%0 Journal Article %T Smoking and Idiopathic Pulmonary Fibrosis %A Chad K. Oh %A Lynne A. Murray %A Nestor A. Molfino %J Pulmonary Medicine %D 2012 %I Hindawi Publishing Corporation %R 10.1155/2012/808260 %X Idiopathic pulmonary fibrosis (IPF) is a disease of unknown etiology with considerable morbidity and mortality. Cigarette smoking is one of the most recognized risk factors for development of IPF. Furthermore, recent work suggests that smoking may have a detrimental effect on survival of patients with IPF. The mechanism by which smoking may contribute to the pathogenesis of IPF is largely unknown. However, accumulating evidence suggests that increased oxidative stress might promote disease progression in IPF patients who are current and former smokers. In this review, potential mechanisms by which cigarette smoking affects IPF, the effects of cigarette smoking on accelerated loss of lung function in patients with IPF, key genetic studies evaluating the potential candidate genes and gene-environment (smoking) interaction, diagnosis, and treatment with emphasis on recently closed and ongoing clinical trials are presented. 1. Introduction Idiopathic pulmonary fibrosis (IPF) is defined as 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 usual interstitial pneumonia (UIP) [1]. Current estimates of IPF prevalence and annual incidence in the United States range from 14 to 42.7 per 100 000 and 6.8¨C16.3 per 100 000, respectively [2]. There is a high unmet need for novel therapies as conventional therapy has limited efficacy or an unfavorable safety profile and there are no US Food and Drug Administration- (FDA-) approved therapies for IPF treatment. In a recent meta-analysis of observational studies examining environmental and occupational risk factors for IPF, significantly increased risk for IPF was associated with cigarette smoking and exposure [3]. Several environmental exposures also have been associated with increased risk for IPF. Occupational factors, primarily metal and wood dust exposure, adjusted for age and smoking, have been found to be significantly associated with IPF [4, 5]. Among these risk factors, cigarette smoking seems to be the most strongly associated risk factor in both sporadic IPF and familial pulmonary fibrosis [3, 6]. The prevalence of tobacco use in IPF ranges from 41% to 83%, depending on the case definition used in the studies [7, 8]. Current or former smokers have consistently been overrepresented in IPF [9¨C13]. In one case-control study, smoking was identified as a potential risk factor for the development of IPF (odds ratio [OR] = 1.6) [14]. The overall OR for %U http://www.hindawi.com/journals/pm/2012/808260/