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  • Journal article
    Philip K, Gaduzo S, Rogers J, Laffan M, Hopkinson Net al., 2019,

    Patient experience of COPD care – outcomes from the British Lung Foundation Patient Passport

    , BMJ Open Respiratory Research, Vol: 6, ISSN: 2052-4439

    Introduction The British Lung Foundation COPD Patient Passport (www.blf.org.uk/passport) was developed as a resource to help people with COPD and clinicians to consider the care received and identify essential omissions. We used the online data collected to evaluate the delivery of COPD care in the UK from a patient perspective. MethodsThe patient passport consists of 13 questions relating to key aspects of COPD care including: spirometry confirmation of diagnosis, understanding their diagnosis, support and a written management plan, vaccinations, smoking cessation, physical activity, exercise, eating well, pulmonary rehabilitation, exacerbations, medications, and yearly reviews. Data were presented as proportions with an answer corresponding to good care, and plotted over time to identify trends.ResultsAfter removing identifiable duplicates, data from 41,769 entries, completed online between November 2014 and April 2019, remained (Table 1). 24% reported getting support to manage their care and a written action plan; 53% could spot the signs of an acute exacerbation; 34% had discussed pulmonary rehabilitation; and 41% stated they understood their COPD, and their doctor or nurse had explained where to find information, advice and emotional support. A quarter reported not receiving flu vaccination and a third of those who smoke were not offered support to quit smoking. Even the strongest areas including spirometry-confirmed diagnosis, and knowing the importance of being active and eating well, achieved only around 80%. Response patterns remained stable or worsened over time. DiscussionResponses to the BLF COPD Patient Passport identify substantial gaps in patients’ experience of care, which did not appear to improve during the 5 years covered. These data provide a unique yet commonly overlooked perspec

  • Journal article
    Rabe KF, Martinez FJ, Ferguson GT, Wang C, Singh D, Wedzicha JA, Trivedi R, St Rose E, Ballal S, McLaren J, Darken P, Reisner C, Dorinsky Pet al., 2019,

    A phase III study of triple therapy with budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler 320/18/9.6 μg and 160/18/9.6 μg using co-suspension delivery technology in moderate-to-very severe COPD: The ETHOS study protocol

    , Respiratory Medicine, Vol: 158, Pages: 59-66, ISSN: 0954-6111

    BACKGROUND: Single inhaler triple therapies providing an inhaled corticosteroid, a long-acting muscarinic antagonist, and a long-acting β2-agonist (ICS/LAMA/LABAs) are an emerging treatment option for chronic obstructive pulmonary disease (COPD). Nevertheless, questions remain regarding the optimal patient population for triple therapy as well as the benefit:risk ratio of ICS treatment. METHODS: ETHOS is an ongoing, randomized, double-blind, multicenter, parallel-group, 52-week study in symptomatic patients with moderate-to-very severe COPD and a history of exacerbation(s) in the previous year. Two doses of single inhaler triple therapy with budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler (BGF MDI 320/18/9.6 μg and 160/18/9.6 μg) will be compared to glycopyrrolate/formoterol fumarate (GFF) MDI 18/9.6 μg and budesonide/formoterol fumarate (BFF) MDI 320/9.6 μg, all formulated using co-suspension delivery technology. Outcomes include the rate of moderate/severe (primary endpoint) and severe COPD exacerbations, symptoms, quality of life, and all-cause mortality. Sub-studies will assess lung function and cardiovascular safety. STUDY POPULATION: From June 2015-July 2018, 16,044 patients were screened and 8572 were randomized. Preliminary baseline demographics show that 55.9% of patients had experienced ≥2 moderate/severe exacerbations in the previous year, 79.1% were receiving an ICS-containing treatment at study entry, and 59.9% had blood eosinophil counts ≥150 cells/mm3. CONCLUSIONS: ETHOS will provide data on exacerbations, patient-reported outcomes, mortality, and safety in 8572 patients with moderate-to-very severe COPD receiving triple and dual fixed-dose combinations. For the first time, ICS/LAMA/LABA triple therapy with two different doses of ICS will be compared to dual ICS/LABA and LAMA/LABA therapies. CLINICAL TRIAL REGISTRATION NUMBER: NCT02465567.

