Stephen T Holgate

Summary

Affiliation: University of Southampton
Country: UK

Publications

  1. ncbi request reprint The mechanisms, diagnosis, and management of severe asthma in adults
    Stephen T Holgate
    AIR Division, Level D Centre Block, Southampton General Hospital, Southampton, UK
    Lancet 368:780-93. 2006
  2. pmc A brief history of asthma and its mechanisms to modern concepts of disease pathogenesis
    Stephen T Holgate
    Division of Infection, Inflammation and Immunity, School of Medicine, University of Southampton, Southampton, United Kingdom
    Allergy Asthma Immunol Res 2:165-71. 2010
  3. pmc Epithelial stress and structural remodelling in childhood asthma
    I A Fedorov
    City Clinical Hospital 1, Chelyabinsk, Russia
    Thorax 60:389-94. 2005
  4. pmc Stratified approaches to the treatment of asthma
    Stephen T Holgate
    Faculty of Medicine, University of Southampton, Southampton, UK
    Br J Clin Pharmacol 76:277-91. 2013
  5. doi request reprint Immune circuits in asthma
    Stephen T Holgate
    Clinical and Experimental Sciences, Mail Point 810, Level F South Block, Southampton General Hospital, Southampton SO16 6YD, UK
    Curr Opin Pharmacol 13:345-50. 2013
  6. doi request reprint Trials and tribulations in identifying new biologic treatments for asthma
    Stephen T Holgate
    Inflammation, Infection and Immunity Division, Sir Henry Wellcome Laboratories, Mail Point 810, Level F, South Block, Southampton General Hospital, Southampton SO16 6YD, UK
    Trends Immunol 33:238-46. 2012
  7. doi request reprint Innate and adaptive immune responses in asthma
    Stephen T Holgate
    Clinical and Experimental Sciences, Sir Henry Wellcome Laboratories, Southampton General Hospital, UK
    Nat Med 18:673-83. 2012
  8. doi request reprint Asthma: a simple concept but in reality a complex disease
    Stephen T Holgate
    School of Medicine, University of Southampton, Southampton, UK
    Eur J Clin Invest 41:1339-52. 2011
  9. pmc Improving outcomes for asthma patients with allergic rhinitis: conclusions from the MetaForum conferences
    David Price
    Department of General Practice and Primary Care, University of Aberdeen, Foresterhill Health Centre, Westburn Road, Aberdeen AB25 2AY, UK
    BMC Pulm Med 6:S7. 2006
  10. ncbi request reprint Novel targets of therapy in asthma
    Stephen T Holgate
    IIR Division, School of Medicine, Southampton General Hospital, Southampton, UK
    Curr Opin Pulm Med 15:63-71. 2009

Detail Information

Publications164 found, 100 shown here

  1. ncbi request reprint The mechanisms, diagnosis, and management of severe asthma in adults
    Stephen T Holgate
    AIR Division, Level D Centre Block, Southampton General Hospital, Southampton, UK
    Lancet 368:780-93. 2006
    ....
  2. pmc A brief history of asthma and its mechanisms to modern concepts of disease pathogenesis
    Stephen T Holgate
    Division of Infection, Inflammation and Immunity, School of Medicine, University of Southampton, Southampton, United Kingdom
    Allergy Asthma Immunol Res 2:165-71. 2010
    ....
  3. pmc Epithelial stress and structural remodelling in childhood asthma
    I A Fedorov
    City Clinical Hospital 1, Chelyabinsk, Russia
    Thorax 60:389-94. 2005
    ..In adult asthma the bronchial epithelium shows high expression of the epidermal growth factor receptor (EGFR) and the cyclin dependent kinase inhibitor, p21waf, linked to ongoing stress and injury...
  4. pmc Stratified approaches to the treatment of asthma
    Stephen T Holgate
    Faculty of Medicine, University of Southampton, Southampton, UK
    Br J Clin Pharmacol 76:277-91. 2013
    ..In order to achieve this effectively, a closer interaction will be required between industry (therapeutic and diagnostic), academia and health workers. ..
  5. doi request reprint Immune circuits in asthma
    Stephen T Holgate
    Clinical and Experimental Sciences, Mail Point 810, Level F South Block, Southampton General Hospital, Southampton SO16 6YD, UK
    Curr Opin Pharmacol 13:345-50. 2013
    ..This mandates a new view of the disease in which causal pathways linked to biomarkers are found and treatments targeted to these pathways as described in a more personalised approach to medicine...
  6. doi request reprint Trials and tribulations in identifying new biologic treatments for asthma
    Stephen T Holgate
    Inflammation, Infection and Immunity Division, Sir Henry Wellcome Laboratories, Mail Point 810, Level F, South Block, Southampton General Hospital, Southampton SO16 6YD, UK
    Trends Immunol 33:238-46. 2012
    ..To achieve this goal, a different type of relationship is needed between academia and industry, and also within industry, to promote collaboration in the precompetitive space...
  7. doi request reprint Innate and adaptive immune responses in asthma
    Stephen T Holgate
    Clinical and Experimental Sciences, Sir Henry Wellcome Laboratories, Southampton General Hospital, UK
    Nat Med 18:673-83. 2012
    ....
  8. doi request reprint Asthma: a simple concept but in reality a complex disease
    Stephen T Holgate
    School of Medicine, University of Southampton, Southampton, UK
    Eur J Clin Invest 41:1339-52. 2011
    ..Over the 2 decades that followed, these drugs have been progressively improved by increasing their therapeutic index and duration of action...
