Skip to main content
Top
Published in: BMC Medicine 1/2011

Open Access 01-12-2011 | Minireview

Emerging therapies for severe asthma

Authors: Neil C Thomson, Rekha Chaudhuri, Mark Spears

Published in: BMC Medicine | Issue 1/2011

Login to get access

Abstract

Many patients with asthma have poorly controlled symptoms, and particularly for those with severe disease, there is a clear need for improved treatments. Two recent therapies licensed for use in asthma are omalizumab, a humanized monoclonal antibody that binds circulating IgE antibody, and bronchial thermoplasty, which involves the delivery of radio frequency energy to the airways to reduce airway smooth muscle mass. In addition, there are new therapies under development for asthma that have good potential to reach the clinic in the next five years. These include biological agents targeting pro-inflammatory cytokines such as interleukin-5 and interleukin-13, inhaled ultra long-acting β2-agonists and once daily inhaled corticosteroids. In addition, drugs that block components of the arachidonic acid pathway that targets neutrophilic asthma and CRTH2 receptor antagonists that inhibit the proinflammatory actions of prostaglandin D2 may become available. We review the recent progress made in developing viable therapies for severe asthma and briefly discuss the idea that development of novel therapies for asthma is likely to increasingly involve the assessment of genotypic and/or phenotypic factors.
Appendix
Available only for authorised users
Literature
2.
go back to reference British Thoracic Society Scottish Intercollegiate Guidelines Network: Thorax. 2008, 63: iv1-iv121.CrossRef British Thoracic Society Scottish Intercollegiate Guidelines Network: Thorax. 2008, 63: iv1-iv121.CrossRef
3.
go back to reference Expert Panel Report 3 (EPR-3): Guidelines for the Diagnosis and Management of Asthma-Summary Report 2007. J Allergy Clin Immunol. 2007, 120: S94-S138. Expert Panel Report 3 (EPR-3): Guidelines for the Diagnosis and Management of Asthma-Summary Report 2007. J Allergy Clin Immunol. 2007, 120: S94-S138.
4.
go back to reference Partridge M, van der Molen T, Myrseth S-E, Busse W: Attitudes and actions of asthma patients on regular maintenance therapy: the INSPIRE study. BMC Pulm Med. 2006, 6: 13.CrossRefPubMedPubMedCentral Partridge M, van der Molen T, Myrseth S-E, Busse W: Attitudes and actions of asthma patients on regular maintenance therapy: the INSPIRE study. BMC Pulm Med. 2006, 6: 13.CrossRefPubMedPubMedCentral
5.
go back to reference Dockrell M, Partridge M, Valovirta E: The limitations of severe asthma: the results of a European survey. Allergy. 2007, 62: 134-141.CrossRefPubMed Dockrell M, Partridge M, Valovirta E: The limitations of severe asthma: the results of a European survey. Allergy. 2007, 62: 134-141.CrossRefPubMed
6.
go back to reference Spears M, Cameron E, Chaudhuri R, Thomson NC: Challenges of treating asthma in people who smoke. Expert Rev Clin Immunol. 2010, 6: 257-268.CrossRefPubMed Spears M, Cameron E, Chaudhuri R, Thomson NC: Challenges of treating asthma in people who smoke. Expert Rev Clin Immunol. 2010, 6: 257-268.CrossRefPubMed
7.
go back to reference Chaudhuri R, McSharry C, McCoard A, Livingston E, Hothersall E, Spears M, Lafferty J, Thomson NC: Role of symptoms and lung function in determining asthma control in smokers with asthma. Allergy. 2008, 63: 132-135.CrossRefPubMed Chaudhuri R, McSharry C, McCoard A, Livingston E, Hothersall E, Spears M, Lafferty J, Thomson NC: Role of symptoms and lung function in determining asthma control in smokers with asthma. Allergy. 2008, 63: 132-135.CrossRefPubMed
8.
go back to reference Heaney LG, Brightling CE, Menzies-Gow A, Stevenson M, Niven RM, British Thoracic Society Difficult Asthma Network: Refractory asthma in the UK: cross-sectional findings from a UK multicentre registry. Thorax. 2010, 65: 787-794.CrossRefPubMedPubMedCentral Heaney LG, Brightling CE, Menzies-Gow A, Stevenson M, Niven RM, British Thoracic Society Difficult Asthma Network: Refractory asthma in the UK: cross-sectional findings from a UK multicentre registry. Thorax. 2010, 65: 787-794.CrossRefPubMedPubMedCentral
9.
go back to reference Bel E, Sousa A, Fleming L, Bush A, Chung K, Versnel J, Wagener A, Wagers S, Sterk P, Compton C, the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcome (U-BIOPRED) Consortium, Consensus Generation: Diagnosis and definition of severe refractory asthma: an international consensus statement from the Innovative Medicine Initiative (IMI). Thorax. 2011, 153643 Published Online First: 23 November 2010 Bel E, Sousa A, Fleming L, Bush A, Chung K, Versnel J, Wagener A, Wagers S, Sterk P, Compton C, the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcome (U-BIOPRED) Consortium, Consensus Generation: Diagnosis and definition of severe refractory asthma: an international consensus statement from the Innovative Medicine Initiative (IMI). Thorax. 2011, 153643 Published Online First: 23 November 2010
10.
go back to reference Holgate ST, Polosa R: The mechanisms, diagnosis, and management of severe asthma in adults. The Lancet. 2006, 368: 780-793.CrossRef Holgate ST, Polosa R: The mechanisms, diagnosis, and management of severe asthma in adults. The Lancet. 2006, 368: 780-793.CrossRef
11.
go back to reference Adcock IM, Caramori G, Chung KF: New targets for drug development in asthma. Lancet. 2008, 372: 1073-1087.CrossRefPubMed Adcock IM, Caramori G, Chung KF: New targets for drug development in asthma. Lancet. 2008, 372: 1073-1087.CrossRefPubMed
12.
go back to reference Barnes PJ: New therapies for asthma: is there any progress?. Trends Pharmacolog Sci. 2010, 31: 335-343.CrossRef Barnes PJ: New therapies for asthma: is there any progress?. Trends Pharmacolog Sci. 2010, 31: 335-343.CrossRef
13.
go back to reference Hamelmann E: The rationale for treating allergic asthma with anti-IgE. Eur Respir Rev. 2007, 16: 61-66.CrossRef Hamelmann E: The rationale for treating allergic asthma with anti-IgE. Eur Respir Rev. 2007, 16: 61-66.CrossRef
14.
go back to reference Walker S, Monteil M, Phelan K, Lasserson T, Walters E: Anti-IgE for chronic asthma in adults and children. Cochrane Database of Systematic Reviews. 2006 Walker S, Monteil M, Phelan K, Lasserson T, Walters E: Anti-IgE for chronic asthma in adults and children. Cochrane Database of Systematic Reviews. 2006
15.
go back to reference Rodrigo GJ, Neffen H, Castro-Rodriguez JA: Efficacy and Safety of Subcutaneous Omalizumab vs Placebo as Add-on Therapy to Corticosteroids for Children and Adults With Asthma. Chest. 2011, 139: 28-35.CrossRefPubMed Rodrigo GJ, Neffen H, Castro-Rodriguez JA: Efficacy and Safety of Subcutaneous Omalizumab vs Placebo as Add-on Therapy to Corticosteroids for Children and Adults With Asthma. Chest. 2011, 139: 28-35.CrossRefPubMed
16.