  • Journal article
    Wedzicha JA, Ritchie AI, Martinez FJ, 2019,

    Can macrolide antibiotics prevent hospital readmissions?

    , American Journal of Respiratory and Critical Care Medicine, Vol: 200, Pages: 796-798, ISSN: 1073-449X
  • Journal article
    Celli BR, Wedzicha JA, 2019,

    Update on clinical aspects of chronic obstructive pulmonary disease

    , New England Journal of Medicine, Vol: 381, Pages: 1257-1266, ISSN: 0028-4793

    Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide; COPD led to 3.2 million deaths in 2017, a toll expected to reach 4.4 million yearly by 2040.1,2 With a worldwide prevalence of 10.1%, COPD afflicts many people in low-income, middle-income, and wealthy countries (Figure 1), and years of life lost prematurely increased 13.2% between 2007 and 2017.1 Although COPD has traditionally been considered a disease that affects men, in some countries, the prevalence and associated mortality are higher among women than among men. In this review, we update the clinical face of COPD, concentrating on the pulmonary aspects of the disease, which also affects many other organ systems. The pathogenesis of COPD is discussed in a companion article by Agustí and Hogg in this issue of the Journal,3 and the review of muco-obstructive lung diseases in a recent issue of the Journal4 complements this article.

  • Journal article
    Hopkinson NS, Arnott D, Voulvoulis N, 2019,

    Environmental consequences of tobacco production and consumption

    , The Lancet, Vol: 394, Pages: 1007-1008, ISSN: 0140-6736
  • Journal article
    Boutou AK, Raste Y, Demeyer H, Troosters T, Polkey M, Vogiatzis I, Louvaris Z, Rabinovich RA, van der Molen T, Garcia-Aymerich J, Hopkinson Net al., 2019,

    Progression of physical inactivity in COPD patients: the effect of time and climate conditions – a multicentre prospective cohort study

    , International Journal of COPD, Vol: 14, Pages: 1979-1992, ISSN: 1176-9106

    Purpose: Longitudinal data on the effect of time and environmental conditions on physical activity (PA) among COPD patients are currently scarce, but this is an important factor in the design of trials to test interventions that might impact on it. Thus, we aimed to assess the effect of time and climate conditions (temperature, day length and rainfall) on progression of PA in a cohort of COPD patients.Patients and methods: This is a prospective, multicentre, cohort study undertaken as part of the EU/IMI PROactive project, in which we assessed 236 COPD patients simultaneously wearing two activity monitors (Dynaport MiniMod and Actigraph GT3X). A multivariable generalised linear model analysis was conducted to describe the effect of the explanatory variables on PA measures, over three time points (baseline, 6- and 12-month). Results: At 12 months (n=157; Forced Expiratory Volume in 1 second (FEV1) %predicted=57.7±21.9) there was a significant reduction in all PA measures (Actigraph step count (4284±3533 vs. 3533±293), Actigraph moderate- to vigorous-intensity physical activity ratio (8.8 (18.8) vs. 6.1(15.7)), Actigraph vector magnitude units (374902.4 (265269) vs. 336240 (214432)), Minimod walking time (59.1(34.9) vs. 56.9(38.7) minutes) and Minimod PA intensity (0.183(0) vs. 0.181(0)). Time had a significant, negative effect on most PA measures in multivariable analysis, after correcting for climate factors, study centre, age, FEV1 %predicted, 6 Minute Walking Distance and other disease severity measures. Rainfall was the only climate factor with a negative effect on most PA parameters. Conclusions:COPD patients demonstrate a significant decrease in physical activity over 1 year follow up, which is further affected by hours of rainfall, but not by other climate considerations.

