Bronchiolitis Obliterans Organizing Pneumonia

							BOOP
BRONCHIOLITIS OBLITERANS ORGANIZING PNEUMONIA ( a review )
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BUHMC
THE BROOKDALE UNIVERSITY HOSPITAL & MEDICAL CENTER BROOKLYN, NEW YORK, NY, 11212
SIVAKUMAR PADMANABHAN, MD FELLOW, PULMONARY MEDICINE

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BOOP--INTRODUCTION
• Bronchiolitis Obliterans - refers to a generic term of non-specific inflammatory reaction of small airways in response to exogenous/endogenous stimuli • Comprises two types - based on histopathology • Clinical features mimic pneumonia without response to antibacterial therapy

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BOOP - INTRODUCTION
• Once BOOP is documented - look for a precipitating factor • Rx: Steroids/Immunosuppressive agents
• Prognosis: Excellent for idiopathic BOOP
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OB vs BOOP
• Constrictive or Obliterative Bronchiolitis• Concentric Narrowing of Bronchioles with fibrous tissue -> airflow limitation • Proliferative Bronchiolitis• Exuberant Granulation tissue and intraluminal plugs of connective tissue(Masson body) in respiratory bronchiole, alveolar duct and alveoli
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BOOP- EPIDEMIOLOGY
• • • • • • First described in 1901 by Lange 1985-- More cases reported by Epler et al Age incidence: 4th- 7th decades No gender predominance seen Incidence: 6-7 per 100,000 admissions Smoking is not a risk factor
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BOOP- Classification
• SECONDARY • BOOP • IDIOPATHIC • BOOP

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SECONDARY BOOP
• Connective tissue disorders - SLE, RA, Polymyositis - Dermatomyositis, Sjogren’s syndrome, MCTD, Ulcerative Colitis, Vasculitis • Inhaled/Systemic Toxins - gases, nicotine, cocaine, CO, nitrogen, chlorine • Drugs - Penicillamine, Amiodarone, Gold, Bleomycin, Mitomycin-c, Methotrexate, Sulfasalazine
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SECONDARY BOOP
• Interferon Rx for Hepatitis C - reported

Chest 1994 Aug; 106 (2):612-3 Ogata k, Koga T, Yagawa K, Japan

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SECONDARY BOOP
• Infections:
– Mycoplasma, HIV, HSV, CMV, Rubeola, Klebsiella, Hemophilus, Legionella, Grp BStrep, Cryptococcus, Nocardia, PCP

• Pediatric
– RSV, Parainfluenza, Adenovirus, Mycoplasma

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SECONDARY BOOP
• • • • • • • Obstructive Pneumonitis Hypersensitivity Pneumonitis Aspiration Pneumonitis Chronic Eosinophilic Pneumonia Diffuse Alveolar Damage Myelodysplastic Syndrome Hematological malignancy
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SECONDARY BOOP
• Allograft transplant
– Heart, Lung, Bone Marrow – 5-15% in those with GVHD – 1% of Allogenic transplant recepients without GVHD or in Autologous transplant recepients – IPF, ARDS

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BOOP - CLINICAL FEATURES
• SUBACUTE illness:
– non-productive cough – exertional dyspnea - few weeks

• Constitutional symptoms:
– fever, malaise, weight loss

• one- third have a preceding upper respiratory tract infection • MIMICS Community Acquired Pneumonia
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BOOP- CLINICAL FEATURES
• Physical exam :
– Tachypnea, Crackles – Clubbing is rare

• Rarely BOOP can mimic Bronchogenic CA by presenting as a solitary pulmonary nodule with cavity and hemoptysis • Unilateral BOOP has been described
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BOOP- LAB TESTS
• High ESR & CRP - secondary to inflammatory process • 1/3rd have a leukocytosis • Chest Xray: Patchy peripheral bilateral migratory alveolar infiltrates • 20-30% - reticular or nodular infiltrate • Pleural effusions in 30% due to secondary BOOP
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BOOP- Imaging
• CXR- can be normal in 4-10%
• Cavitation & lymphadenopathy are absent • Focal consolidation is a marker for a good response to steroid therapy
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BOOP- IMAGING
• High Resolution CAT scan of Chest: patchy consolidation, ground glass opacity, nodularity with subpleural lower lobe predeliction. • Bronchial wall thickening and dilatation denote severe disease • Honey combing not seen in idiopathic BOOP
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PFTs in BOOP
• • • • Restrictive Defect with Low Vital capacity Low DLCo Resting and exercise induced Hypoxemia Pressure-Volume curve shifted down and right due to decreased lung compliance • Obstructive defect is not a feature unless patient is a smoker
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BOOP- Bronchoscopy
• • • • BAL- High lymphocytes and Neutrophils Foamy macrophages Low CD4-CD8 ratio Transbronchial Biopsy may miss representative lesions but may still be useful • Gold standard- Open lung or thoracoscopic lung biopsy for histopathology
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BOOP-Pathogenesis
• Accelerated host response to injury• Bacterial or viral antigen; • Inhaled or noxious stimulus  Lung injury  Inflammatory cascade  subsequent repair

