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BMC Infectious Diseases
Published in: BMC Infectious Diseases 1/2018

Open Access 01-12-2018 | Study protocol

Sputum signatures for invasive pulmonary aspergillosis in patients with underlying respiratory diseases (SPARED): study protocol for a prospective diagnostic trial

Authors: Wei Xiao, De-ying Gong, Bing Mao, Xin-miao Du, Lin-Li Cai, Min-yu Wang, Juan-juan Fu

Published in: BMC Infectious Diseases | Issue 1/2018

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Abstract

Background

Invasive pulmonary aspergillosis (IPA) has been increasingly reported in patients with underlying respiratory diseases (URD). Early diagnosis of IPA is crucial for mortality reduction and improved prognosis, yet remains difficult. Existing diagnostic tools for IPA largely rely on the detection of biomarkers based on serum or bronchoalveolar lavage fluid (BALF), both of which have their limitations. The use of sputum sample is non-invasive, and Aspergillus detection is feasible; however, the usefulness of sputum biomarkers for the diagnosis of IPA, especially in patients with URD, has not been systematically studied.

Methods

This is a prospective diagnostic trial. At least 118 participants will be recruited from respiratory wards and intensive care units. IPA is defined according to the EORTC/MSG criteria modified for patients with URD. Induced sputum and blood will be collected, and BALF will be obtained by bronchoscopy. Sputum biomarkers, including galactomannan, Aspergillus DNA, triacetylfusarinine and bis(methylthio)gliotoxin will be determined, and the presence of a JF5 antigen will be examined with a lateral fluid device. The sensitivity, specificity, negative predictive value, positive predictive value and diagnostic odds ratio will be computed for different biomarkers and compared using the McNemar χ2 test. Receiver operating characteristic analyses will be performed, and the cut-off values will be established. Participants will receive follow-up evaluations at 3 months and 6 months after recruitment. The difference in hospital stay and survival will be analysed, and the relationships between the levels of biomarkers and hospital stay and survival will be analysed via regression models.

Discussion

We have developed and verified the feasibility of Aspergillus-related biomarker assays for sputum. The study findings will contribute to a novel look at the diagnostic performance of sputum biomarkers in IPA and provide important insight into the improvement of the early diagnosis of IPA, particularly in patients with URD.

Trial registration

This study has been registered with the Chinese Clinical Trial Registry (ChiCTR-DPD-16009070) on 24th of August 2016.
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Metadata
Title
Sputum signatures for invasive pulmonary aspergillosis in patients with underlying respiratory diseases (SPARED): study protocol for a prospective diagnostic trial
Authors
Wei Xiao
De-ying Gong
Bing Mao
Xin-miao Du
Lin-Li Cai
Min-yu Wang
Juan-juan Fu
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2018
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-018-3180-z

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