Department of Internal Medicine, University of California at Davis, Sacramento, CA.
Division of Pulmonary, Critical Care and Sleep Medicine, University of California at Davis, Sacramento, CA.
Chest. 2021 May;159(5):1913-1921. doi: 10.1016/j.chest.2021.01.026. Epub 2021 Jan 21.
BACKGROUND: A number of genetic markers linked to familial pulmonary fibrosis predict differential survival in interstitial lung disease (ILD) patients. Although genetic testing is not performed routinely for ILD, family history commonly is obtained and may inform outcome risk. RESEARCH QUESTION: Does survival vary between patients with and without self-reported familial pulmonary fibrosis? METHODS: Family history was acquired systematically for consecutive ILD patients who consented to clinical registry enrollment at the University of Texas Southwestern and the University of California at Davis. Patients were stratified by idiopathic pulmonary fibrosis (IPF) and non-IPF ILD diagnosis and were substratified by presence or absence of familial pulmonary fibrosis, defined as one or more additional affected family members. Transplant-free survival was compared using multilevel, mixed-effects Cox proportional hazards regression. RESULTS: Of the 1,262 patients included, 534 (42%) had IPF ILD and 728 (58%) had non-IPF ILD. Of those with non-IPF ILD, 18.5% had connective tissue disease, 15.6% had chronic hypersensitivity pneumonitis, and 23.5% had unclassifiable ILD. Familial pulmonary fibrosis was reported in 134 IPF ILD patients (25.1%) and 90 non-IPF ILD patients (12.4%). Those with familial IPF showed an 80% increased risk of death or transplantation compared with those with sporadic IPF (hazard ratio [HR], 1.8; 95% CI, 1.37-2.37; P < .001), whereas those with familial non-IPF ILD showed a twofold increased risk compared with their counterparts with sporadic disease (HR, 2.08; 95% CI, 1.46-2.96; P < .001). Outcome risk among those with familial non-IPF ILD was no different than for those with sporadic IPF ILD (HR, 1.27; 95% CI, 0.89-1.84; P = .19). INTERPRETATION: Patient-reported familial pulmonary fibrosis is predictive of reduced transplant-free survival in IPF and non-IPF ILD patients. Because survival among patients with familial non-IPF ILD approximates that of sporadic IPF ILD, early intervention should be considered for such patients. Until clinical genetic testing is widely available and provides actionable results, family history should be ascertained and considered in risk stratification.
背景：一些与家族性肺纤维化相关的遗传标记可预测间质性肺疾病（ILD）患者的生存差异。尽管ILD 患者不常规进行基因检测，但通常会获取家族史，这可能提示预后风险。
研究问题：有或没有自我报告的家族性肺纤维化的患者之间的生存是否存在差异？
方法：德克萨斯大学西南分校和加利福尼亚大学戴维斯分校连续登记的 ILD 患者均同意入组临床登记研究，系统性地获取家族史。根据特发性肺纤维化（IPF）和非 IPFILD 诊断对患者进行分层，并根据是否存在家族性肺纤维化进行亚分层，家族性肺纤维化定义为一个或多个其他受影响的家庭成员。使用多层次、混合效应 Cox 比例风险回归比较无移植生存率。
结果：在纳入的 1262 名患者中，534 名（42%）患有 IPFILD，728 名（58%）患有非 IPFILD。在非 IPFILD 患者中，18.5%患有结缔组织疾病，15.6%患有慢性过敏性肺炎，23.5%患有未分类的ILD。134 名 IPFILD 患者（25.1%）和 90 名非 IPFILD 患者（12.4%）报告有家族性肺纤维化。与散发性 IPF 相比，家族性 IPF 患者的死亡或移植风险增加 80%（风险比[HR]，1.8；95%CI，1.37-2.37；P<0.001），而家族性非 IPFILD 患者的风险增加两倍（HR，2.08；95%CI，1.46-2.96；P<0.001）。家族性非 IPFILD 患者的预后风险与散发性 IPFILD 患者无差异（HR，1.27；95%CI，0.89-1.84；P=0.19）。
解释：患者报告的家族性肺纤维化可预测 IPF 和非 IPFILD 患者无移植生存率降低。由于家族性非 IPFILD 患者的生存情况与散发性 IPFILD 患者相似，应考虑对此类患者进行早期干预。在临床基因检测广泛应用并提供可操作的结果之前，应确定家族史并将其纳入风险分层。
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