S T Holgate

University of Southampton, Southampton, England, United Kingdom

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Publications (938)6089.56 Total impact

  • [Show abstract] [Hide abstract]
    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.
    Thorax 01/2015; DOI:10.1136/thoraxjnl-2014-206648 · 8.56 Impact Factor
  • Stephen T Holgate
    EMBO Reports 01/2015; DOI:10.15252/embr.201439972 · 7.86 Impact Factor
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    ABSTRACT: Asthma is a chronic inflammatory disease. Reticular basement membrane (RBM) thickening is considered feature of airway remodelling (AR) particularly in severe asthma (SA). Omalizumab, mAb to IgE is effective in SA and can modulate AR. Herein we describe protein profiles of bronchial biopsies to detect biomarkers of anti-IgE effects on AR and to explain potential mechanisms/pathways. We defined the bronchial biopsy protein profiles, before and after treatment. Unsupervised clustering of baseline proteomes resulted in very good agreement with the morphometric analysis of AR. Protein profiles of omalizumab responders (ORs) were significantly different from those of non-omalizumab responders (NORs). The major differences between ORs and NORs lied to smooth muscle and extra cellular matrix proteins. Notably, an IgE-binding protein (galectin-3) was reliable, stable and predictive biomarker of AR modulation. Omalizumab down-regulated bronchial smooth muscle proteins in SA. These findings suggest that omalizumab may exert disease-modifying effects on remodelling components.
    Immunology Letters 11/2014; 162(1). DOI:10.1016/j.imlet.2014.08.010 · 2.37 Impact Factor
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    ABSTRACT: IgE is central to the pathophysiology of allergic asthma. Omalizumab, a humanized anti-IgE mAb, specifically binds free IgE and interrupts the allergic cascade by preventing binding of IgE with its high-affinity FcεRI receptors on mast cells, antigen-presenting cells, and other inflammatory cells. The clinical efficacy of omalizumab has been well documented in a number of clinical trials that involve adults, adolescents, and children with moderate-to-severe and severe allergic asthma. In these studies, omalizumab reduced exacerbations, asthma symptoms, inhaled corticosteroid and rescue medication use, and improved quality of life relative to placebo or best standard of care. Similar benefits have been reported in observational studies in “real-world” populations of patients. Results from recent pooled data from randomized clinical trials and from a large prospective cohort study provide reassurance about the long-term safety of omalizumab. Omalizumab dosing is individualized according to body weight and serum-IgE level, and recent adjustments to the dosing algorithm in Europe have enabled more patients to be eligible for treatment. Ongoing and future research is investigating the optimal duration of therapy, accurate predictors of response to treatment, and efficacy in nonatopic asthma as well as other IgE-mediated conditions.
    09/2014; DOI:10.1016/j.jaip.2014.03.010
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    Stephen T Holgate
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    ABSTRACT: IgE has long been known as a therapeutic target for allergic disease, but the difficulty has been in selecting agents that don't trigger cross linkage of IgE when bound to its high affinity receptor (FceR1) on mast cells and basophils. By "designing" a monoclonal antibody (mAb) which targets that part of IgE that binds to that binds to the a-chain of FceR1, the allergic cascade can be effectively interrupted and diseases such as asthma greatly improved, providing a substantial part of their phenotype engages IgE. Clinical trials and real life studies confirm this. Beyond asthma, a whole range of other diseases dependent upon IgE initiation and triggering are being identified. These diseases are now being explored as being amenable to anti-IgE therapy some of which are comorbidities of asthma and others not. The advent of an even more potent anti-IgE mAb - QGE031 - is creating further opportunities for anti-IgE therapy to improve the lives of so many people with IgE-related diseases.
    World Allergy Organization Journal 07/2014; 7(1):17. DOI:10.1186/1939-4551-7-17
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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.
