Reviews and feature articlesNoneosinophilic asthma: A distinct clinical and pathologic phenotype
Section snippets
Defining noneosinophilic asthma
There are 4 important elements to this diagnosis: the presence of typical symptoms, objective evidence of variable airflow obstruction and/or airway hyperresponsiveness, the consistent absence of a sputum eosinophil count, and the absence of an alternative explanation for the symptoms and findings on investigation (Table I). Values for the upper limit of the eosinophil count that constitutes noneosinophilic disease have varied between studies. Green et al19 used <1.9%, the upper limit of the
Stability of noneosinophilic asthma
There is limited evidence from longitudinal studies to address the question of whether noneosinophilic asthma is a consistent phenotype over time. Simpson et al32 have recently shown that the absence of a sputum eosinophilia is a consistent finding at 4 weeks and 5 years after first sputum induction, and Green et al16 identified a subgroup of patients with refractory asthma who had predominantly noneosinophilic sputum on repeated observations made over a period of 12 months. However, 70% of
Histopathologic features of noneosinophilic asthma
In a study of patients with severe asthma, Wenzel et al24 have shown that noneosinophilic disease defined histologically by the absence of eosinophils in the mucosa was associated with normal thickness of the subepithelial basement membrane and a lower number of CD3+ cells and macrophages, compared with severe eosinophilic asthma. These differences were present despite the use of comparable doses of corticosteroid therapy by patients in each group. Berry et al21 reported similar differences in
Mechanisms of airway inflammatory response and disordered airway function
It has been suggested that the different inflammatory profiles now recognized in asthma populations are a result of different patterns of antigen exposure in the airways.36 Thus, eosinophilic disease is considered a consequence of allergen mediated activation of mast cells and T cells in the airway with release of TH2 cytokines. In contrast, neutrophilic inflammation is the product of innate and cell mediated immune responses. Numerous etiologic factors are believed to evoke responses along
Is noneosinophilic asthma clinically important?
The view that noneosinophilic asthma represents a clinically important asthma phenotype would be strengthened if there were evidence of differences in epidemiology, natural history, or treatment response. These possibilities have not been explored extensively, and much of the available work is limited by the population size and the uncontrolled, observational nature of the studies. However, there is growing evidence that noneosinophilic asthma is associated with a difference in epidemiology,
Conclusion
There does seem to be sufficient evidence to support the existence of a subgroup of patients with asthma who have stable noneosinophilic and often neutrophilic disease. In comparison with eosinophilic asthma, patients with noneosinophilic asthma have differences in airway histopathology, airway structure, mechanisms of airway dysfunction, potential etiologic factors, response to treatment, and perhaps prognosis. The identification of this phenotype at the time of diagnosis is important, because
References (87)
- et al.
Non-eosinophilic corticosteroid unresponsive asthma
Lancet
(1999) - et al.
Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response
Lancet
(2000) - et al.
Sputum analysis, bronchial hyperresponsiveness, and airway function in asthma: results of a factor analysis
J Allergy Clin Immunol
(1999) - et al.
Asthma exacerbations and sputum eosinophil counts: a randomised controlled trial
Lancet
(2002) - et al.
Heterogeneity of airway inflammation in persistent asthma: evidence of neutrophilic inflammation and increased sputum interleukin-8
Chest
(2001) - et al.
Identifying “well-controlled” and “not well-controlled” asthma using the Asthma Control Questionnaire
Respir Med
(2006) - et al.
Endotoxin-stimulated innate immunity: a contributing factor for asthma
J Allergy Clin Immunol
(2001) - et al.
Eosinophil influx to the nasal airway after local, low-level LPS challenge in humans
J Allergy Clin Immunol
(1999) - et al.
Accelerated decline of lung function in COPD patients with chronic hepatitis C virus infection: a preliminary study based on small numbers of patients
Chest
(2003) - et al.