  • Journal article
    Barnes PJ, Baker J, Donnelly LE, 2019,

    Cellular senescence as a mechanism and target in chronic lung diseases

    , American Journal of Respiratory and Critical Care Medicine, Vol: 200, ISSN: 1073-449X

    Cellular senescence is now considered an important driving mechanism for chronic lung diseases, particularly COPD and idiopathic pulmonary fibrosis. Cellular senescence is due to replicative and stress-related senescence with activation of p53 and p16INK4a respectively, leading to activation of p21CIP1 and cell cycle arrest. Senescent cells secrete multiple inflammatory proteins known as the senescence-associated secretory phenotype (SASP), leading to low grade chronic inflammation, which further drives senescence. Loss of key anti-aging molecules sirtuin-1 and sirtuin-6 may be important in acceleration of aging and arises from oxidative stress reducing phosphatase PTEN, thereby activating PI3K (phosphoinositide-3-kinase) and mTOR (mammalian target of rapamycin). MicroRNA-34a, which is regulated by PI3K-mTOR signaling, plays a pivotal role in reducing sirtuin-1/6 and its inhibition with an antagomir results in their restoration, reducing markers of senescence, reducing SASP and reversing cell cycle arrest in epithelial cells from peripheral airways of COPD patients. MiR-570 is also involved in reduction of sirtuin-1 and cellular senescence and is activated by p38 MAP kinase. These miRNAs may be released from cells in extracellular vesicles that are taken up by other cells, thereby spreading senescence locally within the lung but outside the lung through the circulation; this may account for comorbidities of COPD and other lung diseases. Understanding the mechanisms of cellular senescence may result in new treatments for chronic lung disease, either by inhibiting PI3K-mTOR signaling, by inhibiting specific miRNAs or by deletion of senescent cells with senolytic therapies, already shown to be effective in experimental lung fibrosis.

  • Journal article
    Bourdin A, Bjermer L, Brightling C, Brusselle GG, Chanez P, Chung KF, Custovic A, Diamant Z, Diver S, Djukanovic R, Hamerlijnck D, Horvath I, Johnston SL, Kanniess F, Papadopoulos N, Papi A, Russell RJ, Ryan D, Samitas K, Tonia T, Zervas E, Gaga Met al., 2019,

    ERS/EAACI statement on severe exacerbations in asthma in adults: facts, priorities and key research questions

    , European Respiratory Journal, Vol: 54, Pages: 1-25, ISSN: 0903-1936

    Despite the use of effective medications to control asthma, severe exacerbations in asthma are still a major health risk and require urgent action on the part of the patient and physician to prevent serious outcomes such as hospitalisation or death. Moreover, severe exacerbations are associated with substantial healthcare costs and psychological burden, including anxiety and fear for patients and their families. The European Academy of Allergy and Clinical Immunology (EAACI) and the European Respiratory Society (ERS) set up a task force to search for a clear definition of severe exacerbations, and to also define research questions and priorities. The statement includes comments from patients who were members of the task force.

  • Journal article
    Laverty AA, Vamos EP, Millett C, Chang KC-M, Filippidis FT, Hopkinson NSet al., 2019,

    Child awareness of and access to cigarettes: impacts of the point-of-sale display ban in England.

    , Tob Control, Vol: 28, Pages: 526-531

    INTRODUCTION: England introduced a tobacco display ban for shops with >280 m2 floor area ('partial ban') in 2012, then a total ban in 2015. This study assessed whether these were linked to child awareness of and access to cigarettes. METHODS: Data come from the Smoking, Drinking and Drug Use survey, an annual survey of children aged 11-15 years for 2010-2014 and 2016. Multivariate logistic regression models assessed changes in having seen cigarettes on display, usual sources and ease of access to cigarettes in shops RESULTS: During the partial display ban in 2012, 89.9% of children reported seeing cigarettes on display in the last year, which was reduced to 86.0% in 2016 after the total ban (adjusted OR 0.58, 95% CI 0.50 to 0.66). Reductions were similar in small shops (84.1% to 79.3%)%) and supermarkets (62.6% to 57.3%)%). Although the ban was associated with a reduction in the proportion of regular child smokers reporting that they bought cigarettes in shops (57.0% in 2010 to 39.8% in 2016), we did not find evidence of changes in perceived difficulty or being refused sale among those who still did. DISCUSSION: Tobacco point-of-sale display bans in England reduced the exposure of children to cigarettes in shops and coincided with a decrease in buying cigarettes in shops. However, children do not report increased difficulty in obtaining cigarettes from shops, highlighting the need for additional measures to tackle tobacco advertising, stronger enforcement of existing laws and measures such as licencing for tobacco retailers.

