Journal article
Airway mucin MUC5AC and MUC5B concentrations and the initiation and progression of chronic obstructive pulmonary disease: an analysis of the SPIROMICS cohort
The lancet respiratory medicine, Vol.9(11), pp.1241-1254
11/2021
DOI: 10.1016/S2213-2600(21)00079-5
PMCID: PMC8570975
PMID: 34058148
Abstract
We previously described the contributions of increased total airway mucin concentrations to the pathogenesis and diagnosis of the chronic bronchitic component of chronic obstructive pulmonary disease (COPD). Here, we investigated the relative contribution of each of the major airway gel-forming mucins, MUC5AC and MUC5B, to the initiation, progression, and early diagnosis of airways disease in COPD.
SPIROMICS was a multicentre, observational study in patients aged 40-80 years recruited from six clinical sites and additional subsites in the USA. In this analysis, MUC5AC and MUC5B were quantitated by stable isotope-labelled mass spectrometry in induced sputum samples from healthy never-smokers, ever-smokers at risk for COPD, and ever-smokers with COPD. Participants were extensively characterised using results from questionnaires, such as the COPD assessment test (CAT) and St George's Respiratory Questionnaire; quantitative CT, such as residual volume/total lung capacity ratio (RV/TLC) and parametric response mapping-functional small airway disease (PRM-fSAD); and pulmonary function tests, such as FEV
, forced vital capacity (FVC), and forced expiratory flow, midexpiratory phase (FEF
). Absolute concentrations of both MUC5AC and MUC5B were related to cross-sectional (baseline, initial visit) and 3-year follow-up longitudinal data, including lung function, small airways obstruction, prospective acute exacerbations, and smoking status as primary outcomes. This study is registered with ClinicalTrials.gov (NCT01969344).
This analysis included 331 participants (mean age 63 years [SEM 9·40]), of whom 40 were healthy never-smokers, 90 were at-risk ever-smokers, and 201 were ever-smokers with COPD. Increased MUC5AC concentrations were more reliably associated with manifestations of COPD than were MUC5B concentrations, including decreased FEV
and FEF
, and increased prospective exacerbation frequency, RV/TLC, PRM-fSAD, and COPD assessment scores. MUC5AC concentrations were more reactive to cigarette smoke exposure than were MUC5B concentrations. Longitudinal data from 3-year follow-up visits generated a multivariate-adjusted odds ratio for two or more exacerbations of 1·24 (95% CI 1·04-1·47, p=0·015) for individuals with high baseline MUC5AC concentration. Increased MUC5AC, but not MUC5B, concentration at baseline was a significant predictor of FEV
, FEV
/FVC, FEF
, and CAT score decline during the 3-year follow-up. Moreover, current smokers in the at-risk group showed raised MUC5AC concentrations at initial visits and decreased lung function over 3 years. By contrast, former smokers in the at-risk group showed normal MUC5AC concentrations at the initial visit and preserved lung function over 3 years.
These data indicate that increased MUC5AC concentration in the airways might contribute to COPD initiation, progression, exacerbation risk, and overall pathogenesis. Compared with MUC5B, greater relative changes in MUC5AC concentrations were observed as a function of COPD severity, and MUC5AC concentration seems to be an objective biomarker to detect disease in at-risk and pre-COPD individuals. These data suggest that MUC5AC-producing pathways could be potential targets for future therapeutic strategies. Thus, MUC5AC could be a novel biomarker for COPD prognosis and for testing the efficacy of therapeutic agents.
National Institutes of Health; National Heart, Lung, and Blood Institute.
Details
- Title: Subtitle
- Airway mucin MUC5AC and MUC5B concentrations and the initiation and progression of chronic obstructive pulmonary disease: an analysis of the SPIROMICS cohort
- Creators
- Giorgia Radicioni - University of North Carolina at Chapel HillAgathe Ceppe - University of North Carolina at Chapel HillAmina A Ford - University of North Carolina at Chapel HillNeil E Alexis - University of North Carolina at Chapel HillR Graham Barr - Columbia University Irving Medical CenterEugene R Bleecker - University of ArizonaStephanie A Christenson - University of California, San FranciscoChristopher B Cooper - University of California, Los AngelesMeiLan K Han - University of MichiganNadia N Hansel - Johns Hopkins MedicineAnnette T Hastie - Wake Forest UniversityEric A Hoffman - University of IowaRichard E Kanner - University of UtahFernando J Martinez - Cornell UniversityEsin Ozkan - University of North Carolina at Chapel HillRobert Paine III - University of UtahPrescott G Woodruff - University of California, San FranciscoWanda K O'Neal - University of North Carolina at Chapel HillRichard C Boucher - University of North Carolina at Chapel HillMehmet Kesimer - University of North Carolina at Chapel Hill
- Resource Type
- Journal article
- Publication Details
- The lancet respiratory medicine, Vol.9(11), pp.1241-1254
- DOI
- 10.1016/S2213-2600(21)00079-5
- PMID
- 34058148
- PMCID
- PMC8570975
- NLM abbreviation
- Lancet Respir Med
- ISSN
- 2213-2600
- eISSN
- 2213-2619
- Grant note
- UH3 HL123645 / NHLBI NIH HHS HHSN268200900017C / NHLBI NIH HHS HHSN268200900019C / NHLBI NIH HHS HHSN268200900020C / NHLBI NIH HHS U24 HL141762 / NHLBI NIH HHS U01 HL137880 / NHLBI NIH HHS HHSN268200900015C / NHLBI NIH HHS HHSN268200900013C / NHLBI NIH HHS P50 HL120100 / NHLBI NIH HHS R01 HL136961 / NHLBI NIH HHS P30 DK065988 / NIDDK NIH HHS R01 HL135642 / NHLBI NIH HHS R01 HL110906 / NHLBI NIH HHS HHSN268200900016C / NHLBI NIH HHS R01 HL103940 / NHLBI NIH HHS P01 HL110873 / 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
- 11/2021
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Internal Medicine
- Record Identifier
- 9984318787602771
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