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.