Transcript Cryptogenic organizing pneumonia

PULMONARY GRAND ROUNDS
Eduardo Santiago
March 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 Obliterans
Organizing 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.