Ian D Pavord

University of Oxford, Oxford, England, United Kingdom

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Publications (342)3361.46 Total impact

  • Andrew Bush · Ian Pavord
    Thorax 09/2015; 70(9). DOI:10.1136/thoraxjnl-2015-207508 · 8.56 Impact Factor
  • The Lancet Respiratory Medicine 08/2015; 3(8):e27. DOI:10.1016/S2213-2600(15)00259-3 · 9.63 Impact Factor
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    ABSTRACT: The UK Refractory Asthma Stratification Programme (RASP-UK) will explore novel biomarker stratification strategies in severe asthma to improve clinical management and accelerate development of new therapies. Prior asthma mechanistic studies have not stratified on inflammatory phenotype and the understanding of pathophysiological mechanisms in asthma without Type 2 cytokine inflammation is limited. RASP-UK will objectively assess adherence to corticosteroids (CS) and examine a novel composite biomarker strategy to optimise CS dose; this will also address what proportion of patients with severe asthma have persistent symptoms without eosinophilic airways inflammation after progressive CS withdrawal. There will be interactive partnership with the pharmaceutical industry to facilitate access to stratified populations for novel therapeutic studies. 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 07/2015; DOI:10.1136/thoraxjnl-2015-207326 · 8.56 Impact Factor
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    ABSTRACT: Several unmet needs have been identified in allergic rhinitis: identification of the time of onset of the pollen season, optimal control of rhinitis and comorbidities, patient stratification, multidisciplinary team for integrated care pathways, innovation in clinical trials and above all patient empowerment. MASK-rhinitis (MACVIA-ARIA Sentinel NetworK for allergic rhinitis) is a simple system centred around the patient which was devised to fill many of these gaps using Information and Communications Technology (ICT) tools and a clinical decision support system (CDSS) based on the most widely used guideline in allergic rhinitis and its asthma co-morbidity (ARIA 2015 revision). It is one of the implementation systems of the Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA). Three tools are used for the electronic monitoring of allergic diseases: a cell phone-based daily visual analogue scale (VAS) assessment of disease control, CARAT (Control of Allergic Rhinitis and Asthma Test) and the e-Allergy screening (Premedical system of early diagnosis of allergy and asthma based on online tools). These tools are combined with a clinical decision support system (CDSS) and are available in many languages. An e-CRF and an e-learning tool complete MASK. MASK is flexible and other tools can be added. It appears to be an advanced, global and integrated ICT answer for many unmet needs in allergic diseases which will improve policies and standards. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Allergy 07/2015; DOI:10.1111/all.12686 · 6.00 Impact Factor
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    ABSTRACT: Potentially pathogenic microorganisms can be detected by quantitative real-time polymerase chain reaction (qPCR) in sputum from patients with COPD, although how this technique relates to culture and clinical measures of disease is unclear. We used cross-sectional and longitudinal data to test the hypotheses that qPCR is a more sensitive measure of bacterial presence and is associated with neutrophilic airway inflammation and adverse clinical outcomes. Sputum was collected from 174 stable COPD subjects longitudinally over 12 months. Microbial sampling using culture and qPCR was performed. Spirometry and sputum measures of airway inflammation were assessed. Sputum was qPCR-positive (>10(6) copies/mL) in 77/152 samples (Haemophilus influenzae [n=52], Moraxella catarrhalis [n=24], Streptococcus pneumoniae [n=19], and Staphylococcus aureus [n=7]). Sputum was culture-positive in 50/174 samples, with 49 out of 50 culture-positive samples having pathogen-specific qPCR bacterial loads >10(6) copies/mL. Samples that had qPCR copy numbers >10(6)/mL, whether culture-positive or not, had increased sputum neutrophil counts. H. influenzae qPCR copy numbers correlated with sputum neutrophil counts (r=0.37, P<0.001), were repeatable within subjects, and were >10(6)/mL three or more times in 19 patients, eight of whom were repeatedly sputum culture-positive. Persistence, whether defined by culture, qPCR, or both, was associated with a higher sputum neutrophil count, lower forced expiratory volume in 1 second (FEV1), and worsened quality of life. qPCR identifies a significant number of patients with potentially bacteria-associated neutrophilic airway inflammation and disease that are not identified by traditional culture-based methods.