17.
go back to reference Corren J, Casale TB, Lanier B, Buhl R, Holgate S, Jimenez P: Safety and tolerability of omalizumab. Clin Exp Allergy. 2009, 39: 788-797.CrossRefPubMed Corren J, Casale TB, Lanier B, Buhl R, Holgate S, Jimenez P: Safety and tolerability of omalizumab. Clin Exp Allergy. 2009, 39: 788-797.CrossRefPubMed
18.
go back to reference Aidan AL, James EF, Abdelkader R, Mary KM, Mary SB, Hassan NT, Anthony ND, Stephen AT, Stanley JS: Baseline characteristics of patients enrolled in EXCELS: a cohort study. Ann Allergy Asthma Immunol. 2009, 103: 212-219.CrossRef Aidan AL, James EF, Abdelkader R, Mary KM, Mary SB, Hassan NT, Anthony ND, Stephen AT, Stanley JS: Baseline characteristics of patients enrolled in EXCELS: a cohort study. Ann Allergy Asthma Immunol. 2009, 103: 212-219.CrossRef
19.
go back to reference Omalizumab: potential risk of arterial thrombotic events. Drug Safety Update. 2011, 4: A4. Omalizumab: potential risk of arterial thrombotic events. Drug Safety Update. 2011, 4: A4.
20.
go back to reference Holgate ST, Arshad HS, Roberts GC, Howarth PH, Thurner P, Davies DE: A new look at the pathogenesis of asthma. Clin Sci. 2010, 118: 439-450.CrossRef Holgate ST, Arshad HS, Roberts GC, Howarth PH, Thurner P, Davies DE: A new look at the pathogenesis of asthma. Clin Sci. 2010, 118: 439-450.CrossRef
21.
go back to reference Levine S, Wenzel S: Narrative review: the role of Th2 immune pathway modulation in the treatment of severe asthma and its phenotypes. Ann Intern Med. 2010, 152: 232-237.CrossRefPubMedPubMedCentral Levine S, Wenzel S: Narrative review: the role of Th2 immune pathway modulation in the treatment of severe asthma and its phenotypes. Ann Intern Med. 2010, 152: 232-237.CrossRefPubMedPubMedCentral
22.
go back to reference Howarth PH, Babu KS, Arshad HS, Lau L, Buckley M, McConnell W, Beckett P, Al Ali M, Chauhan A, Wilson SJ, Reynolds A, Davies DE, Holgate ST: Tumour necrosis factor (TNF{alpha}) as a novel therapeutic target in symptomatic corticosteroid dependent asthma. Thorax. 2005, 60: 1012-1018.CrossRefPubMedPubMedCentral Howarth PH, Babu KS, Arshad HS, Lau L, Buckley M, McConnell W, Beckett P, Al Ali M, Chauhan A, Wilson SJ, Reynolds A, Davies DE, Holgate ST: Tumour necrosis factor (TNF{alpha}) as a novel therapeutic target in symptomatic corticosteroid dependent asthma. Thorax. 2005, 60: 1012-1018.CrossRefPubMedPubMedCentral
23.
go back to reference Berry M, Hargadon B, Shelley M, Parker D, Shaw D, Green R, Bradding P, Brightling C, Wardlaw A, Pavord I: Inhibition of Tumor Necrosis Factor α for Refractory Asthma. N Eng J Med. 2006, 354: 754-758.CrossRef Berry M, Hargadon B, Shelley M, Parker D, Shaw D, Green R, Bradding P, Brightling C, Wardlaw A, Pavord I: Inhibition of Tumor Necrosis Factor α for Refractory Asthma. N Eng J Med. 2006, 354: 754-758.CrossRef
24.
go back to reference Wenzel SE, Barnes PJ, Bleecker ER, Bousquet J, Busse W, Dahlen S-E, Holgate ST, Meyers DA, Rabe KF, Antczak A, Baker J, Horvath I, Mark Z, Bernstein D, Kerwin E, Schlenker-Herceg R, Lo KH, Watt R, Barnathan ES, Chanez P, T03 Asthma Investigators: A Randomized, Double-blind, Placebo-controlled Study of Tumor Necrosis Factor-{alpha} Blockade in Severe Persistent Asthma. Am J Respir Crit Care Med. 2009, 179: 549-558.CrossRefPubMed Wenzel SE, Barnes PJ, Bleecker ER, Bousquet J, Busse W, Dahlen S-E, Holgate ST, Meyers DA, Rabe KF, Antczak A, Baker J, Horvath I, Mark Z, Bernstein D, Kerwin E, Schlenker-Herceg R, Lo KH, Watt R, Barnathan ES, Chanez P, T03 Asthma Investigators: A Randomized, Double-blind, Placebo-controlled Study of Tumor Necrosis Factor-{alpha} Blockade in Severe Persistent Asthma. Am J Respir Crit Care Med. 2009, 179: 549-558.CrossRefPubMed
25.
go back to reference Holgate ST, Noonan M, Chanez P, Busse W, Dupont L, Pavord I, Hakulinen A, Paolozzi L, Wajdula J, Zang C, Nelson H, Raible D: Efficacy and safety of etanercept in moderate-to-severe asthma: a randomised, controlled trial. Eur Respir J. 2011, 37: 1352-1359.CrossRefPubMed Holgate ST, Noonan M, Chanez P, Busse W, Dupont L, Pavord I, Hakulinen A, Paolozzi L, Wajdula J, Zang C, Nelson H, Raible D: Efficacy and safety of etanercept in moderate-to-severe asthma: a randomised, controlled trial. Eur Respir J. 2011, 37: 1352-1359.CrossRefPubMed
26.
go back to reference Nair P, Pizzichini MMM, Kjarsgaard M, Inman MD, Efthimiadis A, Pizzichini E, Hargreave FE, O'Byrne PM: Mepolizumab for Prednisone-Dependent Asthma with Sputum Eosinophilia. N Engl J Med. 2009, 360: 985-993.CrossRefPubMed Nair P, Pizzichini MMM, Kjarsgaard M, Inman MD, Efthimiadis A, Pizzichini E, Hargreave FE, O'Byrne PM: Mepolizumab for Prednisone-Dependent Asthma with Sputum Eosinophilia. N Engl J Med. 2009, 360: 985-993.CrossRefPubMed
27.
