title: Increased chitinase expression and fungal-specific antibodies in the bronchoalveolar lavage fluid of asthmatic children.
abstract: BACKGROUND
  Increasing evidence highlights the contribution of chitinases and fungal infection to the development of asthma.
  
  
  OBJECTIVE
  The purpose of this study was to characterize chitinase expression and serological markers of fungal infection in children with severe asthma.
  
  
  METHODS
  Bronchoalveolar lavage fluid (BALF) was collected from children undergoing clinically indicated flexible bronchoscopy. A diagnosis of asthma was confirmed by pulmonary function testing. BALF was tested for chitinase activity and YKL-40 (an enzymatically inactive chitinase) concentrations. Specimens were cultured for fungal organisms and tested for cryptococcal antigen by ELISA. IgG and IgA reactivity to whole extract fungal (Aspergillus fumigatus, Alternaria alternata, Cryptococcus neoformans and Candida albicans) proteins were determined by immunoblot assay.
  
  
  RESULTS
  Among the 37 patients studied, 30 were asthmatic and 7 were non-asthmatic. Asthmatics exhibited elevated serum IgE levels (median: 748 IU/mL, IQR: 219-1765 IU/mL). Chitinase activity was greater in the BALF of asthmatics (mean, 0.85 ± 1.2 U/mL) compared with non-asthmatics (mean: 0.23 ± 0.21 U/mL, P = 0.012). Likewise YKL-40 concentrations were higher in the BALF of asthmatics and correlated with chitinase activity. There was a trend towards increased fungal-specific IgG in the BALF of asthmatics compared with non-asthmatics and for C. albicans this difference reached statistical significance. IgA reactivity to C. neoformans and A. fumigatus was greater in the BALF of asthmatics compared with non-asthmatics.
  
  
  CONCLUSIONS
  Compared with non-asthmatics, asthmatic children exhibited increased chitinase activity and increased YKL-40 levels in BALF. Increased IgG and IgA reactivity to fungal proteins in the BALF of asthmatics may reflect a local response to fungal infection. Our findings are consistent with and suggest a role for chitinases in asthma pathogenesis among Bronx children and provide serological evidence of an association between fungal infection and severe asthma.
authors.affiliation: Department of Pediatrics, Childrens' Hospital at Montefiore and Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461, USA. david.goldman@einstein.yu.edu
authors.forename: D L
authors.initials: DL
authors.lastname: Goldman
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.forename: K
authors.initials: K
authors.lastname: Tsirilakis
authors.forename: C
authors.initials: C
authors.lastname: Andrade
authors.forename: A
authors.initials: A
authors.lastname: Casadevall
authors.forename: A G
authors.initials: AG
authors.lastname: Vicencio
mesh_terms: D000908:Antibodies, Fungal / Q000097:blood* / Q000276:immunology; D001249:Asthma / Q000201:enzymology* / Q000382:microbiology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D002648:Child; D002688:Chitinases / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D009181:Mycoses / Q000097:blood / Q000150:complications / Q000276:immunology*
chemical_list: D000908:Antibodies, Fungal; D002688:Chitinases