
P[mm Hg]
60
PO2
50
PCO2
40
30
20
Pap,m
H Matthys
thromboembolic complications), hypoventilation,
fatigue, dyspnea, cyanosis, clubbing of the fingers
and leg edema with cor pulmonale. If the patient
descends to lower altitudes, preferably at sea level,
these symptoms disappear within months without
need for further treatment. It seems that increasing
the respiratory dead space by a fitted mask improves disordered breathing and might improve erythrocytosis and pulmonary hypertension also in
CMS [12]. The Pickwickian-like syndrome is characterized by a primary depression of breathing
without upper airway obstruction, such as in patients with obstructive sleep apnea syndrome
(OSAS). The diagnosis requires exclusion of other
causes of chronic respiratory insufficiency such as
chronic obstructive pulmonary disease (COPD),
obesity related hypoventilation or primary heart diseases causing polycythemia. CMS was first described in 1928 in mine workers living in the Andes
of south America at an altitude between 3,000 and
5,000 m. Chronic altitude exposure during pregnancy leads to a reduced birth-weight of the child.
Deliveries at altitudes above 2,500 m for non-residents (also in aircraft) have an increased risk of
neonatal death compared to non-hypoxic environments (early closure of ductus botalli and hypoxic
vasoconstriction of the placenta vessels). Children
exposed to high altitude have less periodic breathing at night than adults.
10pm 11pm12pm 1am 2am 3am 4am 5am 6am TIME
The patient shows a poor sleep quality due to frequent awakenings, and continuous hypercapnic (transcutaneous PCO2), hypoxic
(transcutaneous PO2) and pulmonary hypertension (mean pulmonary artery pressure, Pap,m) recordings.
FIGURE 3: THE SAME COPD PATIENT AS IN FIGURE 2
BREATHING 2 L/MIN SUPPLEMENTAL NASAL O2 AT NIGHT
Sleep Stage
Awake
REM
I
II
III+IV
P[mm Hg]
80
70
60
50
PO2
PCO2
40
30
Pap,m
20
10pm 11pm12pm 1am 2am 3am 4am 5am 6am TIME
Sleep quality and pulmonary hypertension are improved, arterial
hypoxemia is normalized with unchanged hypercapnia. This patient
could tolerate a 7 hour flight breathing 4 L/min nasal O2 at rest in
a commercial aircraft with a cabin pressure equivalent to an altitude
of 2,500 m without additional mechanical ventilatory support.
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41
of hypoxic patients who intend to travel for extended periods by plane, car or train in hypoxic environments. It may be important to correct for anemia
(Hb), because the O2-content of the blood is more
informative for assessing O2 delivery to the tissues
than SaO2 and PaO2-values. ECG recordings breathing supplemental nasal O2 (2 L/min) compared to
the night without shows in many COPD-patients also a dramatic fall of hypoxia-induced ventricular
premature beats (Figure 4).
Pneumothorax and other forms of “trapped air”
Air in the pleural cavity will expand during ascent
and cause tension pneumothorax if it cannot escape
through a chest tube, preferably equipped with a
one-way valve (Figure 5). Patients with residual
“trapped air” after thoracic surgery or incompletely
expanded lungs and captured air in pleural or other
closed air-containing spaces in the body should not
be exposed to rapid altitude changes.
Asthma
Exposure of patients to moderate altitude, (such as
in Davos, Switzerland or Denver, US) breathing dry
air without strenuous exercise tends to improve
asthmatic symptoms, probably because of the lower
allergen load. This is especially the case for house
dust mite sensitive subjects, because the house dust
mite cannot reproduce at altitude levels with low
humidity. Acute exposure to higher altitudes or
breathing cold air during exercise may trigger hyperventilation-induced or so-called exercise-induced asthma. Longer stays at altitudes of more
than 4,000 m generally reduce the bronchial hyperresponsiveness of mildly asthmatic patients [15].
Asthmatic subjects should maintain their pre-exist-
FIGURE 4: REDUCTION OF VENTRICURALR PREMATURE
BEATS (VPBs) DURING 2 L/MIN O2 BREATHING AT NIGHT IN
13 COPD PATIENTS
log Number of ventricular premature beats
8 p.m. - 6 a.m. (n = 13)
1000
Lown`s classification
of VPBs
100
Grade 0 : no VPBs
I : < 30 VPBs / hour
II : > 30 VPBs / hour
III : multiform VPBs
10
A multifocal VPBs
B bigeminus
IV : repetitive VPBs
A pairs (couplets)
B runs >3 in sequence
V : early VPBs (R on T) 1
air
2 L/min O2
The ECG recordings during the night when breathing 2 litres nasal
O2/min compared with the night breathing only air show a significant reduction of ventricular premature beats in all 13 COPD
patients and allow an additional risk evaluation (vis-à-vis Lown`s
classification) of the intended altitude exposure.
42 MRM
FIGURE 5: PNEUMOTHORAX MANAGEMENT FIT FOR HIGH
ALTITUDE TRANSPORT
Closed (non-ventilated) air spaces expand with increasing altitude
(= closed pneumothorax) and shrink during descent. Therefore
patients with pneumothorax need a chest tube with one way valve
which also prevents tension pneumothorax due to ambient pressure reduction during various altitude exposures (MATTHYS
DRAIN®).
ing ‘controller’ medication and be equipped with
an adequate supply of ‘rescue’ medications in the
form of inhaled bronchodilators and oral steroids
with appropriate instructions on their use. Breathing
cold dry air through a face mask may help to humidify and warm the air entering the upper airways
to BTPS-conditions and hence reduce bronchoconstriction and airway inflammation.
It is not uncommon in non-asthmatic subjects, as a
result of the increasing hypoxic drive, to develop
clinical signs of an emotional hyperventilation syndrome without bronchial obstruction and/or a vocal
cord dysfunction syndrome. It is possible to differentiate these “asthma” patients often clinically with
the help of a stethoscope.
Pulmonary hypertension due to other lung diseases
HAPE is a consequence of hypoxic pulmonary
vasoconstriction (HPV) and may be associated with
other diseases that cause a significant reduction of
the pulmonary vascular bed [16]. These include interstitial and vascular lung diseases (primary forms
of pulmonary hypertension and thromboembolic
pulmonary diseases). Patients with lung diseases associated with pre-existing pulmonary hypertension
(mean PAP > 25 mm Hg at rest) are advised against
high altitude travel. If travel at altitudes above 2,500
m is unavoidable, supplemental oxygen should be
administered in all patients who have pulmonary
hypertension at sea level. The non-hypoxic component of pulmonary hypertension should be treated
according to the therapy necessary for the specific
lung disease under normobaric conditions. If the
patient has no pre-existing pharmacotherapy for
pulmonary hypertension they should be given as
prophylaxis slow release nifedipine (20 mg b.i.d.)
All patients increased their mean PAP far more than normal subjects range. One patient had a pre-flight PAP of more than 30 mm Hg
(complete vascular recruitment) and could not tolerate the altitude exposure. Residual volume correlated best with PAP, all patients fell
asleep during the hypobaric exposure and showed a decrease in FEV1 from 1.08 to 0.78 L, the FEV1/IVC ratio diminishing from 45.7 to
40.2%. Arterial hypoxia and alveolar arterial O2-difference did not restore pre-exposure levels or mean PAP one hour after altitude exposure.
From [24].
for the duration of the stay at altitude. Alternatives,
depending on the underlying lung disease, include
sildenafil, tadalafil and dexamethasone to reduce
the hypoxic increase of pulmonary hypertension
due to altitude exposure. The acute therapeutic response of phosphodiesterase-5 inhibitors, corticosteroids, calcium channel blockers and other pulmonary vasodilators (bosentan, iloprost) makes it
impossible to predict the long-term effect of these
drugs on pulmonary artery pressure either at sea
level or at altitude (16).
COPD
The situation in which patients with COPD are most
often exposed to altitude is when flying (Figure 6),
but some times they are also exposed as long-term
residents. An important issue for them is the presence of bullous lung disease. In contrast to decompression in divers the expansion of these structures
during altitude exposure does not appear to be a
risk for pneumothorax. Increases of pulmonary artery pressure (pulmonary hypertension) are dependent on the initial pressure at departure level, the
possibility of recruitment of the pulmonary vascular
bed and the availability of oxygen to compensate
the alveolar hypoxia induced vasoconstriction.
H Matthys
FIGURE 6: MEAN PULMONARY ARTERY PRESSURE (PAP) ABOVE 30 MM HG EXCLUDES FROM FLYING WITHOUT O2 INCREASES
IN ALL 10 COPD PATIENTS EXPOSED TO A CABIN PRESSURE EQUIVALENT TO AN ALTITUDE OF 2,500 M ABOVE SEA LEVEL
Since non-invasive pulmonary artery pressure measurements with ECHO are not easy to perform in
COPD patients, spirometry is recommended. Patients
with FEV1 < 1,5 L should be assessed with pulsoximetry and an arterial CO2 measurement. These allow to
detect hypoxemia and hypercapnia today also non-invasively. If supplemental O2-breathing (2-4 L/min)
does not lead to a sufficient O2 saturation of 94%
(equivalent to 70-75 mm Hg PaO2) at the altitude level
of assessment, the patient should not be recommended for hypoxic exposures above 2,500 m.
The same evaluation criteria can be applied to patients with cystic fibrosis [17].
Patients with hypercapnic ventilatory failure (global
respiratory insufficiency) at sea level are generally
not able to sustain the increased hypoxic drive at altitude without additional oxygen breathing. Often
they need also ventilatory support (non invasive
ventilation). An optimal antiobstructive inhalation
therapy with tiotropium bromide, indacaterol, topical steroids and possibly oral theophylline, which
has also a positive effect on AMS, should be established [18].
Interstitial lung diseases (ILD)
ILD generally present with hypoxemia and normoMRM
43
or hypocapnia. If at rest and during exercise supplemental oxygen breathing restores normal arterial
pO2 values at sea level, these patients can travel to
moderate altitudes without problems as long as they
do not also suffer from pulmonary hypertension. In
contrast to obstructive lung diseases the response of
pulmonary artery pressures on O2-breathing is more
limited in patients with ILD than in those with
COPD (Figure 7). The restriction of the vascular bed
in ILD patients is generally less functional (alveolar
hypoventilation induced) but more structural.
Pulmonary vasodilators (nifedipine, sildenafil) oth-
FIGURE 7: DEPENDENCY OF MEAN PULMONARY ARTERY PRESSURE (PAP) RESPONSE ON O2-BREATHING AS A FUNCTION OF
RESIDUAL VOLUME (RV) AND AIRWAY RESISTANCE (RAW) % PREDICTED
Responders
Non-responders
02 responders show an obstructive pattern
A
B
PAP mm Hg
RV % pred.
RAW % pred.
Legenda: open circles: baseline at; full circles: on oxygen.
A: The response of mean PAP on O2-breathing is lower in interstitial lung disease patients with low residual volume (RV% pred) and subnormal airway resistance (RAW %pred) compared to patients with increased airway resistance and over-inflation.
B: Chest x-ray of a typical patient with interstitial lung disease variations in PAP and blood gases between baseline conditions and when
breathing O2 are reported.
TABLE I: LAKE LOUISE ACUTE MOUNTAIN SICKNESS SCORING SYSTEM
Self reported symptoms: (Score)
Headache:
Gastrointestinal:
Fatigue and/or weakness:
Dizziness or light headedness:
Difficulty to sleep:
Clinical assessment: (Score)
Change in mental status:
Ataxia (heel-to-toe walking):
no (0), mild (1), moderate (2), severe, incapacitating (3)
no (0), poor appetite or nausea (1), moderate nausea or
nausea (2), severe nausea and vomiting, incapacitating (3)
no (0), mild (1), moderate (2), severe (3)
no (0), mild (1), moderate (2), severe, incapacitating (3)
as well as usual (0), not as well as usual (1), poor night sleep,
woke up many times (2), could not sleep at all (3)
no (0), lethargy or lassitude (1), disorientated or confused (2),
stupor or semi-consciousness (3), coma (4)
no (0), manoeuvres to maintain balance (1), steps off line (2),
falls down (3), cannot stand (4)
no (0), at one location (1), at two or more locations (2),
Peripheral edema:
If you have any symptoms
how do they affect your activity?: no reduction (0), mild (1),
moderate (2), severe reduction, e.g bed rest (3)
The scoring system tries to quantify the severity of acute mountain sickness (AMS). A score (sum of the points) of 3 or more on the
self-reported symptoms section, or for the combined self-reported questionnaire and clinical assessment of more than 3, while at
altitude above 2,500 m, indicates AMS.
44 MRM
Pulmonary thromboembolic disease
Patients with known thromboembolic complications, including smoking females with underlying
coagulopathy and/or oral contraceptive use, are at
increased risk during long distance flights or bus
travel or other activities with a high degree of immobility. Restricted leg movement, venous occlusion (backpacking) and dehydration should be
avoided. Any anticoagulant therapy started at sea
level should be continued at altitude together with
all other drugs prescribed to reduce pulmonary hypertension and disease-specific symptoms. There
are anecdotal reports that lung emboli after thoracic
surgery are less frequent if the operation is performed above 1,800 m compared to in lowland
hospitals.
Respiratory pump disorders
Few studies have examined patients with respiratory
pump disorders. Patients needing non-invasive ventilation (NIV) as a consequence of pump failure,
alone or in combination with lung diseases and respiratory muscle fatigue, are generally not fit for travelling to altitudes above 2,500 m. They should also
avoid long distance flights without supplemental
O2-breathing and the support of a mechanical ventilator.
Obesity hypoventilation
Patients with this syndrome are at risk of cor pulmonale and hence acute right heart failure under an
additional hypoxic stress at altitude inducing more
pulmonary vasoconstriction. Nocturnal hypoxemia
(especially during REM sleep) due to obesity induced hypoventilation predisposes to both AMS
and HAPE. Pulmonary artery pressures at altitude
increase in proportion to the body mass index (BMI
> 30 kg/m2, PaCO2 during the day > 45 mm Hg).
Patients without daytime pulmonary hypertension
who need only continuous positive airway pressure
(CPAP) or non-invasive ventilation (NIV) at night
can travel to moderate altitudes with their devices,
but should also get prophylactic drug therapy as
needed.
Obstructive and/or central sleep apnea
Patients with OSAS develop already subclinical
HAPE at moderate altitudes of 2,500-3,000 m [19].
Their symptoms of AMS benefit from 750 mg/d
acetazolamide as well as fluid retention and systemic blood pressure elevation. Pulmonary gas exchange improved during the verum compared to
the placebo night [20]. Patients with pulmonary hypertension and/or day time hypoxemia at sea level
need slow release nifedipine 20 mg b.i.d. with supplemental oxygen at night.
Carotid surgery and control of breathing
The hypoxemic ventilatory response is reduced in
patients who have undergone endarterectomy with
damage to the carotid body. These patients may
show no increase of ventilation under hypoxic
stress and therefore they have a high risk of developing AMS and HACE. If these patients need to travel
at altitude, they should be first tested for their hyperoxic ventilatory response, to verify if there is a supplemental O2-induced hypoventilation.