    International Journal of COPD 06/2015; 10:1075-83. DOI:10.2147/COPD.S80091
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    ABSTRACT: This review focuses on the methods available for measuring reversible airways obstruction, bronchial hyperresponsiveness (BHR) and inflammation as hallmarks of asthma, and their role in monitoring children with asthma. Persistent bronchial obstruction may occur in asymptomatic children and is considered a risk factor for severe asthma episodes and is associated with poor asthma outcome. Annual measurement of forced expiratory volume in 1 s using office based spirometry is considered useful. Other lung function measurements including the assessment of BHR may be reserved for children with possible exercise limitations, poor symptom perception and those not responding to their current treatment or with atypical asthma symptoms, and performed on a higher specialty level. To date, for most methods of measuring lung function there are no proper randomised controlled or large longitudinal studies available to establish their role in asthma management in children. Noninvasive biomarkers for monitoring inflammation in children are available, for example the measurement of exhaled nitric oxide fraction, and the assessment of induced sputum cytology or inflammatory mediators in the exhaled breath condensate. However, their role and usefulness in routine clinical practice to monitor and guide therapy remains unclear, and therefore, their use should be reserved for selected cases. Copyright ©ERS 2015.
    European Respiratory Review 06/2015; 24(136):204-215. DOI:10.1183/16000617.00003914
  • Ian Pavord · Andrew Bush
    Thorax 05/2015; 70(7). DOI:10.1136/thoraxjnl-2015-207228 · 8.56 Impact Factor
  • Andrew Bush · Ian Pavord
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    ABSTRACT: Two vast collective family sighs of relief from Oxford and London were heard this month as news of the appointment of the new editorial team for Thorax was … [Full text of this article]
    Thorax 05/2015; 70(5):403. DOI:10.1136/thoraxjnl-2015-207103 · 8.56 Impact Factor
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    Bart Hilvering · Luzheng Xue · Ian D Pavord
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    ABSTRACT: Two recent phase III trials in patients with severe eosinophilic asthma have shown that anti-interleukin 5 (IL-5) therapy with mepolizumab reduces the frequency of asthma attacks, improves symptoms and allows patients to reduce oral glucocorticoid use without loss of control of asthma. An earlier large 616 patient Dose Ranging Efficacy And safety with Mepolizumab in severe asthma (DREAM) study had shown that the only variables associated with treatment efficacy were a prior history of asthma attacks and the peripheral blood eosinophil count. The link between blood eosinophil counts and treatment efficacy is biologically obvious given that IL-5 has a pivotal role in eosinophil production, proliferation and chemotaxis. It is also clinically relevant as the blood eosinophil count is routinely measured and thus readily available in patients with asthma. Recognition of the link between airway or blood eosinophilia and treatment response was also important in the clinical testing of the alternative IL-5 blocker, such as reslizumab, which is currently being evaluated in a phase III randomized controlled trial (RCT) after having shown to improve lung function, improve symptom score and reduce sputum eosinophilia in a smaller phase IIb study. In addition, benralizumab, an IL-5α receptor blocker, has shown good effects in a phase IIb RCT with patients with severe asthma that had sputum eosinophilia and more recently in a phase IIa trial with patients with eosinophilic chronic obstructive pulmonary disease. Therefore anti-IL-5 treatment seems generally effective in eosinophilic asthma, either assessed by blood or airway eosinophilia. This factor together with the impressive clinical efficacy and good safety profile make anti-IL-5 (mepolizumab, reslizumab) and benralizumab (anti-IL-5 receptor α) very promising drugs for the treatment of patients with severe eosinophilic asthma, a subgroup that is in desperate need of better treatments. © The Author(s), 2015.
