Interstitial lung disease (ILD) is an umbrella term representing a heterogeneous group of restrictive lung disorders with destructive abnormalities in the lung interstitium. The overlapping clinical onset of various ILD subtypes poses significant challenges in diagnosis and management of the disease. Various omics technologies have explored disease-specific molecular markers, crucial for understanding the complex pathophysiology underlying disease progression. Proteomics, a rapidly advancing high-throughput omics tool, captures dynamic protein changes within a biological system, depicting its actual functional state. This enables comprehensive proteome profiling, facilitating the identification of specific biomarkers and pathways, thereby enhancing diagnostic precision and paving the way for targeted therapeutic interventions. This review highlights recent proteomic discoveries in idiopathic pulmonary fibrosis, autoimmune ILDs, exposure-related ILDs, and sarcoidosis, including emerging therapeutic avenues. It summarizes dysregulated pathways and potential biomarkers crucial for differential diagnosis, prognosis, disease progression, and treatment responses. The pathogenesis of ILD involves complex interactions of complement activation, humoral immune responses, and extracellular matrix organization pathways, and the expression levels of these pathway mediators vary across ILD stages and subtypes. Further validation of these pathways and their mediators through multicentric, large-cohort studies across diverse geographical locations is needed to enhance disease understanding and develop ”true” clinical biomarkers.

Background: Hypersensitivity pneumonitis (HP), an immune-mediated form of diffuse parenchymal lung disease (DPLD), is triggered by inhalation of a wide variety of allergens in susceptible individuals. Several studies suggest that the death rate associated with this disease has increased significantly in recent years. This meta-analysis investigates the significant clinico-radiological characteristics which may be appraised as potential risk factors associated with disease mortality. Methods: Extensive literature search was conducted for original articles published between 1st January 2009 and 30th April 2021 through PubMed, Google Scholar, EMBASE, and Cochrane Library using the keywords: “hypersensitivity pneumonitis”, “hazard ratio” and “mortality”. Results: A total of 21 independent studies related to mortality of HP subjects could be identified. The combined results of univariate and multivariate analysis suggest that older age [univariate odds ratio (OR): 1.038; multivariate OR: 1.036], male subjects [univariate OR: 1.508; multivariate OR: 1.396], honeycombing [univariate OR: 1.086; multivariate OR: 1.121] and traction bronchiectasis [univariate OR: 1.141; multivariate OR: 1.107] are significantly associated with mortality risk of HP subjects. Further, forced vital capacity, diffusing capacity for carbon monoxide, ground glass opacity and mosaic attenuation were associated with lower risk of all-cause mortality. Although smoking status correlated with mortality risk, the findings appeared to be insignificant. Conclusion: Individual male subjects with older age and presence of extensive fibrosis, i.e., honeycombing and traction bronchiectasis experience an increased mortality risk. Additional observational and interventional studies are required to validate the findings and to identify extent of the risk factors and their association with disease mortality.