COPD - Aristea

Forth Mediterranean Congress
Innovative Scenario in Internal Medicine
Palermo 7 Giugno 2014
BPCO : epidemiologia ed inquadramento di
una sindrome complessa
Leonardo M. Fabbri
Clinica di Malattie dell’Apparato Respiratorio
Università degli Studi di Modena e Reggio Emilia
CONFLICTS OF INTEREST
Leonardo M. Fabbri, 2014
BPCO : epidemiologia ed inquadramento
di una sindrome complessa
Leonardo M. Fabbri
 BPCO COME COMPONENTE POLMONARE DELLA
MULTIMORBIDITA’ CRONICA
 ALTERAZIONI FUNZIONALI RESPIRATORIE IN
PAZIENTI CON CARDIOPATIE CRONICHE
 INTERESSAMENTO POLMONARE NELLE MALATTIE
CRONICHE
 COMPLESSITA’ DEL PAZIENTE CON DISPNEA ACUTA
 IL MALATO CRITICO CRONICO
BPCO : epidemiologia ed inquadramento
di una sindrome complessa
Leonardo M. Fabbri
 BPCO COME COMPONENTE POLMONARE DELLA
MULTIMORBIDITA’ CRONICA
 ALTERAZIONI FUNZIONALI RESPIRATORIE IN
PAZIENTI CON CARDIOPATIE CRONICHE
 INTERESSAMENTO POLMONARE NELLE MALATTIE
CRONICHE
 COMPLESSITA’ DEL PAZIENTE CON DISPNEA ACUTA
 IL MALATO CRITICO CRONICO
Global Strategy for Diagnosis, Management and Prevention of COPD
Definition of COPD 2011
COPD, a common preventable and treatable
disease, is characterized by persistent airflow
limitation that is usually progressive and
associated with an enhanced chronic
inflammatory response in the airways and the
lung to cigarette smoking
Exacerbations and comorbidities contribute to
the overall severity in individual patients.
QUANTIFYING COMORBIDITY IN INDIVIDUALS WITH
CHRONIC OBSTRUCTIVE PULMONARY DISEASE: A
POPULATION STUDY
Among 7,241,591 adults
909,948 (12.6%) had COPD
50% of all lung cancer,
33% all lower respiratory tract infection
33% of all cardiovascular disease, a
25% of all low trauma fracture
20% all psychiatric, musculoskeletal,
non-lung cancer and diabetes
ambulatory care visits
emergency department visits
hospitalizations in Ontario
were used by people with COPD
Gershon A et al, Eur Respir J 2014; 7 june 2014, in press
COMORBIDITIES IN INDIVIDUALS WITH COPD
Individuals with COPD used about 5 times more health
services for lung cancer and 2 times more health services
for lower respiratory tract infections and 2or
cardiovascular disease than people without COPD
Gershon A et al, Eur Respir J 2014; 7 june 2014, in press
Pathogenesis of COPD
Cigarette smoke
or air pollutant
?
Alveolar
macrophage
CD8+ T-cell
CXCR3
Inflammatory cytokines
(IL-8, LTB4)
Neutrophil
CXCL-10
Alveolar wall destruction
EMPHYSEMA
Proteases
Mucus hypersecretion
BRONCHIOLITIS
Adapted from PJ Barnes, 2000; Fabbri, Sinigaglia, Papi, Saetta 2002; Cosio,
Saetta and Cosio 2012
Leading Causes of
Death in U.S.
1. Myocardial
Infarction
2. Cancer
3. Cerebrovascular
Diseases
4. COPD
Cigarette Related Diseases
Leading Causes of
Death Worldwide 2010
COPD AS THE PULMONARY
COMPONENT OF MULTIMORBIDITY
Rabe K. NEJM; 356:851-854 (2007)
Global Strategy for Diagnosis, Management and Prevention of COPD
Definition of COPD 2011
COPD, a common preventable and treatable
disease, is characterized by persistent airflow
limitation that is usually progressive and
associated with an enhanced chronic
inflammatory response in the airways and the
lung to noxious particles or gases
Exacerbations and comorbidities contribute to
the overall severity in individual patients.
