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Fibrinogen does not relate to cardiovascular or muscle manifestations in COPD: cross-sectional data from the ERICA study (2018)
Journal Article
Mohan, D., Forman, J. R., Allinder, M., McEniery, C. M., Bolton, C. E., Cockcroft, J. R., MacNee, W., Fuld, J., Marchong, M., Gale, N. S., Fisk, M., Nagarajan, S., Cheriyan, J., Lomas, D. A., Calverley, P. M., Miller, B. E., Tal-Singer, R., Wilkinson, I. B., & Polkey, M. I. (2018). Fibrinogen does not relate to cardiovascular or muscle manifestations in COPD: cross-sectional data from the ERICA study. Thorax, 73(12), 1182-1185. https://doi.org/10.1136/thoraxjnl-2018-211556

Cardiovascular and skeletal muscle manifestations constitute important comorbidities in COPD, with systemic inflammation proposed as a common mechanistic link. Fibrinogen has prognostic role in COPD. We aimed to determine whether aortic stiffness and... Read More about Fibrinogen does not relate to cardiovascular or muscle manifestations in COPD: cross-sectional data from the ERICA study.

Risk of fall in patients with COPD (2018)
Journal Article
Hakamy, A., Bolton, C. E., Gibson, J. E., & McKeever, T. M. (2018). Risk of fall in patients with COPD. Thorax, 73(11), 1079-1080. https://doi.org/10.1136/thoraxjnl-2017-211008

A matched cohort study was conducted to determine the incidence of falls in patients following a diagnosis of COPD using a UK primary care database. 44 400 patients with COPD and 175 545 non-COPD subjects were identified. The incidence rate of fall p... Read More about Risk of fall in patients with COPD.

Variation in lung function and alterations in cardiac 1 structure and function: analysis of the UK Biobank 2 cardiovascular magnetic resonance imaging substudy (2018)
Journal Article
Thomson, R. J., Aung, N., Sanghvi, M. M., Paiva, J. M., Lee, A. M., Fung, K., …Petersen, S. E. (2018). Variation in lung function and alterations in cardiac 1 structure and function: analysis of the UK Biobank 2 cardiovascular magnetic resonance imaging substudy. PLoS ONE, 13(3), Article e0194434. https://doi.org/10.1371/journal.pone.0194434

Background

Reduced lung function is common and associated with increased cardiovascular morbidity and mortality, even in asymptomatic individuals without diagnosed respiratory disease. Previous studies have identified relationships between lung fu... Read More about Variation in lung function and alterations in cardiac 1 structure and function: analysis of the UK Biobank 2 cardiovascular magnetic resonance imaging substudy.

Suberanilohydroxamic acid prevents TGF-β1-induced COX-2 repression in human lung fibroblasts post-transcriptionally by TIA-1 downregulation (2018)
Journal Article
Pasini, A., Brand, O. J., Jenkins, G., Knox, A. J., & Pang, L. (2018). Suberanilohydroxamic acid prevents TGF-β1-induced COX-2 repression in human lung fibroblasts post-transcriptionally by TIA-1 downregulation. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 1861(5), https://doi.org/10.1016/j.bbagrm.2018.03.007

Cyclooxygenase-2 (COX-2), with its main antifibrotic metabolite PGE, is regarded as an antifibrotic gene. Repressed COX-2 expression and deficient PGE have been shown to contribute to the activation of lung fibroblasts and excessive deposition of col... Read More about Suberanilohydroxamic acid prevents TGF-β1-induced COX-2 repression in human lung fibroblasts post-transcriptionally by TIA-1 downregulation.

Altered DNA methylation is associated with aberrant gene expression in parenchymal but not airway fibroblasts isolated from individuals with COPD (2018)
Journal Article
Clifford, R. L., Fishbane, N., Patel, J., MacIsaac, J. L., McEwen, L. M., Fisher, A. J., Brandsma, C.-A., Nair, P., Kobor, M. S., Hackett, T.-L., & Knox, A. J. (2018). Altered DNA methylation is associated with aberrant gene expression in parenchymal but not airway fibroblasts isolated from individuals with COPD. Clinical Epigenetics, 10(1), https://doi.org/10.1186/s13148-018-0464-5

Background: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease of the lungs that is currently the fourth leading cause of death worldwide. Genetic factors account for only a small amount of COPD risk, but epigenetic mechanisms, i... Read More about Altered DNA methylation is associated with aberrant gene expression in parenchymal but not airway fibroblasts isolated from individuals with COPD.

