Epidemiology
- 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
Etiology
Infection
- Human Immunodeficiency Virus (HIV) (see Human Immunodeficiency Virus, [[Human Immunodeficiency Virus]])
- Pneumocystis Jirovecii (see Pneumocystis Jirovecii, [[Pneumocystis Jirovecii]])
Drugs
- 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
- Behcet’s Disease (see Behcet’s Disease, [[Behcets Disease]])
- Polydermatomyositis (see Polydermatomyositis, [[Polydermatomyositis]])
- Rheumatoid Arthritis (RA) (see Rheumatoid Arthritis, [[Rheumatoid Arthritis]])
- Scleroderma (see Scleroderma, [[Scleroderma]])
- Sjogren’s Syndrome (see Sjogren’s Syndrome, [[Sjogrens Syndrome]])
- Systemic Lupus Erythematosus (SLE) (see Systemic Lupus Erythematosus, [[Systemic Lupus Erythematosus]])
Other
- Aspiration Pneumonia (see Aspiration Pneumonia, [[Aspiration Pneumonia]])
- Hypersensitivity Pneumonitis (HP) (see Hypersensitivity Pneumonitis, [[Hypersensitivity Pneumonitis]])
- Post-Acute Lung Injury-ARDS (see Acute Lung Injury-ARDS, [[Acute Lung Injury-ARDS]])
- Post-Bone Marrow/Stem Cell Transplant (see Bone Marrow Transplant, [[Bone Marrow Transplant]])
- Post-Heart-Lung/Lung Transplant
- Post-XRT (see Radiation Pneumonitis and Fibrosis, [[Radiation Pneumonitis and Fibrosis]])
- Ulcerative Colitis (see Ulcerative Colitis, [[Ulcerative Colitis]])
- Idiopathic Cryptogenic Organizing Pneumonia
Pathology
- Organizing Pneumonia Pattern
- Absence of granulomas, interstitial fibrosis, hemorrhage, and hyaline membranes
- With or without bronchiolitis obliterans
Diagnosis
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)
Clinical
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]])
Treatment
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
Prognosis
- 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
References
- Interferon-related bronchiolitis obliterans organizing pneumonia. Chest. 1994 Aug;106(2):612-3 [MEDLINE]