eMedicine Specialties > Radiology > Chest

Bronchiolitis Obliterans Organizing Pneumonia

Author: Ali Nawaz Khan, MBBS, FRCS, FRCP, FRCR, Consultant Radiologist and Honorary Professor, North Manchester General Hospital Pennine Acute NHS Trust, UK
Coauthor(s): Klaus L Irion, MD, PhD, Consulting Staff, The Cardiothoracic Centre Liverpool NHS Trust, The Royal Liverpool University Hospital, UK; Simon Hanley, MBBS, MRCP, FRCP, DM, MHS, Consulting Staff, Department of Internal Medicine, North Manchester General Hospital; Sumaira MacDonald, MBChB, PhD, MRCP, FRCR, Lecturer, Sheffield University Medical School; Endovascular Fellow, Sheffield Vascular Institute; Muthusamy Chandramohan, MBBS, DMRD, FRCR, Consultant Radiologist, Bradford Teaching Hospitals, UK; Sarah Al Ghanem, MBBS, Consulting Staff, Department of Medical Imaging, King Fahad National Guard Hospital, Saudi Arabia
Contributor Information and Disclosures

Updated: Oct 6, 2009

Introduction

Background

Organizing pneumonia is characterized by the presence of granulation tissue in the distal air spaces. When organizing pneumonia is associated with granulation tissue in the bronchiolar lumen, the qualifying term bronchiolitis obliterans (BO) is added.

Chest radiograph in a 56-year-old woman with syst...

Chest radiograph in a 56-year-old woman with systemic lupus erythematosus shows a left-sided unilateral focal/lobar consolidation associated with some loss of volume.

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Chest radiograph in a 56-year-old woman with syst...

Chest radiograph in a 56-year-old woman with systemic lupus erythematosus shows a left-sided unilateral focal/lobar consolidation associated with some loss of volume.


Standard nonenhanced axial thoracic computed tomo...

Standard nonenhanced axial thoracic computed tomography (CT) scan in a 56-year-old woman with systemic lupus erythematosus (same patient as in Image above) shows left–lower-lobe consolidation with some loss of volume and an air bronchogram. Transbronchial lung biopsy confirmed the diagnosis of bronchiolitis obliterans organizing pneumonia.

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Standard nonenhanced axial thoracic computed tomo...

Standard nonenhanced axial thoracic computed tomography (CT) scan in a 56-year-old woman with systemic lupus erythematosus (same patient as in Image above) shows left–lower-lobe consolidation with some loss of volume and an air bronchogram. Transbronchial lung biopsy confirmed the diagnosis of bronchiolitis obliterans organizing pneumonia.


A case of pulmonary disease may be classified as organizing pneumonia on the basis of the following criteria1 :
  • The cause has been determined.
  • The cause remains undetermined but is occurring in a specific and relevant context.
  • The disease is cryptogenic (idiopathic) organizing pneumonia (COP).

Cryptogenic organizing pneumonia (COP) is often confused with bronchiolitis obliterans organizing pneumonia (BOOP).2 COP is a clinicopathologic syndrome that rapidly resolves with the use of corticosteroids but that is also marked by frequent relapses when treatment is tapered or stopped.

Radiologically identical peripheral airspace consolidation occurs in patients with chronic eosinophilic pneumonia (CEP) and BOOP. CEP primarily involves the upper lobe; by contrast, in BOOP, consolidation is predominantly in the lower zones, although some patients have pathologic characteristics of CEP and BOOP.

A tissue biopsy specimen is needed for a precise diagnosis, but clinicoradiologic characteristics determined through biopsy-based studies may provide enough diagnostic information. This article discusses BOOP in the general context of organizing pneumonia; it combines data from BOOP and COP patient research. Organizing pneumonias that are of known cause are indistinguishable from those that are of unknown cause.3,4,5,6,7,8,9,10,11

Recent studies

In a retrospective study by Vasu et al of 33 patients with BOOP on surgical lung biopsy over a 10-year period, dyspnea was found to be the most common symptom, followed by dry cough and fever, and the main radiologic finding was bilateral patchy consolidation. Crackles was the most common physical finding. Although most patients had a favorable prognosis, 17% did not respond to therapy. Compared with patients with idiopathic BOOP, patients with secondary BOOP had more frequent fevers and were generally more symptomatic. In addition, pleural effusion was present in 60% of patients with secondary BOOP, whereas none of the patients with idiopathic BOOP had pleural effusion.2