    Therapeutic Advances in Respiratory Disease 04/2015; 9(4). DOI:10.1177/1753465815581279 · 1.95 Impact Factor
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    ABSTRACT: The short-term benefits of inhaled corticosteroids for patients with chronic obstructive pulmonary disease (COPD) are greater in patients with evidence of eosinophilic airway inflammation. We investigated whether blood eosinophil count is a useful biomarker of the long-term effect of the inhaled corticosteroid fluticasone furoate on exacerbation frequency. We did a post-hoc analysis of data from two replicate, randomised, double-blind trials of 12 months' duration (Sept 25, 2009 to Oct 21, 2011 and Oct 17, 2011) in which once a day vilanterol 25 μg was compared with 25 μg vilanterol plus 50 μg, 100 μg, or 200 μg fluticasone furoate in patients with moderate-to-severe COPD and a history of one or more exacerbation in the previous year. We compared exacerbation rates according to two baseline eosinophil cell count strata (<2% and ≥2%), and according to four baseline percentage groupings. We also assessed lung function and incidence of pneumonia per strata in treatment groups. We included 3177 patients in the analyses, with 2083 patients (66%) having an eosinophil count of 2% or higher at study entry. Across all doses of inhaled corticosteroids, fluticasone furoate and vilanterol reduced exacerbations by 29% compared with vilanterol alone (mean 0·91 vs 1·28 exacerbations per patient per year; p<0·0001) in patients with eosinophil counts of 2% or higher, and by 10% (0·79 vs 0·89; p=0·2827) in patients with eosinophil counts lower than 2%. Reductions in exacerbations with fluticasone furoate and vilanterol, compared with vilanterol alone, were 24% in patients with baseline eosinophil counts of ≥2-<4%, 32% for those with counts of 4-<6%, and 42% for those with eosinophil counts of ≥6%. In patients treated with vilanterol alone, exacerbation rates increased progressively with increasing eosinophil count percentage category. Improvement in trough forced expiratory volume in 1 s (FEV1) and the increased risk of pneumonia with fluticasone furoate and vilanterol compared with vilanterol alone were not associated with eosinophil count. Blood eosinophil count is a promising biomarker of response to inhaled corticosteroids in patients with COPD. Blood eosinophil count could potentially be used to stratify patients for different exacerbation rate reduction strategies. GlaxoSmithKline (study ID 201595). Copyright © 2015 Elsevier Ltd. All rights reserved.
    04/2015; 3(6). DOI:10.1016/S2213-2600(15)00106-X
  • Andrew Bush · Sabine Kleinert · Ian D Pavord
    The Lancet 04/2015; 385(9975). DOI:10.1016/S0140-6736(15)60654-7 · 45.22 Impact Factor
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    ABSTRACT: Some patients with refractory asthma have evidence of uncontrolled eosinophilic inflammation in the distal airways. While traditional formulations of inhaled steroids settle predominantly in the large airways, newer formulations with an extra-fine particle size have a more peripheral pattern of deposition. Specifically treating distal airway inflammation may improve asthma control. 30 patients with refractory asthma despite high dose inhaled corticosteroids were identified as having persistent airway eosinophilia. Following 2 weeks of prednisolone 30 mg, patients demonstrating an improvement in asthma control were randomised to receive either ciclesonide 320 µg twice daily or placebo in addition to usual maintenance therapy for 8 weeks. The primary outcome measure was sputum eosinophil count at week 8. Alveolar nitric oxide was measured as a marker of distal airway inflammation. There was continued suppression of differential sputum eosinophil counts with ciclesonide (median 2.3%) but not placebo (median 4.5%) though the between-group difference was not significant. When patients who had changed their maintenance prednisolone dose during the trial were excluded the difference between groups was significant (1.4% vs 4.5%, p=0.028). Though alveolar nitric oxide decreased with ciclesonide the value did not reach statistical significance. These data demonstrate that patients with ongoing eosinophilic inflammation are not truly refractory, and that suppression of airway eosinophilia may be maintained with additional inhaled corticosteroid. Further work is needed with a focus on patient-orientated outcome measures such as exacerbation rate, with additional tests of small airway function. NCT01171365. Protocol available at http://www.clinicaltrials.gov. 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 04/2015; 70(6). DOI:10.1136/thoraxjnl-2014-206481 · 8.56 Impact Factor
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    ABSTRACT: Childhood wheezing is common particularly in children under the age of six years and in this age-group is generally referred to as preschool wheezing. Particular diagnostic and treatment uncertainties exist in these young children due to the difficulty in obtaining objective evidence of reversible airways narrowing and inflammation. A diagnosis of asthma depends on the presence of relevant clinical signs and symptoms and the demonstration of reversible airways narrowing on lung function testing, which is difficult to perform in young children. Few treatments are available and inhaled corticosteroids are the recommended preventer treatment in most international asthma guidelines. There is however considerable controversy about its effectiveness in children with preschool wheeze and a corticosteroid responder phenotype has not been established. These diagnostic and treatment uncertainties in conjunction with the knowledge of corticosteroid side-effects, in particular the reduction of growth velocity, has resulted in a variable approach to inhaled corticosteroid prescribing by medical practitioners and a reluctance in carers to regularly administer the treatment. Identifying children who are likely responders to corticosteroid therapy would be a major benefit in the management of this condition. Eosinophils have emerged as a promising biomarker of corticosteroid responsive airways disease and evaluation of this biomarker in sputum has successfully been employed to direct management in adults with asthma. Obtaining sputum from young children is time-consuming and difficult and it is hard to justify more invasive procedures such as a bronchoscopy in young children routinely. Recently, in children, interest has shifted to assessing the value of less invasive biomarkers of likely corticosteroid response and the biomarker 'blood eosinophils' has emerged as an attractive candidate. The aim of this review is to summarise the evidence for blood eosinophils as a predictive biomarker for corticosteroid responsive disease with a particular focus on the difficult area of preschool wheeze. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Clinical & Experimental Allergy 03/2015; DOI:10.1111/cea.12535 · 4.32 Impact Factor
  • Ian D Pavord · Andrew Bush · Stephen Holgate
    The Lancet Respiratory Medicine 03/2015; 3(5). DOI:10.1016/S2213-2600(15)00056-9 · 9.63 Impact Factor
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    ABSTRACT: The goal of asthma treatment is to obtain clinical control and reduce future risks to the patient. To reach this goal in children with asthma, ongoing monitoring is essential. While all components of asthma, such as symptoms, lung function, bronchial hyperresponsiveness and inflammation, may exist in various combinations in different individuals, to date there is limited evidence on how to integrate these for optimal monitoring of children with asthma. The aims of this ERS Task Force were to describe the current practise and give an overview of the best available evidence on how to monitor children with asthma. 22 clinical and research experts reviewed the literature. A modified Delphi method and four Task Force meetings were used to reach a consensus. This statement summarises the literature on monitoring children with asthma. Available tools for monitoring children with asthma, such as clinical tools, lung function, bronchial responsiveness and inflammatory markers, are described as are the ways in which they may be used in children with asthma. Management-related issues, comorbidities and environmental factors are summarised. Despite considerable interest in monitoring asthma in children, for many aspects of monitoring asthma in children there is a substantial lack of evidence. Copyright ©ERS 2015.