USING PULMONARY IMAGING TO
MOVE COPD BEYOND FEV1
Thoracic imaging using MRI and CT provides
new opportunities to develop surrogate
measurements that improve our understanding
of COPD and its outcomes
The use of pulmonary imaging methods and
measurements has important implications for
COPD biomarker and therapy discovery and
development.
Coxson HO et al, Am J Resp Cr Care Med, 5 June 2014
COMPLEX CHRONIC COMORBIDITIES OF COPD
Fabbri LM, Luppi F, Beghe B, and Rabe KF - Eur Respir J 2008;31:204-212
SIMULTANEOUS DEVELOPMENT OF
CHRONIC DISEASES
Courtesy of K.F. Rabe, 2014.
Chronic diseases represent a huge
proportion of human illness
58 million deaths in 2005:
Cardiovascular disease
30%
Cancer
13%
Chronic respiratory diseases
7%
Diabetes
2%
Beaglehole R et al. Lancet 2007;370:2152-57.
NUMBER OF CHRONIC DISORDERS BY AGE-GROUP
100
90
80
Patients (%)
70
60
50
0 disorders
1 disorder
2 disorders
3 disorders
4 disorders
5 disorders
6 disorders
7 disorders
≥ 8 disorders
40
30
20
10
0
Age groups (years)
Barnett, K et al, Lancet, 2012 Jul 7;380(9836):37-43
Martinis M et al. Exp. Mol. Pathol. 80 (3):219-227, 2006
BPCO : epidemiologia ed inquadramento
di una sindrome complessa
Leonardo M. Fabbri
 BPCO COME COMPONENTE POLMONARE DELLA
MULTIMORBIDITA’ CRONICA
 ALTERAZIONI FUNZIONALI RESPIRATORIE IN
PAZIENTI CON CARDIOPATIE CRONICHE
 INTERESSAMENTO POLMONARE NELLE MALATTIE
CRONICHE
 COMPLESSITA’ DEL PAZIENTE CON DISPNEA ACUTA
 IL MALATO CRITICO CRONICO
CARDIOVASCULAR MORTALITY
IN COPD
For every 10% decrease in
FEV1, cardiovascular mortality
increases by approximately 28%
and non-fatal coronary event
increases by approximately 20%
in mild to moderate COPD
Sin DD et al, Proc Am Thorac Soc 2005;2:8-11
COPD
vs.
CHF
 Up to 1\5 of elderly pts. with COPD have CHF
 Up to 1\3 of elderly pts. with CHF have COPD
The risk ratio of developing HF in
COPD pts is 4.5
14 million
Americans have
COPD
and
5 million have
CHF
The rate-adjusted hospital
prevalence of CHF is 3 times
greater among pts. discharged with
a diagnosis of COPD compared with
patients discharged without mention
of COPD
M. Padeletti-LeJemtel et al Int. J Cardiology, 2008
How common is COPD in CHF?
62,8
44,2
40,5
%
32,5
26.7
21
19,4
10,4
9,2
7,5
3,7
Biagi P et al. Intern J Cardiol 2011;152:88-94
Common pathogenetic mechanisms of COPD and CVD
Roversi S et al. Eur J Clin Invest 2014;44:93
UNRECOGNIZED HEART FAILURE IN ELDERLY
PATIENTS WITH STABLE COPD
405 elderly with a diagnosis of
COPD, but no CHF by GPs
no CHF, no COPD:
128 (32)%
Echo + spiro
reassessment
COPD only: 194
(48%)
COPD + CHF:
50 (12%)
CHF only: 33 (8%)
Rutten FH et al, Eur Heart J 2005
Echocardiography, Spirometry, and Systemic AcutePhase Inflammatory Proteins in Smokers with COPD or
CHF: An Observational Study
60
34%
29 %
66%
CHF
71 %
50
% of patients
34 CHF +
66%
COPD
34 %
40
30
20
10
0
GOLD I
GOLD II
GOLD III
CHF patients
Only 10 of 42 (<25%) pts. with both CHF and COPD were aware of
airflow limitation and properly treated
Beghé B. et al. PlosOne 2013 Nov 11;8
COPD masks or mimics heart failure
pulmonary
vascular
remodeling
masks alveolar
shadowing
asymmetric
and regional
patterns
radiology
hyperinflation
reduces
cardiothoracic
ratio
vascular bed
loss causes
upper lobe
venous
diversion
Gehlbach BK. Chest 2004; 125:669-82
Caution diagnosing COPD in HF
Airway
