Publications
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Donaldson G, Wedzicha J, 2014, The causes and consequences of seasonal variation in COPD exacerbations, International Journal of Chronic Obstructive Pulmonary Disease, Vol: 9, Pages: 1101-1110, ISSN: 1176-9106
The time of year when patients experience exacerbations of chronic obstructive pulmonary disease is a much-overlooked feature of the disease. The higher incidence of exacerbations in winter has important consequences for patients in terms of increased morbidity and mortality. The seasonality also imposes a considerable burden on already-overloaded health care services, with both primary care consultations and hospital admissions increasing in number. The seasonality of exacerbations varies with latitude, and is greater in more temperate climates, where there may be less protection from outdoor and indoor cold exposure. The precise causes of the seasonality are unknown, but thought to be partly due to the increased prevalence of respiratory viral infections circulating in cold, damp conditions. Increased susceptibility to viral infection may also be a mechanism mediated through increased airway inflammation or possibly reduced vitamin D levels. The seasonality of exacerbations informs us about the triggers of exacerbations and suggests possible strategies to reduce their number.
James GD, Donaldson GC, Wedzicha JA, et al., 2014, Trends in management and outcomes of COPD patients in primary care, 2000-2009: a retrospective cohort study, npj Primary Care Respiratory Medicine, Vol: 24, Pages: 14015-14015, ISSN: 2055-1010
Background:Since the introduction of the Quality and Outcomes framework, there has been some evidence of improvement in the management of chronic obstructive pulmonary disease (COPD) patients in the United Kingdom through increasing rates of smoking cessation advice and immunisations against influenza. However, it is unknown whether disease-specific management criteria, disease outcomes and diagnosis have improved.Aims:To describe changes in the management and outcomes of patients with COPD in UK general practice between 2000 and 2009.Methods:The study was done on a retrospective cohort using data from The Health Improvement Network UK primary care database. We calculated age at diagnosis of COPD and death, total number of short-term oral corticosteroid courses and consultations, and proportion of patients with very severe COPD and on triple inhaled therapy for each year between 2000 and 2009.Results:We identified 92,576 patients with COPD. The mean age at COPD diagnosis decreased from 68.1 years in 2000 to 66.7 years in 2009. The mean age at death increased from 78.2 years in 2000 to 78.8 years in 2009. The number of prescribed courses of oral corticosteroids increased from 0.6 in 2000 to 0.8 in 2009. The number of consultations increased from 9.4 in 2004 to 11.3 in 2009. The risk of having very severe COPD decreased from 9.4% in 2004 to 6.8% in 2009. The likelihood of patients with very severe COPD receiving triple therapy increased from 25% in 2004 to 59% in 2009.Conclusions:The trends suggest that management and outcomes observed in patients with COPD may have improved since the year 2000.
George SN, Garcha DS, Mackay AJ, et al., 2014, Human rhinovirus infection during naturally occurring COPD exacerbations, European Respiratory Journal, Vol: 44, Pages: 87-96, ISSN: 0903-1936
Human rhinovirus (HRV) infection is an important trigger of exacerbations of chronic obstructive pulmonary disease (COPD) but its role in determining exacerbation frequency phenotype or the time-course of HRV infection in naturally occurring exacerbations is unknown. Sputum samples from 77 patients were analysed by real-time quantitative PCR for both HRV (388 samples), and Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis (89 samples). Patients recorded worsening of respiratory symptoms on daily diary cards, from which exacerbations were identified. HRV prevalence and load at exacerbation presentation were significantly higher than in the stable state (prevalence 53.3% versus 17.2%, respectively; p<0.001) but 0% by day 35 post-exacerbation. HRV load was higher in patients with cold symptoms (p=0.046) or sore throats (p=0.006) than those without. 73% of bacterium-negative but HRV-positive exacerbations were bacterium-positive by day 14. Patients with HRV detected at exacerbation had a higher exacerbation frequency (interquartile range) of 3.01 (2.02-5.30) per year compared with patients without HRV (2.51 (2.00-3.51)) (p=0.038). HRV prevalence and load increased at COPD exacerbation, and resolved during recovery. Frequent exacerbators were more likely to experience HRV infection. Secondary bacterial infection is common after HRV infection, and provides a possible mechanism for exacerbation recurrence and a potential target for novel therapies.
