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

Abstract

BackgroundInvasive 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.MethodsThis 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.DiscussionWe 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 registrationThis study has been registered with the Chinese Clinical Trial Registry (ChiCTR-DPD-16009070) on 24th of August 2016.

Application of Precise Positioning for Sputum Expectoration in ICU Patients with Pulmonary Infection

“…CRP and PCT are diagnostic indicators of clinical infectious diseases. PCT can reflect the activity of systemic inflammatory reaction, while CRP is an acute inflammatory phase protein that is commonly used in the detection of inflammatory reaction [ 18 ]. It is reported that many patients with PI have increased secretion of pulmonary inflammatory factors, which will lead to substantial inflammation of alveolar cavity, interstitial lung, and airway.…”

Aspergillus fumigatus and Aspergillosis in 2019

“…The search for a circulating molecule that can serve as a disease biomarker is hampered by the following unresolved issues: (i) the low concentration of circulating fungal molecules, which requires detection by use of either a monoclonal antibody with high-affinity and -avidity characteristics (e.g., galactomannan [GM]) or by a process of signal amplification (␤1,3 glucans and DNA), and (ii) an incomplete understanding of the kinetics of release of the various circulating fungal molecules. Biomarkers can be searched in serum urine, BAL fluid, and even sputum (104)(105)(106).…”

Existing tests vs. novel non-invasive assays for detection of invasive aspergillosis in patients with respiratory diseases

“…Induced sputum samples were collected and processed as previously described [ 22 ] for GM, LFD, PCR, TAFC, and bmGT assays. Specimens with a squamous cell percentage >50% or cell viability <40% were deemed unqualified and excluded.…”

“…[ 22 ] The method has a limit of detection of ≤1 ng/mL and a lower limit of quantitation of 1.56 ng/mL for both TAFC and bmGT. [ 22 ]…”