ORCID Profile
0000-0003-2252-1248
Current Organisations
Saint Mary's Hospital
,
University of Southampton
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Publisher: Wiley
Date: 21-01-2009
DOI: 10.1111/J.1398-9995.2008.01779.X
Abstract: No study has compared allergic sensitization patterns in infants with atopic eczema from different countries. The aim of this study was to investigate the patterns of allergic sensitization in a cohort of infants with atopic eczema participating in a multicentre, international study. Two thousand one hundred and eighty-four infants (mean age 17.6 months) with atopic eczema from allergic families were screened in 94 centres in 12 countries to participate in a randomized trial for the early prevention of asthma. Clinical history, Severity Scoring of Atopic Dermatitis Index, measurements for total serum IgE and specific IgE antibodies to eight food and inhalant allergens were entered into a database before randomization to treatment. A history of type of feeding in the first weeks of life and exposure to animals was recorded. A total of 52.9% of the infants had raised total IgE, and 55.5% were sensitized to at least one allergen. There was a wide difference in the total IgE values and in the sensitization rates to foods and aeroallergens among infants from different countries. The highest prevalence rates of allergen-sensitized infants were found in Australia (83%), the UK (79%) and Italy (76%). Infants from Belgium and Poland consistently had the lowest sensitization rates. In each country, a characteristic pattern of sensitization was found for aeroallergens (house dust mite > cat > grass pollen > Alternaria), but not for food allergens. In infants with atopic eczema, there is a wide variation in the pattern of allergic sensitization between countries, and data from one country are not necessarily generalizable to other countries.
Publisher: Wiley
Date: 07-01-2020
DOI: 10.1002/PPUL.24630
Abstract: Fractional exhaled nitric oxide (F An in idual patient data analysis was performed using data from seven randomized clinical trials which used F Data were available in 1112 randomized controlled trial participants and ≥1 stable period was present for 665 in iduals. The interquartile range (IQR) and limits of agreement (LoA) for change in absolute F Over a 3-month period where F
Publisher: Wiley
Date: 13-12-2019
DOI: 10.1111/PAI.13177
Abstract: More than 17 million people across Europe have allergies to food and the burden of food allergies is increasing. In 2014, the European Academy of Allergy and Clinical Immunology (EAACI) published guidelines for preventing food allergy. Important research has been published since then and it is essential to ensure the guidelines reflect the latest evidence. A systematic review will be undertaken to help prepare new guidelines due to be published in 2020. Eleven bibliographic databases will be searched from inception to 31 October 2019 for randomized controlled trials about any intervention designed to prevent the development of new cases of immediate-type/IgE-mediated food allergy in infants, children and adults. There are few randomized controlled trials about the impact of breastfeeding on food allergy so prospective cohort studies about breastfeeding with at least 1000 participants at general risk or 200 at high risk of food allergy will also be eligible. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach will be used to assess the certainty of the evidence and tabulate summary data. The risk of bias in in idual trials will be assessed using the Cochrane risk of bias tool. All data extraction and quality appraisal will be undertaken independently by two reviewers in partnership with a taskforce of EAACI members. Preventing food allergy has the potential to improve personal well-being and reduce societal healthcare costs. It is important that forthcoming European guidelines take the latest research into account. Past reviews have tended to focus on single interventions or combined food allergy with other outcomes, making it difficult to draw robust conclusions about potential impacts for policy and practice.
