S T Holgate

University of Southampton, Southampton, England, United Kingdom

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Publications (671)3753.55 Total impact

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    ABSTRACT: Advancing drug development for airway diseases beyond the established mechanisms and symptomatic therapies requires redefining the classifications of airway diseases, considering systemic manifestations, developing new tools and encouraging collaborations.
    No preview · Article · May 2015 · Nature Reviews Drug Discovery
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    ABSTRACT: Asthma represents an area of significant unmet medical need, with few new drugs making it to the clinic in the past 50 years. Much asthma research is currently carried out in non-human models. However, as asthma is a uniquely human condition, it is difficult to translate findings from these models to efficacious therapies. Based on the results of a survey of the UK asthma research community carried out jointly between the NC3Rs, Asthma UK, the UK Respiratory Research Collaborative and the Human Tissue Authority, we propose that more emphasis be placed on the use of human tissue studies to provide more relevant models that better translate to the clinic and which reduce the reliance of the asthma community on less predictive animal models. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Full-text · Article · Jan 2015 · Thorax
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    ABSTRACT: Background Although asthma is characterized by variable airways obstruction, most studies of asthma phenotypes are cross-sectional. The stability of phenotypes defined either by biomarkers or by physiological variables was assessed by repeated measures over 1 year in the Pan-European BIOAIR cohort of adult asthmatics.MethodsA total of 169 patients, 93 with severe asthma (SA) and 76 with mild-to-moderate asthma (MA), were examined at six or more visits during 1 year. Asthma phenotype clusters were defined by physiological variables (lung function, reversibility and age of onset of the disease) or by biomarkers (eosinophils and neutrophils in induced sputum).ResultsAfter 1 year of follow-up, the allocation to clusters was changed in 23.6% of all asthma patients when defined by physiological phenotypes and, remarkably, in 42.3% of the patients when stratified according to sputum cellularity (P = 0.034). In the SA cohort, 30% and 48.6% of the patients changed allocation according to physiological and biomarker clustering, respectively. Variability of phenotypes was not influenced by change in oral or inhaled corticosteroid dose, nor by the number of exacerbations. Lower stability of single and repeated measure was found for all evaluated biomarkers (eosinophils, neutrophils and FeNO) in contrast to good stability of physiological variables (FEV1), quality of life and asthma control.Conclusion Phenotypes determined by biomarkers are less stable than those defined by physiological variables, especially in severe asthmatics. The data also imply that definition of asthma phenotypes is improved by repeated measures to account for fluctuations in lung function, biomarkers and asthma control.
    No preview · Article · Jul 2014 · Allergy
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    ABSTRACT: Molecular-based allergy (MA) diagnostics is an approach used to map the allergen sensitization of a patient at a molecular level, using purified natural or recombinant allergenic molecules (allergen components) instead of allergen extracts. Since its introduction, MA diagnostics has increasingly entered routine care, with currently more than 130 allergenic molecules commercially available for in vitro specific IgE (sIgE) testing. MA diagnostics allows for an increased accuracy in allergy diagnosis and prognosis and plays an important role in three key aspects of allergy diagnosis: (1) resolving genuine versus cross-reactive sensitization in poly-sensitized patients, thereby improving the understanding of triggering allergens; (2) assessing, in selected cases, the risk of severe, systemic versus mild, local reactions in food allergy, thereby reducing unnecessary anxiety for the patient and the need for food challenge testing; and (3) identifying patients and triggering allergens for specific immunotherapy (SIT). Singleplex and multiplex measurement platforms are available for MA diagnostics. The Immuno-Solid phase Allergen Chip (ISAC) is the most comprehensive platform currently available, which involves a biochip technology to measure sIgE antibodies against more than one hundred allergenic molecules in a single assay. As the field of MA diagnostics advances, future work needs to focus on large-scale, population-based studies involving practical applications, elucidation and expansion of additional allergenic molecules, and support for appropriate test interpretation. With the rapidly expanding evidence-base for MA diagnosis, there is a need for allergists to keep abreast of the latest information. The aim of this consensus document is to provide a practical guide for the indications, determination, and interpretation of MA diagnostics for clinicians trained in allergology.
    Full-text · Article · Oct 2013 · World Allergy Organization Journal