  9. pmc Improving outcomes for asthma patients with allergic rhinitis: conclusions from the MetaForum conferences
    David Price
    Department of General Practice and Primary Care, University of Aberdeen, Foresterhill Health Centre, Westburn Road, Aberdeen AB25 2AY, UK
    BMC Pulm Med 6:S7. 2006
  10. ncbi request reprint Novel targets of therapy in asthma
    Stephen T Holgate
    IIR Division, School of Medicine, Southampton General Hospital, Southampton, UK
    Curr Opin Pulm Med 15:63-71. 2009
    ..However, none of these therapies are specifically directed to the underlying causal pathways of asthma. In this review the role of selective inhibitors of the inflammatory cascade are presented with a particular emphasis on biologics...
  11. ncbi request reprint Treatment strategies for allergy and asthma
    Stephen T Holgate
    IIR Division, F Level, South Block, Southampton General Hospital, Southampton, SO16 6YD, UK
    Nat Rev Immunol 8:218-30. 2008
    ....
  12. ncbi request reprint The anti-inflammatory effects of omalizumab confirm the central role of IgE in allergic inflammation
    Stephen Holgate
    RCMB Research Division, Southampton General Hospital, United Kingdom
    J Allergy Clin Immunol 115:459-65. 2005
    ....
  13. ncbi request reprint Efficacy of omalizumab, an anti-immunoglobulin E antibody, in patients with allergic asthma at high risk of serious asthma-related morbidity and mortality
    S Holgate
    RCMB Research Division, Southampton General Hospital, UK
    Curr Med Res Opin 17:233-40. 2001
    ..The aim of the present study was to determine the efficacy of omalizumab in a subgroup of patients at high risk of serious asthma-related morbidity and mortality...
  14. ncbi request reprint Epithelium dysfunction in asthma
    Stephen T Holgate
    Allergy and Inflammation Research, Division of Infection, School of Medicine, Southampton General Hospital and the University of Southampton, Southampton, United Kingdom
    J Allergy Clin Immunol 120:1233-44; quiz 1245-6. 2007
    ....
  15. ncbi request reprint Consensus Group on New-Generation Antihistamines (CONGA): present status and recommendations
    S T Holgate
    Respiratory Cell and Molecular Biology, Infection, Inflammation, and Repair Division, School of Medicine, University of Southampton, UK
    Clin Exp Allergy 33:1305-24. 2003
  16. ncbi request reprint Local genetic and environmental factors in asthma disease pathogenesis: chronicity and persistence mechanisms
    S T Holgate
    Allergy and Inflammation Research, Southampton General Hospital, Southampton SO16 6YD, UK
    Eur Respir J 29:793-803. 2007
    ....
  17. ncbi request reprint Susceptibility genes in severe asthma
    Stephen T Holgate
    Infection, Inflammation and Repair Division, MP810, F Level, South Block, Southampton General Hospital, Southampton, SO16 6YD, UK
    Curr Allergy Asthma Rep 6:345-8. 2006
    ..In this review, we bring together recent literature in the field of genetic influences over disease severity and discuss some of the clinical implications in terms of drug discovery and personalized medicine...
  18. ncbi request reprint ADAM33: a newly identified gene in the pathogenesis of asthma
    Stephen T Holgate
    Infection, Inflammation, and Repair Division, School of Medicine, University of Southampton, Southampton General Hospital, Tremona Road, Southampton, Hampshire, SO16 6YD, UK
    Immunol Allergy Clin North Am 25:655-68. 2005
    ..For each of these genes, as is the case for ADAM33, determining their normal function(s) and how these become disordered in asthma is the future challenge...
  19. ncbi request reprint Mechanisms of airway epithelial damage: epithelial-mesenchymal interactions in the pathogenesis of asthma
    S T Holgate
    Division of Infection, Inflammation and Repair, Mailpoint 810, Level D, Centre Block, Southampton General Hospital, Southampton SO16 6YD, UK
    Eur Respir J Suppl 44:24s-29s. 2003
  20. ncbi request reprint Introduction: the anti-inflammatory role of cysteinyl leukotriene receptor antagonists in asthma
    Stephen T Holgate
    Respiratory Division, University of Southampton School of Medicine, Southampton, United Kingdom
    J Allergy Clin Immunol 111:S1-4. 2003
  21. ncbi request reprint Anti-immunoglobulin E treatment with omalizumab in allergic diseases: an update on anti-inflammatory activity and clinical efficacy
    S T Holgate
    Southampton General Hospital, Southampton, UK
    Clin Exp Allergy 35:408-16. 2005
    ..These impressive clinical data and the studies elucidating the anti-inflammatory profile of omalizumab also serve to emphasize the fundamental importance of IgE in the pathogenesis of allergic diseases...
  22. pmc Asthma out of control? A structured review of recent patient surveys
    Stephen T Holgate
    Infection, Inflammation and Repair AIR Division, Level F, South Block, MP810, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK
    BMC Pulm Med 6:S2. 2006
    ..The primary goal of the present review was to assess patient perspectives on key issues in asthma and its management, as captured in patient surveys...
  23. ncbi request reprint The genetics of asthma: ADAM33 as an example of a susceptibility gene
    Stephen T Holgate
    Infection, Inflammation, and Repair Division, MP810, F Level, South Block, Southampton General Hospital, Southampton SO16 6YD, UK
    Proc Am Thorac Soc 3:440-3. 2006
    ....