    Allergy 07/2014; 69(9). DOI:10.1111/all.12445 · 6.00 Impact Factor
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    ABSTRACT: Rationale Ex vivo asthmatic bronchial epithelial cells are more susceptible to rhinovirus infection due to deficient induction of the anti-viral protein, interferon-beta. Exogenous interferon-beta restores anti-viral activity. Objectives To compare the efficacy and safety of inhaled interferon-beta to placebo administered to asthmatic patients after onset of cold symptoms for the prevention or attenuation of asthma symptoms caused by respiratory viruses. Methods 147 asthmatics on inhaled corticosteroids (British Thoracic Society Steps 2-5), with a history of virus-associated exacerbations, underwent 14-day treatment with inhaled interferon-beta (n=72) or placebo (n=75) within 24 hours of developing cold symptoms and were assessed clinically, with relevant samples collected to assess virus infection and anti-viral responses. Patients were randomised according to a pre-specified computer-generated schedule, stratified by site. Results 91% of randomised patients developed a defined cold. In this modified intention-to-treat population, asthma symptoms did not get clinically significantly worse (mean change in 6-item Asthma Control Questionnaire <0.5) and interferon-beta treatment had no significant effect. However, in a subset of more difficult-to-treat, Step 4/5 asthmatics (n=27 interferon-beta; n=31 Placebo) Asthma Control Questionnaire-6 increased significantly on placebo; this was prevented by interferon-beta (p=0.004). Additionally, in the whole modified intention-to-treat population, interferon-beta enhanced morning peak expiratory flow recovery (p=0.033), reduced the need for additional treatment, and boosted innate immunity as assessed by blood and sputum biomarker responses. Interferon-beta was well tolerated. Conclusions This trial suggests that inhaled interferon-beta is a potential treatment for virus-induced exacerbations in difficult-to-treat asthmatics and justifies further, adequately powered, trials in this patient population. Trial registration ClinicalTrials.gov: NCT01126177 Funding Synairgen Research Limited, U.K.
    American Journal of Respiratory and Critical Care Medicine 06/2014; DOI:10.1164/rccm.201312-2235OC · 11.99 Impact Factor
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    ABSTRACT: In the past, asthma was considered mainly as a childhood disease. However, asthma is an important cause of morbidity and mortality in the elderly nowadays. In addition, the burden of asthma is more significant in the elderly than in their younger counterparts, particularly with regard to mortality, hospitalization, medical costs or health-related quality of life. Nevertheless, asthma in the elderly is still been underdiagnosed and undertreated. Therefore, it is an imperative task to recognize our current challenges and to set future directions. This project aims to review the current literature and identify unmet needs in the fields of research and practice for asthma in the elderly. This will enable us to find new research directions, propose new therapeutic strategies, and ultimately improve outcomes for elderly people with asthma. There are data to suggest that asthma in older adults is phenotypically different from young patients, with potential impact on the diagnosis, assessment and management in this population. The diagnosis of AIE in older populations relies on the same clinical findings and diagnostic tests used in younger populations, but the interpretation of the clinical data is more difficult. The challenge today is to encourage new research in AIE but to use the existing knowledge we have to make the diagnosis of AIE, educate the patient, develop a therapeutic approach to control the disease, and ultimately provide a better quality of life to our elderly patients.
    World Allergy Organization Journal 05/2014; 7(1):16. DOI:10.1186/1939-4551-7-16
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    ABSTRACT: Unbiased genetic approaches, especially genome-wide association studies, have identified novel genetic targets in the pathogenesis of asthma, but so far these targets account for only a small proportion of the heritability of asthma. Recognition of the importance of disease heterogeneity, the need for improved disease phenotyping, and the fact that genes involved in the inception of asthma are likely to be different from those involved in severity widens the scope of asthma genetics. The identification of genes implicated in several causal pathways suggests that genetic scores could be used to capture the effect of genetic variations on individuals. Gene-environment interaction adds another layer of complexity, which is being successfully explored by epigenetic approaches. Pharmacogenetics is one example of how gene-environment interactions are already being taken into account in the identification of drug responders and non-responders, and patients most susceptible to adverse effects. Such applications represent one component of personalised medicine, an approach that places the individual at the centre of health care.
    The Lancet Respiratory Medicine 05/2014; 2(5). DOI:10.1016/S2213-2600(14)70012-8
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    ABSTRACT: In response to viral infection, bronchial epithelial cells increase inflammatory cytokine release to activate the immune response and curtail viral replication. In atopic asthma, enhanced expression of Th2 cytokines is observed and we postulated that Th2 cytokines may augment the effects of rhinovirus-induced inflammation. Primary bronchial epithelial cell cultures from pediatric subjects were treated with Th2 cytokines for 24 h before infection with RV16. Release of IL-8, IP-10 and GM-CSF was measured by ELISA. Infection was quantified using RTqPCR and TCID50. Phosphatidyl inositol 3-kinase (PI3K) and P38 mitogen activated protein kinase (MAPK) inhibitors and dexamethasone were used to investigate differences in signaling pathways. The presence of Th2 cytokines did not affect RV replication or viral titre, yet there was a synergistic increase in IP-10 release from virally infected cells in the presence of Th2 cytokines. Release of IL-8 and GM-CSF was also augmented. IP-10 release was blocked by a PI3K inhibitor and IL-8 by dexamethasone. Th2 cytokines increase release of inflammatory cytokines in the presence of rhinovirus infection. This increase is independent of effects of virus replication. Inhibition of the PI3K pathway inhibits IP-10 expression.