go back to reference Haldar P, Brightling CE, Hargadon B, Gupta S, Monteiro W, Sousa A, Marshall RP, Bradding P, Green RH, Wardlaw AJ, Pavord ID: Mepolizumab and Exacerbations of Refractory Eosinophilic Asthma. N Engl J Med. 2009, 360: 973-984.CrossRefPubMedPubMedCentral Haldar P, Brightling CE, Hargadon B, Gupta S, Monteiro W, Sousa A, Marshall RP, Bradding P, Green RH, Wardlaw AJ, Pavord ID: Mepolizumab and Exacerbations of Refractory Eosinophilic Asthma. N Engl J Med. 2009, 360: 973-984.CrossRefPubMedPubMedCentral
28.
go back to reference Wenzel SE: Eosinophils in Asthma-Closing the Loop or Opening the Door?. N Engl J Med. 2009, 360: 1026-1028.CrossRefPubMed Wenzel SE: Eosinophils in Asthma-Closing the Loop or Opening the Door?. N Engl J Med. 2009, 360: 1026-1028.CrossRefPubMed
29.
go back to reference Gamble J, Stevenson M, McClean E, Heaney LG: The Prevalence of Nonadherence in Difficult Asthma. Am J Respir Crit Care Med. 2009, 180: 817-822.CrossRefPubMed Gamble J, Stevenson M, McClean E, Heaney LG: The Prevalence of Nonadherence in Difficult Asthma. Am J Respir Crit Care Med. 2009, 180: 817-822.CrossRefPubMed
30.
go back to reference Corren J: Cytokine inhibition in severe asthma: Current knowledge and future directions. Curr Opin Pulm Med. 2011, 17: 29-33.CrossRefPubMed Corren J: Cytokine inhibition in severe asthma: Current knowledge and future directions. Curr Opin Pulm Med. 2011, 17: 29-33.CrossRefPubMed
31.
go back to reference Elias JA, Lee CG: IL-13 in Asthma: The Successful Integration of Lessons from Mice and Humans. Am J Respir Crit Care Med. 2011, 183: 957-958.CrossRefPubMed Elias JA, Lee CG: IL-13 in Asthma: The Successful Integration of Lessons from Mice and Humans. Am J Respir Crit Care Med. 2011, 183: 957-958.CrossRefPubMed
32.
go back to reference Gauvreau GM, Boulet L-P, Cockcroft DW, FitzGerald JM, Carlsten C, Davis BE, Deschesnes F, Duong M, Durn BL, Howie KJ, Hui L, Kasaian MT, Killian KJ, Strinich TX, Watson RM, Y N, Zhou S, Raible D, O'Byrne PM: The Effects of IL-13 Blockade on Allergen-Induced Airway Responses in Mild Atopic Asthma. Am J Respir Crit Care Med. 2011, 183: 1007-1014.CrossRefPubMed Gauvreau GM, Boulet L-P, Cockcroft DW, FitzGerald JM, Carlsten C, Davis BE, Deschesnes F, Duong M, Durn BL, Howie KJ, Hui L, Kasaian MT, Killian KJ, Strinich TX, Watson RM, Y N, Zhou S, Raible D, O'Byrne PM: The Effects of IL-13 Blockade on Allergen-Induced Airway Responses in Mild Atopic Asthma. Am J Respir Crit Care Med. 2011, 183: 1007-1014.CrossRefPubMed
33.
go back to reference Wenzel S, Wilbraham D, Fuller R, Getz EB, Longphre M: Effect of an interleukin-4 variant on late phase asthmatic response to allergen challenge in asthmatic patients: results of two phase 2a studies. The Lancet. 2007, 370: 1422-1431.CrossRef Wenzel S, Wilbraham D, Fuller R, Getz EB, Longphre M: Effect of an interleukin-4 variant on late phase asthmatic response to allergen challenge in asthmatic patients: results of two phase 2a studies. The Lancet. 2007, 370: 1422-1431.CrossRef
34.
go back to reference Busse WW, Israel E, Nelson HS, Baker JW, Charous BL, Young DY, Vexler V, Shames RS, the Daclizumab Asthma Study Goup: Daclizumab Improves Asthma Control in Patients with Moderate to Severe Persistent Asthma: A Randomized, Controlled Trial. Am J Respir Crit Care Med. 2008, 178: 1002-1008.CrossRefPubMed Busse WW, Israel E, Nelson HS, Baker JW, Charous BL, Young DY, Vexler V, Shames RS, the Daclizumab Asthma Study Goup: Daclizumab Improves Asthma Control in Patients with Moderate to Severe Persistent Asthma: A Randomized, Controlled Trial. Am J Respir Crit Care Med. 2008, 178: 1002-1008.CrossRefPubMed
35.
go back to reference Message SD, Laza-Stanca V, Mallia P, Parker HL, Zhu J, Kebadze T, Contoli M, Sanderson G, Kon OM, Papi A, Jeffery PK, Stanciu LA, Johnston SL: Rhinovirus induced lower respiratory illness is increased in asthma and related to virus load and Th1/2 cytokine and IL-10 production. Proc Nat Acad Sci USA. 2008, 105: 13562-13567.CrossRefPubMedPubMedCentral Message SD, Laza-Stanca V, Mallia P, Parker HL, Zhu J, Kebadze T, Contoli M, Sanderson G, Kon OM, Papi A, Jeffery PK, Stanciu LA, Johnston SL: Rhinovirus induced lower respiratory illness is increased in asthma and related to virus load and Th1/2 cytokine and IL-10 production. Proc Nat Acad Sci USA. 2008, 105: 13562-13567.CrossRefPubMedPubMedCentral
36.
go back to reference Cazzola M, Segreti A, Matera M: Novel bronchodilators in asthma. Curr Opin Pulm Med. 2010, 16: 6-12.CrossRefPubMed Cazzola M, Segreti A, Matera M: Novel bronchodilators in asthma. Curr Opin Pulm Med. 2010, 16: 6-12.CrossRefPubMed
38.
go back to reference Thomson NC, Spears M: The role of cigarette smoking on persistent airflow obstruction in asthma. Annals Resp Med. 2011. Thomson NC, Spears M: The role of cigarette smoking on persistent airflow obstruction in asthma. Annals Resp Med. 2011.
