The AENEAS study: the Application of an Electronic Nose in the Early detection of ASpergillosis.

Introduction

There is a need for new diagnostic methods to facilitate earlier diagnosis and treatment of invasive pulmonary mycosis (IPM) during prolonged chemotherapy-induced neutropenia (PCIN). Exhaled breath analysis could fulfill this need.



Objective

Before studying serial samples during neutropenia, we will first establish the accuracy of exhaled breath analysis to discriminate patients with invasive pulmonary aspergillosis (IPA), the most frequent cause of IPM, from neutropenic controls with fever.



Study design

Single center study with a prospective cohort design. Patients will be sampled once.



Population

Patients that will undergo treatment for a hematological malignancy expected to result in grade 4 neutropenia for more than 7 days (PCIN).

Cases: Patients with probable or proven IPA and a positive galactomannan assay on bronchoalveolar lavage (BAL).

Controls: Patients with fever but no possible, probable or proven IPM and no positive galactomannan assay performed on serum and BAL.



Diagnostic intervention

Exhaled breath analysis using an electronic nose (eNose) and gas chromatography-mass spectrometry
(GC-MS). GC-MS will be used to unravel the molecular mechanisms by which the eNose detects aspergillosis.



Primary endpoint

The accuracy with which an eNose can discriminate between cases and controls as measured by the
cross-validated accuracy of the predictive algorithm. Raw data are analysed by discriminant analysis on principal component reduction after which the results will be validated using the “leave-one-out” method.



Sample size

Our aim is to include 125 neutropenic episodes in 80 patients resulting in 10 cases and 10 controls.

Time line

Accrual will take an estimated 18 months, data analysis and writing the publication 6 months. During the accrual we will in parallel perform additional research in vitro and in CF patients for our GC-MS analyses.



Economic evaluation

A limited economic evaluation will be performed by modelling the diagnosis of IPA using a decision tree. The cost and accuracy of various combinations of diagnostic procedures will be determined. We will establish whether the addition of the eNose to the non-invasive work-up of suspected IPA obviates BAL without a loss in health.

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Exhaled breath analysis using an electronic nose and gas chromatography-mass spectometry.