  • No preview · Article · Sep 2013 · European Respiratory Journal
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    ABSTRACT: Biodiversity loss and climate change secondary to human activities are now being associated with various adverse health effects. However, less attention is being paid to the effects of biodiversity loss on environmental and commensal (indigenous) microbiotas. Metagenomic and other studies of healthy and diseased individuals reveal that reduced biodiversity and alterations in the composition of the gut and skin microbiota are associated with various inflammatory conditions, including asthma, allergic and inflammatory bowel diseases (IBD), type1 diabetes, and obesity. Altered indigenous microbiota and the general microbial deprivation characterizing the lifestyle of urban people in affluent countries appear to be risk factors for immune dysregulation and impaired tolerance. The risk is further enhanced by physical inactivity and a western diet poor in fresh fruit and vegetables, which may act in synergy with dysbiosis of the gut flora. Studies of immigrants moving from non-affluent to affluent regions indicate that tolerance mechanisms can rapidly become impaired in microbe-poor environments. The data on microbial deprivation and immune dysfunction as they relate to biodiversity loss are evaluated in this Statement of World Allergy Organization (WAO). We propose that biodiversity, the variability among living organisms from all sources are closely related, at both the macro- and micro-levels. Loss of the macrodiversity is associated with shrinking of the microdiversity, which is associated with alterations of the indigenous microbiota. Data on behavioural means to induce tolerance are outlined and a proposal made for a Global Allergy Plan to prevent and reduce the global allergy burden for affected individuals and the societies in which they live.
    Full-text · Article · Jan 2013 · World Allergy Organization Journal
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    ABSTRACT: BACKGROUND: Tryptase, a major secretory product of human mast cells has been implicated as a key mediator of allergic inflammation. Genetic variation in the tryptases is extensive, and α-tryptase, an allelic variant of the more extensively studied β-tryptase, is absent in substantial numbers of the general population. The degree to which α-tryptase expression may be associated with asthma has not been studied. We have investigated the α-tryptase gene copy number variation and its potential associations with phenotypes of asthma. OBJECTIVES: Caucasian families (n=341) with at least two asthmatic siblings (n=1350) were genotyped for the α-tryptase alleles, using high resolution melting assays. Standards for the possible α-/β-tryptase ratios were constructed by cloning α-and β-tryptase PCR products to generate artificial templates. Association analysis of asthma affection status and related phenotypes (total and allergen-specific serum IgE, bronchial hyperresponsiveness to methacholine, FEV1 , and atopy and asthma severity scores) were undertaken using family based association tests (FBAT). RESULTS: Four consistent melting patterns for the α-tryptase genotype were identified with alleles carrying null, one or two copies of the α-tryptase allele. Possessing one copy of α-tryptase was significantly associated with lower serum levels of total and dust mite-specific IgE levels and higher FEV1 measurements, while two copies were related to higher serum concentrations of total and dust mite-specific IgE and greater atopy severity scores. CONCLUSIONS AND CLINICAL RELEVANCE: Associations of α-tryptase copy number with serum IgE levels, atopy scores and bronchial function may reflect roles for tryptases in regulating IgE production and other processes in asthma.
    No preview · Article · Jan 2013
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    ABSTRACT: Boasting a worldwide reputation as the leading text in allergy and immunology, Middletons Allergy continues its steadfast tradition of providing comprehensive coverage of state-of-the-art basic science, as well as authoritative guidance on the clinical concepts of day-to-day diagnosis and management of allergic disorders. Offering timely information that's suited for clinicians and researchers alike, Middleton's is a user-friendly and versatile source for the knowledge you need to provide optimal care to your patients!. "A valuable source of reference and pre-sifted information ...the editors are to be commending in keeping the book up-to-date and clinically valuable." Reviewed by: Imnunology News Date: March 2015.
    No preview · Article · Jan 2013

