BPCO : epidemiologia ed inquadramento di una sindrome...

Leonardo M. Fabbri

Forth Mediterranean Congress Innovative Scenario in Internal Medicine

Palermo 7 Giugno 2014

Clinica di Malattie dell’Apparato Respiratorio

Università degli Studi di Modena e Reggio Emilia

BPCO : epidemiologia ed inquadramento di una sindrome complessa

CONFLICTS OF INTEREST

Leonardo M. Fabbri, 2014


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






CRONICHE




Leonardo M. Fabbri

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

Gershon A et al, Eur Respir J 2014; 7 june 2014, in press

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

Pathogenesis of COPD

Adapted from PJ Barnes, 2000; Fabbri, Sinigaglia, Papi, Saetta 2002; Cosio,

Saetta and Cosio 2012

Cigarette smoke

or air pollutant

Alveolar

macrophage

Neutrophil

Proteases

? CD8+ T-cell

Alveolar wall destruction

EMPHYSEMA

Mucus hypersecretion

BRONCHIOLITIS

Inflammatory cytokines

(IL-8, LTB4) CXCL-10

CXCR3

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

Rabe K. NEJM; 356:851-854 (2007)

COPD AS THE PULMONARY COMPONENT OF MULTIMORBIDITY


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

Coxson HO et al, Am J Resp Cr Care Med, 5 June 2014

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.

COMPLEX CHRONIC COMORBIDITIES OF COPD

Fabbri LM, Luppi F, Beghe B, and Rabe KF - Eur Respir J 2008;31:204-212

Courtesy of K.F. Rabe, 2014.

SIMULTANEOUS DEVELOPMENT OF

CHRONIC DISEASES

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

70

60

50

40

30

20

10

0

Age groups (years)

Pati

en

ts (

%)

0 disorders

1 disorder

2 disorders

3 disorders

4 disorders

5 disorders

6 disorders

7 disorders

≥ 8 disorders

Barnett, K et al, Lancet, 2012 Jul 7;380(9836):37-43

Martinis M et al. Exp. Mol. Pathol. 80 (3):219-227, 2006






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Leonardo M. Fabbri

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

14 million Americans have

COPD and 5 million have

CHF

M. Padeletti-LeJemtel et al Int. J Cardiology, 2008

The risk ratio of developing HF in COPD pts is 4.5 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

How common is COPD in CHF?

Biagi P et al. Intern J Cardiol 2011;152:88-94

26.7

62,8

21

44,2

10,4

40,5

19,4

3,7 7,5

32,5

9,2

%

Roversi S et al. Eur J Clin Invest 2014;44:93

Common pathogenetic mechanisms of COPD and CVD

COPD only: 194 (48%)

CHF only: 33 (8%)

no CHF, no COPD: 128 (32)%

COPD + CHF: 50 (12%)

Rutten FH et al, Eur Heart J 2005

UNRECOGNIZED HEART FAILURE IN ELDERLY PATIENTS WITH STABLE COPD

405 elderly with a diagnosis of COPD, but no CHF by GPs

Echo + spiro reassessment

CHF only: 33 (8%)

COPD + CHF: 50 (12%)

29 %

71 %

Only 10 of 42 (<25%) pts. with both CHF and COPD were aware of

airflow limitation and properly treated

% o

f patients

0

10

20

30

40

50

60

GOLD I GOLD II GOLD III

CHF 34 CHF +

COPD

Echocardiography, Spirometry, and Systemic Acute- Phase Inflammatory Proteins in Smokers with COPD or CHF: An Observational Study

34 %

CHF patients

66%

Beghé B. et al. PlosOne 2013 Nov 11;8

66%

34%

hyperinflation reduces cardiothoracic ratio

pulmonary

vascular

remodeling

masks alveolar

shadowing

asymmetric

and regional

patterns

vascular bed

loss causes

upper lobe

venous

diversion

Gehlbach BK. Chest 2004; 125:669-82

radiology

COPD masks or mimics heart failure

Caution diagnosing COPD in HF

Airway compression

Bronchial hyper-responsiveness

always perform

Spirometry… and always

when euvolaemic

misdiagnosis overestimate severity

Inappropriate bronchodilators

Inappropriate avoidance of β-blockers

HIGH PREVALENCE AND UNDERDIAGNOSIS

OF LUNG FUNCTION ABNORMALITIES IN

PATIENTS WITH ISHEMIC HEART DISEASE

Soriano J ……. and Fabbri LM, 2014 in preparation

No AL

n=1,957

(70.5%)

AL

n=819

(29.5%)

No

Diagnosis

(70.3%)

Prior

Diagnosis *

(29.7%)

IMPACT OF COPD ON LONG-TERM OUTCOME AFTER STEMI RECEIVING PRIMARY PCI

Campo G., et al. Chest 2013 ;144:750-7

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)

AIRFLOW OBSTRUCTION, LUNG FUNCTION AND INCIDENCE OF ATRIAL FIBRILLATION

Li J et al Circulation 2014;129:971-80

In this large population-based study with a long-term follow-up, reduced FEV1 and obstructive respiratory disease were associated with a higher AF incidence after adjustment for measured confounders.