  24. ncbi request reprint Understanding the pathophysiology of severe asthma to generate new therapeutic opportunities
    Stephen T Holgate
    Division of Infection, Inflammation and Repair, School of Medicine, University of Southampton, Southampton General Hospital, UK
    J Allergy Clin Immunol 117:496-506; quiz 507. 2006
    ....
  25. ncbi request reprint Has the time come to rethink the pathogenesis of asthma?
    Stephen T Holgate
    University of Southampton, Hampshire, UK
    Curr Opin Allergy Clin Immunol 10:48-53. 2010
    ..However, ranges of approaches that have targeted this immunological component have so far been disappointing. Most asthma therapy still relies on bronchodilators and corticosteroids rather than treating underlying disease mechanisms...
  26. ncbi request reprint The role of the airway epithelium and its interaction with environmental factors in asthma pathogenesis
    Stephen T Holgate
    Infection, Inflammation and Immunity Division, School of Medicine, Southampton University, Southampton General Hospital, Southampton SO166YD, UK
    Proc Am Thorac Soc 6:655-9. 2009
    ..Viewing asthma primarily as an epithelial disease with adoption of a chronic wound scenario also provides a route to airway wall remodeling and the varying asthma phenotypes over the life course...
  27. ncbi request reprint The epidemic of allergy and asthma
    S T Holgate
    Respiratory, Cell and Molecular Biology Research Division of the School of Medicine, University of Southampton, Southampton General Hospital, UK
    Nature 402:B2-4. 1999
    ....
  28. doi request reprint Chronic fatigue syndrome: understanding a complex illness
    Stephen T Holgate
    University of Southampton, Infection, Inflammation and Immunity Division, School of Medicine, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK
    Nat Rev Neurosci 12:539-44. 2011
    ..Nature Reviews Neuroscience asked four scientists involved in CFS research about their views on the condition, its causes and the future of research aimed at improving our understanding of this chronic illness...
  29. doi request reprint The sentinel role of the airway epithelium in asthma pathogenesis
    Stephen T Holgate
    Allergy and Inflammation Research, Division of Infection, Inflammation and Immunity, School of Medicine, Southampton University and General Hospital, Southampton, Hampshire, UK
    Immunol Rev 242:205-19. 2011
    ....
  30. ncbi request reprint The airway epithelium is central to the pathogenesis of asthma
    Stephen T Holgate
    School of Medicine, Southampton General Hospital, Southampton, UK
    Allergol Int 57:1-10. 2008
    ....
  31. ncbi request reprint Invited lecture: activation of the epithelial mesenchymal trophic unit in the pathogenesis of asthma
    S T Holgate
    Respiratory Cell and Molecular Biology Division, School of Medicine, Southampton General Hospital, Southampton, UK
    Int Arch Allergy Immunol 124:253-8. 2001
    ..This report describes a series of studies that identify aberrant epithelial mesenchymal signalling in the airways as an important event in maintaining inflammation and driving remodelling in response to environmental injury...
  32. ncbi request reprint Efficacy and safety of a recombinant anti-immunoglobulin E antibody (omalizumab) in severe allergic asthma
    S T Holgate
    RCMB Research Division, Southampton General Hospital, Southampton, UK
    Clin Exp Allergy 34:632-8. 2004
    ..Patients with severe asthma are often inadequately controlled on existing anti-asthma therapy, constituting an unmet clinical need...
  33. ncbi request reprint Lessons learnt from the epidemic of asthma
    S T Holgate
    Allergy and Inflammation Research Division, Southampton General Hospital, Southampton, UK
    QJM 97:247-57. 2004
  34. doi request reprint Efficacy and safety of etanercept in moderate-to-severe asthma: a randomised, controlled trial
    S T Holgate
    School of Medicine, University of Southampton, III Division, Mail Point 810, Level F, South Block, Southampton General Hospital, Southampton, Hampshire, SO16 6YD, UK
    Eur Respir J 37:1352-9. 2011
    ..However, ETN treatment was a well-tolerated therapy. Studies in specific subsets of patients with asthma with longer-term follow-up may be needed to fully evaluate the clinical efficacy of ETN in this population...
  35. ncbi request reprint ADAM metallopeptidase domain 33 (ADAM33): identification and role in airways disease
    Stephen T Holgate
    Infection, Inflammation and Immunity Division, Southampton General Hospital, Southampton, UK
    Drug News Perspect 23:381-7. 2010
    ..These all point to ADAM33 being a key molecule in the development and progression of asthma by contributing to smooth muscle and vascular modeling and remodeling...
  36. doi request reprint Pathophysiology of asthma: what has our current understanding taught us about new therapeutic approaches?
    Stephen T Holgate
    Division of Infection, Inflammation and Immunity, University of Southampton School of Medicine, Southampton General Hospital, Southampton, United Kingdom
    J Allergy Clin Immunol 128:495-505. 2011
    ....
  37. pmc A new look at the pathogenesis of asthma
    Stephen T Holgate
    University of Southampton, Southampton General Hospital, UK
    Clin Sci (Lond) 118:439-50. 2010
    ..It also raises the possibility of developing treatments that increase the lung's resistance to the inhaled environment rather than concentrating all efforts on trying to suppress inflammation once it has become established...
  38. ncbi request reprint Epithelial-mesenchymal communication in the pathogenesis of chronic asthma
    Stephen T Holgate
    Respiratory Cell and Molecular Biology, Infection, Inflammation and Repair Division, School of Medicine, University of Southampton, D Level Centre Block, Southampton General Hospital, Southampton SO16 6YD, UK
    Proc Am Thorac Soc 1:93-8. 2004
    ....
