Clonal haematopoiesis of indeterminate potential: a risk factor for future exacerbation in patients with COPD.

Background: There are limited data regarding the clinical significance of clonal haematopoiesis of indeterminate potential (CHIP) in patients with COPD. We aimed to evaluate whether CHIP could serve as a biomarker for the long-term prognosis of patients with COPD. Methods: Next-generation sequencing was used to detect CHIP in peripheral blood mononuclear cell samples. Participants with COPD were enrolled in a prospective observational cohort between January 2013 and December 2023. We investigated the association of CHIP status with the risk of subsequent acute exacerbation and longitudinal changes in lung function, by using negative binomial regression and linear mixed regression models, respectively. Results: Among 125 patients with COPD, the CHIP-positive group was 32 (25.6%). Higher smoking intensity and COPD Assessment Test score were significantly associated with increased risk of positive CHIP status, especially in current smokers. Positive CHIP of specific genes was significantly associated with a higher risk of subsequent mild and total acute exacerbation. Positive CHIP of ASXL transcriptional regulator 1 had a lower risk of subsequent total acute exacerbation (adjusted OR 0.19, 95% CI 0.04-0.95). CHIP status did not show a statistically significant association with longitudinal changes in lung function. Conclusions: In patients with COPD, CHIP positivity was significantly associated with an increased risk of subsequent acute exacerbations, but not with longitudinal changes in lung function.