Severe asthma: Definition and mechanisms

Allergy: European Journal of Allergy and Clinical Immunology

Volumn 56, Issue 9, 2001, Pages 825-840

  Stirling, R G ^a   Chung, K F ^a  

^a NATIONAL HEART AND LUNG INSTITUTE   (United Kingdom)

Author keywords

Asthma; Inflammation; Severity; Treatment

Indexed keywords

ACETYLSALICYLIC ACID; ALLERGEN; ANTIBODY; ARACHIDONATE 5 LIPOXYGENASE; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; BETA ADRENERGIC RECEPTOR STIMULATING AGENT; CD14 ANTIGEN; CD8 ANTIGEN; CHEMOKINE; COLLAGEN; CORTICOSTEROID; CYTOKINE; ENDOTHELIN 1; FOOD ADDITIVE; GLUTATHIONE TRANSFERASE; GROWTH FACTOR; HISTAMINE; IMMUNOGLOBULIN E; LEUKOTRIENE; LEUKOTRIENE C4 SYNTHASE; METHACHOLINE; NEUROPEPTIDE; NEUROTROPHIN; NITRIC OXIDE; NONSTEROID ANTIINFLAMMATORY AGENT; PREDNISOLONE; RECEPTOR; SALBUTAMOL; TOBACCO SMOKE; UNINDEXED DRUG;

ASTHMA; ATOPY; COMORBIDITY; DIFFERENTIAL DIAGNOSIS; DISEASE SEVERITY; FORCED EXPIRATORY VOLUME; GASTROESOPHAGEAL REFLUX; GENE EXPRESSION; GENETIC POLYMORPHISM; HUMAN; INFLAMMATION; PATHOPHYSIOLOGY; PREVALENCE; PRIORITY JOURNAL; RESPIRATORY TRACT INFECTION; REVIEW; RHINITIS; SINUSITIS; SOCIAL PSYCHOLOGY; SYMPTOMATOLOGY;

ASTHMA; DIAGNOSIS, DIFFERENTIAL; HUMANS; PREVALENCE; RISK FACTORS; SEVERITY OF ILLNESS INDEX;

EID: 0034861628     PISSN: 01054538     EISSN: None     Source Type: Journal    
DOI: 10.1034/j.1398-9995.2001.00143.x     Document Type: Review

References (181)

