Journal article
Airway Mucin Concentration as a Marker of Chronic Bronchitis
The New England journal of medicine, Vol.377(10), pp.911-922
09/07/2017
DOI: 10.1056/NEJMoa1701632
PMCID: PMC5706541
PMID: 28877023
Abstract
Chronic obstructive pulmonary disease (COPD) is characterized by chronic bronchitic and emphysematous components. In one biophysical model, the concentration of mucin on the airway surfaces is hypothesized to be a key variable that controls mucus transport in healthy persons versus cessation of transport in persons with muco-obstructive lung diseases. Under this model, it is postulated that a high mucin concentration produces the sputum and disease progression that are characteristic of chronic bronchitis.
We characterized the COPD status of 917 participants from the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) using questionnaires administered to participants, chest tomography, spirometry, and examination of induced sputum. Total mucin concentrations in sputum were measured with the use of size-exclusion chromatography and refractometry. In 148 of these participants, the respiratory secreted mucins MUC5AC and MUC5B were quantitated by means of mass spectrometry. Data from chronic-bronchitis questionnaires and data on total mucin concentrations in sputum were also analyzed in an independent 94-participant cohort.
Mean (±SE) total mucin concentrations were higher in current or former smokers with severe COPD than in controls who had never smoked (3166±402 vs. 1515±152 μg per milliliter) and were higher in participants with two or more respiratory exacerbations per year than in those with zero exacerbations (4194±878 vs. 2458±113 μg per milliliter). The absolute concentrations of MUC5B and MUC5AC in current or former smokers with severe COPD were approximately 3 times as high and 10 times as high, respectively, as in controls who had never smoked. Receiver-operating-characteristic curve analysis of the association between total mucin concentration and a diagnosis of chronic bronchitis yielded areas under the curve of 0.72 (95% confidence interval [CI], 0.65 to 0.79) for the SPIROMICS cohort and 0.82 (95% CI, 0.73 to 0.92) for the independent cohort.
Airway mucin concentrations may quantitate a key component of the chronic bronchitis pathophysiologic cascade that produces sputum and mediates disease severity. Studies designed to explore total mucin concentrations in sputum as a diagnostic biomarker and therapeutic target for chronic bronchitis appear to be warranted. (Funded by the National Heart, Lung, and Blood Institute and others.).
Details
- Title: Subtitle
- Airway Mucin Concentration as a Marker of Chronic Bronchitis
- Creators
- Mehmet Kesimer - From the Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill (M.K., A.A.F., A.C., G.R., R.C., C.W.D., C.M.D., N.E.A., W.H.A., A.G.H., W.K.O., R.C.B.), and the Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem (E.R.B., A.T.H.) - both in North Carolina; the Department of Medicine, Columbia University Medical Center, and the Department of Epidemiology, Mailman School of Public Health at Columbia University (R.G.B.), and the Department of Medicine, Weill Cornell Medical College (F.M.), New York; the Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, Department of Medicine, University of California San Francisco Medical Center, San Francisco (S.A.C., P.G.W.); the Department of Medicine and Physiology, David Geffen School of Medicine, University of California, Los Angeles (C.B.C.); the Division of Pulmonary and Critical Care Medicine, University of Michigan Health System, Ann Arbor (M.K.H.); the Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore (N.N.H.); the Department of Radiology, Division of Physiologic Imaging, University of Iowa Hospitals and Clinics, Iowa City (E.A.H.); and the Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Utah, Veterans Affairs Medical Center, Salt Lake City (R.E.K., R.P.)Amina A Ford - From the Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill (M.K., A.A.F., A.C., G.R., R.C., C.W.D., C.M.D., N.E.A., W.H.A., A.G.H., W.K.O., R.C.B.), and the Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem (E.R.B., A.T.H.) - both in North Carolina; the Department of Medicine, Columbia University Medical Center, and the Department of Epidemiology, Mailman School of Public Health at Columbia University (R.G.B.), and the Department of Medicine, Weill Cornell Medical College (F.M.), New York; the Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, Department of Medicine, University of California San Francisco Medical Center, San Francisco (S.A.C., P.G.W.); the Department of Medicine and Physiology, David Geffen School of Medicine, University of California, Los Angeles (C.B.C.); the Division of Pulmonary and Critical Care Medicine, University of Michigan Health System, Ann Arbor (M.K.H.); the Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore (N.N.H.); the Department of Radiology, Division of Physiologic Imaging, University of Iowa Hospitals and Clinics, Iowa City (E.A.H.); and the Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Utah, Veterans Affairs Medical Center, Salt Lake City (R.E.K., R.P.)Agathe Ceppe - From the Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill (M.K., A.A.F., A.C., G.R., R.C., C.W.D., C.M.D., N.E.A., W.H.A., A.G.H., W.K.O., R.C.B.), and the Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem (E.R.B., A.T.H.) - both in North Carolina; the Department of Medicine, Columbia University Medical Center, and the Department of Epidemiology, Mailman School of Public Health at Columbia University (R.G.B.), and the Department of Medicine, Weill Cornell Medical College (F.M.), New York; the Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, Department of Medicine, University of California San Francisco Medical Center, San Francisco (S.A.C., P.G.W.); the Department of Medicine and Physiology, David Geffen School of Medicine, University of California, Los Angeles (C.B.C.); the Division of Pulmonary and Critical Care Medicine, University of Michigan Health System, Ann Arbor (M.K.H.); the Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore (N.N.H.); the Department of Radiology, Division of Physiologic Imaging, University of Iowa Hospitals and Clinics, Iowa City (E.A.H.); and the Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Utah, Veterans Affairs Medical Center, Salt Lake City (R.E.K., R.P.)Giorgia Radicioni - From the Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill (M.K., A.A.F., A.C., G.R., R.C., C.W.D., C.M.D., N.E.A., W.H.A., A.G.H., W.K.O., R.C.B.), and the Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem (E.R.B., A.T.H.) - both in North Carolina; the Department of Medicine, Columbia University Medical Center, and the Department of Epidemiology, Mailman School of Public Health at Columbia University (R.G.B.), and the Department of Medicine, Weill Cornell Medical College (F.M.), New York; the Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, Department of Medicine, University of California San Francisco Medical Center, San Francisco (S.A.C., P.G.W.); the Department of Medicine and Physiology, David Geffen School of Medicine, University of California, Los Angeles (C.B.C.); the Division of Pulmonary and Critical Care Medicine, University of Michigan Health System, Ann Arbor (M.K.H.); the Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore (N.N.H.); the Department of Radiology, Division of Physiologic Imaging, University of Iowa Hospitals and Clinics, Iowa City (E.A.H.); and the Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Utah, Veterans Affairs Medical Center, Salt Lake City (R.E.K., R.P.)Rui Cao - From the Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill (M.K., A.A.F., A.C., G.R., R.C., C.W.D., C.M.D., N.E.A., W.H.A., A.G.H., W.K.O., R.C.B.), and the Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem (E.R.B., A.T.H.) - both in North Carolina; the Department of Medicine, Columbia University Medical Center, and the Department of Epidemiology, Mailman School of Public Health at Columbia University (R.G.B.), and the Department of Medicine, Weill Cornell Medical College (F.M.), New York; the Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, Department of Medicine, University of California San Francisco Medical Center, San Francisco (S.A.C., P.G.W.); the Department of Medicine and Physiology, David Geffen School of Medicine, University of California, Los Angeles (C.B.C.); the Division of Pulmonary and Critical Care Medicine, University of Michigan Health System, Ann Arbor (M.K.H.); the Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore (N.N.H.); the Department of Radiology, Division of Physiologic Imaging, University of Iowa Hospitals and Clinics, Iowa City (E.A.H.); and the Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Utah, Veterans Affairs Medical Center, Salt Lake City (R.E.K., R.P.)C William Davis - University of North Carolina at Chapel HillClaire M Doerschuk - From the Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill (M.K., A.A.F., A.C., G.R., R.C., C.W.D., C.M.D., N.E.A., W.H.A., A.G.H., W.K.O., R.C.B.), and the Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem (E.R.B., A.T.H.) - both in North Carolina; the Department of Medicine, Columbia University Medical Center, and the Department of Epidemiology, Mailman School of Public Health at Columbia University (R.G.B.), and the Department of Medicine, Weill Cornell Medical College (F.M.), New York; the Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, Department of Medicine, University of California San Francisco Medical Center, San Francisco (S.A.C., P.G.W.); the Department of Medicine and Physiology, David Geffen School of Medicine, University of California, Los Angeles (C.B.C.); the Division of Pulmonary and Critical Care Medicine, University of Michigan Health System, Ann Arbor (M.K.H.); the Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore (N.N.H.); the Department of Radiology, Division of Physiologic Imaging, University of Iowa Hospitals and Clinics, Iowa City (E.A.H.); and the Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Utah, Veterans Affairs Medical Center, Salt Lake City (R.E.K., R.P.)Neil E Alexis - From the Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill (M.K., A.A.F., A.C., G.R., R.C., C.W.D., C.M.D., N.E.A., W.H.A., A.G.H., W.K.O., R.C.B.), and the Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem (E.R.B., A.T.H.) - both in North Carolina; the Department of Medicine, Columbia University Medical Center, and the Department of Epidemiology, Mailman School of Public Health at Columbia University (R.G.B.), and the Department of Medicine, Weill Cornell Medical College (F.M.), New York; the Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, Department of Medicine, University of California San Francisco Medical Center, San Francisco (S.A.C., P.G.W.); the Department of Medicine and Physiology, David Geffen School of Medicine, University of California, Los Angeles (C.B.C.); the Division of Pulmonary and Critical Care Medicine, University of Michigan Health System, Ann Arbor (M.K.H.); the Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore (N.N.H.); the Department of Radiology, Division of Physiologic Imaging, University of Iowa Hospitals and Clinics, Iowa City (E.A.H.); and the Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Utah, Veterans Affairs Medical Center, Salt Lake City (R.E.K., R.P.)Wayne H Anderson - From the Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill (M.K., A.A.F., A.C., G.R., R.C., C.W.D., C.M.D., N.E.A., W.H.A., A.G.H., W.K.O., R.C.B.), and the Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem (E.R.B., A.T.H.) - both in North Carolina; the Department of Medicine, Columbia University Medical Center, and the Department of Epidemiology, Mailman School of Public Health at Columbia University (R.G.B.), and the Department of Medicine, Weill Cornell Medical College (F.M.), New York; the Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, Department of Medicine, University of California San Francisco Medical Center, San Francisco (S.A.C., P.G.W.); the Department of Medicine and Physiology, David Geffen School of Medicine, University of California, Los Angeles (C.B.C.); the Division of Pulmonary and Critical Care Medicine, University of Michigan Health System, Ann Arbor (M.K.H.); the Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore (N.N.H.); the Department of Radiology, Division of Physiologic Imaging, University of Iowa Hospitals and Clinics, Iowa City (E.A.H.); and the Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Utah, Veterans Affairs Medical Center, Salt Lake City (R.E.K., R.P.)Ashley G Henderson - From the Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill (M.K., A.A.F., A.C., G.R., R.C., C.W.D., C.M.D., N.E.A., W.H.A., A.G.H., W.K.O., R.C.B.), and the Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem (E.R.B., A.T.H.) - both in North Carolina; the Department of Medicine, Columbia University Medical Center, and the Department of Epidemiology, Mailman School of Public Health at Columbia University (R.G.B.), and the Department of Medicine, Weill Cornell Medical College (F.M.), New York; the Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, Department of Medicine, University of California San Francisco Medical Center, San Francisco (S.A.C., P.G.W.); the Department of Medicine and Physiology, David Geffen School of Medicine, University of California, Los Angeles (C.B.C.); the Division of Pulmonary and Critical Care Medicine, University of Michigan Health System, Ann Arbor (M.K.H.); the Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore (N.N.H.); the Department of Radiology, Division of Physiologic Imaging, University of Iowa Hospitals and Clinics, Iowa City (E.A.H.); and the Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Utah, Veterans Affairs Medical Center, Salt Lake City (R.E.K., R.P.)R Graham Barr - Columbia University Irving Medical CenterEugene R Bleecker - From the Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill (M.K., A.A.F., A.C., G.R., R.C., C.W.D., C.M.D., N.E.A., W.H.A., A.G.H., W.K.O., R.C.B.), and the Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem (E.R.B., A.T.H.) - both in North Carolina; the Department of Medicine, Columbia University Medical Center, and the Department of Epidemiology, Mailman School of Public Health at Columbia University (R.G.B.), and the Department of Medicine, Weill Cornell Medical College (F.M.), New York; the Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, Department of Medicine, University of California San Francisco Medical Center, San Francisco (S.A.C., P.G.W.); the Department of Medicine and Physiology, David Geffen School of Medicine, University of California, Los Angeles (C.B.C.); the Division of Pulmonary and Critical Care Medicine, University of Michigan Health System, Ann Arbor (M.K.H.); the Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore (N.N.H.); the Department of Radiology, Division of Physiologic Imaging, University of Iowa Hospitals and Clinics, Iowa City (E.A.H.); and the Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Utah, Veterans Affairs Medical Center, Salt Lake City (R.E.K., R.P.)Stephanie A Christenson - University of California, San FranciscoChristopher B Cooper - University of California, Los AngelesMeiLan K Han - From the Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill (M.K., A.A.F., A.C., G.R., R.C., C.W.D., C.M.D., N.E.A., W.H.A., A.G.H., W.K.O., R.C.B.), and the Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem (E.R.B., A.T.H.) - both in North Carolina; the Department of Medicine, Columbia University Medical Center, and the Department of Epidemiology, Mailman School of Public Health at Columbia University (R.G.B.), and the Department of Medicine, Weill Cornell Medical College (F.M.), New York; the Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, Department of Medicine, University of California San Francisco Medical Center, San Francisco (S.A.C., P.G.W.); the Department of Medicine and Physiology, David Geffen School of Medicine, University of California, Los Angeles (C.B.C.); the Division of Pulmonary and Critical Care Medicine, University of Michigan Health System, Ann Arbor (M.K.H.); the Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore (N.N.H.); the Department of Radiology, Division of Physiologic Imaging, University of Iowa Hospitals and Clinics, Iowa City (E.A.H.); and the Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Utah, Veterans Affairs Medical Center, Salt Lake City (R.E.K., R.P.)Nadia N Hansel - Johns Hopkins UniversityAnnette T Hastie - From the Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill (M.K., A.A.F., A.C., G.R., R.C., C.W.D., C.M.D., N.E.A., W.H.A., A.G.H., W.K.O., R.C.B.), and the Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem (E.R.B., A.T.H.) - both in North Carolina; the Department of Medicine, Columbia University Medical Center, and the Department of Epidemiology, Mailman School of Public Health at Columbia University (R.G.B.), and the Department of Medicine, Weill Cornell Medical College (F.M.), New York; the Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, Department of Medicine, University of California San Francisco Medical Center, San Francisco (S.A.C., P.G.W.); the Department of Medicine and Physiology, David Geffen School of Medicine, University of California, Los Angeles (C.B.C.); the Division of Pulmonary and Critical Care Medicine, University of Michigan Health System, Ann Arbor (M.K.H.); the Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore (N.N.H.); the Department of Radiology, Division of Physiologic Imaging, University of Iowa Hospitals and Clinics, Iowa City (E.A.H.); and the Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Utah, Veterans Affairs Medical Center, Salt Lake City (R.E.K., R.P.)Eric A Hoffman - University of Iowa, RadiologyRichard E Kanner - From the Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill (M.K., A.A.F., A.C., G.R., R.C., C.W.D., C.M.D., N.E.A., W.H.A., A.G.H., W.K.O., R.C.B.), and the Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem (E.R.B., A.T.H.) - both in North Carolina; the Department of Medicine, Columbia University Medical Center, and the Department of Epidemiology, Mailman School of Public Health at Columbia University (R.G.B.), and the Department of Medicine, Weill Cornell Medical College (F.M.), New York; the Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, Department of Medicine, University of California San Francisco Medical Center, San Francisco (S.A.C., P.G.W.); the Department of Medicine and Physiology, David Geffen School of Medicine, University of California, Los Angeles (C.B.C.); the Division of Pulmonary and Critical Care Medicine, University of Michigan Health System, Ann Arbor (M.K.H.); the Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore (N.N.H.); the Department of Radiology, Division of Physiologic Imaging, University of Iowa Hospitals and Clinics, Iowa City (E.A.H.); and the Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Utah, Veterans Affairs Medical Center, Salt Lake City (R.E.K., R.P.)Fernando Martinez - From the Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill (M.K., A.A.F., A.C., G.R., R.C., C.W.D., C.M.D., N.E.A., W.H.A., A.G.H., W.K.O., R.C.B.), and the Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem (E.R.B., A.T.H.) - both in North Carolina; the Department of Medicine, Columbia University Medical Center, and the Department of Epidemiology, Mailman School of Public Health at Columbia University (R.G.B.), and the Department of Medicine, Weill Cornell Medical College (F.M.), New York; the Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, Department of Medicine, University of California San Francisco Medical Center, San Francisco (S.A.C., P.G.W.); the Department of Medicine and Physiology, David Geffen School of Medicine, University of California, Los Angeles (C.B.C.); the Division of Pulmonary and Critical Care Medicine, University of Michigan Health System, Ann Arbor (M.K.H.); the Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore (N.N.H.); the Department of Radiology, Division of Physiologic Imaging, University of Iowa Hospitals and Clinics, Iowa City (E.A.H.); and the Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Utah, Veterans Affairs Medical Center, Salt Lake City (R.E.K., R.P.)Robert Paine III - From the Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill (M.K., A.A.F., A.C., G.R., R.C., C.W.D., C.M.D., N.E.A., W.H.A., A.G.H., W.K.O., R.C.B.), and the Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem (E.R.B., A.T.H.) - both in North Carolina; the Department of Medicine, Columbia University Medical Center, and the Department of Epidemiology, Mailman School of Public Health at Columbia University (R.G.B.), and the Department of Medicine, Weill Cornell Medical College (F.M.), New York; the Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, Department of Medicine, University of California San Francisco Medical Center, San Francisco (S.A.C., P.G.W.); the Department of Medicine and Physiology, David Geffen School of Medicine, University of California, Los Angeles (C.B.C.); the Division of Pulmonary and Critical Care Medicine, University of Michigan Health System, Ann Arbor (M.K.H.); the Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore (N.N.H.); the Department of Radiology, Division of Physiologic Imaging, University of Iowa Hospitals and Clinics, Iowa City (E.A.H.); and the Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Utah, Veterans Affairs Medical Center, Salt Lake City (R.E.K., R.P.)Prescott G Woodruff - University of California, San FranciscoWanda K O'Neal - From the Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill (M.K., A.A.F., A.C., G.R., R.C., C.W.D., C.M.D., N.E.A., W.H.A., A.G.H., W.K.O., R.C.B.), and the Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem (E.R.B., A.T.H.) - both in North Carolina; the Department of Medicine, Columbia University Medical Center, and the Department of Epidemiology, Mailman School of Public Health at Columbia University (R.G.B.), and the Department of Medicine, Weill Cornell Medical College (F.M.), New York; the Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, Department of Medicine, University of California San Francisco Medical Center, San Francisco (S.A.C., P.G.W.); the Department of Medicine and Physiology, David Geffen School of Medicine, University of California, Los Angeles (C.B.C.); the Division of Pulmonary and Critical Care Medicine, University of Michigan Health System, Ann Arbor (M.K.H.); the Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore (N.N.H.); the Department of Radiology, Division of Physiologic Imaging, University of Iowa Hospitals and Clinics, Iowa City (E.A.H.); and the Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Utah, Veterans Affairs Medical Center, Salt Lake City (R.E.K., R.P.)Richard C Boucher - From the Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill (M.K., A.A.F., A.C., G.R., R.C., C.W.D., C.M.D., N.E.A., W.H.A., A.G.H., W.K.O., R.C.B.), and the Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem (E.R.B., A.T.H.) - both in North Carolina; the Department of Medicine, Columbia University Medical Center, and the Department of Epidemiology, Mailman School of Public Health at Columbia University (R.G.B.), and the Department of Medicine, Weill Cornell Medical College (F.M.), New York; the Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, Department of Medicine, University of California San Francisco Medical Center, San Francisco (S.A.C., P.G.W.); the Department of Medicine and Physiology, David Geffen School of Medicine, University of California, Los Angeles (C.B.C.); the Division of Pulmonary and Critical Care Medicine, University of Michigan Health System, Ann Arbor (M.K.H.); the Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore (N.N.H.); the Department of Radiology, Division of Physiologic Imaging, University of Iowa Hospitals and Clinics, Iowa City (E.A.H.); and the Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Utah, Veterans Affairs Medical Center, Salt Lake City (R.E.K., R.P.)
- Resource Type
- Journal article
- Publication Details
- The New England journal of medicine, Vol.377(10), pp.911-922
- DOI
- 10.1056/NEJMoa1701632
- PMID
- 28877023
- PMCID
- PMC5706541
- NLM abbreviation
- N Engl J Med
- ISSN
- 0028-4793
- eISSN
- 1533-4406
- Grant note
- HHSN268200900017C / NHLBI NIH HHS P30 ES005605 / NIEHS NIH HHS HHSN268200900019C / NHLBI NIH HHS HHSN268200900020C / NHLBI NIH HHS HHSN268200900015C / NHLBI NIH HHS HHSN268200900013C / NHLBI NIH HHS P50 HL120100 / NHLBI NIH HHS K24 HL137013 / NHLBI NIH HHS R01 HL110906 / NHLBI NIH HHS HHSN268200900016C / NHLBI NIH HHS R01 HL103940 / NHLBI NIH HHS HHSN268200900018C / NHLBI NIH HHS HHSN268200900014C / NHLBI NIH HHS P01 HL108808 / NHLBI NIH HHS P30 DK054759 / NIDDK NIH HHS
- Language
- English
- Date published
- 09/07/2017
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Internal Medicine
- Record Identifier
- 9984051728702771
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