Clonal Hematopoiesis of Indeterminate Potential Is Associated with Current Smoking Status and History of Exacerbation in Patients with Chronic Obstructive Pulmonary Disease

Background: There is limited data regarding the clinical outcomes of clonal hematopoiesis of indeterminate potential (CHIP) in patients with chronic obstructive pulmonary disease (COPD). This study aimed to evaluate the clinical significance of CHIP as a COPD biomarker. Methods: This retrospective study was conducted on patients with COPD who were enrolled prospectively in the Seoul National University Hospital Airway Registry from January 2013 to December 2019 and underwent pulmonary function and blood tests. We evaluated the CHIP score according to smoking status and severity of airflow ob - struction. Results: We analyzed next -generation sequencing data to detect CHIP in 125 patients with COPD. Current smokers had a higher prevalence of CHIP in combination of DNMT3A, TET2, and PPM1 D (DTP), DNA methyltransferase 3 alpha (DNMT3A), and protein phosphatase, Mg 2+ /Mn 2+ dependent 1D (PPM1D) genes than in never- or ex -smokers. CHIP of DTP and DNMT3A genes was significantly associated with current smokers (adjusted odds ratio [aOR], 2.80; 95% confidence interval [CI], 1.01 to 7.79) (aOR, 4.03; 95% CI, 1.09 to 14.0). Patients with moderate -to -severe airflow obstruction had a higher prevalence of CHIP in most of the explored genes than those with mild obstruction, although the difference was not statistically significant. CHIP in ASXL tran - scriptional regulator 1 (ASXL1) genes was significantly associated with history of mild, severe, and total acute exacerbation. Conclusion: Given that CHIP in specific genes was significantly associated with cur - rent smoking status and acute exacerbation, CHIP can be considered as a candidate biomarker for COPD patients.