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BOOP-HISTOLOGY
• Exuberant inflammation and fibrosis in terminal & respiratory bronchioles. • Terminal bronchioles plugged with granulation tissue, neutrophils, edema, fibrin, connective tissue, myoblasts, fibroblasts. • Extends to peribronchiolar region, alveolar duct and alveolar space - organizing pneumonia component
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BOOP-HISTOLOGY
• Cells-mononuclear, neutrophils, eosinophils, mutinucleate giant cells. • Lesions in peribronchiolar distribution seen on low power is a clue to diagnosis. • Preserved underlying alveolar architecture • Fibrosis usually does not occur • Stereotypic response to lung injury ie lesions are of same age
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BOOP- DIFFERENTIAL DIAGNOSIS
• • • • • • Community Acquired Pneumonia Drug Reactions, ARDS, Chronic Eosinophilic Pneumonia, Lymphoproliferative malignancy, Bronchogenic ca (bronchoalveolar cell) Histology may resemble usual intersitial pneumonitis or organising diffuse alveolar damage
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BOOP

VS OB

• Obliterative Bronchiolitis due to RA, toxic fumes, bone marrow or lung transplant • CXR - may be normal • PFTs - obstructive or mixed defect • Pathology - concentric bronchiolar narrowing by intramural fibrosis without interstital involvement
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BOOP vs OB
• OB- Poor response to steroids • OB- Poor prognosis • OB- No spontaneous recovery

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BOOP--Treatment
• • • • • Spontaneous recovery occurs rarely Antibiotic therapy for underlying infections Withdrawal of offending toxin/ drug Supportive therapy Steroids for idiopathic BOOP and BOOP secondary to connective tissue disorders
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BOOP-STEROID Rx
• Prednisone- 0.5-1.0 mg/kg/day x 1-3 mos • Taper slowly over several months on individual basis • Duration of Rx 6- 12 months • Relapse may occur during steroid taper • Monitor by clinical, CXR and PFTs. • Response occurs in days to weeks
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BOOP-- STEROID Rx
• Idiopathic BOOP responds to steroids better than BOOP due to connective tissue disorders

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BOOP-Prognosis
• 65%- idiopathic BOOP cases have complete clinical, radiographic and physiologic resolution • 20%-Residual pulmonary fibrosis • 3-10%- mortality rate • Secondary BOOP has poor response to steroid Rx
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BOOP- Rx
• Immunosuppressive agents cyclophosphamide, azathioprine for those who fail to respond to steroid Rx
• Low dose erythromycin has an immunomodulatory effect

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FULMINANT BOOP
• Rapidly progressive to respiratory failure requiring mechanical ventilation (9 0f 10 patients in a series by Cohen & Colleagues) • Predisposed by Smoking, drugs, connective tissue disorders and environmental agents • Necropsy-septal inflammation, interstitial fibrosis & honeycombing
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FULMINANT BOOP
• Rx: High dose steroids and immunosuppressive agents • Course: Death or severe residual pulmonary fibrosis

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Summary--BOOP
• BOOP represents a nonspecific reaction pattern of lung to a wide variety of insults. • Clinical/Histologic correlation aids in correct assessment of diagnostic, therapeutic and prognostic significance

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BOOP- References
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Fishman’s Pulmonary Diseases & Disorders: vol 1, 3rd ed, ch. 54 p 825-847 Comprehensive Respiratory Medicine by R Albert, S Spiro, J Jett, 9 48.4-48.6 ACCP Pulmonary Board Review 1998-99 p.163-166 J P Lynch III ,MD, FCCP MKSAP- Pulmonary & Critical Care , 2nd ed,ch.4.S B Fiel, J P Lynch III p 108-116 BOOP associated with acute Mycoplasma infection Clin Inf Dis 1997 Dec, 25(6):1340-2,Llibre JM, Urban A, Garcia E, Carrasco MA, Murcia C Low dose erythromycin for treatment of BOOP Kurume Med J, 1993; 40(2);65-7 Ichikawa Y, Ninomiya H, Katsuki M, Hotta M, Tanaka M, Oizumi K A case of Unilateral BOOP, Nebr Med J,1996 May;81(5):149-51 Kanwar BA,Shehan CJ,Campbell JC, Dewan N, O’Donohue WJ Jr
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