{"doi":"10.1172/jci.insight.174124","title":"Persistent mucus plugs in proximal airways are consequential for airflow limitation in asthma","abstract":"BACKGROUNDInformation about the size, airway location, and longitudinal behavior of mucus plugs in asthma is needed to understand their role in mechanisms of airflow obstruction and to rationally design muco-active treatments.METHODSCT lung scans from 57 patients with asthma were analyzed to quantify mucus plug size and airway location, and paired CT scans obtained 3 years apart were analyzed to determine plug behavior over time. Radiologist annotations of mucus plugs were incorporated in an image-processing pipeline to generate size and location information that was related to measures of airflow.RESULTSThe length distribution of 778 annotated mucus plugs was multimodal, and a 12 mm length defined short (\"stubby\", ≤12 mm) and long (\"stringy\", >12 mm) plug phenotypes. High mucus plug burden was disproportionately attributable to stringy mucus plugs. Mucus plugs localized predominantly to airway generations 6-9, and 47% of plugs in baseline scans persisted in the same airway for 3 years and fluctuated in length and volume. Mucus plugs in larger proximal generations had greater effects on spirometry measures than plugs in smaller distal generations, and a model of airflow that estimates the increased airway resistance attributable to plugs predicted a greater effect for proximal generations and more numerous mucus plugs.CONCLUSIONPersistent mucus plugs in proximal airway generations occur in asthma and demonstrate a stochastic process of formation and resolution over time. Proximal airway mucus plugs are consequential for airflow and are in locations amenable to treatment by inhaled muco-active drugs or bronchoscopy.TRIAL REGISTRATIONClinicaltrials.gov; NCT01718197, NCT01606826, NCT01750411, NCT01761058, NCT01761630, NCT01716494, and NCT01760915.FUNDINGAstraZeneca, Boehringer-Ingelheim, Genentech, GlaxoSmithKline, Sanofi-Genzyme-Regeneron, and TEVA provided financial support for study activities at the Coordinating and Clinical Centers beyond the third year of patient follow-up. These companies had no role in study design or data analysis, and the only restriction on the funds was that they be used to support the SARP initiative.","journal":"JCI Insight","year":2023,"id":326774,"datarank":1.014536367792207,"base_score":3.4011973816621555,"endowment":3.4011973816621555,"self_citation_contribution":0.5101796072493234,"citation_network_contribution":0.5043567605428837,"self_endowment_contribution":0.5101796072493234,"citer_contribution":0.5043567605428837,"corpus_percentile":null,"corpus_rank":null,"citation_count":29,"citer_count":26,"citers_with_citation_signal":17,"citers_with_endowment":17,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9649,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT01750411","NCT01761058","NCT01716494","NCT01606826","NCT01718197","NCT01761630","NCT01760915"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":250073,"name":"Brett M. 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