Cryptogenic organizing pneumonia

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Manpreet Kaur, MD [2]

Cryptogenic organizing pneumonia is an idiopathic diffuse interstitial lung disease that affects the distal bronchioles, respiratory bronchioles, alveolar ducts, and alveolar walls. The injury occurs within the alveolar wall. Cryptogenic organizing pneumonia has no identifiable etiology. Some of the causes of organizing pneumonia include infectious agents, drugs, inflammatory diseases, and toxic exposures. The symptoms of cryptogenic organizing pneumonia usually develop in the fifth or sixth decade of life and start with symptoms such as a cough, dyspnea, and weight loss. Cryptogenic organizing pneumonia patients have the good prognosis after the course of corticosteroids. Fatal outcome of cryptogenic organizing pneumonia is very rare. Patients with cryptogenic organizing pneumonia usually appear in mild distress. On examination, the patient is usually febrile, in tachypnea, tachycardia with the regular pulse. On lung auscultation there are bilateral vesicular breath sounds, fine crackles and wheezing is heard. On a chest X-ray in cryptogenic organizing pneumonia findings like consolidation, which may be unilateral/ bilateral, migratory and affects all lung zone and foci of granulation tissue can also be seen. On CT scan findings are subpleural and peribronchovascularconsolidation, ground-glass attenuation and nodules, irregular linear opacities, bronchial wall thickening and dilatation and reverse halo sign (atoll sign). On pulmonary function testing, the restrictive pattern is seen mostly. Corticosteroids are used as first-line treatment for patients with the symptomatic and progressive disease. Treatment is planned according to the severity of the disease. For treatment of mild disease is close monitoring is required, if there is worsening of symptoms or pulmonary function, then macrolides are used in the treatment of mild disease.For persistent or gradually worsening disease, corticosteroids are used for treatment and for severe disease cytotoxic agents are added. Relapses are common with corticosteriods therapy, azathioprine is used. Surgical treatment is preferred for focal organizing pneumonia. For preventive measures, the patient should be educated about the risk factors and signs of worsening of the disease.

Initial descriptions of organizing pneumonia can be traced back to 1877 Paris, in the lectures of J.M. Charcot. The first report of non-infectious organizing pneumonia without an identifiable underlying etiology was published in 1983. Soon after, the term “bronchiolitis obliterans organizing pneumonia (BOOP)” was introduced. This nomenclature was abandoned in 2002 by the American Thoracic Society/European Respiratory Society International Consensus Panel and the term cryptogenic organizing pneumonia was adopted.

There is no established system for the classification of cryptogenic organizing pneumonia.

Cryptogenic organizing pneumonia is an idiopathic diffuse interstitial lung disease that affects the distal bronchioles, respiratory bronchioles, alveolar ducts, and alveolar walls. The injury occurs within the alveolar wall. There is proliferation of granulation tissue which involves alveolar ducts and alveoli. There are 4 phases lead to the formation of mature fibrotic bud. There are no specific laboratory findings associated with cryptogenic organizing pneumonia. If there are symptoms of fever, cough and dyspnea, then tests like CBC, creatinine, urinalysis, ESR, CRP should be done. Further tests are done to rule out the etiology of the cryptogenic organizing pneumonia.

Cryptogenic organizing pneumonia has no identifiable etiology. Some of the causes of organizing pneumonia include infectious agents, drugs, inflammatory diseases, and toxic exposures.

Cryptogenic organizing pneumonia is approximately accounting to 5 to 10% of the chronic infiltrative lung disease in the United States. The incidence of cryptogenic organizing pneumonia is approximately 1.1 per 100,000 individuals in Iceland and 6-7 cases per 100,000 individuals in Canada. Cryptogenic organizing pneumonia commonly affects people of 50-60 years of age and rarely affects children. It affects men and women equally.

Common risk factors in the development of cryptogenic organizing pneumonia include infectious pneumonia, connective tissue diseases, immunologic diseases and inflammatory bowel disease, organ transplantation, medication use, breast radiation therapy and exposure to the toxin.

There is no screening for cryptogenic organizing pneumonia.

The symptoms of cryptogenic organizing pneumonia usually develop in the fifth or sixth decade of life and start with symptoms such as a cough, dyspnea, and weight loss.Cryptogenic organizing pneumonia patients have the good prognosis after the course of corticosteroids. Fatal outcome of cryptogenic organizing pneumonia is very rare.