Quadrupling inhaled glucocorticoid dose to abort asthma exacerbations (2018)
Journal Article
McKeever, T., Mortimer, K., Wilson, A., Walker, S., Brightling, C., Skeggs, A., …Harrison, T. (2018). Quadrupling inhaled glucocorticoid dose to abort asthma exacerbations. New England Journal of Medicine, 378(10), 902-910. https://doi.org/10.1056/NEJMoa1714257

Copyright © 2018 Massachusetts Medical Society. BACKGROUND Asthma exacerbations are frightening for patients and are occasionally fatal. We tested the concept that a plan for patients to manage their asthma (self-management plan), which included a te... Read More about Quadrupling inhaled glucocorticoid dose to abort asthma exacerbations.

A Genome-Wide Association Study in Hispanics/Latinos Identifies Novel Signals for Lung Function. The Hispanic Community Health Study/Study of Latinos (2018)
Journal Article
Burkart, K. M., Sofer, T., London, S. J., Manichaikul, A., Hartwig, F. P., Yan, Q., …Barr, R. G. (2018). A Genome-Wide Association Study in Hispanics/Latinos Identifies Novel Signals for Lung Function. The Hispanic Community Health Study/Study of Latinos. American Journal of Respiratory and Critical Care Medicine, 198(2), 208-219. https://doi.org/10.1164/rccm.201707-1493OC

Rationale: Lung function and chronic obstructive pulmonary disease (COPD) are heritable traits. Genome-wide association studies (GWAS) have identified numerous pulmonary function and COPD loci, primarily in cohorts of European ancestry.
Objectives:... Read More about A Genome-Wide Association Study in Hispanics/Latinos Identifies Novel Signals for Lung Function. The Hispanic Community Health Study/Study of Latinos.

Chloride intracellular channel 1 (CLIC1) contributes to modulation of cyclic AMP-activated whole cell chloride currents in human bronchial epithelial cells (2018)
Journal Article
Liu, B., Billington, C. K., Henry, A. P., Bhaker, S. K., Kheirallah, A. K., Swan, C., & Hall, I. P. (in press). Chloride intracellular channel 1 (CLIC1) contributes to modulation of cyclic AMP-activated whole cell chloride currents in human bronchial epithelial cells. Physiological Reports, 6(2), Article e13508. https://doi.org/10.14814/phy2.13508

Chloride channels are known to play critical physiological roles in many cell types. Here we describe the expression of anion channels using RNA Seq in primary cultures of human Bronchial Epithelial Cells (hBECs). Chloride intracellular channel (CLIC... Read More about Chloride intracellular channel 1 (CLIC1) contributes to modulation of cyclic AMP-activated whole cell chloride currents in human bronchial epithelial cells.

PINX1 and TERT are required for TNF-α-induced airway smooth muscle chemokine gene expression (2018)
Journal Article
Deacon, K., & Knox, A. J. (2018). PINX1 and TERT are required for TNF-α-induced airway smooth muscle chemokine gene expression. Journal of Immunology, 200(4), https://doi.org/10.4049/jimmunol.1700414

Airway smooth muscle (ASM) cells contribute to asthmatic lung pathology with chemokine hypersecretion and increased ASM cell mass. With little recent progress in the development of asthma therapies, a greater understanding of lung inflammation mechan... Read More about PINX1 and TERT are required for TNF-α-induced airway smooth muscle chemokine gene expression.

