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Idiopathic Pulmonary Fibrosis

Outcome in Relation to Smoking Status

¹ Interstitial Lung Disease Unit, Royal Brompton Hospital, London, United Kingdom; ² Department of Thoracic Medicine, University of Crete, Heraklion, Greece; ³ Department of Radiology, Royal Brompton Hospital, London, United Kingdom; ⁴ Department of Radiology, King's College Hospital, London, United Kingdom; and ⁵ Department of Histopathology, Royal Brompton Hospital, London, United Kingdom

Correspondence and requests for reprints should be addressed to Athol U. Wells, M.D., Interstitial Lung Disease Unit, c/o Emmanuel Kaye Building, Manresa Road, London SW3 6LR, UK. E-mail: a.wells{at}rbh.nthames.nhs.uk

Rationale: The pathogenic importance of smoking status in idiopathic pulmonary fibrosis (IPF) is uncertain. In theory, increased oxidative stress in current and former smokers might promote disease progression. However, better survival has been reported for current smokers with IPF, although this might reflect less severe disease at presentation (a "healthy smoker effect").

Objectives: To determine whether smoking status is associated with survival differences in IPF.

Methods: A total of 249 patients with IPF were studied (current smokers, n = 20; former smokers, n = 166; never-smokers, n = 63). Survival was evaluated against smoking status, using proportional hazards analysis, adjusting for sex, age, disease severity (extent of the disease on high-resolution computed tomography, composite physiologic index [CPI], percentage predicted diffusing capacity for carbon monoxide in separate models), and the degree of honeycombing.

Measurements and Main Results: Current smokers had milder disease than did former smokers, with lower CPI scores (P < 0.0001), less extensive disease on high-resolution computed tomography (P < 0.005), and higher unadjusted survival (hazard ratio = 0.44; 95% confidence interval = 0.24, 0.80; P = 0.007). However, survival did not differ between current and former smokers (P = 0.39) after adjustment for CPI levels. By contrast, the increase in survival seen in nonsmokers than in former smokers (hazard ratio = 0.51; 95% confidence interval = 0.41, 0.83; P = 0.008) was amplified (P < 0.0005) by adjustment for CPI levels.

Conclusions: In IPF, survival and severity-adjusted survival are higher in nonsmokers than in former smokers or the combined group of former and current smokers. By contrast, a better outcome in current smokers, compared with former smokers, reflects less severe disease at presentation and may represent a healthy smoker effect.

Key Words: idiopathic pulmonary fibrosis • cigarette smoking • outcome • survival

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject In idiopathic pulmonary fibrosis (IPF), survival is higher in nonsmokers than in smokers. By contrast, a better outcome in current smokers, compared with former smokers, reflects less severe disease at presentation and thus represents a "healthy smoker effect." What This Study Adds to the Field In IPF, survival and severity-adjusted survival are higher in nonsmokers than in former smokers or the combined group of former and current smokers. Our major finding is the negative influence of cigarette smoking on IPF outcome.

 

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