Publisher: Wiley
Date: 29-03-2021
DOI: 10.1111/PAI.13496
Abstract: This guideline from the European Academy of Allergy and Clinical Immunology (EAACI) recommends approaches to prevent the development of immediate‐onset / IgE‐mediated food allergy in infants and young children. It is an update of a 2014 EAACI guideline. The guideline was developed using the AGREE II framework and the GRADE approach. An international Task Force with representatives from 11 countries and different disciplinary and clinical backgrounds systematically reviewed research and considered expert opinion. Recommendations were created by weighing up benefits and harms, considering the certainty of evidence and examining values, preferences and resource implications. The guideline was peer‐reviewed by external experts, and feedback was incorporated from public consultation. All of the recommendations about preventing food allergy relate to infants (up to 1 year) and young children (up to 5 years), regardless of risk of allergy. There was insufficient evidence about preventing food allergy in other age groups. The EAACI Task Force suggests avoiding the use of regular cow's milk formula as supplementary feed for breastfed infants in the first week of life. The EAACI Task Force suggests introducing well‐cooked, but not raw egg or uncooked pasteurized, egg into the infant diet as part of complementary feeding. In populations where there is a high prevalence of peanut allergy, the EAACI Task Force suggests introducing peanuts in an age‐appropriate form as part of complementary feeding. According to the studies, it appears that the most effective age to introduce egg and peanut is from four to 6 months of life. The EAACI Task Force suggests against the following for preventing food allergy: (i) avoiding dietary food allergens during pregnancy or breastfeeding and (ii) using soy protein formula in the first 6 months of life as a means of preventing food allergy. There is no recommendation for or against the following: use of vitamin supplements, fish oil, prebiotics, probiotics or synbiotics in pregnancy, when breastfeeding or in infancy altering the duration of exclusive breastfeeding and hydrolysed infant formulas, regular cow's milk–based infant formula after a week of age or use of emollients. Key changes from the 2014 guideline include suggesting (i) the introduction of peanut and well‐cooked egg as part of complementary feeding (moderate certainty of evidence) and (ii) avoiding supplementation with regular cow's milk formula in the first week of life (low certainty of evidence). There remains uncertainty in how to prevent food allergy, and further well‐powered, multinational research using robust diagnostic criteria is needed.
Publisher: European Respiratory Society (ERS)
Date: 13-10-2022
DOI: 10.1183/13993003.00606-2022
Abstract: Effectiveness studies with biological therapies for asthma lack standardised outcome measures. The COMSA (Core Outcome Measures sets for paediatric and adult Severe Asthma) Working Group sought to develop Core Outcome Measures (COM) sets to facilitate better synthesis of data and appraisal of biologics in paediatric and adult asthma clinical studies. COMSA utilised a multi-stakeholder consensus process among patients with severe asthma, adult and paediatric clinicians, pharmaceutical representatives, and health regulators from across Europe. Evidence included a systematic review of development, validity and reliability of selected outcome measures plus a narrative review and a pan-European survey to better understand patients’ and carers’ views about outcome measures. It was discussed using a modified GRADE (Grading of Recommendations Assessment, Development and Evaluation) Evidence to Decision framework. Anonymous voting was conducted using predefined consensus criteria. Both adult and paediatric COM sets include forced expiratory volume in 1 s (FEV 1 ) as z-scores, annual frequency of severe exacerbations and maintenance oral corticosteroid use. Additionally, the paediatric COM set includes the Paediatric Asthma Quality of Life Questionnaire and Asthma Control Test or Childhood Asthma Control Test, while the adult COM set includes the Severe Asthma Questionnaire and Asthma Control Questionnaire-6 (symptoms and rescue medication use reported separately). This patient-centred collaboration has produced two COM sets for paediatric and adult severe asthma. It is expected that they will inform the methodology of future clinical trials, enhance comparability of efficacy and effectiveness of biological therapies, and help assess their socioeconomic value. COMSA will inform definitions of non-response and response to biological therapy for severe asthma.
