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

Area of Science:

• Pulmonary Medicine
• Genetics
• Epidemiology

Background:

• Blood leukocyte counts, particularly eosinophils, are key biomarkers in chronic obstructive pulmonary disease (COPD).
• The precise causal links between leukocyte counts and COPD pathogenesis remain incompletely understood.
• Establishing these causal relationships is crucial for developing effective COPD treatment strategies.

Purpose of the Study:

• To investigate the causal relationships between blood leukocyte counts (specifically eosinophils and neutrophils) and COPD.
• To determine if eosinophil and neutrophil counts influence COPD risk, severity (FEV1/FVC ratio), and hospitalization.
• To explore the potential of targeting eosinophils as a therapeutic strategy for COPD.

Main Methods:

• Employed two-sample bi-directional univariable and multivariable Mendelian Randomization (MR) analyses.
• Utilized genetic variants as instrumental variables to infer causal effects.
• Analyzed data on COPD risk, COPD-related hospitalization, and FEV1/FVC ratio in relation to blood eosinophil and neutrophil counts.

Main Results:

• Elevated blood eosinophil count significantly increases COPD risk (OR=1.22) and COPD-related hospitalization (OR=1.44).
• Higher eosinophil counts are associated with a significant decrease in the FEV1/FVC ratio (OR=0.942).
• COPD onset and decreased FEV1/FVC ratio causally increase blood neutrophil count (OR=1.03 and OR=0.947, respectively).

Conclusions:

• High blood eosinophil count is an independent causal factor for COPD risk, FEV1/FVC decline, and hospitalization.
• Increased neutrophil count is a consequence of COPD onset or FEV1/FVC decline, not a primary cause.
• Eosinophils represent a potential therapeutic target for preventing COPD onset and exacerbations, while neutrophils may not be suitable for such targeting.