Role of Aspergillus Specific IgG Titres as a Therapeutic Target for Chronic Pulmonary Aspergillosis: A Longitudinal Study

Introduction: Chronic Pulmonary Aspergillosis (CPA) continues to be an enigma to clinicians in regions with a high prevalence of pulmonary tuberculosis and is often misdiagnosed as the latter, attributable to the significant overlap in symptoms and radiology. Moreover, although the diagnostic criteria for CPA have been standardised, the role of serological markers in monitoring disease activity and response to therapy is still not well characterised. Aim: To understand the characteristics, risk factors and treatment outcomes in patients developing CPA and to determine the role of serological markers as indicators of disease activity. Materials and Methods: The present longitudinal study was conducted in the Department of Respiratory Medicine, University College of Medical Sciences and its associated Guru Teg Bahadur Hospital, Delhi, India from February 2021 to June 2022. Study included 46 patients suspected of harbouring CPA attributable to their clinico-radiological presentation. The diagnosis of CPA was made using the established criteria. Patients with a confirmed diagnosis of CPA received oral azole antifungals for 6 months and were monitored at 3-monthly intervals for reduction in baseline parameters to determine treatment success/failure. Paired and unpaired parametric variables were compared using the t-test and non parametric methods were compared using the Chisquare test. Results: The diagnosis of CPA was established in 31 (67.4%) patients of whom 77.6% were males and the mean age was 47.3±2.2 years. These patients had been symptomatic for 5.8±1.2 years. Underlying risk factors (such as the history of tuberculosis, chronic obstructive pulmonary disease, diabetes mellitus, history of long-term glucocorticoid use etc.) had been present for 6.9±1.3 years. Patients harboured an average of two risk factors with tuberculosis and diabetes mellitus being the most common local and systemic affliction, respectively. Patients with tuberculosis (p-value=0.001) and chronic steroid use (p-value=0.029) were significantly at higher risk of developing CPA. 6 months of azole therapy led to significant reduction in specific IgG titres (p-value=0.001), and serum precipitins (p-value=0.004). Two patients on itraconazole relapsed within 12 months but were successfully treated with voriconazole. Conclusion: Tuberculosis was the most significant local risk factor leading to the development of CPA, which developed soon after diagnosis of another systemic risk factor. Six months of azole therapy was adequate to induce remission of the disease, activity of which can be monitored though the measurement of serum IgG antibody titres.