Neuromuscular diseases and thoracic malformations
Patients with muscular dystrophies, diaphragmatic
paralysis, amyotrophic lateral sclerosis (ALS),
Guillain-Barré syndrome or severe kyphoscolioses
have limited ability to increase their ventilation as
required for altitude adaptation. Often they first
hypoventilate during sleep at night and later during
day time at sea level and need non-invasive ventilation (NIV) or bi-level positive airway pressure
(BiPAP). Any prior treatment with BiPAP or NIV
should be continued at altitude. Nocturnal or even
24 hour supplemental O2-breathing may be indicated to avoid at altitude an additional alveolar hypoxiainduced pulmonary vasoconstriction. Patients with
kyphoscoliosis and pulmonary hypertension need
additional oxygen combined with slow release
nifedipine 20 mg b.i.d. In patients with bilateral diaphragmatic paralysis NIV is already indicated during moderate altitude exposure.
H Matthys
er than supplemental O2 have limited therapeutic
potential, but if it can be demonstrated in an acute
setting that one or a combination of these drugs
lowers pulmonary hypertension, they should be
administered especially for short altitude exposures [19].
CONCLUSION
In conclusion, what do we need to evaluate if a patient is fit for altitude exposure? In the first instance,
the patient’s clinical diagnosis, medical examination and history (former experience with altitude exposures) are required. Specific examinations that
should be carried out are: pulsoximetry (Hb,
PaCO2), spirometry, chest X-ray, RR (echocardiography). If one or more of these are abnormal, for altitude exposures above 2,500 m further tests should
be carried out on air- versus O2-breathing: SaO2-,
PaCO2-, PAP-response under supplemental
O2-breathing. If still abnormal, prophylactic drug
therapy is recommended: acetazolamide (250 mg
b.i.d.), dexamethasone (2 mg b.i.d.), sildenafil
(20 mg b.i.d.) [11,23], nifedipine slow release (20
mg b.i.d.). In the case of ventilatory (respiratory
pump, periodic breathing) insufficiency with and
without lung and heart failure: polysomnography
should be performed in all patients, if necesssary
with and without supplemental O2-breathing and/or
mechanical aids at night (CPAP, BiPAP, IPPV, added
dead space) and drug therapy [9,12,20,22].
CONFLICT OF INTEREST STATEMENT: The Matthys-Drain® was
developed by the author for the drainage of air and liquid from
body cavities, and is produced by [email protected].
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45
46 MRM
References
1. Nussbaumer-Ochsner Y, Bloch KE. Lessons from high-altitude physiology. Breathe 2007;4:123-132.
2. Mohr LC. The hypoxia altitude simulation test: an increasingly performed test for the evaluation of patients prior to air
travel. Chest 2008;133:839-842.
3. Dillard TA, Moores LK, Bilello KL, Phillips YY. The preflight
evaluation. A comparison of the hypoxia inhalation test
with hypobaric exposure. Chest 1995;107:352-357.
4. West JB, Schoene RB, Milledge JS, eds. High Altitude
Medicine and Physiology. 4th ed. London: Hodder Arnold,
2007.
5. Hornbein TF, Schoene RB, eds. High altitude: an exploration of human adaptation. New York, Basel: Marcel
Dekker Inc, 2001.
6. Maggiorini M, Müller A, Hofstetter D, Bärtsch P, Oelz O.
Assessment of acute mountain sickness by different score
protocols in the Swiss Alps. Aviat Space Environ Med
1998;69:1186-1192.
7. Bärtsch P. High altitude pulmonary edema. Respiration
1997;64:435-443.
8. Bärtsch P, Maggiorini M, Ritter M, Noti C, Vock P, Oelz O.
Prevention of high-altitude pulmonary edema by nifedipine.
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9. Lovis A, de Riedmatten M, Greiner D, Delaloye A, Sartori C,
Scherrer U, Heinzer R. Effects of added dead space on sleep
disordered breathing at altitude (abstr). Swiss Med Wkly
2010;140(Suppl 179):3.
10. Nussbaumer-Ochsner Y, Ursprung J, Siebenmann C,
Schüpfer N, Maggiorini M, Bloch KE. Effect of dexamethasone prophylaxis on sleep and breathing disturbances in
HAPE susceptible subjects after rapid ascent up 4559m
(abstr). Swiss Med Wkly 2010;140(Suppl 179):2.
11. Ghofrani HA, Reichenberger F, Kohstall MG, Mrosek EH,
Seeger T, Olschewski H, Seeger W, Grimminger F. Sildenafil
increased exercise capacity during hypoxia at low altitudes
and at Mount Everest base camp: a randomized, doubleblind, placebo-controlled crossover trial. Ann Intern Med
2004;141:169-177.
12. Rexhaj E, Lovis A, Jayet PY, Rimoldi S, Allemann Y, Heinzer R,
Scherrer U, Sartori C. Increasing respiratory dead space
improves sleep disordered breathing and hypoxemia in patients
with CMS (abstr). Swiss Med Wkly 2010;140(Suppl 179):2.
13. Coker RK, Shiner RJ, Partridge MR. Is air travel safe for those
with lung disease? Eur Respir J 2007;30:1057-1063.
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Managing passengers with respiratory disease planning air
travel: British Thoracic Society recommendations. Thorax
2002;57:289-304.
15. Allegra L, Cogo A, Legnani D, Diano PL, Fasano V, Negretto
GG. High altitude exposure reduces bronchial responsiveness to hypo-osmolar aerosol in lowland asthmatics. Eur
Respir J 1995;8:1842-1846.
16. Galié N, Hoeper MM, Humbert M, Torbicki A, Vachiery JL,
Barbera JA, Beghetti M, Corris P, Gaine S, Gibbs JS, GomezSanchez MA, Jondeau G, Klepetko W, Opitz C, Peacock A,
Rubin L, Zellweger M, Simonneau G; ESC Committee for
Practice Guidelines (CPG). Guidelines for the diagnosis and
treatment of pulmonary hypertension: the Task Force for the
Diagnosis and Treatment of Pulmonary Hypertension of the
European Society of Cardiology (ESC) and the European
Respiratory Society (ERS), endorsed by the International
Society of Heart and Lung Transplantation (ISHLT). Eur
Heart J 2009;30:2493-2537.
17. Oades PJ, Buchdahl RM, Bush A. Prediction of hypoxaemia
at high altitude in children with cystic fibrosis. BMJ
1994;308:15-18.
18. Fischer R, Lang SM, Steiner U, Toepfer M, Hautmann H,
Pongratz H, Huber RM. Theophylline improves acute
mountain sickness. Eur Respir J 2000;15:123-127.
19. Behr J, Ryu JH. Pulmonary hypertension in interstital lung
disease. Eur Respir J 2008;31:1357-1367.
20. Latshang T, Nussbaumer-Ochsner Y, Ulrich-Somaini S,
Kohler M, Bloch KE. Do obstructive sleep apnea patients
develop subclinical HAPE even at moderate altitude?
(abstr). Swiss Med Wkly 2010;140(Suppl 179):2.
21. Latshang T, Nussbaumer-Ochsner Y, Ulrich-Somaini S,
Kohler M, Bloch KE. Combined autoCPAP and acetazolamide treatment controls breathing disturbances in patients
with OSAS at altitude (abstr). Swiss Med Wkly
2010;140(Suppl 179):2.
22. Nickol AH, Leverment J, Richards P, Seal P, Harris GA,
Cleland J, Dubowitz G, Collier DJ, Milledge J, Stradling JR,
Morrell MJ. Temazepam at high altitude reduces periodic
breathing without impairing next-day performance: a randomized cross-over double-blind study. J Sleep Res
2006;15:445-454.
23. Maggiorini M, Brunner-La Rocca HP, Peth S, Fischler M,
Böhm T, Bernheim A, Kiencke S, Bloch KE, Dehnert C,
Naeije R, Lehmann T, Bärtsch P, Mairbäurl H. Both tadalafil
and dexamethasone may reduce the incidence of high-altitude pulmonary edema: a randomized trial. Ann Intern Med
2006;145:497-506.
24. Matthys H, Volz H, Ernst N, Konietzko N. Hemodynamic
and ventilatory changes in patients with obstructive airway
disease exposed to a simulated altitude of 2500 m. Prog
Respir Res 1975;9:187-194.
Congress report / Resoconto congressuale
Time for physicians to be aware of molecular
genetic testing
Report from the 3rd Viareggio Health Festival
È tempo per i medici di essere consapevoli
delle possibilità della genetica molecolare
Resoconto dal III Festival della Salute di Viareggio
Cecilia Nardini
PhD student in 'Foundations of the Life Sciences and their Ethical Consequences', European School of Molecular
Medicine, IFOM-IEO Campus, Milan, Italy
In the last few years there has been growing excitement about the ‘molecular revolution’ that seems to
offer both a promise and a threat at the same time.
As more and more diseases are shown by research
to be linked to a genetic cause, the field of prevention will potentially be revolutionized: genetic research has highlighted the fact that the conditions
depending on the genetic makeup of a person are
much more than the traditionally known Mendelian
diseases, and range from metabolic disorders to susceptibility to certain types of cancer. In addition to
this, it is well known that most of diseases causing
disability and death in the western world are chronic
diseases, best dealt with through prevention rather
than treatment. There are few doubts that future
medicine will move in the direction of “testing before” rather than “curing after”. In this scenario, the
healthcare system of the next decades will be able
to dispense with most of the clinical activity as we
know it today, as genetic knowledge will provide a
“gateway” for referring patients to the form of treatment most adequate to each individual case. As a
result, physicians will probably have to face the
challenge of playing a completely new role.
However, so far, genetic knowledge has affected
only marginally the everyday practice of medical
professionals, who therefore run the risk of being
“overcome” by their sudden impact in the near future. An opportunity to reflect upon genetic technologies and their impact on the medical profession
was provided by the International Workshop held
on September 22nd at the Ospedale della Versilia,
within the 3rd edition of the Viareggio Health
Festival. This year’s Festival had the title “Genetic
Testing and Hereditary Diseases: Between the Right
not to Know and the Duty to Inform”, and was
aimed to investigate the ethical and legal aspects of
medical genetic information, and the establishment
of proper ways of handling it within the patientclinician relationship.
The first form of genetic knowledge is the deterministic one that exists in the case of Mendelian diseases like cystic fibrosis or chromosomal abnormalities such as the Down syndrome. These diseases
cannot be cured, but the presence of the chromosomal or genetic abnormality can be established before birth by performing a test on the pregnant
woman. In Italy, the law (DM 10/10/98, D. lgs. 22910/06/1999, “Decreto Bindi”) has established that
all pregnant women considered to be in a risk category - familial or age-related - have the right to free
access to the test, leaving it to each region to set up
specific screening programs. The tests in question
are invasive and represent a risk for the pregnancy;
+ Cecilia Nardini
PhD student in 'Foundations of the Life Sciences and their Ethical Consequences',
European School of Molecular Medicine, IFOM-IEO Campus
Via Adamello 16, 20139 Milano, Italia
Data di arrivo del testo: 13/12/2010 - Accettato per la pubblicazione: 12/01/2011
MRM
47
48 MRM
therefore they are not suited for population-wide
screening programs. In recent years, however, technical advances have made a non-invasive test possible, at least for the Down syndrome, by examining
fetal proteins in maternal serum [1]. At present,
non-invasive tests are not reliable on their own but
they could be effective as a screening method (first
step) for the pre-selection of candidates for the invasive tests, and for this reason they could be offered
on a routine basis, as is already happening in some
countries, namely the UK. A further reason why the
management of prenatal genetic testing could move
in this direction is that - at least in Italy - maternal
age is no longer considered a satisfactory discriminator given the constant rise of the age of first pregnancy in Italian women [1].
Indeed, some of the presentations at the workshop
dealt with the ethical consequences of prenatal testing. Matti Häyry and Tujia Takala from the
University of Helsinki conducted a philosophic and
historical analysis of the concept of parental rights
and the form they have taken in different societal
models. They argued that genetic screening empowers prospective parents, increasing their rights
in reproductive matters. Societal interference upon
the reproductive act is at the same time lessened, a
result which is generally considered fair in liberal
societies. On the other hand, Rebecca Bennett from
the University of Manchester warned in her lecture
that making prenatal tests routine might exert coercive pressure on those women who might not want
to know their future child’s makeup. Since the genetic condition cannot be cured, in most cases the
information provided by the test only leaves the
prospective parents with the painful choice of abortion or not. It is for this reason that prenatal genetic
tests are criticized as “not preventing harm but preventing children”. Bennett argued that, while testing
does not actually bring any advantage to women or
to their children, the routine setting causes the test
to be perceived as something beneficial. Of course
Bennett’s point is not about advocating a ‘blissful
ignorance’ about genetic conditions: what she contended is that routine prenatal genetic tests may not
be the best possible use of public funds, given that
they do not result in beneficial effects either for the
mother or child while, at the same time, they might
be infringing upon the woman’s ‘right not to know’.
It was to a close scrutiny - philosophical, ethical
and legal - of this ‘right not to know’ that most of the
meeting was devoted. Apart from the case mentioned above of a possible desire not to know genetic information about one’s yet unborn child, this
notion is classically applied to genetic information
about one’s own self regarding late onset diseases Huntington’s disease to name one – or conditions
that imply only an increased risk or susceptibility
for a disease. The best known instance of this latter
case is probably represented by the pair of BRCA
mutations that are involved in familiar breast cancer; however, BRCA mutations are just the leader of
a pack of genetic alterations that have been identified so far and that have a widely variable degree of
correlation with increased risk for many types of
cancer. The level of increased susceptibility associated with BRCA mutations is high enough to push
many women who test positive to BRCA to have
prophylactic mastectomy. The problem is that at the
moment medicine has not much more to offer in
this field in terms of prevention, hence it is understandable that people may prefer not to have the information about their genetic alterations - particularly if the associated risk is low - in order to avoid
the additional worries and anxieties posed by information which is in any case only probabilistic. On
the other hand, some might want to have this information in order to better plan their life and to take
informed decisions about their future. The problem,
at this point, is that genetic information is shared
between family members; therefore the information
about one’s genetic makeup generally brings with it
information about the makeup of parents or siblings
who may instead not want to know. How should
physicians deal with the right not to know? Should
they respect it, or are there over-ruling considerations? A well known challenge to the right of a person to remain in ignorance is the objection that
knowledge is a form of empowerment; therefore ignorance about relevant aspects of one’s health
would undermine the person's autonomy and capability to plan their future life in an informed way.
This in turn could be perceived as an additional burden on the shoulders of the practitioner, who may
feel they are responsible for their patient’s uninformed choices.
Lisa Bortolotti from the University of Birmingham
took up precisely this point in her lecture. Drawing
an analogy between the form of self-knowledge
represented by genetic information and that associated with psychological features, she concluded
that not knowing does not imply by necessity an impairment of personal autonomy. But can a guideline, or a default state, be chosen regarding whether
information should be given to patients? Matteo
Mameli from King’s College, London, confronted
this in his lecture. Clearly, the default cannot be
withholding the information, since this attitude
would be unacceptably paternalistic and patently
harming the interest of the patient. However, the
option cannot be to inform by default either, since
in this case the interest of those who do not want to
know would be infringed. The right not to know indeed configures itself more as an interest, or a
prima facie right that can be overridden by other
considerations and particularly other people’s rights
and interests. It is ultimately a legal matter to define
the boundaries and the most appropriate forms of
realization of this right: this legal analysis was undertaken by Roberto Andorno from the University of
Zurich. At the EU level, the right not to know is outlined in the framework of the Oviedo convention,
within Art. 10.2 “Everyone is entitled to know any
information collected about his or her health.
However, the wishes of individuals not to be so informed shall be observed” and in Art. 10.3 “In exceptional cases, restrictions might be placed by law
nies do not offer any kind of counselling on the results: patients have to seek healthcare professionals
for help with the interpretation.
