Abstract：
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.
CONCLUSIONS: 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.
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.
CONCLUSIONS: 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.
摘要：
背景：亚洲和西方间质性肺病（ILD）队列中描述了疾病行为和基因型的差异。在西方ILD队列中，短的白细胞端粒长度（LTL）与不良结局相关，但其在亚洲人群中的意义尚不清楚。我们旨在描述新加坡ILD患者短期LTL的负担和临床意义。
方法：前瞻性招募在新加坡总医院诊断为ILD的患者，并与36名健康对照进行比较。主要结果是无移植存活。提取来自外周血的基因组DNA并使用定量聚合酶链反应测定(qPCR)测量LTL。
结果：在165名患者中，37%有短LTL。短LTL合并肺纤维化和肺气肿（CPFE）患者的比例更高（n=21，34.4％vsn=16，15.4％；p<0.001）。短LTL患者在12-时生存率降低，24个月和36个月以及24个月的中位生存期（p<0.001），在调整吸烟后仍然显着，GAP阶段和放射性UIP模式(危险比(HR)，2.74；95CI：1.46，5.11；p=0.002）。他们增加了与呼吸有关的死亡率和急性加重发生率。尽管基线肺功能相似，与正常LTL患者的-58.2(95%CI:82.9,-33.6)mL/年相比,短LTL患者的绝对用力肺活量(FVC)下降更快,为-105.3(95%CI:151.4,-59.1)mL/年(p<0.001).
结论：在我们的新加坡ILD队列中，短LTL与死亡率增加和肺功能下降更快相关，其幅度与西方ILD队列相似。需要进一步的研究将LTL评估整合到临床实践中。
方法：前瞻性招募在新加坡总医院诊断为ILD的患者，并与36名健康对照进行比较。主要结果是无移植存活。提取来自外周血的基因组DNA并使用定量聚合酶链反应测定(qPCR)测量LTL。
结果：在165名患者中，37%有短LTL。短LTL合并肺纤维化和肺气肿（CPFE）患者的比例更高（n=21，34.4％vsn=16，15.4％；p<0.001）。短LTL患者在12-时生存率降低，24个月和36个月以及24个月的中位生存期（p<0.001），在调整吸烟后仍然显着，GAP阶段和放射性UIP模式(危险比(HR)，2.74；95CI：1.46，5.11；p=0.002）。他们增加了与呼吸有关的死亡率和急性加重发生率。尽管基线肺功能相似，与正常LTL患者的-58.2(95%CI:82.9,-33.6)mL/年相比,短LTL患者的绝对用力肺活量(FVC)下降更快,为-105.3(95%CI:151.4,-59.1)mL/年(p<0.001).
结论：在我们的新加坡ILD队列中，短LTL与死亡率增加和肺功能下降更快相关，其幅度与西方ILD队列相似。需要进一步的研究将LTL评估整合到临床实践中。