  • Journal article
    Singanayagam A, Glanville N, Cuthbertson L, Bartlett NW, Finney LJ, Turek E, Bakhsoliani E, Calderazzo MA, Trujillo-Torralbo M-B, Footitt J, James PL, Fenwick P, Kemp SV, Clarke TB, Wedzicha JA, Edwards MR, Moffatt M, Cookson WO, Mallia P, Johnston SLet al., 2019,

    Inhaled corticosteroid suppression of cathelicidin drives dysbiosis and bacterial infection in chronic obstructive pulmonary disease

    , Science Translational Medicine, Vol: 11, Pages: 1-13, ISSN: 1946-6234

    Bacterial infection commonly complicates inflammatory airway diseases such as chronic obstructive pulmonary disease (COPD). The mechanisms of increased infection susceptibility and how use of the commonly prescribed therapy inhaled corticosteroids (ICS) accentuates pneumonia risk in COPD are poorly understood. Here, using analysis of samples from patients with COPD, we show that ICS use is associated with lung microbiota disruption leading to proliferation of streptococcal genera, an effect that could be recapitulated in ICS-treated mice. To study mechanisms underlying this effect, we used cellular and mouse models of streptococcal expansion with Streptococcus pneumoniae, an important pathogen in COPD, to demonstrate that ICS impairs pulmonary clearance of bacteria through suppression of the antimicrobial peptide cathelicidin. ICS impairment of pulmonary immunity was dependent on suppression of cathelicidin because ICS had no effect on bacterial loads in mice lacking cathelicidin (Camp-/-) and exogenous cathelicidin prevented ICS-mediated expansion of streptococci within the microbiota and improved bacterial clearance. Suppression of pulmonary immunity by ICS was mediated by augmentation of the protease cathepsin D. Collectively, these data suggest a central role for cathepsin D/cathelicidin in the suppression of antibacterial host defense by ICS in COPD. Therapeutic restoration of cathelicidin to boost antibacterial immunity and beneficially modulate the lung microbiota might be an effective strategy in COPD.

  • Journal article
    Gilworth G, Lewin S, Wright AJ, Taylor SJ, Tuffnell R, Hogg L, Hopkinson NS, Singh SJ, White Pet al., 2019,

    The lay health worker-patient relationship in promoting pulmonary rehabilitation (PR) in COPD: What makes it work?

    , Chronic Respiratory Disease, Vol: 16, ISSN: 1479-9723

    Lay health workers (LHWs) can improve access to services and adherence to treatment, as well as promoting self-care and prevention. Their effect in promoting uptake and adherence in pulmonary rehabilitation (PR) for chronic obstructive pulmonary disease (COPD) has not been tested. PR is the most effective treatment for the symptoms and disability of COPD, but this effectiveness is undermined by poor rates of completion. Trained LHWs with COPD, who also have first-hand experience of PR, are well placed to help overcome the documented barriers to its completion. The relationship between LHWs and patients may be one of the keys to their effectiveness but it has been little explored. Semi-structured qualitative interviews were used with the aim of examining the LHW-patient partnership in a feasibility study of trained PR-experienced LHWs used to support COPD patients referred to PR. Twelve volunteers with COPD who completed LHW training supported 66 patients referred for PR. All 12 of these LHWs gave end-of-study interviews, 21 COPD patients supported by LHWs were also interviewed. Patients reported that the LHWs were keen to share their experiences of PR, and that this had a positive impact. The enthusiasm of the LHWs for PR was striking. The common bond between LHWs and patients of having COPD together with the LHWs positive, first-hand experience of PR were dominant and recurring themes in their relationship.