39.
go back to reference Park HW, Yang MS, Park CS, Kim TB, Moon HB, Min KU, Kim YY, Cho SH: Additive role of tiotropium in severe asthmatics and Arg16Gly in ADRB2 as a potential marker to predict response. Allergy. 2009, 64: 778-783.CrossRefPubMed Park HW, Yang MS, Park CS, Kim TB, Moon HB, Min KU, Kim YY, Cho SH: Additive role of tiotropium in severe asthmatics and Arg16Gly in ADRB2 as a potential marker to predict response. Allergy. 2009, 64: 778-783.CrossRefPubMed
40.
go back to reference De Bosscher K, Haegeman G, Elewaut D: Targeting inflammation using selective glucocorticoid receptor modulators. Curr Opin Pharmacol. 2010, 10: 497-504.CrossRefPubMed De Bosscher K, Haegeman G, Elewaut D: Targeting inflammation using selective glucocorticoid receptor modulators. Curr Opin Pharmacol. 2010, 10: 497-504.CrossRefPubMed
41.
go back to reference Schacke H, Schottelius A, Docke W-D, Strehlke P, Jaroch S, Schmees N, Rehwinkel H, Hennekes H, Asadullah K: Dissociation of transactivation from transrepression by a selective glucocorticoid receptor agonist leads to separation of therapeutic effects from side effects. Proc Natl Acad Sci USA. 2004, 101: 227-232.CrossRefPubMed Schacke H, Schottelius A, Docke W-D, Strehlke P, Jaroch S, Schmees N, Rehwinkel H, Hennekes H, Asadullah K: Dissociation of transactivation from transrepression by a selective glucocorticoid receptor agonist leads to separation of therapeutic effects from side effects. Proc Natl Acad Sci USA. 2004, 101: 227-232.CrossRefPubMed
42.
go back to reference Schäcke H, Zollner TM, Döcke WD, Rehwinkel H, Jaroch S, Skuballa W, Neuhaus R, May E, Zügel U, Asadullah K: Characterization of ZK 245186, a novel, selective glucocorticoid receptor agonist for the topical treatment of inflammatory skin diseases. Br J Pharmacol. 2009, 158: 1088-1103.CrossRefPubMedPubMedCentral Schäcke H, Zollner TM, Döcke WD, Rehwinkel H, Jaroch S, Skuballa W, Neuhaus R, May E, Zügel U, Asadullah K: Characterization of ZK 245186, a novel, selective glucocorticoid receptor agonist for the topical treatment of inflammatory skin diseases. Br J Pharmacol. 2009, 158: 1088-1103.CrossRefPubMedPubMedCentral
43.
go back to reference Zhang J, Cavet M, VanderMeid K, Salvador-Silva M, López F, Ward K: BOL-303242-X, a novel selective glucocorticoid receptor agonist, with full anti-inflammatory properties in human ocular cells. Mol Vis. 2009, 15: 2606-2616.PubMedPubMedCentral Zhang J, Cavet M, VanderMeid K, Salvador-Silva M, López F, Ward K: BOL-303242-X, a novel selective glucocorticoid receptor agonist, with full anti-inflammatory properties in human ocular cells. Mol Vis. 2009, 15: 2606-2616.PubMedPubMedCentral
44.
go back to reference Evans JF, Ferguson AD, Mosley RT, Hutchinson JH: What's all the FLAP about?: 5-lipoxygenase-activating protein inhibitors for inflammatory diseases. Trends Pharmacol Sc. 2008, 29: 72-78.CrossRef Evans JF, Ferguson AD, Mosley RT, Hutchinson JH: What's all the FLAP about?: 5-lipoxygenase-activating protein inhibitors for inflammatory diseases. Trends Pharmacol Sc. 2008, 29: 72-78.CrossRef
45.
go back to reference Balzar S, Fajt ML, Comhair SAA, Erzurum SC, Bleecker E, Busse WW, Castro M, Gaston B, Israel E, Schwartz LB, Curran-Everett D, Moore CG, Wenzel SE: Mast Cell Phenotype, Location, and Activation in Severe Asthma: Data from the Severe Asthma Research Program. Am J Respir Crit Care Med. 2011, 183: 299-309.CrossRefPubMed Balzar S, Fajt ML, Comhair SAA, Erzurum SC, Bleecker E, Busse WW, Castro M, Gaston B, Israel E, Schwartz LB, Curran-Everett D, Moore CG, Wenzel SE: Mast Cell Phenotype, Location, and Activation in Severe Asthma: Data from the Severe Asthma Research Program. Am J Respir Crit Care Med. 2011, 183: 299-309.CrossRefPubMed
46.
go back to reference Schuligoi R, Sturm E, Luschnig P, Konya V, Philipose S, Sedej M, Waldhoer M, Peskar BA, Heinemann A: CRTH2 and D-Type Prostanoid Receptor Antagonists as Novel Therapeutic Agents for Inflammatory Diseases. Pharmacology. 2010, 85: 372-382.CrossRefPubMed Schuligoi R, Sturm E, Luschnig P, Konya V, Philipose S, Sedej M, Waldhoer M, Peskar BA, Heinemann A: CRTH2 and D-Type Prostanoid Receptor Antagonists as Novel Therapeutic Agents for Inflammatory Diseases. Pharmacology. 2010, 85: 372-382.CrossRefPubMed
47.
go back to reference Cox PG, Miller J, Mitzner W, Leff AR: Radiofrequency ablation of airway smooth muscle for sustained treatment of asthma: preliminary investigations. Eur Respir J. 2004, 24: 659-663.CrossRefPubMed Cox PG, Miller J, Mitzner W, Leff AR: Radiofrequency ablation of airway smooth muscle for sustained treatment of asthma: preliminary investigations. Eur Respir J. 2004, 24: 659-663.CrossRefPubMed
48.
go back to reference Danek CJ, Lombard CM, Dungworth DL, Cox PG, Miller JD, Biggs MJ, Keast TM, Loomas BE, Wizeman WJ, Hogg JC, Leff AR: Reduction in airway hyperresponsiveness to methacholine by the application of RF energy in dogs. J Appl Physiol. 2004, 97: 1946-1953.CrossRefPubMed Danek CJ, Lombard CM, Dungworth DL, Cox PG, Miller JD, Biggs MJ, Keast TM, Loomas BE, Wizeman WJ, Hogg JC, Leff AR: Reduction in airway hyperresponsiveness to methacholine by the application of RF energy in dogs. J Appl Physiol. 2004, 97: 1946-1953.CrossRefPubMed
49.
go back to reference Brown RH, Wizeman W, Danek C, Mitzner W: In vivo evaluation of the effectiveness of bronchial thermoplasty with computed tomography. J Appl Physiol. 2005, 98: 1603-1606.CrossRefPubMed Brown RH, Wizeman W, Danek C, Mitzner W: In vivo evaluation of the effectiveness of bronchial thermoplasty with computed tomography. J Appl Physiol. 2005, 98: 1603-1606.CrossRefPubMed
50.
