Abstract

Diagnosis of pulmonary aspergillosis (PA), a fungal disease caused by Aspergillus species, is challenging since symptoms are unspecific. The galactomannan (antigen secreted by Aspergillus species) test in bronchoalveolar lavage (BAL) fluid is a valuable diagnostic adjunct test in the diagnosis of PA. However, BAL collection is invasive and may not be suitable to severely ill patients. Sputum is non-invasive, easily collected, and lung specific and may be an alternative to BAL. The aim of this research was to retrospectively evaluate the utility of sputum galactomannan in the diagnosis of pulmonary aspergillosis in patients with chronic respiratory diseases and to estimate the sputum galactomannan cut-off value. We collected data from patients with clinical suspicion of pulmonary aspergillosis who had sputum galactomannan, culture, and Aspergillus IgG tests performed within four weeks. Sputum galactomannan was validated against the clinical diagnosis of aspergillosis, Aspergillus culture, and Aspergillus IgG tests. In total, 218 patients met inclusion criteria. Overall, sputum GM showed satisfactory agreement with clinical diagnosis of aspergillosis, Aspergillus culture, and Aspergillus IgG. When a receiver operating characteristic curve was constructed using Aspergillus culture/IgG and clinical diagnosis, the same cut-off (CO) of 0.71 (AUC: 0.83; CI: 0.69–0.86, p < 0.001) was determined. Against clinical diagnosis, sputum GM gave sensitivity and specificity of 70% and 71%, respectively. Sensitivity of 77% and specificity of 78% were found when sputum GM was evaluated against Aspergillus culture/IgG. In conclusion, this study showed that sputum galactomannan antigen testing has utility in the diagnosis of chronic forms of pulmonary aspergillosis and further prospective validation is indicated.

Highlights

  • Aspergillosis refers to a spectrum of fungal diseases which are caused by Aspergillus species; these include invasive aspergillosis (IA), allergic bronchopulmonary aspergillosis (ABPA), and chronic pulmonary aspergillosis (CPA)

  • ABPA is a hypersensitive reaction to Aspergillus species and is common in patient with asthma and cystic fibrosis [1,2]

  • We report retrospective clinical validation of sputum GM against a chronic lung disease cohort including chronic pulmonary aspergillosis (CPA), allergic bronchopulmonary aspergillosis (ABPA), Aspergillus colonisation, and disease control groups (idiopathic bronchiectasis, cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), asthma, and interstitial lung disease (ILD))

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Summary

Introduction

Aspergillosis refers to a spectrum of fungal diseases which are caused by Aspergillus species; these include invasive aspergillosis (IA), allergic bronchopulmonary aspergillosis (ABPA), and chronic pulmonary aspergillosis (CPA). IA is a fatal and difficult to treat infection that mainly affects immunocompromised and critically ill patients, while CPA manifests primarily in patients with chronic respiratory disease. Laboratory tests include culture and antigen detection from respiratory samples, and detection of serum Aspergillus antigen and antibodies. Detection of the galactomannan antigen (a polysaccharide that is released by Aspergillus species) in bronchoalveolar (BAL) samples is a useful and reliable diagnostic antigen test for the screening and management of aspergillosis [3]. Sputum could be an alternative sample to BAL in galactomannan antigen testing. Sputum is the commonest respiratory sample sent for microbiological investigations, since it is collected and lung specific. Kimura et al evaluated sputum GM in neutropenic patients whereas

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