Plate M, Lawson P, Hill M, et al., 2014, Impact of a functional polymorphism in the PAR-1 gene promoter in COPD and COPD exacerbations, American Journal of Physiology-Lung Cellular and Molecular Physiology, ISSN: 1522-1504
Wedzicha JA, Singh D, Vestbo J, et al., 2014, Extrafine beclomethasone/formoterol in severe COPD patients with history of exacerbations, Respiratory Medicine, Vol: 108, Pages: 1153-1162, ISSN: 1532-3064
The FORWARD study is a randomised, double-blind trial that compares the efficacy and safety of 48 weeks treatment with extrafine beclomethasone dipropionate/formoterol fumarate (BDP/FOR), 100/6 μg pMDI, 2 inhalations BID, vs. FOR 12 μg pMDI, 1 inhalation BID, in severe COPD patients with a history of exacerbations. Co-primary endpoints were exacerbation rate over 48 weeks and pre-dose morning FEV1 at 12 weeks.The ITT population included 1186 patients (69% males, mean age 64 years) with severe airflow limitation (mean post-bronchodilator FEV1 42% predicted). Salbutamol as rescue therapy, theophylline and tiotropium (if stable regimen prior to screening) were allowed.Compared to FOR, BDP/FOR: (1) reduced the exacerbation rate (rate ratio: 0.72 [95% confidence interval 0.62–0.84], p < 0.001); (2) improved pre-dose morning FEV1 (mean difference: 0.069 L [0.043–0.095] p < 0.001); (3) prolonged the time to first exacerbation; (4) improved the SGRQ total score. The percentage of patients with adverse events was similar (52.1% with BDP/FOR and 49.2% with FOR). Pneumonia incidence was low, slightly higher with BDP/FOR (3.8%) than with FOR (1.8%). No difference for laboratory values, ECG or vital signs.Extrafine BDP/FOR significantly reduces the exacerbation rate and improves lung function of patients with severe COPD and history of exacerbations as compared to FOR alone.
Alahmari AD, Patel AR, Kowlessar BS, et al., 2014, Daily activity during stability and exacerbation of chronic obstructive pulmonary disease, BMC Pulmonary Medicine, Vol: 14, Pages: 98-98, ISSN: 1471-2466
BACKGROUND: During most COPD exacerbations, patients continue to live in the community but there is little information on changes in activity during exacerbations due to the difficulties of obtaining recent, prospective baseline data. METHODS: Patients recorded on daily diary cards any worsening in respiratory symptoms, peak expiratory flow (PEF) and the number of steps taken per day measured with a Yamax Digi-walker pedometer. Exacerbations were defined by increased respiratory symptoms and the number of exacerbations experienced in the 12 months preceding the recording of daily step count used to divide patients into frequent (> = 2/year) or infrequent exacerbators. RESULTS: The 73 COPD patients (88% male) had a mean (+/-SD) age 71(+/-8) years and FEV1 53(+/-16)% predicted. They recorded pedometer data on a median 198 days (IQR 134-353). At exacerbation onset, symptom count rose by 1.9(+/-1.3) and PEF fell by 7(+/-13) l/min. Mean daily step count fell from 4154(+/-2586) steps/day during a preceding baseline week to 3673(+/-2258) step/day during the initial 7 days of exacerbation (p = 0.045). Patients with larger falls in activity at exacerbation took longer to recover to stable level (rho = -0.56; p < 0.001). Recovery in daily step count was faster (median 3.5 days) than for exacerbation symptoms (median 11 days; p < 0.001). Recovery in step count was also faster in untreated compared to treated exacerbation (p = 0.030).Daily step count fell faster over time in the 40 frequent exacerbators, by 708 steps/year, compared to 338 steps/year in 33 infrequent exacerbators (p = 0.002). CONCLUSIONS: COPD exacerbations reduced physical activity and frequent exacerbations accelerate decline in activity over time.