  • Journal article
    Mills JT, Schwenzer A, Marsh EK, Edwards MR, Sabroe I, Midwood KS, Parker LCet al., 2019,

    Airway Epithelial Cells Generate Pro-inflammatory Tenascin-C and Small Extracellular Vesicles in Response to TLR3 Stimuli and Rhinovirus Infection

    , FRONTIERS IN IMMUNOLOGY, Vol: 10, ISSN: 1664-3224
  • Journal article
    van Gemert F, de Jong C, Kirenga B, Musinguzi P, Buteme S, Sooronbaev T, Tabyshova A, Emilov B, Mademilov M, Le An P, Quynh NN, Dang TN, Hong LHTC, Chartier R, Brakema EA, van Boven JFMet al., 2019,

    Effects and acceptability of implementing improved cookstoves and heaters to reduce household air pollution: a FRESH AIR study

    , npj Primary Care Respiratory Medicine, Vol: 29, ISSN: 2055-1010

    The objective was to evaluate the effectiveness and acceptability of locally tailored implementation of improved cookstoves/heaters in low- and middle-income countries. This interventional implementation study among 649 adults and children living in rural communities in Uganda, Vietnam and Kyrgyzstan, was performed after situational analyses and awareness programmes. Outcomes included household air pollution (PM2.5 and CO), self-reported respiratory symptoms (with CCQ and MRC-breathlessness scale), chest infections, school absence and intervention acceptability. Measurements were conducted at baseline, 2 and 6–12 months after implementing improved cookstoves/heaters. Mean PM2.5 values decrease by 31% (to 95.1 µg/m3) in Uganda (95%CI 71.5–126.6), by 32% (to 31.1 µg/m3) in Vietnam (95%CI 24.5–39.5) and by 65% (to 32.4 µg/m3) in Kyrgyzstan (95%CI 25.7–40.8), but all remain above the WHO guidelines. CO-levels remain below the WHO guidelines. After intervention, symptoms and infections diminish significantly in Uganda and Kyrgyzstan, and to a smaller extent in Vietnam. Quantitative assessment indicates high acceptance of the new cookstoves/heaters. In conclusion, locally tailored implementation of improved cookstoves/heaters is acceptable and has considerable effects on respiratory symptoms and indoor pollution, yet mean PM2.5 levels remain above WHO recommendations.

  • Journal article
    Huang K, Yang T, Xu J, Yang L, Zhao J, Zhang X, Bai C, Kang J, Ran P, Shen H, Wen F, Chen Y, Sun T, Shan G, Lin Y, Xu G, Wu S, Wang C, Wang R, Shi Z, Xu Y, Ye X, Song Y, Wang Q, Zhou Y, Li W, Ding L, Wan C, Yao W, Guo Y, Xiao F, Lu Y, Peng X, Zhang B, Xiao D, Wang Z, Chen Z, Bu X, Zhang H, Zhang X, An L, Zhang S, Zhu J, Cao Z, Zhan Q, Yang Y, Liang L, Tong X, Dai H, Cao B, Wu T, Chung KF, He J, Wang C, China Pulmonary Health CPH Study Groupet al., 2019,

    Prevalence, risk factors, and management of asthma in China: a national cross-sectional study

    , Lancet, Vol: 394, Pages: 407-418, ISSN: 0140-6736

    BACKGROUND: Asthma is a common chronic airway disease worldwide. Despite its large population size, China has had no comprehensive study of the national prevalence, risk factors, and management of asthma. We therefore aimed to estimate the national prevalence of asthma in a representative sample of the Chinese population. METHODS: A representative sample of 57 779 adults aged 20 years or older was recruited for the national cross-sectional China Pulmonary Health (CPH) study using a multi-stage stratified sampling method with parameters derived from the 2010 census. Ten Chinese provinces, representative of all socioeconomic settings, from six geographical regions were selected, and all assessments were done in local health centres. Exclusion criteria were temporary residence, inability to take a spirometry test, hospital treatment of cardiovascular conditions or tuberculosis, and pregnancy and breastfeeding. Asthma was determined on the basis of a self-reported history of diagnosis by a physician or by wheezing symptoms in the preceding 12 months. All participants were assessed with a standard asthma questionnaire and were classed as having or not having airflow limitation through pulmonary function tests before and after the use of a bronchodilator (400 μg of salbutamol). Risk factors for asthma were examined by multivariable-adjusted analyses done in all participants for whom data on the variables of interest were available. Disease management was assessed by the self-reported history of physician diagnosis, treatments, and hospital visits in people with asthma. FINDINGS: Between June 22, 2012, and May 25, 2015, 57 779 participants were recruited into the CPH study. 50 991 (21 446 men and 29 545 women) completed the questionnaire survey and had reliable post-bronchodilator pulmonary function test results and were thus included in the final analysis. The overall prevalence of asthma in our sample was 4·2% (95% CI 3·1-5·6), representing 45&mid