A randomised pragmatic trial of corticosteroid optimization in severe asthma using a composite biomarker algorithm to adjust corticosteroid dose versus standard care: study protocol for a randomised trial (2018)
Journal Article
Hanratty, C. E., Matthews, J. G., Arron, J. R., Choy, D. F., Pavord, I. D., Bradding, P., …Heaney, L. G. (2018). A randomised pragmatic trial of corticosteroid optimization in severe asthma using a composite biomarker algorithm to adjust corticosteroid dose versus standard care: study protocol for a randomised trial. Trials, 19, Article 5. https://doi.org/10.1186/s13063-017-2384-7

Background: Patients with difficult-to-control asthma consume 50–60% of healthcare costs attributed to asthma and cost approximately five-times more than patients with mild stable disease. Recent evidence demonstrates that not all patients with asthm... Read More about A randomised pragmatic trial of corticosteroid optimization in severe asthma using a composite biomarker algorithm to adjust corticosteroid dose versus standard care: study protocol for a randomised trial.

Accurate identification of hospital admissions from care homes: development and validation of an automated algorithm (2017)
Journal Article
Housley, G., Lewis, S., Usman, A., Gordon, A. L., & Shaw, D. E. (2018). Accurate identification of hospital admissions from care homes: development and validation of an automated algorithm. Age and Ageing, 47(3), 387-391. https://doi.org/10.1093/ageing/afx182

Background: measuring the complex needs of care home residents is crucial for resource allocation. Hospital patient administration systems (PAS) may not accurately identify admissions from care homes.
Objective: to develop and validate an accurate,... Read More about Accurate identification of hospital admissions from care homes: development and validation of an automated algorithm.

An epithelial biomarker signature for idiopathic pulmonary fibrosis: an analysis from the multicentre PROFILE cohort study (2017)
Journal Article
Maher, T. M., Oballa, E., Simpson, J. K., Porte, J., Habgood, A., Fahy, W. A., Flynn, A., Molyneux, P. L., Braybrooke, R., Divyateja, H., Parfrey, H., Rassl, D., Russell, A.-M., Saini, G., Renzoni, E., Duggan, A.-M., Hubbard, R., Wells, A. U., Lukey, P. T., Marshall, R. P., & Jenkins, R. G. (in press). An epithelial biomarker signature for idiopathic pulmonary fibrosis: an analysis from the multicentre PROFILE cohort study. Lancet Respiratory Medicine, 5(12), https://doi.org/10.1016/S2213-2600%2817%2930430-7

Background: Idiopathic Pulmonary Fibrosis (IPF) is a progressive, fatal condition with a variable disease trajectory. The aim of this study was to evaluate potential biomarkers that predict outcome for people with IPF.
Method: The PROFILE study is a... Read More about An epithelial biomarker signature for idiopathic pulmonary fibrosis: an analysis from the multicentre PROFILE cohort study.

Interplay between EZH2 and G9a regulates CXCL10 gene repression in idiopathic pulmonary fibrosis (2017)
Journal Article
Coward, W. R., Brand, O. J., Pasini, A., Jenkins, G., Knox, A. J., & Pang, L. (in press). Interplay between EZH2 and G9a regulates CXCL10 gene repression in idiopathic pulmonary fibrosis. American Journal of Respiratory Cell and Molecular Biology, https://doi.org/10.1165/rcmb.2017-0286OC

Selective repression of the antifibrotic gene CXCL10 contributes to tissue remodelling in idiopathic pulmonary fibrosis (IPF). We have previously reported that histone deacetylation and histone H3 lysine 9 (H3K9) methylation are involved in CXCL10 re... Read More about Interplay between EZH2 and G9a regulates CXCL10 gene repression in idiopathic pulmonary fibrosis.

Genetic variants associated with susceptibility to idiopathic pulmonary fibrosis in people of European ancestry: a genome-wide association study (2017)
Journal Article
Allen, R. J., Porte, J., Braybrooke, R., Flores, C., Fingerlin, T. E., Oldham, J. M., …Jenkins, R. G. (2017). Genetic variants associated with susceptibility to idiopathic pulmonary fibrosis in people of European ancestry: a genome-wide association study. Lancet Respiratory Medicine, 5(11), https://doi.org/10.1016/S2213-2600%2817%2930387-9

Background
Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease with high mortality, uncertain cause, and few treatment options. Studies have identified a significant genetic risk associated with the development of IPF; however,... Read More about Genetic variants associated with susceptibility to idiopathic pulmonary fibrosis in people of European ancestry: a genome-wide association study.

