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Targeted sequencing of lung function loci in chronic obstructive pulmonary disease cases and controls (2017)
Journal Article
Artigas, M. S., Wain, L. V., Shrine, N., McKeever, T. M., Sayers, I., Hall, I. P., & Tobin, M. D. (2017). Targeted sequencing of lung function loci in chronic obstructive pulmonary disease cases and controls. PLoS ONE, 12(1), Article e0170222. https://doi.org/10.1371/journal.pone.0170222

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide; smoking is the main risk factor for COPD, but genetic factors are also relevant contributors. Genome-wide association studies (GWAS) of the lung function meas... Read More about Targeted sequencing of lung function loci in chronic obstructive pulmonary disease cases and controls.

Evidence for large-scale gene-by-smoking interaction effects on pulmonary function (2017)
Journal Article
Aschard, H., Tobin, M. D., Hancock, D. B., Skurnik, D., Sood, A., James, A., Vernon Smith, A., Manichaikul, A. W., Campbell, A., Prins, B. P., Hayward, C., Loth, D. W., Porteous, D. J., Strachan, D. P., Zeggini, E., O’Connor, G. T., Brusselle, G. G., Boezen, H. M., Schulz, H., Deary, I. J., …Kraft, P. (in press). Evidence for large-scale gene-by-smoking interaction effects on pulmonary function. International Journal of Epidemiology, Article dyw318. https://doi.org/10.1093/ije/dyw318

Background: Smoking is the strongest environmental risk factor for reduced pulmonary function. The genetic component of various pulmonary traits has also been demonstrated, and at least 26 loci have been reproducibly associated with either FEV1 (forc... Read More about Evidence for large-scale gene-by-smoking interaction effects on pulmonary function.

Socioeconomic deprivation and the outcome of pulmonary rehabilitation in England and Wales (2017)
Journal Article
Steiner, M. C., Lowe, D., Beckford, K., Blakey, J., Bolton, C. E., Elkin, S., Man, W. D. .-C., Roberts, C. M., Sewell, L., Walker, P., & Singh, S. J. (2017). Socioeconomic deprivation and the outcome of pulmonary rehabilitation in England and Wales. Thorax, 72(6), 530-537. https://doi.org/10.1136/thoraxjnl-2016-209376

Background: Pulmonary rehabilitation (PR) improves exercise capacity and health status in patients with COPD, but many patients assessed for PR do not complete therapy. It is unknown whether socioeconomic deprivation associates with rates of completi... Read More about Socioeconomic deprivation and the outcome of pulmonary rehabilitation in England and Wales.

sTREM-1 is elevated in cystic fibrosis and correlates with proteases (2017)
Journal Article
Forrester, D., Barr, H. L., Fogarty, A., & Knox, A. (2017). sTREM-1 is elevated in cystic fibrosis and correlates with proteases. Pediatric Pulmonology, 52(4), 467-471. https://doi.org/10.1002/ppul.23650

Background: sTREM-1 (soluble triggering receptor expressed on myeloid cells-1) is a novel inflammatory marker that may be of clinical use in cystic fibrosis (CF). Dysregulation of the TREM pathway has been demonstrated in other inflammatory diseases... Read More about sTREM-1 is elevated in cystic fibrosis and correlates with proteases.

Effect of epigenetic inhibitors on lung fibroblast phenotype change in idiopathic pulmonary fibrosis (2016)
Journal Article
Pasini, A., Brand, O. J., Jenkins, G., Knox, A. J., & Pang, L. (2016). Effect of epigenetic inhibitors on lung fibroblast phenotype change in idiopathic pulmonary fibrosis. Thorax, 71(Supp3), Article A32. https://doi.org/10.1136/thoraxjnl-2016-209333.59

Introduction and objectives: Idiopathic Pulmonary Fibrosis (IFP) is a fatal interstitial lung disease with unknown aetiology. Lung myofibroblasts (activated fibrobalsts) are the major effector cells in the pathogenesis of IPF. Transforming growth fac... Read More about Effect of epigenetic inhibitors on lung fibroblast phenotype change in idiopathic pulmonary fibrosis.

