• Ivan O Rosas, Hilary J Goldberg, Harold R Collard, Souheil El-Chemaly, Kevin Flaherty, Gary M Hunninghake, Joseph A Lasky, David J Lederer, Roberto Machado, Fernando J Martinez, Rie Maurer, Danielle Teller, Imre Noth, Elizabeth Peters, Ganesh Raghu, GarciaJoe G NJGNDivision of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Arizona College of Medicine, Tucson, AZ., and ChoiAugustine M KAMKJoan and Sanford I. Weill Department of Medicine, Weill Cornell Medical College, New York, NY. Electronic address: amc2056@med.cornell.edu..
• Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
• Chest. 2018 Jan 1; 153 (1): 94-104.

BackgroundPreclinical studies have demonstrated that low-dose carbon monoxide (CO) can abrogate experimental lung fibrosis. To test the therapeutic role of inhaled CO, we designed a clinical study in patients with idiopathic pulmonary fibrosis (IPF).MethodsWe conducted a multicenter, phase IIa, double-blinded, sham-controlled, clinical trial. Patients with IPF were randomized to treatment with inhaled CO at 100 to 200 parts per million or to inhaled 21% oxygen for 2 h daily, twice weekly, for 12 weeks. The primary study end point was the difference in change in matrix metalloproteinase-7 (MMP7) serum concentration after 12 weeks of treatment. Secondary end points included pulmonary function test measures, 6-min walk distance, rates of adverse events, acute exacerbation, hospitalization and death, and quality of life measures.ResultsFifty-eight subjects were randomized to treatment with inhaled CO (n = 29) or placebo (n = 29). Despite modest increases in CO blood levels, the change in MMP7 concentrations after 12 weeks of treatment did not significantly differ between the study arms (MMP7 difference at week 12, -0.90 ng/mL; 95% CI, -4.18 to 2.38 ng/mL). No differences were observed in physiologic measures, incidence of acute exacerbations, hospitalization, death, or patient-reported outcomes. Importantly, no differences in distribution of adverse events were noted between the treatment arms.ConclusionsInhaled CO is well tolerated and can be safely administered to patients with IPF in the ambulatory setting; however, inhaled CO did not result in significant changes in study end points. Our findings support testing the efficacy of inhaled therapies in future IPF clinical trials.Trial RegistryClinicalTrials.gov; No.: NCT01214187; URL: www.clinicaltrials.gov.Copyright © 2017. Published by Elsevier Inc.

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