Increased chitinase expression and fungal‐specific antibodies in the bronchoalveolar lavage fluid of asthmatic children

Clinical and Experimental Allergy - Tập 42 Số 4 - Trang 523-530 - 2012
David L. Goldman1, X. Li2, Kalliope Tsirilakis1,3, Cristiane Conte Paim de Andrade1, Arturo Casadevall2, Alfin G. Vicencio1,3
1Department of Pediatrics, Childrens' Hospital at Montefiore and Albert Einstein College of Medicine
2Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA
3Department of Pediatrics, Cohen Children’s Medical Center, New Hyde Park, NY, USA

Tóm tắt

SummaryBackgroundIncreasing evidence highlights the contribution of chitinases and fungal infection to the development of asthma.ObjectiveThe purpose of this study was to characterize chitinase expression and serological markers of fungal infection in children with severe asthma.MethodsBronchoalveolar 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.ResultsAmong 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 and Clinical RelevanceCompared 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.

Từ khóa


Tài liệu tham khảo

10.1111/j.1365-2222.1996.tb00610.x

10.1136/bmj.325.7361.411

10.1016/S0091-6749(99)70247-2

10.1016/0091-6749(94)90125-2

10.1136/thx.7.4.317

10.1086/376525

Sandhu RS, 1979, Role of Aspergillus and Candida species in allergic bronchopulmonary mycoses. A comparative study, Scand J Respir Dis, 60, 235

10.1136/thx.45.6.489

10.1016/S0091-6749(99)70321-0

10.2165/00003495-200464040-00002

10.1164/rccm.200805-737OC

Littman ML, 1959, Cryptococcus neoformans in pigeon excreta in New York City, Am J Hyg, 69, 49

Campbell GD, 1966, Primary pulmonary cryptococcosis, Am Rev Respir Dis, 94, 236

10.7326/0003-4819-69-6-1109

10.1111/j.1365-2249.1995.tb05568.x

10.1111/j.1462-5822.2005.00676.x

10.1097/INF.0b013e318047e073

10.4049/jimmunol.174.2.1027

10.1111/j.1348-0421.2000.tb02573.x

10.1086/593068

10.1086/501363

10.1080/13693780802641904

10.4049/jimmunol.180.9.6000

10.1128/CMR.16.3.517-533.2003

10.1007/s00018-009-8765-7

10.1126/science.1095336

10.1056/NEJMoa073600

10.1183/09031936.00034409

10.1186/1465-9921-9-40

10.1093/glycob/6.6.627

10.1080/13693780801961345

10.1080/15572536.2006.11832675

10.1128/CVI.00242-07

10.1016/j.prrv.2004.01.006

10.1136/thorax.56.5.345

10.1074/jbc.M106223200

10.1056/NEJMc073406

10.1542/peds.2010-0321

10.1164/rccm.201001-0087OC

10.1016/0091-6749(88)90995-5

10.1074/jbc.275.11.8032

10.1128/IAI.69.4.2723-2727.2001

10.1093/intimm/dxh328

10.1111/j.1744-313X.2006.00597.x

10.1164/rccm.200506-890OC

10.1016/j.jaci.2008.04.030

10.1056/NEJMoa0708801

10.1164/rccm.201003-0322OC

Thông tin
Thông tin xuất bản

Clinical and Experimental Allergy

Tập 42 Số 4

523-530

Thông tin tác giả