Shah, AnandMarghlani, DareenAlramadhan, Mohammed Mahdi2024-11-172024Vancouver Stylehttps://hdl.handle.net/20.500.14154/73632Background: Aspergillus species are fungi that can cause a spectrum of respiratory diseases, including chronic pulmonary aspergillosis (CPA) and allergic pulmonary aspergillosis (ABPA). CPA often occurs in individuals with pre-existing underlying lung comorbidities, while ABPA is developed due to hypersensitivity reaction to Aspergillus. There is however overlap between the two conditions in some individuals, which is defined as a (CPA/ABPA crossover syndrome), There are few studies on this phenomenon with little data on the underlying risk factors and whether CPA/ABPA crossover leads to a worse prognosis than CPA or ABPA alone. Objective: In this research, we aim to investigate and understand the existing evidence and effects of ABPA crossover in proven cases of CPA, analysing prevalence, risk factors and impact on prognosis. Methods: This study utilises a retrospective cohort design to analyse data from 167 patients diagnosed with CPA at a single centre in London, UK, over a five-year period from 2018 to December 2023, with the data extracted from electronic health records. ABPA was defined as per the 2024 International Society for Human and Animal Mycology (ISHAM) criteria. The primary outcome was mortality. Independent t-test or Mann-Whitney, Chi-square and Kaplan-Meier survival analysis coupled with Cox-regression hazards models were used to assess the impact of ABPA on the mortality of patients with CPA/ABPA crossover and risk factors related to CPA/ABPA crossover. Results: The prevalence rate in this large retrospective analysis of 167 confirmed CPA cases was 43 (25.8%) patients who had CPA/ABPA crossover syndrome with confirmed diagnoses of ABPA according to revised 2024 criteria from ISHAM. The overall 5-year mortality in the cohort was 16.1%, and 4%, for 3-year mortality. Survival analysis showed no significant difference between CPA and CPA/ABPA crossover (HR: 1.36, P: 0.490). The risk factors for mortality; univariate analysis revealed old age, low BMI, low albumin, low %TLCO, male gender, and A. fumigatus IgE were significantly associated with higher mortality rates. Multivariable Cox proportional hazards regression analysis confirmed that male gender, A. fumigatus specific IgE, and low albumin were risk factors for increased mortality in CPA (HR: 16.6, 1.02, 0.61, P: 0.025, 0.023, 0.003 respectively). Moreover, risk factors for CPA/ABPA syndrome; univariate logistic analysis revealed a background of asthma as a risk factor for CPA/ABPA crossover with the presence of sarcoidosis and interstitial lung disease as negative factors, while multivariate analysis confirmed asthma as the significant risk factor (OR: 5.9, P: 0.023). Conclusion: Our results show that CPA/ABPA crossover is highly prevalent in a large UK CPA cohort. Although mortality was similar to CPA alone, A. fumigatus sensitisation was significantly associated with a worse outcome, suggesting a potential pathological effect of T2 sensitisation on CPA outcomes. Further larger scale global studies are required to confirm findings with in-depth immunological analysis to better understand the interplay between allergy and CPA pathogenesis.48enCPAABPAAspergillosisLungPrognostic factorsThesis