Airway Mucus Plugs in Community-Living Adults: A Study Protocol

IntroductionMucus pathology plays a critical role in airway diseases like chronic bronchitis (CB) and chronic obstructive pulmonary disease (COPD). Up to 32% of community-living persons report clinical manifestations of mucus pathology (e.g., cough and sputum production). However, airway mucus pathology has not been systematically studied in community-living individuals. In this study, we will use an objective, reproducible assessment of mucus pathology on chest computed tomography (CT) scans from community-living individuals participating in the Coronary Artery Risk Development in Young Adults (CARDIA) and Framingham Heart Study (FHS) cohorts. Methods and analysisWe will determine the clinical relevance of CT-based mucus plugs and modifiable and genetic risk and protective factors associated with this process. We will evaluate the associations of mucus plugs with lung function, respiratory symptoms, and chronic bronchitis and examine whether 5-yr. persistent CT-based mucus plugs are associated with the decline in FEV1 and future COPD. Also, we will assess whether modifiable factors, including air pollution and marijuana smoking are associated with increased odds of CT-based mucus plugs and whether cardiorespiratory fitness is related in an opposing manner. Finally, we will determine genetic resilience/susceptibility to mucus pathology. We will use CT data from the FHS and CARDIA cohorts and genome-wide sequencing data from the TOPMed initiative to identify common and rare variants associated with CT-based mucus plugging. Ethics and DisseminationThe Mass General Brigham Institutional Review Board approved the study. Findings will be disseminated through peer-reviewed journals and at professional conferences. Strengths and limitations of this studyO_LIUtilization of data from two well-characterized large community-based US cohorts. C_LIO_LIUse of chest CT scans to identify and quantify mucus plugs, providing a more objective and reproducible measure of airway pathology. C_LIO_LIUse of whole-genome sequencing to identify common and rare genetic variants associated with mucus pathology. C_LIO_LIOnly the inclusion of participants self-identified as non-Hispanic white and non-Hispanic black. C_LIO_LIA limitation of retrospective study design using prospectively collected data. C_LI