Paul W Jones

St George's, University of London, Londinium, England, United Kingdom

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Publications (111)476.87 Total impact

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    ABSTRACT: Background: Previous studies on chronic bronchitis (CB) have used varying definitions. We sought to compare an alternative CB definition using the St. George's Respiratory Questionnaire, a commonly used assessment tool, with the classic definition and to investigate if it had independent or additive value. Methods: We analyzed data from 4513 GOLD 1-4 subjects in the COPDGene cohort. We compared the classic definition of CB with the SGRQ definition, defined by their answers to the questions about both cough and phlegm. We compared the Classic CB+ vs. CB- groups, and the SGRQ CB+ and CB- groups. We also analyzed the cohort split into four groups: Classic CB+/SGRQ CB+, Classic CB+/SGRQ CB-, Classic CB-/SGRQ CB+, Classic CB-/SGRQ CB-. Results: 26.1% were Classic CB+, whereas 39.9% were SGRQ CB+. When the SGRQ definition was compared with the Classic CB definition, using this as the gold standard, the SGRQ CB definition had a sensitivity and specificity of 0.87 and 0.77, respectively. The SGRQ CB+ and Classic CB+ groups were strikingly similar with more respiratory symptoms, exacerbations, worse lung function, and greater airway wall thickness. In addition, the Classic CB+/SGRQ CB+, Classic CB+/SGRQ CB-, Classic CB-/SGRQ CB+ groups shared similar characteristics as well. Conclusions: The SGRQ CB definition identifies more subjects with chronic cough and sputum that share a similar phenotype identified by the Classic CB definition. The addition of the SGRQ CB definition to the classic one can be used to identify more COPD patients at risk for poor outcomes.
    Annals of the American Thoracic Society. 01/2015;
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    ABSTRACT: Rationale: Radiographically-confirmed pneumonia risk has not been assessed with inhaled corticosteroid use in chronic obstructive pulmonary disease (COPD). Objectives: To determine the incidence of pneumonia, risk factors and clinical attributes with inhaled fluticasone furoate in COPD patients with an exacerbation history. Methods: Two replicate, 1-year, double-blind clinical trials enrolled COPD subjects with moderate to very severe airflow limitation and at least one exacerbation in the prior year. Subjects were randomized 1:1:1:1 to receive inhaled once-daily vilanterol 25 µg or vilanterol 25 µg combined with 50 µg, 100 µg, or 200 µg fluticasone furoate. Subjects were required to have a chest radiograph at screening and within 48 hours of any suspected pneumonia or exacerbation. Measurements and Main Results: Of 3255 randomized subjects, 205 pneumonia events occurred in 181 subjects. Chest imaging was available for 195 (95%) of these events. Chest radiographs were also obtained for 1793 (70%) of the 2545 moderate and severe exacerbations. For vilanterol alone and the combination with 50 µg, 100 µg, or 200 µg fluticasone furoate, reported pneumonia incidence was 3%, 6%, 6% and 7%, respectively. However, for events with compatible parenchymal infiltrates, respective incidences were 2%, 4%, 4% and 5%. Factors associated with at least a two-fold increase in the risk of pneumonia with FF/VI were being a current smoker, having prior pneumonia, BMI < 25kg/m2, and severe airflow limitation. Conclusions: Although the incidence of pneumonia is low, radiographically-confirmed pneumonia risk is increased with inhaled FF/VI, although lower than investigator-defined rates. Clinical trial registered with clinicaltrials.gov NCT01009463 (HZC102871); NCT01017952 (HZC102970).