  39. ncbi request reprint Characterization of ciliated bronchial epithelium 1, a ciliated cell-associated gene induced during mucociliary differentiation
    Hajime Yoshisue
    Infection, Inflammation, and Repair Division, University of Southampton School of Medicine, Southampton General Hospital, Southampton, United Kingdom
    Am J Respir Cell Mol Biol 31:491-500. 2004
    ..Regulated expression during differentiation and the subcellular localization of CBE1 suggest that it may play an important role in the differentiation and/or function of ciliated cells in human airways...
  40. ncbi request reprint IFN-gamma-induced protein 10 is a novel biomarker of rhinovirus-induced asthma exacerbations
    Peter A B Wark
    Brooke Laboratories, University of Southampton, Southampton, United Kingdom
    J Allergy Clin Immunol 120:586-93. 2007
    ..Rhinovirus-induced acute asthma is the most frequent trigger for asthma exacerbations...
  41. ncbi request reprint ADAM33 expression in asthmatic airways and human embryonic lungs
    Hans Michael Haitchi
    Roger Brooke Laboratories, Division of Infection, Inflammation, and Repair, and Human Genetics Division, School of Medicine, University of Southampton, Southampton General Hospital, United Kingdom
    Am J Respir Crit Care Med 171:958-65. 2005
    ..Polymorphic variation in ADAM33 (A Disintegrin And Metalloprotease) is strongly associated with asthma and bronchial hyperresponsiveness in different populations...
  42. ncbi request reprint IL-4 receptor alpha is an important modulator of IL-4 and IL-13 receptor binding: implications for the development of therapeutic targets
    Allison Lynn Andrews
    The Brooke Laboratories, Division of Infection, Inflammation, and Repair, Southampton General Hospital, UK
    J Immunol 176:7456-61. 2006
    ....
  43. ncbi request reprint Beta-catenin/T-cell factor-mediated transcription is modulated by cell density in human bronchial epithelial cells
    Mark D Steel
    The Brooke Laboratories, School of Medicine, Southampton General Hospital, Southampton SO16 6YD, UK
    Int J Biochem Cell Biol 37:1281-95. 2005
    ..Recognising that many chronic inflammatory disorders of the airways involve epithelial damage and repair, altered Wnt signalling might contribute to disease pathogenesis or progression...
  44. ncbi request reprint Cooperative effects of Th2 cytokines and allergen on normal and asthmatic bronchial epithelial cells
    James L Lordan
    School of Medicine, Respiratory Cell and Molecular Biology Division, Southampton General Hospital, Southampton, United Kingdom
    J Immunol 169:407-14. 2002
    ....
  45. ncbi request reprint Epigenetic mechanisms silence a disintegrin and metalloprotease 33 expression in bronchial epithelial cells
    Youwen Yang
    Brooke Laboratories, Division of Infection, Inflammation and Repair, School of Medicine, University of Southampton, Southampton, United Kingdom
    J Allergy Clin Immunol 121:1393-9, 1399.e1-14. 2008
    ..Although considered to be a mesenchymal cell-specific gene, recent reports have suggested epithelial expression of ADAM33 in patients with severe asthma...
  46. ncbi request reprint Increased expression of p21(waf) cyclin-dependent kinase inhibitor in asthmatic bronchial epithelium
    Sarah M Puddicombe
    The Brooke Laboratory, Division of Infection, Inflammation and Repair, School of Medicine, Southampton General Hospital, Southampton, United Kingdom
    Am J Respir Cell Mol Biol 28:61-8. 2003
    ..We conclude that p21(waf) overexpression in asthma influences cell proliferation and survival. This may cause abnormal repair responses that contribute to airway inflammation and remodeling...
  47. ncbi request reprint Barrier responses of human bronchial epithelial cells to grass pollen exposure
    Cornelia Blume
    Brooke Laboratory, Clinical and Experimental Sciences, Faculty of Medicine, University Hospital Southampton, Southampton, UK
    Eur Respir J 42:87-97. 2013
    ..The differential response of cells from normal and asthmatic donors suggests the potential for the bronchial epithelium to promote immune dysfunction in asthma. ..
  48. doi request reprint TNF-α-mediated bronchial barrier disruption and regulation by src-family kinase activation
    Michelle A Hardyman
    Academic Unit of Clinical and Experimental Sciences, Sir Henry Wellcome Laboratories, University of Southampton Faculty of Medicine, University Hospital Southampton, United Kingdom
    J Allergy Clin Immunol 132:665-675.e8. 2013
    ..We further hypothesized that src-family kinase inhibition would improve barrier function in healthy cells in the presence of TNF-α and directly in cultures of severe asthmatic cells where the barrier is disrupted...
  49. ncbi request reprint Asthmatic bronchial epithelium is more susceptible to oxidant-induced apoptosis
    Fabio Bucchieri
    School of Medicine, University of Southampton, Southampton General Hospital, Southampton, United Kingdom
    Am J Respir Cell Mol Biol 27:179-85. 2002
    ..This susceptibility may contribute to the rising trends in asthma associated with air pollution and diets low in antioxidants...
  50. pmc Transforming growth factor-beta promotes rhinovirus replication in bronchial epithelial cells by suppressing the innate immune response
    Nicole Bedke
    Academic Unit of Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, University Hospital Southampton, Southampton, United Kingdom
    PLoS ONE 7:e44580. 2012
    ..Our results suggest that endogenous TGF-β contributes to a suppressed IFN response to RV infection possibly via SOCS-1 and SOCS-3...