In the latest issue of the New England Journal of
Medicine, two comments dealt with the possibilities and risks posed by the so-called “Consumer-driven Genomic Age” [3-4]. In the scenario in which
genetic medicine would be fuelled by the individual patient’s private initiative, the role of healthcare
professionals in this field would be likewise reduced to counselling and follow up on the results of
the genetic test. DTCs have recently appeared in
Italy in a context that is cosmetic rather than strictly
medical. An international company does in fact offer through chemist’s shops the possibility to be tested for one’s ‘metabolic profile’, in order to get personalized dietary advice based on genetic information on metabolism. It is still open to development
whether DTC in Italy will remain at this level of cosmetic application or if it will be extended to more
comprehensive health aspects like the situation is in
the US.
A further impulse in this direction is the fact that,
under the current trend, the cost of sequencing
technology is continuously shrinking and it is possible to foresee that in the not too distant future full
access to one’s own genetic information will be
within the possibilities of a sizeable portion of the
population in wealthy industrialized countries. On
this aspect the last speaker, Søren Holm from the
University of Manchester, focused attention in his
lecture entitled ‘The 1000$ genome and the duty
not to worry (too much)’. He stressed the fact that
virtually every person carries in their own genome
at least one allele that is a putative risk factor for
common diseases: there is an effective problem
about how this information could negatively affect
people’s lives if not properly managed. Actually, genetic information is less relevant than other factors
for people’s health: however, this message has to be
passed on to the public and to physicians. Genetic
counselling is likely to cost more than genome sequencing in the future, and it is equally likely that
the onus to provide it will be on the traditional
healthcare providers’ shoulders.
References
1. Perona M, Altare F, Bollati C, Dall’Amico D, Guaraldo V,
Pavanello E. Un programma di screening prenatale per la
trisomia 21: 14 anni di esperienza torinese. LigandAssay
2004;9:334-340.
2. Katsnelson A. Consumer gene testing in the hotseat. Nature
News. Published online 29/07/2010. http://www.nature.com/
news/2010/100729/full/news.2010.382.html
3. Evans JP, Dale DC, Fomous C. Preparing for a consumer-driven genomic age. N Engl J Med 2010;363:1099-1103.
4. Annes JP, Giovanni MA, Murray MF. Risks of presymptomatic direct-to-consumer genetic testing. N Engl J Med
2010;363:1100-1101.
C Nardini
Congress report, 3rd Viareggio Health Festival, Viareggio, September 2010 – Resoconto congressuale, III Viareggio Festival della Salute, Viareggio, Settembre 2010
on the exercise of the rights contained in paragraph
2 in the interest of the patient”.
As we see, the Convention states the right not to
know in the same terms that emerged from the discussion reported above: as an interest of people that
ought to be respected, but that can be overridden in
consideration of other factors. In general in almost
all legal settings the right or, better, interest of a person not to know is honoured under the condition
that no harm results to others, and that such interest
has been made explicit.
There is an additional facet of genetic information,
one that is probably not so familiar to the Italian
public. It is the case of Direct-to-consumer genetic
tests (DTCs) that are offered in the US by private
companies, which advertise and market them generally online, completely outside the clinical setting. What these companies offer is the possibility to
send a biological sample and have it analyzed, obtaining at the end of the process a personal table
with the risk factors determined from genetic data
for a number of diseases. The main problem is that,
contrary to what happens for pharmaceutical products, there is at the moment very little supervision of
the marketing of genetic tests. The need for regulation was perceived only recently, when one of the
companies offering this service, Pathway Genomics,
announced its intention to make its test kit available
in a big retail chain. Concerns voiced by many parts
upon this announcement prompted the FDA to
make a concrete plan for the regulation of genetictesting companies [2]. What is at issue is the clinical
utility of these tests, i.e. the fact that the benefits
they provide may not be enough to outweigh the
risks. The risk in this case is to have patients left to
make complex medical decisions without counselling and support from healthcare professionals.
In fact, even if the tests offered are totally reliable
and the results presented are aligned to state-of-theart genomic knowledge, there is still the problem
that the information that the test client receives is
probabilistic. The data that are given are in fact percentages of an increase/decrease of risk with respect to a reference population, information which
is admittedly difficult to interpret, particularly so for
the non-specialist. And yet genetic testing compa-
MRM
49
ATP Corner / L’Angolo dell’ATP
RUBRICA
EDITED BY /A CURA DI MARIO POLVERINO
Prosegue su Multidisciplinary Respiratory Medicine la pubblicazione dell’“ATP corner”, per le comunicazioni dell’Alleanza per le Malattie Toraco-Polmonari (ATP) e per la presentazione delle Società aderenti
a questa nuova Associazione, primo progetto (ambizioso) di una condivisione e diffusione federativa delle
mission e attività specifiche delle numerose Società scientifiche operanti in Italia con interessi nella medicina respiratoria.
Presentazione di UNA (Unione Nazionale Asmatici)
Presentation of UNA (National Union of Asthmatics)
Un nuovo ingresso nell’ATP: si aggiunge l’UNA
(Unione Nazionale Asmatici), fondata oltre 10 anni
fa da pazienti respiratori e da alcuni specialisti
pneumologi. La mission dell’UNA è basata su ‘protezione’, ‘partecipazione’ e ‘informazione’ dei pazienti affetti da malattie respiratorie. In un momento
particolarmente delicato e difficile della sanità in
genere, molte regioni hanno definito piani di riorganizzazione dell’offerta assistenziale. Tale operazione, indubbiamente indispensabile, deve avvenire
qualificando le direttive attraverso cui tale riorganizzazione deve svolgersi alla luce di linee guida,
razionali scientifici, e razionalizzazione delle misu-
re. I percorsi assistenziali nell’ambito dei quali vengono applicate le linee guida internazionali per la
diagnosi e cura delle malattie respiratorie devono
anche precisare dove e come l’utente può trovare
risposta ai propri bisogni di salute. Per tale motivo è
indispensabile che vengano proposti percorsi condivisi innanzitutto con i rappresentanti dei pazienti
al fine di creare atti di indirizzo indispensabili alla
qualificazione dell’offerta assistenziale in un momento critico di limitate risorse disponibili.
Mario Polverino
L’Unione Nazionale Asmatici (UNA)
Mission e prospettive
National Union of Asthmatics (UNA)
Mission and future prospects
Roberto W. Dal Negro
Referente Scientifico di UNA
L’Unione Nazionale Asmatici (UNA) è stata fondata
a Verona il 30 dicembre 1996 da un gruppo di intraprendenti pazienti respiratori ed alcuni specialisti
pneumologi particolarmente attenti e sensibili al
coinvolgimento consapevole dei soggetti affetti da
malattie respiratorie (in primis asma bronchiale
e BPCO).
La “mission” di UNA fu riassunta fin da subito in tre
50 MRM
parole: ‘protezione’, ‘partecipazione’, ‘informazione’
che, non a caso, fanno parte integrante dello statuto
dell’Associazione. Protezione dei pazienti da parte di
un organo associativo in grado, se necessario, di far
sentire la propria voce; partecipazione, intendendo
con ciò che anche i pazienti erano tenuti a mantenere un ruolo attivo nel panorama nazionale e a vivacizzarlo con le loro proposte; informazione, in quan-
to è stata immediatamente identificata la necessità
della divulgazione culturale presso l’opinione pubblica e i decisori politici dei messaggi, purtroppo
progressivamente sempre più allarmanti, inerenti alle
problematiche sanitarie e sociali dei soggetti affetti
da patologie respiratorie.
Ecco quindi l’immediata necessità di disporre di uno
strumento di comunicazione affidabile, snello e
adatto alle necessità dei pazienti: nacque così Il
Soffio, il periodico trimestrale che ha avuto il compito di rappresentare al meglio le loro istanze, oltre che
di pungolare decisori e istituzioni verso scelte serie e
responsabili a favore dei pazienti respiratori. Il Soffio,
oltre ad essere credibile ed aggiornato, doveva anche
essere penetrante: da qui la grande attenzione da
parte di tutta la redazione ai contenuti ed alla loro
forma di partecipazione all’utenza, ma anche alla distribuzione capillare sul territorio nazionale.
L’iniziativa, fin dall’origine molto apprezzata dai pazienti e dalle loro famiglie, è stata poi sempre più valorizzata anche dall’opinione pubblica (semplici curiosi o interessati) e dalle Istituzioni, soprattutto in
virtù della completezza, semplicità ed indipendenza
dei messaggi, sempre asetticamente orientati a favore
delle istanze dei malati respiratori, pur mantenendosi
lontani da derive improntate ad un velleitarismo di
parte.
A tale proposito va detto che non è mai stato facile
affrontare argomenti scientificamente ostici o complessi (a volte anche per gli “addetti ai lavori”) e distillarne messaggi semplici da trasferire al paziente
respiratorio medio. Negli anni, sulle colonne de Il
Soffio sono stati affrontati gli argomenti più disparati:
dalla biologia cellulare delle malattie respiratorie,
all’epidemiologia e alla genetica delle stesse; dagli
effetti dell’inquinamento ambientale, a quelli degli
allergeni indoor e outdoor; dall’urbanistica virtuosa,
alla rubrica della posta; dalle campagne vaccinali,
alla politica sanitaria; dalle novità terapeutiche, all’appropriatezza gestionale; dalle iniziative di divulgazione sociale (es. le giornate a Gardaland), alle iniziative editoriali e culturali specificatamente rivolte
all’infanzia (Giochi all’aria, AriUNA; Monthy, Il punto su…, ecc.). Il tutto autogestito ed elargito gratuitamente non solo a tutti gli iscritti su scala nazionale
(oltre 4.000), ma anche messo a disposizioni di tutti
gli interessati tramite le filiali che si sono via via moltiplicate nel Paese, fino a coprire tutte le regioni italiane.
Mediante UNA è stata anche fatta “ricerca sociale”,
cioè sondaggi condotti su tutto il territorio nazionale
con tutti i crismi della scientificità e che hanno consentito, fra l’altro, di indagare e quantificare per la
prima volta la sottostima nei confronti di asma e
BPCO nel nostro Paese; valutare la qualità di vita del
paziente con BPCO, oltre che comprendere le aspettative ed i desiderata dei pazienti asmatici in Italia,
raccogliendo le indicazioni su quali criticità essi addebitavano alle Istituzioni politiche e sanitarie relativamente alla scarsa attenzione sociale dimostrata nei
confronti delle malattie respiratorie croniche. Tramite
UNA sono state anche validate le misure spirometriche mediante PIKO-1, spirometro tascabile che l’as-
sociazione ha successivamente messo gratuitamente
a disposizione dei pazienti più gravi o in difficoltà.
Dai risultati di queste ricerche sono originate pubblicazioni scientifiche su riviste internazionali e questionari validati in Italia e all’estero; inoltre, da queste
ricerche sono, almeno in parte, dipese decisioni politiche importanti a favore della rimborsabilità dei farmaci respiratori.
La credibilità e l’accettazione di UNA sono andate
progressivamente crescendo sulla base di un lavoro
quotidiano e silenzioso, nulla concedendo a facili ed
inflazionati presenzialismi. I riconoscimenti sono cominciati ad arrivare dopo alcuni anni dalla sua fondazione: UNA è stata chiamata, come unica associazione, a rappresentare le istanze dei pazienti respiratori nel Board dell’Italian Asthma Coalition (braccio
nazionale afferente all’American College of Chest
Physicians). UNA è tuttora parte integrante
dell’Alleanza per le Malattie Toraco-Polmonari (ATP)
e, assieme ad altre associazioni di pazienti, fa parte
della GARD Italia (Global Alliance against
Respiratory Diseases dell’Organizzazione Mondiale
della Sanità) fin dalla fondazione di quest’ultimo importantissimo ente.
Ad UNA non è mai mancata inoltre la sensibilità,
l’attenzione e il senso di solidarietà nei confronti delle realtà più fragili e deboli. Con cadenza circa biennale, infatti, UNA si è fatta promotrice di importanti
ed onerose iniziative a favore di realtà geografiche in
Italia e nel mondo, per vari motivi particolarmente
disagiate dal punto di vista della gestione delle malattie respiratorie (es. terremotati dell’Abruzzo).
Anche per l’impegno richiesto, spicca l’iniziativa
“Un respiro per l’Africa”, a sostegno dell’ospedale di
Lacor in Uganda, dove UNA ha fondato e sostenuto
un centro specialistico per le malattie respiratorie,
fornendo tecnologie e know-how, dopo aver formato
in Italia il personale medico ugandese.
La più recente iniziativa è l’indagine epidemiologica
condotta in Ghana con personale formato localmente ed avente come obiettivo la misura della prevalenza della BPCO e dell’abitudine tabagica in quella regione africana, oltre che la misura del ricorso alle
strutture sanitarie locali.
A livello italiano, nel 2009 UNA ha contribuito attivamente al Progetto Nazionale PEP (Piano
Nazionale per il Paziente asmatico) patrocinato dalla Società Italiana di Medicina Respiratoria (SIMeR),
contribuendo fattivamente all’identificazione e validazione dei “dieci punti che ogni asmatico dovrebbe conoscere”.
Che dire per il futuro: non sono questi tempi facili né
per la divulgazione, né tantomeno per l’autosostenibilità di questo genere di iniziative associazionistiche
a sfondo sociale. Confidiamo comunque sull’appoggio e sul supporto di chi da sempre ha creduto in
UNA e nelle sue attività, oltre che nella forza e nella
libertà intellettuale del suo continuo impegno a favore dei pazienti respiratori, con l’immutata speranza
che UNA possa continuare a rappresentare il loro
supporto e sia riferimento informativo e culturale anche negli anni a venire.
MRM
51
Presentazione del Capitolo Italiano dell’American
College of Chest Physicians (ACCP)
Presentation of the Italian Chapter of the American
College of Chest Physicians (ACCP)
L’ACCP è la più grande Associazione scientifica
mondiale in campo pneumologico, grazie anche alle attività locali con i suoi National Chapters, e
quello italiano è il capitolo più numeroso in Europa
e, al di fuori del Nordamerica, secondo solo
all’India. Tutti coloro che hanno partecipato a un
convegno ACCP, in America o in Italia, sanno che la
peculiarità dell’associazione è quella di un taglio
eminentemente clinico-pratico, con interazione anche interdisciplinare. Pur essendo la più antica so-
cietà scientifica, essa ha saputo immediatamente
adattarsi alle nuove realtà e alle nuove problematiche. Peraltro, essa si è sempre occupata anche di
cultura educazionale. Come non citare la sua iniziativa di ottenere il bando del fumo di sigarette sulle linee aeree?
Benvenuta nell’ATP.
Mario Polverino
Capitolo Italiano dell’American College of Chest
Physicians (ACCP)
Italian Chapter of the American College of Chest
Physicians (ACCP)
Stefano Picciolo
Segretario Nazionale ACCP Capitolo Italiano
www.chest.it
L'American College of Chest Physicians (ACCP) è
un'associazione scientifica internazionale che, con i
suoi 75 anni di storia e gli oltre 17.000 iscritti distribuiti in quasi 100 Paesi nel mondo, è la più antica e
rinomata Società scientifica che si occupa di patologia toracica.