MMP-1 activation contributes to airway smooth muscle growth and asthma severity (2016)
Journal Article
Naveed, S.-U.-N., Clements, D., Jackson, D. J., Philp, C., Billington, C. K., Soomro, I. N., Reynolds, C., Harrison, T. W., Johnston, S. L., Shaw, D. E., & Johnson, S. R. (2017). MMP-1 activation contributes to airway smooth muscle growth and asthma severity. American Journal of Respiratory and Critical Care Medicine, 195(8), 1000-1009. https://doi.org/10.1164/rccm.201604-0822OC

Introduction: Matrix metalloproteinase-1 and mast cells are present in the airways of people with asthma. We hypothesised that matrix metalloproteinase-1 could be activated by mast cells and increase asthma severity. Methods: Patients with stable ast... Read More about MMP-1 activation contributes to airway smooth muscle growth and asthma severity.

NMR hyperpolarization techniques of gases (2016)
Journal Article
Barskiy, D. A., Coffey, A. M., Nikolaou, P., Mikhaylov, D. M., Goodson, B. M., Branca, R. T., Lu, G. J., Shapiro, M. G., Telkki, V.-V., Zhivonitko, V. V., Koptyug, I. V., Salnikov, O. G., Kovtunov, K. V., Bukhtiyarov, V. I., Rosen, M. S., Barlow, M. J., Safavi, S., Hall, I. P., Schröder, L., & Chekmenev, E. Y. (2017). NMR hyperpolarization techniques of gases. Chemistry - A European Journal, 23(4), 725-751. https://doi.org/10.1002/chem.201603884

Nuclear spin polarization can be significantly increased through the process of hyperpolarization, leading to an increase in the sensitivity of nuclear magnetic resonance (NMR) experiments by 4–8 orders of magnitude. Hyperpolarized gases, unlike liqu... Read More about NMR hyperpolarization techniques of gases.

What are the pros and cons of electronically monitoring inhaler use in asthma? A multistakeholder perspective (2016)
Journal Article
Howard, S., Lang, A. R., Sharples, S., & Shaw, D. E. (in press). What are the pros and cons of electronically monitoring inhaler use in asthma? A multistakeholder perspective. BMJ Open Respiratory Research, 3(1), Article e000159. https://doi.org/10.1136/bmjresp-2016-000159

Introduction

Electronic monitoring devices (EMDs) are the optimal method for collecting objective data on inhaler use in asthma. Recent research has investigated the attitudes of patients with asthma towards these devices. However, no research to... Read More about What are the pros and cons of electronically monitoring inhaler use in asthma? A multistakeholder perspective.

S133 Investigating genome wide dna methylation in airway and parenchymal fibroblasts from healthy individuals and individuals with copd (2016)
Presentation / Conference Contribution
Clifford, R. L., Fishbane, N., Rajasekar, P., Fisher, A., Kobor, M., Knox, A., & Hackett, T. S133 Investigating genome wide dna methylation in airway and parenchymal fibroblasts from healthy individuals and individuals with copd

Rationale: Lung fibroblasts are implicated in respiratory disease pathology including chronic obstructive pulmonary disease (COPD). Phenotypic differences between fibroblasts isolated from the airway versus the parenchyma have been described but no s... Read More about S133 Investigating genome wide dna methylation in airway and parenchymal fibroblasts from healthy individuals and individuals with copd.

P238 Investigating genome wide dna methylation in airway smooth muscle cells from asthmatic and non-asthmatic donors (2016)
Presentation / Conference Contribution
Clifford, R. L., Patel, J., Shaw, D., Knox, A., & Kobor, M. P238 Investigating genome wide dna methylation in airway smooth muscle cells from asthmatic and non-asthmatic donors

Rationale: Genetic mechanisms fail to fully explain asthma pathogenesis and environmental factors are considered to play an important role. Environmental factors may lead to permanent changes in epigenetic patterns and contribute to asthma. Epigeneti... Read More about P238 Investigating genome wide dna methylation in airway smooth muscle cells from asthmatic and non-asthmatic donors.