Noneosinophilic CD4 lymphocytic airway inflammation in menopausal women with chronic dry cough
Chest
(2005)
Smoking and airway inflammation in patients with mild asthma
Chest
Relationship between airway inflammation, hyperresponsiveness, and obstruction in asthma
J Allergy Clin Immunol
Multicentre randomised placebo-controlled trial of inhaled fluticasone propionate in patients with chronic obstructive pulmonary disease. International COPD Study Group
Lancet
Low sputum eosinophils predict the lack of response to beclomethasone in symptomatic asthmatic patients
Chest
Interferon therapy induces the improvement of lung function by inhaled corticosteroid therapy in asthmatic patients with chronic hepatitis C virus infection: a preliminary study
Chest
The Salmeterol Multicenter Asthma Research Trial: a comparison of usual pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol
Chest
Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention: NHLBI/WHO Workshop report. 02-3659
Mucosal inflammation in asthma
Am Rev Respir Dis
Eosinophils and mast cells in bronchoalveolar lavage in subjects with mild asthma: relationship to bronchial hyperreactivity
Am Rev Respir Dis
Eosinophilic inflammation in asthma
N Engl J Med
Prednisolone treatment in asthma: reduction in the numbers of eosinophils, T cells, tryptase-only positive mast cells, and modulation of IL-4, IL-5, and interferon-gamma cytokine gene expression within the bronchial mucosa
Am J Respir Crit Care Med
Cellular events in the bronchi in mild asthma and after bronchial provocation
Am Rev Respir Dis
The use of induced sputum to investigate airway inflammation
Thorax
Cellular profiles in asthmatic airways: a comparison of induced sputum, bronchial washings, and bronchoalveolar lavage fluid
Thorax
Induced sputum, bronchoalveolar lavage and blood from mild asthmatics: inflammatory cells, lymphocyte subsets and soluble markers compared
Eur Respir J
Comparison of leukocyte counts in sputum, bronchial biopsies, and bronchoalveolar lavage
Am J Respir Crit Care Med
Anti-IL-5 treatment reduces deposition of ECM proteins in the bronchial subepithelial basement membrane of mild atopic asthmatics
J Clin Invest
Eosinophilic bronchitis: clinical manifestations and implications for treatment
Thorax
Determining asthma treatment by monitoring sputum cell counts: effect on exacerbations
Eur Respir J
Eosinophilic bronchitis: an important cause of prolonged cough
Ann Med
Analysis of induced sputum in adults with asthma: identification of subgroup with isolated sputum neutrophilia and poor response to inhaled corticosteroids
Thorax
Mast-cell infiltration of airway smooth muscle in asthma
N Engl J Med
Occupational asthma due to low molecular weight agents: eosinophilic and non-eosinophilic variants
Thorax
Evidence that severe asthma can be divided pathologically into two inflammatory subtypes with distinct physiologic and clinical characteristics
Am J Respir Crit Care Med
Exacerbations of asthma without sputum eosinophilia
Thorax
Prominent neutrophilic inflammation in sputum from subjects with asthma exacerbation
J Allergy Clin Immunol
Induced sputum cell counts in healthy adults
Am J Respir Crit Care Med
Induced sputum cellularity: reference values and distribution in normal volunteers
Am J Respir Crit Care Med
The use of exhaled nitric oxide concentration to identify eosinophilic airway inflammation: an observational study in adults with asthma
Clin Exp Allergy
Development and validation of a questionnaire to measure asthma control
Eur Respir J
Inflammatory subtypes in asthma: assessment and identification using induced sputum
Respirology
Airway inflammation, basement membrane thickening and bronchial hyperresponsiveness in asthma
Thorax
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(Supported by an unrestricted educational grant from Genentech, Inc. and Novartis Pharmaceuticals Corporation)
Series editors: Donald Y. M. Leung, MD, PhD, and Dennis K. Ledford, MD
Disclosure of potential conflict of interest: I. D. Pavord has received grant support from GlaxoSmithKline and is on the speakers' bureau for GlaxoSmithKline and AstraZeneca. P. Haldar has declared that he has no conflict of interest.