Rationale: Idiopathic pulmonary fibrosis (IPF) affects the subpleural lung but is considered to spare small airways. Micro-computed tomography (micro-CT) studies demonstrated small airway reduction in end-stage IPF explanted lungs, raising questions about small airway involvement in early-stage disease. Endobronchial optical coherence tomography (EB-OCT) is a volumetric imaging modality that detects microscopic features from subpleural to proximal airways. Objectives: In this study, EB-OCT was used to evaluate small airways in early IPF and control subjects in vivo. Methods: EB-OCT was performed in 12 subjects with IPF and 5 control subjects (matched by age, sex, smoking history, height, and body mass index). Subjects with IPF had early disease with mild restriction (FVC: 83.5% predicted), which was diagnosed per current guidelines and confirmed by surgical biopsy. EB-OCT volumetric imaging was acquired bronchoscopically in multiple, distinct, bilateral lung locations (total: 97 sites). IPF imaging sites were classified by severity into affected (all criteria for usual interstitial pneumonia present) and less affected (some but not all criteria for usual interstitial pneumonia present). Bronchiole count and small airway stereology metrics were measured for each EB-OCT imaging site. Measurements and Main Results: Compared with the number of bronchioles in control subjects (mean = 11.2/cm3; SD = 6.2), there was significant bronchiole reduction in subjects with IPF (42% loss; mean = 6.5/cm3; SD = 3.4; P = 0.0039), including in IPF affected (48% loss; mean: 5.8/cm3; SD: 2.8; P < 0.00001) and IPF less affected (33% loss; mean: 7.5/cm3; SD: 4.1; P = 0.024) sites. Stereology metrics showed that IPF-affected small airways were significantly larger, more distorted, and more irregular than in IPF-less affected sites and control subjects. IPF less affected and control airways were statistically indistinguishable for all stereology parameters (P = 0.36-1.0). Conclusions: EB-OCT demonstrated marked bronchiolar loss in early IPF (between 30% and 50%), even in areas minimally affected by disease, compared with matched control subjects. These findings support small airway disease as a feature of early IPF, providing novel insight into pathogenesis and potential therapeutic targets.

中文翻译：

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使用支气管内光学相干断层扫描在体内鉴定早期特发性肺纤维化的微观小气道异常。


理由：特发性肺纤维化 (IPF) 影响胸膜下肺，但被认为不会影响小气道。微型计算机断层扫描 (micro-CT) 研究表明，终末期 IPF 移植肺中小气道减少，引发了早期疾病中小气道受累的问题。支气管内光学相干断层扫描 (EB-OCT) 是一种体积成像方式，可检测从胸膜下到近端气道的微观特征。目的：在本研究中，EB-OCT 用于评估早期 IPF 和对照受试者的小气道体内情况。方法：对 12 名 IPF 受试者和 5 名对照受试者进行 EB-OCT（按年龄、性别、吸烟史、身高和体重指数进行匹配）。患有 IPF 的受试者患有轻度限制的早期疾病（FVC：预测的 83.5%），这是根据现行指南诊断的，并通过手术活检证实。 EB-OCT 体积成像是通过支气管镜在多个不同的双侧肺部位置（总共：97 个位置）获得的。 IPF 成像部位根据严重程度分为受影响（存在常见间质性肺炎的所有标准）和较不受影响（存在常见间质性肺炎的部分但不是全部标准）。测量每个 EB-OCT 成像部位的细支气管计数和小气道体视学指标。测量和主要结果：与对照受试者的细支气管数量（平均值 = 11.2/cm3；SD = 6.2）相比，IPF 受试者的细支气管数量显着减少（减少 42%；平均值 = 6.5/cm3；SD = 3.4；SD = 3.4）。 P = 0.0039），包括受影响的 IPF（48% 损失；平均值：5.8/cm3；SD：2.8；P < 0.00001）和 IPF 受影响较小（33% 损失；平均值：7.5/cm3；SD：4.1；P = 0.024 ）网站。 体视学指标显示，与未受 IPF 影响的部位和对照受试者相比，受 IPF 影响的小气道明显更大、更扭曲且更不规则。对于所有体视学参数，IPF 受影响较小的气道和对照气道在统计学上无法区分 (P = 0.36-1.0)。结论：与匹配的对照受试者相比，EB-OCT 显示早期 IPF 中细支气管明显丧失（30% 至 50%），即使是在受疾病影响最小的区域也是如此。这些发现支持小气道疾病是早期 IPF 的一个特征，为发病机制和潜在治疗靶点提供了新的见解。