compression
Bronchial
hyper-responsiveness
overestimate
severity
Inappropriate
avoidance
of β-blockers
misdiagnosis
always perform
Spirometry…
and always
when euvolaemic
Inappropriate
bronchodilators
HIGH PREVALENCE AND UNDERDIAGNOSIS
OF LUNG FUNCTION ABNORMALITIES IN
PATIENTS WITH ISHEMIC HEART DISEASE
No AL
n=1,957
(70.5%)
AL
n=819
(29.5%)
No
Diagnosis
(70.3%)
Prior
Diagnosis *
(29.7%)
Soriano J ……. and Fabbri LM, 2014 in preparation
IMPACT OF COPD ON LONG-TERM OUTCOME
AFTER STEMI RECEIVING PRIMARY PCI
As compared to patients without COPD, patients with
STEMI and concomitant COPD are at greater risk for
> death (25% vs 16.5%)
> hospital readmissions due to cardiovascular causes
(recurrent MI, HF and bleedings)
Campo G., et al. Chest 2013 ;144:750-7
AIRFLOW OBSTRUCTION, LUNG FUNCTION
AND INCIDENCE OF ATRIAL FIBRILLATION
In this large population-based study with a long-term followup, reduced FEV1 and obstructive respiratory disease were
associated with a higher AF incidence after adjustment for
measured confounders.
Li J et al Circulation 2014;129:971-80
DIABETES AS A RISK FACTOR FOR STROKE IN WOMEN
COMPARED WITH MEN: A SYSTEMATIC REVIEW AND METAANALYSIS 775 385 INDIVIDUALS AND 12 539 STROKES
The excess risk of stroke
associated with diabetes
is > in women than men
Need for further work to
clarify
the biological,
behavioural, or social
mechanisms involved.
Peters SAE et al, Lancet 2014; 383: 1973–80
SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS
COMPARING ANTITHROMBOTIC AGENTS FOR THE
PREVENTION OF STROKE AND MAJOR BLEEDING IN
PATIENTS WITH ATRIAL FIBRILLATION
Compared with standard adjusted
dose of VKA, new oral
anticoagulants (NOA) were
associated with modest
reductions in the absolute risk of
stroke and major bleeding
People on antiplatelet drugs
experienced more strokes
compared with anticoagulant
drugs without any reduction in
bleeding risk
Cameron C, Coyle D, Richter T, et al. BMJ Open 2014;4:e004301.
SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS
COMPARING ANTITHROMBOTIC AGENTS FOR THE
PREVENTION OF STROKE AND MAJOR BLEEDING IN
PATIENTS WITH ATRIAL FIBRILLATION
Compared with VKA, new oral
anticoagulants (NOA) were
associated with modest
reductions in the absolute risk
of stroke and major bleeding
People on antiplatelet drugs
experienced more strokes
compared with anticoagulant
drugs without any reduction in
bleeding risk
Cameron C, Coyle D, Richter T, et al. BMJ Open 2014;4:e004301
Why is diagnosis important?
Renin-angiotensinaldosterone system
inhibition
Heart failure
Bronchodilators
beta-blockers
OUTCOMES
COPD
beta-agonists
Devices
Smoking cessation
Global Strategy for Diagnosis, Management and Prevention of COPD
GOLD 4
C
D
ICS + LABA
ICS + LABA
LAMA
LAMA
or
GOLD 3
GOLD 2
GOLD 1
>2
and/or
A
B
SAMA prn
LABA
SABA prn
LAMA
or
mMRC 0-1
CAT < 10
or
mMRC > 2
CAT > 10
1
0
Exacerbations per year
Manage Stable COPD: Pharmacologic Therapy
FIRST CHOICE
GOLD 2013
1.0
Bronchodilators are associated
with increased mortality
CHARM trial: patients with HF
0.8
No bronchodilator
and beta-blocker
No bronchodilator
and no betablocker
Bronchodilator
and beta-blocker
0.7
Survival Rate
0.9
receiving bronchodilators (n=674 of
7599)
0
0.5
1.0
1.5
2.0
2.5
3.0
Bronchodilator
and no beta3.5 blocker
Time (years)
Hawkins NM. Eur J Heart Fail 2010: In Press.