The role of histone arginine methylation in gene expression of airway smooth muscle cells in asthma (2016)
Journal Article
Kaczmarek, K., Clifford, R. L., Patel, J., Shaw, D., Dowden, J., & Knox, A. (2016). The role of histone arginine methylation in gene expression of airway smooth muscle cells in asthma. Thorax, 71(Suppl3), A214-A215. https://doi.org/10.1136/thoraxjnl-2016-209333.379

Introduction and objectives: Asthma is estimated to affect at least 300 million people globally. About 25% of the patients do not respond to therapy; therefore we need to develop novel treatments. ASM cells have a crucial role in asthma, contributing... Read More about The role of histone arginine methylation in gene expression of airway smooth muscle cells in asthma.

S53 Effect of epigenetic inhibitors on lung fibroblast phenotype change in idiopathic pulmonary fibrosis (2016)
Journal Article
Pasini, A., Brand, O. J., Jenkins, G., Knox, A. J., & Pang, L. (2016). S53 Effect of epigenetic inhibitors on lung fibroblast phenotype change in idiopathic pulmonary fibrosis. Thorax, 71(Suppl 3), A32.1-A32. https://doi.org/10.1136/thoraxjnl-2016-209333.59

Introduction and objectives:

Idiopathic Pulmonary Fibrosis (IFP) is a fatal interstitial lung disease with unknown aetiology. Lung myofibroblasts (activated fibrobalsts) are the major effector cells in the pathogenesis of IPF. Transforming growth... Read More about S53 Effect of epigenetic inhibitors on lung fibroblast phenotype change in idiopathic pulmonary fibrosis.

Suberanilohydroxamic acid (SAHA) inhibits collagen deposition in a transforming growth factor β1-driven precision cut lung slice (PCLS) model of pulmonary fibrosis (2016)
Presentation / Conference Contribution
Brand, O. J., Pasini, A., Habgood, A., Knox, A. J., Jenkins, G., & Pang, L. Suberanilohydroxamic acid (SAHA) inhibits collagen deposition in a transforming growth factor β1-driven precision cut lung slice (PCLS) model of pulmonary fibrosis. Presented at British Thoracic Society Winter Meeting 2016

Introduction and Objectives: Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive interstitial lung disease that is refractory to current treatment options. Transforming growth factor (TGF)-β1 is a key pro-fibrotic cytokine that plays a cruc... Read More about Suberanilohydroxamic acid (SAHA) inhibits collagen deposition in a transforming growth factor β1-driven precision cut lung slice (PCLS) model of pulmonary fibrosis.

Genome-wide association studies in asthma (2016)
Journal Article
Portelli, M. A., & Sayers, I. (in press). Genome-wide association studies in asthma. https://doi.org/10.1002/9780470015902.a0024639

Asthma is a complex respiratory disease, with both genetic and environmental factors contributing to disease susceptibility. Genome-wide association studies (GWAS) have now identified novel risk alleles and loci associated with asthma diagnosis and m... Read More about Genome-wide association studies in asthma.

Loss of epithelial Gq and G11 signaling inhibits TGFβ production but promotes IL-33–mediated macrophage polarization and emphysema (2016)
Journal Article
John, A. E., Wilson, M. R., Habgood, A., Porte, J., Tatler, A. L., Stavrou, A., Miele, G., Jolly, L., Knox, A. J., Takata, M., Offermanns, S., & Jenkins, R. G. (2016). Loss of epithelial Gq and G11 signaling inhibits TGFβ production but promotes IL-33–mediated macrophage polarization and emphysema. Science Signaling, 9(451), Article ra104. https://doi.org/10.1126/scisignal.aad5568

Heterotrimeric guanine nucleotide–binding protein (G protein) signaling is a ubiquitous signaling system that links hundreds of G protein–coupled receptors (GPCRs) with four G protein signaling pathways. Two of these pathways, one mediated by Gq and... Read More about Loss of epithelial Gq and G11 signaling inhibits TGFβ production but promotes IL-33–mediated macrophage polarization and emphysema.

