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Airway Mucin Concentration as a Marker of Chronic Bronchitis.

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 ?g 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 ?g 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.).

SUBMITTER: Kesimer M

PROVIDER: S-EPMC5706541 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Airway Mucin Concentration as a Marker of Chronic Bronchitis.

Kesimer Mehmet M Ford Amina A AA Ceppe Agathe A Radicioni Giorgia G Cao Rui R Davis C William CW Doerschuk Claire M CM Alexis Neil E NE Anderson Wayne H WH Henderson Ashley G AG Barr R Graham RG Bleecker Eugene R ER Christenson Stephanie A SA Cooper Christopher B CB Han MeiLan K MK Hansel Nadia N NN Hastie Annette T AT Hoffman Eric A EA Kanner Richard E RE Martinez Fernando F Paine Robert R Woodruff Prescott G PG O'Neal Wanda K WK Boucher Richard C RC

The New England journal of medicine 20170901 10

<h4>Background</h4>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 charact ...[more]

PMID: 28877023

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Project description:BackgroundChronic bronchitis (CB) is associated with poor outcomes in patients with chronic obstructive pulmonary disease. The aim of this study was to identify the characteristics that distinguish chronic bronchitis (CB) from non-CB. In addition, the features of mild CB versus severe CB were compared and a cut-off level was defined according to CAT1 and CAT2 scores.MethodsThis study was based on the Korea COPD Subgroup Study (KOCOSS) database, constructed in a multicenter COPD cohort study that recruited patients from 54 centers. CB was defined as CAT1 and CAT2 scores ≥ 3; severe CB was defined as CAT1 and CAT2 scores ≥ 4, while mild CB was defined as either a CAT1 or a CAT2 score < 4. Baseline characteristics, 1-year exacerbation rate, and 3-year FEV1 decline were compared in non-CB versus CB patients and in patients with mild CB versus severe CB.ResultsAmong the 2162 patients enrolled in this study, 497 (23%) had CB. These patients were more likely than non-CB patients to be current smokers; they also had higher symptom and depression/anxiety scores. Lung function tests showed lower FEV1, FEV1/FVC, and DLco values in CB patients. Among CB patients, 67.6% had mild disease. Symptom and depression/anxiety scores were worse in patients with severe CB than in patients with mild CB. There were no significant differences in the lung function tests of the two groups. Analysis of 1-year exacerbation rates in CB patients and non-CB patients revealed that patients with CB more frequently had moderate-to-severe exacerbations (OR = 1.46, p < 0.01). More severe exacerbation was also present in patients with severe CB than in patients with mild CB (OR = 2.52, p = 0.01). The difference in annual FEV1 decline rate did not significantly differ either between CB patients and non-CB patients or between patients with severe CB and patients with mild CB.ConclusionsCB patients had worse symptoms and lung function than non-CB patients; CB patients also had more frequent moderate-to-severe exacerbation. Patients with severe CB had higher symptom scores and more frequent severe exacerbation than did patients with mild CB.

Dataset Information

Airway Mucin Concentration as a Marker of Chronic Bronchitis.

Publications

Airway Mucin Concentration as a Marker of Chronic Bronchitis.

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