Section of Pulmonary & Critical Care, Department of Medicine, The University of Chicago, Chicago, IL, USA.
Committee on Genetics, Genomics and Systems Biology, The University of Chicago, Chicago, IL, USA.
Nat Commun. 2023 Mar 17;14(1):1489. doi: 10.1038/s41467-023-37193-6.
Pulmonary fibrosis (PF) is characterized by profound scarring and poor survival. We investigated the association of leukocyte telomere length (LTL) with chronological age and mortality across racially diverse PF cohorts. LTL measurements among participants with PF stratified by race/ethnicity were assessed in relation to age and all-cause mortality, and compared to controls. Generalized linear models were used to evaluate the age-LTL relationship, Cox proportional hazards models were used for hazard ratio estimation, and the Cochran-Armitage test was used to assess quartiles of LTL. Standardized LTL shortened with increasing chronological age; this association in controls was strengthened in PF (R = -0.28; P < 0.0001). In PF, age- and sex-adjusted LTL below the median consistently predicted worse mortality across all racial groups (White, HR = 2.21, 95% CI = 1.79-2.72; Black, HR = 2.22, 95% CI = 1.05-4.66; Hispanic, HR = 3.40, 95% CI = 1.88-6.14; and Asian, HR = 2.11, 95% CI = 0.55-8.23). LTL associates uniformly with chronological age and is a biomarker predictive of mortality in PF across racial groups.
肺纤维化(PF)的特征是严重的瘢痕形成和生存率低。我们研究了白细胞端粒长度(LTL)与不同种族 PF 队列的年龄和死亡率之间的关系。根据种族/民族对 PF 患者的 LTL 测量与年龄和全因死亡率进行了分层评估,并与对照组进行了比较。使用广义线性模型评估年龄与 LTL 的关系,使用 Cox 比例风险模型估计风险比,使用 Cochran-Armitage 检验评估 LTL 的四分位间距。随着年龄的增长,标准化 LTL 缩短;在 PF 中,这种关联得到了加强(R=−0.28;P<0.0001)。在 PF 中,年龄和性别调整后的 LTL 低于中位数始终预测所有种族的死亡率更高(白人,HR=2.21,95%CI=1.79-2.72;黑人,HR=2.22,95%CI=1.05-4.66;西班牙裔,HR=3.40,95%CI=1.88-6.14;和亚洲人,HR=2.11,95%CI=0.55-8.23)。LTL 与年龄呈一致相关,是预测 PF 不同种族全因死亡率的生物标志物。