Presentazione di PowerPoint

CONVEGNO MEDICO UNISALUTE
Influenza degli stili di vita sulle malattie croniche
non trasmissibili
Torre Unipol, Bologna
11 ottobre 2013
STILI DI VITA E MALATTIE
RESPIRATORIE CRONICHE
Leonardo M. Fabbri
Fabrizio Luppi
Leonardo M. Fabbri
Clinica di Malattie dell’Apparato Respiratorio
Università degli Studi di Modena e Reggio Emilia
Azienda Ospedaliero-Universitaria - Policlinico di
Modena
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
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
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
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)
Schulte PA et al, Am J Public Health. 2012;102:434–448.
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
Fabbri, Sinigaglia, Papi, Saetta 2002, adapted from PJ Barnes, 2000
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
Small Airway
Obstruction
Emphysema
COPD: EVASION AND
PROGRESSION
STEP 1
GOLD I ?
Factors
controlling
innate
immunity,
TLR’s
STEP 2
GOLD I, II ?
Adaptive
immunity
control.
Tregs
STEP 3
GOLD III, IV?
AUTOIMMUNITY
Tolerance failure.
Genetic
predisposition.
Epigenetics ?
Cosio, Saetta, Agusti. N Engl J Med 2009;360:2445-54
Cigarette smoking induces an inflammatory response in all
smokers
(normal non-specific response)
Autoimmune response
Non-susceptible smokers
Susceptible smokers
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
Complex Chronic Co-morbidities of COPD
Debolezza/Deperimento
Muscolo
TNFa
Sindrome Metabolica
Diabete di Tipo 2
IL-6
Infiammazione
Locale
Eventi
Cardiovascolari
PCR
?
Osteoporosi
Fegato
Fabbri, Beghé, Luppi and Rabe et al., Eur Respir J 2008; 31: 204-12
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
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.
Hunter DJ and Reddy KS. N Engl J Med 2013; 369:1336-1343
INTERACTION OF OCCUPATIONAL AND
PERSONAL RISK FACTORS IN WORKFORCE
HEALTH AND SAFETY
Age
Genetics
Smoking
Diet/Obesity
Inactivity
Alcohol use
Indoor/Outdoor/Occupational pollution
Schulte PA et al, Am J Public Health. 2012;102:434–448.
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
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, 2012 Jul 7;380(9836):37-43
EPIDEMIOLOGY OF MULTIMORBIDITY AND
IMPLICATIONS FOR HEALTH CARE,
RESEARCH, AND MEDICAL EDUCATION:
A CROSS-SECTIONAL STUDY
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.
Barnett, K et al, 2012 Jul 7;380(9836):37-43
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
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.
Janssen W et al, Am J Respir Cr Care Med, 2013, in press
“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”
Am J Respir Crit Care Med 2011; 183: 788-824
WHO IS MISTER IPF?
Male
65 years old
Smoker or former smoker
Dry cough
Dyspnea at exertion
Bilateral velcro-type crackles
Clubbing
Previous different diagnosis
Raghu G et al, AJRCCM 2011
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
Complex Chronic Multimorbidities
Debolezza/Deperimento
Muscolo
TNFa
Sindrome Metabolica
Diabete di Tipo 2
IL-6
Infiammazione
Locale
Eventi
Cardiovascolari
PCR
?
Osteoporosi
Fegato
Fabbri, Beghé, Luppi and Rabe et al., Eur Respir J 2008; 31: 204-12