Low-Blood Lymphocyte Number and Lymphocyte Decline as Key Factors in COPD Outcomes: A Longitudinal Cohort Study

Respiration. 2021;100(7):618-630. doi: 10.1159/000515180. Epub 2021 Apr 26.

Abstract

Background: Smokers with and without chronic obstructive pulmonary disease (COPD) are at risk of severe outcomes like exacerbations, cancer, respiratory failure, and decreased survival. The mechanisms for these outcomes are unclear; however, there is evidence that blood lymphocytes (BL) number might play a role.

Objective: The objective of this study is to investigate the relationship between BL and their possible decline over time with long-term outcomes in smokers with and without COPD.

Methods: In 511 smokers, 302 with COPD (COPD) and 209 without COPD (noCOPD), followed long term, we investigated whether BL number and BL decline over time might be associated with long-term outcomes. Smokers were divided according to BL number in high-BL (≥1,800 cells/µL) and low-BL (<1,800 cells/µL). Clinical features, cancer incidence, and mortality were recorded during follow-up. BL count in multiple samples and BL decline over time were calculated and related to outcomes.

Results: BL count was lower in COPD (1,880 cells/µL) than noCOPD (2,300 cells/µL; p < 0.001). 43% of COPD and 23% of noCOPD had low-BL count (p < 0.001). BL decline over time was higher in COPD than noCOPD (p = 0.040). 22.5% of the whole cohort developed cancer which incidence was higher in low-BL subjects and in BL decliners than high-BL (31 vs. 18%; p = 0.001) and no decliners (32 vs. 19%; p = 0.002). 26% in the cohort died during follow-up. Furthermore, low-BL count, BL decline, and age were independent risk factors for mortality by Cox regression analysis.

Conclusion: BL count and BL decline are related to worse outcomes in smokers with and without COPD, which suggests that BL count and decline might play a mechanistic role in outcomes deterioration. Insights into mechanisms inducing the fall in BL count could improve the understanding of COPD pathogenesis and point toward new therapeutic measures.

Keywords: COPD outcomes; COPD survival; Lymphocyte decline.

MeSH terms

  • Female
  • Forced Expiratory Volume
  • Humans
  • Longitudinal Studies
  • Lymphocyte Count*
  • Male
  • Middle Aged
  • Neoplasms / complications
  • Prognosis
  • Pulmonary Disease, Chronic Obstructive / blood*
  • Pulmonary Disease, Chronic Obstructive / complications
  • Pulmonary Disease, Chronic Obstructive / mortality
  • Risk Factors
  • Smoking / adverse effects
  • Smoking / blood
  • Smoking / immunology*