Publications
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Brill S, Law M, El-Emir E, et al., 2015, Effects of different antibiotic classes on airwaybacteria in stable COPD using culture and molecularQ1 techniques: a randomised controlled trial, Thorax, Vol: 70, Pages: 930-938, ISSN: 1468-3296
BackgroundLong term antibiotic therapy is used to prevent exacerbations of chronic obstructive pulmonary disease (COPD) but there is uncertainty over whether this reduces airway bacteria. The optimum antibiotic choice remains unknown. We conducted an exploratory trial in stable patients with COPD comparing three antibiotic regimens against placebo. MethodsThis was a single-centre, single-blind, randomised placebo-controlled trial (clinicaltrials.gov number NCT01398072). Patients ≥45 years with COPD, FEV1<80% predicted and chronic productive cough were randomised to receive either moxifloxacin 400mg daily for 5 days/4 weeks, doxycycline 100mg/day, azithromycin 250mg 3x/week or one placebo tablet daily for 13 weeks. The primary outcome was the change in total cultured bacterial load in sputum from baseline; secondary outcomes included bacterial load by 16S qPCR, sputum inflammation and antibiotic resistance. Results99 patients were randomised; 86 completed follow-up, were able to expectorate sputum and were analysed. After adjustment, there was a mean reduction in bacterial load of 0.42 log10 cfu/ml (95% CI -0.08, 0.91, p=0.10) with moxifloxacin, 0.11 (-0.33, 0.55, p=0.62) with doxycycline, and 0.08 (-0.38, 0.54, p=0.73) with azithromycin from placebo, respectively. There were also no significant changes in bacterial load measured by 16S qPCR or in airway inflammation. More treatment-related adverse events occurred with moxifloxacin. Of note, mean inhibitory concentrations of cultured isolates increased by at least 3 times over placebo in all treatment arms.ConclusionsTotal airway bacterial load did not decrease significantly after three months of antibiotic therapy. Large increases in antibiotic resistance were seen in all treatment groups and this has important implications for future studies.
Donaldson GC, Law M, Kowlessar B, et al., 2015, Impact of prolonged exacerbation recovery in chronic obstructive pulmonary disease, American Journal of Respiratory and Critical Care Medicine, Vol: 192, Pages: 943-950, ISSN: 1535-4970
INTRODUCTION: COPD exacerbations are important and heterogeneous events, but the consequences of prolonged exacerbation recovery are unknown. METHODS: A cohort of 384 COPD patients (FEV1 % predicted 45.8 (SD 16.6) and a median exacerbation rate of 2.13 per year (IQR 1.0-3.2)) were followed for 1039 days (IQR 660-1814) between October 1995 and January 2013. Patients recorded daily worsening of respiratory symptoms and peak expiratory flow (PEF), and when stable underwent 3-monthly spirometry, and completed the St. George's Respiratory Questionnaire (SGRQ) annually. Exacerbations were diagnosed as two consecutive days with one major symptom plus another respiratory symptom. Exacerbation duration was defined as the time from onset to the day preceding two consecutive symptom-free and recovery in PEF as return to pre-exacerbation levels. RESULTS: 351 patients had 1 or more exacerbations. Patients with a longer symptom duration (mean 14.5 days) had a worse SGRQ total score (0.2 units per 1 day; p=0.040). A longer symptomatic duration was associated with a shorter interval between exacerbation recovery and onset of the next exacerbation (Hazard Ratio=1.004; p=0.013). For 257 (7.3%) exacerbations, PEF did not recover within 99 days. These exacerbations were associated with symptoms of a viral infection (cold and sore throat). Patients with these non-recovered exacerbations showed a 10.8 ml/year (p<0.001) faster decline in FEV1. CONCLUSION: Prolonged exacerbation symptomatic duration is associated with poorer health status and a greater risk of a new event. Exacerbations where lung function does not recover are associated with symptoms of viral infections and accelerated decline in FEV1.