go back to reference Brown RH, Wizeman W, Danek C, Mitzner W: Effect of bronchial thermoplasty on airway distensibility. Eur Respir J. 2005, 26: 277-282.CrossRefPubMed Brown RH, Wizeman W, Danek C, Mitzner W: Effect of bronchial thermoplasty on airway distensibility. Eur Respir J. 2005, 26: 277-282.CrossRefPubMed
51.
go back to reference Cox G, Miller JD, McWilliams A, FitzGerald JM, Lam S: Bronchial Thermoplasty for Asthma. Am J Respir Crit Care Med. 2006, 173: 965-969.CrossRefPubMed Cox G, Miller JD, McWilliams A, FitzGerald JM, Lam S: Bronchial Thermoplasty for Asthma. Am J Respir Crit Care Med. 2006, 173: 965-969.CrossRefPubMed
52.
go back to reference Cox G, Thomson NC, Rubin AS, Niven RM, Corris PA, Siersted HC, Olivenstein R, Pavord ID, McCormack D, Chaudhuri R, Miller JD, Laviolette M, AIR Trial Study Group: Asthma Control during the Year after Bronchial Thermoplasty. N Eng J Med. 2007, 356: 1327-1337.CrossRef Cox G, Thomson NC, Rubin AS, Niven RM, Corris PA, Siersted HC, Olivenstein R, Pavord ID, McCormack D, Chaudhuri R, Miller JD, Laviolette M, AIR Trial Study Group: Asthma Control during the Year after Bronchial Thermoplasty. N Eng J Med. 2007, 356: 1327-1337.CrossRef
53.
go back to reference Pavord ID, Cox G, Thomson NC, Rubin AS, Corris PA, Niven RM, Chung KF, Laviolette M, the RISA Trial Study Group: Safety and Efficacy of Bronchial Thermoplasty in Symptomatic, Severe Asthma. Am J Respir Crit Care Med. 2007, 176: 1185-1191.CrossRefPubMed Pavord ID, Cox G, Thomson NC, Rubin AS, Corris PA, Niven RM, Chung KF, Laviolette M, the RISA Trial Study Group: Safety and Efficacy of Bronchial Thermoplasty in Symptomatic, Severe Asthma. Am J Respir Crit Care Med. 2007, 176: 1185-1191.CrossRefPubMed
54.
go back to reference Castro M, Rubin AS, Laviolette M, Fiterman J, De Andrade Lima M, Shah PL, Fiss E, Olivenstein R, Thomson NC, Niven RM, Pavord ID, Simoff M, Duhamel DR, McEvoy C, Barbers R, Ten Hacken NH, Wechsler ME, Holmes M, Phillips MJ, Erzurum S, Lunn W, Israel E, Jarjour N, Kraft M, Shargill NS, Quiring J, Berry SM, Cox G, AIR2 Trial Study Group: Effectiveness and Safety of Bronchial Thermoplasty in the Treatment of Severe Asthma: A Multicenter, Randomized, Double-Blind, Sham-Controlled Clinical Trial. Am J Respir Crit Care Med. 2010, 181: 116-124.CrossRefPubMedPubMedCentral Castro M, Rubin AS, Laviolette M, Fiterman J, De Andrade Lima M, Shah PL, Fiss E, Olivenstein R, Thomson NC, Niven RM, Pavord ID, Simoff M, Duhamel DR, McEvoy C, Barbers R, Ten Hacken NH, Wechsler ME, Holmes M, Phillips MJ, Erzurum S, Lunn W, Israel E, Jarjour N, Kraft M, Shargill NS, Quiring J, Berry SM, Cox G, AIR2 Trial Study Group: Effectiveness and Safety of Bronchial Thermoplasty in the Treatment of Severe Asthma: A Multicenter, Randomized, Double-Blind, Sham-Controlled Clinical Trial. Am J Respir Crit Care Med. 2010, 181: 116-124.CrossRefPubMedPubMedCentral
55.
go back to reference Thomson N, Rubin A, Niven R, Corris P, Siersted H, Olivenstein R, Pavord I, McCormick D, Laviolette M, Shargill N, Cox G, AIR Trial Study Group: Long term (5 Year) safety of bronchial thermoplasty: Asthma Intervention Research (AIR) trial. BMC Pulm Med. 2011, 11: 8.CrossRefPubMedPubMedCentral Thomson N, Rubin A, Niven R, Corris P, Siersted H, Olivenstein R, Pavord I, McCormick D, Laviolette M, Shargill N, Cox G, AIR Trial Study Group: Long term (5 Year) safety of bronchial thermoplasty: Asthma Intervention Research (AIR) trial. BMC Pulm Med. 2011, 11: 8.CrossRefPubMedPubMedCentral
56.
go back to reference Lipworth BJ: Phosphodiesterase-4 inhibitors for asthma and chronic obstructive pulmonary disease. The Lancet. 2005, 365: 167-175.CrossRef Lipworth BJ: Phosphodiesterase-4 inhibitors for asthma and chronic obstructive pulmonary disease. The Lancet. 2005, 365: 167-175.CrossRef
57.
go back to reference Bateman ED, Izquierdo JL, Harnest U, Hofbauer P, Magyar P, Schmid-Wirlitsch C, Leichtl S, Bredenbroker D: Efficacy and safety of roflumilast in the treatment of asthma. Ann Allergy Asthma & Immunol. 2006, 96: 679-686.CrossRef Bateman ED, Izquierdo JL, Harnest U, Hofbauer P, Magyar P, Schmid-Wirlitsch C, Leichtl S, Bredenbroker D: Efficacy and safety of roflumilast in the treatment of asthma. Ann Allergy Asthma & Immunol. 2006, 96: 679-686.CrossRef
58.
go back to reference Bousquet J, Aubier M, Sastre J, Izquierdo JL, Adler LM, Hofbauer P, Rost KD, Harnest U, Kroemer B, Albrecht A, Bredenbröker D: Comparison of roflumilast, an oral anti-inflammatory, with beclomethasone dipropionate in the treatment of persistent asthma. Allergy. 2006, 61: 72-78.CrossRefPubMed Bousquet J, Aubier M, Sastre J, Izquierdo JL, Adler LM, Hofbauer P, Rost KD, Harnest U, Kroemer B, Albrecht A, Bredenbröker D: Comparison of roflumilast, an oral anti-inflammatory, with beclomethasone dipropionate in the treatment of persistent asthma. Allergy. 2006, 61: 72-78.CrossRefPubMed
59.