    PLoS ONE 04/2014; 9(4):e94010. DOI:10.1371/journal.pone.0094010 · 3.53 Impact Factor
  • European Respiratory Journal 04/2014; 43(4):927-32. DOI:10.1183/09031936.00221613 · 7.13 Impact Factor
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    ABSTRACT: Diesel exhaust is associated with cardiovascular and respiratory mortality and morbidity. Acute exposure leads to increased IL-8 expression and airway neutrophilia, however the mechanism of this response is unknown. Objectives: As cigarette smoke-induced IL-8 expression by epithelial cells involves transactivation of the epidermal growth factor receptor (EGFR), we studied the effects of diesel exhaust particles (DEP) on IL-8 release and the role of the EGFR. Primary bronchial epithelial cells (PBEC) were exposed to DEPs or carbon black. IL-8 and EGFR ligand expression (transforming growth factor alpha (TGFalpha), heparin-binding EGF-like growth factor, and amphiregulin (AR)) were assessed by quantitative RT-PCR and ELISA. DEP, but not carbon black, caused a dose-dependent increase in mitogen-activated protein kinase (MAPK) activation and IL-8 expression, however above 50mug/ml there was an increase in cytotoxicity. At 50mug/ml, DEPs stimulated transcription and release of IL-8 and EGFR ligands. IL-8 release was blocked by EGFR neutralizing antibodies, an EGFR-selective tyrosine kinase inhibitor and by the metalloprotease inhibitor, GM6001, which blocks EGFR ligand shedding. Neutralizing antibodies to AR, TGFalpha and heparin-binding (HB)-EGF reduced DEP-induced IL-8 by >50%.Conclusion Expression of IL-8 in response to DEPs is dependent on EGFR activation and that autocrine production of EGFR ligands makes a substantial contribution to this response. Capsule Summary: This study identifies a mechanism whereby diesel particles stimulates IL-8 release from bronchial epithelial cells. This mechanism may help to explain the recruitment of neutrophils into the airways of people exposed to particulate air pollution.
    Respiratory research 02/2014; 15(1):22. DOI:10.1186/1465-9921-15-22 · 3.38 Impact Factor
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    ABSTRACT: Rationale: Interleukin (IL)-17 signaling has been implicated in development and persistence of asthma. Cytokine-targeted strategies blocking IL-17 receptor signaling may be beneficial in asthma treatment. Objectives: To determine efficacy and safety of brodalumab, a human anti-IL-17 receptor A monoclonal antibody, in subjects with inadequately controlled moderate-severe asthma taking regular inhaled corticosteroids. Methods: 302 subjects were randomized to brodalumab (140, 210, or 280 mg) or placebo. Primary endpoint was change in Asthma Control Questionnaire (ACQ) score from baseline to week 12. Secondary endpoints included FEV1, symptom scores, and symptom-free days. Pre-specified subgroup analyses were conducted to identify potential responsive subpopulations. Analyses included randomized subjects receiving ≥1 dose of investigational product using last-observation-carried-forward imputation. Measurements and Main Results: Demographics and baseline characteristics were generally balanced among groups (N=302; n=226 brodalumab). For the overall study population, no treatment differences were observed. Nine prespecified subgroups were examined without corrections for multiple testing. In only the high reversibility subgroup (post-bronchodilator FEV1 improvement ≥20%; n=112) was an ACQ change with nominal significance noted; ACQ responses were nominally significant in the 210 mg group (estimated treatment difference 0.53), but not significant in the higher 280 mg group (estimated treatment difference 0.38). AEs, generally balanced among groups, were most commonly asthma, upper respiratory tract infection, and injection site reaction. Conclusion: Inhibition of IL-17 receptor A did not produce a treatment effect in subjects with asthma. The results of the high reversibility subgroup analysis are of uncertain significance, requiring further study of brodalumab in this asthma subpopulation.
