White blood cell count and chronic obstructive pulmonary disease: A Mendelian Randomization study

Zhifa Han; Huiyuan Hu; Peiran Yang; Baicun Li; Guiyou Liu; Junling Pang; Hongmei Zhao; Jing Wang; Chen Wang

doi:10.1016/j.compbiomed.2022.106187

White blood cell count and chronic obstructive pulmonary disease: A Mendelian Randomization study

Comput Biol Med. 2022 Dec;151(Pt A):106187. doi: 10.1016/j.compbiomed.2022.106187. Epub 2022 Oct 13.

Authors

Zhifa Han¹, Huiyuan Hu², Peiran Yang³, Baicun Li³, Guiyou Liu⁴, Junling Pang⁵, Hongmei Zhao⁶, Jing Wang⁷, Chen Wang⁸

Affiliations

¹ Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, 100084, China; State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Pathophysiology, Peking Union Medical College, Beijing, 100730, China.
² State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Pathophysiology, Peking Union Medical College, Beijing, 100730, China; First Clinical College, Xi'an Jiaotong University, Yanta West Road No.76, Xi'an, ShaanXi, 710061, China.
³ State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Pathophysiology, Peking Union Medical College, Beijing, 100730, China.
⁴ Beijing Institute for Brain Disorders, Capital Medical University, Beijing, 100069, China; Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China; National Engineering Laboratory of Internet Medical Diagnosis and Treatment Technology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China.
⁵ State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Pathophysiology, Peking Union Medical College, Beijing, 100730, China. Electronic address: pjl_happy@ibms.pumc.edu.cn.
⁶ State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Pathophysiology, Peking Union Medical College, Beijing, 100730, China. Electronic address: pumczhaohm@sina.com.
⁷ State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Pathophysiology, Peking Union Medical College, Beijing, 100730, China. Electronic address: wangjing@ibms.pumc.edu.cn.
⁸ Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, 100084, China; State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Pathophysiology, Peking Union Medical College, Beijing, 100730, China; Tsinghua University-Peking University Joint Center for Life Sciences, Beijing, 100084, China.

PMID: 36327882
DOI: 10.1016/j.compbiomed.2022.106187

Abstract

Blood leukocyte counts (e.g., eosinophil count) are important biomarkers for the onset, classification, and exacerbation of chronic obstructive pulmonary disease (COPD). The causal relationships between them are necessary for the development of COPD treatment strategy, but remain unclear. Here, we implement two-sample bi-directional univariable Mendelian Randomization (MR) and multivariable MR to investigate the causal relationships. Univariable MR find that elevated blood eosinophil count significantly increases the risk of COPD (odds ratio (OR) = 1.22, 95% confidence interval (CI): 1.14-1.30, P = 1.54 × 10^-09) and COPD-related hospitalization (OR = 1.44, 95% CI: 1.15-1.80, P = 1.36 × 10^-03). Besides, it also significantly decreases the ratio of forced expiratory volume in the first second over forced vital capacity (FEV₁/FVC ratio) (OR = 0.942, 95% CI: 0.914-0.971, P = 1.02 × 10^-04). These findings are fully supported by multivariate MR results. Interestingly, univariable MR reveals a weak causal relationship between elevated blood eosinophil count and COPD risk in younger people (<65 years) (OR = 1.39, 95% CI: 1.10-1.75, P = 5.52 × 10^-03), but not older individuals (OR = 1.20, 95% CI: 0.926-1.55, P = 0.17). Finally, reverse univariable MR reveals the onset of COPD and the decreased FEV₁/FVC ratio both lead to increased blood neutrophil count (OR = 1.03, 95% CI: 1.01-1.05, P = 3.40 × 10^-03 and OR = 0.947, 95% CI: 0.91-0.986, P = 8.75 × 10^-03 respectively). In summary, this MR study demonstrates that high blood eosinophil count is an independent causal mediator of COPD risk, FEV₁/FVC decline, and COPD-related hospitalization. The increase in neutrophil count is induced by COPD onset or FEV₁/FVC decline. This suggests eosinophil, but not neutrophil, may be used as a therapeutic target for preventing the onset and exacerbation of COPD and FEV₁/FVC decline. Therefore, a non-neutrophil-targeted therapeutic strategy for neutrophilic COPD is required in the future.

Keywords: Chronic obstructive pulmonary disease; Eosinophil; Mendelian randomization; Neutrophil.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Forced Expiratory Volume
Humans
Leukocyte Count
Mendelian Randomization Analysis*
Pulmonary Disease, Chronic Obstructive* / genetics
Vital Capacity

Abstract

Publication types

MeSH terms

Grants and funding