Because bronchiolitis combined with interstitial pneumonitis has been equated with BOOP, according to Mark and Ruangchira-urai, the authors compared the findings in 31 patients with lung biopsies revealing both bronchiolar and interstitial pneumonitis with the clinical and pathologic findings in bronchiolitis obliterans, BOOP, nonspecific interstitial pneumonitis, usual interstitial pneumonitis, airway-centered interstitial fibrosis, and idiopathic bronchiolocentric interstitial pneumonia, along with findings in 10 cases of cystic fibrosis. The common finding was a combination of bronchiolitis and interstitial inflammation and fibrosis but little or no intra-alveolar organizing pneumonia. BOOP involved less area than the interstitial pneumonitis in each case. Of the 31 cases noted, 19 had follow-up, and all received corticosteroids, but the response was less than that seen with BOOP; however, disease generally did not progress in the patients given corticosteroids.4

Pathophysiology

About 50% of cases of bronchiolitis obliterans organizing pneumonia are idiopathic.12 The following conditions are associated with BOOP:

  • Conditions in which the cause is determined
    • Radiation therapy — In patients treated with radiation therapy for small cell bronchogenic carcinoma or breast cancer, BOOP may affect the ipsilateral or contralateral lung.
    • Infections — BOOP may be caused by Coxiella burnetii and Pseudomonas aeruginosa, as well as by Mycoplasma species. BOOP possibly may be associated with human herpesvirus 7 infection following lung transplantation and with Pneumocystis jiroveci (formerly, P. carinii) in patients receiving tacrolimus (after liver transplantation). Infection also may be caused by influenza A virus, measles virus, parvovirus B19, human immunodeficiency virus (HIV), Chlamydia species, Plasmodium vivax, and Plasmodium malariae.
    • Drugs and toxins — BOOP is associated with exposure to minocycline, gold, cephalosporin, acebutolol, sulfasalazine, mesalazine, bucillamine, interferon beta-1a, nitrofurantoin, amiodarone, ticlopidine, carbamazepine, phenytoin, sotalol, and rapid intravenous cyclophosphamide pulse therapy; a combination of cytosine arabinoside, anthracyclines, and massive L-tryptophan ingestion; Sauropus androgynus vegetable poisoning; exposure to paint aerosols (seen in textile workers); nylon flock – related disease; silo-filler's disease; freebase cocaine use; and smoke inhalation.
  • Associated pathologies
    • Connective tissue diseases — Rheumatoid arthritis, Sjögren syndrome, ankylosing spondylitis, polymyositis-dermatomyositis, cutaneous vasculitis, Behçet syndrome, Wegener granulomatosis, ulcerative colitis, regional enteritis, systemic sclerosis, systemic lupus erythematosus, systemic lupus erythematosus with antiphospholipid-antibody syndrome, primary biliary cirrhosis, and thyroiditis
    • Immunosuppressed states — Hematopoietic stem cell transplantation (HSCT), graft versus host disease of the liver after allogeneic bone marrow transplantation, renal transplantation, coronary artery bypass graft surgery, kidney transplantation with Fabry disease, T-cell leukemia, primary non-Hodgkin lymphoma, malignancies in children, myelodysplastic syndrome, recent surgery, severe pneumonia, adult respiratory distress syndrome, and acquired immunodeficiency syndrome (AIDS)
    • Miscellaneous conditions
      • Sarcoidosis, lung cancer, lung atelectasis, asthma, cystic fibrosis, secondary amyloidosis, acute febrile neutrophilic dermatosis (Sweet disease), idiopathic thrombocytopenic purpura, Evans syndrome, essential mixed cryoglobulinemia, and chronic sinusitis
      • A seasonal variety
      • Menstruation; pregnancy

Presentation

Demographics

  • It is believed that bronchiolitis obliterans organizing pneumonia (BOOP) is the source of 20-30% of all cases of chronic infiltrative lung disease.13
  • No significant difference has been reported between the rate of bronchiolitis obliterans organizing pneumonia in the United States and the rate in other countries.
  • The overall mortality rate of patients with bronchiolitis obliterans organizing pneumonia is 10%. Pulmonary complications—including BOOP, bronchiolitis obliterans (BO), and idiopathic pneumonia syndrome (IPS)—develop in 30-60% of patients with hematopoietic stem cell transplantation (HSCT). BO and BOOP, which have a 61% and 21% mortality rate, respectively, occur exclusively in patients who have undergone allogeneic HSCT. Patients with BOOP respond favorably to treatment with steroids, whereas patients with IPS have a 1-year survival rate of less than 15%.3
  • No racial predilection is reported.
  • No sex predilection is described.
  • Most patients with bronchiolitis obliterans organizing pneumonia are 40-70 years of age, but BOOP has been reported in children, particularly in those with underlying malignancy.13,14

