Cryptogenic Organizing Pneumonia (COP)


  • History: first clinical-pathologic correlation was established in the 1980’s
    • Previously called Bronchiolitis Obliterans Organizing Pneumonia (BOOP)
  • Sex: M = F
  • Mean Age of Onset: 50-60 y/o (few rare cases have been reported in children)
  • Smoking Exposure: non-smokers or ex-smokers are twice as likely to develop disease as smokers (however, proportion on non-smokers may be higher in females)
  • Seasonal Variation: cases with recurrence during early Spring have been reported
  • Relationship to Menses: recurrent cases related to menses have been reported




  • Abacavir (Ziagen) (see Abacavir, [[Abacavir]])
  • Amiodarone (Cordarone) (see Amiodarone, [[Amiodarone]])
  • Amphotericin B (see Amphotericin, [[Amphotericin]])
  • Azathioprine (Imuran) (see Azathioprine, [[Azathioprine]])
  • Barbiturates (see Barbiturates, [[Barbiturates]])
  • Beta Blockers (see β-Adrenergic Receptor Antagonists, [[β-Adrenergic Receptor Antagonists]])
    • Acebutolol (Sectral, Prent) (see Acebutolol, [[Acebutolol]])
    • Betaxalol (Betoptic, Lokren, Kerlone) (see Betaxalol, [[Betaxalol]])
    • Oxprenolol
    • Sotalol (Betapace, Betapace AF, Sotalex, Sotacor) (see Sotalol, [[Sotalol]])
    • Timolol (Blocadren, Timoptic) (see Timolol, [[Timolol]])
  • Bleomycin (see Bleomycin, [[Bleomycin]]): with nodular pattern on CXR
  • Carbamazepine (Tegretol) (see Carbamazepine, [[Carbamazepine]])
  • Cephalosporins (see Cephalosporins, [[Cephalosporins]])
  • Chlorambucil (see Chlorambucil, [[Chlorambucil]])
  • Clomipramine (Anafranil, Clofranil) (see Clomipramine, [[Clomipramine]])
  • Cyclophosphamide (Cytoxan) (see Cyclophosphamide, [[Cyclophosphamide]])
  • Ergots
    • Dihydroergocryptine
    • Dihydroergotamine
  • Gold (see Gold, [[Gold]])
  • Hexamethonium
  • HMG-CoA Reductase Inhibitors (Statins) (see HMG-CoA Reductase Inhibitors, [[HMG-CoA Reductase Inhibitors]])
    • Pravastatin (Pravachol) (see Pravastatin, [[Pravastatin]])
    • Simvastatin (Zocor) (see Simvastatin, [[Simvastatin]])
  • Hydralazine (see Hydralazine, [[Hydralazine]])
  • Hydroxyurea (Hydroxycarbamide, Hydrea, Droxia) (see Hydroxyurea, [[Hydroxyurea]])
  • Interferons (see Interferons, [[Interferons]])
    • Interferon Alfa-2a (Roferon-A) (see Interferon Alfa-2a, [[Interferon Alfa-2a]])
    • Interferon Alfa-2b (Intron A, Reliferon, Uniferon) (see Interferon Alfa-2b, [[Interferon Alfa-2b]])
  • Lenalidomide (Revlimid) (see Lenalidomide, [[Lenalidomide]])
  • Mammalian Target of Rapamycin (mTOR) Inhibitors
    • Everolimus (Afinitor) (see Everolimus, [[Everolimus]])
    • Sirolimus (Rapamune, Rapamycin) (see Sirolimus, [[Sirolimus]])
  • Mecamylamine
  • Mesalamine (see Mesalamine, [[Mesalamine]])
  • Methotrexate (see Methotrexate, [[Methotrexate]])
  • Minocycline (see Minocycline, [[Minocycline]])
  • Mitomycin (see Mitomycin, [[Mitomycin]])
  • Nilutamide
  • Nitrofurantoin (Macrodantin, Macrobid, Furadantin) (see Nitrofurantoin, [[Nitrofurantoin]])
  • Non-Steroidal Anti-Inflammatory Drugs (NSAID’s)
    • Loxoprofen
    • Sulindac (Clinoril) (see Sulindac, [[Sulindac]])
  • Penicillamine (see Penicillamine, [[Penicillamine]])
  • Phenytoin (Dilantin) (see Phenytoin, [[Phenytoin]])
  • Risedronate (see Risedronate, [[Risedronate]])
  • Sulfasalazine (Azulfidine) (see Sulfasalazine, [[Sulfasalazine]])
  • Tacrolimus (see Tacrolimus, [[Tacrolimus]])
  • Temozolomide (Temodar, Temodal) (see Temozolomide, [[Temozolomide]])
  • Thalidomide (see Thalidomide, [[Thalidomide]])
  • Ticlopidine (Ticlid) (see Ticlopidine, [[Ticlopidine]])
  • Topotecan (Hycamtin) (see Topotecan, [[Topotecan]])
  • Trastumab (Herceptin) (see Trastuzumab, [[Trastuzumab]])

