Asthma and lower airway diseaseAnalyses of asthma severity phenotypes and inflammatory proteins in subjects stratified by sputum granulocytes
Section snippets
Methods
Characterization of severe and not severe asthma was performed according to the SARP protocol.15 Nonsmoking subjects (<5 pack-years) met American Thoracic Society criteria for diagnosis of asthma and provided informed consent approved by the institutional review board. Comprehensive evaluation included spirometry, bronchodilator reversibility and bronchial responsiveness, assessment of atopy, collection of blood, exhaled nitric oxide, sputum induction, and an administered questionnaire that
Subject stratification on the basis of sputum inflammation percent eosinophils and percent neutrophils
There were no significant differences in sputum cell percentages for severe compared with nonsevere subjects (see this article's Table E2 in the Online Repository at www.jacionline.org), and therefore, these were combined for stratification by granulocytes: <2% eosinophils + <40% neutrophils, <2% eosinophils + ≥40% neutrophils, ≥2% eosinophils + <40% neutrophils, and ≥2% eosinophils + ≥40% neutrophils (Table I and see Table E7 in this article's Online Repository at www.jacionline.org). The
Discussion
Sputum represents the best available noninvasive assessment of bronchial inflammation in asthma and reflects underlying pathology caused by infiltrating cells and soluble mediators. Instead of comparing sputum cellular and biochemical components between healthy subjects and subjects with asthma, our objective was to assess whether comprehensive analysis of induced sputum over a spectrum of asthma severity improves our understanding of the factors that characterize different asthma phenotypes.
References (53)
- et al.
Clinical assessment of asthma severity partially corresponds to sputum eosinophilic airway inflammation
Respir Med
(2004) - et al.
Airway inflammation assessed by invasive and noninvasive means in severe asthma: eosinophilic and noneosinophilic phenotypes
J Allergy Clin Immunol
(2006) - et al.
Profiles of proinflammatory cytokines in sputum from different groups of severe asthmatic patients
Ann Allergy Asthma Immunol
(2006) - et al.
Characterization of the severe asthma phenotype by the NHLBI Severe Asthma Research Program
J Allergy Clin Immunol
(2007) - et al.
Relationship between airway inflammation, hyperresponsiveness, and obstruction in asthma
J Allergy Clin Immunol
(2001) - et al.
The influence of age on induced sputum differential cell counts in normal subjects
Chest
(2004) - et al.
Noneosinophilic asthma: a distinct clinical and pathologic phenotype
J Allergy Clin Immunol
(2007) - et al.
Heterogeneity of airway inflammation in persistent asthma: Evidence of neutrophilic inflammation and increased sputum interleukin-8
Chest
(2001) - et al.
Protein microarray analysis in patients with asthma: elevation of the chemokine PARC/CCL18 in sputum
Chest
(2009) - et al.
Effect of beclomethasone dipropionate on basic fibroblast growth factor levels in induced sputum samples from asthmatic patients
Ann Allergy Asthma Immunol
(2005)
Imbalance between vascular endothelial growth factor and endostatin levels in induced sputum from asthmatic subjects
J Allergy Clin Immunol
Interleukin-13 and interleukin-5 in induced sputum of eosinophilic bronchitis: comparison with asthma
Chest
Airway epithelial cells produce neurotrophins and promote the survival of eosinophils during allergic airway inflammation
J Allergy Clin Immunol
IL-1b release from cultured bronchial epithelial cells and bronchoalveolar lavage cells from allergic and normal humans following segmental challenge with ragweed
Cytokine
Asthmatic bronchial epithelium activated by the proteolytic allergen Der p 1 increases selective dendritic cell recruitment
J Allergy Clin Immunol
Neurotrophins and asthma: novel insight into neuroimmune interaction
J Allergy Clin Immunol
Release of nerve growth factor by human pulmonary epithelial cells: role in airway inflammatory diseases
Eur J Pharmacol
Tumor necrosis factor-a and interleukin-6 regulate secretion of brain-derived neurotrophic factor in human monocytes
J Neuroimmunol
Monocyte-like and mature macrophages produce CXCL13 (B cell-attracting chemokine 1) in inflammatory lesions with lymphoid neogenesis
Blood
Effects of tumor necrosis factor-alpha, epidermal growth factor and transforming growth factor-alpha on interleukin-8 production by, and human rhinovirus replication in, bronchial epithelial cells
Internat Immunopharcacol
Expression of c-erbB receptors and ligands in the bronchial epithelium of asthmatic subjects
J Allergy Clin Immunol
The relationship between airways inflammation and asthma severity
Am J Respir Crit Care Med
The ENFUMOSA cross-sectional European multicentre study of the clinical phenotype of chronic severe asthma
Eur Respir J
Analysis of induced sputum in adults with asthma: identification of subgroup with isolated sputum neutrophilia and poor response to inhaled corticosteroids
Thorax
Neutrophilic inflammation in severe persistent asthma
Am J Respir Crit Care Med
Refractory" eosinophilic airway inflammation in severe asthma: effect of parenteral corticosteroids
Am J Respir Crit Care Med
Cited by (380)
GLUT1 mediates the release of HMGB1 from airway epithelial cells in mixed granulocytic asthma
2024, Biochimica et Biophysica Acta - Molecular Basis of DiseaseSputum microbiota and inflammatory subtypes in asthma, COPD, and its overlap
2024, Journal of Allergy and Clinical Immunology: GlobalInhibition of non-receptor tyrosine kinase LCK partially mitigates mixed granulocytic airway inflammation in a murine model of asthma
2023, International ImmunopharmacologyBronchial epithelial cell transcriptional responses to inhaled corticosteroids dictate severe asthmatic outcomes
2023, Journal of Allergy and Clinical ImmunologyInflammatory Markers to Inform Treatment of Asthma With Biologicals: FeNO Versus Blood Eosinophils
2023, Journal of Allergy and Clinical Immunology: In Practice
Supported by the NHLBI Severe Asthma Research Program Awards (HL69167) and the Wake Forest University General Clinical Research Center (MO1 RR07122).
Disclosure of potential conflict of interest: D. A. Meyers and S. P. Peters have received research support from the National Institutes of Health/National Heart, Lung, and Blood Institute. The rest of the authors have declared that they have no conflict of interest.