1. Current understanding, recommendations, and unanswered questions
2. British guidelines on asthma management: 1995 Review and position statement
3. Canadian Asthma Consensus Report 1999
4. Neutrophilic inflammation in severe persistent asthma
5. Guideline for the management of chronic asthma in adults - 2000 update
6. Asthma control versus asthma severity
7. Assessment of the severity of asthma by an expert system. Description and evaluation
8. Evidence for the increase in asthma worldwide
9. A national estimate of the economic costs of asthma
10. A cost analysis on the pattern of asthma prescribing in the UK
11. Morbidity from asthma in relation to regular treatment: A community based study
12. Using Global Initiative for Asthma guidelines to assess asthma severity in populations
13. Pharmaceutically-based severity stratification of an asthmatic population
14. Severity and associated risk factors in adult asthma patients in Turkey
15. Efficacy and safety of inhaled corticosteroids. New developments
16. The natural history of asthma in adults: The problem of irreversibility
17. Airway remodeling and persistent airway obstruction in asthma
18. The natural history of asthma in adults: The problem of irreversibility
19. Irreversibility of obstructive changes in severe asthma in childhood
20. Consequences of long-term inflammation. The natural history of asthma
21. Clinical features of vocal cord dysfunction
22. Airway obstruction and bronchial hyperresponsiveness in left ventricular failure and mitral stenosis
23. Therapeutic compliance in asthma; its magnitude and implications
24. Noncompliance and treatment failure in children with asthma
25. Comparison of patients' compliance with prescribed oral and inhaled asthma medications
26. Compliance with oral corticosteroids during steroid trials in chronic airways obstruction
27. Prevalence of gastroesophageal reflux symptoms in asthma
28. The role of "occult" gastroesophageal reflux in chronic pulmonary disease in children
29. Methacholine bronchial hyperresponsiveness in chronic sinusitis
30. Nasal inhalation of the glucocorticoid budesonide from a spacer for the treatment of patients with pollen rhinitis and asthma
31. Treatment of allergic rhinitis with intranasal corticosteroids in patients with mild asthma: Effect on lower airway responsiveness
32. Oesophageal function and symptoms in moderate and severe asthma
33. The relationship of gastroesophageal reflux to nocturnal wheezing in children with asthma
34. Relationship between asthma and gastrooesophageal reflux
35. Intraesophageal perfusion of acid increases the bronchomotor response to methacholine and to isocapnic hyperventilation in asthmatic subjects
36. Antireflux treatment for asthma. Improvement in patients with associated gastroesophageal reflux
37. Further investigation of the association between gastroesophageal reflux and bronchoconstriction
38. Chronic cough due to gastroesophageal reflux. Clinical, diagnostic, and pathogenetic aspects
39. Omeprazole in the treatment of asthmatics with nocturnal symptoms and gastro-oesophageal reflux: A placebo-controlled cross-over study
40. Medical and surgical treatment of nonallergic asthma associated with gastroesophageal reflux
41. Asthma and bacterial sinusitis in children
42. Chronic sinus disease with associated reactive airway disease in children
43. Toluene diisocyanate induced asthma: Outcome according to persistence or cessation of exposure
44. Effect of natural allergen exposure during the grass pollen season on airways inflammatory cells and asthma symptoms
45. Expression of interleukin (IL)-4 and IL-5 proteins in asthma induced by toluene diisocyanate (TDI)
46. Role of the indoor environment in determining the severity of asthma
47. Allergen exposure decreases glucocorticoid receptor binding affinity and steroid responsiveness in atopic asthmatics
48. Indoor air pollution and asthma. Results from a panel study
49. Severity of asthma is related to endotoxin in house dust
50. Domestic endotoxin exposure and clinical severity of asthma
51. Endotoxins, asthma, and allergic immune responses
52. Effect of inhaled endotoxin on bronchial reactivity in asthmatic and normal subjects
53. A second-generation genomewide screen for asthma-susceptibility alleles in a founder population
54. Salicylates in foods
55. Alcoholic drinks: Important triggers for asthma
56. 4 synthase in bronchial biopsies from patients with aspirin-intolerant asthma
57. 4 synthase promoter polymorphism and risk of aspirin-induced asthma
58. Effect of the leukotriene receptor antagonist MK-0679 on baseline pulmonary function in aspirin sensitive asthmatic subjects
59. Benefits from adding the 5-lipoxygenase inhibitor zileuton to conventional therapy in aspirin-intolerant asthmatics
60. The pivotal role of 5-lipoxygenase products in the reaction of aspirin-sensitive asthmatics to aspirin
61. Timolol eyedrop-induced fatal bronchospasm in an asthmatic patient
62. Viral respiratory tract infection and exacerbations of asthma in adult patients
63. Respiratory viral and Mycoplasma infections in patients hospitalized for acute asthma
64. Virus-specific CD8+ cells can switch to interleukin 5 production and induce airway eosinophilia
65. Persistent adenoviral infection and chronic airway obstruction in children
66. Rhinovirus infections: Induction and modulation of airways inflammation in asthma
67. Respiratory syncytial virus induces the expression of 5-lipoxygenase and endothelin-1 in bronchial epithelial cells
