Telomere length and immunosuppression in non-idiopathic pulmonary fibrosis interstitial lung disease.
Telomere length and immunosuppression in non-idiopathic pulmonary fibrosis interstitial lung disease.
复制标题
DOI：
10.1183/13993003.00441-2023
复制
发表时间：
2023-11
影响因子：
24.3
通讯作者：
Newton, Chad A.
中科院分区：
文献类型：
--
作者：
Zhang, David;Adegunsoye, Ayodeji;Oldham, Justin M.;Kozlitina, Julia;Garcia, Nicole;Poonawalla, Maria;Strykowski, Rachel;Linderholm, Angela L.;Ley, Brett;Ma, Shwu-Fan;Noth, Imre;Strek, Mary E.;Wolters, Paul J.;Garcia, Christine Kim;Newton, Chad A.
研究表明，在特发性肺纤维化（IPF）中，白细胞端粒长度短（LTL）和免疫抑制剂之间存在有害的药物基因组学相互作用。在非ipf间质性肺疾病（ILD）中是否存在类似的相互作用尚不清楚。对来自5个中心的纤维化超敏性肺炎（fHP）、无法分类的ILD （uILD）和结缔组织病(CTD)-ILD患者进行回顾性多中心队列分析。LTL通过发现和复制队列的定量PCR测量，并以正常年龄调整百分位数表示。使用加权Cox比例风险回归，结合时间依赖性免疫抑制剂暴露，基于倾向评分的治疗权重逆概率评估霉酚酸盐或硫唑嘌呤暴露与年龄调整的2年无移植生存LTL之间的关系。发现组和重复组分别包括613例和325例患者。总的来说，40%的患者暴露于免疫抑制，22%的患者LTL <正常的第10百分位。在发现队列中，LTL <10百分位的fHP和ild患者在暴露于霉酚酸盐或硫唑嘌呤时生存率降低(死亡率风险比（HR） 4.97, 95% CI 2.26-10.92；p<0.001)和重复队列（死亡率比4.90,95% CI 1.74-13.77; p=0.003）。在LTL≥10百分位的患者中，免疫抑制剂暴露与差异生存无关。LTL <10百分位与免疫抑制剂暴露之间存在显著的相互作用（发现相互作用=0.013；复制相互作用=0.011）。低事件发生率和LTL患病率<10百分位排除了CTD-ILD的亚组分析。与IPF类似，年龄调整LTL <10百分位的fHP和ild患者在暴露于免疫抑制时可能会降低生存率。年龄调整的白细胞端粒长度<10百分位数的纤维化过敏性肺炎和无法分类的ILD患者在暴露于免疫抑制时可能会降低生存率，类似于IPF患者https://bit.ly/3DJDLYg
Studies suggest a harmful pharmacogenomic interaction exists between short leukocyte telomere length (LTL) and immunosuppressants in idiopathic pulmonary fibrosis (IPF). It remains unknown if a similar interaction exists in non-IPF interstitial lung disease (ILD). A retrospective, multicentre cohort analysis was performed in fibrotic hypersensitivity pneumonitis (fHP), unclassifiable ILD (uILD) and connective tissue disease (CTD)-ILD patients from five centres. LTL was measured by quantitative PCR for discovery and replication cohorts and expressed as age-adjusted percentiles of normal. Inverse probability of treatment weights based on propensity scores were used to assess the association between mycophenolate or azathioprine exposure and age-adjusted LTL on 2-year transplant-free survival using weighted Cox proportional hazards regression incorporating time-dependent immunosuppressant exposure. The discovery and replication cohorts included 613 and 325 patients, respectively. In total, 40% of patients were exposed to immunosuppression and 22% had LTL <10th percentile of normal. fHP and uILD patients with LTL <10th percentile experienced reduced survival when exposed to either mycophenolate or azathioprine in the discovery cohort (mortality hazard ratio (HR) 4.97, 95% CI 2.26–10.92; p<0.001) and replication cohort (mortality HR 4.90, 95% CI 1.74–13.77; p=0.003). Immunosuppressant exposure was not associated with differential survival in patients with LTL ≥10th percentile. There was a significant interaction between LTL <10th percentile and immunosuppressant exposure (discovery pinteraction=0.013; replication pinteraction=0.011). Low event rate and prevalence of LTL <10th percentile precluded subgroup analyses for CTD-ILD. Similar to IPF, fHP and uILD patients with age-adjusted LTL <10th percentile may experience reduced survival when exposed to immunosuppression. Fibrotic hypersensitivity pneumonitis and unclassifiable ILD patients who have age-adjusted leukocyte telomere length <10th percentile may experience reduced survival when exposed to immunosuppression, similar to IPF patients https://bit.ly/3DJDLYg
登录
查看更多内容
影响因子：
5.5
作者：
Duke, Joseph W.;Lewandowski, Adam J.;Abman, Steven H.;Lovering, Andrew T.
通讯作者：
Lovering, Andrew T.
影响因子：
3.3
作者：
Duke, Joseph W.;Elliott, Jonathan E.;Lovering, Andrew T.
通讯作者：
Lovering, Andrew T.
DOI：
10.1249/00005768-198205000-00012
发表时间：
1982-01-01
期刊：
MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
影响因子：
--
作者：
BORG, GAV
通讯作者：
BORG, GAV
影响因子：
3
作者：
Charloux, A;Lonsdorfer-Wolf, E;Lonsdorfer, J
通讯作者：
Lonsdorfer, J
影响因子：
5.4
作者：
Bertagnolli M;Xie LF;Paquette K;He Y;Cloutier A;Fernandes RO;Béland C;Sutherland MR;Delfrate J;Curnier D;Bigras JL;Rivard A;Thébaud B;Luu TM;Nuyt AM
通讯作者：
Nuyt AM