  51. ncbi request reprint IL-13 receptor alpha 2: a regulator of IL-13 and IL-4 signal transduction in primary human fibroblasts
    Allison Lynn Andrews
    Brooke Laboratories, Division of Infection, Inflammation, and Repair, UK
    J Allergy Clin Immunol 118:858-65. 2006
    ..The nonsignaling receptor IL-13 receptor alpha 2 (IL-13Ralpha2) binds IL-13 with high affinity and specificity and is believed to be a decoy receptor for IL-13...
  52. ncbi request reprint The splicing and fate of ADAM33 transcripts in primary human airways fibroblasts
    Robert M Powell
    Brooke Laboratories, Division of Infection, School of Medicine, Southampton General Hospital, Southampton, UK
    Am J Respir Cell Mol Biol 31:13-21. 2004
    ..These findings demonstrate that ADAM33 exists in multiple isoforms, suggesting that it is a complex molecule that plays multiple roles within mesenchymal cells...
  53. ncbi request reprint Double-stranded RNA induces disproportionate expression of thymic stromal lymphopoietin versus interferon-beta in bronchial epithelial cells from donors with asthma
    Lena Uller
    The Brooke Laboratories, Sir Henry Wellcome Laboratories, South Block, Southampton General Hospital, Southampton SO16 6YD, UK
    Thorax 65:626-32. 2010
    ....
  54. doi request reprint Defective epithelial barrier function in asthma
    Chang Xiao
    Synairgen Research Ltd, Southampton General Hospital, Southampton, United Kingdom
    J Allergy Clin Immunol 128:549-56.e1-12. 2011
    ..The bronchial epithelium forms the interface with the external environment and is pivotally involved in controlling tissue homeostasis through provision of a physical barrier controlled by tight junction (TJ) complexes...
  55. ncbi request reprint Autocrine ligands for the epidermal growth factor receptor mediate interleukin-8 release from bronchial epithelial cells in response to cigarette smoke
    Audrey Richter
    Respiratory Cell and Molecular Biology Division, School of Medicine, Southampton General Hospital, United Kingdom
    Am J Respir Cell Mol Biol 27:85-90. 2002
    ..Our data indicate that secretion of IL-8 in response to CSE is dependent on EGFR activation and that autocrine production of TGF-alpha makes a substantial contribution to this response...
  56. ncbi request reprint ADAM 33 and its association with airway remodeling and hyperresponsiveness in asthma
    Stephen T Holgate
    Respiratory Cell and Molecular Biology Research Division, School of Medicine, University of Southampton, UK, University of Cambridge, UK
    Clin Rev Allergy Immunol 27:23-34. 2004
    ..The potential for therapeutic intervention with ADAM 33 is extremely attractive and further work will not only focus on the specific domains of ADAM 33, but also the mechanisms by which they lead to bronchial hyperreactivity...
  57. pmc Barrier disrupting effects of alternaria alternata extract on bronchial epithelium from asthmatic donors
    Marina S Leino
    Academic Unit of Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Sir Henry Wellcome Laboratories, South Block, University Hospital Southampton, Southampton, United Kingdom
    PLoS ONE 8:e71278. 2013
    ..Only cultures from asthmatic donors were susceptible to the barrier-weakening effects of Alternaria. Therefore, the bronchial epithelium of severely asthmatic individuals may be more susceptible to the deleterious effects of Alternaria. ..
  58. ncbi request reprint The discovery and role of ADAM33, a new candidate gene for asthma
    John W Holloway
    Human Genetics Division, School of Medicine, University of Southampton, Southampton General Hospital, Southampton, SO16 6YD, UK
    Expert Rev Mol Med 6:1-12. 2004
    ..ADAM33 might play a key role in predisposing to the reduced lung function characteristic of asthma, possibly by influencing airway wall remodelling...
  59. ncbi request reprint Cysteinyl leukotrienes synergize with growth factors to induce proliferation of human bronchial fibroblasts
    Hajime Yoshisue
    Division of Infection, Inflammation and Repair, University of Southampton School of Medicine, Southampton General Hospital, UK
    J Allergy Clin Immunol 119:132-40. 2007
    ..Cysteinyl leukotrienes (cys-LTs) are potent asthma-related mediators that function through their G protein-coupled receptors, cys-LT receptor type 1 (CysLT1R) and cys-LT receptor type 2 (CysLT2R)...
  60. pmc Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus
    Peter A B Wark
    The Brooke Laboratories, University of Southampton, Southampton SO16 6YD, UK
    J Exp Med 201:937-47. 2005
    ..These data suggest a novel use for type I interferons in the treatment or prevention of virus-induced asthma exacerbations...
  61. ncbi request reprint Contribution of bronchial fibroblasts to the antiviral response in asthma
    Nicole Bedke
    Division of Infection, Inflammation, and Repair, School of Medicine, University of Southampton, Southampton General Hospital, Southampton, United Kingdom
    J Immunol 182:3660-7. 2009
    ..Their ability to support viral replication coupled with their vigorous proinflammatory response following infection may contribute to asthma exacerbations...
  62. ncbi request reprint Roles of cysteinyl leukotrienes in airway inflammation, smooth muscle function, and remodeling
    Stephen T Holgate
    Respiratory, Cell, and Molecular Biology Research Division, University of Southampton School of Medicine, Southampton, UK
    J Allergy Clin Immunol 111:S18-34; discussion S34-6. 2003
    ....