Alahmari AD, Mackay AJ, Patel ARC, et al., 2015, Influence of weather and atmospheric pollution on physical activity in patients with COPD, Respiratory Research, Vol: 16, ISSN: 1465-993X
RationaleInformation concerning how climate and atmospheric pollutants affects physical activity in COPD patients is lacking and might be valuable in determining when physical activity should be encouraged.MethodsSeventy-three stable COPD patients recorded on daily diary cards worsening of respiratory symptoms, peak expiratory flow rate, hours spent outside the home and the number of steps taken per day. Pedometry data was recorded on 16,478 days, an average of 267 days per patient (range 29-658). Daily data for atmospheric PM 10 and ozone (O 3 ) were obtained for Bloomsbury Square, Central London from the Air Quality Information Archive databases. Daily weather data were obtained for London Heathrow from the British Atmospheric Data Archive.ResultsColder weather below 22.5 °C, reduced daily step count by 43.3 steps day per°C (95 % CI 2.14 to 84.4; p = 0.039) and activity was lower on rainy than dry days (p = 0.002) and on overcast compared to sunny days (p < 0.001). Daily step count was 434 steps per day lower on Sunday than Saturday (p < 0.001) and 353 steps per day lower on Saturday than Friday (p < 0.001). After allowance for these effects, higher O 3 levels decreased activity during the whole week (-8 steps/ug/m3; p = 0.005) and at weekends (-7.8 steps/ug/m3; p = 0.032). Whilst, during the week PM 10 reduced activity (p = 0.018) but not during the weekend.ConclusionsInactivity of COPD patients is greatest on cold, wet and overcast days and at the weekends. This study also provides evidence of an independent effect of atmospheric pollution at high levels.Keywords: COPD; Atmospheric pollution; Weather; Daily step-count; Physical activity; Daily monitoring
Huerta A, Donaldson G, Singh R, et al., 2015, Upper respiratory symptoms worsen over time and relate to clinical phenotype in COPD., Annals of the American Thoracic Society, Vol: 12, Pages: 997-1004, ISSN: 2329-6933
RATIONALE: How nasal symptoms in patients with COPD change over time and resolve during natural occurring exacerbation have never been described. METHODS: Patients in the London COPD cohort were asked about the presence of nasal symptoms (nasal discharge, sneezing, post-nasal drip (PND), blocked nose and anosmia) over an 8-year period (2005-2013) every three months at routine clinic visits at stable state and daily during exacerbations with the use of diary cards. Data was prospectively collected and in a subgroup of patients COPD Assessment Test (CAT) and human rhinovirus (HRV) identification by PCR was available. Patients were also defined as infrequent/frequent exacerbators (<2 or ≥2 exacerbations/year). RESULTS: On 4368 visits, 209 patients with COPD were asked about their nasal symptoms. On 2033 visits, when the patients were stable, the odds ratio (OR) for nasal discharge increased by 1.32% per year (95% CI 1.19-1.45; p<0.001); sneezing 1.16% (1.05-1.29; p=0.005); PND 1.18% (1.03-1.36; p=0.016) and anosmia 1.19% (1.03-1.37; p=0.015). At exacerbation, nasal discharge was present for 7-daysand blocked nose, sneezing and PND increased for just 3 days; anosmia did not change. Nasal discharge was more likely in frequent exacerbators; OR 1.96 (1.17-3.28; p=0.011) and when present, CAT scores were higher by 1.06 units (0.32-1.80; p=0.005) when stable and 1.30 units (0.05 to 2.57; p=0.042) at exacerbation. CONCLUSION: Upper airway symptoms increase over time in COPD patients and are related to the frequent exacerbator phenotype. These longitudinal changes may be due to increasing airway inflammation or the disease progression.
