Pentraxin-3 as a novel prognostic biomarker in non-neutropenic invasive pulmonary aspergillosis patients

The incidence of invasive pulmonary aspergillosis (IPA) in non-neutropenic patients is increasing. This study aimed to evaluate the clinical outcomes and risk factors for mortality in non-neutropenic IPA patients. We conducted a prospective, multicenter study from August 2020 to February 2024, enrolling 565 patients with suspected IPA. The study cohort comprised 195 IPA (non-neutropenic) cases and 370 non-IPA cases. Peripheral blood and bronchoalveolar lavage fluid (BALF) specimens were collected to measure pentraxin-3 (PTX3) levels. Additionally, demographic data, clinical characteristics, and antifungal therapy of each patient were recorded. We analyzed factors associated with 30- and 90-day mortality. IPA patients exhibited higher mortality rates compared to non-IPA patients, with 30-day rates of 26.15% versus 8.38% (<i>P</i> < 0.001) and 90-day rates of 34.36% versus 13.24% (<i>P</i> < 0.001). Higher plasma and BALF PTX3 levels were associated with poor prognosis in IPA patients. ROC curve analysis identified optimal PTX3 thresholds of 4.29 ng/mL in BALF (sensitivity, 67.1%; specificity, 81.4%) and 7.11 ng/mL in plasma (sensitivity, 73.4%; specificity, 82.8%) for predicting mortality. Multivariate Cox regression analysis confirmed PTX3 levels in plasma (hazard ratio [HR] 3.87, 95%CI [1.87-8.00], <i>P</i>＜0.001) and BALF (HR 2.40 [1.19-4.84], <i>P</i> = 0.014) were independent prognostic factors for IPA mortality. Additionally, positive galactomannan test results in both BALF and plasma were initially correlated with increased mortality in IPA patients. However, after adjusting for potential confounding factors, this correlation no longer remained statistically significant. In conclusion, PTX3 is a promising prognostic biomarker of mortality in IPA patients.IMPORTANCEStudies have confirmed the value of pentraxin-3 (PTX3) in the diagnosis of invasive pulmonary aspergillosis (IPA), yet its prognostic significance in IPA remains unclear. This study found that in non-neutropenic IPA patients, plasma and bronchoalveolar lavage fluid (BALF) levels of PTX3 are independently associated with poor outcomes. Furthermore, the optimal cutoff values of PTX3 for predicting a poor prognosis of IPA are 4.29 ng/mL in BALF and 7.11 ng/mL in plasma. These findings could help us better manage IPA in non-neutropenic patients, potentially enhancing the prognosis of patients with this condition.