  63. ncbi request reprint Effects of treatment with anti-immunoglobulin E antibody omalizumab on airway inflammation in allergic asthma
    Ratko Djukanovic
    Respiratory Cell and Molecular Biology, Division of Infection, Inflammation, and Repair, University of Southampton, Southampton, UK
    Am J Respir Crit Care Med 170:583-93. 2004
    ..The lack of effect of omalizumab on methacholine responsiveness suggests that IgE or eosinophils may not be causally linked to airway hyperresponsiveness to methacholine in mild to moderate asthma...
  64. ncbi request reprint Induction of a disintegrin and metalloprotease 33 during embryonic lung development and the influence of IL-13 or maternal allergy
    Hans Michael Haitchi
    Division of Infection Inflammation and Immunity, Roger Brooke Laboratory, School of Medicine, University of Southampton, Southampton, UK
    J Allergy Clin Immunol 124:590-7, 597.e1-11. 2009
    ..ADAM33 is almost exclusively expressed in mesenchymal cells, including mesenchymal progenitors in developing lungs...
  65. ncbi request reprint Leukotriene and prostanoid pathway enzymes in bronchial biopsies of seasonal allergic asthmatics
    M L Seymour
    Division of Respiratory Cell and Molecular Biology, Southampton General Hospital, Southampton, United Kingdom
    Am J Respir Crit Care Med 164:2051-6. 2001
    ..Inverse correlations between PEF and 5-LO(+) cell counts link increased expression of 5-LO pathway enzymes in eosinophils and macrophages within the bronchial mucosa to deterioration of lung function during seasonal allergen exposure...
  66. ncbi request reprint Effect of IL-13 receptor alpha2 levels on the biological activity of IL-13 variant R110Q
    Allison Lynn Andrews
    Infection, Inflammation and Repair Division, School of Medicine, University of Southampton, Southampton General Hospital, Southampton, UK
    J Allergy Clin Immunol 120:91-7. 2007
    ..Recently a polymorphic variant of IL-13 (R110Q) has been shown to be associated with atopy...
  67. pmc Regulation of a disintegrin and metalloprotease-33 expression by transforming growth factor-β
    Youwen Yang
    Southampton General Hospital, Southampton, UK
    Am J Respir Cell Mol Biol 46:633-40. 2012
    ..This may provide a mechanism for fine regulation of levels of ADAM33 expression in fibroblasts, and may self-limit TGF-β(2)-induced ectodomain shedding of ADAM33...
  68. ncbi request reprint The soluble form of a disintegrin and metalloprotease 33 promotes angiogenesis: implications for airway remodeling in asthma
    Ilaria Puxeddu
    Division of Infection, Inflammation, and Repair, School of Medicine, Southampton General Hospital, University of Southampton, Southampton, United Kingdom
    J Allergy Clin Immunol 121:1400-6, 1406.e1-4. 2008
    ..A disintegrin and metalloprotease (ADAM)-33 is a susceptibility gene for asthma and chronic obstructive pulmonary disease whose function remains unknown...
  69. ncbi request reprint Airway remodeling in asthma: new insights
    Donna E Davies
    Brooke Laboratories, Division of Infection, Inflammation and Repair, School of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK
    J Allergy Clin Immunol 111:215-25; quiz 226. 2003
    ....
  70. pmc Human bronchial fibroblasts express the 5-lipoxygenase pathway
    Anna J James
    Division of Infection, Inflammation and Repair IIR, University of Southampton, School of Medicine, Southampton General Hospital, Southampton, SO16 6YD, UK
    Respir Res 7:102. 2006
    ..Fibroblast activity is influenced by members of the leukotriene family of bronchoconstrictor and inflammatory mediators, but it is not known whether human bronchial fibroblasts can synthesize leukotrienes...
  71. doi request reprint Exogenous IFN-β has antiviral and anti-inflammatory properties in primary bronchial epithelial cells from asthmatic subjects exposed to rhinovirus
    Julie A Cakebread
    Division of Infection, Inflammation and Immunity, University of Southampton School of Medicine and National Institute for Health Research Respiratory Biomedical Research Unit, Southampton General Hospital, Southampton, United Kingdom
    J Allergy Clin Immunol 127:1148-54.e9. 2011
    ....
  72. ncbi request reprint Association of tumor necrosis factor-alpha polymorphisms and ozone-induced change in lung function
    Ian A Yang
    Asthma Genetics Laboratory, Human Genetics Division, University of Southampton, United Kingdom
    Am J Respir Crit Care Med 171:171-6. 2005
    ..The results of this study support TNF as a genetic factor for susceptibility to ozone-induced changes in lung function in humans, and has potential implications for stratifying health risks of air pollution...
  73. ncbi request reprint NF-kappa B and TNF-alpha: a positive autocrine loop in human lung mast cells?
    William R Coward
    Division of Infection, Inflammation and Repair, School of Medicine, Southampton General Hospital, United Kingdom
    J Immunol 169:5287-93. 2002
    ....
  74. ncbi request reprint Genetic and environmental influences on airway inflammation in asthma
    S T Holgate
    University Medicine, Southampton General Hospital, UK
    Int Arch Allergy Immunol 107:29-33. 1995
    ..These latter findings, being more evident in severe chronic disease, suggest that the 'formed' airway elements are also important in mediating the ongoing inflammation characteristic of asthma...
  75. ncbi request reprint The cysteinyl-leukotriene type 1 receptor polymorphism 927T/C is associated with atopy severity but not with asthma
    L Hao
    Division of Human Genetics, University of Southampton School of Medicine, Southampton, UK
    Clin Exp Allergy 36:735-41. 2006
    ..We screened the CYSLTR1 gene on chromosome Xq13-21 for coding region polymorphisms, and investigated their associations with allergy and asthma...
