Malerba Mario, Purghè Beatrice, Ragnoli Beatrice, Manfredi Marcello, Baldanzi Gianluca
Respiratory Unit, S. Andrea Hospital, Vercelli, Italy.
Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy.
Ann Med. 2025 Dec;57(1):2537910. doi: 10.1080/07853890.2025.2537910. Epub 2025 Jul 24.
Respiratory disorders, , continue to pose a major global health burden. Their complexity and heterogeneity challenge accurate diagnosis, effective monitoring, and therapeutic decision-making. Exhaled breath condensate (EBC) provides a reliable, non-invasive means of sampling the molecular environment of the airways.
This review presents the state-of-the-art in EBC-based omics approaches-particularly metabolomics and proteomics-to characterize molecular signatures associated with chronic respiratory (e.g. asthma, chronic obstructive pulmonary disease, and rhinitis) and infectious diseases (e.g. COVID-19).
We critically examine findings from studies applying nuclear magnetic resonance (NMR), mass spectrometry (MS), and sensor-based technologies to analyze EBC across various respiratory conditions. NMR, valued for its reproducibility and minimal sample preparation, consistently discriminates among disease phenotypes, identifies distinct metabotypes, and monitors treatment response over time. MS-based approaches afford enhanced sensitivity and specificity, enabling detailed profiling of inflammatory mediators, such as lipid-derived eicosanoids and amino acid derivatives. Proteomic studies reveal protein-level alterations associated with inflammation and tissue remodeling. In COVID-19 and long COVID, metabolomic and volatile compound profiling distinguishes affected individuals from healthy controls suggesting clinical potential. However, inconsistent sample processing and lack of analytical standardization remain limiting factors.
EBC profiling shows clear promise for improving diagnosis, monitoring, and stratification in respiratory medicine. Yet, translation into clinical practice is hindered by limited standardization and validation. Broader, longitudinal studies will be essential to establish robust molecular signatures across disease states. This review underscores the timely need to implement breathomics investigations to gain mechanistic insight into the underlying biology of respiratory diseases.
呼吸系统疾病仍然是全球主要的健康负担。其复杂性和异质性对准确诊断、有效监测及治疗决策构成挑战。呼出气冷凝液（EBC）提供了一种可靠的、非侵入性的气道分子环境采样方法。
本综述介绍了基于EBC的组学方法（尤其是代谢组学和蛋白质组学）的最新进展，以表征与慢性呼吸道疾病（如哮喘、慢性阻塞性肺疾病和鼻炎）及传染病（如COVID-19）相关的分子特征。
我们批判性地审视了应用核磁共振（NMR）、质谱（MS）和基于传感器的技术分析各种呼吸状况下EBC的研究结果。NMR因其可重复性和最少的样品制备而受到重视，它始终能够区分疾病表型，识别不同的代谢型，并随时间监测治疗反应。基于MS的方法具有更高的灵敏度和特异性，能够对炎症介质进行详细分析，如脂质衍生的类二十烷酸和氨基酸衍生物。蛋白质组学研究揭示了与炎症和组织重塑相关的蛋白质水平变化。在COVID-19和新冠后综合征中，代谢组学和挥发性化合物分析可将受影响个体与健康对照区分开来，显示出临床应用潜力。然而，样本处理不一致和缺乏分析标准化仍然是限制因素。
EBC分析在改善呼吸医学的诊断、监测和分层方面显示出明显的前景。然而，由于标准化和验证有限，其转化为临床实践受到阻碍。更广泛的纵向研究对于建立跨疾病状态的强大分子特征至关重要。本综述强调了及时开展呼吸组学研究以深入了解呼吸系统疾病潜在生物学机制的必要性。