Fondata nel 1935, l'ACCP ha inizialmente focalizzato l'attenzione sul trattamento e la prevenzione della
tubercolosi. Successivamente, con la riduzione dell’incidenza e della mortalità legata a questa malattia,
il College si è dedicato al trattamento ed alla prevenzione di tutte le patologie del torace, caratterizzandosi fin dall'inizio per l'interesse ed il coinvolgimento multidisciplinare dei suoi affiliati. L’ACCP è stata
fra le prime società scientifiche a riconoscere il danno da fumo di sigaretta nel determinismo delle principali patologie dell’apparato respiratorio, ed è stata
di fondamentale aiuto nell’approvazione della legge
che obbliga a stampare gli avvisi di danno potenziale
52 MRM
sui pacchetti di sigarette. Successivamente, il College
ha spinto l’approvazione della legge per bandire il
fumo di sigaretta sugli aeroplani.
Tra i suoi soci vede annoverati specialisti in
Pneumologia, Chirurgia Toracica, Cardiochirurgia,
Anestesia e Rianimazione, Cardiologia, Pediatria,
Allergologia, ma anche terapisti della Riabilitazione
e tecnici di Fisiopatologia Respiratoria. Il giornale ufficiale dell'associazione è Chest, prestigiosa rivista
clinica di patologia toracica che ha raggiunto la terza
posizione nella classifica delle riviste scientifiche con
il più alto "impact factor", ovvero, che sono maggiormente citate nelle bibliografie internazionali. La diffusione della versione in italiano della rivista è curata, dall'anno 2000, da Midia Edizioni cui va il grande
merito di averle dato una grande rilevanza ed averne
promosso una capillare distribuzione ad oltre 5.000
medici specialisti italiani.
Nel 1996 è nata la Chest Foundation, braccio filan-
tropico dell’ACCP, che ha lo scopo di sviluppare programmi educazionali, supportare la ricerca e informare l'opinione pubblica sulle principali problematiche respiratorie, proponendo campagne di prevenzione.
A livello mondiale l'ACCP mantiene rapporti di stretta collaborazione con le massime organizzazioni sanitarie: il National Heart Lung and Blood Institute
(NHLBI), la Food and Drug Administration (FDA), il
Center for Medicare and Medicaid (che riunisce le
massime associazioni ed enti mutualistici americani). Inoltre, l'ACCP intrattiene stretti rapporti con i
membri del Congresso Americano, organizzando periodiche riunione politiche e contribuendo a proposte legislative su temi di prevenzione e cura delle patologie toraciche.
I circa 2.500 soci internazionali dell'ACCP sono riuniti in Capitoli Nazionali. Il Capitolo Italiano è il più
importante d'Europa (secondo al mondo solo
all’India) sia come numero (i soci italiani sono oltre
200) che, principalmente, per l'attività dei suoi membri. Esso organizza periodicamente riunioni scientifiche su temi di patologia cardio-respiratoria nel corso
delle quali ha luogo un fruttuoso scambio di conoscenze scientifiche. Il Capitolo Italiano è stato costituito oltre 50 anni fa (nel 1950) per opera del Prof.
Attilio Omodei Zorini di Roma ed Antonio Blasi di
Napoli, allievi della Grande Scuola PneumoTisiologica Italiana, che faceva capo a maestri come
Carlo Forlanini e Vincenzo Monaldi. Nel passato,
prestigiosi medici napoletani hanno ricoperto il ruolo
di Regent del Capitolo Italiano ACCP. Tra questi si ricordano il Prof. Antonio Blasi (1978-1985) ed il Prof.
Mario Condorelli (1985-1993). Più recentemente ricordiamo il Prof. Giuseppe Di Maria, il Prof. Dario
Olivieri (attuale Regent) e il Dott. Francesco de
Blasio.
Recenti iniziative del Capitolo Italiano ACCP
Il progetto “Italian Asthma Coalition” del Capitolo
Italiano ACCP (www.chest.it/asthmacoalition) intende contribuire ad aumentare la percentuale di pazienti con asma bronchiale controllato, per il miglioramento della loro salute, della qualità di vita e la
conseguente riduzione dell’incidenza della mortalità
per asma.
Il progetto, nella sua prima fase, si propone, attraverso interventi a diversi livelli, i seguenti obiettivi:
1. aggiornare i medici specialisti coinvolti nella patologia dell’asma;
2. creare una rete di specialisti che, a vario titolo, si
occupano di asma bronchiale e di agevolare la loro
collaborazione e lo scambio di informazioni;
3. aumentare la consapevolezza della popolazione
sulla patologia.
Il Capitolo Italiano ACCP ha recentemente promosso
un corso FAD il cui argomento è "La responsabilità
medico-legale dello specialista pneumologo" che si
svolge secondo il primo dei tre mezzi a disposizione
della FAD, ovvero la fruizione mediante dispense
dattiloscritte e la successiva compilazione e restituzione di un questionario di valutazione. Il corso ha
ricevuto 6 punti ECM FAD. Questa prima esperienza
- tra le prime in assoluto in ambito pneumologico sarà foriera di altre analoghe nel 2011, che porteranno ulteriore lustro all'ACCP Italia come società scientifica all'avanguardia della FAD.
Infine, durante il 2011 si svolgerà il 1° Congresso
Congiunto ACCP/AIMAR che si terrà a Stresa (VB) nei
giorni 16-18 marzo 2011, ed il cui programma può
essere visionato sul nostro sito ufficiale www.chest.it
(vedi anche www.accp-aimar.it e www.aimarnet.it,
ndr). L'unità di intenti delle due società scientifiche
ha reso possibile questa "fusione congressuale" che,
senza ombra di dubbio, rappresenterà l'evento pneumologico di spicco del 2011. Infatti, è prevista una
partecipazione ampia e qualificata e circa 150 relatori/moderatori, inclusa una fitta rappresentanza di
ospiti internazionali, tra i quali il presidente
dell'ACCP David G. Gutterman e il presidente
dell'ERS Marc Decramer.
ACCP vision
Il College rappresenta la risorsa principale per il miglioramento globale della salute cardio-toracica e la
terapia intensiva respiratoria nel mondo.
ACCP mission
Promuovere la prevenzione ed il trattamento delle
patologie del torace attraverso la sua leadership, l'educazione, la ricerca e la comunicazione.
I nuovi Fellow dell'ACCP in occasione della cerimonia di
"iniziazione".
MRM
53
RUBRICA
AIMAR Newsletter / Notiziario AIMAR
EDITED BY /A CURA DI STEFANO NARDINI
Negli ultimi anni AIMAR ha avviato una riflessione
sui “doveri” di una Società scientifica medica di
Specialità nei confronti dei propri associati, dato
che ritiene che la corrente “stagione” imponga
cambiamenti sia alle strategie sia alle attività di
qualsiasi raggruppamento professionale sanitario.
Sull’onda della crisi economica i decisori - dopo
aver illuso gli elettori che si potessero ottenere migliori servizi sanitari (in un Paese come l’Italia che,
secondo quanto ci dice l’OMS, già si trova ai primissimi posti nel mondo per qualità dell’assistenza
sanitaria) pagando meno tasse (cioè investendo meno quattrini in un settore strategico - quale la salute
della comunità - cui la tecnologia e le nuove scoperte farmacologiche conferiscono potenzialità impensabili fino a qualche anno fa, impensabili ma
costose) i decisori, si diceva, intervengono tagliando, chiudendo, “razionalizzando”, spesso senza
una precisa strategia in mente, ma solo sulla spinta
di impellenti necessità e ristrettezze, quando non di
vero e proprio timor panico.
Di fronte ai rischi che questo modo di agire comporta, la vera sfida - oggi - per ogni sanitario italiano è fare il possibile per salvare il servizio sanitario
nazionale e, con esso, salvaguardare la salute della
popolazione. E non vi è dubbio che i custodi della
salute respiratoria della popolazione siano in primis
gli specialisti pneumologi e che il compito di tradurre la sfida suddetta in strategie e azioni specialistiche
pneumologiche sia delle relative associazioni scientifiche, d’intesa con gli organi programmatori competenti e le associazioni di pazienti.
A parere di chi scrive (ma tali convinzioni sono diffuse anche negli Organi Direttivi della nostra
Società) la sfida si vince ottimizzando la propria
professionalità, contemperando la sostenibilità
economica di ciascun intervento professionale con
la cooperazione e la condivisione a tutti i livelli del
sistema sanitario nazionale. Non è un caso che due
54 MRM
anni fa circa AIMAR abbia scelto di riassumere la
propria mission nel motto “Visione e condivisione
in Medicina Respiratoria”.
Se è vero che la disciplina pneumologica ha visto
accrescere la propria importanza negli ultimi anni,
è anche vero che in Italia ciò è avvenuto meno per
merito di noi specialisti e delle nostre associazioni
che non per la comprensione dell’emergenza epidemiologica rappresentata dalle pneumopatie.
Ma la battaglia per affermare la propria importanza
di specialisti non è certo vinta con passaggi programmatici nei quali si riconosce l’importanza di
una patologia d’organo. Noi specialisti dobbiamo
dimostrare in concreto che siamo in grado di occuparcene, di saperlo fare meglio di altri (specialisti e
non) e di essere in grado di farlo con minor impatto
economico sul bilancio della comunità.
Per questo, anche per noi Pneumologi, l’odierna
pratica clinica si deve misurare non solo con gli
standard stabiliti sulla base delle evidenze scientifiche, ma anche sui limiti tracciati dalle evidenze
“economiche”: non vi è dubbio che oggi - e sempre
più in futuro - come specialisti concorreremo con le
altre discipline per le dotazioni di uomini e mezzi.
La riflessione che AIMAR ha avviato ha prodotto risultati cui si è fatto cenno in precedenti notiziari. In
quello che precede immediatamente questo, si era
data una sommaria descrizione di quelli che
AIMAR considera i propri obiettivi nell’ottica dell’assistenza alla professione dei propri associati:
1. migliorare la formazione professionale
2. esplorare modelli organizzativi innovativi
3. aumentare la visibilità della nostra disciplina
4. aumentare la visibilità dello specialista
Pneumologo a livello sia locale sia regionale.
La scorsa edizione del notiziario AIMAR si era
chiusa con la menzione dell’iniziativa dei cosiddetti “gruppi di progetto” tesi alla valorizzazione dei
giovani aderenti alla società.
Questo è stato il punto di partenza anche del
Consiglio Nazionale AIMAR tenutosi a Milano il 16
dicembre 2010, illustrato dai due Vice-Presidenti.
Si tratta di un’iniziativa originale che AIMAR ha
proposto a una grande azienda farmaceutica con
un ruolo importante nell’ambito del settore respiratorio. L’iniziativa è tesa da un lato, come detto, a
valorizzare e responsabilizzare la componente
“giovane” di AIMAR e dall’altro a qualificare ulteriormente l’Associazione mediante la produzione
di documenti e la realizzazione di indagini/studi
clinici. Per questo l’iniziativa coinvolgerà - oltre ai
membri dell’Esecutivo, scelti in base alla competenza - anche colleghi di età inferiore ai 45-50 anni
che si siano distinti come Pneumologi qualificati
attivi nella ricerca clinica.
Nel corso del Consiglio Nazionale sono stati discussi e approvati gli argomenti oggetto dei gruppi
di progetto e sono stati esaminati curricula e competenze - e proposti e approvati i nomi- dei colleghi che, indicativamente, dovranno comporre le
“task force”.
L’azienda farmaceutica sopra citata dovrebbe, in linea di massima, erogare il finanziamento per supportare quest’iniziativa per gli anni 2011-2014 con
un budget specifico per ciascun anno. La formazione ufficiale dei gruppi è prevista per la prima metà
del 2011 e l’inizio delle attività per settembre
2011.
Nel Consiglio si è discusso di come fare per conciliare le attività suddette (e le altre in corso, necessarie per la qualificazione della società, nell’ottica
descritta) con la situazione economica della società stessa, che con un eufemismo potremmo definire “non particolarmente florida”.
Il Presidente ha tracciato - nella sua relazione di
apertura - il quadro dell’attuale situazione finanziaria, partendo dalla constatazione che il successo
economico della Consensus Conference di maggio
2010 è stato di molto inferiore al successo “scientifico”. Sommando tale consuntivo con la congiuntura sfavorevole secondaria alle riorganizzazioni in
corso nel settore farmaceutico le entrate societarie
si sono sensibilmente ridotte
Poiché però la nostra Associazione intende restare
impegnata nella crescita della specialità e degli
specialisti si è decisa una riorganizzazione societaria che ha ridotto gli uffici centrali di Borgomanero
al minimo, con il trasferimento di alcune delle persone ivi impiegate all’agenzia che si occupa di organizzare gli eventi AIMAR.
In tal modo si sono ridotte le spese senza privare i
soci di una serie di servizi, dato che - pur svolgendo il loro incarico prevalentemente per l’agenzia
citata - le due persone impiegate sono comunque
dedicate alle attività AIMAR. Sempre nell’ottica delle
riduzione delle spese di AIMAR si è proceduto alla
chiusura dell’edizione italiana dell’American Journal
of Respiratory and Critical Care Medicine (AJRCCM),
anche in seguito ad una pesante violazione del contratto da parte della testata americana.
Le decisioni prese hanno consentito, anche se non
si esclude la necessità di futuri ulteriori tagli (se,
permanendo lo stato di crisi, l’andamento delle entrate e delle uscite dovesse continuare a essere negativo) di conciliare le esigenze di bilancio, esposte
in apertura, con quelle di supporto societario alla
crescita della disciplina.
E queste iniziative di supporto non mancano.
È iniziato lo studio e-DIAL, sta per partire un altro
studio (OTTIMO) sulla qualità della spirometria. È
in fase di avanzata realizzazione il 1° Congresso
congiunto ACCP-AIMAR in programma a Stresa dal
16 al 18 marzo 2011. Sono iniziati i preparativi del
Congresso Nazionale elettivo del 2012 che si terrà
a con ogni probabilità o a Torino o a Genova.
Procedono anche le attività editoriali che, dopo la
chiusura dell’edizione italiana dell’AJRCCM si sono concentrate su MRM, con il supplemento periodico per i medici di Medicina Generale.
La rivista ora procede bene e raccoglie numerosi articoli anche dall’estero. È stata rinnovata nei mesi
scorsi l’application per l’indicizzazione in Medline.
Pubblicazioni scientifiche per aiutare a migliorare
la formazione professionale, documenti e protocolli per supportare l’esplorazione di modelli organizzativi innovativi, studi clinici per aumentare sia la
visibilità della nostra disciplina, sia la visibilità dello specialista Pneumologo a livello sia locale sia regionale: AIMAR si sforza di fornire tutto questo ai
propri Soci e al mondo pneumologico più in generale; ciò che chiede ai propri associati è condivisione e partecipazione, non solo con il contributo professionale di ciascuno, ma anche - per quanto prosaico possa sembrare - con la regolarizzazione della quota di iscrizione.
MRM
55
RUBRICA
From the CFC Bulletin / Notiziario CFC
Prosegue su Multidisciplinary Respiratory Medicine, a fronte della collaborazione tra AIMAR e Collegio
Federativo Cardiologia (CFC), la pubblicazione di estratti del bollettino CFC, mensile di informazione e
aggiornamento del Collegio.
