Rationale: The preclinical natural history of progressive lung fibrosis is poorly understood.Objectives: Our goals were to identify risk factors for interstitial lung abnormalities (ILA) on high-resolution computed tomography (HRCT) scans and to determine progression toward clinical interstitial lung disease (ILD) among subjects in a longitudinal cohort of self-reported unaffected first-degree relatives of patients with familial interstitial pneumonia.Methods: Enrollment evaluation included a health history and exposure questionnaire and HRCT scans, which were categorized by visual assessment as no ILA, early/mild ILA, or extensive ILA. The study endpoint was met when ILA were extensive or when ILD was diagnosed clinically. Among subjects with adequate study time to complete 5-year follow-up HRCT, the proportion with ILD events (endpoint met or radiographic ILA progression) was calculated.Measurements and Main Results: Among 336 subjects, the mean age was 53.1 (SD, 9.9) years. Those with ILA (early/mild [n = 74] or extensive [n = 3]) were older, were more likely to be ever smokers, had shorter peripheral blood mononuclear cell telomeres, and were more likely to carry the MUC5B risk allele. Self-reported occupational or environmental exposures, including aluminum smelting, lead, birds, and mold, were independently associated with ILA. Among 129 subjects with sufficient study time, 25 (19.4%) had an ILD event by 5 years after enrollment; of these, 12 met the study endpoint and another 13 had radiologic progression of ILA. ILD events were more common among those with early/mild ILA at enrollment (63.3% vs. 6.1%; P < 0.0001).Conclusions: Rare and common environmental exposures are independent risk factors for radiologic abnormalities. In 5 years, progression of ILA occurred in most individuals with early ILA detected at enrollment.

中文翻译：

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有家族性间质性肺病风险的个体放射学异常的发展和进展。

理由：进行性肺纤维化的临床前自然病程知之甚少。 ILD) 在自报未受影响的家族性间质性肺炎患者的一级亲属的纵向队列中的受试者中。 /轻度ILA，或广泛的ILA。当 ILA 广泛或临床诊断 ILD 时，达到研究终点。在有足够研究时间完成 5 年随访 HRCT 的受试者中，计算了 ILD 事件（终点事件或影像学 ILA 进展）的比例。测量和主要结果：在 336 名受试者中，平均年龄为 53.1 (SD, 9.9) 岁。患有 ILA（早期/轻度 [n = 74] 或广泛 [n = 3]）的人年龄较大，更有可能吸烟，外周血单核细胞端粒较短，并且更有可能携带 MUC5B 风险等位基因。自我报告的职业或环境暴露，包括铝冶炼、铅、鸟类和霉菌，与 ILA 独立相关。在有足够学习时间的 129 名受试者中，25 名（19.4%）在入组后 5 年发生了 ILD 事件；其中，12 人达到了研究终点，另外 13 人有 ILA 的放射学进展。ILD 事件在入组时患有早期/轻度 ILA 的患者中更为常见（63.3% 对 6.1%；P < 0.0001）。结论：罕见和常见的环境暴露是放射学异常的独立危险因素。在 5 年内，大多数在入组时检测到早期 ILA 的个体发生 ILA 进展。