Presentation and natural history

Approximately 50% of all patients with bronchiolitis obliterans organizing pneumonia have a history of an influenzalike illness followed by a second illness that lasts about 3 months (1-4 mo) and features a persistent, nonproductive cough; effort dyspnea; low-grade pyrexia; malaise; and weight loss. Less common symptoms include pleuritic chest pain and hemoptysis.13,15

Symptoms do not respond to broad-spectrum antibiotics. A significant number of patients have associated collagen disease (16%) and a history of inhalation exposure to toxins (17%). BOOP may be the first manifestation of non-Hodgkin lymphoma and collagen disease.16 In most patients, clinical examination of the thorax demonstrates fine, dry lung crepitations. Clubbing is unusual. The erythrocyte sedimentation rate not only is invariably higher but may be greatly increased. Pulmonary function tests characteristically show a restrictive pattern. The diffusing capacity is reduced, the resting alveolar arterial oxygen gradient is widened, and exercise-related hypoxemia is present. By contrast, chronic eosinophilic pneumonia (CEP) involves an obstructive pattern of lung physiology.17,18

Bronchoalveolar lavage reveals the following cytologic and immunocytologic characteristics in patients with BOOP19 :

  • Cytologic examination demonstrates a mixed cell pattern, with an increase in lymphocytes (20-40%), neutrophils (10%), eosinophils (5%), mast cells, foamy macrophages, and, occasionally, plasma cells.
  • An increase in the percentages of neutrophils and lymphocytes in patients with BOOP differentiates the condition from idiopathic pulmonary fibrosis.
  • Eosinophils are increased significantly in patients with CEP, with a small overlap with BOOP.
  • The CD4+/CD8+ ratio is decreased.
  • The percentage of CD57+ cells is within the reference range.
  • Activation of T cells is increased in terms of human leukocyte antigen-DR (HLA-DR) expression and, occasionally, interleukin-2 receptor (CD25+) expression.
  • All of the above findings are similar in extrinsic allergic alveolitis, except that CD25+ expression is always within the reference range in patients with BOOP and that levels of CD57+ cells are always increased in extrinsic allergic alveolitis.
  • In patients with BOOP, the ratio of lymphocytes to CD8+ cells is significantly increased, and the CD4+/CD8+ ratio is significantly lower than the ratios in patients with usual interstitial pneumonia.

Treatment
Most patients with bronchiolitis obliterans organizing pneumonia require open lung biopsy for diagnosis. However, some evidence suggests that combining the cytologic bronchoalveolar lavage and histologic transbronchial lung biopsy data obtained during a fiberoptic procedure appears to be an effective method for initially investigating cases of BOOP in which there are radiographic findings of patchy shadows. Percutaneous lung biopsy has been used in a few patients, but on the whole, it appears to be inadequate.

BOOP may resolve spontaneously; however, patients usually require treatment with steroids. Most patients recover with treatment, and symptoms resolve within days or weeks. Radiographic findings reportedly demonstrate improvement in 50-86% of patients; however, in a minority of patients, the disease may persist. Approximately 30% of patients experience relapse upon withdrawal of treatment. Patients with BOOP respond favorably to treatment with steroids.20

Differential Diagnoses

Wegener Granulomatosis, Thoracic

Other Problems to Be Considered

Chronic interstitial pneumonia (organizing interstitial pneumonia, chronic diffuse sclerosing alveolitis)
Acute interstitial pneumonia (AIP)
Focal organizing pneumonia
Interstitial lung disease
Hypogammaglobulinemia
Pulmonary metastasis and primary adenocarcinoma
Pulmonary tuberculosis
Community-acquired pneumonia
Chronic eosinophilic pneumonia
Usual interstitial pneumonia
Bronchoalveolar carcinoma

