Dataset Information

Black Carbon Content in Airway Macrophages is Associated with Reduced CD80 Expression and Increased Exacerbations in Former Smokers With COPD.

ABSTRACT: Chronic obstructive pulmonary disease (COPD) is characterized by recurrent exacerbations. Macrophages play a critical role in immune response and tissue repair in COPD. Airway macrophages (AM) are exposed to environmental exposures which are retained in the cytoplasmic material. Both biomass and particulate matter have been linked to higher AM black carbon. It is unknown if AM black carbon is associated with COPD morbidity and macrophage phenotype. Former smokers with COPD were enrolled and sputum induction was performed to obtain airway macrophages. Macrophages underwent black carbon quantification and flow cytometry phenotyping. Health information was obtained the same day as sputum induction and prospective exacerbations were assessed by monthly telephone calls. We studied 30 former smokers with COPD who had a mean age of 67 years and mean forced expiratory volume in 1 second (FEV1)% predicted of 60.8%. Higher AM black carbon content was associated with increased total exacerbations and severe exacerbations and reduced CD80 expression. AM black carbon association with respiratory morbidity is largely unexplored and this is the first study to identify association with prospective exacerbations. Macrophages expressed reduced CD80, a surface marker providing costimulatory signals required for development of antigen-specific immune responses. Our findings suggest that reduced CD80 expression is the pathophysiologic mechanism for the association of AM black carbon content and increased exacerbations. Therefore, beyond solely serving as a marker for increased exposures, AM black carbon content may be a predictor of future exacerbations given a macrophage less equipped to respond to an acute infectious exposure.

SUBMITTER: Tejwani V

PROVIDER: S-EPMC8047619 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Black Carbon Content in Airway Macrophages is Associated with Reduced CD80 Expression and Increased Exacerbations in Former Smokers With COPD.

Tejwani Vickram V Moughames Eric E Suresh Karthik K Tang Shih-En SE Mair Laura G LG Romero Karina K Putcha Nirupama N Alexis Neil E NE Woo Han H D'Alessio Franco R FR Hansel Nadia N NN

Chronic obstructive pulmonary diseases (Miami, Fla.) 20210101 1

<h4>Background</h4>Chronic obstructive pulmonary disease (COPD) is characterized by recurrent exacerbations. Macrophages play a critical role in immune response and tissue repair in COPD. Airway macrophages (AM) are exposed to environmental exposures which are retained in the cytoplasmic material. Both biomass and particulate matter have been linked to higher AM black carbon. It is unknown if AM black carbon is associated with COPD morbidity and macrophage phenotype.<h4>Methods</h4>Former smoker ...[more]

PMID: 33156984

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Project description:ObjectivesMuscle wasting is a recognised extra-pulmonary complication in chronic obstructive pulmonary disease and has been associated with increased risk of death. Acute respiratory exacerbations are associated with reduction of muscle function, but there is a paucity of data on their long-term effect. This study explores the relationship between acute respiratory exacerbations and long-term muscle loss using serial measurements of CT derived pectoralis muscle area (PMA).Design and settingParticipants were included from two prospective, longitudinal, observational, multicentre cohorts of ever-smokers with at least 10 pack-year history.ParticipantsThe primary analysis included 1332 (of 2501) participants from Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) and 4384 (of 10 198) participants from Genetic Epidemiology of COPD (COPDGene) who had complete data from their baseline and follow-up visits.InterventionsPMA was measured on chest CT scans at two timepoints. Self-reported exacerbation data were collected from participants in both studies through the use of periodic longitudinal surveys.Main outcome measuresAge-related and excess muscle loss over time.ResultsAge, sex, race and body mass index were associated with baseline PMA. Participants experienced age-related decline at the upper end of reported normal ranges. In ECLIPSE, the exacerbation rate over time was associated with an excess muscle area loss of 1.3% (95% CI 0.6 to 1.9, p<0.001) over 3 years and in COPDGene with an excess muscle area loss of 2.1% (95% CI 1.2 to 2.8, p<0.001) over 5 years. Excess muscle area decline was absent in 273 individuals who participated in pulmonary rehabilitation.ConclusionsExacerbations are associated with accelerated skeletal muscle loss. Each annual exacerbation was associated with the equivalent of 6 months of age-expected decline in muscle mass. Ameliorating exacerbation-associated muscle loss represents an important therapeutic target.

Project description:Upregulation of Expression of the Ubiquitin Carboxyl Terminal Hydrolase L1 Gene in Human Airway Epithelium of Cigarette Smokers The microarray data deposited here is from 39 HG-U133 Plus 2.0 GeneChips, from 12 normal non-smokers, 12 phenotypic normal smokers, 9 Early COPD and 6 COPD individuals, all small airways, all small airway. A subset of these samples have been already submitted under GEO Accession Number GSE 4498. These are: 12 non-smokers samples (GSM101095-GSM101106) and 10 smoker samples (GSM101107-GSM101116). These 22 samples that are also in GSE4498 were described in Harvey, B-G; Heguy, A.; Leopold, P.L.; Carolan, B.; Ferris, B. and Crystal R.G. Modification of Gene Expression of the Small Airway Epithelium in Response to Cigarette Smoking. J. Mol. Med (in press). These data are part of a study aimed at understanding how cigarette smoking modifies neuroendocrine cells, in which microarray analysis with TaqMan confirmation was used to assess airway epithelial samples obtained by fiberoptic bronchoscopy from 81 individuals (normal nonsmokers, normal smokers, smokers with early COPD and smokers with established COPD). Of 11 genes considered to be neuroendocrine cell-specific, only ubiquitin C-terminal hydrolase L1(UCHL1), a member of the ubiquitin proteasome pathway, was consistently upregulated in smokers compared to nonsmokers. Up-regulation of UCHL1 at the protein level was observed with immunohistochemistry of bronchial biopsies of smokers compared to nonsmokers. Interestingly, however, while UCHL1 expression was present only in neuroendocrine cells of the airway epithelium in nonsmokers, UCHL1 expression was also expressed in ciliated epithelial cells in smokers, an intriguing observation in light of recent observations that ciliated cells can are capable of transdifferentiating to other airway epithelium. In the context that UCHL1 is involved in the degradation of unwanted, misfolded or damaged proteins within the cell and is overexpressed in >50% of lung cancers, its overexpression in chronic smokers may represent an early event in the complex transformation from normal epithelium to overt malignancy. Keywords: non-smokers vs phenotypic normal smokers, smokers with early COPD, and smokers with COPD

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Black Carbon Content in Airway Macrophages is Associated with Reduced CD80 Expression and Increased Exacerbations in Former Smokers With COPD.

Publications

Black Carbon Content in Airway Macrophages is Associated with Reduced CD80 Expression and Increased Exacerbations in Former Smokers With COPD.

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