<b>Background:</b> Fibrotic Interstitial lung diseases (ILD) are a heterogeneous group of chronic lung diseases characterized by diverse degrees of lung inflammation and remodeling. They include idiopathic ILD such as idiopathic pulmonary fibrosis (IPF), and ILD secondary to chronic inflammatory diseases such as connective tissue disease (CTD). Precise differential diagnosis of ILD is critical since anti-inflammatory and immunosuppressive drugs, which are beneficial in inflammatory ILD, are detrimental in IPF. However, differential diagnosis of ILD is still difficult and often requires an invasive lung biopsy. The primary aim of this study is to identify volatile organic compounds (VOCs) patterns in exhaled air to non-invasively discriminate IPF and CTD-ILD. As secondary aim, the association between the IPF and CTD-ILD discriminating VOC patterns and functional impairment is investigated. <b>Methods:</b> Fifty-three IPF patients, 53 CTD-ILD patients and 51 controls donated exhaled air, which was analyzed for its VOC content using gas chromatograph-<i>time of flight</i>-mass spectrometry. <b>Results:</b> By applying multivariate analysis, a discriminative profile of 34 VOCs was observed to discriminate between IPF patients and healthy controls whereas 11 VOCs were able to distinguish between CTD-ILD patients and healthy controls. The separation between IPF and CTD-ILD could be made using 16 discriminating VOCs, that also displayed a significant correlation with total lung capacity and the 6 min’ walk distance. <b>Conclusions:</b> This study reports for the first time that specific VOC profiles can be found to differentiate IPF and CTD-ILD from both healthy controls and each other. Moreover, an ILD-specific VOC profile was strongly correlated with functional parameters. Future research applying larger cohorts of patients suffering from a larger variety of ILDs should confirm the potential use of breathomics to facilitate fast, non-invasive and proper differential diagnosis of specific ILDs in the future as first step towards personalized medicine for these complex diseases.

中文翻译：

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ILD：呼吸纹的 VOC 分析是一种很有前途的非侵入性诊断方法

<b>背景：</b> 纤维化间质性肺病（ILD）是一组异质性的慢性肺病，以不同程度的肺部炎症和重塑为特征。它们包括特发性 ILD，如特发性肺纤维化 (IPF)，以及继发于慢性炎症性疾病如结缔组织病 (CTD) 的 ILD。ILD 的精确鉴别诊断至关重要，因为对炎症性 ILD 有益的抗炎和免疫抑制药物对 IPF 有害。然而，ILD 的鉴别诊断仍然很困难，并且通常需要进行侵入性肺活检。本研究的主要目的是识别呼出空气中的挥发性有机化合物 (VOC) 模式，以无创地区分 IPF 和 CTD-ILD。作为次要目标，研究了 IPF 和 CTD-ILD 区分 VOC 模式和功能障碍之间的关联。<b>方法：</b> 53 名 IPF 患者、53 名 CTD-ILD 患者和 51 名对照捐赠了呼出的空气，并使用气相色谱仪-<i>飞行时间</i>-质量分析了其 VOC 含量光谱学。<b>结果：</b> 通过应用多变量分析，观察到 34 种 VOC 的判别特征可以区分 IPF 患者和健康对照，而 11 种 VOC 能够区分 CTD-ILD 患者和健康对照。IPF 和 CTD-ILD 之间的分离可以使用 16 种可区分的 VOC 进行，这也显示出与总肺活量和 6 分钟步行距离的显着相关性。<b>结论：</b> 这项研究首次报告说，可以发现特定的 VOC 特征来区分 IPF 和 CTD-ILD 与健康对照以及彼此之间的差异。此外，ILD 特定的 VOC 曲线与功能参数密切相关。未来的研究将应用更多患有多种 ILD 的患者群体，应确认呼吸组学的潜在用途，以促进未来对特定 ILD 的快速、非侵入性和适当的鉴别诊断，作为针对这些复杂疾病的个性化医疗的第一步。