More on Bronchiolitis Obliterans Organizing Pneumonia

Overview: Bronchiolitis Obliterans Organizing Pneumonia
Imaging: Bronchiolitis Obliterans Organizing Pneumonia
Follow-up: Bronchiolitis Obliterans Organizing Pneumonia
Multimedia: Bronchiolitis Obliterans Organizing Pneumonia
References
Further Reading
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Keywords

bronchiolitis obliterans organizing pneumonia, BOOP, bronchiolitis obliterans, BO, cryptogenic organizing pneumonia, COP, usual interstitial pneumonia, UIP, chronic interstitial pneumonia, CEP, interstitial pneumonia (IP), hematopoietic stem cell transplantation, HSCT, Ardystil syndrome, nonspecific interstitial pneumonia with fibrosis, proliferative bronchiolitis, pulmonary disease, pneumonia, organizing pneumonia, idiopathic organizing pneumonia

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Contributor Information and Disclosures

Author

Ali Nawaz Khan, MBBS, FRCS, FRCP, FRCR, Consultant Radiologist and Honorary Professor, North Manchester General Hospital Pennine Acute NHS Trust, UK
Ali Nawaz Khan, MBBS, FRCS, FRCP, FRCR is a member of the following medical societies: American Association for the Advancement of Science, American Institute of Ultrasound in Medicine, British Medical Association, British Society of Interventional Radiology, Royal College of Physicians, Royal College of Physicians and Surgeons of the United States, Royal College of Radiologists, and Royal College of Surgeons of England
Disclosure: Nothing to disclose.

Coauthor(s)

Klaus L Irion, MD, PhD, Consulting Staff, The Cardiothoracic Centre Liverpool NHS Trust, The Royal Liverpool University Hospital, UK
Klaus L Irion, MD, PhD is a member of the following medical societies: American Roentgen Ray Society and Radiological Society of North America
Disclosure: Nothing to disclose.

Simon Hanley, MBBS, MRCP, FRCP, DM, MHS, Consulting Staff, Department of Internal Medicine, North Manchester General Hospital
Simon Hanley, MBBS is a member of the following medical societies: British Cardiac Society
Disclosure: Nothing to disclose.

Sumaira MacDonald, MBChB, PhD, MRCP, FRCR, Lecturer, Sheffield University Medical School; Endovascular Fellow, Sheffield Vascular Institute
Sumaira MacDonald, MBChB, PhD, MRCP, FRCR is a member of the following medical societies: British Medical Association, Royal College of Physicians, and Royal College of Radiologists
Disclosure: Nothing to disclose.

Muthusamy Chandramohan, MBBS, DMRD, FRCR, Consultant Radiologist, Bradford Teaching Hospitals, UK
Disclosure: Nothing to disclose.

Sarah Al Ghanem, MBBS, Consulting Staff, Department of Medical Imaging, King Fahad National Guard Hospital, Saudi Arabia
Disclosure: Nothing to disclose.

Medical Editor

Jeffrey A Miller, MD, Associate Professor of Clinical Radiology, University of Medicine and Dentistry of New Jersey; Associate Chief of Service, Department of Radiology, Veterans Affairs of New Jersey Health Care System
Jeffrey A Miller, MD is a member of the following medical societies: North American Society for Cardiac Imaging, Society for Health Services Research in Radiology, and Society of Thoracic Radiology
Disclosure: Nothing to disclose.

Pharmacy Editor

Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand
Disclosure: Nothing to disclose.

Managing Editor

John D Newell Jr, MD, Professor of Radiology, Co-Director of Thoracic Imaging, Department of Radiology, University of Colorado Health Sciences Center; Professor of Medicine, Medical Director of Lung Imaging Center, National Jewish Medical and Research Center
John D Newell Jr, MD is a member of the following medical societies: American College of Chest Physicians, American College of Radiology, American Roentgen Ray Society, American Thoracic Society, Association of University Radiologists, Radiological Society of North America, and Society of Thoracic Radiology
Disclosure: Siemens Medical Grant/research funds Consulting; Forevision Technologies Ownership interest Consulting; Vida Corporation Ownership interest Board membership; TeraRecon Grant/research funds Consulting; eMedicine Honoraria Consulting

CME Editor

Robert M Krasny, MD, Resolution Imaging Medical Corporation
Robert M Krasny, MD is a member of the following medical societies: American Roentgen Ray Society and Radiological Society of North America
Disclosure: Nothing to disclose.

Chief Editor

Eugene C Lin, MD, Consulting Radiologist, Virginia Mason Medical Center; Clinical Assistant Professor of Radiology, University of Washington School of Medicine
Eugene C Lin, MD is a member of the following medical societies: American College of Nuclear Medicine, American College of Radiology, Radiological Society of North America, and Society of Nuclear Medicine
Disclosure: Nothing to disclose.

 
 
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