Sinopulmonary Syndromes
Most, if not all, patients with AFS and concomitant severe lower airways obstruction could be at risk for the development of ABPM. We suspect that the diagnosis of coexistent disease may sometimes be overlooked since at least 50% of patients with AFS have asthma, which is one of the diagnostic criteria for ABPM.
Why all atopic individuals who demonstrate fungal-specific IgE do not develop one or both of these diseases is unclear. This could reflect a dose-response relationship between obstruction and disease or a more robust IgE-mediated inflammatory response in those patients who develop this form of fungal hypersensitivity. Most patients with AFS have evidence of a fungal-specific IgE response to multiple fungal allergens, as was the case with our patient.
In our patient, Chrysosporium, a fungus previously implicated in the pathogenesis of AFS, grew from a culture of surgical material obtained from the sinuses and appeared to be the culprit allergen.
Mast cell-derived products released in such IgE mediated reactions include histamine, a mucus secretagogue. Variations in the viscosity of the mucus produced or the induction of nasal polyposis, also contributing to airways obstruction, also could play a role in the process. There is no evidence to suggest that AFS or ABPM results from an underlying immunodeficiency. However, the association between ABPM and CF has been known for some time.
Some reports suggest that mutations in the CFTR gene are present in patients with ABPM who may have normal sweat chloride levels and lack many of the typical clinical features of CF. Miller et all analyzed the CFTR gene in 11 patients with ABPM and found that 1 patient carried two CF mutations (F508/R347H) and 5 patients carried one mutation (F508, 4 patients; R117H, 1 patient).
In a study by Marchand et al, the frequency of CFTR gene mutations was also higher in patients with ABPM than it was either in patients with allergic asthma or in subjects seeking genetic counseling.