  • No preview · Article · Jan 2013

  • No preview · Conference Paper · Dec 2012
  • F Braido · S Holgate · G.W. Canonica
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    ABSTRACT: Advances in basic research and research and development plans of pharmaceutical companies are radically changing the kind of available drugs and therapeutic targets. We are switching from predominantly chemical molecules, aimed at treating large populations of patients (blockbuster drugs), to a new generation of products, mostly biotech, aimed at modifying a specific pathogenetic mechanism. In other word we are moving fast to targeted therapy, which represents the first step toward personalized therapy, where the right drug at the right dose is administered to the right person, at the right time. Like the patent expiration of chemical products has corresponded to the development of generic drugs, the expiration of new biotech products will witness the appearance of biosimilars. The latter are biologic products that are highly similar but not identical to the reference medical products in terms of quality, safety and efficacy. This implies specific research, clinical monitoring, physicians updating of knowledge for a safe and appropriate use of these products. We are the beginning of a devolution in patient's care and physicians' practice.
    No preview · Article · Sep 2012 · Pulmonary Pharmacology & Therapeutics
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    Full-text · Article · May 2012
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    ABSTRACT: Allergist/clinical immunologist maintenance of certification and training program reaccreditation are mandatory in some countries. The World Allergy Organization conducted surveys in 2009 and 2011 to assess where such programs were available and to promote the establishment of such programs on a global level. This was done with the presumption that after such an "inventory," World Allergy Organization could offer guidance to its Member Societies on the promotion of such programs to assure the highest standards of practice in the field of allergy and clinical immunology. This review draws on the experience of countries where successful programs are in place and makes recommendations for those wishing to implement such programs for the specialty.
    Full-text · Article · Apr 2012 · World Allergy Organization Journal
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    Full-text · Article · Feb 2012 · Allergy
  • Article: Allergy
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    ABSTRACT: The new edition of Allergy, by Drs. Stephen Holgate, Martin Church, David Broide, and Fernando Martinez, uses an enhanced clinical focus to provide the clear, accessible guidance you need to treat allergy patients. A more consistent format throughout features new differential diagnosis and treatment algorithms, updated therapeutic drug information in each chapter, and additional coverage of pediatric allergies. With current discussions of asthma, allergens, pollutants, drug treatment, and more, as well as access to the full text and illustrations online at www.expertconsult.com, this comprehensive resource is ideal for any non-specialist who treats patients with allergies. Prescribe appropriate therapies and effectively manage patients' allergies using detailed treatment protocols. Identify allergic conditions quickly and easily with algorithms that provide at-a-glance assistance. Explore topics in greater detail using extensive references to key literature. Access the fully searchable text online at www.expertconsult.com, along with a downloadable image bank. Manage allergies in both adult and pediatric patients using coverage of treatment practices for both in each chapter. Stay current on hot topics including asthma, allergens, pollutants, and more. Get up-to-date coverage of cell-based condition with brand new chapters on Eosinophilia: Clinical Manifestations and Therapeutic Options and Systemic Mastocytosis. Apply the latest best practices through new and updated treatment algorithms. Find therapeutic drug information more easily with guidance incorporated into each chapter. The best allergy resource for the non-specialist.
    No preview · Article · Jan 2012 · Allergy
  • R. Pawankar · G. Canonica · S. Holgate · R. Lockey

    No preview · Article · Jan 2012
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    ABSTRACT: A major part of the burden of asthma is caused by acute exacerbations. Exacerbations have been strongly and consistently associated with respiratory infections. Respiratory viruses and bacteria are therefore possible treatment targets. To have a reasonable estimate of the burden of disease induced by such infectious agents on asthmatic patients, it is necessary to understand their nature and be able to identify them in clinical samples by employing accurate and sensitive methodologies. This systematic review summarizes current knowledge and developments in infection epidemiology of acute asthma in children and adults, describing the known impact for each individual agent and highlighting knowledge gaps. Among infectious agents, human rhinoviruses are the most prevalent in regard to asthma exacerbations. The newly identified type-C rhinoviruses may prove to be particularly relevant. Respiratory syncytial virus and metapneumovirus are important in infants, while influenza viruses seem to induce severe exacerbations mostly in adults. Other agents are relatively less or not clearly associated. Mycoplasma and Chlamydophila pneumoniae seem to be involved more with asthma persistence rather than with disease exacerbations. Recent data suggest that common bacteria may also be involved, but this should be confirmed. Although current information is considerable, improvements in detection methodologies, as well as the wide variation in respect to location, time and populations, underline the need for additional studies that should also take into account interacting factors.
    Full-text · Article · Nov 2010 · Allergy
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    ABSTRACT: Increased tumour necrosis factor-α levels have been observed in bronchial biopsies and induced sputum from subjects with severe asthma. We investigated etanercept (ETN) as a therapeutic option for treating moderate-to-severe persistent asthma. In this 12-week, randomised, double-blind, placebo-controlled, phase 2 trial, subjects (n=132) with moderate-to-severe persistent asthma received subcutaneous injections of 25 mg ETN or placebo twice weekly, and were evaluated at baseline, and at weeks 2, 4, 8 and 12. The primary end-point was the change from baseline to week 12 in pre-bronchodilator forced expiratory volume in 1 s (FEV1)% predicted. Secondary end-points included morning peak expiratory flow, FEV1% pred, Asthma Control Questionnaire (5-item version), asthma exacerbations, provocative concentration of methacholine causing a 20% decrease in FEV1, and the Asthma Quality of Life Questionnaire. No significant differences were observed between ETN and placebo for any of the efficacy end-points. ETN treatment was well tolerated, with no unexpected safety findings observed during the study. Clinical efficacy of ETN was not shown in subjects with moderate-to-severe persistent asthma over 12 weeks. 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.
    No preview · Article · Nov 2010 · European Respiratory Journal

