Validation of Serum Galactomannan for Invasive Pulmonary Aspergillosis Outcome Prediction

Abstract Objectives The galactomannan enzyme immunoassay optical density index (GMI) is widely used in the diagnosis of invasive pulmonary aspergillosis (IPA). However, its clinical utility as a prognostic factor has not yet been fully validated. Methods Patients with proven and probable invasive pulmonary aspergillosis (IPA) who had a serum GMI (sGMI) result between 2013 and 2020 at a tertiary referral center in Taiwan (NTUH-IPA cohort) were identified. A systematic review was conducted to identify studies investigating different sGMI static or kinetic markers for IPA prognosis, and then validated these markers using the NTUH-IPA cohort in a retrospective cohort study design. A multivariable logistic regression model was used to assess the prognostic ability of various sGMI markers for 30-day mortality, 90-day mortality, and in-hospital mortality, Results Our study included 268 IPA patients (14 with proven IPA and 254 with probable IPA) with a 30-day, 90-day, and in-hospital mortality rates of 38.1%, 60.1%, and 61.6% respectively. Our systematic review extracted 28 studies with 12 different sGMI markers were included for validation. In our multivariable logistic regression, a baseline sGMI ≥2 at IPA diagnosis was independently 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 of 2.99, 95% CI 1.62─5.51, p<0.001). A day 7 sGMI ≥1.5 was also independently 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. Conclusions A baseline sGMI ≥2 and day 7 sGMI ≥1.5 at diagnosis can be useful predictive markers for mortality in IPA patients, whereas kinetic markers cannot.