Publisher: European Respiratory Society (ERS)
Date: 26-01-2023
DOI: 10.1183/23120541.00444-2022
Abstract: Biologics have proven efficacy for patients with severe asthma but there is lack of consensus on defining response. We systematically reviewed and appraised methodologically developed, defined and evaluated definitions of non-response and response to biologics for severe asthma. We searched four bibliographic databases from inception to 15 March 2021 . Two reviewers screened references, extracted data, and assessed methodological quality of development, measurement properties of outcome measures and definitions of response based on COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN). A modified GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach and narrative synthesis were undertaken. 13 studies reported three composite outcome measures, three asthma symptoms measures, one asthma control measure and one quality of life measure. Only four measures were developed with patient input none were composite measures. Studies utilised 17 definitions of response: 10 out of 17 (58.8%) were based on minimal clinically important difference (MCID) or minimal important difference (MID) and 16 out of 17 (94.1%) had high-quality evidence. Results were limited by poor methodology for the development process and incomplete reporting of psychometric properties. Most measures rated “very low” to “low” for quality of measurement properties and none met all quality standards. This is the first review to synthesise evidence about definitions of response to biologics for severe asthma. While high-quality definitions are available, most are MCIDs or MIDs, which may be insufficient to justify continuation of biologics in terms of cost-effectiveness. There remains an unmet need for universally accepted, patient-centred, composite definitions to aid clinical decision making and comparability of responses to biologics.
Publisher: European Respiratory Society (ERS)
Date: 10-2021
Publisher: American Thoracic Society
Date: 15-04-2022
Publisher: Elsevier BV
Date: 08-2015
DOI: 10.1016/J.JACI.2015.06.001
Abstract: The purpose of this brief communication is to highlight emerging evidence to existing guidelines regarding potential benefits of supporting early, rather than delayed, peanut introduction during the period of complementary food introduction in infants. This document should be considered as interim guidance based on consensus among the following organizations: American Academy of Allergy, Asthma & Immunology, American Academy of Pediatrics, American College of Allergy, Asthma & Immunology, Australasian Society of Clinical Immunology and Allergy, Canadian Society of Allergy and Clinical Immunology, European Academy of Allergy and Clinical Immunology, Israel Association of Allergy and Clinical Immunology, Japanese Society for Allergology, Society for Pediatric Dermatology, and World Allergy Organization. More formal guidelines regarding early-life, complementary feeding practices and the risk of allergy development will follow in the next year from the National Institute of Allergy and Infectious Diseases-sponsored Working Group and the European Academy of Allergy and Clinical Immunology.
Publisher: F1000 Research Ltd
Date: 17-05-2018
DOI: 10.12688/WELLCOMEOPENRES.14489.1
Abstract: Background. Childhood asthma is a common complex condition whose aetiology is thought to involve gene-environment interactions in early life occurring at the airway epithelium, associated with immune dysmaturation. It is not clear if abnormal airway epithelium cell (AEC) and cellular immune system functions associated with asthma are primary or secondary. To explore this, we will (i) recruit a birth cohort and observe the evolution of respiratory symptoms (ii) recruit children with and without asthma symptoms and (iii) use existing data from children in established STELAR birth cohorts. Novel pathways identified in the birth cohort will be sought in the children with established disease. Our over-arching hypothesis is that epithelium function is abnormal at birth in babies who subsequently develop asthma and progression is driven by abnormal interactions between the epithelium, genetic factors, the developing immune system, and the microbiome in the first years of life. Methods. One thousand babies will be recruited and nasal AEC collected at 5-10 days after birth for culture. Transcriptomes in AEC and blood leukocytes and the upper airway microbiome will be determined in babies and again at one and three years of age. In a subset of 100 in iduals, AEC transcriptomes and microbiomes will also be assessed at three and six months. In iduals will be assigned a wheeze category at age three years. In a cross sectional study, 300 asthmatic and healthy children aged 1 to 16 years will have nasal and bronchial AEC collected for culture and transcriptome analysis, leukocyte transcriptome analysis, and upper and lower airway microbiomes ascertained. Genetic variants associated with asthma symptoms will be confirmed in the STELAR cohorts. Conclusions. This study is the first to comprehensively study the temporal relationship between aberrant AEC and immune cell function and asthma symptoms in the context of early gene-microbiome interactions.
Publisher: Springer Science and Business Media LLC
Date: 08-02-2021
DOI: 10.1186/S12931-021-01642-X
Abstract: An amendment to this paper has been published and can be accessed via the original article.
Publisher: Wiley
Date: 23-10-2021
DOI: 10.1111/ALL.14422
Abstract: Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.
