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  • 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
  • Journal article
    Schofield JPR, Burg D, Nicholas B, Strazzeri F, Brandsma J, Staykova D, Folisi C, Bansal AT, Xian Y, Guo Y, Rowe A, Corfield J, Wilson S, Ward J, Lutter R, Shaw DE, Bakke PS, Caruso M, Dahlen S-E, Fowler SJ, Horváth I, Howarth P, Krug N, Montuschi P, Sanak M, Sandström T, Sun K, Pandis I, Riley J, Auffray C, De Meulder B, Lefaudeux D, Sousa AR, Adcock IM, Chung KF, Sterk PJ, Skipp PJ, Djukanović R, U-BIOPRED Study Groupet al., 2019,

    Stratification of asthma phenotypes by airway proteomic signatures

    , Journal of Allergy and Clinical Immunology, Vol: 144, Pages: 70-82, ISSN: 0091-6749

    BACKGROUND: Stratification by eosinophil and neutrophil counts increases our understanding of asthma and helps target therapy, but there is room for improvement in our accuracy to predict treatment responses and a need for better understanding of the underlying mechanisms. OBJECTIVE: Identify molecular sub-phenotypes of asthma defined by proteomic signatures for improved stratification. METHODS: Unbiased label-free quantitative mass spectrometry and topological data analysis were used to analyse the proteomes of sputum supernatants from 246 participants (206 asthmatics) as a novel means of asthma stratification. Microarray analysis of sputum cells provided transcriptomics data additionally to inform on underlying mechanisms. RESULTS: Analysis of the sputum proteome resulted in 10 clusters, proteotypes, based on similarity in proteomics features, representing discrete molecular sub-phenotypes of asthma. Overlaying granulocyte counts onto the 10 clusters as metadata further defined three of these as highly eosinophilic, three as highly neutrophilic, and two as highly atopic with relatively low granulocytic inflammation. For each of these three phenotypes, logistic regression analysis identified candidate protein biomarkers, and matched transcriptomic data pointed to differentially activated underlying mechanisms. CONCLUSION: This study provides further stratification of asthma currently classified by quantifying granulocytic inflammation and gives additional insight into their underlying mechanisms which could become targets for novel therapies.

  • Journal article
    Perotin J-M, Schofield JPR, Wilson SJ, Ward J, Brandsma J, Strazzeri F, Bansal A, Yang X, Rowe A, Corfield J, Lutter R, Shaw DE, Bakke PS, Caruso M, Dahlén B, Fowler SJ, Horváth I, Howarth P, Krug N, Montuschi P, Sanak M, Sandström T, Sun K, Pandis I, Auffray C, De Meulder B, Lefaudeux D, Riley JH, Sousa AR, Dahlen S-E, Adcock IM, Chung KF, Sterk PJ, Skipp PJ, Collins JE, Davies DE, Djukanović R, U-BIOPRED Study Groupet al., 2019,

    Epithelial dysregulation in obese severe asthmatics with gastro-oesophageal reflux

    , European Respiratory Journal, Vol: 53, ISSN: 0903-1936
  • Journal article
    Ciano M, Mantellato G, Connolly M, Paul-Clark M, Mitchell J, Wilson-Owen S, Cookson W, Moffatt M, Hughes S, Polkey M, Kemp P, Natanek Set al., 2019,

    EGF receptor (EGFR) inhibition promotes a slow-twitch oxidative, over a fast-twitch, muscle phenotype

    , Scientific Reports, Vol: 9, ISSN: 2045-2322

    A low quadriceps slow-twitch (ST), oxidative (relative to fast-twitch) fiber proportion is prevalent in chronic diseases such Chronic Obstructive Pulmonary Disease (COPD) and is associated with exercise limitation and poor outcomes. Benefits of an increased ST fiber proportion are demonstrated in genetically modified animals. Pathway analysis of published data of differentially expressed genes in mouse ST and FT fibers, mining of our microarray data and a qPCR analysis of quadriceps specimens from COPD patients and controls were performed. ST markers were quantified in C2C12 myotubes with EGF-neutralizing antibody, EGFR inhibitor or an EGFR-silencing RNA added. A zebrafish egfra mutant was generated by genome editing and ST fibers counted. EGF signaling was (negatively) associated with the ST muscle phenotype in mice and humans, and muscle EGF transcript levels were raised in COPD. In C2C12 myotubes, EGFR inhibition/silencing increased ST, including mitochondrial, markers. In zebrafish, egfra depletion increased ST fibers and mitochondrial content. EGF is negatively associated with ST muscle phenotype in mice, healthy humans and COPD patients. EGFR blockade promotes the ST phenotype in myotubes and zebrafish embryos. EGF signaling suppresses the ST phenotype, therefore EGFR inhibitors may be potential treatments for COPD-related muscle ST fiber loss.

