Ian D Pavord

University of Oxford, Oxford, England, United Kingdom

Are you Ian D Pavord?

Claim your profile

Publications (379)3640.51 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Cough is a common symptom of pulmonary sarcoidosis. This study aimed to quantify cough frequency, and investigate its relationship with cough reflex sensitivity, pulmonary function and health status.32 patients with pulmonary sarcoidosis were compared with 40 healthy controls. Cough reflex sensitivity to capsaicin, objective 24-h cough counts, cough-specific health status, cough severity and cough triggers were measured. The predictors of cough frequency in sarcoidosis were determined in a multivariate analysis.Objective cough frequency was significantly raised in patients with sarcoidosis compared with healthy controls (p<0.001) and patients with cough had an impaired health status. Patients with pulmonary sarcoidosis had a heightened cough reflex sensitivity compared with healthy controls (p<0.001). Only cough reflex sensitivity was significantly associated with objective cough frequency in multivariate analysis, explaining 42% of the variance (p<0.001). There was no association between cough frequency, lung function, number of organs involved, chest radiograph stage or serum angiotensin-converting enzyme levels.Cough is a common and significant symptom in patients with sarcoidosis. Ambulatory objective cough monitoring provides novel insights into the determinants of cough in sarcoidosis, suggesting that cough reflex sensitivity may be more important than lung function and other measures of disease severity, and this should be investigated further.
    No preview · Article · Feb 2016 · European Respiratory Journal

  • No preview · Article · Feb 2016 · European Respiratory Journal
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this review was to evaluate the clinical effectiveness of fractional exhaled nitric oxide (FeNO) measured in a clinical setting for the management of asthma in adults.13 electronic databases were searched and studies were selected against predefined inclusion criteria. Quality assessment was conducted using QUADAS-2. Class effect meta-analyses were performed.Six studies were included. Despite high levels of heterogeneity in multiple study characteristics, exploratory class effect meta-analyses were conducted. Four studies reported a wider definition of exacerbation rates (major or severe exacerbation) with a pooled rate ratio of 0.80 (95% CI 0.63-1.02). Two studies reported rates of severe exacerbations (requiring oral corticosteroid use) with a pooled rate ratio of 0.89 (95% CI 0.43-1.72). Inhaled corticosteroid use was reported by four studies, with a pooled standardised mean difference of -0.24 (95% CI -0.56-0.07). No statistically significant differences for health-related quality of life or asthma control were found.FeNO guided management showed no statistically significant benefit in terms of severe exacerbations or ICS use, but showed a statistically significant reduction in exacerbations of any severity. However, further research is warranted to clearly define which management protocols (including cut-off points) offer best efficacy and which patient groups would benefit the most.
    No preview · Article · Feb 2016 · European Respiratory Journal
  • [Show abstract] [Hide abstract]
    ABSTRACT: Fractional exhaled nitric oxide (FeNO) is a non-invasive biomarker of eosinophilic inflammation which may be used to guide the management of asthma in childhood. To synthesise the available evidence on the efficacy of FeNO-guided management of childhood asthma. Databases including MEDLINE and the Cochrane Library were searched, and randomised controlled trials (RCTs) comparing FeNO-guided management with any other monitoring strategy were included. Study quality was assessed using the Cochrane risk of bias tool for RCTs, and a number of outcomes were examined, including: exacerbations, medication use, quality of life, adverse events, and other markers of asthma control. Meta-analyses were planned if multiple studies with suitable heterogeneity were available. However, due to wide variations in study characteristics, meta-analysis was not possible. Seven RCTs were identified. There was some evidence that FeNO-guided monitoring results in improved asthma control during the first year of management, although few results attained statistical significance. The impact on severe exacerbations was unclear. Similarly, the impact on use of anti-asthmatic drugs was unclear, and appears to depend on the step up/down protocols, and the clinical characteristics of patients. The potential benefit of FeNO monitoring is equivocal. Trends toward reduced exacerbation and increased medication use were seen, but typically failed to reach statistical significance. There are a number of issues that complicate data interpretation, including differences in the likely severity of included cohorts and variations in treatment algorithms. Further work is needed to systematically explore the impact of these parameters. Pediatr Pulmonol.
    No preview · Article · Feb 2016 · Pediatric Pulmonology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Patients with moderate exacerbations of chronic obstructive pulmonary disease (COPD) and the eosinophilic phenotype have better outcomes with prednisolone. Whether this is the case in patients hospitalised with a severe exacerbation of COPD is unclear. We investigate the rate of recovery of eosinophilic and non-eosinophilic exacerbations from subjects participating in a multi-centre randomised control trial assessing health outcomes in hospitalised exacerbations (clinical trial registration ISRCTN05557928). Methods: Subjects were recruited at presentation to hospital with an exacerbation of COPD and stratified into eosinophilic exacerbations if the peripheral blood eosinophil on admission was ≥200 cells/μL and/or ≥2% of the total leukocyte count. Admission details, serum CRP, length of stay and subsequent re-hospitalisation were compared between groups. Results: We recruited 243 COPD subjects (117 males) with a mean age (range) of 71 years (45-93). The inpatient mortality rate was 3% (median time to death 12 days, range 9-16). The median absolute eosinophil count was 100 cells/μL (range 10 to 1500 cells/μL) and 25% met our criteria for an eosinophilic exacerbation. In this population, the mean length of stay was shorter than in patients with non-eosinophilic exacerbations (5.0 (1-19) vs. 6.5 (1-33), p=0.015) following treatment with oral corticosteroids and independent of treatment prior to admission. Readmission rates at 12 months was similar between the groups. Conclusions: Patients presenting to hospital with a severe eosinophilic exacerbation of COPD have a shorter length of stay. These exacerbations are usually not associated with an elevated CRP, suggesting that better treatment stratification of exacerbations can be utilised.
    Preview · Article · Feb 2016 · Chest

