Systemic Markers of Adaptive and Innate Immunity Are Associated with Chronic Obstructive Pulmonary Disease Severity and Spirometric Disease Progression

• Published in: American journal of respiratory cell and molecular biology Vol. 58; no. 4; pp. 500 - 509
• Main Authors: Halper-Stromberg, Eitan, Yun, Jeong H., Parker, Margaret M., Singer, Ruth Tal, Gaggar, Amit, Silverman, Edwin K., Leach, Sonia, Bowler, Russell P., Castaldi, Peter J.
• Format: Journal Article
• Language: English
• Published: United States American Thoracic Society 01.04.2018
• Subjects: Cell culture; Chronic obstructive pulmonary disease; Gene expression; Hypotheses; Immune response; Immune response (cell-mediated); Immunity (Disease); Immunological memory; Innate immunity; Leukocytes (eosinophilic); Leukocytes (neutrophilic); Lung diseases; Lymphocytes; Lymphocytes B; Memory cells; Monocytes; Neutrophils; Obstructive lung disease; Original Research; Population studies; Respiratory function; Singers; Smoking; Studies; Systematic review; computational biology; immunology; gene expression; chronic obstructive pulmonary disease
• ISSN: 1044-1549; 1535-4989; 1535-4989
• DOI: 10.1165/rcmb.2017-0373OC

The progression of chronic obstructive pulmonary disease (COPD) is associated with marked alterations in circulating immune cell populations, but no studies have characterized alterations in these cell types across the full spectrum of lung function impairment in current and former smokers. In 6,299 subjects from the COPDGene and ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) studies, we related Coulter blood counts and proportions to cross-sectional forced expiratory volume in 1 second (FEV ), adjusting for current smoking status. We also related cell count measures to 3-year change in FEV in ECLIPSE subjects. In a subset of subjects with blood gene expression data, we used cell type deconvolution methods to infer the proportions of immune cell subpopulations, and we related these to COPD clinical status. We observed that FEV levels are positively correlated with lymphocytes and negatively correlated with myeloid populations, such as neutrophils and monocytes. In multivariate models, absolute cell counts and proportions were associated with cross-sectional FEV , and lymphocytes, monocytes, and eosinophil counts were predictive of 3-year change in lung function. Using cell type deconvolution to study immune cell subpopulations, we observed that subjects with COPD had a lower proportion of CD4 resting memory cells and naive B cells compared with smokers without COPD. Alterations in circulating immune cells in COPD support a mixed pattern of lymphocyte suppression and an enhanced myeloid cell immune response. Cell counts and proportions contribute independent information to models predicting lung function, suggesting a critical role for immune response in long-term COPD outcomes. Cell type deconvolution is a promising method for immunophenotyping in large cohorts.