1. Steroid resistant BOOP (Bronchiolitis Obliterans Organizing Pneumonia)
호흡기 내과 노태준

2. Order 1. Introduction 2. Classification
3. Review of Korean case reports – Efficacy of Steroid
4. Pathogenesis and Role of steroid in BOOP
5. Refractory BOOP
6. Relationship between Relapse and Steroid resistant BOOP

3. Introduction Clinico-radiological-pathologic entity
Subacute clinical course – flu like illness, cough, fever, DOE…
Davison et al (1983) : “ COP (Cryptogenic organizing pneumonia)”
Epler et al (1985) : “ BOOP (Bronchiolitis Obliterans Organizing Pn) ”
→ organized granulation tissue plug
70% : idiopathic, 20% : connective tissue disease
Organized granulation tissue plug within alveolar duct / alveoli

4. Classification Idiopathic Rapidly progressive Focal nodular
Post infection
Chlamydia, Legionella,
Adenovirus, CMV, Influenza
Malaria, PCP…
Drug
Antibiotics: Amphotericin B,
Cephalosporin, sulfasalazine
Bleomycin, Gold, amiodarone
Carbamazepine, Phenytoin…
Connetive tissue disease
Polymyositis, SLE, RA…
Immunologic disorder
Organ transplantation
BM, Lung, kidney
Radiotherapy
Environmental exposures
Miscellaneous
IBD, Lymphoma, cancer
T-Cell CLL, HIV infection
MDS, Chr thyroiditis
alcholoic LC
CABG…
Arch Intern Med 2001;161:

7. 이대목동병원 5예+
Case reports 19예

8. 외국 저널은 steroid 효과를 63-96%로 보고 ( 특히 NEJM 1985 찾아볼것 )
Good response

9. Pathogenesis
Injury to capillary endothelial cells and alveolar epithelial cell
Leakage of plasma proteins ( especillay, coagulation factors )
Into Alveolar lumen, activaion of extrinsic coagulation ptwy
Fibrin deposit : fibrinolytic process ↓
Biological activity on fibroblast : chemotactic, activating

10. Role of cytokines in BOOP
Role in organised fibrotic intraalveolar buds ??
Degradation of connective matrix : Requires of enzymes
MMP ( Metalloproteinases), Gelatinases, stromelysins
← produce by leukocytes & fibroblasts
Cytokines
J Clin Invest 1996;98:

11. Mechanisms of steroid
Inhibit transcription of several inflammatory cytokines
( IL-1,3,4,5,6,8, TNF-α, GM-CSF )
AP-1, NF-κB : upregulation of cytokines
Inhibit of ICAM-1, E-selectin
Synthesis of SLPI (Secretory leukocyte protease inhibitor)
: reduce airway inflammation
Inhibit of MIP-1α (Macrophage Inflammatory protein-1)
MCP-1 (Monocyte chemotactic protein-1)
Am J Crit Care Med 1999;160:

12. Mechanisms of steroid
Inhibit transcription of several inflammatory cytokines
( IL-1,3,4,5,6,8, TNF-α, GM-CSF )
AP-1, NF-κB : upregulation of cytokines
Inhibit of ICAM-1, E-selectin
Synthesis of SLPI (Secretory leukocyte protease inhibitor)
: reduce airway inflammation
Inhibit of MIP-1α (Macrophage Inflammatory protein-1)
MCP-1 (Monocyte chemotactic protein-1)
Am J Crit Care Med 1999;160:

13. Corticosteroids in Acute Respiratory Failure
ARDS
PCP
Acute eosinophilic pneumonia
Alveolar hemorrhage syndromes
SLE, Wegener’s granulomatosis, Microscopic polyangiitis
Good pasture’s syndrome, BMT
Acute lupus pneumonitis
BOOP
Radiation pneumonitis
Miliary TB
Pul. Toxicity to2ndary Drugs or toxins - Bleomycin, Amiodarone
Am J Crit Care Med 1999;160:

14. Treatment Corticosteroids : standard
Improve within 48 hrs, but radiologic findings – several wks
Dose : mg/kg/day for 1-3 Mo – tapering for 6 – 12 Mo
Relapse

15. Self limited BOOP Vascular growth factor in BOOP
Apoptotic activity ↑in fibromyxoid lesion of BOOP compared with IPF
Lung 1999;177:

17. PI) progressive dyspnea (o/s: 3 wks) with nonproductive cough
49/M, nonsmoker
PI) progressive dyspnea (o/s: 3 wks) with nonproductive cough
Drug Hx) imipramine and carbamazepine for depression
Chest PA) bilat. Sym. Interstitial and alveolar shadow at lung base
HRCT ) multiple air space consolidation with ground glass opacity
Serology ) negative
TBLB ) lymphocytic infiltration & fibroblastic tissue
filling with alveoli and alveolar duct
이 약때문에 BOOP가 생겼다는 report도 없다.
Respir Med 1997;91:

18. Cont’d Prednisolone 1 mg/kg/day ( 60 mg ) and Drug continued
But, Worsening respiratory failure and progression of X-ray over 3 wks
: FiO2 60% and MV considered
Added Cyclophosphamide 150 mg/day
Day 7 – improve
Over 6 wks – dramatic recovery ( lab, X-ray )
CP and PDL – continued for 6 Mo, PDL tappering by 5 mg every 2 wks
No relapse over 18 Mo
Definitive한 recommendation은 아직 보고된바가 많지 않아 아직 고려할수 없지만, 저자들은 호전을 보고한다.
Respir Med 1997;91: