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

Patients with severe asthma have increased granulocytes in their sputum compared with patients with mild to moderate asthma. We hypothesized that inflammatory granulocytes in sputum may identify specific asthma severity phenotypes and are associated with different patterns of inflammatory proteins i...

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Vydané v:	Journal of allergy and clinical immunology Ročník 125; číslo 5; s. 1028 - 1036.e13
Hlavní autori:	Hastie, Annette T., Moore, Wendy C., Meyers, Deborah A., Vestal, Penny L., Li, Huashi, Peters, Stephen P., Bleecker, Eugene R.
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	New York, NY Mosby, Inc 01.05.2010 Elsevier Elsevier Limited
Predmet:	Adolescent Adult Allergy and Immunology Asthma Asthma - physiopathology Asthma phenotypes BDNF Biological and medical sciences CCL18 CCL20 Child Child, Preschool Chronic obstructive pulmonary disease, asthma CXCL13 Enzyme-Linked Immunosorbent Assay Female Fundamental and applied biological sciences. Psychology Fundamental immunology Granulocytes - cytology Humans Immunopathology Inflammation - immunology Inflammation - physiopathology Inflammation Mediators - analysis Linear Models Male Medical sciences Meetings Methods Phenotype Pneumology Protein Array Analysis protein microarrays Proteins Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis Severity of Illness Index Sputum - cytology TNFSF14 Young Adult Asthma phenotypes TNFSF14 BDNF CCL20 EGF PARC SARP CXCL13 FVC BLC ICS MIP-3α MCP protein microarrays CCL18 SAM Forced vital capacity Epidermal growth factor B-lymphocyte chemoattractant/CXCL13 Severe Asthma Research Program of the National Heart, Lung, and Blood Institute Inhaled corticosteroid Macrophage inflammatory protein 3α/CCL20 TNF superfamily factor 14/LIGHT, Lymphotoxin homologous, Inducible expression, competes with HSV Glycoprotein D for HVEM receptor on T lymphocytes Pulmonary and regulated chemokine/CCL18 Brain-derived neurotrophic factor Monocyte chemoattractant protein Significance Analysis of Microarrays Human Lung disease Immunopathology Chemokine CC Exodus Respiratory disease Granulocyte LIGHT ligand CXCLl3 Inflammation Protein microarray CC chemokine Protein Asthma Phenotype Immunology Sputum Bronchus disease Obstructive pulmonary disease
ISSN:	0091-6749, 1097-6825, 1097-6825
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Shrnutí:	Patients with severe asthma have increased granulocytes in their sputum compared with patients with mild to moderate asthma. 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. This hypothesis was tested in 242 patients with asthma 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. Stratified by sputum granulocytes, <2% or ≥2% eosinophils and <40% or ≥40% neutrophils, subjects with both increased eosinophils and neutrophils had the lowest lung function and increased symptoms and health care use. Subjects with elevated eosinophils with or without increased neutrophils had significantly increased fraction exhaled nitric oxide (FeNO) and serum eosinophils and greater frequency of daily β-agonist use. Microarray data stratified by granulocytes revealed 25 to 28 inflammatory proteins increased >2-fold in sputa with ≥40% neutrophils. Microarray analyses stratified by severity of asthma identified 6 to 9 proteins increased >2-fold in sputa in subjects with severe asthma compared with nonsevere asthma. ELISA data stratified by sputum granulocytes showed significant increases in brain-derived neurotrophic factor, IL-1β, and macrophage inflammatory protein 3α/CCL20 for those with ≥40% neutrophils; these mediators demonstrated positive associations with neutrophil counts. Combined increased sputum eosinophils and neutrophils identified patients with asthma with the lowest lung function, worse asthma control, and increased symptoms and health care requirements. Inflammatory protein analyses of sputum supernatants found novel mediators increased in patients with asthma, predominantly associated with increased sputum neutrophils.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 ObjectType-Article-2 ObjectType-Feature-1
ISSN:	0091-6749 1097-6825 1097-6825
DOI:	10.1016/j.jaci.2010.02.008