Cryptogenic organizing pneumonia pathophysiology

Cryptogenic organizing pneumonia is an idiopathic diffuse interstitial lung disease that affects the distal bronchioles, respiratory bronchioles, alveolar ducts, and alveolar walls. The injury occurs within the alveolar wall. There is proliferation of granulation tissue which involves alveolar ducts and alveoli. There are 4 phases lead to the formation of mature fibrotic bud.

Cryptogenic organizing pneumonia is caused by excessive proliferation of granulation tissue which involves alveolar ducts and alveoli. Granulation tissue may extend from one alveolus to the adjacent one leading to the formation of mature fibrotic bud which gives characteristic “butterfly” pattern.

Various phases involved in the pathogenesis of cryptogenic organizing pneumonia are:^[1]

1) Injury phase – The early phase of cryptogenic organizing pneumonia.

• It is characterized by the deposition of plasma proteins in the alveolar lumen.
• Mechanism of early phase is an imbalance between coagulation and fibrinolytic cascade and activation of coagulation process which leads to fibrin deposition.^[2]

2) Proliferating phase – The second stage of the cryptogenic organizing pneumonia in which there is a formation of fibro-inflammatory buds.

• Macrophages and inflammatory cells help in fragmentation of fibrin.
• Activated fibroblasts differentiate into myofibroblasts which are migrating through gaps of the basal lamina.
• Inflammatory cells and fibrin are progressively replaced by aggregated fibroblasts/myofibroblasts intermixed with a loose connective matrix tissue rich in collagen (especially collagen I), fibronectin, procollagen type III and proteoglycans.
• Alveolar epithelial cells proliferate, restoring the continuity of the alveolar-capillary membrane and the integrity of the alveolar unit.

3) Mature phase – The third stage is characterized by the formation of mature fibrotic buds which gives characteristic “butterfly” pattern.

• In alveolar buds, there are myofibroblasts, organized in concentric rings alternating with layers of collagen bundles.

4)Resolution phase – The fourth stage, this stage usually resolves if there is the preservation of alveolar basal laminae.

Cryptogenic organizing pneumonia is associated with the following conditions:^[3][4]

• Infectious pneumonia
• Lung abscess
• Empyema
• Lung cancer
• Chronic pulmonary fibrosis
• Aspiration pneumonia
• Adult respiratory distress syndrome
• Pulmonary infarction
• Middle lobe syndrome

On gross pathology of cryptogenic organizing pneumonia, following features are seen:

• There is the firm area with preservation of lung pattern which extends to thickened pleura.^[3]

On microscopic histopathological analysis:^[5][6]

• It is characterized by chronic mild interstitial inflammation without fibrosis.
• There is the formation of buds of granulation tissue which is made of fibrous tissue (Masson bodies), mononuclear cells and foamy macrophages, in the distal airspaces which cause secondary bronchiolar occlusion due to the presence of the inflammatory process.

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