marcelo basso gazzana serviço de pneumologia hospital de clínicas de porto alegre e-mail:...
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Marcelo Basso Gazzana
Serviço de Pneumologia Hospital de Clínicas de Porto Alegre
E-mail: [email protected]
Congresso Brasileiro de Pneumologia e TisiologiaBrasília, 23 de Novembro de 2008
Fibrose Pulmonar Idiopática
FPI e Tabagismo( IPF and Smoking )
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Potenciais Conflitos de Interesse( CFM nº 1.595 de 18 / 5 / 2000 e ANVISA nº 120 de 30 / 11 / 2000 )( CFM nº 1.595 de 18 / 5 / 2000 e ANVISA nº 120 de 30 / 11 / 2000 )
• Médico do Serviço de Pneumologia do Hospital de Clinicas de Porto Alegre
• Médico Intensivista do Hospital Moinhos de Vento
• Participação em pesquisas da indústria farmacêutica no tema: Não
• Remuneração para conferências no tema: Não
• Patrocínio para congressos no tema: Não
MBGazzana
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Objectives
• Smoking as a etiologic factorSmoking as a etiologic factor
• Diagnostic contextDiagnostic context
• Concomitant smoking-related diseaseConcomitant smoking-related disease
• Prognostic implicationsPrognostic implications
• Smoking cessation as a therapySmoking cessation as a therapy
MBGazzana
IPF and Smoking
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Auerbach O et al. New Engl J Med 1963; 269: 1045
Smoking Habits and Age in Relation to Pulmonary Changes.
Rupture of Alveolar Septums, Fibrosis and Thickning of Walls of Small Arteries and Arterioles
• Lungs obtained at autopsy
• Changes attributable to cigarette smoking:
― Rupture of the alveolar septa
― Fibrosis of alveolar septa
― Thickening of the walls of the vessels
• Changes were associated with aging, but more common in smokers
• Nonsmokers more than 70 years had less changes than cigarette
smokers less than 45 years of age
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Weiss W. Am Rev Respir Dis 1969; 99: 67
Cigarette Smoking and Diffuse Pulmonary Fibrosis
Smoking Habits No Pulmonary fibrosis
No % age-ajusted
Nonsomokers 839 5 0,6
Cigarrete Smokers 1.860 35 2,1
Current 1.513 27 2,2
Ex-smokers ( > 12 m) 347 8 1,7
Survey of 2.825 adults came to Association’s Central X-ray Unit, Philadelphia
• Good relationship between DPF and smoking duration ( not daily amount )
• Negligible DPF if smoking duration less than 20 years
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Baumgartner KB et al. Am J Resp Crit Care Med 1997; 155: 242
Cigarette Smoking :A Risk Factor for Idiopathic Pulmonary Fibrosis
• Multicenter case-control study
• 248 cases and 491 control subjects
• Odds ratio (OR) for ever smoking: 1.6 ( 95% CI: 1.1 to 2.4 )
• OR for smokers wtih 21 to 40 pack-year : 2.3 ( 1.3 to 3.8 )
• OR for smokers plus any occupationl exposure : 4.1 ( 1.3 to 13.3 )
Conclusion: “ IPF may be another lung disease caused or
exacerbated by cigarette smoking ”
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IPF Pathogenesis
Maher TM, Wells AU et al. Eur Resp J 2007; 30: 835
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IPF PathologyUsual Interstitial Pneumonia ( UIP pattern )
• Patchy fibrosis with normal areas
• Minimal inflamation
• Fibroblastic foci
• Honeycombing
Low power view High power view
Dempsey OJ et al. Q J Med 2006; 99: 643
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Chapman HA. J Clin Invest 1999; 104: 1
IPF pathgenesis – Fas Pathway
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IPF PathogenesisCigarette Smoking and CD8+Fas ligand
• N = 21 patients with non-treated IPF – 7 smokers
• BAL cytology and immunotyping
• Smokers versus nonsmokers
• More lymphocytes CD8 cells (p <0.05)
• More lymphocytes CD8 cells carrying Fas ligand (p<0.05)
• More apoptosis rate in macrophages and lymphocites
• Negative correlation between CD8-Fas ligand and vital capacity
Kopinski P et al. Przegl Lek 2007: 64:689 ( Abstr )
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Diagnostic Cenario :Smoking and Diffuse Lung Disease
IPF versus
Other smoking-related lung disease
IPFplus
Other smoking-related lung disease
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Smoking and Diffuse Lung Disease
Usual Interstitial Pneumonia (UIP)
Descamative Interstitial Pneumonia (DIP) Respiratory Bronchiolitis associeted-Interstitial Lung Disease (RB-ILD)
Nonspecific Interstitial Pneumonia (NSIP)
Eosinophilic Granuloma (EG)
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Smoking-related Diffuse Lung Disease
Katzenstein ALA, Myers JL. Am J Resp Crit Care Med 1997; 157: 1301Ryu JH et al. Eur Resp J 2001; 17: 122
Features UIP DIP RBILD NSIP Eos gr
Mean age, yr 57 42 36 49 34
Smoking, % 71 97 80 31 (?) 94
Mortality rate, % 68 27 0 11 0
Mean survival, y 5-6 12 0 1.5 0
Response to steroids No Yes Yes Yes Yes ?
