Airway Mucin Concentration as a Marker of Chronic Bronchitis

作者：Mehmet Kesımer, Amina A. Ford, Agathe Ceppe, Giorgia Radicioni, Rui Cao, C. William Davis, Claire M. Doerschuk, Neil E. Alexis, Wayne H. Anderson, Ashley G. Henderson, R. Graham Barr, Eugene R. Bleecker, Stephanie A. Christenson, Christopher B. Cooper, MeiLan K. Han, Nadia N. Hansel, Annette T. Hastie, Eric A. Hoffman, Richard E. Kanner, Fernando J. Martínez, Robert Paine, Prescott G. Woodruff, Wanda K. O’Neal, Richard C. Boucher · 发表于：New England Journal of Medicine · 年份：2017 · DOI：10.1056/nejmoa1701632 · 被引用次数：387 · 研究领域：Asthma and respiratory diseases、Chronic Obstructive Pulmonary Disease (COPD) Research、Inhalation and Respiratory Drug Delivery

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 v...