An Airway-Centric View of Idiopathic Pulmonary Fibrosis.

Abstract

Idiopathic pulmonary fibrosis (IPF) is the cumulative manifestation of countless, spatially and temporally distinct, microscopic foci of maladaptive repair in response to recurrent lung injury. However, the key drivers, essential cells, and critical mechanisms of maladaptive repair in IPF remain elusive. Decades of research have focused on alveolar injury and alveolar-mesenchymal crosstalk with their association to type II alveolar epithelial defects, fibroblast activation, and progressive lung fibrosis resulting in diminished organ function. Additionally, it has been well documented that immune and endothelial cell-types are involved in IPF. However, the airway epithelium has been incompletely described in IPF, even with significant evidence of airway-specific involvement. One of the first descriptions of distal airway dysfunction in IPF was over four-decades ago; however, since this discovery, our understanding of distal airway epithelial contributions to IPF pathogenesis has not kept pace with other tissues-types or anatomical regions of the lung. Healthy distal, which is defined here as an airway < 2 mm in internal diameter, airway epithelium is composed primarily of progenitor, mucus-producing, and multiciliated cell populations. Large increases in progenitor population diversity, misexpression of mucus, and possible aberrant ciliation observed in IPF has reinvigorated interest in the distal airway epithelium.