    Annals of the American Thoracic Society. 12/2014;
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    ABSTRACT: Aclidinium/formoterol is a twice-daily (BID) fixed-dose combination (FDC) in development for chronic obstructive pulmonary disease (COPD). The efficacy and safety of aclidinium/formoterol versus monotherapy and placebo in patients with COPD was assessed. In this 24-week double-blind, parallel-group, active- and placebo-controlled, multicentre Phase III study, patients (>=40 years, post-bronchodilator forced expiratory volume in 1 second [FEV1]/forced vital capacity <70% and FEV1 >=30% but <80% predicted normal) were randomised 2:2:2:2:1 to aclidinium/formoterol 400/12 mug (n = 385) or 400/6 mug (n = 381), aclidinium 400 mug (n = 385), formoterol 12 mug (n = 384) or placebo (n = 194) BID via Genuair(R)/Pressair(R)a. At Week 24, aclidinium/formoterol 400/12 mug and 400/6 mug lead to significant improvements from baseline in 1-hour post-dose FEV1 versus aclidinium (125 mL [95% CI: 90, 160; p < 0 . 001] and 69 mL [95% CI: 34, 105; p < 0.001], respectively) and trough FEV1 versus formoterol (85 mL [95% CI: 51, 119; p < 0.001] and 53 mL [95% CI: 19, 87; p < 0.01], respectively; co-primary endpoints). Additionally, aclidinium/formoterol 400/12 mug and 400/6 mug provided significant improvements in Transition Dyspnoea Index (TDI) focal score versus placebo (1.29 units [95% CI: 0.73, 1.86; p < 0.001] and 1.16 units [95% CI: 0.59, 1.73; p < 0.001], respectively; secondary endpoint). All treatments were well tolerated, with safety profiles of the FDCs similar to those of placebo and monotherapy. Both aclidinium/formoterol BID doses significantly improved bronchodilation versus monotherapy, and dyspnoea versus placebo, with no increase in safety risk. Aclidinium/formoterol may be an effective treatment for patients with COPD.Trial registration: ClinicalTrials.gov: NCT01462942.
    BMC Pulmonary Medicine 11/2014; 14(1):178. · 2.49 Impact Factor
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    ABSTRACT: Background Symptomatic relief is an important treatment goal for patients with COPD. To date, no diary for evaluating respiratory symptoms in clinical trials has been developed and scientifically-validated according to FDA and EMA guidelines. The EXACT ¿ Respiratory Symptoms (E-RS) scale is a patient-reported outcome (PRO) measure designed to address this need. The E-RS utilizes 11 respiratory symptom items from the existing and validated 14-item EXACT, which measures symptoms of exacerbation. The E-RS total score quantifies respiratory symptom severity, and 3 domains assess breathlessness, cough and sputum, and chest symptoms.Methods This study examined the performance of the E-RS in each of 3 controlled trials with common and unique validation variables: one 6-month (N¿=¿235, US) and two 3-month (N¿=¿749; N¿=¿597; international). Subjects completed the E-RS as part of a daily eDiary. Tests of reliability, validity, and responsiveness were conducted in each dataset.ResultsIn each study, RS-Total score was internally consistent (Cronbach ¿) (0.88, 0.92, 0.92) and reproducible (intra-class correlation) in stable patients (2 days apart: 0.91; 7 days apart: 0.71, 0.74). RS-Total scores correlated significantly with the following criterion variables (Spearman¿s rho; p¿<¿0.01, all comparisons listed here): FEV1% predicted (¿0.19, ¿0.14, ¿0.15); St. George¿s Respiratory Questionnaire (SGRQ) (0.65, 0.52, 0.51); Breathlessness, Cough, and Sputum Scale (BCSS) (0.89, 0.89); modified Medical Research Council dyspnoea scale (mMRC) (0.40); rescue medication use (0.43, 0.42); Functional Performance Inventory Short-Form (FPI-SF) (0.43); 6-minute walk distance (6-MWT) (¿0.30, ¿0.14) and incremental shuttle walk (ISWT) (¿0.18) tests. Correlations between these variables and RS-Breathlessness, RS-Cough and Sputum, RS-Chest Symptoms scores supported subscale validity. RS-Total, RS-Breathlessness, and RS-Chest Symptoms differentiated mMRC levels of breathlessness severity (p¿<¿0.0001). RS-Total and domain scores differentiated subjects with no rescue medication use and 3 or more puffs (p¿<¿0.0001). Sensitivity to changes in health status (SGRQ), symptoms (BCSS), and exercise capacity (6MWT, ISWT) were also shown and responder definitions using criterion- and distribution-based methods are proposed.Conclusions Results suggest the E-RS is a reliable, valid, and responsive measure of respiratory symptoms of COPD suitable for use in natural history studies and clinical trials.Trial registrationMPEX: NCT00739648; AZ1: NCT00949975; AZ 2: NCT01023516.
