Mucus plugging on computed tomography and chronic bronchitis in chronic obstructive pulmonary disease

Kim, Victor; Dolliver, W.R.; Nath, Hrudaya; Grumley, S.; Terry, Nina; Ahmed, Asmaa; Yen, Andrew; Jacobs, Kathleen; Kligerman, Seth; Díaz, Alejandro A.

doi:10.1186/s12931-021-01712-0

Cited by 12 publications

(5 citation statements)

References 8 publications

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“…Accumulated mucus could form mucus plaques and plugs within airway lumens serving as the nidus for inflammation, intermittent infection and airflow obstruction (35)(36)(37). Luminal plugging has been identified by CT scan as a frequent finding significantly associated to chronic bronchitis, a finding that may play an important role in the pathophysiology of airflow obstruction in smokers, even without COPD (38).…”

Section: Discussionmentioning

confidence: 99%

Symptomatic smokers without COPD have physiological changes heralding the development of COPD

et al. 2022

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BackgroundChronic Obstructive Pulmonary Disease (COPD) is a major health problem, mainly due to cigarette smoking. Most studies in COPD are dedicated to fully developed COPD in older subjects, even though development of COPD may start soon after smoking initiation. Therefore, there is a need to diagnose this “early disease” by detecting the initial events responsible for ultimate development of COPD.MethodsMeasurement of maximum mid expiratory flow between 25–75 of vital capacity (MMEF) in a routine spirometry, that detects small airways disease, was used to investigate if MMEF abnormalities in smokers without COPD (noCOPD) would relate to respiratory symptoms and identify smokers that might progress to COPD. For this purpose we studied 511 smokers, 302 COPD and 209 noCOPD, followed long term with spirometry including MMEF, CO diffusion capacity (DLCO), 6-minute walking test (6MWT), MRC Dyspnoea Scale, and COPD Assessment Test (CAT). Three spirometries V1,V2,V3 (5±2.5 and 10±4 years apart respectively from V1) were performed to assess functional decline and development of COPD.Results65% of noCOPD had an abnormal MMEF (<80%) and 38% an abnormal DLCO. NoCOPD with MMEF<80% performed worse in the 6MWT (p=0.01), were more dyspnoeic (p=0.01) and had higher prevalence of chronic bronchitis than noCOPD with MMEF>80% (p=0.04). 21% of noCOPD with MMEF<80%, and 2.7% with MMEF>80% developed COPD by V3 (p=0.0004).ConclusionsThe MMEF, a functional test available in a routine spirometry, can detect early lung abnormalities and identify the subset of symptomatic smokers with pathologic changes that might lead to COPD.

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Section: Discussionmentioning

confidence: 99%

Symptomatic smokers without COPD have physiological changes heralding the development of COPD

et al. 2022

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“…These factors modify the biophysical properties of mucous and contribute, alongside altered ciliary beat frequency, to impaired mucociliary clearance efficiency 42 . Together this can result in the development of airway mucous plugs and lead to airway collapse 43 . COPD patients suffering with chronic bronchitis are more likely to experience frequent exacerbations, hospitalization, and higher mortality 44 .…”

Section: Discussionmentioning

confidence: 99%

Hypoxic conditions promote a proliferative, poorly differentiated, and pro-secretory phenotype in COPD lung tissue progenitor cells in vitro

Dale

Santer

Haris

et al. 2022

Preprint

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Chronic obstructive pulmonary disease patients experience variable symptoms dependent on the presence of an emphysematous versus a chronic bronchitis phenotype. Both presentations can be associated with lung tissue and systemic hypoxia, at its most severe leading to Cor pulmonale. Despite this, minimal attention has been given to the effects of hypoxia at the cellular disease level.We isolated and cultured progenitor cells from the distal lung tissue of a 64 year-old, male, emphysematous donor in ambient (21%) and hypoxic (2%) oxygen conditions. Proliferative capacity was determined on collagen coated culture plastic and growth-inactivated 3T3-J2 co-cultures. Epithelial (E-cadherin and pan-cytokeratin) and progenitor (TP63, cytokeratin 5) marker expression were examined. Expanded cells were differentiated at air-liquid interface and ciliated, mucous producing, and club cell populations identified.Isolated cells were positive for the epithelial, pan-cytokeratin and E-cadherin, and progenitor, TP63 and cytokeratin 5, cell markers at isolation and again at passage 5. Passage 5 expanded cells in hypoxia had increased the proportion of TP63 expressing cells by 10% from 51.6 ± 1.2% to 62.6 ± 2.3% (p ≤ 0.01). Proliferative capacity was greater in 3T3J2 co-cultured cells overall and in 2% oxygen this supported the emergence of a proliferation unrestricted population with a limited differentiation capacity. Cells expanded on collagen I in either oxygen underwent differentiation having been expanded with the production of ciliated cells positive for βIV tubulin, and mucin 5ac, mucin 5b and CC10 positive secretory cells. Epithelial barrier formation was reduced significantly (p ≤ 0.0001) in hypoxia-expanded cells compared to normoxia. qRT-PCR showed higher expression of mucins in 2% expanded cells, significantly so with MUC5B (P ≤ 0.05) although mucin protein secretion was greater in 21% expanded cells.Concomitantly these results demonstrate that hypoxia promotes a proliferative phenotype while reducing the overall differentiation capacity of the cells. Further, the retained differentiation potential becomes skewed to a more secretory phenotype demonstrating that hypoxia may be contributing to disease symptom and severity in COPD patients.

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“…Mucus pathology plays a critical role in airway diseases, such as chronic bronchitis (CB), asthma, and chronic obstructive pulmonary disease (COPD) [1][2][3][4][5][6][7][8][9]. COPD affects ~29 million people and is the 4th leading cause of death in the US [10,11].…”

Section: Introduction and Rationalementioning

confidence: 99%

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

Abdalla,

Elalami,

Cho

et al. 2024

Preprint

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Introduction: Mucus 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 analysis: We 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 Dissemination: The Mass General Brigham Institutional Review Board approved the study. Findings will be disseminated through peer-reviewed journals and at professional conferences.

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Mucus plugging on computed tomography and chronic bronchitis in chronic obstructive pulmonary disease

Cited by 12 publications

References 8 publications

Symptomatic smokers without COPD have physiological changes heralding the development of COPD

Symptomatic smokers without COPD have physiological changes heralding the development of COPD

Hypoxic conditions promote a proliferative, poorly differentiated, and pro-secretory phenotype in COPD lung tissue progenitor cells in vitro

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

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