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Title: Allergic bronchopulmonary aspergillosis in cystic fibrosis : prevalence, clinical complications, diagnosis and influence on the outcome
Author: Lim, Yick-Hou
ISNI:       0000 0004 2686 6662
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 2009
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Allergic bronchopulmonary aspergillosis (ABPA) is an inflammatory lung disease characterised by a local immunological reaction to the intra-luminal antigen of aspergillus fumigatus (A. fumigatus) that has colonised the airway, with a prevalence of 2 to 15 % had been reported in patients with cystic fibrosis (CF). The difficulties of diagnosing ABPA in the context of CF are because of overlapping clinical, radiographic, microbiologic and immunological features. Untreated ABPA may lead to lung damage, including proximal bronchiectasis and segmental , lobar or whole lung collapse. This thesis describes a cross-sectional study on prevalence of ABPA, atopy as a risk factor in the development of ABPA and reveals a prevalence of 21% of ABPA in our cohort of adult patients with CF, a 1 in 4 risk of developing ABPA in patients who have serum sensitisation >3 common aeroallergens. A longitudinal study on the impact of ABPA shows a significant decline of spirometric lung function for at least 2.8 years before the diagnosis, treatment of ABPA is associated with a significant improvement of lung function that sustained for at least 6 months. A longitudinal study on the impact of aspergillus sensitisation confirms the rate of decline of spirometric lung function became significantly faster after the development of aspergillus sensitisation. The cross sectional study on exhaled nitric oxide (NO) level shows a significantly decreased level of exhaled NO in patients with high risk of developing ABPA. The prospective study reveals a specific pattern of specific IgG and subclass antibodies to water soluble somatic hyphal (WSSH) antigen with increase IgG, IgG1, IgG2 and IgG4 antibodies levels in patents with ABPA. Patients with asthma and 4 Nelson criteria may have a similar pattern of specific IgG and subclass antibodies. On studying correlation between the specific IgG and subclass antibodies , spirometric lung function and Nelson criteria; The combination of total IgE level above 500 KU/L or a recent (within 4 months) doubling level to 200-500 KU/L and specific IgE to A. fumigatus RAST score >3 would confirm ABPA in adult CF patients and warrants treatment. An increase of specific IgG, IgG1, IgG2 and IgG4 antibodies levels would confirm ABPA. In particular, an increase of specific IgG and IgG4 antibodies levels (89 % and 9 EU respectively) would warrant ABPA treatment. It is known that the soluble aspergillus antigens are responsible for the development of ABPA. Soluble enzymes such as manganese superoxide dismutase and soluble glycoproteins from hyphae with certain antigenic fractions have shown to have increase activities and reacted with sera of ABPA patients. The advantages of WSSH A. fumigatus antigen are being a multivalent purified soluble antigen, untreated with alcohol, a cytoplasmic antigen from the mycelium, previous animal and CF studies have shown to be specific in the diagnosis of ABPA.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: R Medicine (General)