68. Low grade rhinovirus infection induces a prolonged release of IL-8 in pulmonary epithelium
69. Influenza vaccine for patients with chronic obstructive pulmonary disease (Cochrane Review)
70. Detection of Mycoplasma pneumoniae in the airways of adults with chronic asthma
71. Chronic Chlamydia pneumoniae infection and asthma exacerbations in children
72. Evidence for Chlamydia pneumoniae infection in steroid-dependent asthma
73. Circumstances surrounding the deaths of children due to asthma. A case-control study
74. A district confidential enquiry into deaths due to asthma
75. Provoking factors in asthma
76. Brittle asthma
77. Psychological morbidity and coping skills in patients with brittle and non-brittle asthma: A case-control study
78. Is the association between inhaled beta-agonist use and life-threatening asthma because of confounding by severity?
79. Ventilatory responses to hypoxia and hypercapnia in asthmatics with previous respiratory failure
80. Chemosensitivity and perception of dyspnea in patients with a history of near-fatal asthma
81. Corticosteroid-resistant asthma. Definitions
82. Difficult-to-control asthma: Clinical characteristics of steroid-insensitive asthma
83. Fatal asthma
84. Potentially fatal asthma
85. The diagnosis of potentially fatal asthma in hospitalized adults. Patient characteristics and increased severity of asthma
86. Markers of risk of asthma death or readmission in the 12 months following a hospital admission for asthma
87. Asthma variation with menstruation
88. Morbidity in asthma in relation to the menstrual cycle
89. Premenstrual exacerbation of asthma
90. Severe premenstrual exacerbations of asthma: Effect of intramuscular progesterone
91. Sudden death in asthma
92. Upregulation of alpha GM-CSF-receptor in nonatopic asthma but not in atopic asthma
93. Cytokine serum profiles in allergic and non-allergic asthma. Increased production of IL-10 by non-allergic asthmatic patients
94. T cell subsets and cytokines in allergic and non-allergic children. I. Analysis of IL-4, IFN-gamma and IL-13 mRNA expression and protein production
95. Dissociation of production of interleukin-4 and interleukin-5
96. Expression of IL-4 and IL-5 mRNA and protein product by CD4+ and CD8+ T cells, eosinophils, and mast cells in bronchial biopsies obtained from atopic and nonatopic (intrinsic) asthmatics
97. Comparison of the immunopathology of extrinsic, intrinsic and occupational asthma
98. Relation between airway responsiveness and serum IgE in children with asthma and in apparently normal children
99. Association of asthma with serum IgE levels and skin-test reactivity to allergens
100. Serum IgE levels, atopy, and asthma in young adults: Results from a longitudinal cohort study
101. Relationship between serum IgE and airway responsiveness in adults with asthma
102. A 15-year follow-up study of ventilatory function in adults with asthma
103. Rate of decline of lung function in subjects with asthma
104. Effects of asthma on pulmonary function in children. A longitudinal population-based study
105. Relationship of serum IgE concentration to level and rate of decline of pulmonary function: The Normative Aging Study
106. Prolonged episodes of persistent asthma: A distinct clinical pattern with characteristic clinical features
107. 1 in two cohort studies
108. Epidemiological study of the genetics and environment of asthma, bronchial hyperresponsiveness, and atopy: Phenotype issues
109. Treatment of allergic asthma with monoclonal anti-IgE antibody
110. Elevation of total serum immunoglobulin E is associated with asthma in nonallergic individuals
111. Eosinophilic inflammation in asthma
112. Expression of mRNA for interleukin-5 in mucosal bronchial biopsies from asthma
113. Cytokines in symptomatic asthma airways
114. Activated T cells and eosinophilia in bronchoalveolar lavages from subjects with asthma correlated with disease severity
115. Bronchoscopic evaluation of severe asthma. Persistent inflammation associated with high dose glucocorticoids
116. Eosinophil-associated TGF-beta1 mRNA expression and airways fibrosis in bronchial asthma
117. Sudden-onset fatal asthma. A distinct entity with few eosinophils and relatively more neutrophils in the airway submucosa?
118. Increase in exhaled nitric oxide levels in patients with difficult asthma and correlation with symptoms and disease severity despite treatment with oral and inhaled corticosteroids
119. Airways inflammation in nocturnal asthma
120. Enhanced production of oxygen radicals in nocturnal asthma
121. Alveolar tissue inflammation in asthma
122. Effect of 5-lipoxygenase inhibition on bronchoconstriction and airway inflammation in nocturnal asthma
123. Relationship between IL-4 and IL-5 mRNA expression and disease severity in atopic asthma
124. IL-11 expression is increased in severe asthma: Association with epithelial cells and eosinophils
125. Enhanced expression of eotaxin and CCR3 mRNA and protein in atopic asthma. Association with airway hyperresponsiveness and predominant co-localization of eotaxin mRNA to bronchial epithelial and endothelial cells
126. Eotaxin and impaired lung function in asthma
127. Activated memory T helper cells in bronchoalveolar lavage fluid from patients with atopic asthma: Relation to asthma symptoms, lung function, and bronchial responsiveness
128. CD4 T-lymphocyte activation in acute severe asthma. Relationship to disease severity and atopic status
129. Serum eosinophil cationic protein as a marker of eosinophilic inflammation in asthma