Bateman ED, Mahler DA, Vogelmeier CF, et al., 2014, Recent advances in COPD disease management with fixed-dose long-acting combination therapies, EXPERT REVIEW OF RESPIRATORY MEDICINE, Vol: 8, Pages: 357-379, ISSN: 1747-6348
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- Citations: 27
Seemungal TAR, Wedzicha JA, 2014, Exacerbation frequency and FEV1 decline of COPD: is it geographic?, EUROPEAN RESPIRATORY JOURNAL, Vol: 43, Pages: 1220-1222, ISSN: 0903-1936
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- Citations: 7
Wedzicha JA, Singh R, Mackay AJ, 2014, Acute COPD Exacerbations, CLINICS IN CHEST MEDICINE, Vol: 35, Pages: 157-+, ISSN: 0272-5231
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- Citations: 93
Wedzicha JA, Steinbrook R, Kassirer JP, 2014, Should medical journals publish sponsored content?, BMJ-BRITISH MEDICAL JOURNAL, Vol: 348, ISSN: 1756-1833
Jones PW, Beeh KM, Chapman KR, et al., 2014, Minimal Clinically Important Differences in Pharmacological Trials, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 189, Pages: 250-255, ISSN: 1073-449X
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- Citations: 315
Wedzicha JA, Rabe KF, Martinez FJ, et al., 2014, Evidence Roflumilast Reduces Severe Exacerbations? <i>Response</i>, CHEST, Vol: 145, Pages: 428-428, ISSN: 0012-3692
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- Citations: 1
Donaldson GC, Wedzicha JA, 2014, The CODEX index: a collection or digest of laws: a code, Chest, Vol: 145, Pages: 934-935, ISSN: 1931-3543
Wedzicha JA, Donaldson GC, 2014, Rapid FEV1 decline, early COPD, and angiotensin-converting enzymes?, Chest, Vol: 145, Pages: 671-672, ISSN: 1931-3543
Singh R, Such K, Kowlessar BS, et al., 2013, MACROPHAGE PHAGOCYTOSIS IN COPD PATIENTS AT EXACERBATION COMPARED TO STABLE STATE, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A159-A159, ISSN: 0040-6376
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- Citations: 1
Quint JK, Herrett E, Bhaskaran K, et al., 2013, Effect of β blockers on mortality after myocardial infarction in adults with COPD: Population based cohort study of UK electronic healthcare records, British Medical Journal, Vol: 347, ISSN: 1468-5833
Objectives: To investigate whether the use and timing of prescription of β blockers in patients with chronic obstructive pulmonary disease (COPD) having a first myocardial infarction was associated with survival and to identify factors related to their use. Design: Population based cohort study in England. Setting: UK national registry of myocardial infarction (Myocardial Ischaemia National Audit Project (MINAP)) linked to the General Practice Research Database (GPRD), 2003-11. Participants: Patients with COPD with a first myocardial infarction in 1 January 2003 to 31 December 2008 as recorded in MINAP, who had no previous evidence of myocardial infarction in their GPRD or MINAP record. Data were provided by the Cardiovascular Disease Research using Linked Bespoke studies and Electronic Health Records (CALIBER) group at University College London. Main outcome measure: Cox proportional hazards ratio for mortality after myocardial infarction in patients with COPD in those prescribed β blockers or not, corrected for covariates including age, sex, smoking status, drugs, comorbidities, type of myocardial infarction, and severity of infarct. Results: Among 1063 patients with COPD, treatment with β blockers started during the hospital admission for myocardial infarction was associated with substantial survival benefits (fully adjusted hazard ratio 0.50, 95% confidence interval 0.36 to 0.69; P<0.001; median follow-up time 2.9 years). Patients already taking a β blocker before their myocardial infarction also had a survival benefit (0.59, 0.44 to 0.79; P<0.001). Similar results were obtained with propensity scores as an alternative method to adjust for differences between those prescribed and not prescribed β blockers. With follow-up started from date of discharge from hospital, the effect size was slightly attenuated but there was a similar protective effect of treatment with β blockers started during hospital admission for myocardial inf
Wedzicha JA, 2013, Dual PDE 3/4 inhibition: a novel approach to airway disease?, LANCET RESPIRATORY MEDICINE, Vol: 1, Pages: 669-670, ISSN: 2213-2600
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- Citations: 10
James GD, Petersen I, Nazareth I, et al., 2013, Use of long-term antibiotic treatment in COPD patients in the UK: a retrospective cohort study, Primary Care Respiratory Journal, Vol: 22, Pages: 271-277, ISSN: 1475-1534
BACKGROUND: Exacerbations of chronic obstructive pulmonary disease (COPD) are a burden to patients and impose a major cost on health services. Long-term antibiotic therapy may prevent exacerbations, but at present it is not recommended by management guidelines. AIMS: To identify the type and prevalence of long-term oral antibiotic treatments prescribed to patients with COPD and to assess the patient characteristics associated with long-term antibiotic use. METHODS: A retrospective cohort using all eligible practices in The Health Improvement Network (THIN) UK primary care database between 2000 and 2009 was studied. We identified patients with COPD and then those who received a course of long-term antibiotics. Long-term courses were defined as >6 months in duration with <50% concomitant oral corticosteroid treatment. RESULTS: We identified 92,576 patients with COPD, but only 567 patients (0.61%) who received 998 long-term antibiotic courses. Mean follow-up time was 3 years and 10 months. The median long-term antibiotic course length was 280 days (interquartile range 224, 394) and 58 patients (0.06%) were continuously prescribed antibiotics for >2 years. The most commonly used long-term antibiotics were oxytetracycline, doxycycline, and penicillin. Azithromycin, erythromycin, and clarithromycin were less frequently used. There was little evidence of the use of rotating courses of antibiotics. Men, people aged 50-79 years, non-smokers, and patients with poorer lung function were more likely to receive long-term antibiotic treatment. CONCLUSIONS: Relatively few COPD patients are currently prescribed long-term antibiotics. Further clinical trials are required to determine the efficacy of this therapy. If beneficial, the use of such treatments should be incorporated into clinical guidelines.
