Leonardo M. Fabbri

Clinica di Malattie dell’Apparato Respiratorio

Università degli Studi di Modena e Reggio Emilia

Azienda Ospedaliero-Universitaria - Policlinico di Modena

STILI DI VITA E MALATTIE RESPIRATORIE CRONICHE

Leonardo M. Fabbri

Fabrizio Luppi

CONVEGNO MEDICO UNISALUTE

Influenza degli stili di vita sulle malattie croniche

non trasmissibili Torre Unipol, Bologna

11 ottobre 2013

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.

Risk Factors for chronic respiratory disease

Nutrition

Infections

Socio-economic status

Aging Populations

Health risks of maternal smoking

• Miscarriage

• Placental disruption

• Sudden Infant Death

Syndrome (SIDS)

• Preterm labor

• Low birth weight

Courtesy of Machteld Hylkema, Groningen

1: Salvi S, Barnes PJ. Is exposure to biomass smoke the biggest risk factor for COPD

globally? Chest. 2010 Jul;138(1):3-6.

Salvi SS, Barnes PJ. COPD in non-smokers. Lancet 2009; 374:733-43

PROPORTION OF HOUSEHOLD USING BIOMASS FUELS FOR COOKING

PROPORTION OF HOUSEHOLD USING BIOMASS FUELS FOR COOKING

1: Salvi S, Barnes PJ. Is exposure to biomass smoke the biggest risk factor for COPD

globally? Chest. 2010 Jul;138(1):3-6.

Salvi SS, Barnes PJ. COPD in non-smokers. Lancet 2009; 374:733-43

INTERACTION OF OCCUPATIONAL AND

PERSONAL RISK FACTORS IN WORKFORCE

HEALTH AND SAFETY

Schulte PA et al, Am J Public Health. 2012;102:434–448.

Most diseases, injuries, and other health conditions

experienced by working people are multi-factorial, especially

as the workforce ages

We evaluated the influence of both occupational and

personal risk factors on workforce health

We present 32 examples illustrating 4 combinatorial models

of occupational hazards and personal risk factors (genetics,

age, gender, chronic disease, obesity, smoking, alcohol use,

prescription drug use)

Pathogenesis of COPD

Fabbri, Sinigaglia, Papi, Saetta 2002, adapted from PJ Barnes, 2000

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

COPD

• GOLD Definition: the presence of airflow limitation that is not fully reversible and a history of exposure to a noxious agent / risk factor (cigarette smoke)

• Airflow limitation

– Small airways

• Remodeling, fibrosis

– Alveoli: Emphysema

– Destruction and enlargement

– of mature Airspace distal to

– terminal bronchioles

Emphysema Small Airway

Obstruction

STEP 1 STEP 2 STEP 3

GOLD I ? GOLD I, II ? GOLD III, IV?

Factors

controlling

innate

immunity,

TLR’s

Adaptive

immunity

control.

Tregs

AUTOIMMUNITY

Tolerance failure.

Genetic

predisposition.

Epigenetics ?

COPD: EVASION AND PROGRESSION

Cosio, Saetta, Agusti. N Engl J Med 2009;360:2445-54

Cigarette smoking induces an inflammatory response in all

smokers

(normal non-specific response)

Non-susceptible smokers Susceptible smokers

Autoimmune response

Lee et al, Nat Med. 2007;13(5):567-9

Inhaled particles:

pulmonary and heart co-morbidity

Courtesy of W MacNee

Global Strategy for Diagnosis, Management and Prevention of COPD

Assess COPD Comorbidities

COPD patients are at increased risk for:

• Cardiovascular diseases • Osteoporosis • Respiratory infections • Anxiety and Depression • Diabetes • Lung cancer

These comorbid conditions may influence

mortality and hospitalizations and should be

looked for routinely, and treated appropriately.