  • No preview · Article · Feb 2016 · European Respiratory Journal

  • No preview · Article · Jan 2016 · The Lancet Respiratory Medicine
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Lung function measures are used in the diagnosis of chronic obstructive pulmonary disease. In 38,199 European ancestry individuals, we studied genome-wide association of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC with 1000 Genomes Project (phase 1)-imputed genotypes and followed up top associations in 54,550 Europeans. We identify 14 novel loci (P<5 × 10-8) in or near ENSA, RNU5F-1, KCNS3, AK097794, ASTN2, LHX3, CCDC91, TBX3, TRIP11, RIN3, TEKT5, LTBP4, MN1 and AP1S2, and two novel signals at known loci NPNT and GPR126, providing a basis for new understanding of the genetic determinants of these traits and pulmonary diseases in which they are altered.
    Full-text · Article · Dec 2015 · Nature Communications
  • [Show abstract] [Hide abstract]
    ABSTRACT: Rationale: Pulmonary infection and malnutrition in cystic fibrosis are associated with decreased survival. Glutamine has a possible anti-microbial effect, with a specific impact against Pseudomonas aeruginosa. We aimed to test the hypothesis that oral glutamine supplementation (21 g/day) for 8 weeks in adults with cystic fibrosis would decrease pulmonary inflammation and improve clinical status. Methods: The study design was a randomized double-blind placebo-controlled study design with an iso-nitrogenous placebo. The primary analysis was intention to treat, and the primary outcome was change in induced sputum neutrophils. Results: Thirty-nine individuals were recruited and thirty-six completed the study. Glutamine supplementation had no impact on any of the outcome measures in the intention-to-treat analysis. In the per protocol analysis, glutamine supplementation was associated with an increase in induced sputum neutrophils (P = 0.046), total cells (P = 0.03), and in Pseudomonas isolation agar colony forming units (P = 0.04) compared to placebo. Conclusions: There was no effect of glutamine supplementation on markers of pulmonary inflammation in the intention-to-treat analysis. Pediatr Pulmonol. © 2015 Wiley Periodicals, Inc.
    No preview · Article · Dec 2015 · Pediatric Pulmonology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective: We performed a review of studies of fluticasone propionate (FP)/salmeterol (SAL) (combination inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA)) in patients with COPD, which measured baseline (pretreatment) blood eosinophil levels, to test whether blood eosinophil levels ≥2% were associated with a greater reduction in exacerbation rates with ICS therapy. Methods: Three studies of ≥1-year duration met the inclusion criteria. Moderate and severe exacerbation rates were analysed according to baseline blood eosinophil levels (<2% vs ≥2%). At baseline, 57-75% of patients had ≥2% blood eosinophils. Changes in FEV1 and St George's Respiratory Questionnaire (SGRQ) scores were compared by eosinophil level. Results: For patients with ≥2% eosinophils, FP/SAL was associated with significant reductions in exacerbation rates versus tiotropium (INSPIRE: n=719, rate ratio (RR)=0.75, 95% CI 0.60 to 0.92, p=0.006) and versus placebo (TRISTAN: n=1049, RR=0.63, 95% CI 0.50 to 0.79, p<0.001). No significant difference was seen in the <2% eosinophil subgroup in either study (INSPIRE: n=550, RR=1.18, 95% CI 0.92 to 1.51, p=0.186; TRISTAN: n=354, RR=0.99, 95% CI 0.67 to 1.47, p=0.957, respectively). In SCO30002 (n=373), no significant effects were observed (FP or FP/SAL vs placebo). No relationship was observed in any study between eosinophil subgroup and treatment effect on FEV1 and SGRQ. Discussion: Baseline blood eosinophil levels may represent an informative marker for exacerbation reduction with ICS/LABA in patients with COPD and a history of moderate/severe exacerbations.
    Full-text · Article · Nov 2015 · Thorax