ECM crosslinking enhances fibroblast growth and protects against matrix proteolysis in lung fibrosis (2017)
Journal Article
Philp, C. J., Siebeke, I., Clements, D., Miller, S., Habgood, A., John, A. E., …Johnson, S. R. (2018). ECM crosslinking enhances fibroblast growth and protects against matrix proteolysis in lung fibrosis. American Journal of Respiratory Cell and Molecular Biology, 58(5), 594–603. https://doi.org/10.1165/rcmb.2016-0379OC

Idiopathic pulmonary fibrosis (IPF) is characterised by accumulation of extra cellular matrix (ECM) proteins and fibroblast proliferation. ECM cross-linking enzymes have been implicated in fibrotic diseases and we hypothesised that the ECM in IPF is... Read More about ECM crosslinking enhances fibroblast growth and protects against matrix proteolysis in lung fibrosis.

The recording and characteristics of pulmonary rehabilitation in patients with COPD using The Health Information Network (THIN) primary care database (2017)
Journal Article
Hakamy, A., McKeever, T. M., Gibson, J. E., & Bolton, C. E. (in press). The recording and characteristics of pulmonary rehabilitation in patients with COPD using The Health Information Network (THIN) primary care database. npj Primary Care Respiratory Medicine, 27(1), Article 58. https://doi.org/10.1038/s41533-017-0058-2

Pulmonary rehabilitation is recommended for patients with COPD to improve physical function, breathlessness and quality of life. Using The Health Information Network (THIN) primary care database in UK, we compared the demographic and clinical paramet... Read More about The recording and characteristics of pulmonary rehabilitation in patients with COPD using The Health Information Network (THIN) primary care database.

Lung function response and side effects to rapamycin for lymphangioleiomyomatosis: a prospective national cohort study (2017)
Journal Article
Bee, J., Fuller, S., Miller, S., & Johnson, S. R. (2018). Lung function response and side effects to rapamycin for lymphangioleiomyomatosis: a prospective national cohort study. Thorax, 73(4), 369-375. https://doi.org/10.1136/thoraxjnl-2017-210872

Rationale

Mechanistic target of rapamycin inhibitors reduce loss of lung function in lymphangioleiomyomatosis (LAM), although their benefit varies between individuals. We examined lung function response and side effects to rapamycin in a national... Read More about Lung function response and side effects to rapamycin for lymphangioleiomyomatosis: a prospective national cohort study.

Transcriptomic gene signatures associated with persistent airflow limitation in patients with severe asthma (2017)
Journal Article
Hekking, P.-P., Loza, M. J., Pavlidis, S., De Meulder, B., Lefaudeux, D., Baribaud, F., …Sterk, P. J. (2017). Transcriptomic gene signatures associated with persistent airflow limitation in patients with severe asthma. European Respiratory Journal, 50(3), https://doi.org/10.1183/13993003.02298-2016

A proportion of severe asthma patients suffers from persistent airflow limitation (PAL), often associated with more symptoms and exacerbations. Little is known about the underlying mechanisms. Here, our aim was to discover unexplored potential mechan... Read More about Transcriptomic gene signatures associated with persistent airflow limitation in patients with severe asthma.

Targeted inhibition of Gq signaling induces airway relaxation in mouse models of asthma (2017)
Journal Article
Matthey, M., Roberts, R., Seidinger, A., Simon, A., Schröder, R., Kuschak, M., …Wenzel, D. (in press). Targeted inhibition of Gq signaling induces airway relaxation in mouse models of asthma. Science Translational Medicine, 9(407), https://doi.org/10.1126/scitranslmed.aag2288

Obstructive lung diseases are common causes of disability and death worldwide. A hallmark feature is aberrant activation of Gq protein–dependent signaling cascades. Currently, drugs targeting single G protein (heterotrimeric guanine nucleotide–bindin... Read More about Targeted inhibition of Gq signaling induces airway relaxation in mouse models of asthma.