What are the causes of organizing pneumonia?

Causes of Organizing Pneumonia

Organizing pneumonia occurs in a variety of conditions including infection, connective tissue disease, malignancy, drug reactions, radiation therapy, and immunodeficiency, with cryptogenic organizing pneumonia (COP) diagnosed only when exhaustive testing fails to identify an underlying cause. 1

Primary Etiological Categories

Secondary Organizing Pneumonia (Identifiable Causes)

When a specific triggering factor is identified, the condition is termed "secondary organizing pneumonia" rather than cryptogenic. 2, 3 The major causes include:

Infections

• Various infectious agents can trigger the organizing pneumonia pattern 1, 2
• Chlamydia pneumoniae has been specifically documented in case series 4, 5
• Post-infectious organizing pneumonia represents a pulmonary reaction to the initial injury 2

Drug-Induced

• Numerous medications can cause organizing pneumonia 1, 2
• New biological therapies including interferon, monoclonal antibodies, anti-interleukin antibodies, and PD1/PDL-1 inhibitors are increasingly recognized triggers 2
• Drug-induced cases have shown an increase in reported frequency 2

Connective Tissue Diseases

• Polymyositis and antisynthetase syndrome are particularly associated with organizing pneumonia patterns 1
• Various other collagen vascular diseases can trigger this response 2, 6, 4

Malignancy

• Cancer itself can be associated with organizing pneumonia 1, 2, 6
• The mechanism involves aberrant healing response to tumor-related lung injury 1

Radiation Therapy

• Post-radiation organizing pneumonia occurs as a reaction to therapeutic radiation exposure 1, 2, 6

Toxic Exposures

• Inhalation of toxic fumes and substances 2, 4
• Chronic aspiration syndrome 6

Transplantation

• Post-bone marrow transplantation 2
• Post-organ transplantation 2

Other Interstitial Lung Diseases

• Organizing pneumonia can occur as a component of other ILDs, including hypersensitivity pneumonitis 6
• May be seen in acute exacerbations of idiopathic pulmonary fibrosis 1

Cryptogenic Organizing Pneumonia (COP)

When exhaustive testing fails to reveal any underlying cause, the diagnosis is cryptogenic organizing pneumonia. 1 This represents:

• An idiopathic form with no identifiable trigger 1, 2
• Annual incidence of approximately 1:100,000 1
• Believed to have an autoimmune etiology in a proportion of cases 1
• Represents an aberrant healing response to unidentified injuries 1, 2

Clinical Pitfalls and Diagnostic Approach

Critical Exclusions Required

Before diagnosing cryptogenic organizing pneumonia, you must systematically exclude:

• Infectious etiologies through bronchoscopy with bronchoalveolar lavage for cultures and cytology 7
• Drug exposures by obtaining detailed medication history including recent biologics 2
• Connective tissue disease through serological testing and clinical evaluation 6
• Malignancy through appropriate imaging and tissue sampling 6
• Environmental/occupational exposures including radiation and toxic fumes 2, 6

Diagnostic Confirmation

Multidisciplinary discussion involving pulmonologists, radiologists, and pathologists is essential for accurate diagnosis. 7 Consider surgical lung biopsy when diagnosis remains uncertain after non-invasive testing. 7

Special Variants with Distinct Causes

• Fibrosing variant: Some patients develop organizing pneumonia with prominent fibrosis, particularly associated with polymyositis or antisynthetase syndrome 1
• Acute fibrinous organizing pneumonia: A distinct histological variant with specific clinical features and worse prognosis 1, 2