RE39 YO died due to SOB 53 YO AA male with Chest pain RE39 YO died due to SOB 53 YO AA male with Chest pain BMHGT05/27/09

53 YO with Chest Pain  Discussants : Dr.Bart WilliamsDr.Bart Williams Dr.ButlerDr.Butler

39 YO AAF with SOB  39 has DM II ; HTN ; Hx of CHF,Anemia  CKD -3 with heavy proteinuria (5/08)  ANA panel negative C3 C4 NORMAL  RENAL USD Echogenic kidneys  Chronic Shortness of breath  Chronic pyuria  Chronic LE edema on diuretics

Chronic Shortness of Breath History of CHF: echo normal 2/09 Lung infiltrates : Transbronchial Biopsy BOOP Started on Cytoxan PLUS STEROIDS IN 5/08

  Admitted 5/1/09 with Dx CHF   Echo normal   Diuretics stopped   Pulmonary consult obtained Events of 05/2009

Test results   ESR >120   CRP 6.3; >10   CXR/CT Chest bilateral lung infiltrates   Echo Normal; RA –ive ; ANA –ive   MRI brain normal   ANCA –ive   Got better with steroids and Nebs and cytoxan

Course of Events on 5/10/09   Came to ER with SOB   Treated with steroids   Went home   Died following week

BOOP  First described in 1901  More cases reported by Epler in 1985  Age incidence 4 th -7 th decades  Incidence 6-7/100,000 admissions  Not related to smoking

BOOP  aka.. cryptogenic organizing pneumonia  Pathological entity  Excessive proliferation of granulation tissue within small airways and alveolar ducts, associated chronic inflammation of surrounding airways

BOOP  Classification Idiopathic Idiopathic Post infection- mycoplasma, legionella, CMV, adneovirus, influenza, chlamydia, PCP, crytococcus Post infection- mycoplasma, legionella, CMV, adneovirus, influenza, chlamydia, PCP, crytococcus Drug induced-amiodarone, bleomycin, gold, dilantin, cocaine, carbamezapine Drug induced-amiodarone, bleomycin, gold, dilantin, cocaine, carbamezapine Rheumatologic-SLE, RA, DM- PM, Sjogren’s, AS, Behcet syndrome, PMR Rheumatologic-SLE, RA, DM- PM, Sjogren’s, AS, Behcet syndrome, PMR Immunologic disorders- common variable immunodeficiency, essential mixed cryglobulinemia, GVHD Immunologic disorders- common variable immunodeficiency, essential mixed cryglobulinemia, GVHD  Classification Focal nodule Bone marrow transplantation Lung transplantation Miscellaneous- HIV, XRT, myelodysplastic syndrome, lymphoma, chronic thyroiditis, alcoholic cirrhosis, IBD, tryptophan, textile dye printing, seasonal syndrome with cholestasis

KEY FEATURES  Intraluminal organizing fibrosis in distal airspaces  Patchy distribution  Preserved lung architecture  Uniform temporal appearance  Mild interstitial chronic inflammation  Fibrinous exudates  Accumulation of foamy MACS in alveoli  Connective tissue polyps

KEY NEGATIVE FINDINGS  Lack of interstitial fibrosis  Absence of granulomas  Lack of neutrophils/abscesses  Absence of necrosis  Lack of hyaline membranes  Lack of prominent eosinophil infiltration  Lack of vasculitis

BOOP vs Bronchiolitis Obliterans  BOOP Alveolar ducts Alveolar ducts interstitial disorder interstitial disorder late crackles late crackles patchy infiltrates on CXR patchy infiltrates on CXR Reduced TLC and DLCO Reduced TLC and DLCO Lymphocytes in BAL Lymphocytes in BAL Good response to RX Good response to RX Good prognosis Good prognosis  BO Distal bronchioles Airflow disorder Early crackles Normal CXR Reduced FEV1, FEV1/FVC Neutrophils in BAL Poor response to Rx Poor prognosis

RADIOGRAPHIC FINDINGS  CXR- bilateral, diffuse, patch, peripheral alveolar opacities Reticular interstitial pattern in minority of cases Reticular interstitial pattern in minority of cases Ground glass opacities in > 2/3 of cases Ground glass opacities in > 2/3 of cases Pleural effusions, cavities, pleural thickening and honeycombing (RARE) Pleural effusions, cavities, pleural thickening and honeycombing (RARE) All lung zones may be affected All lung zones may be affected Severity correlates with the extent of histological involvement of respiratory and alveolar ducts Severity correlates with the extent of histological involvement of respiratory and alveolar ducts  HRCT- patchy air space consolidation in peripheral and lower lung zones, ground glass opacities, small nodular opacities, bronchial wall thickening and dilatation

INVESTIGATIONS  BAL- higher percentage of lymphocytes, neutrophils, eosinophils, low CD4/CD8  “mixed pattern” of cellularity  Video assisted thorascopic lung biopsy…GOLD STANDARD  Transbronchial biopsy not ideal as may miss representative lesion, and does not adequately allow exclusion of associated lesions

INVESTIGATIONS  Routine labs non-specific  Leucocytosis-50%  Increased ESR -100mm/hr or >  + CRP  Auto Ab (-) or in very low titre  PFT’s- decreased VC with normal flow rates...mild to moderate restrictive defect, decr. DLCO

TREATMENT  Spontaneous improvement is rare  1mg/kg/d for 1-3 mths, then 40mg/d x 3mths, then 10-20mg/d or every other day x 1 year  Methylprednisone 125 to 250mg Q6hx 3-5 days

TREATMENT  If deterioration occurs despite steroids or if not tolerated  cytotoxic agent…… cyclophosphamide 2mg/kg/d as a single dose (not to exceed 150 mg/d)  Erythromycin, inhaled triamcinolone have been used anecdotally

TREATMENT  Relapses may occur when steroids withdrawn  Monitor clinically with CXR, PFTs  Normalization of CXR and clinical improvement in 2/3 of patients over weeks to months  If > 3 recurrences may require continuous prednisone, cyclophosphamide or both

OUTCOMES  1/3 pts have persistent disease  Total recovery 65 to 85% of patients  Mortality 5%