Interstitial lung abnormalities: a mechanistic window into early fibrotic lung disease

Interstitial lung abnormalities (ILAs) are incidental, non-dependent parenchymal abnormalities detected on chest computed tomography (CT) in individuals without a diagnosis of interstitial lung disease (ILD). Once regarded as non-specific or age-related findings, ILAs are increasingly recognized as clinically relevant entities associated with progression to fibrotic ILD and increased mortality. Emerging molecular and epidemiological evidence indicates that ILAs share key pathogenic pathways with idiopathic pulmonary fibrosis (IPF), the archetypal progressive fibrotic ILD, including alveolar epithelial cell (AEC) stress and injury, innate immune activation, dysregulated repair, fibroblast activation, extracellular matrix (ECM) remodeling, and aging-associated cellular dysfunction. These observations suggest that ILAs may represent the early stage in the continuum of fibrotic lung disease. As such, ILAs provide a valuable opportunity to uncover early disease mechanisms and novel therapeutic targets and enable identification of individuals at increased risk of progression before clinically overt ILD develops. This mini review summarizes emerging mechanistic insights into ILAs and discusses how understanding early disease biology may inform risk stratification and preventative therapeutic strategies.