Diagnostic and prognostic significance of systemic alkyl quinolones for P. aeruginosa in cystic fibrosis: a longitudinal study (2016)
Journal Article
Barr, H. L., Halliday, N., Barrett, D. A., Williams, P., Forrester, D. L., Peckham, D., Williams, K., Smyth, A. R., Honeybourne, D., L. Whitehouse, J., Nash, E. F., Dewar, J., Clayton, A., Knox, A. J., Cámara, M., & Fogarty, A. W. (2017). Diagnostic and prognostic significance of systemic alkyl quinolones for P. aeruginosa in cystic fibrosis: a longitudinal study. Journal of Cystic Fibrosis, 16(2), 230-238. https://doi.org/10.1016/j.jcf.2016.10.005

Background
Pulmonary P. aeruginosa infection is associated with poor outcomes in cystic fibrosis (CF) and early diagnosis is challenging, particularly in those who are unable to expectorate sputum. Specific P. aeruginosa 2-alkyl-4-quinolones are det... Read More about Diagnostic and prognostic significance of systemic alkyl quinolones for P. aeruginosa in cystic fibrosis: a longitudinal study.

U-BIOPRED clinical adult asthma clusters linked to a subset of sputum omics (2016)
Journal Article
Lefaudeux, F., De Meulder, B., Loza, M. J., Peffer, N., Rowe, A., Baribaud, F., Bansal, A. T., Lutter, R., Sousa, A. R., Corfield, J., Pandis, I., Bakke, P. S., Caruso, M., Chanez, P., Dahlén, S.-E., Fleming, L. J., Fowler, S. J., Horvath, I., Krug, N., Montuschi, P., …Chung, K. F. (2017). U-BIOPRED clinical adult asthma clusters linked to a subset of sputum omics. Journal of Allergy and Clinical Immunology, 139(6), https://doi.org/10.1016/j.jaci.2016.08.048

Background: Asthma is a heterogeneous disease in which there is a differential response to asthma treatments. This heterogeneity needs to be evaluated so that a personalized management approach can be provided.
Objectives: We stratified patients wit... Read More about U-BIOPRED clinical adult asthma clusters linked to a subset of sputum omics.

The Ser82 RAGE Variant Affects Lung Function and Serum RAGE in Smokers and sRAGE Production In Vitro (2016)
Journal Article
Miller, S., Henry, A. P., Hodge, E., Kheirallah, A. K., Billington, C. K., Rimington, T. L., Bhaker, S. K., Obeidat, M., Melén, E., Merid, S. K., Swan, C., Gowland, C., Nelson, C. P., Stewart, C. E., Bolton, C. E., Kilty, I., Malarstig, A., Parker, S. G., Moffatt, M. F., Wardlaw, A. J., …Sayers, I. (2016). The Ser82 RAGE Variant Affects Lung Function and Serum RAGE in Smokers and sRAGE Production In Vitro. PLoS ONE, 11(10), Article e0164041. https://doi.org/10.1371/journal.pone.0164041

Introduction

Genome-Wide Association Studies have identified associations between lung function measures and Chronic Obstructive Pulmonary Disease (COPD) and chromosome region 6p21 containing the gene for the Advanced Glycation End Product Recepto... Read More about The Ser82 RAGE Variant Affects Lung Function and Serum RAGE in Smokers and sRAGE Production In Vitro.

FourFold Asthma Study (FAST): a study protocol for a randomised controlled trial evaluating the clinical cost-effectiveness of temporarily quadrupling the dose of inhaled steroid to prevent asthma exacerbations (2016)
Journal Article
Skeggs, A., McKeever, T. M., Duley, L., Mitchell, E., Bradshaw, L., Mortimer, K., Walker, S., Parrott, S., Wilson, A., Pavord, I., Brightling, C., Thomas, M., Price, D., Devereux, G., Higgins, B., Harrison, T. W., & Haydock, R. (2016). FourFold Asthma Study (FAST): a study protocol for a randomised controlled trial evaluating the clinical cost-effectiveness of temporarily quadrupling the dose of inhaled steroid to prevent asthma exacerbations. Trials, 17, https://doi.org/10.1186/s13063-016-1608-6

BACKGROUND: Asthma is one of the commonest chronic diseases in the UK. Acute exacerbations of asthma are unpredictable, disruptive and frightening. They cause considerable morbidity and account for a large component of the health service costs of ast... Read More about FourFold Asthma Study (FAST): a study protocol for a randomised controlled trial evaluating the clinical cost-effectiveness of temporarily quadrupling the dose of inhaled steroid to prevent asthma exacerbations.