    Respiratory Research 10/2014; 15(1):124. · 3.13 Impact Factor
  • Paul W Jones
    European Respiratory Journal 10/2014; 44(4):833-4. · 7.13 Impact Factor
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    ABSTRACT: Lung volume reduction surgery improves quality of life, exercise capacity, and survival in selected patients but is accompanied by significant morbidity. Bronchoscopic approaches may provide similar benefits with less morbidity.
    Journal of bronchology & interventional pulmonology. 10/2014; 21(4):288-297.
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    ABSTRACT: The frequency and impact of exacerbations identified using healthcare resource utilisation (HCRU) or the EXAcerbations of Chronic pulmonary disease Tool (EXACT) were compared prospectively in a 24-week, phase III trial (ATTAIN). Patients with moderate-to-severe chronic obstructive pulmonary disease received twice-daily aclidinium 200 μg, aclidinium 400 μg or placebo. All HCRU events were reported to physicians. "EXACT-identified" events were categorised as "EXACT-reported" (detected by EXACT and reported to the physician) and "EXACT-unreported" (detected but not reported). Health status was measured using the St George's Respiratory Questionnaire (SGRQ). Annualised EXACT-identified event rates were higher in all study arms (placebo 1.39, aclidinium 200 μg 1.00 and aclidinium 400 μg 0.98 per patient per year) versus HCRU (placebo 0.60, aclidinium 200 μg 0.43 and aclidinium 400 μg 0.40 per patient per year). Concordance between methods was low (kappa 0.16). Aclidinium reduced EXACT-identified events (rate ratio versus placebo: aclidinium 200 μg 0.72 and aclidinium 400 μg 0.71; both p<0.05); HCRU events were similarly reduced. At week 24, SGRQ scores improved (-6.6 versus baseline) in patients with no event during weeks 1-12; improvements were significantly smaller in patients with HCRU events (-3.4; p = 0.036) or EXACT-unreported events (-3.0; p = 0.002). Unreported events were more frequent than reported events. Both had similar negative impact on health status. Aclidinium reduced the frequency of both types of event.
    European Respiratory Journal 09/2014; · 7.13 Impact Factor
  • Paul W Jones
    European Respiratory Journal 09/2014; 44(3):570-1. · 7.13 Impact Factor
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    ABSTRACT: The tradition classification of the severity of COPD, based on spirometry, fails to encompass the heterogeneity of the disease. The COPD assessment test (CAT), a multi-dimensional, patient-filled questionnaire, assesses the overall health status of patients, and is recommended as part of the assessment of individuals with COPD. However, information regarding the range of values for the test in a non-COPD population (normative values) is limited, and consequently, knowledge regarding the optimal cut-off, and the minimum clinically important difference (MCID) for the test remain largely empirical.
    Respiratory Research 06/2014; 15(1):68. · 3.13 Impact Factor
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    ABSTRACT: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011 consensus report proposed a new classification system, incorporating symptoms with future risk, in subjects with chronic obstructive pulmonary disease (COPD). We hypothesized it could be applied to Japanese COPD patients. We previously analyzed clinical factors related to 5-year mortality in 150 male outpatients with COPD. We reviewed the data and reanalyzed the relationships between the new GOLD classification and various outcomes including mortality. There were 51 (34.0%), 12 (8.0%), 57 (38.0%), and 30 (20.0%) patients in GOLD A (forced expiratory volume in 1s [FEV1]≥50% predicted and modified Medical Research Council [mMRC] 0-1), GOLD B (FEV1≥50% predicted and mMRC≥2), GOLD C (FEV1<50% predicted and mMRC 0-1), and GOLD D (FEV1 <50% predicted and mMRC≥2), respectively. The GOLD 2011 classification correlated significantly with exercise capacity and multi-dimensional disease staging. Cox proportional hazards analysis revealed that, among several methods categorizing symptoms, the GOLD A-D classification was significantly associated with mortality (p=0.0055). Although the relative number of patients in each category of the combined COPD assessment classification depended on the choice of symptom measures, the categories defined by the mMRC scale (score 0-1 versus ≥2) were most useful for future risk assessed as mortality. GOLD A had the lowest mortality, followed by GOLD B and C, and D had the highest mortality. Exercise capacity was also stratified by the new GOLD classification.
