Airway Mucin Concentration as a Marker of Chronic Bronchitis.

MS#: 
MS082
TitleAirway Mucin Concentration as a Marker of Chronic Bronchitis.
Publication TypePublication
Year2017
AuthorsKesimer M, Ford AA, Ceppe A, Radicioni G, Cao R, C Davis W, Doerschuk CM, Alexis NE, Anderson WH, Henderson AG, R Barr G, Bleecker ER, Christenson SA, Cooper CB, Han MK, Hansel NN, Hastie AT, Hoffman EA, Kanner RE, Martinez F, Paine R, Woodruff PG, O'Neal WK, Boucher RC
JournalN Engl J Med
Volume377
Issue10
Pagination911-922
Date Published2017 09 07
ISSN1533-4406
KeywordsAged, Analysis of Variance, asthma, biomarkers, Bronchitis, Chronic, Disease Progression, Female, Humans, Male, Mass Spectrometry, Middle Aged, Mucin 5AC, Mucin-5B, Mucins, Pulmonary Disease, Chronic Obstructive, Respiratory System, ROC Curve, smoking, Sputum, Surveys and Questionnaires
Abstract

BACKGROUND: 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.METHODS: 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.RESULTS: 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.CONCLUSIONS: 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.).

DOI10.1056/NEJMoa1701632
Alternate JournalN. Engl. J. Med.
PubMed ID28877023
PubMed Central IDPMC5706541
Grant ListHHSN268200900019C / HL / NHLBI NIH HHS / United States
R01 HL103940 / HL / NHLBI NIH HHS / United States
P30 ES005605 / ES / NIEHS NIH HHS / United States
K24 HL137013 / HL / NHLBI NIH HHS / United States
HHSN268200900015C / HL / NHLBI NIH HHS / United States
HHSN268200900016C / HL / NHLBI NIH HHS / United States
R01 HL110906 / HL / NHLBI NIH HHS / United States
U01 HL137880 / HL / NHLBI NIH HHS / United States
HHSN268200900018C / HL / NHLBI NIH HHS / United States
P30 DK054759 / DK / NIDDK NIH HHS / United States
HHSN268200900017C / HL / NHLBI NIH HHS / United States
HHSN268200900020C / HL / NHLBI NIH HHS / United States
HHSN268200900013C / HL / NHLBI NIH HHS / United States
HHSN268200900014C / HL / NHLBI NIH HHS / United States
P01 HL108808 / HL / NHLBI NIH HHS / United States
P50 HL120100 / HL / NHLBI NIH HHS / United States
Manuscript Lead/Corresponding Author Affiliation: 
Genomics and Informatics Center (University of North Carolina at Chapel Hill)
ECI: 
Manuscript Status: 
Published