Pulmonary Fibrosis

Disease / Phenomenon

Pulmonary fibrosis is the progressive scarring of lung tissue, in which the thin, elastic walls of the alveoli are replaced by thick, stiff collagen. As scarring accumulates, the lungs lose compliance and oxygen transfer across the alveolar membrane becomes increasingly inefficient, producing breathlessness on exertion that worsens over time, a persistent dry cough, fatigue, weight loss, and in advanced disease clubbing of the fingers. Idiopathic pulmonary fibrosis has no identifiable cause and follows a particularly relentless course; other forms follow occupational dust exposure, autoimmune disease, radiation, certain medications, or hypersensitivity to inhaled antigens. The structural damage is permanent, so slowing progression is the central clinical objective.

The prevailing model begins with repeated micro-injury to alveolar epithelial type II cells in a susceptible, often aged lung. Injured epithelium fails to regenerate properly, undergoes senescence and endoplasmic reticulum stress, and releases mediators — TGF-beta above all, along with PDGF, CTGF, and Wnt ligands — that recruit and activate fibroblasts. These differentiate into myofibroblasts expressing alpha-smooth muscle actin, which deposit excessive collagen and fibronectin while matrix metalloproteinase and TIMP imbalance prevents its clearance. Oxidative stress, mitochondrial dysfunction, and telomere shortening contribute. This page decomposes these processes into their pathways and biomarkers.