Assessment of Volatile Organic Compounds (VOC) for the Diagnosis of Invasive Aspergillosis (IA) in Lung Transplant Recipients

Prospective observational pilot study to evaluate the utility of breath VOCs to detect invasive aspergillosis in lung transplant recipients that are suspected of invasive fungal disease (IFD).

Invasive aspergillosis (IA) remains a major cause of morbidity and mortality in immunosuppressed patients. The diagnosis of IA is challenging due to lack of sensitive and specific clinical and radiological signs, and tissue biopsy is often precluded in many patients. Culture and microscopy of respiratory tract samples are relatively insensitive diagnostic tests. Early detection of IA can lead to specific therapeutic strategies and improved patient outcomes. Breath is a rich and complex sampling medium containing both volatile organic compounds (VOCs) and respiratory droplets carrying non-volatiles, proteins, lipids, viruses and even bacteria. The major advantage of exhaled breath analysis is non-invasiveness, with existing sampling methods already readily available.

The diagnostic or prognostic value of exhaled breath analysis has been evaluated in many respiratory diseases, including asthma, Chronic Obstructive Pulmonary Disease, idiopathic pulmonary fibrosis, as well as in some lung infections such as bacterial pneumonia. In the particular field of aspergillosis diagnosis, using a chromatographic-mass spectrometry analysis of exhaled breath in immunocompromised hosts (organ transplantation, hematological malignancies or HSCT), researchers have been able to identify an exhaled breath metabolic signature (made of β-trans-bergamotene, α-trans-bergamotene, a β-vatirenene-like sesquiterpene, and trans-geranylacetone) that potentially allows the discrimination of probable or proven aspergillosis from other lung infections, with high levels of sensitivity and specificity. Exhaled breath therefore appears as a promising field for the improvement of IA diagnosis, and more broadly of respiratory infections. Volatile organic compound (VOC) detection via thermal desorption/gas chromatography-mass spectrometry has emerged as a promising tool for early diagnosis of IA, however the sample sizes have been limited. As such, the proposed pilot study aims to identify potential VOC biomarkers for both IA and Aspergillus colonization and assess the feasibility of VOCs on breath for the diagnosis of IA in lung transplant recipients.

Eligibility Criteria:
Inclusion Criteria: Patients with the following criteria will be included in the study:

1. Over the age of 18 years
2. Recipient of single/double lung transplant
3. Willingness to participate in the study
4. Suspected of invasive fungal disease or undergo surveillance appointments
5. Capable of providing sample
6. Capable of providing consent

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Exclusion Criteria: Patients with the following criteria will be excluded from the study:

1. On mechanical ventilation, oxygen supplementation including nasal cannula; simple, fixed, or non-rebreathing face mask at presentation.
2. Admitted to the intensive care unit at presentation.
3. The subject is currently diagnosed with a confirmed bacterial or viral respiratory infection or has received a diagnosis of a respiratory viral or bacterial infection within the last 4 weeks.
4. Previous diagnosis of Cystic Fibrosis
5. Use of antifungals in previous 4 weeks
6. Has been previously diagnosed with respiratory fungal infection other than aspergillus within the last 3 months upon presentation.
7. Declines participation in the study.
8. On mold antifungal for \>72 hours.

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