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Recent Advances in Chest Medicine |

Exhaled Nitric Oxide in Pulmonary Diseases: A Comprehensive Review

Peter J. Barnes, DM, DSc, FCCP; Raed A. Dweik, MD, FCCP; Arthur F. Gelb, MD, FCCP; Peter G. Gibson, MD; Steven C. George, MD, PhD; Hartmut Grasemann, MD; Ian D. Pavord, DM; Felix Ratjen, MD, PhD; Philip E. Silkoff, MD, FCCP; D. Robin Taylor, MD; Noe Zamel, MD, FCCP
Author and Funding Information

From the Airway Disease Section (Dr Barnes), Imperial College London, National Heart and Lung Institute, London, England; the Department of Respiratory Medicine, Allergy and Thoracic Surgery (Dr Pavord), University Hospitals of Leicester Trust, Glenfield Hospital, Leicester, England; the Pulmonary Division (Dr Dweik), Department of Medicine, Cleveland Clinic Foundation, Cleveland, OH; the Pulmonary Division (Dr Gelb), Department of Medicine, Lakewood Regional Medical Center, Lakewood, CA; Geffen School of Medicine at UCLA Medical Center (Dr Gelb) Los Angeles, CA; the Department of Biomedical Engineering and Chemical Engineering and Materials Science (Dr George), University of California, Irvine, Irvine, CA; the Department of Respiratory and Sleep Medicine (Dr Gibson), John Hunter Hospital, Woolcock Institute of Medical Research, New Lambton, NSW, Australia; the Division of Respiratory Medicine (Drs Grasemann and Ratjen), Department of Pediatrics and Physiology and Experimental Medicine Program, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada; the Respiratory Division (Dr Zamel), University of Toronto School of Medicine, Toronto, ON, Canada; the Pulmonary Division (Dr Silkoff), Drexel University School of Medicine, Philadelphia, PA; and the Dunedin School of Medicine (Dr Taylor), University of Otago, Dunedin, New Zealand.

Correspondence to: Arthur F. Gelb, MD, FCCP, 3650 E South St, Ste 308, Lakewood, CA 90712; e-mail: afgelb@msn.com


Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).


© 2010 American College of Chest Physicians


Chest. 2010;138(3):682-692. doi:10.1378/chest.09-2090
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The upregulation of nitric oxide (NO) by inflammatory cytokines and mediators in central and peripheral airway sites can be monitored easily in exhaled air. It is now possible to estimate the predominant site of increased fraction of exhaled NO (FeNO) and its potential pathologic and physiologic role in various pulmonary diseases. In asthma, increased FeNO reflects eosinophilic-mediated inflammatory pathways moderately well in central and/or peripheral airway sites and implies increased inhaled and systemic corticosteroid responsiveness. Recently, five randomized controlled algorithm asthma trials reported only equivocal benefits of adding measurements of FeNO to usual clinical guideline management including spirometry; however, significant design issues may exist. Overall, FeNO measurement at a single expiratory flow rate of 50 mL/s may be an important adjunct for diagnosis and management in selected cases of asthma. This may supplement standard clinical asthma care guidelines, including spirometry, providing a noninvasive window into predominantly large-airway-presumed eosinophilic inflammation. In COPD, large/central airway maximal NO flux and peripheral/small airway/alveolar NO concentration may be normal and the role of FeNO monitoring is less clear and therefore less established than in asthma. Furthermore, concurrent smoking reduces FeNO. Monitoring FeNO in pulmonary hypertension and cystic fibrosis has opened up a window to the role NO may play in their pathogenesis and possible clinical benefits in the management of these diseases.


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