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A low exhaled nitric oxide level excludes a short-term benefit from inhaled corticosteroids in suspected asthma: A randomized placebo-controlled trial (2021)
Journal Article
Shaw, D., Martin, M. J., Sutherland, L., Shaw, K., Parrish, C., Singleton, N., …Harrison, T. (2021). A low exhaled nitric oxide level excludes a short-term benefit from inhaled corticosteroids in suspected asthma: A randomized placebo-controlled trial. Respirology, 26(7), 666-672. https://doi.org/10.1111/resp.14055

Background and objective: Fractional exhaled nitric oxide (FeNO) is a non-invasive biomarker that reflects IL-4/IL-13 production and therefore represents T2 allergic inflammation. FeNO has previously been used to guide inhaled corticosteroid (ICS) tr... Read More about A low exhaled nitric oxide level excludes a short-term benefit from inhaled corticosteroids in suspected asthma: A randomized placebo-controlled trial.

Array-based measurements of aero-allergen-specific IgE correlate with skin-prick test reactivity in asthma regardless of specific IgG4 or total IgE measurements (2021)
Journal Article
Hamed, A., Todd, I., Tighe, P. J., Powell, R. J., Harrison, T., & Fairclough, L. (2021). Array-based measurements of aero-allergen-specific IgE correlate with skin-prick test reactivity in asthma regardless of specific IgG4 or total IgE measurements. Journal of Immunological Methods, 492, Article 112999. https://doi.org/10.1016/j.jim.2021.112999

© 2021 Elsevier B.V. Skin prick testing (SPT) and measurement of serum allergen-specific IgE (sIgE) are used to investigate asthma and other allergic conditions. Measurement of serum total IgE (tIgE) and allergen-specific IgG4 (sIgG4) may also be use... Read More about Array-based measurements of aero-allergen-specific IgE correlate with skin-prick test reactivity in asthma regardless of specific IgG4 or total IgE measurements.

Composite type-2 biomarker strategy versus a symptom–risk-based algorithm to adjust corticosteroid dose in patients with severe asthma: a multicentre, single-blind, parallel group, randomised controlled trial (2020)
Journal Article
Heaney, L. G., Busby, J., Hanratty, C. E., Djukanovic, R., Woodcock, A., Walker, S. M., …Yang, F. (2021). Composite type-2 biomarker strategy versus a symptom–risk-based algorithm to adjust corticosteroid dose in patients with severe asthma: a multicentre, single-blind, parallel group, randomised controlled trial. Lancet Respiratory Medicine, 9(1), 57-68. https://doi.org/10.1016/s2213-2600%2820%2930397-0

Background Asthma treatment guidelines recommend increasing corticosteroid dose to control symptoms and reduce exacerbations. This approach is potentially flawed because symptomatic asthma can occur without corticosteroid responsive type-2 (T2)-driv... Read More about Composite type-2 biomarker strategy versus a symptom–risk-based algorithm to adjust corticosteroid dose in patients with severe asthma: a multicentre, single-blind, parallel group, randomised controlled trial.

Predictive value of blood eosinophils and exhaled nitric oxide in adults with mild asthma: a prespecified subgroup analysis of an open-label, parallel-group, randomised controlled trial (2020)
Journal Article
Pavord, I. D., Holliday, M., Reddel, H. K., Braithwaite, I., Ebmeier, S., Hancox, R. J., …Toelle, B. (2020). Predictive value of blood eosinophils and exhaled nitric oxide in adults with mild asthma: a prespecified subgroup analysis of an open-label, parallel-group, randomised controlled trial. Lancet Respiratory Medicine, 8(7), 671-680. https://doi.org/10.1016/s2213-2600%2820%2930053-9

Background Whether blood eosinophil counts and exhaled nitric oxide (FeNO) are associated with important outcomes in mild asthma is unclear. In this prespecified subgroup analysis of a previously published open-label clinical trial, we aimed to asse... Read More about Predictive value of blood eosinophils and exhaled nitric oxide in adults with mild asthma: a prespecified subgroup analysis of an open-label, parallel-group, randomised controlled trial.