DIABETES AS A RISK FACTOR FOR STROKE IN WOMEN

COMPARED WITH MEN: A SYSTEMATIC REVIEW AND META-

ANALYSIS 775 385 INDIVIDUALS AND 12 539 STROKES

Peters SAE et al, Lancet 2014; 383: 1973–80

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.

SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS

COMPARING ANTITHROMBOTIC AGENTS FOR THE

PREVENTION OF STROKE AND MAJOR BLEEDING IN

PATIENTS WITH ATRIAL FIBRILLATION

Cameron C, Coyle D, Richter T, et al. BMJ Open 2014;4:e004301.

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

SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS

COMPARING ANTITHROMBOTIC AGENTS FOR THE

PREVENTION OF STROKE AND MAJOR BLEEDING IN

PATIENTS WITH ATRIAL FIBRILLATION

Cameron C, Coyle D, Richter T, et al. BMJ Open 2014;4:e004301

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

OUTCOMES

Bronchodilators

Heart failure

Devices Smoking cessation

beta-blockers

Renin-angiotensin-aldosterone system inhibition

COPD

beta-agonists

Why is diagnosis important?

Exac

erb

atio

ns p

er

year

> 2

1

0

mMRC 0-1 CAT < 10

GOLD 4

mMRC > 2 CAT > 10

GOLD 3

GOLD 2

GOLD 1

SAMA prn or

SABA prn

LABA or

LAMA

ICS + LABA or

LAMA


Manage Stable COPD: Pharmacologic Therapy FIRST CHOICE

A B

D C ICS + LABA

and/or LAMA

GOLD 2013

Bronchodilators are associated with increased mortality

Hawkins NM. Eur J Heart Fail 2010: In Press.

0.7

0

.8

0.9

1.

0

Sur

viva

l R

ate

0 0.5 1.0 1.5 2.0 2.5 3.0 3.5

Time (years)

No bronchodilator and beta-blocker

No bronchodilator and no beta-blocker Bronchodilator and beta-blocker

Bronchodilator and no beta-blocker

CHARM trial: patients with HF receiving bronchodilators (n=674 of 7599)

Rutten FH et al, Arch Intern Med. 2010;170:880-7

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

EFFECTS OF CARDIOVASCULAR DRUGS ON MORTALITY IN SEVERE COPD PATIENTS

(on Long Term Oxygen Therapy)

Ekström, M. et al. AJRCCM 2013,;187:715-20

Antiplatelet drugs improve survival

ACE inhibitors and statins may improve survival

Beta blockers may decrease survival






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Leonardo M. Fabbri

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 – 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

– Pleural effusions

– Restriction from tense ascites

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 Vasoconstriction

Hepato-pulmonary Syndrome

Portopulmonary Hypertnsion

PSORIASIS AND CHRONIC OBSTRUCTIVE

PULMONARY DISEASE: A CASE–

CONTROL STUDY

Dreiher J et al., Br J Derm 2008; 159: 956-960

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






CRONICHE




Leonardo M. Fabbri

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






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Leonardo M. Fabbri

ACUTE CRITICAL ILLNESS

Recover Quickly Die during Acute

Illness

Require prolonged mechanical ventilation Elective tracheotomy

Continued High Levels of Nursing Care

BECOME CHRONICALLY CRITICALLY ILL

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

Acute Critical Illness Precipitants

Sepsis

Acute

Lung

Injury

Trauma

Chronic Critical Illness End Result

Weakness

Brain

Disfunction

Infection

Risk Factors • Age • Comorbidities • Genetics • Illness severity • Illness Type • Illness Management

Inflammatory Response?

Respir Care 2012; 57:859-864

Am J Respir Crit care med 2010; 182:446-454

CLINICAL FEATURES OF THE CRONIC CRITICAL ILLNESS SYNDROME

Profound Weakness

Myopathy, Neuropaty

Alterations of Body

Composition

Loss in lean body mass,

increased adiposity,

anasarca

Neuroendocrine

Changes

Brain Dysfunction

Coma, Delirium

Increased vulnerability

to infection

Skin Breakdown,

Nutritional Deficiencies,

Prolonged immobility

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

. . . . Take home messages






CRONICHE




Leonardo M. Fabbri

Leonardo M. Fabbri

Forth Mediterranean Congress Innovative Scenario in Internal Medicine

Palermo 7 Giugno 2014

Clinica di Malattie dell’Apparato Respiratorio

Università degli Studi di Modena e Reggio Emilia


BPCO : epidemiologia ed inquadramento di una sindrome...

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