  • No preview · Article · Sep 2010 · Thorax
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    ABSTRACT: First-generation H(1)-antihistamines obtained without prescription are the most frequent form of self-medication for allergic diseases, coughs and colds and insomnia even though they have potentially dangerous unwanted effects which are not recognized by the general public. To increase consumer protection by bringing to the attention of regulatory authorities, physicians and the general public the potential dangers of the indiscriminate use first-generation H(1)-antihistamines purchased over-the counter in the absence of appropriate medical supervision. A GA(2)LEN (Global Allergy and Asthma European Network) task force assessed the unwanted side-effects and potential dangers of first-generation H1-antihistamines by reviewing the literature (Medline and Embase) and performing a media audit of US coverage from 1996 to 2008 of accidents and fatal adverse events in which these drugs were implicated. First-generation H(1)-antihistamines, all of which are sedating, are generally regarded as safe by laypersons and healthcare professionals because of their long-standing use. However, they reduce rapid eye movement (REM)-sleep, impair learning and reduce work efficiency. They are implicated in civil aviation, motor vehicle and boating accidents, deaths as a result of accidental or intentional overdosing in infants and young children and suicide in teenagers and adults. Some exhibit cardiotoxicity in overdose. This review raises the issue of better consumer protection by recommending that older first-generation H(1)-antihistamines should no longer be available over-the-counter as prescription- free drugs for self-medication of allergic and other diseases now that newer second- generation nonsedating H(1)-antihistamines with superior risk/benefit ratios are widely available at competitive prices.
    Full-text · Article · Feb 2010 · Allergy

Publication Stats

29k Citations
3,753.55 Total Impact Points


  • 1981-2015
    • University of Southampton
      • Faculty of Medicine
      Southampton, England, United Kingdom
  • 2013
    • Università degli Studi di Genova
      • Dipartimento di Medicina sperimentale (DIMES)
      Genova, Liguria, Italy
  • 1995-2010
    • University Hospital Southampton NHS Foundation Trust
      • Department of Medical Physics and Bioengineering
      Southampton, England, United Kingdom
  • 2005
    • Νοσοκομείο Σωτηρία
      Athínai, Attica, Greece
  • 2003
    • Ghent University
      Gand, Flanders, Belgium
  • 2001
    • University of Hull
      Kingston upon Hull, England, United Kingdom
    • University of Bristol
      • Medical School
      Bristol, ENG, United Kingdom
    • Umeå University
      Umeå, Västerbotten, Sweden
  • 2000
    • Università degli Studi di Modena e Reggio Emilia
      Modène, Emilia-Romagna, Italy
    • Stellenbosch University
      • Division of General Internal Medicine
      Stellenbosch, Western Cape, South Africa
  • 1999
    • National Heart, Lung, and Blood Institute
      베서스다, Maryland, United States
    • University of Otago
      • Department of Medicine (Christchurch)
      Taieri, Otago, New Zealand
  • 1998
    • University of Ferrara
      • Research Center for the Research of Asthma and BPCO
      Ferrare, Emilia-Romagna, Italy
  • 1980-1998
    • Harvard Medical School
      • Department of Medicine
      Boston, Massachusetts, United States
  • 1997
    • Ealing, Hammersmith & West London College
      Londinium, England, United Kingdom
  • 1996
    • University of Massachusetts Boston
      Boston, Massachusetts, United States
    • Countess Of Chester Hospital NHS Foundation Trust
      Chester, England, United Kingdom
  • 1995-1996
    • University of Catania
      • Department of Clinical and Molecular Biomedicine (MEDBIO)
      Catania, Sicily, Italy
  • 1994
    • Poole Hospital NHS Foundation Trust
      Poole, England, United Kingdom
    • Alfred Hospital
      Melbourne, Victoria, Australia
    • Liverpool Hospital
      Liverpool, New South Wales, Australia
    • University of Groningen
      Groningen, Groningen, Netherlands
  • 1993
    • The Heart Lung Center
      Londinium, England, United Kingdom
    • University of Oulu
      • Department of Paediatrics
      Uleoborg, Northern Ostrobothnia, Finland
  • 1985
    • Clinical pharmacology of Miami
      Miami, Florida, United States