go back to reference Chapman RW, House A, Richard J, Prelusky D, Lamca J, Wang P, Lundell D, Wu P, Ting PC, Lee JF, Aslanian R, Phillips JE: Pharmacology of a potent and selective inhibitor of PDE4 for inhaled administration. Eur J Pharmacol. 2010, 643: 274-281.CrossRefPubMed Chapman RW, House A, Richard J, Prelusky D, Lamca J, Wang P, Lundell D, Wu P, Ting PC, Lee JF, Aslanian R, Phillips JE: Pharmacology of a potent and selective inhibitor of PDE4 for inhaled administration. Eur J Pharmacol. 2010, 643: 274-281.CrossRefPubMed
60.
go back to reference Singh D, Petavy F, Macdonald A, Lazaar A, O'Connor B: The inhaled phosphodiesterase 4 inhibitor GSK256066 reduces allergen challenge responses in asthma. Resp Res. 2010, 11: 26.CrossRef Singh D, Petavy F, Macdonald A, Lazaar A, O'Connor B: The inhaled phosphodiesterase 4 inhibitor GSK256066 reduces allergen challenge responses in asthma. Resp Res. 2010, 11: 26.CrossRef
61.
go back to reference Cohen S, Fleischmann R: Kinase inhibitors: a new approach to rheumatoid arthritis treatment. Curr Opin Rheumatol. 2010, 22: 330-335.CrossRefPubMed Cohen S, Fleischmann R: Kinase inhibitors: a new approach to rheumatoid arthritis treatment. Curr Opin Rheumatol. 2010, 22: 330-335.CrossRefPubMed
63.
go back to reference Bhavsar P, Khorasani N, Hew M, Johnson M, Chung KF: Effect of p38 MAPK inhibition on corticosteroid suppression of cytokine release in severe asthma. Eur Respir J. 2010, 35: 750-756.CrossRefPubMed Bhavsar P, Khorasani N, Hew M, Johnson M, Chung KF: Effect of p38 MAPK inhibition on corticosteroid suppression of cytokine release in severe asthma. Eur Respir J. 2010, 35: 750-756.CrossRefPubMed
64.
go back to reference Denning DW, O'Driscoll BR, Hogaboam CM, Bowyer P, Niven RM: The link between fungi and severe asthma: a summary of the evidence. Eur Respir J. 2006, 27: 615-626.CrossRefPubMed Denning DW, O'Driscoll BR, Hogaboam CM, Bowyer P, Niven RM: The link between fungi and severe asthma: a summary of the evidence. Eur Respir J. 2006, 27: 615-626.CrossRefPubMed
65.
go back to reference Denning DW, O'Driscoll BR, Powell G, Chew F, Atherton GT, Vyas A, Miles J, Morris J, Niven RM: Randomized Controlled Trial of Oral Antifungal Treatment for Severe Asthma with Fungal Sensitization: The Fungal Asthma Sensitization Trial (FAST) Study. Am J Respir Crit Care Med. 2009, 179: 11-18.CrossRefPubMed Denning DW, O'Driscoll BR, Powell G, Chew F, Atherton GT, Vyas A, Miles J, Morris J, Niven RM: Randomized Controlled Trial of Oral Antifungal Treatment for Severe Asthma with Fungal Sensitization: The Fungal Asthma Sensitization Trial (FAST) Study. Am J Respir Crit Care Med. 2009, 179: 11-18.CrossRefPubMed
66.
go back to reference Parma J, Howell T, Kelly J, Bilton D: Profound adrenal suppression secondary to treatment with low dose inhaled steroids and itraconazole in allergic bronchopulmonary aspergillosis in cystic fibrosis. Thorax. 2002, 57: 749-750.CrossRef Parma J, Howell T, Kelly J, Bilton D: Profound adrenal suppression secondary to treatment with low dose inhaled steroids and itraconazole in allergic bronchopulmonary aspergillosis in cystic fibrosis. Thorax. 2002, 57: 749-750.CrossRef
67.
go back to reference Skov M, Main K, Sillesen I, Müller J, Koch C, Lanng S: Iatrogenic adrenal insufficiency as a side-effect of combined treatment of itraconazole and budesonide. Eur Respir J. 2002, 20: 127-133.CrossRefPubMed Skov M, Main K, Sillesen I, Müller J, Koch C, Lanng S: Iatrogenic adrenal insufficiency as a side-effect of combined treatment of itraconazole and budesonide. Eur Respir J. 2002, 20: 127-133.CrossRefPubMed
68.
go back to reference Spears M, McSharry C, Thomson NC: Peroxisome proliferator-activated receptor-gamma agonists as potential anti-inflammatory agents in asthma and chronic obstructive pulmonary disease. Clin Exp Allergy. 2006, 36: 1494-1504.CrossRefPubMed Spears M, McSharry C, Thomson NC: Peroxisome proliferator-activated receptor-gamma agonists as potential anti-inflammatory agents in asthma and chronic obstructive pulmonary disease. Clin Exp Allergy. 2006, 36: 1494-1504.CrossRefPubMed
69.
go back to reference Spears M, Donnelly I, Jolly L, Brannigan M, Ito K, McSharry C, Lafferty J, Chaudhuri R, Braganza G, Bareille P, Sweeney L, Adcock IM, Barnes PJ, Wood S, Thomson NC: Bronchodilatory Effect of the PPAR-[gamma] Agonist Rosiglitazone in Smokers With Asthma. Clin Pharmacol Ther. 2009, 86: 49-53.CrossRefPubMed Spears M, Donnelly I, Jolly L, Brannigan M, Ito K, McSharry C, Lafferty J, Chaudhuri R, Braganza G, Bareille P, Sweeney L, Adcock IM, Barnes PJ, Wood S, Thomson NC: Bronchodilatory Effect of the PPAR-[gamma] Agonist Rosiglitazone in Smokers With Asthma. Clin Pharmacol Ther. 2009, 86: 49-53.CrossRefPubMed
71.
go back to reference Kim DY, Ryu SY, Lim JE, Lee YS, Ro JY: Anti-inflammatory mechanism of simvastatin in mouse allergic asthma model. Eur J Pharmacol. 2007, 557: 76-86.CrossRefPubMed Kim DY, Ryu SY, Lim JE, Lee YS, Ro JY: Anti-inflammatory mechanism of simvastatin in mouse allergic asthma model. Eur J Pharmacol. 2007, 557: 76-86.CrossRefPubMed
72.
go back to reference Chiba Y, Sato S, Misawa M: Inhibition of antigen-induced bronchial smooth muscle hyperresponsiveness by lovastatin in mice. J Smooth Muscle Res. 2008, 44: 123-128.CrossRefPubMed Chiba Y, Sato S, Misawa M: Inhibition of antigen-induced bronchial smooth muscle hyperresponsiveness by lovastatin in mice. J Smooth Muscle Res. 2008, 44: 123-128.CrossRefPubMed
73.
