Effects of Adjunctive Thymosin Alpha 1 on Chronic Obstructive Pulmonary Disease-Associated Invasive Pulmonary Aspergillosis

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory airway disorder characterized by irreversible airflow limitation, frequently exacerbated by recurrent infections. Objectives: The present study aimed to assess the clinical efficacy and microbiological outcomes of sequential therapy using thymosin alpha 1 (Tα1) in combination with voriconazole in COPD patients with invasive pulmonary aspergillosis (IPA), and to investigate the relationship among voriconazole trough concentrations, fungal clearance, and adverse events. Methods: In this case-control study, 100 COPD patients with proven or probable IPA were randomized to receive voriconazole monotherapy [control group (CG)] or voriconazole plus Tα1 [observation group (OG)] for 6 weeks. Aspergillus species were identified by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) and internal transcribed spacer (ITS) sequencing. Antifungal susceptibility testing (AST) was performed according to the Clinical and Laboratory Standards Institute (CLSI) M38-A3 guidelines. Clinical response, immune profiles, cytokine levels, fungal burden, and adverse events were evaluated. Results: Aspergillus fumigatus was the predominant isolate (84%), followed by A. flavus (9%) and A. terreus (5%). Voriconazole resistance was identified in 3% of isolates. The OG exhibited a higher clinical effective rate (96.0% vs. 80.0%, P = 0.014) and fungal clearance (90% vs. 76%, P = 0.047). The median colony-forming unit (CFU) reduction was 92% in the OG compared to 78% in the CG. Trough voriconazole levels > 1.0 µg/mL were associated with improved clearance (P = 0.031), whereas levels > 4.0 µg/mL increased toxicity (P < 0.05). The Tα1 significantly enhanced CD4+/CD8+ ratios and reduced interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) levels (P < 0.0001). Conclusions: Adjunctive Tα1 promotes immune recovery and fungal clearance in COPD-associated IPA without increasing safety risks. Microbiological monitoring — including species identification, AST, and drug concentration measurements — is critical for optimizing outcomes.