Treatment with beta-blockers may
reduce the risk of exacerbations and
improve survival in patients with
COPD, possibly as a result of dual
cardiopulmonary protective properties
Rutten FH et al, Arch Intern Med. 2010;170:880-7
EFFECTS OF CARDIOVASCULAR DRUGS ON MORTALITY
IN SEVERE COPD PATIENTS
(on Long Term Oxygen Therapy)
 Antiplatelet drugs improve survival
 ACE inhibitors and statins may improve survival
 Beta blockers may decrease survival
Ekström, M. et al. AJRCCM 2013,;187:715-20
BPCO : epidemiologia ed inquadramento
di una sindrome complessa
Leonardo M. Fabbri
 BPCO COME COMPONENTE POLMONARE DELLA
MULTIMORBIDITA’ CRONICA
 ALTERAZIONI FUNZIONALI RESPIRATORIE IN
PAZIENTI CON CARDIOPATIE CRONICHE
 INTERESSAMENTO POLMONARE NELLE MALATTIE
CRONICHE
 COMPLESSITA’ DEL PAZIENTE CON DISPNEA ACUTA
 IL MALATO CRITICO CRONICO
HEART FAILURE AS A
SYSTEMIC DISEASE
Myocardial infarction causes the release
of inflammatory cells from the spleen
and bone marrow and their myocardial
infiltration
This leads to an accumulation of
monocytes in the heart, predominantly
located in the infarct border zone, and a
decrease of monocytes in the spleen and
bone marrow
This may be mediated by activation of
the sympathetic nervous system,
angiotensin II, and/ or cytokine release.
Hofmasnn and Frantz. Eur Heart J 2014; 35: 314-5.
ASSOCIATION BETWEEN CHRONIC OBSTRUCTIVE
PULMONARY DISEASE AND CHRONIC KIDNEY
DISEASE IN VASCULAR SURGERY PATIENTS
The findings of this study indicate that COPD is
moderately associated with chronic kidney
diseases in a large cohort of vascular surgery
patients
Moderate and severe COPD are related to
increased long-term mortality in patients with
chronic kidney diseases
van Gestel Y. et al, Nephrol Dial Transplant (2009) 24: 2763–2767
METABOLIC SYNDROME IN COPD
A co-exisiting
metabolic
syndrome is
frequent in
patients with
COPD
Watz H, …., and H. Magnussen, Chest 2009
Liver-Related Causes of Dyspnea in
a Patient with Chronic Liver Disease
Pulmonary - Parenchymal
 Alveolar

– Pleural effusions
– Restriction from tense
ascites
– Aspiration pneumonia
– Basal atelectasis

Interstitial lung disease
– Lymphocytic interstitial
pneumonia
– Fibrosing alveolitis
– BOOP
– Noncardiogenic pulmonary
edema

Vascular
– Pulmonary hemorrhage
– Hepatopulmonary Syndrome
– Portal-Pulmonary Hypertension
Extraparenchymal

Extrapulmonary
–
–
–
–
–
Cirrhotic cardiomyopathy
Cirrhotic myopathy
Chronotropic dysfunction
Muscle wasting
Deconditioning from
impaired mobility
Liver Lung Interaction
Liver Failure
Acute Liver Failure
Chronic Liver Failure
ARDS
Vasodilatation
Hepato-pulmonary
Syndrome
Vasoconstriction
Portopulmonary
Hypertnsion
PSORIASIS AND CHRONIC OBSTRUCTIVE
PULMONARY DISEASE: A CASE–
CONTROL STUDY
In this large, population-based case–control study,
psoriasis was found to be associated with COPD
Dermatologists caring for patients with psoriasis
should be aware of this association, consult an
internist or pulmonologist, and advise the patients
to stop smoking and reduce additional risk factors