go back to reference Imamura M, Okunishi K, Ohtsu H, Nakagome K, Harada H, Tanaka R, Yamamoto K, Dohi M: Pravastatin attenuates allergic airway inflammation by suppressing antigen sensitisation, interleukin 17 production and antigen presentation in the lung. Thorax. 2009, 64: 44-49.CrossRefPubMed Imamura M, Okunishi K, Ohtsu H, Nakagome K, Harada H, Tanaka R, Yamamoto K, Dohi M: Pravastatin attenuates allergic airway inflammation by suppressing antigen sensitisation, interleukin 17 production and antigen presentation in the lung. Thorax. 2009, 64: 44-49.CrossRefPubMed
74.
go back to reference Chiba Y, Arima J, Sakai H, Misawa M: Lovastatin inhibits bronchial hyperresponsiveness by reducing RhoA signaling in rat allergic asthma. Am J Physiol Lung Cell Mol Physiol. 2008, 294: L705-713.CrossRefPubMed Chiba Y, Arima J, Sakai H, Misawa M: Lovastatin inhibits bronchial hyperresponsiveness by reducing RhoA signaling in rat allergic asthma. Am J Physiol Lung Cell Mol Physiol. 2008, 294: L705-713.CrossRefPubMed
75.
go back to reference McKay A, Leung BP, McInnes IB, Thomson NC, Liew FY: A Novel Anti-Inflammatory Role of Simvastatin in a Murine Model of Allergic Asthma. J Immunol. 2004, 172: 2903-2908.CrossRefPubMed McKay A, Leung BP, McInnes IB, Thomson NC, Liew FY: A Novel Anti-Inflammatory Role of Simvastatin in a Murine Model of Allergic Asthma. J Immunol. 2004, 172: 2903-2908.CrossRefPubMed
76.
go back to reference Zeki AA, Franzi L, Last J, Kenyon NJ: Simvastatin Inhibits Airway Hyperreactivity: Implications for the Mevalonate Pathway and Beyond. Am J Respir Crit Care Med. 2009, 180: 731-740.CrossRefPubMedPubMedCentral Zeki AA, Franzi L, Last J, Kenyon NJ: Simvastatin Inhibits Airway Hyperreactivity: Implications for the Mevalonate Pathway and Beyond. Am J Respir Crit Care Med. 2009, 180: 731-740.CrossRefPubMedPubMedCentral
77.
go back to reference Menzies D, Nair A, Meldrum KT, Fleming D, Barnes M, Lipworth BJ: Simvastatin does not exhibit therapeutic anti-inflammatory effects in asthma. J Allergy Clin Immunol. 2007, 119: 328-335.CrossRefPubMed Menzies D, Nair A, Meldrum KT, Fleming D, Barnes M, Lipworth BJ: Simvastatin does not exhibit therapeutic anti-inflammatory effects in asthma. J Allergy Clin Immunol. 2007, 119: 328-335.CrossRefPubMed
78.
go back to reference Hothersall EJ, Chaudhuri R, McSharry C, Donnelly I, Lafferty J, McMahon AD, Weir CJ, Meiklejohn J, Sattar N, McInnes I, Wood S, Thomson NC: Effects of atorvastatin added to inhaled corticosteroids on lung function and sputum cell counts in atopic asthma. Thorax. 2008, 63: 1070-1075.CrossRefPubMed Hothersall EJ, Chaudhuri R, McSharry C, Donnelly I, Lafferty J, McMahon AD, Weir CJ, Meiklejohn J, Sattar N, McInnes I, Wood S, Thomson NC: Effects of atorvastatin added to inhaled corticosteroids on lung function and sputum cell counts in atopic asthma. Thorax. 2008, 63: 1070-1075.CrossRefPubMed
79.
go back to reference Cowan DC, Cowan JO, Palmay R, Williamson A, Taylor DR: Simvastatin in the treatment of asthma: lack of steroid-sparing effect. Thorax. 2010, 65: 891-896.CrossRefPubMed Cowan DC, Cowan JO, Palmay R, Williamson A, Taylor DR: Simvastatin in the treatment of asthma: lack of steroid-sparing effect. Thorax. 2010, 65: 891-896.CrossRefPubMed
80.
go back to reference Braganza G, Chaudhuri R, McSharry C, Weir CJ, Donnelly I, Jolly L, Lafferty J, Lloyd SM, Spears M, Mair F, Thomson NC: Effects of short-term treatment with atorvastatin in smokers with asthma-a randomized controlled trial. BMC Pulm Med. 2011, 11: 16.CrossRefPubMedPubMedCentral Braganza G, Chaudhuri R, McSharry C, Weir CJ, Donnelly I, Jolly L, Lafferty J, Lloyd SM, Spears M, Mair F, Thomson NC: Effects of short-term treatment with atorvastatin in smokers with asthma-a randomized controlled trial. BMC Pulm Med. 2011, 11: 16.CrossRefPubMedPubMedCentral
81.
go back to reference Pégorier S, Arouche N, Dombret M-C, Aubier M, Pretolani M: Augmented epithelial endothelin-1 expression in refractory asthma. J Allergy Clin Immunol. 2007, 120: 1301-1307.CrossRefPubMed Pégorier S, Arouche N, Dombret M-C, Aubier M, Pretolani M: Augmented epithelial endothelin-1 expression in refractory asthma. J Allergy Clin Immunol. 2007, 120: 1301-1307.CrossRefPubMed
82.
go back to reference McWhinnie R, Pechkovsky DV, Zhou D, Lane D, Halayko AJ, Knight DA, Bai TR: Endothelin-1 induces hypertrophy and inhibits apoptosis in human airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol. 2007, 292: L278-L286.CrossRefPubMed McWhinnie R, Pechkovsky DV, Zhou D, Lane D, Halayko AJ, Knight DA, Bai TR: Endothelin-1 induces hypertrophy and inhibits apoptosis in human airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol. 2007, 292: L278-L286.CrossRefPubMed
83.
go back to reference Wenzel SE: Asthma: defining of the persistent adult phenotypes. The Lancet. 2006, 368: 804-813.CrossRef Wenzel SE: Asthma: defining of the persistent adult phenotypes. The Lancet. 2006, 368: 804-813.CrossRef
84.
go back to reference Drazen JM, Yandava CN, Dube L, Szczerback N, Hippensteel R, Pillari A, Israel E, Schork N, Silverman ES, Katz DA, Drajesk J: Pharmacogenetic association between ALOX5 promoter genotype and the response to anti-asthma treatment. Nat Genet. 1999, 22: 168-170.CrossRefPubMed Drazen JM, Yandava CN, Dube L, Szczerback N, Hippensteel R, Pillari A, Israel E, Schork N, Silverman ES, Katz DA, Drajesk J: Pharmacogenetic association between ALOX5 promoter genotype and the response to anti-asthma treatment. Nat Genet. 1999, 22: 168-170.CrossRefPubMed
85.