Donaldson GC, Wedzicha JA, 2013, Deprivation, winter season, and COPD exacerbations, Primary Care Respiratory Journal, Vol: 22, Pages: 264-265, ISSN: 1471-4418
Wedzicha JA, Brill SE, Allinson JP, et al., 2013, Mechanisms and impact of the frequent exacerbator phenotype in chronic obstructive pulmonary disease, BMC Medicine, Vol: 11, Pages: 1-10, ISSN: 1741-7015
Exacerbations of chronic obstructive pulmonary disease (COPD) are important events that carry significant consequences for patients. Some patients experience frequent exacerbations, and are now recognized as a distinct clinical subgroup, the 'frequent exacerbator' phenotype. This is relatively stable over time, occurs across disease severity, and is associated with poorer health outcomes. These patients are therefore a priority for research and treatment. The pathophysiology underlying the frequent exacerbator phenotype is complex, with increased airway and systemic inflammation, dynamic lung hyperinflation, changes in lower airway bacterial colonization and a possible increased susceptibility to viral infection. Frequent exacerbators are also at increased risk from comorbid extrapulmonary diseases including cardiovascular disease, gastroesophageal reflux, depression, osteoporosis and cognitive impairment. Overall these patients have poorer health status, accelerated forced expiratory volume over 1 s (FEV1) decline, worsened quality of life, and increased hospital admissions and mortality, contributing to increased exacerbation susceptibility and perpetuation of the frequent exacerbator phenotype. This review article sets out the definition and importance of the frequent exacerbator phenotype, with a detailed examination of its pathophysiology, impact and interaction with other comorbidities.
Donaldson GC, Mullerova H, Locantore N, et al., 2013, Factors associated with change in exacerbation frequency in COPD, Respiratory Research, Vol: 14, Pages: 79-79, ISSN: 1465-9921
BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) can be categorized as having frequent (FE) or infrequent (IE) exacerbations depending on whether they respectively experience two or more, or one or zero exacerbations per year. Although most patients do not change category from year to year, some will, and the factors associated with this behaviour have not been examined. METHODS: 1832 patients completing two year follow-up in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) study were examined at baseline and then yearly. Exacerbations were defined by health care utilisation. Patient characteristics compared between those patients who did or did not change exacerbation category from year 1 to year 2. FINDINGS: Between years 1 and 2, 221 patients (17%) changed from IE to FE and 210 patients (39%) from FE to IE. More severe disease was associated with changing from IE to FE and less severe disease from FE to IE. Over the preceding year, small falls in FEV1 and 6-minute walking distance were associated with changing from IE to FE, and small falls in platelet count associated with changing from FE to IE. CONCLUSION: No parameter clearly predicts an imminent change in exacerbation frequency category. TRIAL REGISTRATION: SCO104960, clinicaltrials.gov identifier NCT00292552.
Wedzicha JA, Decramer M, Ficker JH, et al., 2013, QVA149 versus glycopyrronium for COPD Reply, LANCET RESPIRATORY MEDICINE, Vol: 1, Pages: E23-E23, ISSN: 2213-2600
Wedzicha JA, 2013, Is gastro-oesophageal reflux associated with COPD exacerbations?, JORNAL BRASILEIRO DE PNEUMOLOGIA, Vol: 39, Pages: 257-258, ISSN: 1806-3713
Burgel P-R, Wedzicha JA, 2013, Chronic Cough in Chronic Obstructive Pulmonary Disease: Time for Listening?, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 187, Pages: 902-904, ISSN: 1073-449X
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- Citations: 7
Wedzicha JA, Rabe KF, Martinez FJ, et al., 2013, Efficacy of Roflumilast in the COPD Frequent Exacerbator Phenotype, CHEST, Vol: 143, Pages: 1302-1311, ISSN: 0012-3692
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- Citations: 85
Wedzicha JA, Decramer M, Ficker JH, et al., 2013, Analysis of chronic obstructive pulmonary disease exacerbations with the dual bronchodilator QVA149 compared with glycopyrronium and tiotropium (SPARK): a randomised, double-blind, parallel-group study, LANCET RESPIRATORY MEDICINE, Vol: 1, Pages: 199-209, ISSN: 2213-2600
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- Citations: 388
