Biomarkers of pulmonary fibrosis in bronchoalveolar lavage fluid and saliva. Study methods and pathophysiological significance

This narrative review synthesizes the current evidence of the molecular biomarkers related to pulmonary fibrosis in bronchoalveolar lavage fluid (BALF) and saliva. It has a particular focus on pulmonary fibrosis diseases (IPFs). It provides a detailed description of the pathophysiological bases and clinical relevance of several extracellular matrix (ECM) components and markers of epithelial damage or remodeling. In this review, it is included type I collagen, hydroxyproline, fibronectin, elastin, KL-6 and matrix metalloproteinases (MMPs). Also, the main methodologies used for their detection and quantification are critically reviewed, highlighting their advantages and limitations in each matrix. Exploring the potential alveolus-saliva pathophysiological axis, it is proposed that this disruption of the alveolar-capillary barrier and the increasing vascular permeability may allow high-molecular-weight biomarkers and matrix derived components to reach the saliva. Thereby, it will enable non-invasive monitoring strategies. However, there are not yet studies that simultaneously analyze BALF and saliva in the same patient cohorts together with the lack of standardized protocol for sampling, analytical normalization and salivary reference ranges. Overall, this review identifies key opportunities and knowledge gaps for the development of BALF-saliva multimarker panels with diagnostic, prognostic and treatment-monitoring potential in fibrotic interstitial lung diseases.