go back to reference Lima JJ, Zhang S, Grant A, Shao L, Tantisira KG, Allayee H, Wang J, Sylvester J, Holbrook J, Wise R, Weiss ST, Barnes K: Influence of Leukotriene Pathway Polymorphisms on Response to Montelukast in Asthma. Am J Repir Crit Care Med. 2006, 173: 379-385.CrossRef Lima JJ, Zhang S, Grant A, Shao L, Tantisira KG, Allayee H, Wang J, Sylvester J, Holbrook J, Wise R, Weiss ST, Barnes K: Influence of Leukotriene Pathway Polymorphisms on Response to Montelukast in Asthma. Am J Repir Crit Care Med. 2006, 173: 379-385.CrossRef
86.
go back to reference Klotsman M, York T, Pillai S, Vargas-Irwin C, Sharma S, van den Oord E, Anderson W: Pharmacogenetics of the 5-lipoxygenase biosynthetic pathway and variable clinical response to montelukast. Pharmacogenet Genomics. 2007, 17: 189-196.CrossRefPubMed Klotsman M, York T, Pillai S, Vargas-Irwin C, Sharma S, van den Oord E, Anderson W: Pharmacogenetics of the 5-lipoxygenase biosynthetic pathway and variable clinical response to montelukast. Pharmacogenet Genomics. 2007, 17: 189-196.CrossRefPubMed
87.
go back to reference Haldar P, Pavord ID: Noneosinophilic asthma: A distinct clinical and pathologic phenotype. J Allergy Clin Immunol. 2007, 119: 1043-1052.CrossRefPubMed Haldar P, Pavord ID: Noneosinophilic asthma: A distinct clinical and pathologic phenotype. J Allergy Clin Immunol. 2007, 119: 1043-1052.CrossRefPubMed
88.
go back to reference Simpson J, Scott R, Boyle M, Gibson P: Inflammatory subtypes in asthma: Assessment and identification using induced sputum. Respirology. 2006, 11: 54-61.CrossRefPubMed Simpson J, Scott R, Boyle M, Gibson P: Inflammatory subtypes in asthma: Assessment and identification using induced sputum. Respirology. 2006, 11: 54-61.CrossRefPubMed
89.
go back to reference Pavord I, Brightling C, Woltmann G, Wardlaw A: Non-eosinophilic corticosteroid unresponsive asthma. Lancet. 1999, 353: 2213-2214.CrossRefPubMed Pavord I, Brightling C, Woltmann G, Wardlaw A: Non-eosinophilic corticosteroid unresponsive asthma. Lancet. 1999, 353: 2213-2214.CrossRefPubMed
90.
go back to reference Little S, Chalmers G, MacLeod K, McSharry C, Thomson N: Non-invasive markers of airway inflammation as predictors of oral steroid responsiveness in asthma. Thorax. 2000, 53: 232-234.CrossRef Little S, Chalmers G, MacLeod K, McSharry C, Thomson N: Non-invasive markers of airway inflammation as predictors of oral steroid responsiveness in asthma. Thorax. 2000, 53: 232-234.CrossRef
91.
go back to reference Green RH, Brightling CE, McKenna S, Hargadon B, Parker D, Bradding P, Wardlaw AJ, Pavord ID: Asthma exacerbations and sputum eosinophil counts: a randomised controlled trial. The Lancet. 2002, 360: 1715-1721.CrossRef Green RH, Brightling CE, McKenna S, Hargadon B, Parker D, Bradding P, Wardlaw AJ, Pavord ID: Asthma exacerbations and sputum eosinophil counts: a randomised controlled trial. The Lancet. 2002, 360: 1715-1721.CrossRef
92.
go back to reference Bacci E, Cianchetti S, Bartoli M, Dente FL, Di Franco A, Vagaggini B, Paggiaro P: Low Sputum Eosinophils Predict the Lack of Response to Beclomethasone in Symptomatic Asthmatic Patients. Chest. 2006, 129: 565-572.CrossRefPubMed Bacci E, Cianchetti S, Bartoli M, Dente FL, Di Franco A, Vagaggini B, Paggiaro P: Low Sputum Eosinophils Predict the Lack of Response to Beclomethasone in Symptomatic Asthmatic Patients. Chest. 2006, 129: 565-572.CrossRefPubMed
93.
go back to reference Berry M, Morgan A, Shaw DE, Parker D, Green R, Brightling C, Bradding P, Wardlaw AJ, Pavord ID: Pathological features and inhaled corticosteroid response of eosinophilic and non-eosinophilic asthma. Thorax. 2007, 62: 1043-1049.CrossRefPubMedPubMedCentral Berry M, Morgan A, Shaw DE, Parker D, Green R, Brightling C, Bradding P, Wardlaw AJ, Pavord ID: Pathological features and inhaled corticosteroid response of eosinophilic and non-eosinophilic asthma. Thorax. 2007, 62: 1043-1049.CrossRefPubMedPubMedCentral
94.
go back to reference Simpson JL, Powell H, Boyle MJ, Scott RJ, Gibson PG: Clarithromycin Targets Neutrophilic Airway Inflammation in Refractory Asthma. Am J Respir Crit Care Med. 2008, 177: 148-155.CrossRefPubMed Simpson JL, Powell H, Boyle MJ, Scott RJ, Gibson PG: Clarithromycin Targets Neutrophilic Airway Inflammation in Refractory Asthma. Am J Respir Crit Care Med. 2008, 177: 148-155.CrossRefPubMed
95.
go back to reference Woodruff PG, Modrek B, Choy DF, Jia G, Abbas AR, Ellwanger A, Arron JR, Koth LL, Fahy JV: T-helper Type 2-driven Inflammation Defines Major Subphenotypes of Asthma. Am J Respir Crit Care Med. 2009, 180: 388-395.CrossRefPubMedPubMedCentral Woodruff PG, Modrek B, Choy DF, Jia G, Abbas AR, Ellwanger A, Arron JR, Koth LL, Fahy JV: T-helper Type 2-driven Inflammation Defines Major Subphenotypes of Asthma. Am J Respir Crit Care Med. 2009, 180: 388-395.CrossRefPubMedPubMedCentral
Metadata
Title
Emerging therapies for severe asthma
Authors
Neil C Thomson
Rekha Chaudhuri
Mark Spears
Publication date
01-12-2011
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2011
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/1741-7015-9-102

Other articles of this Issue 1/2011

BMC Medicine 1/2011 Go to the issue