    Respiratory investigation. 03/2014; 52(2):129-35.
  • Paul W Jones
    The lancet. Respiratory medicine. 03/2014; 2(3):167-9.
  • Thorax 02/2014; · 8.56 Impact Factor
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    ABSTRACT: The chronic obstructive pulmonary disease (COPD) Assessment Test (CAT) is a concise health status measure for COPD. COPD patients have a variety of comorbidities, but little is known about their impact on quality of life. This study was designed to investigate comorbid factors that may contribute to high CAT scores. An observational study at Keio University and affiliated hospitals enrolled 336 COPD patients and 67 non-COPD subjects. Health status was assessed by the CAT, the St. Georges Respiratory Questionnaire (SGRQ), and all components of the Medical Outcomes Study Short-Form 36-Item (SF-36) version 2, which is a generic measure of health. Comorbidities were identified based on patients' reports, physicians' records, and questionnaires, including the Frequency Scale for the Symptoms of Gastro-esophageal reflux disease (GERD) and the Hospital Anxiety and Depression Scale. Dual X-ray absorptiometry measurements of bone mineral density were performed. The CAT showed moderate-good correlations with the SGRQ and all components of the SF-36. The presence of GERD, depression, arrhythmia, and anxiety was significantly associated with a high CAT score in the COPD patients. Symptomatic COPD patients have a high prevalence of comorbidities. A high CAT score should alert the clinician to a higher likelihood of certain comorbidities such as GERD and depression, because these diseases may co-exist unrecognized.Trial registration: Clinical trial registered with UMIN (UMIN000003470).
    Respiratory research 02/2014; 15(1):13. · 3.38 Impact Factor
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    ABSTRACT: We evaluated the predictive value of the COPD assessment test (CAT™) for exacerbation in the following six months or time to first exacerbation among COPD patients with previous exacerbations. COPD outpatients with a history of exacerbation from 19 hospitals completed the CAT questionnaire and spirometry over six months. Exacerbation events were prospectively collected using a structured questionnaire. The baseline CAT score categorised into four groups (0–9, 10–19, 20–29, and 30–40) showed strong prediction for time to first exacerbation and modest prediction for any exacerbation or moderate-severe exacerbation (AUC 0.83, 0.64, and 0.63 respectively). In multivariate analyses, the categorised CAT score independently predicted all three outcomes (p=0.001 or p<0.001). Compared with the lowest CAT score category, the higher categories were associated with significantly shorter time to first exacerbation and higher exacerbation risks. The corresponding adjusted median time was >24, 14, 9, and 5 weeks and the adjusted RR was 1.00, 1.30, 1.37, and 1.50 in the category of 0-9, 10-19, 20-29, and 30-40 respectively. Exacerbation history (≥2 vs. 1 event in the past year) was related to time to first exacerbation (adjusted HR 1.35; p=0.023) and any exacerbation during the study period (adjusted RR 1.15; p=0.016). The results of this study support the use of the CAT as a simple tool to assist in the identification of patients at increased risk of exacerbations. This could facilitate timely and cost-effective implementation of preventive interventions, and improve health resource allocation.
    Respiratory Medicine 02/2014; 108. · 2.92 Impact Factor
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    ABSTRACT: The concept of a minimal clinically important difference (MCID) is well established. Here, we review the evidence base and methods used to define MCIDs, as well as their strengths and limitations. Most MCIDs in chronic obstructive pulmonary disease (COPD) are empirically derived estimates applying to populations of patients. Validated MCIDs are available for many commonly used outcomes in COPD, including lung function (100 mL for trough forced expiratory volume in 1 second), dyspnea (improvement of ≥1 unit in the Transition Dyspnea Index total score or 5 units in the University of California, San Diego Shortness of Breath Questionnaire), health status (reduction of 4 units in the St George's Respiratory Questionnaire total score) and exercise capacity (47.5 m for the incremental shuttle walking test, 45-85 seconds for the endurance shuttle walking test and 46-105 seconds for constant-load cycling endurance tests), but there is currently no validated MCID for exacerbations. In a clinical trial setting, many factors, including study duration, withdrawal rate, baseline severity and Hawthorne effects, can influence the measured treatment effect and determine whether it reaches the MCID. We also address recent challenges presented by clinical trials that compare active treatments, and suggest that MCIDs should be used to identify the additional proportion of patients who benefit, for example, when one drug is replaced by another or when a second drug is added to a first. We propose the term 'minimum worthwhile incremental advantage' to describe this parameter.