Controlled Trial of Budesonide–Formoterol as Needed for Mild Asthma (2019)
Journal Article
Beasley, R., Holliday, M., Reddel, H. K., Braithwaite, I., Ebmeier, S., Hancox, R. J., …Weatherall, M. (2019). Controlled Trial of Budesonide–Formoterol as Needed for Mild Asthma. New England Journal of Medicine, 380(21), 1-11. https://doi.org/10.1056/nejmoa1901963

BACKGROUND In double-blind, placebo-controlled trials, budesonide–formoterol used on an as-needed basis resulted in a lower risk of severe exacerbation of asthma than as-needed use of a short-acting β2-agonist (SABA); the risk was similar to that of... Read More about Controlled Trial of Budesonide–Formoterol as Needed for Mild Asthma.

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 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.

Autoantibodies of IgM and IgG classes show differences in recognition of multiple autoantigens in chronic obstructive pulmonary disease (2017)
Journal Article
Shindi, R., Al-Mehairi, A., Negm, O. H., Kalsheker, N., Gale, N., Shale, D. J., …Fairclough, L. C. (2017). Autoantibodies of IgM and IgG classes show differences in recognition of multiple autoantigens in chronic obstructive pulmonary disease. Clinical Immunology, 183, https://doi.org/10.1016/j.clim.2017.09.020

Autoimmunity occurs in chronic obstructive pulmonary disease (COPD). We describe an antigen microarray for detecting serum autoantibodies (AAbs) to determine how IgM, as well as IgG, AAbs distinguish patients with COPD from controls with a history of... Read More about Autoantibodies of IgM and IgG classes show differences in recognition of multiple autoantigens in chronic obstructive pulmonary disease.

Peripheral killer cells do not differentiate between asthma patients with or without fixed airway obstruction (2016)
Journal Article
Tubby, C., Negm, O. H., Harrison, T. W., Tighe, P. J., Todd, I., & Fairclough, L. C. (2017). Peripheral killer cells do not differentiate between asthma patients with or without fixed airway obstruction. Journal of Asthma, 54(5), 456-466. https://doi.org/10.1080/02770903.2016.1236941

Objective: The three main types of killer cells – CD8+ T cells, NK cells and NKT cells – have been linked to asthma and chronic obstructive pulmonary disease (COPD). However, their role in a small subset of asthma patients displaying fixed airway obs... Read More about Peripheral killer cells do not differentiate between asthma patients with or without fixed airway obstruction.

MMP-1 activation contributes to airway smooth muscle growth and asthma severity (2016)
Journal Article
Naveed, S., Clements, D., Jackson, D. J., Philp, C., Billington, C. K., Soomro, I. N., …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.

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., …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.

The differential effects of azithromycin on the airway epithelium in vitro and in vivo (2016)
Journal Article
Slater, M., Torr, E., Harrison, T. W., Forrester, D. L., Knox, A., Shaw, D. E., & Sayers, I. (2016). The differential effects of azithromycin on the airway epithelium in vitro and in vivo. Physiological Reports, 4(18), 1-15. https://doi.org/10.14814/phy2.12960

Macrolides including azithromycin (AZM) can improve clinical symptoms in asthma regardless of infection status. The mechanisms underlying these benefi- cial effects are yet to be elucidated. The aim of this study was to determine the effect of AZM on... Read More about The differential effects of azithromycin on the airway epithelium in vitro and in vivo.

Azithromycin for Acute Exacerbations of Asthma: the AZALEA randomized clinical trial (2016)
Journal Article
Johnson, S. L., Szigeti, M., Cross, M., Brightling, C., Chaudhuri, R., Harrison, T. W., …Chauhan, A. (2016). Azithromycin for Acute Exacerbations of Asthma: the AZALEA randomized clinical trial. JAMA Internal Medicine, 176(11), https://doi.org/10.1001/jamainternmed.2016.5664

IMPORTANCE Guidelines recommend against antibiotic use to treat asthma attacks. A study with telithromycin reported benefit, but adverse reactions limit its use. OBJECTIVE To determine whether azithromycin added to standard care for asthma attacks i... Read More about Azithromycin for Acute Exacerbations of Asthma: the AZALEA randomized clinical trial.