There is no diagnostic study of choice for cryptogenic organizing pneumonia.

Patients with cryptogenic organizing pneumonia may have a positive history of connective tissue diseases, drug intake, malignancy and another interstitial lung disease. Common symptoms are a dry cough, shortness of breath, fever, fatigue and weight loss. Less common symptoms are hemoptysis, chest pain, and night sweats.

Patients with cryptogenic organizing pneumonia usually appear in mild distress. On examination, the patient is usually febrile, in tachypnea, tachycardia with the regular pulse. On lung auscultation there are bilateral vesicular breath sounds, fine crackles and wheezing is heard.

There are no specific laboratory findings associated with cryptogenic organizing pneumonia. If there are symptoms of fever, cough and dyspnea, then tests like CBC, creatinine, urinalysis, ESR, CRP. Further tests are done to rule out the etiology of the cryptogenic organizing pneumonia.

Findings on a chest X-ray in cryptogenic organizing pneumonia are consolidation, which may be unilateral/ bilateral, migratory and affects all lung zone.Foci of granulation tissue can also be seen.

There are no ECG findings associated with cryptogenic organizing pneumonia.

CT scan is used to diagnose cryptogenic organizing pneumonia. Various findings seen on CT scan are subpleural and peribronchovascularconsolidation, ground-glass attenuation and nodules, irregular linear opacities, bronchial wall thickening and dilatation and reverse halo sign (atoll sign).

There are no ultrasound associated with cryptogenic organizing pneumonia.

There are no other imaging findings associated with cryptogenic organizing pneumonia.

Pulmonary function test may be helpful in the diagnosis of cryptogenic organizing pneumonia. The most common finding in cryptogenic organizing pneumonia is mild to moderate restrictive ventilatory defect and DLCO is reduced. Flexible bronchoscopy is performed to obtain bronchoalveolar lavage sample (BAL) and transbronchial biopsy.

The mainstay of the therapy is pharmacotherapy. Corticosteroids are used as first-line treatment for patients with the symptomatic and progressive disease. Treatment is planned according to the severity of the disease. For treatment of mild disease close monitoring is required, if there is worsening of symptoms or pulmonary function, macrolides are used in the treatment of mild disease.For persistent or gradually worsening disease, corticosteroids are used for treatment and for severe disease cytotoxic agents are added. Relapses are common with corticosteriods therapy, azathioprine is used.

Surgical intervention is not recommended for the management of cryptogenic organizing pneumonia. Resection of the solitary nodule is the treatment for focal organizing pneumonia.

Effective measures for the primary prevention of cryptogenic organizing pneumonia is the elimination of the cause and appropriate treatment.

Effective measures for the secondary prevention of cryptogenic organizing pneumonia include educating the patient about the need for early treatment to prevent long term disabling bronchiolitis obliterans and interstitial fibrosis.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Serge Korjian M.D. Manpreet Kaur, MD [2]

Initial descriptions of organizing pneumonia can be traced back to 1877 Paris, in the lectures of J.M. Charcot. The first report of non-infectious organizing pneumonia without an identifiable underlying etiology was published in 1983. Soon after, the term “bronchiolitis obliterans organizing pneumonia (BOOP)” was introduced. This nomenclature was abandoned in 2002 by the American Thoracic Society/European Respiratory Society International Consensus Panel and the term cryptogenic organizing pneumonia was adopted.

• Initial descriptions of organizing pneumonia can be traced back to 1877 Paris, in the lectures of J.M. Charcot.
• However, the idea of organizing pneumonia, which describes the histopathological pattern associated with the syndrome, first appeared in the early 20th century under different names.^[1]
• The first report of non-infectious organizing pneumonia without an identifiable underlying etiology was published in 1983. The syndrome was called “cryptogenic organizing pneumonitis” to differentiate it from post-infective organizing pneumonia.^[2]
• In 1985, the term “bronchiolitis obliterans organizing pneumonia (BOOP)” was introduced. This nomenclature was abandoned in 2002 by the American Thoracic Society/European Respiratory Society International Consensus Panel for the Classification of Idiopathic Interstitial Pneumonia (ATS/ERS) for cryptogenic organizing pneumonia, a term that describes the true pathological lesion associated with the syndrome.^[3][4]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Manpreet Kaur, MD [2]

There is no established system for the classification of cryptogenic organizing pneumonia.

