Time-Normalized Anti-Aspergillus IgG Kinetics for Monitoring Chronic Pulmonary Aspergillosis Progression.

BACKGROUND: Chronic pulmonary aspergillosis (CPA) requires prolonged follow-up combining clinical and radiological evaluation. Although anti-Aspergillus IgG is central for diagnosis, clinically meaningful changes during follow-up remain poorly defined. RESEARCH QUESTION: Do time-normalized anti-Aspergillus IgG kinetics reflect clinico-radiological CPA progression and provide candidate thresholds for intensified reassessment? STUDY DESIGN AND METHODS: In this retrospective single-center study, patients with CPA with ≥2 follow-up visits spaced ≥3 months apart and paired anti-Aspergillus IgG measurements were included. Clinical and chest-CT evolution between visits was adjudicated by a multidisciplinary panel blinded to serology. IgG relative change was normalized to a 3-month interval. Stable/improved and worsening CPA visit-pairs were compared using unadjusted and patient-cluster-adjusted analyses. Receiver operating characteristic analysis and patient-level bootstrap resampling were used to explore candidate thresholds. RESULTS: Twenty-two patients (79 sera; 57 visit-pairs) were analyzed. Fourteen visit-pairs (24.6%) were classified as worsening, of which three (5.3%) were not due to CPA, and 43 (75.4%) as stable/improved. Median time-normalized IgG relative change was higher in worsening than stable/improved CPA (1.28 [IQR: 1.02-1.71] vs 0.84 [IQR: 0.64-1.04], P<0.001). After accounting for within-patient clustering, the ratio of geometric means was 1.84 (95% CI: 0.97-3.48; P=0.059). The area under the curve was 0.84 (95% CI: 0.71-0.96). A candidate time-normalized IgG relative change threshold of 1.45/3 months provided 36.4% sensitivity and 97.7% specificity; while a 1.10/3 months threshold provided 72.7% sensitivity and 83.7% specificity. Patient-level bootstrap estimates supported internal consistency. INTERPRETATION: Time-normalized anti-Aspergillus IgG kinetics were higher during worsening CPA, although cluster-adjusted uncertainty was substantial. A marked increase may serve as an exploratory rule-in signal prompting expedited imaging and microbiological reassessment, but values below the threshold should not exclude progression or delay evaluation. External validation is required before clinical implementation. These findings support the integration of quantitative serological kinetics into multimodal CPA monitoring strategies.