What's on this Page
Cryptogenic Organizing Pneumonia
What is meant by the term cryptogenic organizing pneumonia (COP)
The term COP is applied when organizing pneumonia is present without a clear etiology. Clinically, COP is characterized by months of low-grade fevers, cough, and malaise. Symptoms and imaging features typically rapidly improve with corticosteroid administration, although relapses can occur in 50% of cases.
Cryptogenic organizing pneumonia (COP), previously referred to as bronchiolitis obliterans with organizing pneumonia (BOOP), is a type of diffuse interstitial lung disease. It is the idiopathic form of organizing pneumonia, characterized by organized plugs of granulation tissue in the alveoli and bronchioles on histopathology. Cryptogenic organizing pneumonia has no known underlying cause. Secondary organizing pneumonia due to connective tissue disease, medications, malignancy, or other etiologies must be clinically excluded.
Synonyms
- Bronchiolitis obliterans organizing pneumonia (BOOP)
- COP
Epidemiology & Demographics
Incidence:
Estimated incidence is 6 to 7 cases per 100,000 per yr
Prevalence:
Unknown
Peak Incidence:
Typically, age of onset is 50 to 60 yr
Risk Factors:
Unknown
Genetics:
Unknown
Etiology
The etiology of cryptogenic organizing pneumonia is unknown.
Pathology & Histopathology
- •The pathogenesis may begin with alveolar epithelial injury of unknown cause, leading to recruitment of inflammatory cells and proliferation of fibroblasts.
- •The histopathologic features of organizing pneumonia consist of intraluminal organizing fibrosis in distal airways with intraalveolar buds of granulation tissue composed of connective tissue, fibroblasts, and myofibroblasts.
- •Poorly formed granulomas, prominent eosinophilia, and temporal heterogeneity are histopathologic features suggestive of secondary organizing pneumonia rather than COP and require further evaluation.
Findings & Clinical Presentation
- •Typically presents with acute to subacute onset of nonproductive cough, dyspnea, fevers, malaise, and weight loss.
- •Examination may be notable for inspiratory crackles. Wheezing and clubbing are rare. One fourth of patients will have a normal lung exam.
- •Skin, joint, or muscle findings should prompt further evaluation for connective tissue diseases, as they are often associated with secondary organizing pneumonia.
Diagnosis
A diagnosis of COP depends on compatible clinical history, radiographic pattern, and histopathologic features of organizing pneumonia in the absence of secondary causes.
Differential Diagnosis
Community-acquired pneumonia, chronic eosinophilic pneumonia, and hypersensitivity pneumonitis can have similar clinical presentations and radiographic features.
The differential diagnosis also includes other idiopathic interstitial pneumonias, malignancy, and secondary causes of organizing pneumonia, which need to be excluded
TABLE
Secondary Causes of Organizing Pneumonia
Drug toxicity |
Connective tissue disease |
Solid and hematologic malignancies |
Infection |
Radiation injury |
Immunodeficiency syndromes including postorgan transplantation |
Laboratory Tests and Workup
- •There are no specific laboratory tests for COP. Leukocytosis without peripheral eosinophilia and elevated inflammatory markers, including elevated erythrocyte sedimentation rate and C-reactive protein, are frequently present.
- •Chest imaging should be performed.
- •Pulmonary function testing most commonly demonstrates a mild to moderate restrictive pattern. Reduced diffusion capacity is observed in the majority of patients, and desaturation on 6-min walk test is common.
- •Bronchoscopy with bronchoalveolar lavage (BAL) is performed to evaluate for other disease processes, including infection, eosinophilic pneumonia, hemorrhage, and malignancy. Typical BAL findings in COP are nonspecific and include increased lymphocytes (20%-40%), neutrophils (10%), and eosinophils (5%-25%) and decreased CD4/CD8 ratio.
- •Transbronchial biopsies are of limited utility due to the patchy distribution of disease. When foci of organizing pneumonia are detected, the relatively small tissue specimens may not be sufficient to exclude other coexisting histopathologic processes.
- •Surgical lung biopsy may be needed to make a definitive diagnosis, especially if clinical and radiographic features are not typical. After a histologic diagnosis of organizing pneumonia is made, additional evaluation for secondary causes is necessary. This may include serologic testing for connective tissue diseases, in addition to infectious and hematologic evaluation
Imaging Studies
- •Chest x-ray and chest computed tomography (CT) scan typically show unilateral or bilateral peripheral airspace consolidations or ground-glass opacities. Small nodular opacities can be seen on chest CT scan, and less commonly, masslike opacities or the reverse halo sign (central ground-glass opacity surrounded by dense outer rim of airspace consolidation).
COP has a wide variety of imaging manifestations, but it is most often characterized by chronic waxing and waning patchy lower lobe predominant airspace opacities, which are frequently peripheral and peribronchovascular in distribution. Ground glass opacities and nodules are common accompanying features. The appearance and clinical presentation can be confused with those of pneumonia, often leading to months of delayed appropriate management.
Treatment
- •Initiation of therapy is based on symptom severity, physiologic impairment, extent of radiographic disease, and disease progression.
- •Pharmacologic treatment regimens are based on consensus guidelines and range from clinical monitoring to immunosuppression.
Initial Treatment
- •For patients with persistent or progressive symptoms, moderate physiologic impairment, and diffuse radiographic changes, initial treatment is with oral glucocorticoids, 0.75 to 1 mg/kg PO daily.
- •The initial oral dose is maintained for 4 to 8 wk, followed by a gradual taper if patient remains stable or improved.
- •Chest imaging (conventional chest radiograph or computed tomography) is used to evaluate radiographic improvement.
- •Most patients experience rapid improvement following initiation of glucocorticoids.
- •Relapse is common during taper (up to 50% of patients), although it usually is not associated with poor outcomes. The glucocorticoid dose should be increased to the prior effective dose and taper resumed following disease stabilization or improvement.
- •Close monitoring for adverse effects of glucocorticoid therapy is recommended.
Management of Refractory or Relapsing Disease
- •Patients who do not improve with glucocorticoids should be re-evaluated for alternative diagnoses.
- •Azathioprine and mycophenolate mofetil have been used as glucocorticoid-sparing agents in patients with recurrent relapses or high glucocorticoid requirements, although data are limited.
- •Cyclophosphamide at a dose of 1 to 2 mg/kg/day can be considered in more severe cases.
- •Fulminant cases of COP are rare and managed with intravenous glucocorticoids followed by transition to oral prednisone.
Pearls & Considerations
- •Chest imaging with peripheral airspace consolidations combined with a clinical presentation of an acute, flulike illness or subacute dyspnea and cough that does not respond to antibiotics should raise suspicion for cryptogenic organizing pneumonia.
- •Secondary causes associated with the histologic pattern of organizing pneumonia must be clinically excluded.
- •In the majority of cases, cryptogenic organizing pneumonia responds dramatically to glucocorticoids.
Seek Additional Information
- Drakopanagiotakis F., et al.: Cryptogenic and secondary organizing pneumonia: clinical presentation, radiographic findings, treatment response, and prognosis. Chest 2011; 139 (4): pp. 893-900.
- Travis D., et al.: An Official American Thoracic Society/European Respiratory Society statement: update of the international multidisciplinary classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med 2013; 188: pp. 733-748.