Browsing by Author "Bradding, Peter"
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Item Metadata only Enabling Adults With Severe Asthma to Exercise: A Qualitative Examination of the Challenges for Patients and Health Care Professionals(Elsevier, 2023-07-13) Apps, Lindsay D.; Chantrell, Stacey; Majd, Sally; Eglinton, Elizabeth; Singh, Sally J.; Murphy, Anna C.; Green, Ruth H.; Hudson, Nicky; Bradding, Peter; Evans, Rachael A.Background Adults living with severe asthma have lower physical activity levels, particularly high-intensity physical activity, compared with their healthy peers. Physical inactivity is associated with increased morbidity and mortality. Objective To understand patient and health care professional attitudes toward exercise and physical activity to inform future strategies for the improvement of healthy lifestyle behaviors, including exercise. Methods Participants recruited from a specialist difficult asthma service were interviewed individually, and health care professionals (HCPs) from primary care, secondary care, and a tertiary center were invited to attend focus groups. Interviews and focus groups were transcribed verbatim. We performed thematic analysis on interviews and focus groups separately, followed by an adapted framework analysis to analyze datasets together. Results Twenty-nine people with severe asthma participated in a semi-structured interview. A total of 51 HCPs took part in eight focus groups across the East Midlands, United Kingdom. Final analysis resulted in three major themes: barriers to exercise and exercise counseling - in which patients and HCPs identified disease and non-disease factors affecting those living with severe asthma; attitudes toward HCP support for exercise - highlighting education needs for HCPs and preference for supervised exercise programs; and areas for system improvement in supporting patients and HCPs - challenges exist across health sectors that limit patient support are described. Conclusions Patients identified the important role of HCPs in supporting and advising on lifestyle change. Despite a preference for supervised exercise programs, both patient and HCP barriers existed. To meet patients’ varied support needs, improved integration of services is required and HCP skills need extending.Item Open Access Orai/CRACM1 and KCa3.1 ion channels interact(BioMed Central, 2015-07-16) Duffy, S Mark; Ashmole, I.; Smallwood, Dawn T.; Leyland, Mark L.; Bradding, PeterBACKGROUND: Orai/CRACM1 ion channels provide the major Ca(2+) influx pathway for FcεRI-dependent human lung mast cell (HLMC) mediator release. The Ca(2+)-activated K(+) channel KCa3.1 modulates Ca(2+) influx and the secretory response through hyperpolarisation of the plasma membrane. We hypothesised that there is a close functional and spatiotemporal interaction between these Ca(2+)- and K(+)-selective channels. RESULTS: Activation of FcεRI-dependent HLMC KCa3.1 currents was dependent on the presence of extracellular Ca(2+), and attenuated in the presence of the selective Orai blocker GSK-7975A. Currents elicited by the KCa3.1 opener 1-EBIO were also attenuated by GSK-7975A. The Orai1 E106Q dominant-negative mutant ablated 1-EBIO and FcεRI-dependent KCa3.1 currents in HLMCs. Orai1 but not Orai2 was shown to co-immunoprecipitate with KCa3.1 when overexpressed in HEK293 cells, and Orai1 and KCa3.1 were seen to co-localise in the HEK293 plasma membrane using confocal microscopy. CONCLUSION: KCa3.1 activation in HLMCs is highly dependent on Ca(2+) influx through Orai1 channels, mediated via a close spatiotemporal interaction between the two channels.Item Open Access Patient perceptions of living with severe asthma: Challenges to effective management(JACI in Practice, 2019-06-06) Apps, Lindsay D.; Chantrell, Stacey; Majd, Sally; Eglinton, Elizabeth; Singh, Sally J.; Murphy, Anna C.; Bradding, Peter; Green, Ruth H.; Hudson, Nicky; Evans, Rachael A.Background: The management of severe asthma poses many challenges related to treatment, adherence and psychosocial morbidity. There is little direct data from the patient perspective to understand and negotiate the complexities of managing severe asthma Objective: To explore the patient perceptions of living with severe asthma and the experience of managing severe asthma, in order to better understand the support that might promote more effective self-management for severe asthma. Methods: Participants were recruited from a specialist Difficult Asthma Service. Semi-structured interviews were conducted by researchers independent of the patient’s care. Interviews were transcribed verbatim and inductive Thematic Analysis was performed. Results: Twenty-nine participants [13 male, mean (SD) age 49.5 (13.6) years, mean Asthma Control Questionnaire 2.2 (1.2)] participated in an interview. Analysis resulted in four