Etiology

Organizing pneumonia (OP) can be cryptogenic, where no cause can be found, or secondary to a known factor. Possible causes of secondary OP are listed below.

Infections

  • Chlamydia, Legionella, and Mycoplasma

  • Adenoviridae, Cytomegalovirus, and influenza virus

  • Malaria

  • Pneumocystis[10]

  • Cryptococcus.

Medications[11]

  • Antibiotics: amphotericin-B, cephalosporins, minocycline, nitrofurantoin[12]

  • Cardiovascular drugs: amiodarone, acebutolol

  • Cancer chemotherapy drugs: bleomycin, busulfan, methotrexate, doxorubicin, thalidomide, cytosine-arabinoside (ARA-C), cytarabine, chlorambucil, rituximab

  • Anti-inflammatory agents: gold, sulfasalazine, mesalazine, bucillamine, infliximab

  • Immunosuppressive agents: azathioprine, mercaptopurine, tacrolimus, sirolimus, everolimus

  • Anticonvulsants: carbamazepine, phenytoin

  • Miscellaneous drugs: interferon, ticlopidine, L-tryptophan, risedronate, illicit use of cocaine.

Rheumatologic or connective tissue disorders

  • Rheumatoid arthritis[13][14]

  • Lupus erythematosus

  • Sjogren syndrome

  • Sweet syndrome[15]

  • Polymyositis/dermatomyositis

  • Scleroderma-progressive systemic sclerosis

  • Ankylosing spondylitis

  • Polymyalgia rheumatica

  • Behcet disease.

Immunologic disorders

  • Common variable immunodeficiency syndrome

  • Essential mixed cryoglobulinemia.

Organ transplantation

  • Lung[16]

  • Bone marrow[17][18]

  • Kidney and liver.

Radiation therapy

  • Post breast radiation (1% to 3% of patients).[19][20][21][22]

Environmental or occupational exposures

  • Textile printing dye

  • Penicillium mold dust

  • House fire

  • Food spice processing[23]

  • Paraffin mineral oil.[24]

  • Vaping.[25]​

Miscellaneous

  • Inflammatory bowel disease

  • HIV infection

  • Illicit use of cocaine

  • Myelodysplastic syndrome

  • Hunner interstitial cystitis

  • Chronic thyroiditis and alcoholic cirrhosis

  • Seasonal syndrome with cholestasis

  • Primary biliary cirrhosis

  • Coronary artery bypass graft surgery

  • Cancer and hematologic malignancy[26][27]

  • Aspiration[28][29]

  • Hydatid cyst.[30]

Pathophysiology

Organizing pneumonia (OP) is an inflammatory lung disease caused by a specific cascade of cytokine events. It differs from the inflammation occurring in asthma and chronic bronchitis. The pathogenesis is not a fibrotic process as in usual interstitial pneumonia (UIP). Naturally timed apoptosis may be an important distinction between OP (an inflammatory process) and UIP (a fibrotic process), because apoptotic activity is increased in the fibromyxoid connective tissue of OP but not UIP.[37] The cytokine profile of OP shows an increased degree of macrophage and lymphocyte activation with the T-1 response.[38] In the reovirus model, T cells have an important role in the pathogenesis of OP, demonstrated by the fact that depletion of CD4+ or CD8+ cells and treatment with corticosteroids decrease expression of the proinflammatory and profibrotic cytokines.[39]

On low to medium power light microscopy, the epithelial buds, consisting of granulation tissue obtruding into the distal airspaces, can be seen. Fibrin and proliferating fibroblasts and myofibroblasts comprise the cellular matrix. Cryptogenic OP presents in three main patterns:

  • Multiple patchy alveolar opacities in a perilobular distribution

  • Focal nodules

  • Diffuse infiltrative opacities that are peripheral and bilateral.

Less common patterns are the reverse halo (atoll) sign which consists of an area of inflammation with central clearing, bandlike opacities or crazy paving.[32][40] Over time, a fibrotic pattern may appear with subpleural reticulations and mild volume loss.

Classification

Clinical classification[3]

OP can be classified according to clinico-radiologic pattern:

  • Idiopathic OP, i.e., cryptogenic organizing pneumonia (COP) (no underlying cause established)[1][2][3]

  • Rapidly progressive OP[6][7]

  • Focal nodular OP[8][9]

  • Secondary OP

Secondary OP can be classified according to etiology:

  • Postinfectious OP

    • Chlamydia, Legionella, Mycoplasma

    • Adenoviridae, Cytomegalovirus, and influenza virus

    • Malaria

    • Pneumocystis[10]

    • Cryptococcus

    • COVID-19 (severe acute respiratory syndrome coronavirus 2 [SARS CoV-2]).

  • Drug-related OP[11]

    • Antibiotics: amphotericin-B, cephalosporins, minocycline, nitrofurantoin[12]

    • Cardiovascular drugs: amiodarone, acebutolol

    • Cancer chemotherapy: bleomycin, busulfan, methotrexate, doxorubicin, thalidomide, cytosine-arabinoside (ARA-C), cytarabine, chlorambucil, rituximab

    • Anti-inflammatory agents: gold, sulfasalazine, mesalazine, bucillamine, infliximab

    • Immunosuppressive agents: azathioprine, mercaptopurine, tacrolimus, sirolimus, everolimus

    • Anticonvulsants: carbamazepine, phenytoin

    • Miscellaneous drugs: interferon, ticlopidine, L-tryptophan, risedronate, cocaine (illicit use).

  • Rheumatologic or connective-tissue OP

    • Rheumatoid arthritis[13][14]

    • Lupus erythematosus

    • Sjogren syndrome

    • Sweet syndrome[15]

    • Polymyositis, dermatomyositis

    • Scleroderma-progressive systemic sclerosis

    • Ankylosing spondylitis

    • Polymyalgia rheumatica

    • Behcet disease.

  • Immunologic disorder OP

    • Common variable immunodeficiency syndrome

    • Essential mixed cryoglobulinemia.

  • Organ transplantation OP

    • Lung[16]

    • Bone marrow[17][18]

    • Kidney and liver.

  • Radiation therapy OP

    • Following breast radiation (1% to 3% of patients).[19][20][21][22]

  • Environmental or occupational exposures

    • Textile printing dye

    • Penicillium mold dust

    • House fire

    • Food spice processing[23]

    • Paraffin mineral oil.[24]

    • Vaping.[25]

  • Miscellaneous OP

    • Inflammatory bowel disease

    • HIV infection

    • Illicit use of cocaine

    • Myelodysplastic syndrome

    • Hunner interstitial cystitis

    • Chronic thyroiditis and alcoholic cirrhosis

    • Seasonal syndrome with cholestasis

    • Primary biliary cirrhosis

    • Coronary artery bypass graft surgery

    • Cancer and hematologic malignancy[26][27]

    • Aspiration[28][29]

    • Hydatid cyst.[30]

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