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

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.

SUBMITTER: Halper-Stromberg E

PROVIDER: S-EPMC5894501 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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

Halper-Stromberg Eitan E Yun Jeong H JH Parker Margaret M MM Singer Ruth Tal RT Gaggar Amit A Silverman Edwin K EK Leach Sonia S Bowler Russell P RP Castaldi Peter J PJ

American journal of respiratory cell and molecular biology 20180401 4

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 force ...[more]

PMID: 29206476

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Project description:BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) can experience 'exacerbations' of their conditions. An exacerbation is an event defined in terms of subjective descriptors or symptoms, namely dyspnoea, cough and sputum that worsen sufficiently to warrant a change in medical management. There is a need for reliable markers that reflect the pathological mechanisms that underlie exacerbation severity and that can be used as a surrogate to assess treatment effects in clinical studies. Little is known as to how existing study variables and suggested markers change in both the stable and exacerbation phases of COPD. In an attempt to find the best surrogates for exacerbations, we have reviewed the literature to identify which of these markers change in a consistent manner with the severity of the exacerbation event. METHODS: We have searched standard databases between 1966 to July 2004 using major keywords and terms. Studies that provided demographics, spirometry, potential markers, and clear eligibility criteria were included in this study. Central tendencies and dispersions for all the variables and markers reported and collected by us were first tabulated according to sample size and ATS/ERS 2004 Exacerbation Severity Levels I to III criteria. Due to the possible similarity of patients in Levels II and III, the data was also redefined into categories of exacerbations, namely out-patient (Level I) and in-patient (Levels II & III combined). For both approaches, we performed a fixed effect meta-analysis on each of the reported variables. RESULTS: We included a total of 268 studies reported between 1979 to July 2004. These studies investigated 142,407 patients with COPD. Arterial carbon dioxide tension and breathing rate were statistically different between all levels of exacerbation severity and between in out- and in-patient settings. Most other measures showed weak relationships with either level or setting, or they had insufficient data to permit meta-analysis. CONCLUSION: Arterial carbon dioxide and breathing rate varied in a consistent manner with exacerbation severity and patient setting. Many other measures showed weak correlations that should be further explored in future longitudinal studies or assessed using suggested mathematical modelling techniques.

Dataset Information

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

Publications

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

Similar Datasets

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