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Analyses of asthma severity phenotypes and inflammatory proteins in subjects stratified by sputum granulocytes

Open access
Hastie, Annette T., Moore, Wendy C., Meyers, Deborah A., Vestal, Penny L., Li, Huashi, Peters, Stephen P., Bleecker, Eugene R.·2010·Journal of Allergy and Clinical Immunology

Abstract

Background Patients with severe asthma have increased granulocytes in their sputum compared to patients with mild to moderate asthma. Objective We hypothesized that inflammatory granulocytes in sputum may identify specific asthma severity phenotypes and are associated with different patterns of inflammatory proteins in sputum supernatants. Methods This hypothesis was tested in 242 asthmatics enrolled in the Severe Asthma Research Program who provided sputum samples for cell count, differential cell determinations, cell lysates for Western blot, and supernatant analyses by inflammatory protein microarrays and ELISAs. ANOVA and multiple linear regression models tested mediator associations. Results Stratified by sputum granulocytes, < or ≥2%eosinophils and < or ≥40%neutrophils, subjects with both increased eosinophils and neutrophils had the lowest lung function, increased symptoms and healthcare utilization. Subjects with elevated eosinophils with or without increased neutrophils had significantly increased FeNO, serum eosinophils and greater frequency of daily β-agonist use. Microarray data, stratified by granulocytes revealed 25–28 inflammatory proteins increased >2-fold in sputa with ≥40% neutrophils. Microarray analyses stratified by severity of asthma, identified 6–9 proteins increased >2-fold in sputa in subjects with severe asthma compared to nonsevere asthma. ELISA data, stratified by sputum granulocytes, showed significant increases in BDNF, IL-1β, and MIP-3α/CCL20 for those with ≥40%neutrophils; these mediators demonstrated positive associations with neutrophil counts. Conclusion Combined increased sputum eosinophils and neutrophils identified asthmatics with the lowest lung function and worse asthma control, increased symptoms and healthcare requirements. Inflammatory protein analyses of sputum supernatants found novel mediators increased in asthmatics, predominantly associated with increased sputum neutrophils.

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Metadata

Authors
Hastie, A. T., Moore, W. C., Meyers, D. A., Vestal, P. L., Li, H., Peters, S. P., & Bleecker, E. R.
Venue
Journal of Allergy and Clinical Immunology
Publisher
Elsevier BV
Published
2010-05
Volume
125
Issue
5
Pages
1028-1036.e13
ISSN
0091-6749 (ISSN-L)
OpenAlex
W2051954214
Cited by
463
References
2
FWCI
20.35
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Analyses of asthma severity phenotypes and inflammatory proteins in subjects stratified by sputum granulocytes. https://app.cochat.ai/papers/10.1016/j.jaci.2010.02.008
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Hastie, A. T., Moore, W. C., Meyers, D. A., Vestal, P. L., Li, H., Peters, S. P., & Bleecker, E. R. (2010). Analyses of asthma severity phenotypes and inflammatory proteins in subjects stratified by sputum granulocytes. Journal of Allergy and Clinical Immunology. https://doi.org/10.1016/j.jaci.2010.02.008

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