CUORE E METABOLISMO
LE MALATTIE METABOLICHE E IL CONTENUTO
DI FRUTTOSIO
Gli autori partono dall’osservazione, supportata da
molte evidenze, che una dieta ad alto contenuto di
fruttosio può dare origine a obesità, diabete e dislipidemia nei roditori, mentre nell’uomo lo zucchero
aumenta le concentrazioni plasmatiche dei trigliceridi. In più il fruttosio, consumato in forti quantità come parte di una dieta ipercalorica, può causare insulino-resistenza, aumento della massa grassa viscerale
e totale, e accumulo di grasso ectopico a livello del
fegato e del muscolo scheletrico. Questi effetti precoci potrebbero determinare, a lungo termine, lo sviluppo della sindrome metabolica. Gli autori, però,
spiegano che le evidenze a supporto del ruolo nocivo giocato dal fruttosio, quando è consumato con
moderazione, sono limitate. Alcuni effetti della dieta
ad alto contenuto di fruttosio si osservano anche con
le diete che prevedono forti consumi di grassi o glucosio, suggerendo che il principale fattore coinvolto
nello sviluppo della sindrome metabolica si debba
identificare nell’eccesso di apporto calorico. La principale fonte di fruttosio alimentare è riconosciuta
nelle bevande dolcificate o in altri prodotti che prevedono l’aggiunta di dolcificanti calorici. Resta fermo il fatto che il consumo di bevande dolcificate è
chiaramente associato a un eccesso di apporto calorico e a un aumento del rischio di diabete e di malattie cardiovascolari attraverso l’incremento del peso
corporeo. Quest’ultima osservazione - concludono gli
autori - è alla base della raccomandazione di limitare
l’apporto giornaliero delle calorie dello zucchero.
Tappy L, Lê KA, Tran C, Paquot N. Fructose and metabolic diseases: new findings, new questions.
Nutrition 2010;26:1044-1049.
SOVRAPPESO E MORTALITÀ NEGLI ANZIANI
I ricercatori hanno identificato circa 2.400 anziani
tra i 70-85 anni e li hanno seguiti per 18 anni per
56 MRM
verificare se il semplice sovrappeso costituisse un
rischio aumentato di decesso nelle persone anziane. Dopo vari aggiustamenti per potenziali fattori di
confondimento che avrebbero potuto provocare il
decesso, si è visto che negli anziani il sovrappeso
non comporta un’aumentata mortalità, anzi nelle
donne costituisce una sorta di fattore di protezione.
Questo non significa l’incoraggiamento al sovrappeso, ma invita a non fossilizzare l’attenzione sulla
diminuzione di peso nelle anziane.
Journal of American Geriatric Society 2009;57:
2232.
SCOMPENSO CARDIACO
LA VITAMINA D È UN FATTORE PROGNOSTICO
DI SCOMPENSO
Uno studio olandese (COACH) mostra che la percentuale di sopravvivenza nei pazienti con scompenso cardiaco con ridotti livelli di vitamina D è
più bassa rispetto a quelli con valori normali. Gli
autori, pertanto, consigliano a questi pazienti di assumere più olio di pesce, uova o semplicemente di
esporsi al sole.
FERRO E SCOMPENSO
Anche la carenza di ferro secondo uno studio condotto in Polonia ha un valore prognostico negativo nei
soggetti con scompenso. Essa andrebbe corretta anche perché ha mostrato di migliorare, nei pazienti valutati, la tolleranza allo sforzo e la qualità della vita.
Ponikowski Piotr ESC Congress 2010;RN
298,299,300,301.
Liu L.C.Y. ESC Congress 2010 RN P5675.
ARITMOLOGIA E CARDIOSTIMOLAZIONE
PREVENZIONE: ALTRI DATI SUL FUMO PASSIVO
Lo studio prospettico “Objectively Measured
Secondhand Smoke Exposure and Risk of
Cardiovascular Disease - What Is the Mediating
Role of Inflammatory and Hemostatic Factors?”
condotto su 13.443 participanti (età 53,5 ± 12,6,
52,3% donne) misurando la cotinina salivare (indice di esposizione al fumo passivo) e nuovi biomarker cardiovascolari (PCR, fibrinogeno) ha dimostrato che il 20,8% del campione ha avuto alta
esposizione a fumo passivo e durante un F-U medio di 8 anni, si sono osservate 1.221 morti per tutte le cause e 364 cardiovascolari, in cui tale esposizione ha giocato un ruolo importante. Il fumo
passivo ha determinato un rischio di mortalità per
tutte le cause aggiustato per età con un HR = 1,25,
e per morte CV con un HR = 1,21. Il rischio è risultato esagerato in rapporto all’autodiagnosi di esposizione (HR aggiustato per età = 3,27) a paragone
dell’esposizione misurata oggettivamente (HR:
2,44). I livelli di PCR sono risultati incrementati negli esposti al fumo passivo.
RISCHIO ARITMICO IN ETÀ ADULTA NELLA
TETRALOGIA DI FALLOT OPERATA
Lo studio multicentrico “Arrhythmia Burden in
Adults With Surgically Repaired Tetralogy of Fallot A Multi-Institutional Study” condotto dalla Alliance
for Adult Research in Congenital Cardiology
(AARCC) ha valutato il rischio di aritmia nella tetralogia di Fallot in 556 soggetti, 54% femmine, di età
media 36 anni, reclutati da 11 centri.
Complessivamente il 43,3% ha avuto aritmie sostenute o interventi per aritmie. La prevalenza di aritmie sopraventricolari è stata del 20,1%, con fattori
associati all’analisi multivariata ingrandimento
atriale destro OR: 6,2, ipertensione OR: 2,3 e numero di interventi chirurgici OR: 1,4. L’età (OR:
1,09), la bassa FE (OR: 0,93 per unità), la dilatazione atriale sinistra (OR: 3,2), il numero di interventi
chirurgici (OR: 1,5) sono risultati associati con FA.
Le aritmie ventricolari hanno avuto una prevalenza
del 14,6% ed associate con il numero di interventi
(OR: 1,3), durata del QRS (OR: 1,02 per 1 ms), e disfunzione VS diastolica (OR: 3,3). La prevalenza di
FA e di AIV è risultata marcatamente incrementata
dopo i 45 anni.
http://circ.ahajournals.org/cgi/content/abstract/122/
9/868
GRASSO (PERICARDICO) NON È BELLO PER LA
FIBRILLAZIONE ATRIALE
L’articolo di ricerca clinica “Pericardial Fat Is
Independently Associated With Human Atrial
Fibrillation” può in parte spiegare il rapporto tra
obesità ed incrementato rischio di FA. Tramite TAC
è stato valutato il volume di grasso pericardico,
che, come tutto il tessuto adiposo, possiede proprietà infiammatorie, in 273 soggetti, 76 in RS, 126
con FA parossistica e 71 con FA persistente. I soggetti in FA parossistica hanno dimostrato un volume significativamente più elevato di quelli in RS
(93,9 ± 39,1 ml vs 76,1 ± 36,3 ml, p = 0,02). I soggetti con FA persistente hanno dimostrato grasso in
misura superiore ai soggetti in FA parossistica
(115,4 ± 49,3 ml vs 93,9 ± 39,1 ml, p = 0,001).
Questa associazione è risultata indipendente da altri fattori di rischio confondenti.
http://content.onlinejacc.org/cgi/content/abstract/56/10/784
PROTEINA C REATTIVA E RISCHIO
DI FIBRILLAZIONE ATRIALE
Nello studio clinico “Does Elevated C-Reactive
Protein Increase Atrial Fibrillation Risk?” è stato valutato su circa 47.000 individui del prospective
Copenhagen City Heart Study e del cross-sectional
Copenhagen General Population Study, il livello di
4 geni per il polimorfismo della PCR e la PCR ad alta sensibilità. Un livello di PCR nel più alto vs. più
basso quintile è risultato associato a 2,19 volte
maggior rischio di FA. Dopo aggiustamento per altri fattori il rischio si è ridotto a 1,77 ed a 1,47 correggendo anche per fibrinogeno e scompenso cardiaco. Le combinazioni dei 4 genotipi della PCR
sono risultate accoppiate ad un incremento del
63% dei livelli di PCR plasmatici (p < 0,001), ma
non con incremento del rischio di FA. Pertanto se i
livelli di PCR elevati si associano ad incremento del
rischio di FA, la PCR elevata per motivi genetici
non si associa a tale rischio e la PCR è un marcatore del rischio indice di infiammazione, piuttosto
che un agente causale della FA.
http://content.onlinejacc.org/cgi/content/abstract/56/10/789
PREVENZIONE
BEVANDE ZUCCHERATE E IPERTENSIONE
La ricerca prospettica “Reducing Consumption of
Sugar-Sweetened Beverages Is Associated With
Reduced Blood Pressure - A Prospective Study
Among United States Adults” ha permesso di valutare in 810 soggetti partecipanti allo studio
PREMIER il ruolo che le bevande zuccherate hanno
non solo nell’insorgenza di diabete e sindrome metabolica, ma anche sull’ipertensione. La PA di base
era 134,9 ± 9,6/84,8 ± 4,2 mm Hg. Dopo eliminazione di fattori confondenti, la riduzione di una dose di bevanda zuccherata al giorno è risultata associata alla riduzione della PAS di 1,8 mm Hg e della
PAD di 1,1 mm Hg dopo 18 mesi di F-U.
http://circ.ahajournals.org/cgi/content/abstract/121/22/2398
GIOVANI, DEPRESSIONE, ANSIA E MALATTIE
CARDIOVASCOLARI
La survey nazionale svedese “Early-Onset
Depression, Anxiety, and Risk of Subsequent
Coronary Heart Disease - 37-Year Follow up of
49,321 Young Swedish Men” condotta per 37 anni
su quasi 50.000 giovani di 18-20 anni selezionati
alla visita di leva tra il 1969 ed il 1970 mediante
un’intervista strutturata da psicologi e nei soggetti
con sintomi psichiatrici da visita specialistica, e
mediante la raccolta di dati sui fattori di rischio coronarico, ha evidenziato per la depressione HR aggiustati per fattori multipli di 1,04 e di 1,03 per cardiopatia ischemica e per IMA rispettivamente (95%
MRM
57
CI: 0,65 to 1,65). I corrispondenti valori per l’ansia
sono risultati 2,17 e 2,51. Pertanto l’ansia ma non
la depressione è risultata associata a rischio CV nei
soggetti di giovane età.
ANCORA SULL’ANSIA NELLA CARDIOPATIA
ISCHEMICA
La metanalisi “Anxiety and Risk of Incident
Coronary Heart Disease” ha analizzato i dati di 20
studi comprendenti circa 250.000 soggetti con un
F-U medio di 11,2 anni in cui i partecipanti sono
stati individuati affetti da ansia. Tali soggetti sono risultati a rischio per malattia coronaria (HR: 1,26;
p < 0,0001) e morte cardiaca (HR: 1,48; p = 0,003),
in modo indipendente da variabili demografiche,
fattori di rischio classici e comportamenti a rischio.
Si è osservato un trend non significativo di associazione con l’IMA non fatale (HR: 1,43; p = 0,180).
L’analisi dei sottogruppi non ha rilevato differenze
di genere o per altre caratteristiche.
ANCORA SUI RAPPORTI TRA INQUINAMENTO
ATMOSFERICO E MALATTIA
CARDIOVASCOLARE
La “Contemporary Reviews in Cardiovascular
Medicine” dal titolo “Cardiovascular Effects of
Ambient Particulate Air Pollution Exposure” è
un’interessante rassegna degli effetti dei vari inquinanti atmosferici sull’apparato cardiovascolare. In
particolare vengono analizzate le conseguenze dell’esposizione ai particolati (PM), che in modo sempre più pesante inquinano l’atmosfera, anche in
Italia.
http://circ.ahajournals.org/cgi/content/extract/121/25/2755
AI GOLOSI LASCIAMO IL CIOCCOLATO
L’articolo “Chocolate consumption in relation to
blood pressure and risk of cardiovascular disease in
German adults” descrive i risultati del Potsdam arm
of the European Prospective Investigation into
Cancer and Nutrition in cui sono stati analizzati i
dati di 19.000 soggetti sani di base (1994–98) e dopo un F-U di circa 8 anni. Si sono osservati 166 IMA
e 136 stroke. La PA sistolica è risultata 1,0 mm Hg
[95% confidence interval (CI) ± 1,6 to ± 0,4 mm Hg]
e la diastolica 0,9 mm Hg (95% CI ± 1,3 to ± 0,5
mm Hg) più bassa nel quartile con il massimo consumo di cioccolato rispetto al quartile con consumo minimo, ed il rischio combinato di IMA e stroke
è risultato 0,61 (95% CI 0,44–0,87; p linear trend =
0,014) nel quartile a più alto consumo vs. il quartile a più basso consumo. La PA spiega solo il 12%
di questa riduzione del rischio, e tale riduzione è
più importante per l’ictus che per l’IMA.
http://eurheartj.oxfordjournals.org/content/31/13/
1616.abstract
58 MRM
AGGIUNGERE LA FREQUENZA CARDIACA NEL
CALCOLO DEL RISCHIO CARDIOVASCOLARE
GLOBALE?
Lo studio clinico “Simplifying cardiovascular risk
estimation using resting heart rate” si è proposto di
valutare se l’aggiunta dell’elevata FC a riposo, noto
fattore di rischio CV indipendente, alle carte del rischio CV contribuiscano a migliorare la valutazione di tale rischio. Sono stati analizzati i dati del
FINRISK study (14.997 maschi e 15.861 femmine)
da cui sono state derivate due formule per la stima
del rischio CV a 10 anni.
Nella prima è stata inserita la FC oltre ai comuni
parametri e non si sono osservati miglioramenti
nella discriminazione (AUROC, maschi 0,840 da
0,838, p = 0,5038; femmine: 0,87 da 0,865, p =
0,0522). Nella seconda comprendente solo età,
sesso, superficie corporea e fumo, l’associazione
della FC ha fornito indicazioni significative (AUROC maschi 0,819 da 0,812, p = 0,037; femmine:
0,862 da 0,827, p = 0,023).
http://eurheartj.oxfordjournals.org/content/31/17/2141.abstract
L’ANGOLO DEL POLSO
FUMO ED ARTERIAL STIFFNESS
Arterial stiffness e fumo. Può sembrare un argomento fritto e rifritto. È, invece, un interessante excursus sui danni che il fumo di sigaretta, attivo o passivo, in acuto o cronicamente, può determinare a
livello dell’apparato cardiovascolare. Bastano pochi minuti di fumo per provocare alterazioni vascolari, sono necessari anni per ripristinare, se
possibile, l’integrità delle strutture vascolari colpite da più o meno lunghi periodi di fumo. Vi propongo le linee guida per la prevenzione del fumo
e dei danni da esso provocati, dirette agli adulti ed
alle donne in gravidanza ed una “review” di grande importanza e spessore.
NURSING CARDIOLOGICO
FUMO ED IMA
Studi condotti in diversi Paesi che si sono dotati di
una legislazione per la riduzione del fumo hanno
trovato una piccola, ma significativa riduzione nelle ammissioni in ospedale per infarto miocardico.
Interventi territoriali sono grandemente auspicabili.
BMJ 2010;340:c2161.
Tratto da Bollettino CFC, anno 3, numero 4, settembre 2010, pubblicato da Edizioni Internazionali srl,
Div. EDIMES, Pavia.
A CURA DELLA REDAZIONE
La redazione intende lasciare questo spazio a disposizione per la presentazione di contributi culturali, anche non strettamente inerenti l'area medica. Gli interessati possono pertanto sottoporre alla redazione
qualunque contributo (articolo, poesia, ecc.) che possa essere di interesse per i lettori e/o stimolare una
riflessione ed un eventuale dibattito culturale.
RUBRICA
L'Angolo della Cultura (non solo Medicina...)
