Validation of serum galactomannan antigen assay for invasive pulmonary aspergillosis mortality outcome prediction.

UNLABELLED: The galactomannan antigen assay is crucial in diagnosing invasive pulmonary aspergillosis (IPA). However, its clinical utility as a prognostic factor has not yet been fully validated. Patients with proven or probable invasive pulmonary aspergillosis (IPA) who had a serum galactomannan enzyme immunoassay optical density index (sGMI) (Platelia Aspergillus Antigen immunoassay, Bio-Rad, CA, USA) result between 2013 and 2020 at a tertiary referral center were identified. We conducted a systematic review and identified studies using static or kinetic sGMI markers for IPA prognosis. A multivariable logistic regression model was used to validate these sGMI markers separately for 30-day, 90-day, and in-hospital mortality. Our study included 268 IPA patients (14 proven IPA, 254 probable IPA). The 30-day, 90-day, and in-hospital mortality were 38.1%, 60.1%, and 61.6% respectively. A total of 12 different sGMI predictive markers were included for validation. In our multivariable logistic regression, baseline sGMI ≥2 at IPA diagnosis was associated with 30-day mortality (adjusted odds ratio [aOR] 2.06; 95% confidence interval [CI], 1.16-3.66; P = 0.013), 90-day mortality (aOR 2.33; 95% CI, 1.29-4.21; P = 0.005), and in-hospital mortality (aOR 2.99; 95% CI, 1.62-5.51; P < 0.001). A day 7 sGMI ≥1.5 was also associated with 30-day mortality (aOR 2.34; 95% CI, 1.09-5.02; P = 0.029), 90-day mortality (aOR 2.24; 95% CI, 1.10-4.58; P = 0.027), and in-hospital mortality (aOR 2.30; 95% CI, 1.12-4.71; P = 0.023). No kinetic sGMI marker reached statistical significance for predicting all three outcomes. A baseline sGMI ≥2 at diagnosis can be used as a prognostic marker for IPA mortality outcomes. A day 7 sGMI ≥1.5 during treatment serves as an additional prognostic marker.

IMPORTANCE

Serum galactomannan enzyme immunoassay (sGMI) is a well-established, non-invasive diagnostic tool for invasive aspergillosis and has been incorporated into numerous clinical guidelines. Despite its diagnostic utility, the prognostic value of sGMI in IA patients was not well validated due to limitations in previous studies, including small sample sizes and methodological issues. This study systematically reviewed and validated existing sGMI prognostic markers in a large Taiwanese invasive pulmonary aspergillosis cohort. A sGMI ≥2 at baseline and a day 7 sGMI ≥1.5 were significant predictors for 30-day, 90-day, and in-hospital mortality. We propose that these markers can be used at different stages of IPA treatment to predict patient outcomes. Our research is the first to validate both static and kinetic sGMI markers in a large IPA cohort. The simplicity and practicality of using a baseline sGMI ≥2 at diagnosis for mortality prediction offer significant advantages and support medical decisions.