RE39 YO died due to SOBRE39 YO died due to SOB53 YO AA male with Chest 53 YO AA male with Chest

painpain

BMHGT BMHGT

05/27/0905/27/09

53 YO with Chest Pain

Discussants :Discussants :• Dr.Bart WilliamsDr.Bart Williams• Dr.Butler Dr.Butler

39 YO AAF with SOB

39 has DM II ; HTN ; Hx of CHF,Anemia39 has DM II ; HTN ; Hx of CHF,Anemia CKD -3 with heavy proteinuria (5/08)CKD -3 with heavy proteinuria (5/08) ANA panel negative C3 C4 NORMAL ANA panel negative C3 C4 NORMAL RENAL USD Echogenic kidneys RENAL USD Echogenic kidneys Chronic Shortness of breathChronic Shortness of breath Chronic pyuria Chronic pyuria Chronic LE edema on diuretics Chronic LE edema on diuretics

Chronic Shortness of Breath

History of CHF: echo normal 2/09History of CHF: echo normal 2/09Lung infiltrates : Transbronchial Biopsy Lung infiltrates : Transbronchial Biopsy

BOOP BOOP

Started on Cytoxan PLUS STEROIDS IN 5/08Started on Cytoxan PLUS STEROIDS IN 5/08

Admitted 5/1/09 with Dx CHF Echo normal Diuretics stopped Pulmonary consult obtained

Events of 05/2009Events 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

BOOPBOOP

First described in 1901First described in 1901

More cases reported by Epler in 1985More cases reported by Epler in 1985

Age incidence 4Age incidence 4thth-7-7thth decades decades

Incidence 6-7/100,000 admissionsIncidence 6-7/100,000 admissions Not related to smokingNot related to smoking

BOOPBOOP

aka.. cryptogenic organizing pneumoniaaka.. cryptogenic organizing pneumonia

Pathological entityPathological entity

Excessive proliferation of granulation Excessive proliferation of granulation tissue within small airways and alveolar tissue within small airways and alveolar ducts, associated chronic inflammation ofducts, associated chronic inflammation of surrounding airwayssurrounding airways

BOOP BOOP ClassificationClassification

IdiopathicIdiopathic Post infection- mycoplasma, Post infection- mycoplasma,

legionella, CMV, adneovirus, legionella, CMV, adneovirus, influenza, chlamydia, PCP, influenza, chlamydia, PCP, crytococcuscrytococcus

Drug induced-amiodarone, Drug induced-amiodarone, bleomycin, gold, dilantin, bleomycin, gold, dilantin, cocaine, carbamezapinecocaine, carbamezapine

Rheumatologic-SLE, RA, DM-Rheumatologic-SLE, RA, DM-PM, Sjogren’s, AS, Behcet PM, Sjogren’s, AS, Behcet syndrome, PMRsyndrome, PMR

Immunologic disorders- Immunologic disorders- common variable common variable immunodeficiency, essential immunodeficiency, essential mixed cryglobulinemia, GVHDmixed cryglobulinemia, GVHD

ClassificationClassification Focal noduleFocal nodule Bone marrow transplantationBone marrow transplantation Lung transplantationLung transplantation Miscellaneous- HIV, XRT, Miscellaneous- HIV, XRT,

myelodysplastic syndrome, myelodysplastic syndrome, lymphoma, chronic thyroiditis, lymphoma, chronic thyroiditis, alcoholic cirrhosis, IBD, alcoholic cirrhosis, IBD, tryptophan, textile dye printing, tryptophan, textile dye printing, seasonal syndrome with seasonal syndrome with cholestasischolestasis

KEY FEATURESKEY FEATURES

Intraluminal organizing fibrosis in distal Intraluminal organizing fibrosis in distal airspacesairspaces

Patchy distributionPatchy distribution Preserved lung architecturePreserved lung architecture Uniform temporal appearanceUniform temporal appearance Mild interstitial chronic inflammationMild interstitial chronic inflammation Fibrinous exudatesFibrinous exudates Accumulation of foamy MACS in alveoliAccumulation of foamy MACS in alveoli Connective tissue polypsConnective tissue polyps

KEY NEGATIVE FINDINGSKEY NEGATIVE FINDINGS

Lack of interstitial fibrosisLack of interstitial fibrosis Absence of granulomasAbsence of granulomas Lack of neutrophils/abscessesLack of neutrophils/abscesses Absence of necrosisAbsence of necrosis Lack of hyaline membranes Lack of hyaline membranes Lack of prominent eosinophil infiltrationLack of prominent eosinophil infiltration Lack of vasculitisLack of vasculitis