  • Journal article
    Finney LJ, Padmanaban V, Todd S, Ahmed N, Elkin SL, Mallia Pet al., 2019,

    Validity of the diagnosis of pneumonia in hospitalised patients with COPD.

    , ERJ Open Research, Vol: 5, Pages: 1-8, ISSN: 2312-0541

    Rationale: Exacerbations of chronic obstructive pulmonary disease (COPD) and pneumonia are two of the most common reasons for acute hospital admissions. Acute exacerbations and pneumonia present with similar symptoms in COPD patients, representing a diagnostic challenge with a significant impact on patient outcomes. The objectives of this study were to compare the prevalence of radiographic consolidation with the discharge diagnoses of hospitalised COPD patients. Methods: COPD patients admitted to three UK hospitals over a 3-year period were identified. Participants were included if they were admitted with an acute respiratory illness, COPD was confirmed by spirometry and a chest radiograph was performed within 24 h of admission. Pneumonia was defined as consolidation on chest radiograph reviewed by two independent observers. Results: There were 941 admissions in 621 patients included in the final analysis. In 235 admissions, consolidation was present on chest radiography and there were 706 admissions without consolidation. Of the 235 admissions with consolidation, only 42.9% had a discharge diagnosis of pneumonia; 90.7% of patients without consolidation had a discharge diagnosis of COPD exacerbation. The presence of consolidation was associated with increased rate of high-dependency care admission, increased mortality and prolonged length of stay. Inhaled corticosteroid use was associated with recurrent pneumonia. Conclusions: Pneumonia is underdiagnosed in patients with COPD. Radiographic consolidation is associated with worse outcomes and prolonged length of stay. Incorrect diagnosis could result in inappropriate use of inhaled corticosteroids. Future guidelines should specifically address the diagnosis and management of pneumonia in COPD.

  • Journal article
    Finney LJ, Belchamber KBR, Fenwick PS, Kemp SV, Edwards MR, Mallia P, Donaldson G, Johnston SL, Donnelly LE, Wedzicha JAet al., 2019,

    Human rhinovirus impairs the innate immune response to bacteria in alveolar macrophages in chronic obstructive pulmonary disease

    , American Journal of Respiratory and Critical Care Medicine, Vol: 199, Pages: 1496-1507, ISSN: 1073-449X

    Rationale Human rhinovirus (HRV) is a common cause of COPD exacerbations. Secondary bacterial infection is associated with more severe symptoms and delayed recovery. Alveolar macrophages clear bacteria from the lung and maintain lung homeostasis through cytokine secretion. These processes are defective in COPD. The effect of HRV on macrophage function is unknown. Objectives To investigate the effect of HRV on phagocytosis and cytokine response to bacteria by alveolar macrophages and monocyte derived macrophages (MDM) in COPD and healthy controls. Methods Alveolar macrophages were obtained by bronchoscopy and MDM by adherence. Macrophages were exposed to HRV 16 (multiplicity of infection 5), polyI:C 30μg/ml, interferon (IFN)-β 10μg/ml, IFN-γ 10μg/ml or medium control for 24 hours. Phagocytosis of fluorescently-labelled Haemophilus influenzae or Streptococcus pneumoniae was assessed by fluorimetry. CXCL8, TNF and IL-10 release was measured by ELISA. Main Results HRV significantly impaired phagocytosis of H. influenzae by 23% in MDM (n=37) and 18% in alveolar macrophages (n=20) in COPD. HRV also significantly reduced phagocytosis of S. pneumoniae by 33% in COPD MDM. There was no effect in healthy controls. Phagocytosis of H. influenzae was impaired by polyI:C but not IFN-β or IFN-γ. HRV significantly reduced cytokine responses to H. influenzae. The IL-10 response to H. influenzae was significantly impaired by polyI:C, IFN-β and IFN-γ. Conclusions HRV impairs phagocytosis of bacteria in COPD which may lead to an outgrowth of bacteria. HRV also impairs cytokine responses to bacteria via the TLR3/IFN pathway which may prevent resolution of inflammation leading to prolonged exacerbations in COPD.

