OP is a pattern of repair after injury; it can be cryptogenic or a response to a specific lung injury. COP has no identifying cause and is under the umbrella of Interstitial Lung Disease > Idiopathic Interstitial Pneumonias (IIPs). It is formerly called bronchiolitis obliterans organizing pneumonia (BOOP). Often misdiagnosed, and can be very responsive to treatment.

Secondary forms of OP are due to a specific cause (infection, drug toxicity, inhalation injury, radiation, cancer) or within another clinical context (CTD, aspiration, transplantation, interstitial pneumonia).

Variants

• Focal organizing pneumonia (<15%) which must be distinguished from lung cancer. Might be resectable.
• Fulminant COP. First rule out infection then consider IV steroids. High mortality rate from respiratory failure.
• Cicatricial OP.
• Acute fibrinous OP. Patchy infiltration.

Epidemiology and Pathophysiology

• COP reasonably rare; 7 per 100,000 hospital admissions. 5-10% of ILD diagnoses. Mean age is 50-60, men > women. About 50% smokers.
• Poorly defined pathogenesis. Lung injury occurs as a single event and causes an inflammatory and fibroproliferative process characterized by intra-alveolar fibroproliferation that is reversaible with therapy.
  • Contrasted to other fibrotic processes such as UIP which are not reversible.
  • Alveolar injury --> inflammatory response --> fibroblast response --> protein dysregulation --> interstitial remodeling

Secondary Causes of Organizing Pneumonia

• infection (bacterial, viral, parasitic, fungal)
• drugs (amiodarone, nitrofurantoin, bleomycin, MTX, cocaine)
• CTD (RA, Sjogren's, myositis, SScl, anti-synthetase syndrome, vasculitis)
• Hematologic cancer
• Transplantation (lung, liver, BM)
• Radiation injury
• CVID
• Other ILD (eosinophilic pneumonia, hypersensitivity pneumonia, UIP)
• IBD
• Other
  • other lung processes: abscess, DAH, airway obstruction
  • Inhalation injury

Clinical Presentation

Suspect COP when patients with a ?pneumonia do not respond to antibiotic treatment. Symptoms are often subacute and develop over weeks to months: - dry cough, dyspnea are most common - influenza-like symptoms are possible (10-15%) - fever is common (44%) - hemoptysis is rare (<5%)

Examination reveals inspiratory crackles (60%), rarely clubbing (<3%). Rarely the examination is normal (<5%).

Evaluation

Noninvasive Tests

1. Lab tests reveal evidence of inflammation. Consider testing for CTDs as COP can precede CTD manifestations by weeks to months.
2. PFTs show restricted ventilatory defects and a reduced DLCO, but are normal lung volumes in 25% of patients. Obstruction is not a feature of COP. Hypoxemia is common.
3. Imaging is usually distinctive: bilateral opacities (patchy/diffuse and consolidative or hazy) with normal lung volumes. CT is better than CXR. On CT, the pattern is peripheral and multifocal consolidation +/- bronchograms, with lesions in all lung zones, and slightly predominant subpleural and lower-lung distribution. Other findings:
   1. GGO
   2. Nodules 8 mm in diameter in a well-defined acinar pattern
   3. Reverse halo pattern (<5%)

Invasive Tests

1. BAL is recommended if COP is suspected to rule out infection and other disorders (eosinophilic pneumonia, DAH). Typically BAL shows lymphocytic alveolitis with increased neutrophils and eosinophils.
2. Histopathology is not alway needed to make the diagnosis.

Differential Diagnosis

1. CAP
2. Hypersensitivity pneumonitis
3. Eosinophilic penumonia
4. Alveolar hemorrhage
5. Vasculitis
6. Pulmonary lymphoma, invasive mucinous adenocarcinoma

Management

Treatment of COP is empirical because no prospective RCTs have been done. Less than 10% of patients have spontaneous improvement, but they typically had milder disease.

Steroids

• systemic steroids are the preferred treatment
• Prednisone 0.5 to 1 mg/kg/day up to 60 mg/day, for 2-4 weeks initially then tapered to 0.25 mg/kg/day depending on the clinical response to complete 4-6 months of therapy. Over the next 6 to 12 months the steroids are tapered to zero if the patient's condition allows.
  • Clinical improvement should manifest within 1-3 days. First symptoms decrease then radiologic findings improve within 3 months.
  • PJP ppx recommended for more than 20 mg prednisone per day
• Consider pulse steroids (500-1000 mg methylprednisolone for 3-5 days) for sick patients then step down to oral regimen above.

Relapses

Defined by worsening symptoms or new radiolographic findings during or after steroid treatment. Rare, less than 25% during the first year. Can occur when tapering or stopping therapy too quickly, and generally when prednisone < 15 mg/day.

Associated with delayed diagnosis, delayed treatment, severe disease, traction bronchiectasis, abnormal DLCO, cholestasis, hypoxemia, and advanced fibrosis.

Treat with resuming or increasing steroids, consider <20 mg/d based on studies showing equal efficacy.

Not associated with morbidity or mortality.

Other Therapies

Considered for those who need additional agents or cannot tolerate steroids: - Macrolides - Cytotoxic therapy (AZA, CYC) - Antimetabolites etc (MMF, CsA, RTX, IVIg)

Prognosis

Generally, COP has an excellent prognosis. Progressive respiratory failure or death are rare (<10%), and 5-year survival rate is >90%. Despite this, of course patients have higher mortality than the general population.

Secondary organizing pneumonia has a slightly worse prognosis, due to the underlying illness.

References

1. King TE, Lee JS. Cryptogenic Organizing Pneumonia. New England Journal of Medicine. 2022;386(11):1058-1069. doi:10.1056/NEJMra2116777