Wedzicha JA, 2013, GOLD and ABCD-a good start, but now for the evidence?, LANCET RESPIRATORY MEDICINE, Vol: 1, Pages: 4-5, ISSN: 2213-2600
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- Citations: 7
Singh D, Kampschulte J, Wedzicha JA, et al., 2013, A trial of beclomethasone/formoterol in COPD using EXACT-PRO to measure exacerbations, EUROPEAN RESPIRATORY JOURNAL, Vol: 41, Pages: 12-17, ISSN: 0903-1936
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- Citations: 24
Mackay AJ, Donaldson GC, Patel AR, et al., 2013, Detection and severity grading of COPD exacerbations using the exacerbations of Chronic Obstructive Pulmonary Disease Tool (EXACT), Eur Respir J, Vol: 43, Pages: 735-744, ISSN: 1399-3003
Uncertainty exists over the ability of the Exacerbations of Chronic Obstructive Pulmonary Disease Tool (EXACT) patient-reported outcome diary to quantify exacerbation severity and frequency. To clarify this we investigated the ability of the EXACT to assess severity of exacerbations and examined the relationship between exacerbations diagnosed using London COPD cohort diary cards, physician review and symptom-defined events using the EXACT.58 patients enrolled in the London COPD cohort prospectively completed the EXACT during 128 cohort diary card-defined exacerbations between January 2010 and April 2012.Mean EXACT scores increased from 42.6 (SD 8.6) at baseline to 48.0 (8.6) at exacerbation onset (p<0.001), and rose further to a maximum score of 54.1 (8.9). Maximum EXACT scores were significantly higher in treated than untreated events. Time taken for EXACT scores to return to baseline was significantly related to symptom recovery time as judged by London COPD cohort diary cards, and to PEFR recovery. Approximately 50% of both diary card-defined and HCU exacerbations crossed the EXACT event threshold.However, only 27.9% of diary-card defined and 34.6% of HCU exacerbations fully met the criteria for an EXACT event. Patients exhibited smaller rises in EXACT score at exacerbation as baseline disease severity increased.The EXACT is an effective method of evaluating COPD exacerbation severity. However, concerns remain about the ability of the EXACT to accurately detect exacerbations.
Patel AR, Kowlessar BS, Donaldson GC, et al., 2013, Cardiovascular risk, myocardial injury, and exacerbations of chronic obstructive pulmonary disease, Am J Respir Crit Care Med, Vol: 188, Pages: 1091-1099, ISSN: 1535-4970
RATIONALE: Patients with chronic obstructive pulmonary disease (COPD) have elevated cardiovascular risk, and myocardial injury is common during severe exacerbations. Little is known about the prevalence, magnitude, and underlying mechanisms of cardiovascular risk in community-treated exacerbations. OBJECTIVES: To investigate how COPD exacerbations and exacerbation frequency impact cardiovascular risk and myocardial injury, and whether this is related to airway infection and inflammation. METHODS: We prospectively measured arterial stiffness (aortic pulse wave velocity [aPWV]) and cardiac biomarkers in 98 patients with stable COPD. Fifty-five patients had paired stable and exacerbation assessments, repeated at Days 3, 7, 14, and 35 during recovery. Airway infection was identified using polymerase chain reaction. MEASUREMENTS AND MAIN RESULTS: COPD exacerbation frequency was related to stable-state arterial stiffness (rho = 0.209; P = 0.040). Frequent exacerbators had greater aPWV than infrequent exacerbators (mean +/- SD aPWV, 11.4 +/- 2.1 vs. 10.3 +/- 2.0 ms(-1); P = 0.025). Arterial stiffness rose by an average of 1.2 ms(-1) (11.1%) from stable state to exacerbation (n = 55) and fell slowly during recovery. In those with airway infection at exacerbation (n = 24) this rise was greater (1.4 +/- 1.6 vs. 0.7 +/- 1.3 ms(-1); P = 0.048); prolonged; and related to sputum IL-6 (rho = 0.753; P < 0.001). Increases in cardiac biomarkers at exacerbation were higher in those with ischemic heart disease (n = 12) than those without (n = 43) (mean +/- SD increase in troponin T, 0.011 +/- 0.009 vs. 0.003 +/- 0.006 mug/L, P = 0.003; N-terminal pro-brain natriuretic peptide, 38.1 +/- 37.7 vs. 5.9 +/- 12.3 pg/ml, P < 0.001). CONCLUSIONS: Frequent COPD exacerbators have greater arterial stiffness than infrequent exacerbators. Arterial stiffness rises acutely during COPD exacerbations, particularly with airway infection. Increases in arterial stiffness are related to inflammation
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