    American Journal of Respiratory and Critical Care Medicine 11/2013; 188(11). DOI:10.1164/rccm.201212-2318OC · 11.99 Impact Factor
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    Stephen T Holgate
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    ABSTRACT: My research career has focused on the causes of asthma and its treatment. After establishing the key role that mast cells play in the inflammatory response in asthma, attention was turned towards understanding disease chronicity and variability across the lifecourse. Through a combination of studies on airway biopsies and primary cell cultures we have established that asthma is primarily an epithelial disease driven by increased environmental susceptibility to injury and an altered repair response as depicted by sustained activation of the epithelial mesenchymal trophic unit (EMTU) that is invoked in foetal branching morphogenesis. Varied activation of the EMTU connects the origins of asthma to its progression over time with involvement of epithelial susceptibility through impaired barrier and innate immune functions and altered mesenchymal susceptibility as exemplified by polymorphisms of the metalloprotease gene, ADAM33. Taken together these observations have led to a fundamental re-evaluation of asthma pathogenesis. Rather than placing allergic inflammation as the prime abnormality, it is proposed that the airway epithelium lies at the center of asthma pathogenesis, and that in conjunction with the underlying mesenchyme, it is the principle orchestrator of both the induction of asthma and its evolution over the lifecourse. This concept has provided 'the basis for a new preventative and therapeutic approach focused more on increasing the airways resistance to environmental insults rather than suppressing downstream inflammation once it is established.
    Allergy, asthma & immunology research 11/2013; 5(6):343-347. DOI:10.4168/aair.2013.5.6.343 · 3.08 Impact Factor
  • European Respiratory Journal 09/2013; 42(3):564-7. DOI:10.1183/09031936.00104713 · 7.13 Impact Factor
  • Stephen T Holgate
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    ABSTRACT: Asthma is an inflammatory disorder of the conducting airways that has traditionally been classified according to severity. While this has been helpful in guiding treatment with drugs that are currently available such as β2-adrenoceptor agonists and corticosteroids, it takes little account of disease heterogeneity and causal pathways. This review draws attention to subphenotypes of asthma involving different mechanisms and moves the focus away from the adaptive immune response more towards innate immune mechanisms. 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.
    Current Opinion in Pharmacology 04/2013; 13(3). DOI:10.1016/j.coph.2013.03.008 · 4.23 Impact Factor
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    ABSTRACT: BACKGROUND: Because TNF-α is increased in severe asthma, we hypothesized that TNF-α contributes to barrier dysfunction and cell activation in bronchial epithelial cells. 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. OBJECTIVES: We assessed the effect of TNF-α, with or without src-family kinase inhibitor SU6656, on barrier properties and cytokine release in differentiated human bronchial epithelial cultures. Further, we tested the effect of SU6656 on differentiated primary cultures from severe asthma. METHODS: Barrier properties of differentiated human bronchial epithelial air-liquid interface cultures from healthy subjects and subjects with severe asthma were assessed with transepithelial electrical resistance and fluorescent dextran passage. Proteins were detected by immunostaining or Western blot analysis and cytokines by immunoassay. Mechanisms were investigated with src kinase and other inhibitors. RESULTS: TNF-α lowered transepithelial electrical resistance and increased fluorescent dextran permeability, caused loss of occludin and claudins from tight junctions with redistribution of p120 catenin and E-cadherin from adherens junctions, and also increased endogenous TNF-α, IL-6, IL-1β, IL-8, thymic stromal lymphoprotein, and pro-matrix metalloprotease 9 release. SU6656 reduced TNF-α-mediated paracellular permeability changes, restored occludin, p120, and E-cadherin and lowered autocrine TNF-α release. Importantly, SU6656 improved the barrier properties of severe asthmatic air-liquid interface cultures. Redistribution of E-cadherin and p120 was observed in bronchial biopsies from severe asthmatic airways. CONCLUSIONS: Inhibiting TNF-α or src kinases may be a therapeutic option to normalize barrier integrity and cytokine release in airway diseases associated with barrier dysfunction.
    The Journal of allergy and clinical immunology 04/2013; DOI:10.1016/j.jaci.2013.03.005 · 11.25 Impact Factor
  • Wiparat Manuyakorn, Peter H Howarth, Stephen T Holgate
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    ABSTRACT: Asthma is an airway inflammatory disease with functional and structural changes, leading to bronchial hyperresponsiveness (BHR) and airflow obstruction. Airway structural changes or airway remodelling consist of epithelial injury, goblet cell hyperplasia, subepithelial layer thickening, airway smooth muscle hyperplasia and angiogenesis. These changes were previously considered as a consequence of chronic airway inflammation. However, several studies have demonstrated that inflammation and remodelling can occur as separate but parallel aspects of the asthmatic process. As such there is increasing evidence for the role of mechanocompressive forces within the asthmatic airway contributing to airway structural changes. Furthermore, it is unclear what is the best treatment to modify remodelling and which component to target. There is also a need to identify asthma phenotype that might specifically respond to novel therapies such as anti-IL5, anti-IL13 and tyrosine kinase inhibitors.
