Élie AZOULAY

Hôpital Saint-Louis, Service de Réanimation Médicale

Université Paris-Diderot, Sorbonne Paris-CitéGroupe de Recherche Respiratoire en Réanimation Onco-Hématologique (GRRR-OH)

Thank you for the invitation

Conflict of interest: research grants and lectures for

Gilead, Pfizer, MSD and Astellas (antifungal agents)

1. A major concern

Oncology patients

Hematology patients

Neutropenia

BMT / SCT

Mortality (mec. ventil.)

5%

10-20%

40%

50%

50-90%

Diagnostic Strategy1. Understand pre-test probabiblity of a given diagnosis (before any investigation)

2. Determine the best investigation adapted to patients/topography of lung involvement/severuty and hypoxemia as well as other OF

3. Keep it open (minded).

DIRECT D. Delay

Severe Sepsis/100 neutropenia days

Neutrophils

0

1

2

3

4

5

6

<100/mm3 100-500/mm3 500-1000/mm3 >1000/mm3

Groupe I

Groupe II

Groupe III

P<0.025

P<0.025

P<0.025

Levine et Coll. N. Engl. J. Med. (1973):

Granulocytopoiesis

in the Bone

Marrow

Bact encapsuléesHypogammaMyélome

Bactéries Neutrophiles Myélome et CA

Bact + virusFonction PNI. Rénale

Toute infection Fonction PN, glycémieStéroïdes

MVTEStimulation T cels et

NK

Thalidomide

HSV, VZVT and dendritic cellsBortezomib

Bactéries?Lenalidomide

Toute infection Altération de toutes cellSurcharge ferrique

……Greffe

Bact encapsuléesHypogammaMyélome

Bactéries Neutrophiles Myélome et CA

Bact + virusFonction PNI. Rénale

Toute infection Fonction PN, glycémieStéroïdes

MVTEStimulation T cels et

NK

Thalidomide

HSV, VZVT and dendritic cellsBortezomib

Bactéries?Lenalidomide

Toute infection Altération de toutes cellSurcharge ferrique

……Greffe

What is the Pulmonary Interstitium?

http://www.bioscience.org/1997/v2/d/longwort/2.htm

Portion of the lung between epithelial

and endothelial membranes

Secondary pulmonary lobular anatomy

Ground Glass

Consolidation

Ill defined Nodules

Linear Opacities

Cavitation

Effusion

Bronchiolite à

Haemophilus

Bronchiolite à

PIV 3

Lymphome

T agressif

Hemoptysis in a AML patient: The Halo Sign makes you think about IFI

Shibuya K, et al J Infect Chemother 2004; 10: 138–45

These four patients share 5 characteristics

- Lymphoproliferative disorders

- Long term steroids + fludarabin

- Inadequate PCP prophylaxis

- Subactute ARF, no other organ dysfunction

- These CT scan profiles

CMV

VRS

API

HSV

Invasive or noninvasive ?

Invasive: Biopsy

Semi-invasive: FO-BAL

Non invasive: Blood cultures Sputa Induced sputa NPA Antigenes Echography HRCT

Impact of FOB+BAL

Invasive Fusarium infection

Nucci et al. In Pulmonary Involvement in

Patients with Hematological malignancies. Springer 2011. Editor, E Azoulay

Geotrichum bacteremia

Pulmonary invasive aspergillosis

MMA was far more sensitive than immunofluorescence for

respiratory virus detection.

Patients with RVs detected in the respiratory tract had the

same clinical characteristics and outcomes as other patients.

A true RSV pneumonia

577 BMT (172 Allo),

RT PCR CMV + = 30%

CMV disease = 8 patients (1%)

4/8 negative PCR

CMV pneumonia

Proposed Pneumocystis Life Cycle.

The MiniMax study, Azoulay et al. 2010

Etiologies MAXI

N=113

MINI

N=106

Bacteria 47 (41%) 39 (37%)

Viruses 7 (6%) 19 (18%)

Fongi 14 (12%) 9 (8.5%)

Pneumocystis 9 (8%) 10 (9.4%)

Malignant infiltration 10 (9%) 6 (6%)

Cardiac Pulm. Edem 7 (6%) 3 (3%)

More than one diagnosis 9 (8%) 9 (8.4%)

Etiologies MAXI

N=113

MINI

N=106

Bacteria 47 (41%) 39 (37%)

Viruses 7 (6%) 19 (18%)

Fongi 14 (12%) 9 (8.5%)

Pneumocystis 9 (8%) 10 (9.4%)

Malignant infiltration 10 (9%) 6 (6%)

Cardiac Pulm. Edem 7 (6%) 3 (3%)

More than one diagnosis 9 (8%) 9 (8.4%)

Diagnoses

CPO: 10

Fungi: 23

Aspergilus: 18

Virus: 26

Malignancy: 16

Pneumocystis: 19

Bacteria: 86

Diagnosis made by NIT

10 (100%)

22 (95.6%)

17 (94%)

24 (92.3%)

13 (81%)

15 (79%)

57 (66.3%)

Need for mechanical ventilation

P=0.62

P=0.54D28 Survival

Thank you for your attention !!!