  • No preview · Article · Nov 2015 · Value in Health

  • No preview · Conference Paper · Nov 2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Elevated sputum eosinophil counts predict asthma exacerbations and responsiveness to inhaled corticosteroids but are impractical to measure in primary care. We investigated the relation between blood eosinophil count and prospective annual asthma outcomes for a large UK cohort. Methods: This historical cohort study used anonymised medical record data to identify primary care patients with asthma aged 12-80 years with 2 years of continuous records, including 1 year before (baseline) and 1 year after (outcome) their most recent eosinophil count. Negative binomial regression was used to compare outcome exacerbation rates and logistic regression to compare odds of asthma control for patients with blood eosinophil counts of 400 cells per μL or less versus greater than 400 cells per μL, adjusting for age, sex, body-mass index, smoking status, and Charlson comorbidity index. The study is registered at ClinicalTrials.gov, number NCT02140541. Findings: Overall, 20 929 (16%) of 130 248 patients had blood eosinophil counts greater than 400 cells per μL. During the outcome year, these patients experienced significantly more severe exacerbations (adjusted rate ratio [RR] 1·42, 95% CI 1·36-1·47) and acute respiratory events (RR 1·28, 1·24-1·33) than those with counts of 400 cells per μL or less. They also had significantly lower odds of achieving overall asthma control (OR 0·74, 95% CI 0·72-0·77), defined as limited reliever use and no asthma-related hospital attendance or admission, acute course of oral corticosteroids, or prescription for antibiotics. Exacerbation rates increased progressively with nine ascending categories of blood eosinophil count as compared with a reference category of 200 cells per μL or less. Interpretation: Patients with asthma and blood eosinophil counts greater than 400 cells per μL experience more severe exacerbations and have poorer asthma control. Furthermore, a count-response relation exists between blood eosinophil counts and asthma-related outcomes. Blood eosinophil counts could add predictive value to Global Initiative for Asthma control-based risk assessment. Funding: Teva Pharmaceuticals.
    No preview · Article · Oct 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: High fractions of exhaled nitric oxide (FeNO) in the breath of patients with symptoms of asthma are correlated with high levels of eosinophils and indicate that a patient is likely to respond to inhaled corticosteroids. This may have a role in the diagnosis and management of asthma. Objective: To assess the diagnostic accuracy, clinical effectiveness and cost-effectiveness of the hand-held electrochemical devices NIOX MINO(®) (Aerocrine, Solna, Sweden), NIOX VERO(®) (Aerocrine) and NObreath(®) (Bedfont Scientific, Maidstone, UK) for the diagnosis and management of asthma. Data sources: Systematic searches were carried out between March 2013 and April 2013 from database inception. Databases searched included MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, Science Citation Index Expanded and Conference Proceedings Citation Index - Science. Trial registers such as ClinicalTrials.gov and the metaRegister of Controlled Trials were also searched in March 2013. All searches were updated in September 2013. Review methods: A rapid review was conducted to assess the equivalence of hand-held and chemiluminescent FeNO monitors. Systematic reviews of diagnostic accuracy and management efficacy were conducted. A systematic review of economic analyses was also conducted and two de novo health economic models were developed. All three reviews were undertaken according to robust high-quality methodology. Results: The rapid review (27 studies) found varying levels of agreement between monitors (Bland-Altman 95% limits of agreement up to ±10 parts per billion), with better agreement at lower FeNO values. Correlation was good (generally r > 0.9). The diagnostic accuracy review identified 22 studies in adults (all ages) and four in children. No studies used NObreath or NIOX VERO and seven used NIOX MINO. Estimates of diagnostic accuracy varied widely. FeNO used in combination with another test altered diagnostic accuracy only slightly. High levels of heterogeneity precluded meta-analysis. Limited observations included that FeNO may be more reliable and useful as a rule-in than as a rule-out test; lower cut-off values in children and in smokers may be appropriate; and FeNO may be less reliable in the elderly. The management review identified five randomised controlled trials in adults, one in pregnant asthmatics and seven in children. Despite clinical heterogeneity, exacerbation rates were lower in all studies but not generally statistically significantly so. Effects on inhaled corticosteroid (ICS) use were inconsistent, possibly because of differences in management protocols, differential effectiveness in adults and