major themes describing the experience and challenges to managing severe asthma: Understanding of severe asthma, emotional impact of living with severe asthma (sub-theme: fear of hospitalisation), public perceptions of asthma, and concerns about medications. Conclusion: Healthcare professionals need to consider and discuss with patients their perceptions of severe asthma and the relevant treatments; particular attention should focus around education of disease control and actively exploring thoughts around hospitalisation. Our data highlights the potential for psychological and social support to enhance self-management by directly addressing the wide-ranging individual challenges patients face. There is also a need for greater public awareness and education about severe asthma to minimise patient distress particularly in the work environment.Item Open Access Protocol for a feasibility study to inform the development of a multi centre randomised controlled trial of asthma-tailored pulmonary rehabilitation versus usual care for individuals with severe asthma(BMJ, 2016-03-23) Majd, S.; Apps, L. D.; Hudson, Nicky; Hewitt, S.; Eglinton, E.; Murphy, Anna C.; Bradding, Peter; Singh, S.; Green, R.; Evans, R.Introduction: Pulmonary rehabilitation with core components of exercise training and multiprofessional education is an integral part of the management of patients with chronic lung disease. International guidelines for individuals with asthma recommend exercise as exercise improves symptoms, indices of cardiopulmonary efficiency, health status and psychosocial outcome. However, there is little published evidence evaluating safety and acceptability of exercise training for individuals with severe asthma and there are concerns regarding exercise-induced asthma. We propose a feasibility study for a multicentre randomised controlled trial (RCT) of asthma-tailored pulmonary rehabilitation (asthma- tailored PR) versus usual care in individuals with severe asthma. Methods and analysis: The study will be conducted in three stages. Adults with severe asthma will be included if they have persistent symptoms despite being at step 4 or 5 of the British Thoracic Society guidelines. Stage 1: semistructured interviews will be used in a sample of 20–30 individuals with severe asthma to understand the experience and attitudes of this population towards exercise. Stage 2: eight focus groups of at least six healthcare professionals involved in the care of patients with severe asthma will be conducted to understand their attitudes towards exercise for this population. Stage 3: a small-scale RCT of the proposed multicentre RCT of asthma- tailored PR versus usual care for individuals with severe asthma will be conducted. The primary outcome measures will be recruitment, retention and adverse event rates. Semistructured interviews with participants of stage 3 will be used to identify further barriers or facilitators to participation in PR and the trial. Thematic analysis will be used for the interpretation of all interviews. Ethics and dissemination: The study results will inform the design of a larger multicentre RCT. TheNational Research Ethics Service Committee East Midland approved the study protocol.Item Open Access Tensin1 expression and function in chronic obstructive pulmonary disease(Springer Nature, 2019-12-12) Stylianou, P.; Clark, K.; Gooptu, B.; Smallwood, Dawn T.; Brightling, C. E.; Amrani, Y.; Roach, K.M.; Bradding, PeterChronic obstructive pulmonary disease (COPD) constitutes a major cause of morbidity and mortality. Genome wide association studies have shown significant associations between airflow obstruction or COPD with a non-synonymous SNP in the TNS1 gene, which encodes tensin1. However, the expression, cellular distribution and function of tensin1 in human airway tissue and cells are unknown. We therefore examined these characteristics in tissue and cells from controls and people with COPD or asthma. Airway tissue was immunostained for tensin1. Tensin1 expression in cultured human airway smooth muscle cells (HASMCs) was evaluated using qRT-PCR, western blotting and immunofluorescent staining. siRNAs were used to downregulate tensin1 expression. Tensin1 expression was increased in the airway smooth muscle and lamina propria in COPD tissue, but not asthma, when compared to controls. Tensin1 was expressed in HASMCs and upregulated by TGFβ1. TGFβ1 and fibronectin increased the localisation of tensin1 to fibrillar adhesions. Tensin1 and α-smooth muscle actin (αSMA) were strongly co-localised, and tensin1 depletion in HASMCs attenuated both αSMA expression and contraction of collagen gels. In summary, tensin1 expression is increased in COPD airways, and may promote airway obstruction by enhancing the expression of contractile proteins and their localisation to stress fibres in HASMCs.