effects of adjunctive thymosin alpha 1 on chronic obstructive pulmonary disease-associated invasive pulmonary aspergillosis

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.