BOOP

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BOOP

• BRONCHIOLITIS OBLITERANS ORGANIZING PNEUMONIA
• ( a review )

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BUHMC

• THE BROOKDALE UNIVERSITY HOSPITAL MEDICAL
  CENTERBROOKLYN, 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 --gt 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, Sjogrens
  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 B- Strep,
  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

• Fishmans 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
  May81(5)149-51 Kanwar BA,Shehan CJ,Campbell JC,
  Dewan N, ODonohue WJ Jr