PuSH - Publikationsserver des Helmholtz Zentrums München

Guyatt, A.L.* ; John, C.* ; Williams, A.T.* ; Shrine, N.* ; Reeve, N.F.* ; Sayers, I.* ; Hall, I.P.* ; Wain, L.V.* ; Sheehan, N.* ; Dudbridge, F.* ; SpiroMeta Consortium (Gieger, C. ; Karrasch, S. ; Schulz, H.)

Mendelian randomisation of eosinophils and other cell types in relation to lung function and disease.

Thorax 78, 496-503 (2023)
Verlagsversion DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
RATIONALE: Eosinophils are associated with airway inflammation in respiratory disease. Eosinophil production and survival is controlled partly by interleukin-5: anti-interleukin-5 agents reduce asthma and response correlates with baseline eosinophil counts. However, whether raised eosinophils are causally related to chronic obstructive pulmonary disease (COPD) and other respiratory phenotypes is not well understood. OBJECTIVES: We investigated causality between eosinophils and: lung function, acute exacerbations of COPD, asthma-COPD overlap (ACO), moderate-to-severe asthma and respiratory infections. METHODS: We performed Mendelian randomisation (MR) using 151 variants from genome-wide association studies of blood eosinophils in UK Biobank/INTERVAL, and respiratory traits in UK Biobank/SpiroMeta, using methods relying on different assumptions for validity. We performed multivariable analyses using eight cell types where there was possible evidence of causation by eosinophils. MEASUREMENTS AND MAIN RESULTS: Causal estimates derived from individual variants were highly heterogeneous, which may arise from pleiotropy. The average effect of raising eosinophils was to increase risk of ACO (weighted median OR per SD eosinophils, 1.44 (95%CI 1.19 to 1.74)), and moderate-severe asthma (weighted median OR 1.50 (95%CI 1.23 to 1.83)), and to reduce forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) and FEV1 (weighted median estimator, SD FEV1/FVC: -0.054 (95% CI -0.078 to -0.029), effect only prominent in individuals with asthma). CONCLUSIONS: Broad consistency across MR methods may suggest causation by eosinophils (although of uncertain magnitude), yet heterogeneity necessitates caution: other important mechanisms may be responsible for the impairment of respiratory health by these eosinophil-raising variants. These results could suggest that anti-IL5 agents (designed to lower eosinophils) may be valuable in treating other respiratory conditions, including people with overlapping features of asthma and COPD.
Altmetric
Weitere Metriken?
[➜Einloggen]
Zusatzinfos bearbeiten [➜Einloggen]
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Asthma Epidemiology ; Asthma Genetics ; Asthma Mechanisms ; Copd Epidemiology ; Copd Exacerbations Mechanisms ; Eosinophil Biology ; Respiratory Infection
ISSN (print) / ISBN 0040-6376
e-ISSN 1468-3296
Zeitschrift Thorax
Quellenangaben Band: 78, Heft: 5, Seiten: 496-503 Artikelnummer: , Supplement: ,
Verlag BMJ Publishing Group
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epidemiology II (EPI2)
Institute of Epidemiology (EPI)
Förderungen Wellcome Trust