Clinical impact of chronic pulmonary aspergillosis in patients with pulmonary nontuberculous mycobacterial disease and colonization: a multicentre prospective cohort study

Pulmonary nontuberculous mycobacterial (NTM) infection and chronic pulmonary aspergillosis (CPA) are interconnected diseases, but their relationship remains poorly understood. In this prospective, multi-centre study conducted in Taiwan between August 2020 and January 2024, 365 patients with cultures positive for Mycobacterium avium complex, Mycobacterium kansasii, or Mycobacterium abscessus complex were followed until August 2024. Serum Aspergillus-specific IgG levels were measured at baseline and follow-up. Among these patients, 123 (33.7%) tested positive for Aspergillus-specific IgG (>40 mgA/L), and 33 (9.0%) were diagnosed with CPA (10 at initial diagnosis, 23 developed CPA during a median follow-up of 18 months). Patients with NTM pulmonary disease (NTM-PD) demonstrated significantly higher cumulative incidence of CPA compared to those with NTM pulmonary colonization (NTM-PC) (2.7%, 8.3%, and 14.7% vs. 0%, 2.9%, and 5.3% at 1, 2, and 3 years, respectively; p = 0.0408). CPA development was linked to worse overall survival (adjusted hazard ratio [aHR] 3.96, 95% confidence interval [CI]: 1.47–10.69, p = 0.0066) as well as higher risk of radiographic progression (adjusted odds ratio [aOR] 7.43, 95% CI: 2.17–32.11, p = 0.0030). Longitudinal assessment of Aspergillus-specific IgG in 119 patients showed nine with positive seroconversion, and two were subsequently diagnosed with CPA. These findings indicate that approximately one-third of pulmonary NTM isolation patients have elevated Aspergillus-specific IgG, about 10% develop CPA, and CPA development is associated with poor survival. Therefore, longitudinal monitoring of Aspergillus-specific IgG is warranted to facilitate early detection and management of CPA in patients with pulmonary NTM isolation. Elevated Aspergillus IgG was observed in one-third of NTM patients, and 10% developed CPA.The development of CPA is associated with worse outcomes in this population.Serial monitoring of Aspergillus IgG levels may aid in early diagnosis and intervention. Elevated Aspergillus IgG was observed in one-third of NTM patients, and 10% developed CPA. The development of CPA is associated with worse outcomes in this population. Serial monitoring of Aspergillus IgG levels may aid in early diagnosis and intervention.

肺非结核分枝杆菌（NTM）感染与慢性肺曲霉病（CPA）属于存在关联的两类疾病，但二者间的具体关联机制目前仍未被充分阐明。本研究为一项前瞻性多中心研究，于2020年8月至2024年1月在中国台湾地区开展，共纳入365例培养阳性患者，其分离病原体为鸟分枝杆菌复合群、堪萨斯分枝杆菌或脓肿分枝杆菌复合群，研究随访至2024年8月。研究人员在基线及随访阶段检测了受试者的血清曲霉特异性IgG水平。入组患者中，123例（33.7%）的曲霉特异性IgG水平＞40 mgA/L，结果呈阳性；另有33例（9.0%）被确诊为CPA，其中10例在初始诊断时即已患病，23例在中位随访18个月期间新发CPA。与肺非结核分枝杆菌定植（NTM-PC）患者相比，肺非结核分枝杆菌肺病（NTM-PD）患者的CPA累积发病率显著更高：在随访1、2、3年时，两类患者的CPA发病率分别为2.7%、8.3%、14.7%与0%、2.9%、5.3%（p=0.0408）。CPA的发生与患者更差的总生存率相关（校正后风险比[aHR]=3.96，95%置信区间[CI]：1.47~10.69，p=0.0066），同时也会升高影像学进展风险（校正后优势比[aOR]=7.43，95%置信区间[CI]：2.17~32.11，p=0.0030）。对119例患者开展的曲霉特异性IgG纵向检测显示，其中9例出现血清学阳转，后续有2例被确诊为CPA。本研究结果表明，约三分之一的肺非结核分枝杆菌分离阳性患者存在曲霉特异性IgG水平升高，约10%的患者会进展为CPA，且CPA的发生与不良生存结局相关。因此，临床有必要对肺非结核分枝杆菌分离阳性患者开展曲霉特异性IgG的纵向监测，以实现CPA的早期识别与干预。约三分之一的非结核分枝杆菌患者存在曲霉特异性IgG水平升高，10%的患者会进展为CPA；CPA的发生与该人群的不良临床结局显著相关，定期监测曲霉特异性IgG水平有助于实现CPA的早期诊断与临床干预。