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Smoking-related Diffuse Lung Disease
Bjoraker JA et al. Am J Resp Crit Care Med 1998; 157: 199
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ATS-ERS. Am J Resp Crit Care Med 2000; 161: 646
Idiopathic Pulmonary Fibrosis
Clinical Diagnosis (ATS-ERS)
Major criteria
• Exclusion of others ILD
• Abnormal lung function tests
• Tipical findings on HRCT
• TLB or BAL no other diagnosis
Minor criteria
• Age > 50 yr
• Insidious dyspnea on exertion
• Duration of illness >= 3 mo
• Bibasilar velcro crackles
Smoking is not a criteria
Immunocompetent adult : 4 major AND 3 minor
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IPF in Nonsmokers
Lopes AJ et al. J Bras Pneumol 2007; 33: 671
• N = 30
• Prospective
• 70.9 y – 18 were female – 15 SurgLBx
• Lung function tests versus HRCT findings
• Correlation between CT-score and LFT
(volume, diffusion, dynamic compliance)
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IPF and Lung Cancer
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IPF and Lung Cancer
Daniels CE et al. Curr Opin Pulm Med 2005; 11: 431
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IPF and Lung Cancer
Aubry MC et al. Mayo Clin Proc 2002; 77: 763
• N = 24 patients with biopsy proven IPF and lung cancer
• Control groups: 63 with IPF only and 532 with lung cancer only
• Caractheristics:
• Male : 88 %
• Age ( median, y ) : 72.8
• Smokers ( ever ) : 92 %
• Pack-years ( median ) : 51
• Incidental cancer : 42 %
• 4 months interval : 67 %
• TLC , FEV1 , SpO2 ex
• NSCLC : 95 %
• Mortality : 67 %
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IPF and Lung Cancer
Aubry MC et al. Mayo Clin Proc 2002; 77: 763
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IPF and Lung Cancer
Hubbard R et al. Am J Resp Crit Care Med 2000; 161: 5
• Populational-based cohort (UK)• CFA n = 890 • Controls n = 5.884
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IPF and Emphysema
Thorax 1997; 52: 998-1002 n = 21
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IPF and Emphysema
n = 61
Eur Resp J 2005; 26: 586-593
Resp Med 2005; 99: 948-954
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• N = 11 ( 8 male – 3 female ), 70.2 years-old
• ATS-ERS criteria – exclusion of other ILD
• Normal lung volumes in 7, restriction in 3, hyperinflation in 1
• DLco moderate to severe reduction in all
• 6MWT - dessaturation in 9
• PH by echo in 4
Silva DR et al. J Bras Pneumol 2008; 34: 779
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Silva DR et al. J Bras Pneumol 2008; 34: 779
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Smokers have a better survival ?
King Jr TE et al. Am J Resp Crit Care Med 2001; 164: 1171
n = 63n = 166 n = 20
n = 249
• n = 238
• Prospective
• Survival score
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Smoking and IPFPrognostic Implications
Collard HR et al. Am J Resp Crit Care Med 2003; 168: 538
• Cohort - 81 biopsy-proven IPF patients
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Smoking and IPFPrognostic Implications
Study Design N Change survival
Rudd RM et al, 2007 Prospective 588 No
Alakhras PA et al, 2007 Retrospective 197 No
Pereira CAC et al, 2006 Retrospective 86 No
Flaherty KR et al, 2006 Prospective 197 No
Collard HR et al, 2003 Prospective 81 No
King Jr TE et al, 2001 Prospective 238 Better ?
Rubin AS et al, 2000 Retrospective 117 No
MBGazzana Current versus Ever smoking
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Smokers have a better survival ?
Antoniou KM, Wells AU et al. Am J Resp Crit Care Med 2008; 177: 190
CPI Adjusted-survival
Current = Former
Never > Former
Never > Ever
n = 63n = 166 n = 20
n = 249
“ Healthy smoker
lead-time effect ”
CPI = Composite Physiologic Index
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Smoking Cessation and
Idiopathic Pulmonary Fibrosis
• No specific studies
• Nothig in IPF guidelines
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IPF and SmokingPatients Experiences
• N = 1.448
• Survey – questionnaires ( 52 questions )
• Focus on patient education and resources use
• Smoking status
― Current : 3.2 %
― Former : 65.7 %
― Never : 30.7 %
• In clinical practice, patients stop smoking
Collard HR et al. Resp Med 2007; 101: 1350
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Baumgartner KB et al. Am J Resp Crit Care Med 1997: 155: 242
Smoking Cessation and IPF
• Multicenter case-control study
• 248 cases and 491 control subjects
• Smoking cessation prior to diagnosis:
• Less than 2.5 yr : OR 3.5 ( 95% CI: 1.1 to 11.9 )
• 2.5 to 10 yr : OR 2.3 ( 95% CI: 1.3 to 4.2 )
• 10 to 25 yr : OR 1.9 ( 95% CI: 1.1 to 3.2 )
• 25 or more yr : OR 1.3 ( 95% CI: 0.7 to 2.3 )
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Take Home Messages
• Smoking is a risk factor for IPF, but not essential for diagnosis
• IPF (UIP) is different from others smoking-related lung diseases
• Pay attention in concomitant lung cancer and emphysema
• Prognostic implications of smoking in IPF is on debate
• Smoking cessation has not been proved benefit yet,
but it has been recommended in real world !
• Relationship between IPF and smoking is complex
MBGazzana
IPF and Smoking
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Obrigado pela atenção !
MBGazzana
Hospital de Clínicas de Porto Alegre ( HCPA )Universidade Federal do Rio Grande do Sul ( UFRGS )
Campus da Saúde