    American Journal of Respiratory and Critical Care Medicine 01/2014; · 11.04 Impact Factor
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    ABSTRACT: Cardiovascular disease (CVD) and chronic obstructive pulmonary disease (COPD) commonly coexist and share common risk factors. The prevalence of COPD in outpatients with a smoking history and CVD in Japan is unknown. The aim of this study was to determine the proportion of Japanese patients with a smoking history being treated for CVD who have concurrent airflow limitation compatible with COPD. A secondary objective was to test whether the usage of lung function tests performed in the clinic influenced the diagnosis rate of COPD in the patients identified with airflow limitation.
    International Journal of COPD 01/2014; 9:563-8.
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    ABSTRACT: Elevated plasma B-type natriuretic peptide (BNP) levels and their association with heart failure have been reported in subjects with acute exacerbations of chronic obstructive pulmonary disease (AECOPD). To examine and compare plasma BNP levels and diastolic and systolic dysfunction in subjects with AECOPD and stable chronic obstructive pulmonary disease (COPD). In all, 87 unselected consecutive hospitalizations due to AECOPD in 61 subjects and a total of 190 consecutive subjects with stable COPD were recruited. Plasma BNP levels were compared cross-sectionally and longitudinally. Transthoracic echocardiographic examinations were also performed in the hospitalized subjects. In the hospitalized subjects, the median plasma BNP level (interquartile range) was 55.4 (26.9-129.3) pg/mL and was higher than that of patients with stable COPD: 18.3 (10.0-45.3) for Global Initiative for Chronic Obstructive Lung Disease grade I; 25.8 (11.0-53.7) for grade II; 22.1 (9.1-52.6) for grade III; and 17.2 (9.6-22.9) pg/mL for grade I V, all P<0.001. In 15 subjects studied prospectively, the median plasma BNP level was 19.4 (9.8-32.2) pg/mL before AECOPD, 72.7 (27.7-146.3) pg/mL during AECOPD, and 14.6 (12.9-39.0) pg/mL after AECOPD (P<0.0033 and P<0.0013, respectively). Median plasma BNP levels during AECOPD were significantly higher in ten unsuccessfully discharged subjects 260.5 (59.4-555.0) than in 48 successfully discharged subjects 48.5 (24.2-104.0) pg/mL (P=0.0066). Only 5.6% of AECOPD subjects were associated with systolic dysfunction defined as a left ventricular ejection fraction (LVEF) <50%; a further 7.4% were considered to have impaired relaxation defined as an E/A wave velocity ratio <0.8 and a deceleration time of E >240 ms. BNP levels were weakly correlated with the E/peak early diastolic velocity of the mitral annulus (Ea) ratio (Spearman's rank correlation coefficient =0.353, P=0.018), but they were not correlated with the LVEF (Spearman's rank correlation coefficient =-0.221, P=0.108). A modest elevation of plasma BNP is observed during AECOPD. It appears that AECOPD may have an impact on plasma BNP levels that is not attributable to heart failure.
    International Journal of COPD 01/2014; 9:155-62.