BOOP vs Bronchiolitis ObliteransBOOP vs Bronchiolitis Obliterans

BOOPBOOP Alveolar ductsAlveolar ducts interstitial disorderinterstitial disorder late crackleslate crackles patchy infiltrates on CXRpatchy infiltrates on CXR Reduced TLC and DLCOReduced TLC and DLCO Lymphocytes in BALLymphocytes in BAL Good response to RXGood response to RX Good prognosisGood prognosis

BOBO Distal bronchiolesDistal bronchioles Airflow disorderAirflow disorder Early cracklesEarly crackles Normal CXRNormal CXR Reduced FEV1, FEV1/FVCReduced FEV1, FEV1/FVC Neutrophils in BALNeutrophils in BAL Poor response to RxPoor response to Rx Poor prognosisPoor prognosis

RADIOGRAPHIC FINDINGSRADIOGRAPHIC FINDINGS

CXR- bilateral, diffuse, patch, peripheral alveolar CXR- bilateral, diffuse, patch, peripheral alveolar opacities opacities

Reticular interstitial pattern in minority of casesReticular interstitial pattern in minority of cases Ground glass opacities in > 2/3 of casesGround glass opacities in > 2/3 of cases Pleural effusions , cavities, pleural thickening and honeycombing Pleural effusions , cavities, pleural thickening and honeycombing

(RARE)(RARE) All lung zones may be affectedAll lung zones may be affected Severity correlates with the extent of histological involvement of Severity correlates with the extent of histological involvement of

respiratory and alveolar ductsrespiratory and alveolar ducts

HRCT- patchy air space consolidation in peripheral and HRCT- patchy air space consolidation in peripheral and lower lung zones, ground glass opacities, small nodular lower lung zones, ground glass opacities, small nodular opacities, bronchial wall thickening and dilatationopacities, bronchial wall thickening and dilatation

INVESTIGATIONSINVESTIGATIONS

BAL- higher percentage of lymphocytes, BAL- higher percentage of lymphocytes, neutrophils, eosinophils, low CD4/CD8neutrophils, eosinophils, low CD4/CD8

““mixed pattern” of cellularity mixed pattern” of cellularity Video assisted thorascopic lung biopsy…GOLD Video assisted thorascopic lung biopsy…GOLD

STANDARDSTANDARD Transbronchial biopsy not ideal as may miss Transbronchial biopsy not ideal as may miss

representative lesion, and does not adequately representative lesion, and does not adequately allow exclusion of associated lesionsallow exclusion of associated lesions

INVESTIGATIONSINVESTIGATIONS

Routine labs non-specificRoutine labs non-specific Leucocytosis-50%Leucocytosis-50% Increased ESR -100mm/hr or >Increased ESR -100mm/hr or > + CRP+ CRP Auto Ab (-) or in very low titreAuto Ab (-) or in very low titre PFT’s- decreased VC with normal flow PFT’s- decreased VC with normal flow

rates...mild to moderate restrictive defect, rates...mild to moderate restrictive defect, decr. DLCOdecr. DLCO

TREATMENTTREATMENT

Spontaneous improvement is rareSpontaneous improvement is rare

Prednisone @ 1mg/kg/d for 1-3 mths, then Prednisone @ 1mg/kg/d for 1-3 mths, then 40mg/d x 3mths, then 10-20mg/d or every 40mg/d x 3mths, then 10-20mg/d or every other day x 1 yearother day x 1 year

Methylprednisone 125 to 250mg Q6hx 3-5 Methylprednisone 125 to 250mg Q6hx 3-5 daysdays

TREATMENTTREATMENT

If deterioration occurs despite steroids or if If deterioration occurs despite steroids or if not toleratednot tolerated cytotoxic agent…… cytotoxic agent…… cyclophosphamide 2mg/kg/d as a single cyclophosphamide 2mg/kg/d as a single dose (not to exceed 150 mg/d)dose (not to exceed 150 mg/d)

Erythromycin, inhaled triamcinolone have Erythromycin, inhaled triamcinolone have been used anecdotallybeen used anecdotally

TREATMENTTREATMENT

Relapses may occur when steroids Relapses may occur when steroids withdrawnwithdrawn

Monitor clinically with CXR, PFTsMonitor clinically with CXR, PFTs Normalization of CXR and clinical Normalization of CXR and clinical

improvement in 2/3 of patients over weeks to improvement in 2/3 of patients over weeks to monthsmonths

If > 3 recurrences may require continuous If > 3 recurrences may require continuous prednisone, cyclophosphamide or bothprednisone, cyclophosphamide or both

OUTCOMESOUTCOMES

1/3 pts have persistent disease1/3 pts have persistent disease Total recovery 65 to 85% of patientsTotal recovery 65 to 85% of patients Mortality 5%Mortality 5%