There is no established system for the classification of cryptogenic organizing pneumonia.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Manpreet Kaur, MD [2] Serge Korjian M.D.

Cryptogenic organizing pneumonia is an idiopathic diffuse interstitial lung disease that affects the distal bronchioles, respiratory bronchioles, alveolar ducts, and alveolar walls. The injury occurs within the alveolar wall. There is proliferation of granulation tissue which involves alveolar ducts and alveoli. There are 4 phases lead to the formation of mature fibrotic bud.

Cryptogenic organizing pneumonia is caused by excessive proliferation of granulation tissue which involves alveolar ducts and alveoli. Granulation tissue may extend from one alveolus to the adjacent one leading to the formation of mature fibrotic bud which gives characteristic “butterfly” pattern.

Various phases involved in the pathogenesis of cryptogenic organizing pneumonia are:^[1]

1) Injury phase – The early phase of cryptogenic organizing pneumonia.

• It is characterized by the deposition of plasma proteins in the alveolar lumen.
• Mechanism of early phase is an imbalance between coagulation and fibrinolytic cascade and activation of coagulation process which leads to fibrin deposition.^[2]

2) Proliferating phase – The second stage of the cryptogenic organizing pneumonia in which there is a formation of fibro-inflammatory buds.

• Macrophages and inflammatory cells help in fragmentation of fibrin.
• Activated fibroblasts differentiate into myofibroblasts which are migrating through gaps of the basal lamina.
• Inflammatory cells and fibrin are progressively replaced by aggregated fibroblasts/myofibroblasts intermixed with a loose connective matrix tissue rich in collagen (especially collagen I), fibronectin, procollagen type III and proteoglycans.
• Alveolar epithelial cells proliferate, restoring the continuity of the alveolar-capillary membrane and the integrity of the alveolar unit.

3) Mature phase – The third stage is characterized by the formation of mature fibrotic buds which gives characteristic “butterfly” pattern.

• In alveolar buds, there are myofibroblasts, organized in concentric rings alternating with layers of collagen bundles.

4)Resolution phase – The fourth stage, this stage usually resolves if there is the preservation of alveolar basal laminae.

Cryptogenic organizing pneumonia is associated with the following conditions:^[3][4]

• Infectious pneumonia
• Lung abscess
• Empyema
• Lung cancer
• Chronic pulmonary fibrosis
• Aspiration pneumonia
• Adult respiratory distress syndrome
• Pulmonary infarction
• Middle lobe syndrome

On gross pathology of cryptogenic organizing pneumonia, following features are seen:

• There is the firm area with preservation of lung pattern which extends to thickened pleura.^[3]

On microscopic histopathological analysis:^[5][6]

• It is characterized by chronic mild interstitial inflammation without fibrosis.
• There is the formation of buds of granulation tissue which is made of fibrous tissue (Masson bodies), mononuclear cells and foamy macrophages, in the distal airspaces which cause secondary bronchiolar occlusion due to the presence of the inflammatory process.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Manpreet Kaur, MD [2] Serge Korjian M.D.

Cryptogenic organizing pneumonia has no identifiable etiology. Some of the causes of organizing pneumonia include infectious agents, drugs, inflammatory diseases, and toxic exposures.

Some of the causes of organizing pneumonia include infectious agents, drugs, inflammatory diseases, and toxic exposures.

• Chlamydia pneumoniae
• Coxiella burnetii
• Cryptococcus neoformans
• Herpes virus
• Human immunodeficiency virus
• Influenza virus
• Legionella pneumophila
• Mycoplasma pneumoniae
• Nocardia asteroides
• Parainfluenza virus
• Penicillium janthinellum
• Plasmodium vivax
• Pneumocystis carinii
• Pseudomonas aeruginosa
• Serratia marcescens
• Staphylococcus aureus
• Streptococcus group B
• Streptococcus pneumoniae^[1]