  • Journal article
    Hopkinson NS, Molyneux A, Pink J, Harrisingh MC, Guideline Committee GCet al., 2019,

    Chronic obstructive pulmonary disease: diagnosis and management: summary of updated NICE guidance.

    , BMJ, Vol: 366, Pages: 1-7, ISSN: 0959-8138
  • Journal article
    Elbehairy A, Quint J, Rogers J, Laffan M, Polkey M, Hopkinson Net al., 2019,

    Prevalence of breathlessness and associated consulting behaviour: results of an online survey

    , Thorax, Vol: 74, Pages: 814-817, ISSN: 1468-3296

    The online British Lung Foundation Breath Test provides an opportunity to study the relationship between breathlessness, common sociobehavioural risk factors and interaction with healthcare. We analysed data from 356 799 responders: 71% were ≥50 years old and 18% were smokers. 20% reported limiting breathlessness (Medical Research Council breathlessness score ≥3), and the majority of these (85%) worried about their breathing; of these, 29% had not sought medical advice. Of those who had, 58% reported that the advice received had not helped their breathlessness. Limiting breathlessness was associated with being older, physically inactive, smoking and a higher body mass index. These data suggest a considerable unmet need associated with breathlessness as well as possibilities for intervention.

  • Journal article
    Gaga M, Powell P, Almagro M, Tsiligianni I, Loukides S, Roca J, Cullen M, Simonds AK, Ward B, Saraiva I, Troosters T, Cordeiro CRet al., 2019,

    ERS Presidential Summit 2018: multimorbidities and the ageing population

    , ERJ OPEN RESEARCH, Vol: 5
  • Journal article
    Menzies-Gow A, McBrien CN, Baker JR, Donnelly LE, Cohen RTet al., 2019,

    Update in asthma/airway inflammation 2018

    , American Journal of Respiratory and Critical Care Medicine, Vol: 200, Pages: 14-19, ISSN: 1073-449X

    Throughout 2018, the publications of the AJRCCM and associated ATS journals have continued to focus on the individual and societal impact of asthma and the challenges involved in managing this prevalent, but heterogeneous, condition. Asthma remains the most common chronic respiratory condition with ongoing significant unmet need at all levels of severity. The cardinal features of asthma, i.e. that it affects a significant proportion of all age‐groups, but generates highly individual effects on health and socioeconomic factors, have hampered previous attempts to gauge its true cost at a population level. Nurmagambetov et al. approached this task by utilising data from the 2008‐2013 household component of the Medical Expenditure Panel Survey, examining a total sample size of more than 200,000 persons (more than 10,000 of whom had ‘treated asthma’)[1]. Application of a two‐part regression model indicated the cost of asthma in the USA in 2013 to be $81.9 billion, underlining the huge potential for improvements in asthma care to benefit individuals and populations in multiple aspects, including financially.

  • Journal article
    Doherty DF, Nath S, Poon J, Foronjy RF, Ohlmeyer M, Debo AJ, Salathe M, Birrell M, Belvisi M, Baumlin N, Kim MD, Weldon S, Taggart C, Geraghty Pet al., 2019,

    Protein Phosphatase 2A Reduces Cigarette Smoke-induced Cathepsin S and Loss of Lung Function

    , AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 200, Pages: 51-62, ISSN: 1073-449X
  • Journal article
    Nyga A, Hart A, Tetley TD, 2019,

    Molecular analysis of HIF activation as a potential biomarker for adverse reaction to metal debris (ARMD) in tissue and blood samples

    , JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS, Vol: 107, Pages: 1352-1362, ISSN: 1552-4973

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