    Asian Pacific journal of allergy and immunology / launched by the Allergy and Immunology Society of Thailand 03/2013; 31(1):3-10. · 1.26 Impact Factor
  • Journal of Allergy and Clinical Immunology 02/2013; 131(2):AB230. DOI:10.1016/j.jaci.2012.12.1486 · 11.25 Impact Factor
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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.

Publication Stats

45k Citations
6,089.56 Total Impact Points

Institutions

  • 1977–2015
    • University of Southampton
      • • Faculty of Medicine
      • • Academic Unit of Clinical and Experimental Sciences
      Southampton, England, United Kingdom
  • 2013
    • Mahidol University
      • Faculty of Medicine Ramathibodi Hospital
      Bangkok, Bangkok, Thailand
  • 2012
    • University of British Columbia - Vancouver
      • Department of Anesthesiology, Pharmacology and Therapeutics
      Vancouver, British Columbia, Canada
  • 1985–2012
    • WWF United Kingdom
      Londinium, England, United Kingdom
    • Clinical pharmacology of Miami
      Miami, Florida, United States
  • 2009
    • Poznan University of Medical Sciences
      Posen, Greater Poland Voivodeship, Poland
  • 2008
    • The University of Edinburgh
      Edinburgh, Scotland, United Kingdom
    • National Heart, Lung, and Blood Institute
      Maryland, United States
  • 2007
    • The University of York
      York, England, United Kingdom
    • St George's, University of London
      Londinium, England, United Kingdom
  • 2006
    • Imperial College London
      Londinium, England, United Kingdom
    • The Prince Charles Hospital (Queensland Health)
      Brisbane, Queensland, Australia
  • 1996–2006
    • University of Catania
      • Department of Clinical and Molecular Biomedicine (MEDBIO)
      Catania, Sicily, Italy
    • The Heart Lung Center
      Londinium, England, United Kingdom
    • Countess Of Chester Hospital NHS Foundation Trust
      Chester, England, United Kingdom
  • 2005
    • Νοσοκομείο Σωτηρία
      Athínai, Attica, Greece
  • 2001–2005
    • Umeå University
      Umeå, Västerbotten, Sweden
    • University of Hull
      Kingston upon Hull, England, United Kingdom
  • 2004
    • University of Western Australia
      • School of Medicine and Pharmacology
      Perth City, Western Australia, Australia
    • Cancer Research UK Cambridge Institute
      Cambridge, England, United Kingdom
  • 1998–2003
    • University Hospital Southampton NHS Foundation Trust
      • Department of Medical Physics and Bioengineering
      Southampton, England, United Kingdom
    • Harvard Medical School
      Boston, Massachusetts, United States
  • 2002
    • Harvard University
      Cambridge, Massachusetts, United States
  • 2001–2002
    • Bournemouth University
      Bournemouth, England, United Kingdom
  • 2000–2001
    • University of Bristol
      • Medical School
      Bristol, ENG, United Kingdom
    • Università degli Studi di Modena e Reggio Emilia
      Modène, Emilia-Romagna, Italy
    • Stellenbosch University
      Johannesburg, Gauteng, South Africa
    • Universita degli studi di Ferrara
      • Research Center for the Research of Asthma and BPCO
      Ferrara, Emilia-Romagna, Italy
  • 1999
    • University of Otago
      • Department of Medicine (Christchurch)
      Taieri, Otago, New Zealand
  • 1996–1999
    • St. James University
      Сент-Джеймс, New York, United States
  • 1997
    • McMaster University
      • Health Sciences Centre
      Hamilton, Ontario, Canada
    • University Medical Center Utrecht
      • Department of Pathology
      Utrecht, Provincie Utrecht, Netherlands
    • SickKids
      Toronto, Ontario, Canada
    • Ealing, Hammersmith & West London College
      Londinium, England, United Kingdom
    • University of Nottingham
      Nottigham, England, United Kingdom
    • Ajou University
      • Department of Allergy and Clinical Immunology
      Seoul, Seoul, South Korea
  • 1991–1997
    • Indian Broiler (IB) Group India
      Bhānpuri, Chhattisgarh, India
  • 1994
    • Liverpool Heart And Chest Hospital
      Liverpool, England, United Kingdom
  • 1986
    • Kalamazoo College
      Michigan Center, Michigan, United States