  • European Respiratory Journal 10/2013; · 7.13 Impact Factor
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    ABSTRACT: GOLD proposed a COPD assessment framework focussed on symptoms measured by the COPD Assessment Test™ (CAT) or the mMRC and on exacerbation risk based on poor lung function (FEV1 <50%) or a history of ≥2 exacerbations in the previous year. This analysis examined the characteristics of COPD patients recruited from routine clinical settings and classified using the GOLD framework. 1041 European COPD patients (38.5% from primary care) from the Adelphi Respiratory Disease Specific Programme with information on CAT, mMRC, spirometry and exacerbation history in the previous year were analysed. Their mean age was 64.9 ± 9.9 years and mean FEV1 was 62.5 ± 17.8% predicted; 80% were in GOLD 2 spirometric grade or milder. CAT and mMRC cut points identified different groups of patients; using CAT, the composition was: Group A 9.3%, Group B 48.5%, Group C 0.7% and Group D 41.5%. 80% were classified as high risk based on exacerbation history and 25% of patients in a low risk category (GOLD A and B) had 1 exacerbation in the previous year. The incidence of diabetes, hypertension and hyperlipidaemia rose with worsening GOLD group (all p < 0.0001); diabetes GOLD A 4%, GOLD B 16%, GOLD D 29%; hypertension GOLD A 38%, GOLD B 55%, GOLD D 65%; hyperlipidaemia GOLD A 13%, GOLD B 30%, GOLD D 37%. In patients seen in routine clinical settings, 25% of GOLD low risk patients had one exacerbation per year and the incidence of cardio-vascular and metabolic diseases increases with worsening GOLD group.
    Respiratory medicine 08/2013; · 2.33 Impact Factor
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    ABSTRACT: BACKGROUND: It has been debated whether treatment should be started early in subjects with mild to moderate COPD. An impaired health status score was associated with a higher probability of being diagnosed with COPD as compared with undiagnosed COPD.Purpose: To investigate the health status in a healthy working population, to determine reference scores for healthy non-smoking subjects, and to investigate the relationship between their health status and airflow limitation. METHODS: A total of 1333 healthy industrial workers aged >=40 years performed spirometry and completed the St. George's Respiratory Questionnaire (SGRQ) and the COPD Assessment Test (CAT). RESULTS: The prevalence of COPD defined by the fixed ratio of the forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) was 10.9%, and the prevalence defined by the Lower Limit of Normal was 5.0%. All SGRQ and CAT scores were skewed to the milder end. In 512 non-smoking subjects with normal spirometry, the mean SGRQ score was 5.7, and the mean CAT score was 5.8. In 145 people with COPD defined by the fixed ratio, the mean SGRQ score was 7.9, with a zero score in 6.9% of the subjects. Using the CAT, the mean score was 7.3, with 7.6% of the scores being zero. The scores in patients identified using the Lower Limit of Normal approach were: SGRQ 8.4 (13.4% had a score of zero) and CAT 7.4 (13.4% had a score of zero). Although the 95th percentiles of the Total, Symptoms, Activity, and Impact scores of the SGRQ and CAT sores were 13.8, 34.0, 23.4, 7.2 and 13.6 in the 512 healthy non-smoking subjects, respectively, they were also distributed under their upper limits in over 80% of the COPD subjects. CONCLUSION: The COPD-specific health status scores in a working population were good, even in those with spirometrically diagnosed COPD. All scores were widely distributed in both healthy non-smoking subjects and in subjects with COPD, and the score distribution overlapped remarkably between these two groups. This suggests that symptom-based methods are not suitable screening tools in a healthy general population.
    Respiratory research 06/2013; 14(1):61. · 3.38 Impact Factor

Publication Stats

4k Citations
476.87 Total Impact Points

Institutions

  • 2006–2014
    • St George's, University of London
      • Division of Clinical Sciences
      Londinium, England, United Kingdom
  • 2001–2014
    • St. George's School
      • Division of Physiological Medicine
      Middletown, Rhode Island, United States
  • 2013
    • Keio University
      • School of Medicine
      Edo, Tōkyō, Japan
  • 2006–2013
    • University of London
      Londinium, England, United Kingdom
  • 2012
    • University College London
      • Centre for Respiratory Medicine
      London, ENG, United Kingdom
  • 2011
    • University of Salford
      Salford, England, United Kingdom
    • University of North Carolina at Chapel Hill
      • Department of Medicine
      Chapel Hill, NC, United States
  • 2010–2011
    • United BioSource Corporation
      Maryland, United States
  • 2003
    • Aintree University Hospital NHS Foundation Trust
      Liverpool, England, United Kingdom