The interstitial lung illness fibrotic hypersensitivity pneumonitis (fHP) is induced by sensitization to an inhaled allergen. Researchers wanted to figure out what molecular factors are linked to fibrosis progression. Six new donor lungs (as controls) and nine fHP explant lungs were thoroughly sampled (4 samples/lung). fHP cores were divided into three groups based on microCT measurements: mild, moderate, and severe fibrosis. Weighted Gene Co-expression Network Analysis (WGCNA), xCell, gene ontology, and structure enrichment analysis were used to evaluate gene expression profiles. IPF was also matched to gene expression of the principal molecular characteristics. Using tissue, bronchoalveolar lavage samples, and computed tomography images, they assessed explant lung findings in distinct clinical fHP cohorts.

They discovered six molecular characteristics linked to varying lung involvement levels. In fHP, transcriptomic signatures involved in the extracellular matrix and antigen presentation/sensitization characterized lung zones with only minor structural and histological changes. In contrast, signatures in honeycombing and B-cells dominated the transcriptome in the most severely affected lung zones. Endothelial function was gradually lost as the severity of the disease increased, and normal cellular homeostatic functions got disrupted. All six were likewise detected in IPF, and their correlations with disease microenvironments were virtually the same. In a second clinical fHP cohort, the molecular features associated with in vivo disease behavior. Six molecular features that characterize the morphological evolution of fHP and are linked to in vivo clinical behavior were discovered. When comparing IPF and fHP, the transcriptome landscape was mostly controlled by the amount of local disease rather than diagnosis alone.