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

Fabbri, Beghé, Luppi and Rabe et al., Eur Respir J 2008; 31: 204-12

Debolezza/Deperimento

Muscolo

Sindrome Metabolica

Diabete di Tipo 2

Osteoporosi

PCR

Eventi

Cardiovascolari Fegato

? Infiammazione

Locale

TNFa IL-6

Complex Chronic Co-morbidities of COPD

CLUSTERS OF OBJECTIFIED COMORBIDITIES AND

SYSTEMIC INFLAMMATION IN PATIENTS WITH

CHRONIC OBSTRUCTIVE PULMONARY DISEASE

This study expands our understanding

of the interrelationships between other

chronic conditions in COPD and sheds

new light on the possible etiology and

pathophysiologic role of

systemic inflammation in COPD

Vanfleteren L.E.G.W., et al. AJRCCM 2013 Apr;187(7):728-35

FREQUENCIES OF OBJECTIFIED COMORBIDITIES

Vanfleteren L.E.G.W., et al. AJRCCM 2013 Apr;187(7):728-35

NUMBER OF OBJECTIFIED COMORBIDITIES

Vanfleteren L.E.G.W., et al. AJRCCM 2013 Apr;187(7):728-35

THE FREQUENCIES OF OBJECTIFIED COMORBIDITIES IN COPD

PATIENTS WITH EACH OF THE 13

SELECTED SPECIFIC COMORBIDITIES

Vanfleteren L.E.G.W., et al. AJRCCM 2013 Apr;187(7):728-35

MULTIMORBIDITY CLUSTERS IN COPD

Vanfleteren L.E.G.W., et al. AJRCCM 2013 Apr;187(7):728-35

CLUSTERS OF OBJECTIFIED COMORBIDITIES AND

SYSTEMIC INFLAMMATION IN PATIENTS WITH

CHRONIC OBSTRUCTIVE PULMONARY DISEASE

This study expands our understanding

of the interrelationships between other

chronic conditions in COPD and sheds

new light on the possible etiology and

pathophysiologic role of

systemic inflammation in COPD

Vanfleteren L.E.G.W., et al. AJRCCM 2013 Apr;187(7):728-35

NONCOMMUNICABLE

DISEASES

Hunter DJ and Reddy KS. N Engl J Med 2013; 369:1336-1343

Noncommunicable diseases will be the predominant global

public health challenge of the 21st century

Prevention of premature deaths due to noncommunicable

diseases and reduction of related health care costs will be

the main goals of health policy.

Improving the detection and treatment of noncommunicable

diseases and preventing complications and catastrophic

events will be the major goals of clinical medicine.

INTERACTION OF OCCUPATIONAL AND

PERSONAL RISK FACTORS IN WORKFORCE

HEALTH AND SAFETY

Schulte PA et al, Am J Public Health. 2012;102:434–448.

Age

Genetics

Smoking

Diet/Obesity

Inactivity

Alcohol use

Indoor/Outdoor/Occupational pollution

Global Deaths According to Cause and Sex, 2008.

Hunter DJ, Reddy KS. N Engl J Med 2013;369:1336-1343

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.

Proportion of Deaths from Noncommunicable Diseases among Persons Younger than 60 Years of Age, According to Income Group of Countries.

Hunter DJ, Reddy KS. N Engl J Med 2013;369:1336-1343

Declines in Rates of Death from Major Noncommunicable Diseases in the United States, 1950 to 2010.

Hunter DJ, Reddy KS. N Engl J Med 2013;369:1336-1343

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, 2012 Jul 7;380(9836):37-43

EPIDEMIOLOGY OF MULTIMORBIDITY AND

IMPLICATIONS FOR HEALTH CARE,

RESEARCH, AND MEDICAL EDUCATION:

A CROSS-SECTIONAL STUDY

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

Our findings challenge the single-disease

framework by which most health care, medical

research, and medical education is configured. A

complementary strategy is needed, supporting

generalist clinicians to provide personalised,

comprehensive continuity of care, especially in

socioeconomically deprived areas.

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

Fighting Sloth

RISK FACTORS AND COMORBIDITIES IN

THE PRE-CLINICAL STAGES OF COPD

Janssen W et al, Am J Respir Cr Care Med, 2013, in press

Comorbidities and their associations with

different risk factors in COPD is mainly based on

patient-based samples with an established

diagnosis of moderate to very severe COPD.

The present study conducted in patients with mild

to moderate early COPD show that physical

inactivity and smoking, but not COPD as such,

are associated with their development.

Am J Respir Crit Care Med 2011; 183: 788-824

“The diagnosis of IPF requires:

a) exclusion of other known causes of interstitial lung disease

b) the presence of a UIP pattern on HRCT in patients not subjected to surgical lung biopsy

c) specific combinations of HRCT and surgical lung biopsy pattern in patients subjected to surgical lung biopsy”

Raghu G et al, AJRCCM 2011

Male

65 years old

Smoker or former smoker

Dry cough

Dyspnea at exertion

Bilateral velcro-type crackles

Clubbing

Previous different diagnosis

WHO IS MISTER IPF?

IDIOPATHIC PULMONARY FIBROSIS

A specific form of chronic, progressive fibrosing interstitial pneumonia of unknown cause,

occurring primarily in older adults, limited to the lungs, and associated with the

histopathologic and/or radiologic pattern of UIP.

ATS/ERS/JRS/ALAT Guidelines; AJRCCM 2011.

DIAGNOSIS OF IPF REQUIRES:

• Exclusion of other known causes of ILD

and

• The presence of a UIP pattern on HRCT

or

• Specific combinations of HRCT and surgical lung biopsy pattern

ATS/ERS/JRS/ALAT Guidelines; AJRCCM 2011.

HRCT UIP PATTERN

DEFINITE UIP DEFINITE UIP POSSIBLE UIP

Am J Respir Crit Care Med 2011; 183: 788-824

Idiopathic pulmonary fibrosis (IPF)

“Specific form of chronic fibrosing interstitial pneumonia limited to the lung, associated with UIP on lung biopsy.”

Am J Respir Crit Care Med 2000; 161: 646–664

Fabbri, Beghé, Luppi and Rabe et al., Eur Respir J 2008; 31: 204-12

Debolezza/Deperimento

Muscolo

Sindrome Metabolica

Diabete di Tipo 2

Osteoporosi

PCR

Eventi

Cardiovascolari Fegato

? Infiammazione

Locale

TNFa IL-6

Complex Chronic Multimorbidities