    European Respiratory Journal 03/2015; 45(4). DOI:10.1183/09031936.00088814 · 7.13 Impact Factor
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    Bart Hilvering · Ian D Pavord
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    ABSTRACT: Asthma is a heterogeneous airway disease characterised by typical symptoms in combination with variable airway obstruction. Most patients with asthma have well controlled symptoms and a low risk of asthma attacks with inhaled corticosteroid treatment. However, a clinically important subgroup (~10%) remains symptomatic and/or at risk of asthma attacks despite maximum inhaled therapy. Patients with severe asthma are responsible for a significant proportion of healthcare costs attributable to asthma and have a large unmet need for better treatments. An important advance in recent years has been the recognition that severe asthma is heterogeneous with respect to clinical problems and the pattern of lower airway inflammation. Identification of eosinophilic inflammation in the airways has become an important priority as novel biologicals that target Th2 cytokines, such as anti-IL5, anti- IL-13 and combined anti-IL-4/13 are showing considerable promise as treatments for this sub-group. It has also become clear that anti-IgE (Omalizumab), the first monoclonal antibody registered for treatment of severe asthma, is only active in patients with active eosinophilic airway inflammation. The future will be identification of potentially responsive patients on the basis of raised biomarkers and, as suggested by the title of this review, targeted treatment with specific cytokine blockade that has a direct effect on the biomarkers. In this review we outline an approach to the clinical assessment of patients potentially suitable for biological treatment and describe in detail the likely clinical impact of established and new biological treatments. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Clinical & Experimental Allergy 02/2015; 45(7). DOI:10.1111/cea.12500 · 4.32 Impact Factor
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    Bart Hilvering · Luzheng Xue · Ian D Pavord
    American Journal of Respiratory and Critical Care Medicine 01/2015; 191(2):237. DOI:10.1164/rccm.201411-2067LE · 11.99 Impact Factor
  • American Journal of Respiratory and Critical Care Medicine 01/2015; 191(1):107-10. DOI:10.1164/rccm.201406-1128LE · 11.99 Impact Factor
  • Andrew Bush · Ian Pavord
    Thorax 01/2015; 70(1):11. DOI:10.1136/thoraxjnl-2014-206531 · 8.56 Impact Factor
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    ABSTRACT: To the Editor: In the Withdrawal of Inhaled Steroids during Optimized Bronchodilator Management (WISDOM) study, Magnussen et al. (Oct. 2 issue)(1) report that the withdrawal of inhaled glucocorticoids had no significant effect on exacerbations in patients with severe chronic obstructive pulmonary disease (COPD), a finding that prompted them to cast doubts about the use of these drugs in such patients. We are concerned about this conclusion because the follow-up of less than 1 year was probably not long enough to assess exacerbations, given that such events occur with an average frequency of 1.3 to 2 per year. In addition, there . . .
    New England Journal of Medicine 01/2015; 372(1):92-4. DOI:10.1056/NEJMc1413308#SA3 · 54.42 Impact Factor

Publication Stats

15k Citations
3,361.46 Total Impact Points

Institutions

  • 2013–2015
    • University of Oxford
      Oxford, England, United Kingdom
    • Imperial College London
      Londinium, England, United Kingdom
    • BMJ Group
      Londinium, England, United Kingdom
    • British Medical Journal
      Londinium, England, United Kingdom
  • 2014
    • University of Cape Town
      • Department of Medicine
      Kaapstad, Western Cape, South Africa
  • 2001–2014
    • University Hospitals Of Leicester NHS Trust
      • Department of Respiratory Medicine
      Leiscester, England, United Kingdom
  • 1999–2014
    • University of Leicester
      • • Institute for Lung Health
      • • Department of Infection, Immunity and Inflammation
      Leiscester, England, United Kingdom
    • Nottingham University Hospitals NHS Trust
      • Department of Respiratory Medicine
      Nottigham, England, United Kingdom
  • 2011
    • King's College London
      • Division of Asthma, Allergy and Lung Biology
      London, ENG, United Kingdom
  • 2002–2011
    • Public Health England
      Londinium, England, United Kingdom
    • Leiden University
      Leyden, South Holland, Netherlands
  • 2009
    • University of Otago
      • Department of Medicine (Dunedin)
      Taieri, Otago, New Zealand
  • 2007
    • Università degli Studi di Torino
      Torino, Piedmont, Italy
  • 1998–2007
    • McMaster University
      • Department of Medicine
      Hamilton, Ontario, Canada
  • 2003–2006
    • The Bracton Centre, Oxleas NHS Trust
      Дартфорде, England, United Kingdom
  • 2000
    • Vanderbilt University
      • Department of Medicine
      Нашвилл, Michigan, United States
    • UK Department of Health
      Londinium, England, United Kingdom
  • 1996
    • St. Joseph's Healthcare Hamilton
      Hamilton, Ontario, Canada
  • 1991–1994
    • University of Nottingham
      • Division of Respiratory Medicine
      Nottigham, England, United Kingdom