130. Eosinophil cationic protein levels in induced sputum correlate with the severity of bronchial asthma
131. 4 excretion during aspirin challenges with severity of respiratory responses
132. Effect of differing doses of inhaled budesonide on markers of airway inflammation in patients with mild asthma
133. Inhaled glucocorticoids decrease nitric oxide in exhaled air of asthmatic patients
134. Eosinophil cationic protein (ECP) and eosinophil protein X (EPX) concentrations in serum and bronchial lavage fluid in asthma. Effect of prednisolone treatment
135. Association between a sequence variant in the IL-4 gene promoter and FEV in asthma
136. A repeat polymorphism in interleukin-4 gene is highly associated with specific clinical phenotypes of asthma
137. Polymorphisms in the IL4, IL4RA, and FCERIB genes and asthma severity
138. The R576 IL-4 receptor alpha allele correlates with asthma severity
139. Haplotype associated with low interleukin-10 production in patients with severe asthma
140. Differences in the genotypes and plasma concentrations of the interleukin-1 receptor antagonist in black and white South African asthmatics and control subjects
141. Polymorphisms at the glutathione S-transferase, GSTP1 locus: A novel mechanism for susceptibility and development of atopic airway inflammation
142. Amino-terminal polymorphisms of the human beta 2-adrenergic receptor impart distinct agonist-promoted regulatory properties
143. Association of beta2-adrenergic receptor polymorphisms with severe asthma
144. Asthma exacerbations during long term beta agonist use: Influence of beta (2) adrenoceptor polymorphism
145. 2-Adrenergic receptor haplotypes in mild, moderate and fatal/near fatal asthma
146. Naturally occurring mutations in the human 5-lipoxygenase gene promoter that modify transcription factor binding and reporter gene transcription
147. Pharmacogenetic association between ALOX5 promoter genotype and the response to anti-asthma treatment
148. Novel polymorphism of the 5-lipoxygenase activating protein (FLAP) promoter gene associated with asthma
149. Enhanced expression of the leukotriene C(4) synthase due to overactive transcription of an allelic variant associated with aspirin-intolerant asthma
150. Interleukin-4 gene promoter polymorphism [C590T] and asthma in Kuwaiti Arabs
151. Promoter polymorphism in the candidate genes, IL-4, IL-9, TGF-beta1, for atopy and asthma
152. High-dose intramuscular triamcinolone in severe, chronic, life-threatening asthma
153. Dysregulation of interleukin 4, interleukin 5, and interferon gamma gene expression in steroid-resistant asthma
154. Abnormal glucocorticoid receptor-activator protein 1 interaction in steroid-resistant asthma
155. Steroid resistance in asthma
156. Glucocorticoid receptor localization in normal and asthmatic lung
157. Increased glucocorticoid receptor beta in airway cells of glucocorticoid-insensitive asthma
158. Association of glucocorticoid insensitivity with increased expression of glucocorticoid receptor beta
159. Increased number of glucocorticoid receptor-beta-expressing cells in the airways in fatal asthma
160. Glucocorticoid resistance in asthma is associated with elevated in vivo expression of the glucocorticoid receptor beta-isoform
161. The bronchial epithelium as a key regulator of airway inflammation and remodelling in asthma
162. Airway wall remodelling: Does it occur and what does it mean?
163. Asthma. From bronchoconstriction to airways inflammation and remodeling
164. Dissociation between airway inflammation and airway hyperresponsiveness in allergic asthma
165. Response of airway smooth muscle cells to TGF-beta 1: Effects on growth and synthesis of glycosaminoglycans
166. An optimal condition of bronchial cell proliferation stimulated by insulin-like growth factor-I
167. Involvement of the epidermal growth factor receptor in epithelial repair in asthma
168. Inhaled corticosteroids decrease subepithelial collagen deposition by modulation of the balance between matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 expression in asthma
169. Serum matrix metalloproteinase-9: Tissue inhibitor of metalloproteinase-1 ratio correlates with steroid responsiveness in moderate to severe asthma
170. Nerve growth factor contributes to the generation of inflammatory sensory hypersensitivity
171. Airway inflammation and structural changes in airway hyper-responsiveness and asthma: An overview
172. Bronchial subepithelial fibrosis correlates with airway responsiveness to methacholine
173. Asymptomatic airway hyperresponsiveness: Relationships with airway inflammation and remodelling
174. Airways remodeling is a distinctive feature of asthma and is related to severity of disease
175. Bronchial responsiveness to distilled water and methacholine and its relationship to inflammation and remodeling of the airways in asthma
176. The role of inflammation in airway disease: Remodeling
177. Inhaled corticosteroid reduced lamina reticularis of the basement membrane by modulation of insulin-like growth factor (IGF)-I expression in bronchial asthma
178. Placebo-controlled immunopathologic study of four months of inhaled corticosteroids in asthma
179. Effect of short-term treatment with low-dose inhaled fluticasone propionate on airway inflammation and remodeling in mild asthma: A placebo-controlled study
180. Difficult/therapy-resistant asthma: The need for an integrated approach to define clinical phenotypes, evaluate risk factors, understand pathophysiology and find novel therapies