First ever characterisation of the effects of short telomeres in a Singapore interstitial lung disease cohort.

Autor: Kam MLW; Department of Respiratory and Critical Care Medicine, Singapore General Hospital, Outram Road, 169608, Singapore; Center for Interstitial Lung Disease, National Jewish Health, 1400 Jackson Street, Denver, CO, USA. Electronic address: michelle.kam.l.w@singhealth.com.sg., Chong ST; Lee Kong Chian School of Medicine, Nanyang Technological University, 11 Mandalay Road, 308232, Singapore., Chan SH; Cancer Genetics Service, Division of Medical Oncology, National Cancer Centre Singapore, 30 Hospital Boulevard, 168583, Singapore., Swigris JJ; Center for Interstitial Lung Disease, National Jewish Health, 1400 Jackson Street, Denver, CO, USA., Chew EL; Cancer Genetics Service, Division of Medical Oncology, National Cancer Centre Singapore, 30 Hospital Boulevard, 168583, Singapore., Tan YH; Department of Respiratory and Critical Care Medicine, Singapore General Hospital, Outram Road, 169608, Singapore., Ngeow JYY; Lee Kong Chian School of Medicine, Nanyang Technological University, 11 Mandalay Road, 308232, Singapore; Cancer Genetics Service, Division of Medical Oncology, National Cancer Centre Singapore, 30 Hospital Boulevard, 168583, Singapore., Low SY; Department of Respiratory and Critical Care Medicine, Singapore General Hospital, Outram Road, 169608, Singapore.
Jazyk: angličtina
Zdroj: Respiratory investigation [Respir Investig] 2024 May; Vol. 62 (3), pp. 348-355. Date of Electronic Publication: 2024 Feb 28.
DOI: 10.1016/j.resinv.2024.02.004
Abstrakt: Background: Differences in disease behaviour and genotypes are described in Asian and Western interstitial lung disease (ILD) cohorts. Short leukocyte telomere length (LTL) correlates with poor outcomes in Western ILD cohorts but its significance in Asian populations is unknown. We aim to characterise the burden and clinical implications of short LTL in Singaporean ILD patients.
Methods: Patients diagnosed with ILD at Singapore General Hospital were prospectively recruited and compared against 36 healthy controls. The primary outcome was transplant-free survival. Genomic DNA from peripheral blood was extracted and LTL measured using quantitative polymerase chain reaction assay (qPCR).
Results: Amongst 165 patients, 37% had short LTL. There was a higher proportion of combined pulmonary fibrosis and emphysema (CPFE) patients with short LTL (n = 21, 34.4% vs n = 16, 15.4%; p < 0.001). Short LTL patients had reduced survival at 12-, 24- and 36-months and median survival of 24 months (p < 0.001) which remained significant following adjustment for smoking, GAP Stage and radiological UIP pattern (Hazard Ratio (HR), 2.74; 95%CI:1.46, 5.11; p = 0.002). They had increased respiratory-related mortality and acute exacerbation incidences. Despite similar baseline lung function, short LTL patients had a faster decline in absolute forced vital capacity (FVC) of -105.3 (95% CI: 151.4, -59.1) mL/year compared to -58.2 (95% CI: 82.9, -33.6) mL/year (p < 0.001) in normal LTL patients.
Conclusion: Short LTL correlated with increased mortality and faster lung function decline in our Singaporean ILD cohort with a magnitude similar to that in Western ILD cohorts. Further research is needed to integrate LTL assessment into clinical practice.
Competing Interests: Declaration of competing interest MLW Kam reports having received research funding from Singapore General Hospital, Singapore and Singapore Health Services (Singhealth), Singapore and having received speaker honorarium from Boehringer Ingelheim, Singapore. YH Tan reports having received speaker honorarium from Boehringer Ingelheim, Singapore. SY Low reports having received research funding, consulting fees, speaker honorarium and support for meetings and travel from Boehringer Ingelheim, Singapore and speaker honorarium from Astra Zeneca, Singapore. JYY Ngeow reports having received research funding from Astra Zeneca, Singapore and the National Medical Research Council Clinician Scientist Award, Singapore. The other authors have no conflicts of interest.
(Copyright © 2024 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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