Boutin Sebastien, Frey Dario, Helm Barbara, Guerra Matteo, Hagner Matthias, Lu Junyan, Dittrich Susanne, Wege Sabine, Eberhardt Ralf, Herth Felix, Sommerburg Olaf, Schultz Carsten, Dalpke Alexander, Klingmueller Ursula, Mall Marcus
Institute of Medical Microbiology, University of Lübeck and University Hospital Schleswig-Holstein, Campus Lübeck.
German Cancer Research Center (DKFZ).
Res Sq. 2025 Aug 20:rs.3.rs-6095597. doi: 10.21203/rs.3.rs-6095597/v1.
Cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) are muco-obstructive lung diseases. Knowledge of molecular processes has much improved therapeutic options in CF, whereas much less is known for COPD, a disease affecting an increasing number of patients. Here, we report a multilayer workflow integrating microbiome, inflammation and proteome profiling with clinical data to identify disease specific characteristics in sputum. Our proof-of-concept study shows that CF sputum is dominated by and , exhibits heightened neutrophilic inflammation, and a severe protease-antiprotease imbalance. In contrast, COPD displays heterogeneous microbiome composition, eosinophilic inflammation, and altered extracellular matrix remodeling. Proteome-based cellular deconvolution identifies disease-specific immune cell signatures, underscoring the complexity, especially in COPD. Multi-omics factor analysis establishes matrisome, and nucleotide metabolism changes as key disease discriminators. These findings highlight the potential of our integrated approach to uncover sputum biomarkers as tools for patient stratification and personalized therapeutic strategies in CF and COPD.
囊性纤维化（CF）和慢性阻塞性肺疾病（COPD）是黏液阻塞性肺部疾病。对分子过程的了解极大地改善了CF的治疗选择，而对于COPD这种影响患者数量日益增加的疾病，人们所知甚少。在此，我们报告了一种多层工作流程，将微生物组、炎症和蛋白质组分析与临床数据相结合，以识别痰液中的疾病特异性特征。我们的概念验证研究表明，CF痰液以[此处原文缺失相关内容]为主，表现出嗜中性粒细胞炎症加剧以及严重的蛋白酶-抗蛋白酶失衡。相比之下，COPD表现出微生物组组成的异质性、嗜酸性粒细胞炎症以及细胞外基质重塑改变。基于蛋白质组的细胞反卷积识别出疾病特异性免疫细胞特征，凸显了其复杂性，尤其是在COPD中。多组学因子分析确定了基质组和核苷酸代谢变化是关键的疾病鉴别因素。这些发现突出了我们的综合方法在揭示痰液生物标志物方面的潜力，这些生物标志物可作为CF和COPD患者分层及个性化治疗策略的工具。