The gender debate in medicine
Il dibattito sul genere nella medicina
Flavia Franconi1,2, Anna Maria Moretti2,3
1
Dipartimento di Farmacologia, Università di Sassari, Sassari, Italy
GISeG (Gruppo Italiano Salute e Genere), www.giseg.org
3
Struttura Complessa Malattie Respiratorie, Azienda Ospedaliera-Universitaria Policlinico Bari, Bari, Italy
2
In recent years gender medicine has become an important issue and the use of gender determinants in
health politics has been suggested by the United
Nations (2006), World Health Organization (WHO)
(2009) and European Union. However, genderblindness, i.e. the failure to identify or acknowledge
differences on the basis of gender, has been present
at all levels of medical practice and education right
up to the end of last century. Data arising from studies mainly conducted on men have been extrapolated to represent the experiences of both sexes [1,5].
Nevertheless, it is indisputable that there are substantial biological and social differences between
females and males. Despite the multitude of health
inequity problems, little systematic research has
been done on the social causes of ill-health. Of relevance to this context, in 1991 Bernadine Healy
summarized two studies in the New England
Journal of Medicine that demonstrated a sex bias in
cardiovascular diseases [3]. She spoke of a “Yentl
syndrome”: Yentl is the young heroine in Nobel
prize-winner Isaac Singer’s short story set in the
Lublin Jewish community, who had to dress and act
like a boy to be able to attend school and be educated in the Talmud [7].
Sex and gender differences are the result of multifactorial inputs, which involve genes, hormones,
society, psychology, etc. [5]. The word ‘gender’
comes from the Latin genus (type, descent, family),
cognate with Greek γένος (race, stock, kin). Before
the 14th century, the term genus indicated “things
that have to be treated differently because of their
inherent differences”. From the 14th century onwards, the term ‘gender’ has been used as a synonym for ‘sex’. However, between the 1950s and
1960s, ‘sex’ and ‘gender’ began to be used distinc-
tively [8]. Since then, ‘sex’ has been used to indicate the biological differences and ‘gender’ to refer
to social and cultural influences. This distinction
has also been used to argue against the notion that
“biology is destiny”. In the 1970s, the sex difference
was used to argue that women should not become
airline pilots because they would be hormonally
unstable once a month and, therefore, unable to
perform their duties as well as men. There are many
definitions of gender, but we will recall just one that
defines gender as “self-representation as male or female and how the individual is responded to by social institutions” [9]. This definition includes selfrepresentation, which also includes biological aspects.
The WHO uses gender to refer to “the socially constructed roles, behaviors, activities, and attributes
that a given society considers appropriate for men
and women” [10]. In addition, the WHO recently
stated that “the increased knowledge and evidence
of the impact of gender inequalities on specific
health problems and health services and of successful responses, and developing tools to promote and
expand health sector policies, interventions and
programs that systematically address gender concerns” represents a key issue in human health.
Historically, men have been the investigators and
the doctors. Women became accepted as fullyfledged medical practitioners in the 19th and 20th
centuries, but not without a struggle. The following
article by Corrado Petrocelli describes some of the
struggle that women have had and shows that the
‘Yentl syndrome’ is not only a creation of Isaac
Singer’s fantasy, but reflects the reality of many
women in the past who wanted to be doctors.
MRM
59
References
1. Uhl K, Parekh A, Kweder S. Females in clinical studies:
where are we going? Clin Pharmacol Ther 2007;81:600602.
2. Franconi F, Brunelleschi S, Steardo L, Cuomo V. Gender differences in drug responses. Pharmacol Res 2007;55:81-95.
3. Healy B. The Yentl syndrome. N Engl J Med 1991;325:274276.
4. Wise WT, Pardue ML, eds. Institute of Medicine, Committee
on Understanding the Biology of Sex and Gender
Differences, Board on Health Sciences Policy. Exploring the
Biological Contributions to Human Health: Does Sex
Matter? Washington, DC: National Academy Press, 2001.
5. Leinwand LA. Sex is a potent modifier of the cardiovascular
system. J Clin Invest 2003;112:302-307.
6. Schiebinger L. Women’s health and clinical trials. J Clin
Invest 2003;112:973-977.
7. Singer IB. Yentl the Yeshiva Boy, transl. from the Yiddish by
Magid M, Pallet E. New York: Farrar Straus, 1983.
8. Stoller RJ. Sex and Gender: On The Development of
Masculinity and Femininity. New York: Science House,
1968.
9. Exploring the Biological Contributions to Human Health:
Does Sex Matter? Wizemann TM, Pardue ML, eds.
Washington, D.C.: National Academy Press, 2001.
10. United Nations (1995). Report of the Fourth World
Conference on Women. Beijing, United Nations (On-line).
Retrieved September 26, 2006, from United Nations website:
http://www.un.org/womenwatch/daw/beijing/pdf/Beijing%
20full%20report%20E.pdf What do we mean by "sex"
and
"gender"?"
World
Health
Organization.
http://www.who.int/gender/whatisgender/en/index.html.
Retrieved 2009-09-29.
Women in the history of medicine
Le donne nella storia della medicina
Corrado Petrocelli
Chancellor of the University of Bari “Aldo Moro”, Bari, Italy
In September 1812 James Stuart Barry graduated in
Medicine at the University of Edinburgh. In only a
few short years Barry had become famous for his
ability as a military surgeon. He had served the
British Empire in Africa, in Malta, in the Caribbean
and in the Crimea, and in 1857 he arrived in
Canada as Inspector-General of Hospitals. In all
these places he had become well known not only
for his medical genius, but also for his eccentric
personality and effeminate appearance. He was argumentative and always ready to fight a duel if anyone commented on his voice or androgynous features. However, his medical abilities guaranteed
him a successful career and only when he died in
London in 1865 did the truth come out. James
Stuart Barry was in fact Miranda Barry, a woman
who had dressed as a man all her adult life to be
able to practise as a doctor. But even after her
death, she was still victim of the prejudice that denied women the possibility to be doctors, above all,
to be military surgeons. Appalled by the idea that a
woman could have been a successful surgeon, army
officials locked away Dr. Barry’s service records
and hoped the story would go away.
The story of Dr. Barry is not an exception, but only
one episode in a long tradition. The Roman author
Hyginus tells the story of the Greek maiden
Agnodice, who in the 4th century BC dressed as a
man to learn and practice medicine, which at that
time in Athens was forbidden by law to women.
60 MRM
This ban was a serious, often fatal, problem for
women because, having been taught to be ashamed
of their bodies, they were loath to consult a male
doctor for childbirth or for gynaecological problems. Hyginus says that since Agnodice desired to
learn medicine, she donned the clothes of a man
and became a student of Herophilos, the famous
anatomist, in Alexandria. On returning to Athens
she became very successful at treating women to
whom she naturally revealed her real identity.
Jealous of their “new colleague”’s achievements,
the medical profession accused “him” of seducing
“his” patients who were feigning illness to get visits
from him. Brought before the Areopagus, “he” was
found guilty as charged, forcing Agnodice to lift her
tunic to show that she was a woman. At this point,
her accusers became even more vehement and
once again she was condemned, this time for practising medicine and for working under a false name.
She was saved by the arrival of some aristocratic
women, who said: “you men are not spouses but
enemies of the human race, since you are keeping
women from procreating and perpetuating the human race” (Hyginus, Fab. 274). The protest of the
matrons worked: Agnodice was freed and the law
was changed so that women could study and practice medicine, but obviously only with female patients.
The protest of the ladies of the Athens aristocracy
was not however based on any claim to the rights of
women, but was only a plea based on their physiological needs. The prevailing philosophical theories
of the time were that men and women were two
separate and distinct elements, with men being
complete, while women were a degeneration from
perfect human nature. It was Aristotle and his
school who defined the character of the diversity of
the feminine element as a complex of inferiorities.
Namely that women have smaller brains, less cranial sutures (necessary for the brain to take air and
fulfil its natural functions), a weaker voice and less
powerful muscles. The special characteristic of this
deficiency, according to Aristotle, is a state of weakness that takes form in an imperfect and inferior being; like a child, the woman has a “soul without authority”; and while the male child will acquire it on
becoming an adult, the woman is forever deprived.
Aristotle and his school further explained that,
among those biological phenomena which regulate
the survival of the human species, to be born female
is a teras, to be born a monster; the female organism
is only an outline of a human being, like that of a
male child, however, unlike the male child, the female has no hope of achieving perfection. The female body is an anomaly which has the mark of impotence: to reproduce, the male supplies the form
of the being, while the female supplies the matter,
the nourishment for growth; women are incapable
of producing alone, like a field which remains fallow and gives fruit only if it is seeded or like an
oven which can cook only food prepared by others;
a woman is like a blank slate which has no significance unless something is written on it. To put it
succinctly, in the imagine of the Ancients the
woman was passive, incomplete, deficient, she was
defective ‘by nature’, a human anomaly, but an
anomaly that was necessary for the reproduction of
the species.
Even if men have been writing about science from
their misogynous perspective for thousands of
years, women too have been doing and still do science. Who they are and what they did can be
glimpsed from the meagre leavings that tradition, a
tradition of men and by men, has kept alive, almost
by mistake. We can find names or implicit references and memories, which are often critical of the
women if it has been impossible not to mention
them. From the beginnings of Western culture,
namely the Iliad of Homer, we meet Agamede,
daughter of the king of the Epeans. She treated the
wounded soldiers on the plains of Troy, not as an
amateur nurse but as a real physician “who knew
all herbs that the wide earth nourishes” (Iliad
XI,740-741). Even Helen of Troy, the cause of the
Trojan war, was a skilful healer, having studied under Polydamna, whose name means “she who subdues many diseases”. This should not be a surprise
because, according to Homer, Egypt “bears greatest
store of drugs, many that are healing when mixed,
and many that are baneful; there every man is a
physician, wise above humankind; for they are of
the race of Paeëon” (Odyssey IV,227-232).
In ancient Egypt women practised the medical profession. Female students and teachers from all over
the Mediterranean attended the medical schools at
Sais and Heliopolis. In the temple at Sais we can
read this inscription: “I came from the medical
school in Heliopolis and I studied at the women’s
school in Sais, where the divine mothers taught me
to cure illness”. Moses and his wife Zipporah also
studied at Heliopolis in the 15th century BC, the
same epoch when the female pharaoh Hatshepsut
of the 18th dynasty organised an expedition to find
officinal plants. Various medical Egyptian papyri refer to gynaecological problems, gynaecology being
the only field in which women doctors could operate also in the Nile basin. The Kahun papyrus describes diagnosis for pregnancy, explains studies on
sterility and how to determine the sex of the unborn
child by observing the face of the mother (if it was
green, the baby would be a boy...). Female surgeons
also carried out caesarean sections, operated on tumours and treated bone fractures.
Epigraphic and documentary sources tell us that
there were women physicians and surgeons in the
Greek cities. A school of obstetrics and gynaecology was said to have been founded by Hippocrates
on the island of Kos and though women did not attend this school, they did however attend the rival
school which was in Knidos, on the Anatolian
coast. Hippocrates was well aware of the value of
the medicinal plants discovered by the early
women healers, of whom the most famous was
Artemisia, the powerful queen of Caria who was
credited with knowing the therapeutic properties of
every herb used in medicine.
In the Roman Empire, the study of medicine was a
very important aspect of their scientific culture and
medicine was perhaps the only profession open to
women, allowing them to achieve in this field a
professional status, which they did not again attain
until the beginning of the 20th century. In the Roman
era, though principally dealing with female patients, with pregnancies, childbirth and gynaecological diseases, women doctors were actively
sought after for other remedies. We know of Greek
slave women who worked as physicians in the
Roman hospitals. They also knew Greek scientific
theories as well as did their male colleagues.
Roman matrons were well known for their medical
abilities, which they practised both in the hospitals
and at home. Pliny the Elder tells of Salpe from
Lemnos, an expert in ophthalmology, and of
Olympias from Thebes, a renowned gynaecologist.
One of Galen’s collaborators was Antiochis, who
specialised in arthritis and diseases of the spleen.
Could it perhaps be true what people said, that
Galen copied several treatments from her? We also
hear of Elephantis from Lemnos and Lais. These are
mentioned in derogatory terms by Galen, Soranus
of Ephesus and Pliny the Elder in his Natural
History. Elephantis wrote medical tracts and taught
in Rome and of her it is said that she was so beautiful that she gave lessons from behind a curtain so
as not to distract the students. Lais was also famous,
but neither of them was appreciated by Pliny. He
describes their medical activities in these terms:
“Lais and Elephantis do not agree in their statements about abortive, the burning root of cabbage,
myrtle, or tamarisk extinguished by the menstrual
MRM
61
blood, about asses not conceiving for as many years
as they have eaten grains of barley contaminated
with it, or in their other portentous or contradictory
pronouncements, one saying that fertility, the other
that barrenness is caused by the same measures. It
is better not to believe them” (Nat. Hist. XVIII,
23-81).
Scribonius Largus, who was court physician to the
Roman emperor Claudius, drew up a list of prescriptions which he had known of, both in Rome
and during his travels with the emperor’s court.
Included in this list were remedies from famous
women such as Messalina, Claudius’ third wife,
Livia, the wife of Augustus, Octavia, his sister, and
Julia, his daughter. Giovanni Ruellio, who in 1529
published De compositione medicamentorum of
Scribonius, affirmed that these members of the imperial family were as famous as Galen in their time
for their medical ability. Among the various women
who wrote on gynaecology, but also on dermatology and cosmetics, which were considered a
branch of the same discipline, the most important
was without doubt Cleopatra, who lived in Rome in
the second century AD. Her treatise, De geneticis,
was still being used up to the end of the 6th century,
when it was confused with the work of Muscius.
Thereafter it was copied various times and attributed to various authors, ‘obviously’ all men. The
same treatment was given to her contemporary
Aspasia, specialist in obstetrics, gynaecology and
surgery. Her writings were attributed to a man
called Aspasius, or it was believed that “Aspasia”
was the name of a lost work on female illnesses; this
name was invented in honour of the more famous
Aspasia of Miletus, hetaira of Pericles. However, the
work must have been written by a man.
The treatment of the works of Cleopatra and Aspasia
is not by any means exceptional. The problem of attribution, involving admitting the presence of
women in scientific fields, arises every time there is
research into the role of women in science. An emblematic case is that of Trotula, one of the female
physicians who worked in the Schola Medica
Salernitana, to which we owe a great debt for the
renaissance of Greek medical knowledge and renewed interest in sciences in the West. The most important work attributed to her is De passionibus
mulierum curandarum (Diseases of Women), also
known as Trotula Maior. Even doctors from our
time laud its merits. Kate Hurd-Mead said that it displayed the kind hand of a woman on every page,
was rich in common sense, very advanced for its
time, the 11th century, above all in surgery and
anaesthesiology, but also in gynaecology, obstetrics
and paediatrics. No similar work had been written
before or would be for centuries after (Kate HurdMead, Trotula, “Isis” 1930;14:364). The advice in
Trotula Maior is surprising for its modern ideas: for
example, its emphasis on the importance of hygiene, of a balanced diet and of physical exercise,
and also the reference it makes to the effects of
stress. The wide distribution and extensive copying
of the work has made it very difficult to identify the
original texts. Like the work of Cleopatra, also
Trotula’s treatise was copied as many times as it was
62 MRM
plagiarized. Rarely does the name of the author appear either in the manuscripts or in the first printed
editions, it is often transformed into the male equivalent Trottus or into other names such as Eros or
Erotianus. Eros was the personal doctor of Julia,
Augustus’ daughter, who wrote on gynaecology and
cosmetics, while Erotianus was the doctor of Nero
or Marcus Aurelius, who wrote a commentary on
Hippocratic gynaecology. The work was probably
ascribed to these authors because their works were
originally printed in the same period as Trotula
Maior, though clearly there is no possibility of either of them being the author, they having lived
many centuries before the authors quoted by
Trotula. Nevertheless, historians used these incongruities to ascribe the composition of the work to a
man, a doctor from Salerno. Karl Sudhoff and his
school were the first to openly declare that the
women doctors of Salerno, including Trotula, were
not physicians and scientists, but only nurses and
midwives and could not have had the knowledge of
surgery such as appears in Trotula’s works. For
them, the name was easy to explain, after all it was
a common female name in Salerno in that period,
and for this reason particularly apt for what was
principally a work of obstetrics.
