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Am J Respir Cell Mol Biol. 2018 Apr;58(4):500-509. doi: 10.1165/rcmb.2017-0373OC.

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

Author information

1
1 University of Colorado School of Medicine, Aurora, Colorado.
2
2 National Jewish Health, Denver, Colorado.
3
3 Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
4
4 Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
5
5 GSK, King of Prussia, Pennsylvania.
6
6 Division of Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; and.
7
7 Division of General Internal Medicine and Primary Care, Brigham and Women's Hospital, Boston, Massachusetts.

Abstract

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 (FEV1), adjusting for current smoking status. We also related cell count measures to 3-year change in FEV1 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 FEV1 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 FEV1, 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.

KEYWORDS:

chronic obstructive pulmonary disease; computational biology; gene expression; immunology

PMID:
29206476
PMCID:
PMC5894501
[Available on 2019-04-01]
DOI:
10.1165/rcmb.2017-0373OC

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