• Acebutolol
• Amiodarone
• Amphotericin B
• Atorvastatin
• Azacytidine
• Azathioprine
• Betaxolol
• Bleomycin
• Bortezomib
• Bucillamine
• Busulfan
• Carbamazepine
• Cephalexin
• Chlorambucil
• Cladribine
• Clomipramine
• Cocaine
• Crizotinib
• Cyclophosphamide
• Cytarabine
• Daptomycin
• Doxorubicin
• Dronedarone
• Drug-eluting stents
• Ergot alkaloids
• Erlotinib
• Etanercept
• Everolimus
• Fludarabine
• Fosinopril
• Gold (chrysotherapy)
• Heroin (injected)
• Hexamethonium
• Hydralazine
• Hydroxyurea
• Imatinib
• Imipramine
• Infliximab
• Interferon-alpha/beta
• Ipilimumab
• Leflunomide
• Lenalidomide
• Loxoprofen
• Mecamylamine
• Mesalazine (5-aminosalicylate)
• Methotrexate
• Minocycline
• Nilutamide
• Nitrofurantoin
• Oxaliplatin
• Penicillamine
• Phenytoin (diphenylhydantoin)
• Pravastatin
• Propylthiouracil (PTU)
• Quinine
• Risedronate
• Rituximab
• Sertraline
• Simvastatin
• Sirolimus
• Sotalol
• Sulfasalazine
• Sulindac
• Tacrolimus
• Temozolomide
• Thalidomide
• Ticlopidine
• Timolol
• Tocilizumab
• Topotecan
• Trastuzumab
• Tryptophan^[2]

• Inflammatory bowel disease
• Collagen vascular diseases – Commonly rheumatoid arthritis

• Radiation therapy
• Paraquat
• Talc

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Manpreet Kaur, MD [2]

To review the complete differential diagnosis of cryptogenic organizing pneumonia, click here.

References

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Cryptogenic organizing pneumonia is approximately accounts to 5 to 10% of the chronic infiltrative lung disease in the United States. The incidence of cryptogenic organizing pneumonia is approximately 1.1 per 100,000 individuals in iceland and 6-7 cases per 100,000 individuals in Canada. Cryptogenic organizing pneumonia commonly affects people of 50-60 years of age and rarely affects children. It affects men and women equally.

• The incidence of cryptogenic organizing pneumonia is approximately 1.1 per 100,000 individuals in iceland.^[1]
• The incidence of cryptogenic organizing pneumonia is estimated to be 6-7 cases per 100,000 individuals in Canada.^[2]
• Cryptogenic organizing pneumonia is approximately accounts to 5 to 10% of the chronic infiltrative lung disease in the United States.

• Cryptogenic organizing pneumonia commonly affects people of 50-60 years of age.
• Cryptogenic organizing pneumonia rarely affects children.

• There is no racial predilection to cryptogenic organizing pneumonia.

• Cryptogenic organizing pneumonia affects men and women equally.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Manpreet Kaur, MD [2]

Common risk factors in the development of cryptogenic organizing pneumonia include infectious pneumonia, connective tissue diseases, immunologic diseases and inflammatory bowel disease, organ transplantation, medication use, breast radiation therapy and exposure to the toxin.

Common risk factors in the development of cryptogenic organizing pneumonia include:^[1][2]

• Infectious pneumonia
• Connective tissue diseases
• Immunologic diseases and inflammatory bowel disease
• Organ transplantation
• Medication use
• Breast radiation therapy
• Exposure to the toxin

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ;Associate Editor(s)-in-Chief: Manpreet Kaur, MD [2]

There is no screening for cryptogenic organizing pneumonia.

There is no screening for cryptogenic organizing pneumonia.

Template:WH Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Manpreet Kaur, MD [2]

The symptoms of cryptogenic organizing pneumonia usually develop in the fifth or sixth decade of life and start with symptoms such as a cough, dyspnea, and weight loss. Cryptogenic organizing pneumonia patients have the good prognosis after the course of corticosteroids. Fatal outcome of cryptogenic organizing pneumonia is very rare.

• The symptoms of cryptogenic organizing pneumonia usually develop in the fifth or sixth decade of life and start with symptoms such as a cough, dyspnea, and weight loss.
• Cryptogenic organizing pneumonia patients have the good prognosis after the course of corticosteroids. Fatal outcome of cryptogenic organizing pneumonia is very rare.

• There are no complications associated with cryptogenic organizing pneumonia but there are complications associated with corticosteroids treatment.^[1]
• Complications of long-term treatment with corticosteroids therapy are:^[2]
  • Weight gain
  • Decreased in bone density
  • Muscle weakness
  • Hyperlipidemia
  • Growth suppression
  • Thining of skin
  • Diabetes

• Prognosis is generally good after the treatment with corticosteroids.
• Fatal outcome of cryptogenic organizing pneumonia is rare.^[3]