For the historians of the 19th century it was easy to
dismiss the work of women doctors as they were
heirs of the Age of Enlightenment, when the “doctresses” of the salon were pilloried and ridiculed for
their amateur doctoring. The Goncourt brothers
wrote: “The passion for medicine is universal in this
society, people go mad for surgery. Even many
women have learnt to handle scalpels, while others
are jealous of the Countess De Voisenon, who
learnt from the physicians who attended her grandmother’s salon something about the art of healing
and so practices her treatments among her friends,
that is to say on whoever she can lay hands on.
Anatomy is one of the great female passions. In fact,
the Countess of Coigny is so enamoured of this horrible science that she never travels without a corpse
to dissect”. They intended: she does this in the same
frivolous way as she would take a book to read or a
pattern to embroider. And this making fun was of
course intentionally meant to hurt.
But the brothers had never heard of Mary Wortley
Montague, an elegant and courageous English lady
who introduced variolation into Europe and was
able to convince the English royal family of its benefits. More than 60 million people died of smallpox
all over the world in that time, more than 45,000 in
Britain. However, Lady Mary was not only a woman
of science, she was also one of the most fascinating
women of the period. From a young age she was
self taught and noted for her erudition, wittiness
and strength of will, but above all for the battles she
fought in the name of women’s emancipation “with
a viper’s tongue and a pen as sharp as a razor”, as
the chronicles of the time say. In January 1753 she
wrote to her daughter about her granddaughter’s
education, that the little girl “should hide whatever
culture with the same care with which she would
disguise being lame or halt, because to show any
knowledge of science brings only envy and in con-
sequence instinctive acrimony from all those fools,
both men and women, who compose at least a third
part of the people she knows”. It was the awareness
that she lived in a misogynist society which inspired
her to write exactly these words. In that time, and
almost up to the 20th century, there was the growth
of a scientific movement to prove the inferior intellect of women, in particular that women were biologically unsuitable for scientific activity. It was too
late; from many directions the evidence of women
in science claimed its due role in society, and not
only in the professions but even more so in the
fields of teaching and research.
And yet in the most patriarchal of ancient societies
women too studied medicine. They attended the
school of medicine with their male colleagues in
Baghdad. They are the women physicians of Islam.
Western works of history do not mention them, but
we know of their existence thanks to the stories of
“The Arabian Nights”. Here Shaharazad tells the
story of Tawaddud in 26 nights. Tawaddud is the
slave-girl of Abu Al-Husn, profligate son of a rich father. To save her master from poverty she tells him
to sell her for an enormous sum to the Caliph, who
will have to prove her scientific talents. The Caliph
gathers together the most learned men from all parts
of his dominions to question her. When she is interrogated by a physician she answers him with a discourse on physiology, she describes the bones and
the circulatory system, the internal organs and the
relationship of the four elements with the four humours. She speaks of the symptoms of disease, emphasising the importance of a balanced diet and expatiating with confidence against the usual practice
of blood-letting. She quotes Galen by heart and answers all the questions asked until the physician declares: “O Commander of the Faithful, bear witness
against me that this damsel is more learned than I in
medicine and I cannot cope with her”. The Caliph
pays Abu Al-Husn a larger sum than had been requested and tells the slave to ask for whatever she
wants. Tawaddud asks only to be able to continue
her studies in medicine with her master at the
Caliph’s court. Her wish is granted.
In spite of every legitimate claim, whether strong or
weak in the evolution of scientific thought, the story
of the discrimination against women in medicine is
long and still to be written. At the same time that
Miranda Barry, the doctor James whom we met at
the beginning of this discourse, was dying in
London, Elizabeth Garrett Anderson, who was already a nurse at Middlesex Teaching Hospital, was
completing her studies in anatomy and surgery.
Whenever she passed an exam with brilliant marks,
she was invited to keep her success a secret from
the other students. When, in June of 1861, she answered a question in class that no other student
could answer, the male students drew up a petition
calling for her exclusion on the grounds that she
was interfering with their progress. She was soon
forbidden to attend lessons or enter the hospital.
However, she was able to embark on a career as a
surgeon. She should be remembered because she
fought the “Edinburgh Battle” with Sophia Blake.
This was an episode as noteworthy as it was extraordinary in the history of women and of medicine.
A group of women were able to matriculate at
Edinburgh University and there they formed the first
class of women students in medicine.
Unfortunately, they were more capable than their
male colleagues. Therefore male students and
teachers considered their success as a threat and reported them for fraud. However, after a hard struggle against prejudice from doctors, professors and
other students, they had to abandon their studies
when the Scottish Court of Sessions ruled that the
University had the right to refuse them degrees.
Most of the women moved to Switzerland and graduated in Bern. After a few years they returned to
Ireland and founded the “London School of
Medicine for Women”, where the original students
were able to complete their studies. Finally, following a new law, the Irish College of Physicians
granted medical practice licences to the women.
At least, their aim had been achieved, a victory
had been won. This was an important victory, but
it is only one on a long and difficult road, one battle among many of a war fought at the price of sacrifice and struggle for centuries, and still fought
today.
References
1. Alic M. Hypatia’s heritage: a history of women in science from
antiquity to the late nineteenth century. London: Women’s
Press, 1986.
2. The Arabian Nights. Tales of 1001 Nights, transl. by Lyons MC,
with Lyons U, intr. and annotated by Irwin R. London, 2008.
3. Aristotle. Generation of animals, with an English transl. by
Peck AL. London, 1953.
4. Aristotle. On the parts of animals, transl. with a commentary
by Lennox JG. Oxford, 2001.
5. Bayon HP. Trotula and the Ladies of Salerno: a contribution to
the Knowledge of the transition between ancient and mediaeval physick. Proc R Soc Med 1940;33:471-475.
6. Benton JF. Trotula, women’s problems, and the professionalization of medicine in the Middle Ages. Bull Hist Med
1985;59:30-53.
7. Cosmacini G. L’arte lunga. Storia della medicina dall’antichità
a oggi. Roma-Bari: Laterza,1997.
8. DuBois P. Sowing the body. Psychoanalysis and ancient rep-
resentations of women. Chicago, 1988.
9. Duby G, Perrot M. A history of women in the West. I-V,
Cambridge (Mass.), 1992-1994.
10. De Goncourt E, de Goncourt J. The Woman of the eighteenth
century. Her life, from birth to death, her love and her philosophy in the worlds of salon, shop, and street. New York, 1928.
11. Goodwather L. Women in antiquity: an annotated bibliography. London-Metuchen: Scarecrow Press, 1975.
12. Hamilton G. Trotula. Modern Philology. Chicago, University
of Chicago Press, 1906;4:377-380.
13. Homer. The Odyssey. Books 1-12, with an English transl. by
Murray AT, rev. by Dimock EG. London, 1995.
14. The Myths of Hyginus, transl. and ed. by Grant M. Lawrence,
1960.
15. Pliny. Natural History, with an English transl. in ten volumes,
VIII, by Jones WHS. London, 1963.
16. Du Preez HM. Dr. James Barry: the early years revealed. S Afr
Med J 2008;98:52-58.
MRM
63
Il tonfo della sterlina: la “Cool Britannia” è al
capolinea?
The slump of the British pound: is British ‘cool’
at an end?
Francesco Iodice
Già Direttore U.O. s.c. di Fisiopatologia Respiratoria, Ospedale A. Cardarelli, Naples, Italy
“Niente è più deprimente che dare
un pacchetto di banconote
all’aeroporto prima di un viaggio e ricevere
indietro una mazzetta più sottile”.
The Times
Ad un turista inglese, che in un albergo a cinque
stelle dell’Ucraina chiedeva di cambiare sterline in
valuta locale, è stato risposto: “Non accettiamo più
il pound, solo euro e dollari”. La British Airways, la
British Telecom e la British Airport Autority hanno
tolto dal logo aziendale la parola British e si limitano a presentarsi come BA, BT e BAA (il Governo
britannico si farà forse chiamare BG?). Questi episodi indicano che mai prima d’ora l’Inghilterra aveva raggiunto una così bassa considerazione. La forza centrifuga del “credit crunch”, il credito scricchiolante, ha mandato un sistema intero in confusione, un mondo ribaltato: dalle istituzioni alle bandiere, dagli uomini ai cani. Anche il bulldog - simbolo supremo della churchilliana “inglesitudine” paga il prezzo del cambiamento: dovrà essere più
alto e più magro, meno deformato nella mascella e
nel naso. Lo ha deciso il consiglio dei guru del
Kennel Club - l'associazione che riunisce gli allevatori e ne regolamenta l'attività - che ha approvato
nuove norme in base alle quali l’aspetto classico
verrà radicalmente trasformato. Via la mascella cadente, il bulldog del futuro dovrà avere muso più
asciutto, naso meno pronunciato, gambe più lunghe e corpo più magro. Diventando più simile, per
rendere l'idea, a un boxer, perché, pare, sia politicamente più corretto. La sua fama come simbolo di
“britishness”, britannicità è abbastanza recente: vi
contribuì un poster disegnato nel 1942 dall'artista
Henri Guignon, che mostrava la faccia di Churchill
su un corpo di bulldog, con sullo sfondo l'Union
Jack, la bandiera del Regno Unito, e lo slogan "holding the line" (un messaggio per il Terzo Reich, che
aveva conquistato tutta Europa: "noi resisteremo").
Quando il premier pronunciò un’altra sua famosa
frase (durante il periodo bellico ne pronunziò, in
verità, parecchie), "we will never surrender" (non ci
arrenderemo mai), sembrava di sentire abbaiare sullo sfondo il suo fedele quattro zampe, al quale, secondo un famoso poster della seconda guerra mondiale, Winston Churchill somigliava anche fisica64 MRM
mente: piccolo, tarchiato, dalle guance paffute ma
dai denti aguzzi, un ostacolo insormontabile davanti a Hitler.
Oggi il bulldog è un simbolo della Gran Bretagna,
come il bus a due piani rosso, il taxi nero, la cabina
del telefono. È uno dei simboli del Regno Unito, lo
specchio della britannicità: forza, coraggio e soprattutto rifiuto di arrendersi, in qualsiasi circostanza.
La notizia è talmente grossa che il Times l'ha sparata in prima pagina, con la gigantografia di un bulldog dall'aria triste e il titolo: “R. I. P. - the British
bulldog, victim of breeding laws”: ovvero “Riposa
in Pace - il bulldog britannico, vittima delle leggi
sull'allevamento”.
Ritornando alla crisi economica, aumentano coloro che vorrebbero seppellire il pound sotto lo
schiaffo dell’euro. La globalizzazione tenta di appannare la britishness di realtà planetarie:
Wedgwood, marchio della porcellana, diventa
americana; Woolworths, gloria dei grandi magazzini, sarà solo on line; i pub chiudono perché la
birra cede al vino e perché vengono acquistati da
immobiliaristi palazzinari e la ‘shepherd’s pie’, il
pasticcio di carne, affoga nel ‘sushi’.
Quando Tony Blair diventò primo ministro, nel
1997, uno dei suoi obiettivi principali era quello di
«portare la Gran Bretagna in Europa»: cioè fare di
questo Paese, ancora scioccato dalla perdita dell’impero e dello status di superpotenza, un membro
a pieno titolo dell’Unione Europea. Era venuto il
momento di ribaltare, credeva Blair, il vecchio atteggiamento riassunto dalla nota barzelletta:
«Nebbia sulla Manica, il continente isolato». Era
Londra a rischiare di sentirsi isolata, secondo Blair,
se non si univa completamente all’Europa, magari
con l’ambizione di diventarne leader. Ma nel 2003
le polemiche sulla guerra in Iraq consumarono rapidamente il capitale politico del leader, e a quel
punto egli capì che il popolo non lo avrebbe seguito più.
Del resto il boom economico degli anni del blairismo - quando la Gran Bretagna venne ribattezzata
“Cool Britannia”, ovvero una Britannia fresca, nuova, trendy, vincente - costituiva già di per sé un
ostacolo a ogni passo verso l’euro. La prodigiosa
crescita economica del Regno Unito, sospinta dal
polmone finanziario della City, contrastava con il
lento, burocratico cammino delle economie continentali. Si diceva allora che Londra avrebbe valutato l’opportunità di entrare nell’euro-zona, se e
quando l’Europa avesse marciato al passo economico della Gran Bretagna. Inoltre, a raffreddare gli entusiasmi di Blair ci pensò proprio Gordon Brown allora ministro delle Finanze e vice di Blair - impaziente di prendergli il posto.
Oggi il cambio ufficiale della sterlina sull’euro è circa 1,19, vale a dire che un euro vale attorno a
0,837 pound e le due monete marciano verso la parità. Nel corso degli ultimi anni la valuta britannica
ha perso qualcosa come il 22% su quella
dell’Unione e nessuno sogna più il rapporto di forza
del maggio 2000, quando il cambio era a 1,74. Ma
fin qui si ragiona in termini di tasso ufficiale. Poi c’è
la realtà della strada: se si va su Oxford Street a
Londra, le tabelle di conversione rivelano che la
sterlina è ancora più giù, è scesa addirittura sotto
l'euro. A Liverpool e Birmingham, Travelex cambia
200 sterline con 197 euro e 13 centesimi. Uno
choc per molti inglesi. E nel declino c'è molto di
psicologico. I giornali avvertono i lettori che in queste condizioni «un weekend a Parigi può vuotarvi le
tasche». Seguono tabelle: una cena per due l'anno
scorso a Parigi sarebbe costata in un bel bistrot 80
euro, vale a dire 58 sterline. Oggi servono 73 sterline. Una birra in un bar spagnolo è passata da 2,19
a 2,71 sterline (brutto affare, perché gli inglesi sono
convinti che in Spagna faccia caldo anche in inverno e ingurgitano quantità industriali di cerveza). C'è
anche un esempio italiano: due biglietti per vedere
il Milan a San Siro da 102 sterline a 126. Gli analisti
prevedono che la Bank of England taglierà ancora il
costo del denaro e la sterlina sarà spinta alla parità
ufficiale.
Qualcuno aveva accusato Gordon Brown di aver
causato il tracollo con la sua politica di spesa e indebitamento che è stata definita «Italian style». Ma
il paragone italiano, oltre che sberleffo politico, è
anche uno spettro che si chiama «sorpasso». Per effetto della recessione e del crollo della sterlina
l'Italia, secondo il Centre for Economics and
Business Research, misurata in base al Pil poco
tempo fa era dietro solo del 6% rispetto al Regno
Unito. E in base alle proiezioni si parla di nuovo
sorpasso in vista.
Certo, nessun Paese rinuncia senza qualche rimpianto alla propria moneta. I Paesi europei che hanno adottato l’euro, ormai, si sono abituati e hanno
dimenticato le ansie di anni fa, quando fu creata la
zona euro. Ma all’epoca vi fu un rammarico diffuso
per la fine del franco, del marco, del fiorino e della
lira, specialmente tra i più anziani.