for COPD
Dreiher J et al., Br J Derm 2008; 159: 956-960
BPCO : epidemiologia ed inquadramento
di una sindrome complessa
Leonardo M. Fabbri
 BPCO COME COMPONENTE POLMONARE DELLA
MULTIMORBIDITA’ CRONICA
 ALTERAZIONI FUNZIONALI RESPIRATORIE IN
PAZIENTI CON CARDIOPATIE CRONICHE
 INTERESSAMENTO POLMONARE NELLE MALATTIE
CRONICHE
 COMPLESSITA’ DEL PAZIENTE CON DISPNEA ACUTA
 IL MALATO CRITICO CRONICO
EXACERBATIONS OF RESPIRATORY SYMPTOMS IN
PATIENTS WITH COPD MAY NOT BE EXACERBATIONS
OF COPD
Beghé B, Verduri A, Roca M and Fabbri LM. Eur Respir J 2013; 41: 993-5
Roca M, Verduri A, Clini EM, Fabbri LM and Beghé B. Eur J Clin Invest, 2013;43:510
BPCO : epidemiologia ed inquadramento
di una sindrome complessa
Leonardo M. Fabbri
 BPCO COME COMPONENTE POLMONARE DELLA
MULTIMORBIDITA’ CRONICA
 ALTERAZIONI FUNZIONALI RESPIRATORIE IN
PAZIENTI CON CARDIOPATIE CRONICHE
 INTERESSAMENTO POLMONARE NELLE MALATTIE
CRONICHE
 COMPLESSITA’ DEL PAZIENTE CON DISPNEA ACUTA
 IL MALATO CRITICO CRONICO
ACUTE CRITICAL ILLNESS
Recover Quickly
Die during Acute
Illness
Require prolonged mechanical ventilation
BECOME
CHRONICALLY
CRITICALLY ILL
Elective tracheotomy
Continued High Levels of Nursing Care
Nelson JE et al, Am J Respir Crit Care Med 2010; 182:446-54.
Lamas D. N Engl J Med. 2014 Jan 9;370(2):175-7
Risk Factors For Chronic Critical Illness
Respir Care 2012; 57:859-864
Sepsis
Weakness
Risk Factors
Acute
Lung
Injury
•
•
•
•
•
•
Age
Comorbidities
Genetics
Illness severity
Illness Type
Illness Management
Brain
Disfunction
Trauma
Infection
Acute Critical Illness
Precipitants
Chronic Critical
Illness End Result
Inflammatory
Response?
CLINICAL FEATURES OF THE CRONIC CRITICAL ILLNESS SYNDROME
Skin Breakdown,
Nutritional Deficiencies,
Prolonged immobility
Profound Weakness
Myopathy, Neuropaty
Alterations of Body
Composition
Loss in lean body mass,
increased adiposity,
anasarca
Neuroendocrine
Changes
Increased vulnerability
to infection
Brain Dysfunction
Coma, Delirium
Am J Respir Crit care med 2010; 182:446-454
. . . . Take
home messages
 COPD and CHF often coexist, particularly in elderly
smokers, but often underdiagnosed
 COPD increases risk of hospitalization and mortality in
CHF patients
 Caution should be taken in spirometric diagnosis to
avoid overestimation of airflow limitation and
unjustified use bronchodilators
 COPD is not a contraindication to β-blockers:
metoprololo, bisoprololo and nebivololo are candidates
BPCO : epidemiologia ed inquadramento
di una sindrome complessa
Leonardo M. Fabbri
 BPCO COME COMPONENTE POLMONARE DELLA
MULTIMORBIDITA’ CRONICA
 ALTERAZIONI FUNZIONALI RESPIRATORIE IN
PAZIENTI CON CARDIOPATIE CRONICHE
 INTERESSAMENTO POLMONARE NELLE MALATTIE
CRONICHE
 COMPLESSITA’ DEL PAZIENTE CON DISPNEA ACUTA
 IL MALATO CRITICO CRONICO
Forth Mediterranean Congress
Innovative Scenario in Internal Medicine
Palermo 7 Giugno 2014
BPCO : epidemiologia ed inquadramento di
una sindrome complessa
Leonardo M. Fabbri
Clinica di Malattie dell’Apparato Respiratorio
Università degli Studi di Modena e Reggio Emilia