  76. ncbi request reprint Genetics
    John W Holloway
    Human Genetics, Southampton General Hospital, University of Southampton, Southampton, UK
    Chem Immunol Allergy 84:1-35. 2004
  77. ncbi request reprint Induction of the epidermal growth factor receptor and its ligands in nasal epithelium by ozone
    Riccardo Polosa
    Respiratory Cell and Moleculat Biology Division, School of Medicine, Southampton General Hospital, Southampton, United Kingdom
    J Allergy Clin Immunol 113:120-6. 2004
    ..Although the inflammatory response that occurs in response to ozone inhalation is well characterized, the mechanisms underlying epithelial cell activation are not well understood...
  78. ncbi request reprint Polymorphisms in the interleukin-4 and interleukin-4 receptor alpha chain genes confer susceptibility to asthma and atopy in a Caucasian population
    B Beghe
    Divisions of Human Genetics Infection, Inflammation and Repair, School of Medicine, University of Southampton, UK
    Clin Exp Allergy 33:1111-7. 2003
    ..IL-4 by binding to its receptor (IL-4R) is essential for the development of airway inflammation present in asthma, through the induction of IgE synthesis in B cells and differentiation of T cells to a Th2 phenotype...
  79. ncbi request reprint Inflammatory cytokines can enhance CD44-mediated airway epithelial cell adhesion independently of CD44 expression
    Shih Hsing Leir
    Respiratory Cell and Molecular Biology, Infection Immunity and Repair Division, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK
    Am J Physiol Lung Cell Mol Physiol 285:L1305-11. 2003
    ..These data indicate that CD44 is important for bronchial epithelial cell binding to HA and that cytokines known to be expressed in inflammation can increase HA binding independently of the level of CD44 expression...
  80. ncbi request reprint Genetics of allergic disease
    John W Holloway
    Division of Infection, Inflammation and Immunity, School of Medicine, University of Southampton, Southampton, United Kingdom
    J Allergy Clin Immunol 125:S81-94. 2010
    ....
  81. pmc Dynamics of pro-inflammatory and anti-inflammatory cytokine release during acute inflammation in chronic obstructive pulmonary disease: an ex vivo study
    Tillie Louise Hackett
    School of Biological Sciences, University of Southampton, Southampton, UK
    Respir Res 9:47. 2008
    ..The aim of this study was to asses the kinetics of cytokine release from COPD parenchymal explants using an ex vivo model of lipopolysaccharide (LPS) induced acute inflammation...
  82. ncbi request reprint The role of the epidermal growth factor receptor in sustaining neutrophil inflammation in severe asthma
    L M Hamilton
    Division of Infection, Inflammation and Repair, School of Medicine, University of Southampton, UK
    Clin Exp Allergy 33:233-40. 2003
    ..Although the EGFR is involved in epithelial growth and differentiation, it is unknown whether it also contributes to the inflammatory response in asthma...
  83. ncbi request reprint Effect of desloratadine and loratadine on rhinovirus-induced intercellular adhesion molecule 1 upregulation and promoter activation in respiratory epithelial cells
    A Papi
    University Medicine, University of Southampton, Southampton, UK
    J Allergy Clin Immunol 108:221-8. 2001
    ..CONCLUSION: These effects are unlikely to be mediated by H(1)-receptor antagonism and suggest a novel mechanism of action that may be important for the therapeutic control of virus-induced asthma exacerbations...
  84. ncbi request reprint Interaction of inhaled LTC4 with histamine and PGD2 on airway caliber in asthma
    G D Phillips
    Immunopharmacology Group, Southampton General Hospital, United Kingdom
    J Appl Physiol 66:304-12. 1989
    ..05) but not for FEV1 (P less than 0.05). We conclude that inhaled LTC4 interacts synergistically with histamine and PGD2 and that this effect, although small, may be a relevant interaction in asthma...
  85. ncbi request reprint PLAUR polymorphisms are associated with asthma, PLAUR levels, and lung function decline
    Sheila J Barton
    Division of Infection, Inflammation and Immunity, School of Medicine, University of Southampton, Southampton, United Kingdom
    J Allergy Clin Immunol 123:1391-400.e17. 2009
    ..Several studies have suggested that chromosome 19q13.1-3 contains asthma susceptibility genes...
  86. ncbi request reprint Expression of c-erbB receptors and ligands in the bronchial epithelium of asthmatic subjects
    Riccardo Polosa
    School of Medicine, Division of Respiratory Cell and Molecular Biology, Southampton General Hospital, Southampton, United Kingdom
    J Allergy Clin Immunol 109:75-81. 2002
    ..The c-erbB family of receptor tyrosine kinases act in a combinatorial fashion to regulate cell behavior. Disturbances in this system have been associated with neoplastic and inflammatory diseases...
  87. ncbi request reprint Kinetic analysis of the interleukin-13 receptor complex
    Allison Lynn Andrews
    Infection, Inflammation and Repair Division, School of Medicine, University of Southampton, 97 Tremona Rd, Southampton General Hospital, Southampton SO16 6YD, United Kingdom
    J Biol Chem 277:46073-8. 2002
    ....
  88. pmc Enzyme potentiated desensitisation in treatment of seasonal allergic rhinitis: double blind randomised controlled study
    Michael J Radcliffe
    School of Medicine, Infection Inflammation and Repair Research Division, University of Southampton, Southampton General Hospital, Southampton SO16 6YD
    BMJ 327:251-4. 2003
    ..To assess the efficacy of enzyme potentiated desensitisation in the treatment of severe summer hay fever poorly controlled by pharmacotherapy...
