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

• Published in: BMC infectious diseases 2018-06, Vol.18 (1), p.271-12, Article 271
• Main Authors: Xiao, Wei, Gong, De-Ying, Mao, Bing, Du, Xin-Miao, Cai, Lin-Li, Wang, Min-Yu, Fu, Juan-Juan
• Format: Article
• Language: English
• Subjects: Accuracy; Alveoli; Aspergillosis; Aspergillus; Bioindicators; Biomarker; Biomarkers; Biomarkers - analysis; Bronchoalveolar Lavage Fluid; Bronchoscopy; Bronchus; Causes of; Clinical medicine; Clinical Protocols; Cystic fibrosis; Deoxyribonucleic acid; Diagnosis; Diagnostic software; Diagnostic systems; DNA; Early Diagnosis; Feasibility studies; Fluids; Fungal infections; Galactomannan; Galactose - analogs & derivatives; Gliotoxin; Hematology; Hospitals; Humans; Infectious diseases; Intensive Care Units; Invasive pulmonary aspergillosis; Invasive Pulmonary Aspergillosis - complications; Invasive Pulmonary Aspergillosis - diagnosis; Lateral flow device; Length of Stay; Literature reviews; Mannans - analysis; Metabolites; Mortality; Neutropenia; Patients; Physiological aspects; Polymerase chain reaction; Prognosis; Prospective Studies; Pulmonary aspergillosis; Regression analysis; Regression models; Respiration Disorders - complications; Respiration Disorders - microbiology; Respiratory diseases; ROC Curve; Sensitivity and Specificity; Sputum; Sputum - microbiology; Studies; Study Protocol; Survival; Survival Analysis; Systematic review; Underlying respiratory diseases
• ISSN: 1471-2334; 1471-2334
• DOI: 10.1186/s12879-018-3180-z

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. 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 χ 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. 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. This study has been registered with the Chinese Clinical Trial Registry ( ChiCTR-DPD-16009070 ) on 24th of August 2016.