Association of clonal hematopoiesis with chronic obstructive pulmonary disease

• DOI: 10.1182/blood.2021013531
• Publication Date: 2021-12-02T19:33:19Z
• Authors: Peter G. Miller; Dandi Qiao; Joselyn Rojas-Qui...; Michael C. Honigberg; Adam S. Sperling; Christopher J. Gi...; Alexander G. Bick; Abhishek Niroula; Marie E. McConkey; Brittany Sandoval; Brian C. Miller; Weiwei Shi; Kaushik Viswanathan; Matthew Leventhal; Lillian Werner; Matthew Moll; Brian E. Cade; R. Graham Barr; Adolfo Correa; L. Adrienne Cupples; Sina A. Gharib; Deepti Jain; Stephanie M. Goga...; Leslie A. Lange; Stephanie J. London; Ani Manichaikul; George T. O’Connor; Elizabeth C. Oelsner; Susan Redline; Stephen S. Rich; Jerome I. Rotter; Vasan Ramachandran; Bing Yu; Lynette Sholl; Donna Neuberg; Siddhartha Jaiswal; Bruce D. Levy; Caroline A. Owen; Pradeep Natarajan; Edwin K. Silverman; Peter van Galen; Yohannes Tesfaigzi; Michael H. Cho; Benjamin L. Ebert
• Keywords: Male; 0301 basic medicine; Hematopoiesis and Stem Cells; Smoking; Middle Aged; 3. Good health; Mice; Pulmonary Disease, Chronic Obstructive; 03 medical and health sciences; Risk Factors; Exome Sequencing; Odds Ratio; Animals; Humans; Female; Clonal Hematopoiesis

Abstract Chronic obstructive pulmonary disease (COPD) is associated with age and smoking, but other determinants of the are incompletely understood. Clonal hematopoiesis indeterminate potential (CHIP) a common, age-related state in which somatic mutations clonal blood populations induce aberrant inflammatory responses. Patients CHIP have an elevated risk for cardiovascular disease, association COPD remains unclear. We analyzed whole-genome sequencing whole-exome data to detect 48 835 patients, whom 8444 had moderate very severe COPD, from four separate cohorts phenotyping smoking history. measured emphysema murine models Tet2 was deleted hematopoietic cells. In COPDGene cohort, individuals risks moderate-to-severe, severe, or that were 1.6 (adjusted 95% confidence interval [CI], 1.1-2.2) 2.2 CI, 1.5-3.2) times greater than those noncarriers. These findings consistently observed three additional meta-analyses all patients. also decreased FEV1% predicted cohort (mean between-group differences, −5.7%; adjusted −8.8% −2.6%), finding replicated cohorts. Smoke exposure small significant increased having (odds ratio, 1.03 per 10 pack-years; 1.01-1.05 pack-years) meta-analysis Inactivation mouse cells exacerbated development inflammation cigarette smoke exposure. Somatic severity independent cumulative