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Pathogenesis of idiopathic pulmonary fibrosis

Ganesh Raghu, MD
Carmen Mikacenic, MD
Section Editors
Talmadge E King, Jr, MD
Andrew Nicholson, MD
Deputy Editor
Helen Hollingsworth, MD


Idiopathic pulmonary fibrosis (IPF), previously known as cryptogenic fibrosing alveolitis (CFA) in Europe, is a chronic, relentlessly progressive fibrotic disorder of the lower respiratory tract that typically affects adults over the age of 40 [1]. Idiopathic interstitial pneumonias (IIP) are diffuse parenchymal lung diseases, of which IPF is the most common type of fibrotic lung disease [1,2].

The histopathologic pattern associated with the clinical diagnosis of IPF is referred to as "usual interstitial pneumonia" (UIP). UIP can also be seen in other fibrotic lung diseases associated with connective tissue disorders, chronic hypersensitivity pneumonitis, and asbestosis. (See "Classification and clinical manifestations of hypersensitivity pneumonitis (extrinsic allergic alveolitis)" and "Asbestosis".)

An overview of the pathogenesis of IPF, including the central role of fibroblast proliferation and abnormal collagen metabolism will be presented here. The clinical manifestations, differential diagnosis, evaluation, and treatment of IPF are discussed separately. (See "Approach to the adult with interstitial lung disease: Clinical evaluation" and "Approach to the adult with interstitial lung disease: Diagnostic testing" and "Treatment of idiopathic pulmonary fibrosis".)


The characteristic histopathologic features of usual interstitial pneumonia (UIP) in patients with idiopathic pulmonary fibrosis (IPF) include abnormal proliferation of mesenchymal cells, varying degrees of fibrosis, overproduction and disorganized deposition of collagen and extracellular matrix, distortion of pulmonary architecture and subpleural cystic airspaces (3 to 10 mm diameter) called honeycomb cysts. Fibroblast foci are clusters of fibroblasts and myofibroblasts that lie in continuity with the established fibrosis and are a characteristic histologic feature of UIP (picture 1) [1,3-6]. These abnormalities are typically associated with a mild, patchy chronic inflammatory cell infiltrate.

The end result of the fibrotic process is a complex reticulum that is highly interconnected and extends from pleura into the underlying parenchyma [7] (image 1). The pathology of UIP in comparison with other interstitial pneumonias is discussed in greater detail separately. (See "Idiopathic interstitial pneumonias: Clinical manifestations and pathology", section on 'Usual interstitial pneumonia'.)


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