PULMONARY GRAND ROUNDS
Eduardo SantiagoMarch 08,2012
HPI
• 65 year old woman, no PMH.• Subjective fever, chills, malaise and mild cough
1 month ago.• Progressive shortness of breath.• Dry cough.
HPI
• Seen by her PCP: Diagnosis of CAP.• Azithromycin for 1 week.• Started on oxygen.
• PMH: Unremarkable.• SH: ½ pack per day for 20 years. • Denies any occupational or recreational
exposure. • Denies any prior use of medications.• ROS: Unremarkable.
PE
• HR 70, BP 126/80, RR 14, T 100, O2 SAT 90% on 2 LPM Weight:172.92
• CHEST EXAM: Decreased breath sound at both bases. Diffuse inspiratory crackles at both lower lungs.
• CARDIAC EXAM: RRR, S1 and S2 within normal limits. No S3 or S4.
• EXTREMITIES: No edema. No clubbing or cyanosis.• SKIN: No skin rash.
WBC 9.8
HB 14.4
HT 44
Platelets 366
ESR 44
ANA None detected
RF <7
Jo-1 IgG 0
ANCA <1/20
Scl 70 0
• FVC: 1.36L (46%)• FEV1: 0.91 (40%)• FEV1/FVC: 87%• DLCO:5.89 (25%)
BAL
• Macrophages :46%• Lymphocytes:7%• Neutrophils:43%• Bronchial lining cells:4%
Pathology
• Patchy organizing pneumonia, fibroblastic intra alveolar infiltrate, scattered lymphocytes within the interstitium.
• No significant acute inflammation.• No granulation tissue.• No evidence of vasculitis.
Date FEV1 FVC FEV1/FVC DLCO
Aug 11 0.91 (40%) 1.36L (46%) 87% 5.89 (25%)
Nov 11 1.35(60%) 1.64 (56%) 82% 9.46(40%)
COP
COP
• J.M Charcot 1877–1878.• Milne: Type of pneumonia where the usual
process of resolution has failed and organization of the inflammatory exudate in the air alveoli of the lung by fibrous tissue has resulted.
COP
• Organizing pneumonia: Endobronchial connective tissue masses composed of myxoid fibroblastic tissue resembling granulation tissue.
• Central cluster of mononuclear inflammatory cells.
• Chronic inflammation in the walls of the surrounding alveoli.
• Preserve lung architecture.
COP
• Organizing pneumonia pathologic pattern is a nonspecific reaction that results from alveolar damage with intra-alveolar leakage of plasma protein with alveolar organization.
COP
• Clinical, radiological and pathological diagnosis.
• Pattern of organizing pneumonia must be prominent.
Pathogenesis
• The intra alveolar fibrosis is its usual dramatic reversibility with corticosteroids and not associated with progressive irreversible fibrosis .
Pathogenesis/ First Stage
• Alveolar epithelial injury with necrosis and sloughing of pneumocytes resulting in the denudation of the epithelial basal lamina.
• The endothelial cells are only mildly damaged.• Infiltration of the alveolar interstitium by
inflammatory cells: lymphocytes, neutrophils and eosinophils.
Pathogenesis/ Second Satge
• Intra alveolar stage: formation of fibrinoid inflammatory cell clusters with prominent bands of fibrin and inflammatory cells.
• Formation of fibro inflammatory buds, fibrin is fragmented and reduction of inflammatory cells.
• Migration of fibroblast from the interstitium and proliferation.
Pathogenesis/Second Stage
• Myofibroblast.• Proliferation of the alveolar cells and re
epithelialization of the basal lamina.
Pathogenesis/Third stage
• Inflammatory cells have disappeared.• There is no fibrin within the alveolar lumen.• Concentric rings of fibroblasts alternate with
layers of connective tissue.
Connective Matrix
• Loose connective matrix with high type III collagen content which is more susceptible to degradation and reversal of fibrosis.
Angiogenesis
• Prominent capillarization of the intra alveolar buds.
• Vascular endothelial growth factor and basic fibroblast growth factor.
• Angiogenesis could contribute to the reversal of buds in OP.
Pathogenesis
• The opposing mechanisms of reversibility of fibrosis in COP and ongoing fibrosis in UIP are not yet established.
Radiology
Radiology
• Multiple alveolar opacities: typical COP.• Solitary opacity: focal COP.• Infiltrative opacities: infiltrative COP.
Diagnosis
• Diagnosis of organizing pneumonia.• Exclusion of any possible cause.• Histopathology: Buds of granulation tissue
consisting of fibroblasts myofibroblasts embedded in connective tissue.
Diagnosis
• Definite: compatible clinicoradiologic manifestations and typical pathologic pattern on a pulmonary biopsy of sufficient size.
• Probable: findings of organizing pneumonia on transbronchial biopsy and a typical clinicoradiologic presentation without pathologic confirmation.
• Possible: typical clinicoradiologic presentation without biopsy confirmation.
Treatment
• Rapid clinical improvement and clearing of the opacities.
• The precise dose and duration of treatment have not been established.
• Prednisone 0.75–1.5 mg/kg/day.• 0.75 mg/kg/day during 4 weeks, followed by 0.5
mg/kg for 4 weeks, then 20 mg for 4 weeks, 10 mg for 6 weeks, and then 5mg for 6 weeks.
Treatment
• Complete clinical and physiologic recovery in 65 % of patients.
Gary Epler. Bronchiolitis Obliterans Organizing Pneumonia. NEJM; 1985:152-8
Treatment
• Predictors of relapse: delayed treatment and mildly increased gammaglutamyltransferase and alkaline phosphatase levels.
Treatment
• Severe cases: prednisolone 2mg/kg/day for the first 3-5 days.
Treatment• Spontaneous improvement.• Macrolides:• Patients with minimal symptoms and/or
minimal physiologic impairment.• Adjuvant therapy in patients receiving
steroids.• Patients who cannot tolerate steroids.• 3 to 6 months or longer.
Diane E. Stover.Macrolides: A Treatment Alternative for Bronchiolitis ObliteransOrganizing Pneumonia?. CHEST 2005; 128:3611–3617
Reference• American Thoracic Society/European Respiratory Society.
Classification of the idiopathic interstitial pneumonias: international multidisciplinary consensus. American Thoracic Society/European Respiratory Society. Am J Respir Crit Care Med 2002;165: 277–304.
• J.-F. Cordier. Cryptogenic organizing pneumonia. Clinics in Chest Medicine 2004;25 : 727– 738.
• J.-F. Cordier. Organising pneumonia. Thorax 2000;55:318–328.• J.-F. Cordier. Cryptogenic organizing pneumonia. Eur Respir J
2006; 28: 422–446.
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