children and differences in population severity. One UK diagnostic model and one management model were identified. Aerocrine also submitted diagnostic and management models. All had significant limitations including short time horizons and the selective use of efficacy evidence. The de novo diagnostic model suggested that the expected difference in quality-adjusted life-year (QALY) gains between diagnostic options is likely to be very small. Airway hyper-responsiveness by methacholine challenge test is expected to produce the greatest QALY gain but with an expected incremental cost-effectiveness ratio (ICER) compared with FeNO (NObreath) in combination with bronchodilator reversibility of £1.125M per QALY gained. All remaining options are expected to be dominated. The de novo management model indicates that the ICER of guidelines plus FeNO monitoring using NObreath compared with guidelines alone in children is expected to be approximately £45,200 per QALY gained. Within the adult subgroup, FeNO monitoring using NObreath compared with guidelines alone is expected to have an ICER of approximately £2100 per QALY gained. The results are particularly sensitive to assumptions regarding changes in ICS use over time, the number of nurse visits for FeNO monitoring and duration of effect. Conclusions: Limitations of the evidence base impose considerable uncertainty on all analyses. Equivalence of devices was assumed but not assured. Evidence for diagnosis is difficult to interpret in the context of inserting FeNO monitoring into a diagnostic pathway. Evidence for management is also inconclusive, but largely consistent with FeNO monitoring resulting in fewer exacerbations, with a small or zero reduction in ICS use in adults and a possible increased ICS use in children or patients with more severe asthma. It is unclear which specific management protocol is likely to be most effective. The economic analysis indicates that FeNO monitoring could have value in diagnostic and management settings. The diagnostic model indicates that FeNO monitoring plus bronchodilator reversibility dominates many other diagnostic tests. FeNO-guided management has the potential to be cost-effective, although this is largely dependent on the duration of effect. The conclusions drawn from both models require strong technical value judgements with respect to several aspects of the decision problem in which little or no empirical evidence exists. There are many potential directions for further work, including investigations into which management protocol is best and long-term follow-up in both diagnosis and management studies. Study registration: This study is registered as PROSPERO CRD42013004149. Funding: The National Institute for Health Research Health Technology Assessment programme.
    Full-text · Article · Oct 2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Understanding the genetic basis of airflow obstruction and smoking behaviour is key to determining the pathophysiology of chronic obstructive pulmonary disease (COPD). We used UK Biobank data to study the genetic causes of smoking behaviour and lung health. Methods: We sampled individuals of European ancestry from UK Biobank, from the middle and extremes of the forced expiratory volume in 1 s (FEV1) distribution among heavy smokers (mean 35 pack-years) and never smokers. We developed a custom array for UK Biobank to provide optimum genome-wide coverage of common and low-frequency variants, dense coverage of genomic regions already implicated in lung health and disease, and to assay rare coding variants relevant to the UK population. We investigated whether there were shared genetic causes between different phenotypes defined by extremes of FEV1. We also looked for novel variants associated with extremes of FEV1 and smoking behaviour and assessed regions of the genome that had already shown evidence for a role in lung health and disease. We set genome-wide significance at p<5 × 10-8. Findings: UK Biobank participants were recruited from March 15, 2006, to July 7, 2010. Sample selection for the UK BiLEVE study started on Nov 22, 2012, and was completed on Dec 20, 2012. We selected 50 008 unique samples: 10 002 individuals with low FEV1, 10 000 with average FEV1, and 5002 with high FEV1 from each of the heavy smoker and never smoker groups. We noted a substantial sharing of genetic causes of low FEV1 between heavy smokers and never smokers (p=2·29 × 10-16) and between individuals with and without doctor-diagnosed asthma (p=6·06 × 10-11). We discovered six novel genome-wide significant signals of association with extremes of FEV1, including signals at four novel loci (KANSL1, TSEN54, TET2, and RBM19/TBX5) and independent signals at two previously reported loci (NPNT and HLA-DQB1/HLA-DQA2). These variants also showed association with COPD, including in individuals with no history of smoking. The number of copies of a 150 kb region containing the 5' end of KANSL1, a gene that is important for epigenetic gene regulation, was