  89. pmc Increased expression of inducible nitric oxide synthase and cyclo-oxygenase-2 in the airway epithelium of asthmatic subjects and regulation by corticosteroid treatment
    A E Redington
    University Medicine, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK
    Thorax 56:351-7. 2001
    ..We hypothesised that the in vivo expression of iNOS and COX-2 in the airways would be increased in asthma, and that these cytokine inducible enzymes may represent targets for regulation by corticosteroid treatment...
  90. ncbi request reprint Peripheral blood CD4+ and CD8+ T cell type 1 and type 2 cytokine production in atopic asthmatic and normal subjects
    S H Cho
    University Medicine, Southampton General Hospital, Southampton, UK
    Clin Exp Allergy 32:427-33. 2002
    ..However, CD8+ T cells also produce type 1 and type 2 cytokines and the relative roles of CD4+ and CD8+ T cell cytokine production in asthma have not been previously studied...
  91. ncbi request reprint Altered protein tyrosine phosphorylation in asthmatic bronchial epithelium
    L M Hamilton
    The Brooke Laboratories, Mailpoint 888, Southampton General Hospital, Southampton, SO16 6YD, UK
    Eur Respir J 25:978-85. 2005
    ..The epidermal growth factor receptor and/or other tyrosine kinase pathways may contribute to persistent, corticosteroid-unresponsive inflammation in severe asthma...
  92. ncbi request reprint Promoter polymorphism in the 5-lipoxygenase (ALOX5) and 5-lipoxygenase-activating protein (ALOX5AP) genes and asthma susceptibility in a Caucasian population
    I Sayers
    Divisions of Human Genetics Infection, Inflammation and Repair, University of Southampton School of Medicine, Southampton General Hospital, Tremona Road, Southampton, UK
    Clin Exp Allergy 33:1103-10. 2003
    ..5-Lipoxygenase (5-LO) and 5-lipoxygenase-activating protein (FLAP) are essential for cysteinyl-leukotriene (cys-LT) production, critical mediators in asthma...
  93. ncbi request reprint Inhibition of adenosine 5'-monophosphate- and methacholine-induced bronchoconstriction in asthma by inhaled frusemide
    R Polosa
    Dept of Immunopharmacology, Southampton General Hospital, UK
    Eur Respir J 3:665-72. 1990
    ..Its more potent activity against AMP and other bronchoconstrictor stimuli, that are considered to involve mast cell mediators, suggests an additional action on mast cell functions possibly at the level of the Ca++/Mg(++)-ATPase...
  94. ncbi request reprint The effect of inhaled 15-(s)-hydroxyeicosatetraenoic acid (15-HETE) on airway calibre and non-specific responsiveness in normal and asthmatic human subjects
    C K Lai
    Immunopharmacology Group, Southampton General Hospital, UK
    Eur Respir J 3:38-45. 1990
    ..41-fold of baseline after diluent (p less than 0.01) compared with a 1.1-fold increase after 15-HETE, p less than 0.01). These data suggest 15-HETE may play an autacoid role in airway function...
  95. ncbi request reprint Nedocromil sodium is more potent than sodium cromoglycate against AMP-induced bronchoconstriction in atopic asthmatic subjects
    R Richards
    Medicine I, Level D, Centre Block, Southampton General Hospital, U K
    Clin Exp Allergy 19:285-91. 1989
    ..9 (FEV1) and 8.0 (Vmax30) times more potent than SCG (P less than 0.001). In conclusion, both drugs inhibit the bronchoconstrictor response to inhaled AMP, and nedocromil is at least 4-8 times more potent than SCG...
  96. ncbi request reprint The effects of Mycobacterium vaccae on allergen-induced airway responses in atopic asthma
    L Camporota
    Division of Respiratory Cell and Molecular Biology, Southampton General Hospital, Southampton, UK
    Eur Respir J 21:287-93. 2003
    ..07). This study shows a trend toward significance for the effects of heat-killed Mycobacterium vaccae (SRL172) on allergen-induced airway responses. Further clinical trials, involving multiple dosing, are needed...
  97. ncbi request reprint Signal transducer and activator of transcription 6 (STAT-6) expression and function in asthmatic bronchial epithelium
    R E Mullings
    Division of Respiratory Cell and Molecular Biology, School of Medicine, Southampton General Hospital, United Kingdom
    J Allergy Clin Immunol 108:832-8. 2001
    ..Asthma is associated with increased production of IL-4 and IL-13...
  98. ncbi request reprint A look at the pathogenesis of asthma: the need for a change in direction
    Stephen T Holgate
    Infection, Inflammation and Immunity Division, Southampton General Hospital, School of Medicine, University of Southampton, Southampton, United Kingdom
    Discov Med 9:439-47. 2010
    ....
  99. ncbi request reprint Newer therapies for asthma: a focus on anti-IgE
    K Suresh Babu
    Respiratory Cell and Molecular Biology, Southampton General Hospital, UK
    Indian J Chest Dis Allied Sci 44:107-15. 2002
    ..This review gives a brief overview of the newer therapies under investigation with special reference to omalizumab in the treatment of allergic asthma...
  100. ncbi request reprint Cytoplasmic tail of IL-13Ralpha2 regulates IL-4 signal transduction
    Allison Lynn Andrews
    School of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK
    Biochem Soc Trans 37:873-6. 2009
    ..The receptor has more complicated functions than a simple decoy receptor. In this review, we discuss newly revealed functions of IL-13Ralpha2...