Singh R, Belchamber K, Donaldson GC, et al., 2015, The Independent Effect Of Bacterial And Viral Pathogens On Sputum Inflammatory Markers At COPD Exacerbation, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Mackay AJ, Loza M, Branigan PJ, et al., 2015, Serum Amyloid A And Hepcidin Elevations Characterize Bacterial-Associated Exacerbations In Frequently Exacerbating COPD Patients, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
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Donaldson GC, Mackay AJ, Whitmore GA, et al., 2015, Stable Blood Eosinophil Percentage Predicts Exacerbation Recovery In COPD, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Allinson JP, Hardy R, Donaldson GC, et al., 2015, The Changing Relationship Between Cigarette Smoking And Chronic Mucus Hypersecretion (cmh) Within A Nationally Representative Birth Cohort Over 43 Years Of Adult Life, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
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Mackay AJ, Donaldson GC, Singh R, et al., 2015, Utility Of Objective Cough Monitoring In Stable COPD And At Exacerbation, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
AlAhmari AD, Kowlessar BS, Patel AR, et al., 2015, Exercise Capacity And Systemic Inflammatory Changes During Stability And Exacerbation Recovery In COPD Patients, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
George SN, Mackay AJ, Patel ARC, et al., 2015, Human Rhinovirus Infection And Cat Scores During COPD Exacerbations, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
AlAhmari AD, Kowlessar BS, Patel AR, et al., 2015, Effect Systemic Inflammation At Exacerbation On Daily Activity During Exacerbation Recovery, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
AlAhmari AD, Kowlessar BS, Patel ARC, et al., 2015, Determinants Of The Reduction In Physical Activity And Capacity With COPD Exacerbations, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
George SN, Brill SE, Allinson JP, et al., 2014, TIME-COURSE OF HUMAN RHINOVIRUS INFECTION AND UPPER RESPIRATORY TRACT SYMPTOMS DURING COPD EXACERBATIONS, Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A104-A105, ISSN: 0040-6376
Alahmari AD, Kowlessar BS, Patel ARC, et al., 2014, THE RELATIONSHIP BETWEEN EXERCISE CAPACITY AND INFLAMMATORY MARKERS AT COPD EXACERBATION, Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A19-A19, ISSN: 0040-6376
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Allinson JPA, Hardy RH, Donaldson GCD, et al., 2014, THE OVERLAPPING PREVALENCE OF CHRONIC MUCUS HYPERSECRETION (CMH) AND CHRONIC COUGH (CC), Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A83-A83, ISSN: 0040-6376
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Donnelly LE, Singh R, Mackay AJ, et al., 2014, Inflammatory thresholds and the species-specific effects of colonising bacteria in stable chronic obstructive pulmonary disease, Respiratory Research, Vol: 15, ISSN: 1465-993X
Brill SE, El-Emir E, Allinson JP, et al., 2014, Community-based recruitment of patients with COPD into clinical research, Thorax, Vol: 69, Pages: 951-952, ISSN: 1468-3296
Identifying subjects for clinical trials is difficult and the evidence base for recruitment strategies is limited, particularly in the field of COPD. We compared the efficiency and patient characteristics of different community-based recruitment strategies during a non-commercial COPD trial in the UK. Recruiting from general practice COPD registers was less efficient and identified patients with significantly milder disease than recruiting through pulmonary rehabilitation and patient groups. We report our experience and propose that pulmonary rehabilitation and patient groups may represent an enriched pool of COPD patients to recruit into clinical trials. TRIAL REGISTRATION NUMBER: EudraCT 2011-001063-43.
Wedzicha JA, Donaldson G, Chuecos F, et al., 2014, Effect of aclidinium bromide on exacerbations in patients with moderate-to-severe COPD: Pooled analysis of phase III studies, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Nayha S, Rintamaki H, Donaldson G, et al., 2014, Heat-related thermal sensation, comfort and symptoms in a northern population: the National FINRISK 2007 study, EUROPEAN JOURNAL OF PUBLIC HEALTH, Vol: 24, Pages: 620-626, ISSN: 1101-1262
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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.
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.
AlAhmari AD, Patel ARC, Kowlessar BS, et al., 2014, Recovery Of Daily Activity In Treated And Untreated Chronic Obstructive Pulmonary Disease Exacerbation Patients, Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Huerta AH, Donaldson GC, Singh R, et al., 2014, Upper Nasal Symptoms Worsens Over Time And Are Related To Clinical Phenotype In COPD Patients, Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Allinson JP, Donaldson GC, Kowlessar B, et al., 2014, The Independent Effect Of Chronic Bronchitis On Health-Related Quality Of Life In COPD, Publisher: AMER THORACIC SOC, ISSN: 1073-449X
AlAhmari AD, Mackay AJ, Patel ARC, et al., 2014, The Effect Of Atmospheric Pollution On Physical Activity In Patients With Chronic Obstructive Pulmonary Disease, Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Wedzicha JA, Donaldson GC, 2014, Rapid FEV1 decline, early COPD, and angiotensin-converting enzymes?, Chest, Vol: 145, Pages: 671-672, ISSN: 1931-3543
Mackay AJ, Singh R, Kowlessar B, et al., 2014, Temporal Variability Of Symptom Onset And Intensity During Acute Exacerbations Of COPD, Publisher: AMER THORACIC SOC, ISSN: 1073-449X
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