Cryptogenic Organizing Pneumonia

Cryptogenic organising pneumonia (COP) is a clinicopathological entity of organising pneumonia (granulation tissue plugs in distal airspaces and ducts) without identifiable cause.

Median onset 50 to 60 years; no sex predilection; non smokers more affected.

Secondary organising pneumonia: infection, drugs (amiodarone, nitrofurantoin, bleomycin, checkpoint inhibitors, methotrexate), connective tissue disease, radiation (breast radiotherapy), aspiration, inflammatory bowel disease, malignancy (lymphoma), transplantation.

Variants: acute fibrinous and organising pneumonia, severe forms with respiratory failure, reversed halo.

Typically steroid responsive; relapse in 30 to 50% on taper.

• Subacute flu like illness over weeks: fever, dry cough, dyspnoea, malaise, weight loss, pleuritic pain; often misdiagnosed as pneumonia unresponsive to antibiotics.
• Crackles, rarely wheeze or clubbing.
• Rapidly progressive form can cause acute respiratory failure.

• Chest imaging: bilateral peripheral or peribronchovascular patchy consolidations, migratory or recurrent, with air bronchograms; reversed halo (atoll) sign; nodules; ground glass.
• Raised CRP and ESR, leucocytosis, mild hypoxaemia; restrictive pattern with reduced DLCO.
• Bronchoalveolar lavage: mixed cellular pattern with lymphocytosis, foamy macrophages, mild neutrophils and eosinophils.
• Biopsy (transbronchial cryobiopsy or surgical): Masson bodies (fibroblast plugs) in distal airspaces with preserved architecture.
• Exclude infection, drug cause, connective tissue disease, vasculitis, lymphoma, eosinophilic pneumonia.

• Prednisolone 0.5 to 1 mg/kg daily (40 to 60 mg) for 4 to 6 weeks, then slow taper over 6 to 12 months (total 6 months or more) to reduce relapse. Clinical response in days to weeks; radiological clearance in 1 to 3 months.
• Severe or fulminant disease: methylprednisolone 500 to 1000 mg IV daily for 3 days, then oral taper.
• Relapse: reinstitute prednisolone at 20 to 30 mg and add steroid sparing agent (azithromycin 250 to 500 mg three times weekly, mycophenolate 1 g twice daily, azathioprine 2 mg/kg, cyclophosphamide, rituximab).
• Macrolides (clarithromycin 500 mg twice daily or azithromycin) alone may suffice in mild disease.
• Secondary forms: remove or treat the cause (stop drug, treat infection or connective tissue disease).
• Pneumocystis prophylaxis (co trimoxazole 960 mg three times weekly) and bone protection during steroid therapy; monitor glucose.
• Follow up imaging and spirometry every 3 months in the first year. Prognosis is excellent (over 80% recovery), with progression to fibrosis uncommon.