Toxic Exposure

  • Acramin Inhalation (see Acramin, [[Acramin]])
  • Crack Cocaine (see Cocaine, [[Cocaine]])
  • Heroin (see Heroin, [[Heroin]])
  • Nitrogen Dioxide Inhalation (see Nitrogen Dioxide, [[Nitrogen Dioxide]])

Connective Tissue Disease



  • Organizing Pneumonia Pattern
    • Absence of granulomas, interstitial fibrosis, hemorrhage, and hyaline membranes
    • With or without bronchiolitis obliterans


CXR/Chest CT/HRCT Patterns

  • Typical Cryptogenic Organizing Pneumonia
    • Multiple alveolar opacities
    • Usually bilateral and peripheral
    • Often migratory
    • May involve whole lobe
    • On HRCT: range from ground glass to consolidation
  • Solitary Focal Cryptogenic Organizing Pneumonia
    • Solitary nodule (although may be multiple, mimicking mets)
    • Often located in upper lobes
    • May cavitate
    • May produce false-positive PET scan
    • May spontaneously regress in some cases
    • Usually does not recur after surgical excision
  • Infiltrative Cryptogenic Organizing Pneumonia
    • Interstitial and alveolar infiltrates
    • “Crazy Paving” Pattern: ground-glass with thickening of interlobular and intralobular septa, producing polygonal shapes
  • Other Features

    • Pneumatocele
  • HRCT (predominantly involves periphery, lower lobes):

    • Ground glass opacification with/without consolidation: consolidation present in 87% of cases
    • “Crazy Paving” Pattern: ground-glass with thickening of interlobular and intralobular septa, producing polygonal shapes
    • Bronchiectasis: may be seen
    • Nodules (32% of cases)
    • Lymphadenopathy (13% of cases):
    • Pleural Effusion (20% of cases):
  • FOB:
  • Pulmonary Functon Test (PFT’s)


General Comments

  • Onset: acute or subacute onset
  • Prodrome: may begin with mild flu-like illness
  • Timeliness of Diagnosis : diagnosis may be delayed up to 6-13 wks

Clinical Manifestations

Pulmonary Manifestations

  • Cough (see Cough, [[Cough]])
  • Dyspnea (see Dyspnea, [[Dyspnea]])
  • Focal Crackles: although may be normal exam
  • Hemoptysis (see Hemoptysis, [[Hemoptysis]]): uncommon and seldom severe
  • Pneumothorax (see Pneumothorax, [[Pneumothorax]]): rare presentation
  • Pneumomediastinum (see Pneumomediastinum, [[Pneumomediastinum]]): rare presentation

Other Manifestations

  • Absence of Clubbing
  • Anorexia (see Anorexia, [[Anorexia]])
  • Arthralgias (see Arthralgias, [[Arthralgias]]): uncommon
  • Chest Pain (see Chest Pain, [[Chest Pain]]): uncommon
  • Fever (see Fever, [[Fever]])
  • Malaise
  • Night Sweats (see Night Sweats, [[Night Sweats]]): uncommon
  • Weight Loss (see Weight Loss, [[Weight Loss]])


Corticosteroids (see Corticosteroids, [[Corticosteroids]])

  • Excellent response to steroids (only 10% 5-year mortality)
  • Overall Response Rate: 60-70% (65% of patients experience complete recovery with steroids)
  • Response may occur within 1-2 days of starting therapy (although may take weeks)
  • Relapse upon early cessation, usually occur within 1-3 months
  • Continue steroids for 1-2 mo, then taper slowly (over 4-6 wks)
  • Similar rates of recurrence with steroid cessation
  • Early therapy may prevent irreversible lung damage

Cyclophosphamide (Cytoxan) (see Cyclophosphamide, [[Cyclophosphamide]])

  • Useful for steroid-unresponsive or steroid-intolerant cases


  • Spontaneous Recovery: spontaneous improvement may occur over 3-6 months in some cases
  • Cordier Prognostic Classification
    • Patchy Migratory Pneumonia: recover completely with steroids, but relapse when stopped
    • Diffuse Interstitial Lung Disease: 50% of patients respond to steroids
    • Solitary Foci of Pneumonia: these were resected, due to concern about possible malignancy
      • Recovered without relapse


  • Interferon-related bronchiolitis obliterans organizing pneumonia. Chest. 1994 Aug;106(2):612-3 [MEDLINE]