Exhaled Breath Analysis in the Early Detection of Aspergillosis

NCT02106117 | Completed

• 1 other identifier: AENEAS II
• Study Type: observational
• Target: 120
• Locations: 1 country
• Sites: 2

Brief Summary

Although the clinical outcome in patients with Invasive Aspergillosis (IA) is largely dependent on early initiation of effective treatment with antifungal drugs, diagnosing IA is still a critical problem. Symptoms are non-specific and available diagnostic tools are either invasive or have low sensitivity and specificity. This often results in a diagnostic delay, with patients developing more extensive disease. Furthermore, as long as IA is present, oncological follow-up treatment is not feasible. Inaccuracy in diagnosing IA can cause serious treatment delay and increased mortality. However, an empirical strategy with prophylactic anti-mould therapy is not feasible considering both possible side effects and costs. In order to safely continue the use of a pre-empirical strategy, improved (non-invasive) diagnostic tools are desirable. In a pilot study de Heer et al. showed that it is possible to discriminate between patients with IA and their neutropenic controls by exhaled breath analysis using an electronic nose (eNose). In this study the investigators aim to test whether an eNose could be useful as a diagnostic tool in a prospective setting. The gold standard in exhaled breath analysis is Gas Chromatography - Mass Spectrometry (GC-MS). This technique enables identification of volatile organic compounds (VOCs) in breath of patients. It is possible that there are Aspergillus specific VOCs in the breath of patients with IA. The composition of the lung microbiome seems to be an important factor in both health and disease. It is likely that the microbiome of the lung changes in prolonged neutropenia, therefore possibly creating a niche for molds and yeasts. Comparing the microbiome of patients with prolonged neutropenia who develop IA with those who do not, can learn us more about the pathogenesis of this disease. This knowledge could be used to investigate new treatment options for Invasive Aspergillosis. Hypothesis The investigators hypothesize that airway microbial (viral, bacterial) presence and exhaled molecular profiles as obtained from patients with prolonged neutropenia due to treatment of hematological malignancies, are different between patients who develop IA and patients who do not.

Conditions

Invasive Aspergillosis

Outcome Measures

Primary Outcomes (1)

• molecular profiles in exhaled breath

  Exhaled molecular profiles (by eNose and GC-MS) and the accuracy with which serial analysis of these profiles can discriminate between patients with probable or proven invasive pulmonary aspergillosis and neutropenic controls in terms of sensitivity, specificity and accuracy of the predictive algorithm. Breath will be collected twice weekly during the neutropenic episode, resulting in an average of 5 exhaled breath measurements (eNose as well as GC-MS) per patient. Approximately 150 patients will be included for exhaled breath analysis.

  2 years

Secondary Outcomes (1)

• Microbiome analysis of throat swabs

  3 years

Study Arms (1)

neutropenic patients

Patients receiving treatment for hematological malignancies expected to result in prolonged neutropenia (neutrophil counts \<0.5 x 10 \^9/L for more than seven days).

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

All patients aged 18 or older, admitted at the hematology department of the AMC or UMCU, that will undergo treatment for a hematological malignancy expected to result in prolonged neutropenia (neutrophil counts \<0.5 x 10 \^9/L for more than seven days).

You may qualify if:

• Patients are:
• aged 18 years or older;
• diagnosed with a hematological malignancy;
• treatment is expected to result in prolonged (\>7 days) neutropenia (\<0.5 x 10\^9/L)
• able to give written and dated informed consent prior to any study specific procedures.

You may not qualify if:

• Patients are unable to perform the breathing manoeuvre needed for eNose-analysis of exhaled air

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead
• UMC Utrecht: collaborator

Study Sites (2)

Academic Medical Center

Amsterdam, 1105AZ, Netherlands

Location

University Medical Center Utrecht

Utrecht, 3584CX, Netherlands

Location

Biospecimen

Retention: SAMPLES WITH DNA

Throat Swabs for microbiome analysis Serum samples for Galactomannan detection.

Study Officials

• M.H.J. van Oers, Prof. dr.

  Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

  PRINCIPAL INVESTIGATOR

• M.C. Minnema, MD PhD

  UMC Utrecht

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: prof. dr. M.H.J. van Oers

Study Record Dates

• First Submitted: July 10, 2013
• First Posted: April 8, 2014
• Study Start: December 1, 2012
• Primary Completion: March 1, 2017
• Study Completion: March 1, 2017
• Last Updated: July 3, 2018

Record last verified: 2018-07

Locations

NL (2)