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Idiopathic pulmonary fibrosis (IPF) is a chronic and usually fatal lung disease of unknown etiology. The aim of this study was to describe clinical and polysomnographic features of sleep-related breathing disorders (SRBD) and to identify predictors of obstructive sleep apnea (OSA) in IPF patients. Eight hundred fifty-seven patients with IPF were admitted to the Cleveland Clinic from 2001 to 2005. An all-night polysomnogram (PSG) was performed in 18 of them to investigate complaints suggestive of sleep-disordered breathing. OSA was confirmed in 11 of the 18 IPF patients with complaints suggestive of sleep apnea, while the remain 7 patients had a diagnosis of primary snoring or upper airway resistance syndrome (UARS). All patients showed a reduction in sleep efficiency, REM sleep, and slow wave sleep. The apnea-hypopnea index (AHI) was positively correlated with body mass index (p < 0.0001, r = 0.80). The REM AHI and overall AHI were negatively correlated with FEV(1) (p = 0.008, r = -0.59 and p = 0.04, r = -0.49, respectively) and FVC percentages (p = 0.03, r = -0.50 and p = 0.08, r = -0.42, respectively). Our study is the first describing SRBD in IPF patients. An increased BMI and a significant impairment in pulmonary function testing may be predictors of OSA in this population. In the absence of effective treatments for IPF, the diagnosis and treatment of comorbid SRBD may lead to improvements in quality of life.

Rationale: A cellular prooxidant state promotes cells to neoplastic growth, in part because of modification of proteins and their functions. Reactive nitrogen species formed from nitric oxide (NO) or its metabolites, can lead to protein tyrosine nitration, which is elevated in lung cancer. Objective: To determine the alteration in these NO derivatives and the role they may play in contributing to lung carcinogenesis. Methods: We analyzed levels of NO, nitrite (NO 2 Ϫ ), nitrate (NO 3 Ϫ ), and the location of the protein nitration and identified the proteins that are modified. Measurements and Main Results: Although exhaled NO and NO 2 Ϫ were increased, endothelial NO synthase or inducible NO synthase expression was similar in the tumor and tumor-free regions. However, immunohistochemistry showed that nitrotyrosine was increased in the tumor relative to non-tumor-bearing sections. We used proteomics to identify the modified proteins (two-dimensional polyacrylamide gel electrophoresis; mass spectrometry). Both the degree of nitration and the protein nitration profile were altered. We identified more than 25 nitrated proteins, including metabolic enzymes, structural proteins, and proteins involved in prevention of oxidative damage. Alterations of the biology of NO metabolites and nitration of proteins may contribute to the mutagenic processes and promote carcinogenesis. Conclusions: This study provides evidence in favor of a role for reactive nitrogen and oxygen species in lung cancer.Keywords: lung cancer; nitric oxide; nitrotyrosine; protein nitration; proteomics Nitric oxide (NO) plays a variety of regulatory roles in vivo, including control of vascular tone and host defense. However, recent data have suggested that NO metabolites, such as nitrite or NO-modified peptides or proteins, may also play important physiologic roles. Enzymatic generation of NO in mammals is by three isoforms of NO synthase (NOS), inducible NOS (iNOS), endothelial NOS (eNOS), and neuronal NOS (nNOS) (1). The function and regulation of these proteins reflect the role they play in normal physiology. Excessive or inappropriate production of endogenous or exogenous reactive oxygen species (ROS) and NO are implicated in the pathogenesis of cancer (2, 3). For example, cigarette smoke, a major source of exogenous oxidants, is associated with the development of lung cancer (2, 4). Furthermore, cigarette smoking leads to chronic airway inflammation (Received in original form November 15, 2004; accepted in final form May 18, 2005) Supported in part by grants HL60917, AI70649, HL076491, CA53914, and HL04265 from the National Institutes of Health; Debartolo Endowed Funds; American Heart Association 0325313B; a Betsy DeWindt American Cancer Society fellowship, GCRC M01RR018390; and Cafaro Endowed Funds. with accumulation and activation of leukocytes, which produce high levels of ROS and NO. Both these processes lead to oxidative damage (5). Although it is generally accepted that the prooxidant state promotes cells to neoplastic growth through DNA ...