Una moneta nazionale ha due funzioni. La prima,
di ordine pratico, è quella di fornire i mezzi attraverso i quali i mercati possono funzionare e un modello sul quale poter misurare il prezzo di tutti i beni, compreso quello del lavoro. L’altra funzione è
simbolica: la moneta è una delle espressioni di una
nazione, come la bandiera e l’inno nazionale. La
funzione pratica e quella simbolica si incontrano
nella posizione internazionale della valuta: le mo-
Campagna inglese.
nete e le banconote di un Paese sono la dichiarazione della sua forza e più mantengono il loro valore
nei confronti delle altre valute, più lo Stato è considerato forte, specie dai suoi cittadini.
Quando la maggioranza dei Paesi membri
dell’Unione Europea decise di creare una moneta
comune fece una dichiarazione, allo stesso tempo,
politica e monetaria. Essi rinunciarono non solo al
controllo sulla loro valuta e al relativo tasso d’interesse, alla possibilità di svalutarla per aumentarne
la competitività, ma anche ad un simbolo delle loro
differenze nazionali. Fu un’iniziativa audace, che si
disse irrevocabile, benché potrebbe non esserlo. Fu
un’iniziativa che la Gran Bretagna non si sentì in
grado di assumere; e per gran parte degli ultimi anni
si è congratulata con se stessa per non averla assunta. La sterlina è stata forte sia nei confronti dell’euro
che del dollaro, e l’economia britannica è stata una
delle più forti d’Europa.
Quel che sembrava però impossibile da una posizione di grande forza, oggi appare possibile da una
posizione di debolezza; anzi, oggi la Gran Bretagna
- più dipendente dai servizi finanziari rispetto al
continente e meno sorretta da un’industria manifatturiera - appare perfino più esposta alla recessione
globale di quanto sia il resto dell’Europa. La crisi
trascina in basso la valuta britannica al punto che in
La Gran Bretagna nel 2008 è scesa al quarto posto tra i Paesi
del G6, superata da USA, Francia e Germania.
MRM
65
termini di reddito pro capite l’Italia ha scavalcato il
Regno Unito. Dopo il boom degli anni di Tony Blair,
il mito della “Cool Britannia” sembra al capolinea.
E pertanto i paladini dell’adesione alla moneta unica europea riprendono forza e fiato.
La regina Elisabetta continua a sorridere, appena un
accenno di sorriso in verità, simile a quello della
Gioconda, sulle banconote da cinque, dieci, venti e
cinquanta sterline. Ma i suoi sudditi che avevano
prenotato le vacanze di fine anno in Europa, a sciare sulle Alpi, in visita a Parigi, Roma o Berlino, hanno fatto una smorfia di incredulità e disappunto al
momento di cambiare la moneta britannica in euro.
Accelerando un progressivo declino che durava da
due-tre anni, la loro valuta nazionale sta precipitando, tirata giù dalla crisi finanziaria ed economica
che ha colpito la Gran Bretagna più duramente del
resto del continente: la sterlina - come abbiamo accennato prima - che valeva un euro e quaranta nel
2003 e al tasso praticato ai turisti era spesso cambiata a un euro e mezzo, è ora scambiata alla pari
con l’euro e gli specialisti prevedono che potrebbe
scendere ancora più in basso.
Abituati per anni a potersi permettere le ferie in
Europa con estrema disinvoltura, adesso i cittadini
del Regno Unito devono pensarci due volte e fare
bene i conti; mentre, capovolgendo la situazione,
vedono sbarcare a Londra valanghe di stranieri, per
i quali è diventata all’improvviso una meta economicamente sostenibile. Così, in questo Paese si sentono voci favorevoli all’adozione della moneta comune europea.
Simbolo dell’orgogliosa diversità britannica, icona
dell’euroscetticismo, la sterlina potrebbe essersi avviata sul viale del tramonto. «La sterlina continuerà
a esistere, quest’anno, l’anno prossimo e quello dopo», aveva detto Gordon Brown in tivù.
“Non abbiamo mai avuto tanto bisogno di far parte
dell’Europa come ora di fronte a questa crisi mondiale», si è schierato invece senza mezzi termini il
quotidiano Independent. Più chiaro di tutti ha parlato José Manuel Barroso, presidente della
Commissione Europea: «La Gran Bretagna è più vicina che mai all’adesione all’euro», ha dichiarato in
una conferenza stampa. «La recessione ha indebolito la fiducia nella sterlina”.
Un gruppo di esperti si è radunato nella famosa
Chatham Economics House e dopo un dibattito è
giunto alla conclusione che restare fuori dall’euro
vuol dire per la Gran Bretagna essere esclusa, in
pratica, da più profonde consultazioni economiche
in aree di significativo interesse nazionale. Oggi,
quella britannica è tra le economie più duramente
colpite dalla crisi finanziaria e se l’euro potrà diven-
66 MRM
La crisi economico-finanziaria sta trascinando la valuta britannica ai livelli più bassi della sua storia.
tare la nuova valuta dominante, la riluttanza britannica a rinunciare alla propria moneta potrebbe affievolirsi; ma sarà un processo lento. Una previsione prudente potrebbe essere quella secondo cui la
sterlina resterà - strapazzata, ferita e umiliata - ancora indipendente per qualche anno.
Forse la nebbia sulla Manica non isolerà per sempre
il continente. Chissà se la regina Elisabetta, prima di
lasciare il trono, smetterà di sorridere sulle banconote dei suoi sudditi. Molti pensano che questa crisi finanziaria - rispetto a quelle del 1931 e degli anni
Settanta - sia meno fisica, ma più subdola e che sia il
prodotto di un avvitarsi crescente della complessità,
grazie anche agli strumenti dell’elettronica, sulla
semplicità. Quando le banche funzionavano con
penne e inchiostri - mi si permetta l’iperbole - quando gli amanuensi compilavano le note contabili, tutto ciò non succedeva, non poteva succedere.
Molte altre cose non avvenivano nel piccolo mondo antico cui l’Inghilterra oggi dedica tanti pensieri,
anche senza rimpiangerlo. Venti anni di rincorsa
verso la modernizzazione, che oggi si infrange contro gli slogan neo protezionistici delle raffinerie in
sciopero e la pretesa di assumere la guida della globalizzazione, hanno richiesto visione e determinazione. Per essere eroi ci vogliono molte qualità, ma
il coraggio non ha sostituti, e l’Inghilterra di coraggio in passato ne ha avuto parecchio - sia nel cambiare che nel resistere al cambiamento in difesa delle tante peculiarità della “britishness”- ed è sempre
andata bene. Almeno fino a ieri.
Meeting Calendar
Questa rubrica informa i lettori dei prossimi eventi congressuali, nazionali ed internazionali, nell’ambito
della Medicina Respiratoria; fornisce un recapito a cui rivolgersi per ottenere ulteriori informazioni.
WHEN
WHERE
WHAT
February 2-3
London
(UK)
Naples
(Italy)
5th Annual Conference: “Adaptive Designs
in Clinical Drug Development”
Congresso: “Il Paziente Respiratorio: dalla Clinica
alle Strategie Terapeutiche” 13^ Edizione
Berlin
(Germany)
Milan
(Italy)
Rome
(Italy)
Porto
(Portugal)
Milan
(Italy)
London
(UK)
London
(UK)
Turin
(Italy)
Paris
(France)
Stresa, VB
(Italy)
Sorrento, NA
(Italy)
Course: “Lung Cancer”
RUBRICA
WHO TO CONTACT
2011
February 3-4
February 3-5
February 17-18
February 17-19
February 24-26
February 25-26
March 3-4
March 7-8
March 11-12
March 14-16
*
March 16-18
March 24-26
March 24-26
March 24-26
ATP
Veruno, NO
(Italy)
Monte Carlo
(Monaco)
March 26
Partinico, PA
(Italy)
March 26
Foggia
(Italy)
March 28
Milan
(Italy)
March 30 – April 2 Bari
(Italy)
March 31 – April 2 Estoril
(Portugal)
= evento AIMAR
Seminar: “Quality of the Life-long Personal
Health Record”
Course: “Clinical exercise testing”
16th International Symposium on Infections
in the Critically Ill Patient
4th International meeting on Pulmonary rare
diseases and orphan drugs
2nd National Conference COPD 2011:
from evidence to practice
Conference: "Imaging in Cancer Drug
Development"
12th European Congress:
Perspectives in Lung Cancer
Course: “Paediatric Bronchoscopy”
www.adaptivepharmatrials.com
iDea Congress, Roma
[email protected]
www.ideacpa.com
[email protected]
www.ersnet.org
[email protected]
[email protected]
www.ersnet.org
www.infections-online.com
Victory Project Congressi, Milano
www.ilpolmone.it
[email protected]
www.smi-online.co.uk/2011imaging.asp
[email protected]
[email protected]
www.ersnet.org
Dynamicom, Milano
1° Congresso Congiunto AIMAR-American
College of Chest Physicians
[email protected]
Convegno: “Sorrento Breathing – Update and new Center Comunicazione e
trends in respiratory medicine”
Congressi, Napoli
[email protected]
www.centercongressi.com
Course: “Monitoring of Airway Disease”
[email protected]
www.ersnet.org
9th Anti-Aging Medicine World Congress
AMWC, Monaco
& Medispa – Aesthetic Dermatology and Surgery [email protected]
Preventive and Anti-Aging Medicine
www.euromedicom.com
Convegno: “3° Corso di pneumologia
CicaCongress, Palermo
del territorio – Governo clinico delle Malattie
[email protected]
Respiratorie nel Territorio”
www.cicacongress.com
“Corso Teorico-Pratico di assistenza
e20econvegni, Trani (Bt)
respiratoria domiciliare”
[email protected]
www.e20econvegni.it
Congress: "4th Workshop focus on Aspergillosis
www.arseducandi.it
An update 2011"
8° Congresso Nazionale - 6th International
c.labmeeting, Bari
Conference on Cardiovascular and Respiratory
[email protected]
Disease in Family Medicine “CardioPneumo
www.clabmeeting.it
AIMEF 2011”
2nd International Congress: “Respiratory
Aim Group International, Firenze
and Allergic Diseases from Childhood to Oldness” [email protected]
www.seas2011.com
= evento con patrocinio AIMAR
* = evento AIMAR organizzato con ACCP-Capitolo Italiano
ATP = evento patrocinato da Alleanza per le Malattie Toraco-Polmonari
MRM
67
WHEN
WHERE
March 31 – April 2 Prague
(Czech Republic)
April 1-3
Estoril
(Portugal)
April 7-9
San Diego, CA
(USA)
April 8-9
Ostuni, BR
(Italy)
April 12-15
April 13-14
Marseille
(France)
Varese
(Italy)
WHAT
WHO TO CONTACT
Conference: “Sleep and breathing”
www.sleepandbreathing.com
Conference: “Immune system dysregulation
in chronic lung disease”
Course: “Internal Medicine 2011”
[email protected]
www.ersnet.org
www.acponline.org/im11reg
Convegno “Memorial Blasi II: attualità
diagnostico-terapeutiche in bronchite cronica,
ipertensione polmonare, asma bronchiale,
infezioni polmonari, tromboembolia polmonare,
carcinoma broncogeno"
Course: “Thoracoscopy and Pleural Techniques”
Archeo Congressi, Lecce
[email protected]
www.archeocongressi.it
“Insubria Pneumologia 2011: Aggiornamenti
in Asma Bronchiale e BPCO”
April 16
Bari
(Italy)
“Corso Teorico-Pratico di assistenza
respiratoria domiciliare”
April 18-19
London
(UK)
Paris
(France)
Mesagne, BR
(Italy)
Course: “New Perspectives in Interstitial Lung
Disease: A Multidisciplinary Approach”
IV World Asthma and COPD Forum
April 30 – May 3
May 7
May 12-13
May 13-18
May 21
June 9-11
June 9-11
June 15-18
September 12-14
September 22-24
September 24-28
October 13-15
October 22-27
October 26-30
November 3-5
November 5-7
November 17-19
London
(UK)
Denver, CO
(USA)
Colli del Tronto,
AP (Italy)
“Corso Teorico-Pratico di assistenza respiratoria
domiciliare”
2nd National Conference Clinical Advances
in Cystic Fibrosis 2011
American Thoracic Society Congress
[email protected]
www.ersnet.org
iDea Congress, Roma
[email protected]
www.ideacpa.com
[email protected]
www.e20econvegni.it
[email protected]
www.wipocis.org
[email protected]
www.e20econvegni.it
[email protected]
www.thoracic.org.
Corso: “Ipertensione polmonare: cuore polmonare Centimani, San Benedetto
e polmone cardiaco”
del Tronto, AP
www.centimani.com
Lausanne
Course: “Pulmonary hypertension and pulmonary [email protected]
(Switzerland)
vascular disease”
www.ersnet.org
Pescara
Convegno: "Terzo incontro interdisciplinare
Athena Congressi, Pescara
(Italy)
di Medicina Respiratoria"
www.athenacongressi.it
Maastricht
Congress: “WASOGBAL2011”
www.wasogbal2011.nl
(The Netherlands)
[email protected]
Paris
Course: “Paediatric Bronchoscopy”
[email protected]
(France)
www.ersnet.org
Silvi Marina, TE
XVI Congresso Nazionale Società Italiana
Intermeeting, Bari
(Italy)
di Endoscopia Toracica
[email protected]
www.intermeeting.org
[email protected]
Amsterdam
ERS 21st Annual Congress
(The Netherlands)
www.ersnet.org
Alexandroupolis
Course: “Medical Thoracoscopy”
[email protected]
(Greece)
www.ersnet.org
Honolulu, Hawaii Chest Meeting
www.chestnet.org
(USA)
[email protected]
Lille (France)
42nd Union World Conference on Lung Health
"Partnerships for scaling-up and care”
www.worldlunghealth.org
Athens
Course: “Interventional Bronchoscopy”
[email protected]
(Greece)
www.ersnet.org0.
Bologna
XIII Congresso Nazionale di Oncologia Medica
Aiom, Milano
(Italy)
[email protected]
www.aiom.it
Genova
Congress: "Highlights in Allergy and Respiratory
iDea Congress, Roma
(Italy)
Diseases"
[email protected]
www.ideacpa.com
= evento AIMAR
68 MRM
WHEN
WHERE
WHAT
WHO TO CONTACT
November 22-25
Marseille (France)
Course: “Thoracoscopy and Pleural Techniques”
[email protected]
www.ersnet.org
November 24-26
Taormina
(Italy)
Convegno: "Pneumomeeting 2011:
La gestione integrata in Medicina Respiratoria"
Dynamicom, Milano
Tel. +39 02 89693750
November 30December 3
Bologna
(Italy)
XII Congresso Nazionale UIP - XLI Congresso
www.aiporicerche.it
Nazionale AIPO "Il Sistema delle cure Respiratorie:
la rete pneumologica ed i percorsi assistenziali"
December 4-8
Cancun
(Mexico)
XXII World Allergy Congress
April 18-21
Turin (Italy)
Pulmonary Advances “7th International Conference [email protected]
on Management & Rehabilitation of Chronic
www.aimarnet.it
Respiratory Failure” and “3rd Italian Conference
on a Multidisciplinary Approach to Respiratory
Medicine”
www.worldallergy.org/wac2011
2012
= evento AIMAR
MRM
69
Avviso importante ai Soci
Si rammenta a tutti i Soci che, come più volte comunicato negli
scorsi numeri di MRM, la rivista non sarà più inviata senza
la regolarizzazione dell'iscrizione ad AIMAR.
Le modalità di pagamento della quota societaria per l'anno 2011
sono riportate a pagina 5.
70 MRM

MRM 01-2011_def:Layout 1

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