Introduction: Fungi are important allergens in patients with asthma, and exposure to or colonization with species including Aspergillus, Alternaria, Cladosporium and Penicillium can exacerbate symptoms. Although Cryptococcus neoformans is not widely considered to be associated with asthma, there is emerging evidence that this organism may partly explain geographic variations in asthma severity. C. neoformans is able to colonize pigeon droppings and cause persistent subclinical pulmonary infection in humans. We previously demonstrated a high prevalence of infection among residents of the Bronx, a New York City borough with an extraordinarily high rate of severe asthma. Furthermore, we have demonstrated that pulmonary cryptococcosis results in airway hyper-reactivity, TH2 inflammation and goblet cell hyperplasia in rats. Although the mechanisms underlying fungal-induced asthma remain unclear, induction of YKL-40, a chitinase-like protein implicated in asthma pathogenesis, may be important. We hypothesize that serologic reactivity to C. neoformans antigen is associated with YKL-40 levels in Bronx children with asthma. Methods: Serum was collected from 63 patients hospitalized for an asthma exacerbation under an IRB approved protocol. Serologic reactivity to cryptococcal antigens was determined using a western blot approach developed in our laboratory. Reactivity was characterized as mild, moderate or extensive based on the number of bands present. Levels of YKL-40 were measured using a commercially available ELISA kit (R&D Systems). Protease-treated sera were also tested for the presence of cryptococcal polysaccharide antigen using a previously described capture ELISA. Results: Serologic reactivity against C. neoformans was present in all subjects tested. Mild, moderate and extensive reactivity was found in 10%, 47% and 43% of patients, respectively. Median YKL-40 levels for each group were 19.79ng/mL (1-70), 34.79ng/mL (0-448) and 32.29ng/mL (7.7-164), respectively. Cryptococcal polysaccharide was detected at a concentration > 4 ng/ml in 14.3 % of (9/63) sera. Conclusions: Serologic reactivity against C. neoformans and the presence of low level cryptococcal antigenemia is common in asthmatic children from the Bronx. These findings indicate that subclinical cryptococcosis is common among Bronx children. The relationship between infection, YKL-40 levels and asthma remains to be determined. Ongoing studies include recruitment of control patients and additional asthma patients.
Poster Board # J30
Full conference title:
American Thoracic Society International Conference
- ATS 2010