Assessment of a rapid liquid-based cytology method for measuring sputum cell counts (2016)
Journal Article
Martin, M., Lee, H., Meakin, G., Green, A., Simms, R., Reynolds, C., …Harrison, T. W. (in press). Assessment of a rapid liquid-based cytology method for measuring sputum cell counts. Thorax, https://doi.org/10.1136/thoraxjnl-2016-208817

Differential sputum cell counting is not widely available despite proven clinical utility in the management of asthma. We compared eosinophil counts obtained using liquid-based cytology (LBC), a routine histopathological processing method, and the cu... Read More about Assessment of a rapid liquid-based cytology method for measuring sputum cell counts.

Multiple Circulating Cytokines Are Coelevated in Chronic Obstructive Pulmonary Disease (2016)
Journal Article
Selvarajah, S., Todd, I., Tighe, P. J., John, M., Bolton, C. E., Harrison, T. W., & Fairclough, L. C. (2016). Multiple Circulating Cytokines Are Coelevated in Chronic Obstructive Pulmonary Disease. Mediators of Inflammation, 2016, 1-9. https://doi.org/10.1155/2016/3604842

Inflammatory biomarkers, including cytokines, are associated with COPD, but the association of particular circulating cytokines with systemic pathology remains equivocal. To investigate this, we developed a protein microarray system to detect multipl... Read More about Multiple Circulating Cytokines Are Coelevated in Chronic Obstructive Pulmonary Disease.

Untargeted metabolic profiling of saliva by liquid chromatography-mass spectrometry for the identification of potential diagnostic biomarkers of asthma (2016)
Journal Article
Malkar, A., Wilson, E., Harrison, T., Shaw, D. E., & Creaser, C. (in press). Untargeted metabolic profiling of saliva by liquid chromatography-mass spectrometry for the identification of potential diagnostic biomarkers of asthma. Analytical Methods, 8(27), 5407-5413. https://doi.org/10.1039/C6AY00938G

Current clinical tests employed to diagnose asthma are inaccurate and limited by their invasive nature. New metabolite profiling technologies offer an opportunity to improve asthma diagnosis using non-invasive sampling. A rapid analytical method for... Read More about Untargeted metabolic profiling of saliva by liquid chromatography-mass spectrometry for the identification of potential diagnostic biomarkers of asthma.

The utility of exhaled nitric oxide in patients with suspected asthma (2016)
Journal Article
Martin, M., Wilson, E., Gerrard-Tarpey, W., Meakin, G., Hearson, G., McKeever, T., …Harrison, T. (2016). The utility of exhaled nitric oxide in patients with suspected asthma. Thorax, 71(6), https://doi.org/10.1136/thoraxjnl-2015-208014

The value of FENO measurements in patients with symptoms suggestive of asthma is unclear. We performed an observational study to assess the ability of FENO to diagnose asthma and to predict response to inhaled corticosteroids (ICS). Our findings sugg... Read More about The utility of exhaled nitric oxide in patients with suspected asthma.

The effects of azithromycin in treatment-resistant cough: A randomized, double-blind, placebo-controlled trial (2016)
Journal Article
Hodgson, D., Anderson, J., Reynolds, C., Oborne, J., Meakin, G., Bailey, H., …Harrison, T. (2016). The effects of azithromycin in treatment-resistant cough: A randomized, double-blind, placebo-controlled trial. Chest, 149(4), 1052-1060. https://doi.org/10.1016/j.chest.2015.12.036

Background Chronic cough is a common clinical problem worldwide. Although many patients have underlying precipitating conditions such as asthma, gastroesophageal reflux, or rhinitis, many remain symptomatic despite treating these conditions. New a... Read More about The effects of azithromycin in treatment-resistant cough: A randomized, double-blind, placebo-controlled trial.

Using venous blood gas analysis in the assessment of COPD exacerbations: a prospective cohort study (2015)
Journal Article
McKeever, T. M., Hearson, G., Housley, G., Reynolds, C., Kinnear, W., Harrison, T. W., …Shaw, D. E. (2016). Using venous blood gas analysis in the assessment of COPD exacerbations: a prospective cohort study. Thorax, 71(3), 210-215. https://doi.org/10.1136/thoraxjnl-2015-207573

Introduction: Identifying acute hypercapnic respiratory failure is crucial in the initial management of acute exacerbations of COPD. Guidelines recommend obtaining arterial blood samples but these are more difficult to obtain than venous. We assessed... Read More about Using venous blood gas analysis in the assessment of COPD exacerbations: a prospective cohort study.