  • Journal article
    Bernabé-Rubio M, Bosch-Fortea M, García E, de la Serna JB, Alonso MAet al., 2019,

    The ciliary membrane of polarized epithelial cells stems from a midbody remnant-associated membrane patch with condensed nanodomains

    <jats:title>Abstract</jats:title><jats:p>The primary cilium is a specialized plasma membrane protrusion that harbors receptors involved in important signaling pathways. Despite its central role in regulating cellular behavior, the biogenesis of the primary cilium is not fully understood. In fact, the source of the ciliary membrane remains a mystery in cell types that assemble their primary cilium entirely at the cell surface, such as polarized renal epithelial cells. After cytokinesis, the remnant of the midbody of these cells moves to the center of the apical surface, where it licenses the centrosome for ciliogenesis through an unidentified mechanism. Here, to investigate the origin of the ciliary membrane and the role of the midbody remnant, we analyzed membrane compaction and lipid dynamics at the microscale and nanoscale in living renal epithelial MDCK cells. We found that a specialized patch made of condensed membranes with restricted lipid lateral mobility surrounds the midbody remnant. This patch accompanies the remnant on its journey towards the centrosome and, once the two structures have met, the remnant delivers part of membranes of the patch to build the ciliary membrane. In this way, we have determined the origin of the ciliary membrane and the contribution of the midbody remnant to primary cilium formation in cells whose primary cilium is assembled at the plasma membrane.</jats:p>

  • Journal article
    Kumar R, Fadieieva H, Chipev PM, Simonds Aet al., 2019,

    Noninvasive ventilation (advanced): course report

    , BREATHE, Vol: 15, Pages: 104-107, ISSN: 1810-6838
  • Journal article
    Farre-Garros R, Lee J, Natanek S, Connolly M, Sayer A, Patel H, Cooper C, Polkey M, Kemp Pet al., 2019,

    Quadriceps miR-542-3p and 5p are elevated in COPD and reduce function by inhibiting ribosomal and protein synthesis

    , Journal of Applied Physiology, Vol: 126, Pages: 1514-1524, ISSN: 8750-7587

    Reduced physical performance reduces quality of life in patients with COPD. Impaired physical performance is, in part, a consequence of reduced muscle mass and function, which is accompanied by mitochondrial dysfunction. We recently showed that miR-542-3p and miR-542-5p were elevated in a small cohort of COPD patients and more markedly in critical care patients. In mice these miRNAs promoted mitochondrial dysfunction suggesting that they would affect physical performance in patients with COPD but we did not explore the association of these miRNAs with disease severity or physical performance further. We therefore quantified miR-542-3p/5p and mitochondrial rRNA expression in RNA extracted from quadriceps muscle of patients with COPD and determined their association with physical performance. As miR-542-3p inhibits ribosomal protein synthesis its ability to inhibit protein synthesis was also determined in vitro.Both miR-542-3p and -5p expression were elevated in patients with COPD (5-fold p<0.001) and the degree of elevation associated with impaired lung function (TLCO% and FEV1%) and physical performance (6-minute walk distance %). In COPD patients, the ratio of 12S rRNA to 16S rRNA was suppressed suggesting mitochondrial ribosomal stress and mitochondrial dysfunction and miR-542-3p/5p expression was inversely associated with mitochondrial gene expression and positively associated with p53 activity. miR-542-3p suppressed RPS23 expression and maximal protein synthesis in vitro. Our data show that miR-542-3p and -5p expression is elevated in COPD patients and may suppress physical performance at least in part by inhibiting mitochondrial and cytoplasmic ribosome synthesis and suppressing protein synthesis.

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