associated with extremes of FEV1. We also discovered five new genome-wide significant signals for smoking behaviour, including a variant in NCAM1 (chromosome 11) and a variant on chromosome 2 (between TEX41 and PABPC1P2) that has a trans effect on expression of NCAM1 in brain tissue. Interpretation: By sampling from the extremes of the lung function distribution in UK Biobank, we identified novel genetic causes of lung function and smoking behaviour. These results provide new insight into the specific mechanisms underlying airflow obstruction, COPD, and tobacco addiction, and show substantial shared genetic architecture underlying airflow obstruction across individuals, irrespective of smoking behaviour and other airway disease. Funding: Medical Research Council. © 2015 Wain et al. Open Access article distributed under the terms of CC BY.
    No preview · Article · Oct 2015 · The Lancet Respiratory Medicine
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Understanding the genetic basis of airfl ow obstruction and smoking behaviour is key to determining the pathophysiology of chronic obstructive pulmonary disease (COPD). We used UK Biobank data to study the genetic causes of smoking behaviour and lung health. Methods: We sampled individuals of European ancestry from UK Biobank, from the middle and extremes of the forced expiratory volume in 1 s (FEV1) distribution among heavy smokers (mean 35 pack-years) and never smokers. We developed a custom array for UK Biobank to provide optimum genome-wide coverage of common and low- frequency variants, dense coverage of genomic regions already implicated in lung health and disease, and to assay rare coding variants relevant to the UK population. We investigated whether there were shared genetic causes between diff erent phenotypes defi ned by extremes of FEV1. We also looked for novel variants associated with extremes of FEV1 and smoking behaviour and assessed regions of the genome that had already shown evidence for a role in lung health and disease. We set genome-wide signifi cance at p<5 × 10–⁸. Findings: UK Biobank participants were recruited from March 15, 2006, to July 7, 2010. Sample selection for the UK BiLEVE study started on Nov 22, 2012, and was completed on Dec 20, 2012. We selected 50 008 unique samples: 10 002 individuals with low FEV1, 10 000 with average FEV1, and 5002 with high FEV1 from each of the heavy smoker and never smoker groups. We noted a substantial sharing of genetic causes of low FEV1 between heavy smokers and never smokers (p=2·29 × 10–¹⁶) and between individuals with and without doctor-diagnosed asthma (p=6·06 × 10–¹¹). We discovered six novel genome-wide signifi cant signals of association with extremes of FEV1, including signals at four novel loci (KANSL1, TSEN54, TET2, and RBM19/TBX5) and independent signals at two previously reported loci (NPNT and HLA-DQB1/HLA-DQA2). These variants also showed association with COPD, including in individuals with no history of smoking. The number of copies of a 150 kb region containing the 5ʹ end of KANSL1, a gene that is important for epigenetic gene regulation, was associated with extremes of FEV1. We also discovered fi ve new genome-wide signifi cant signals for smoking behaviour, including a variant in NCAM1 (chromosome 11) and a variant on chromosome 2 (between TEX41 and PABPC1P2) that has a trans eff ect on expression of NCAM1 in brain tissue. Interpretation: By sampling from the extremes of the lung function distribution in UK Biobank, we identifi ed novel genetic causes of lung function and smoking behaviour. These results provide new insight into the specifi c mechanisms underlying airfl ow obstruction, COPD, and tobacco addiction, and show substantial shared genetic architecture underlying airfl ow obstruction across individuals, irrespective of smoking behaviour and other airway disease.
    Full-text · Article · Sep 2015 · The Lancet Respiratory Medicine
  • Andrew Bush · Ian Pavord

    No preview · Article · Sep 2015 · Thorax

  • No preview · Article · Sep 2015 · European Respiratory Journal

  • No preview · Article · Sep 2015 · European Respiratory Journal

  • No preview · Article · Sep 2015 · European Respiratory Journal

Publication Stats

17k Citations
3,640.51 Total Impact Points

Institutions

  • 2013-2016
    • University of Oxford
      Oxford, England, United Kingdom
    • BMJ Group
      Londinium, England, United Kingdom
    • Imperial College London
      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
  • 2002-2011
    • Public Health England
      Londinium, England, United Kingdom
  • 2009
    • University of Otago
      • Department of Medicine (Dunedin)
      Taieri, Otago, New Zealand
  • 2007
    • University of Aberdeen
      Aberdeen, Scotland, United Kingdom
  • 1998-2007
    • McMaster University
      • Department of Medicine
      Hamilton, Ontario, Canada
  • 2006
    • Laval University
      Quebec City, Quebec, Canada
  • 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