Challenges in the diagnosis and treatment of chronic pulmonary aspergillosis in Japan

Abstract

Chronic pulmonary aspergillosis (CPA) is a refractory infectious disease that occurs in patients with mildly compromised immunity or an underlying pulmonary disease. The mortality rate associated with pulmonary aspergillosis has also increased. In the diagnosis and management of CPA, numerous challenges persist. The Aspergillus IgG antibody test is a highly accurate adjunctive diagnostic method for CPA that has been approved in Japan since 2024. However, the diagnostic accuracy for non-fumigatus species is not as high as that for Aspergillus fumigatus. The development of an auxiliary diagnostic method for non-fumigatus CPA is a pressing concern. Azole-resistant strains, related species, and challenges in long-term therapy are significant issues. Currently, most azole-resistant strains in Japan are patient-route strains that harbor CYP51A mutations. Although the prevalence of azole-resistant strains transmitted via environmental routes remains limited, ongoing surveillance and monitoring are essential. Furthermore, the lack of health insurance coverage for drug susceptibility testing is another critical issue. The recommended treatment duration for CPA is a minimum of 6–12 months; however, maintaining long-term therapy is challenging because of the higher incidence of adverse events associated with antifungal agents than with other antimicrobial medications. Additionally, CPA co-infection in patients with non-tuberculosis mycobacteria has recently become a concern owing to poor prognosis and drug-drug interactions between antifungal and antimycobacterial agents. Therefore, the development of treatment agents with improved safety profiles and fewer drug-drug interactions is highly desirable.