Publisher: Elsevier BV
Date: 08-2022
Publisher: Wiley
Date: 25-09-2015
DOI: 10.1111/ALL.12687
Publisher: American Thoracic Society
Date: 12-2022
Publisher: Elsevier BV
Date: 2020
DOI: 10.1016/J.JACI.2019.06.049
Abstract: The selection of pharmacotherapy for patients with allergic rhinitis aims to control the disease and depends on many factors. Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines have considerably improved the treatment of allergic rhinitis. However, there is an increasing trend toward use of real-world evidence to inform clinical practice, especially because randomized controlled trials are often limited with regard to the applicability of results. The Contre les Maladies Chroniques pour un Vieillissement Actif (MACVIA) algorithm has proposed an allergic rhinitis treatment by a consensus group. This simple algorithm can be used to step up or step down allergic rhinitis treatment. Next-generation guidelines for the pharmacologic treatment of allergic rhinitis were developed by using existing GRADE-based guidelines for the disease, real-world evidence provided by mobile technology, and additive studies (allergen chamber studies) to refine the MACVIA algorithm.
Publisher: Wiley
Date: 12-2019
DOI: 10.1111/CEA.13516
Abstract: Food allergy affects a small but important number of children and adults. Much of the morbidity associated with food allergy is driven by the fear of a severe reaction and fatalities continue to occur. Foods are the commonest cause of anaphylaxis. One of the aims of the European Union-funded Integrated Approaches to Food Allergen and Allergy Risk Management (iFAAM) project was to improve the identification and management of children and adults at risk of experiencing a severe reaction. A number of interconnected studies within the project have focused on quantifying the severity of allergic reactions the impact of food matrix, immunological factors on severity of reactions the impact of co-factors such as medications on the severity of reactions utilizing single-dose challenges to understand threshold and severity of reactions and community studies to understand the experience of patients suffering real-life allergic reactions to food. Associated studies have examined population thresholds and co-factors such as exercise and stress. This paper summarizes two workshops focused on the severity of allergic reactions to food. It outlines the related studies being undertaken in the project indicating how they are likely to impact on our ability to identify in iduals at risk of severe reactions and improve their management.
Publisher: Wiley
Date: 06-08-2020
DOI: 10.1111/PAI.13303
Publisher: American Thoracic Society
Date: 15-02-2022
Publisher: Wiley
Date: 10-09-2015
DOI: 10.1111/PDE.12685
Abstract: The purpose of this brief communication is to highlight emerging evidence regarding potential benefits of supporting early rather than delayed peanut introduction during the period of complementary food introduction in infants. This document should be considered as interim guidance based on consensus among the following organizations: American Academy of Allergy, Asthma, and Immunology, American Academy of Pediatrics, American College of Allergy, Asthma, and Immunology, Australasian Society of Clinical Immunology and Allergy, Canadian Society of Allergy and Clinical Immunology, European Academy of Allergy and Clinical Immunology, Israel Association of Allergy and Clinical Immunology, Japanese Society for Allergology, Society for Pediatric Dermatology, and World Allergy Organization. More formal guidelines regarding early-life, complementary feeding practices and the risk of allergy development will follow in the next year from the National Institute of Allergy and Infectious Diseases-sponsored Working Group and the European Academy of Allergy and Clinical Immunology.
Publisher: Wiley
Date: 24-11-2020
DOI: 10.1002/PPUL.25171
Publisher: European Respiratory Society (ERS)
Date: 12-03-2020
DOI: 10.1183/13993003.01879-2019
Abstract: Exhaled nitric oxide fraction ( F ENO ), a biomarker of eosinophilic airway inflammation, may be useful to guide asthma treatment. F ENO -guided treatment may be more effective in certain subgroups for improving asthma outcomes compared to standard treatment. An in idual patient data analysis was performed using data from seven randomised clinical trials (RCTs) which used F ENO to guide asthma treatment. The incidence of an asthma exacerbation and loss of control, and the time to first exacerbation and loss of control were described between five subgroups of RCT participants. Data were available in 1112 RCT participants. Among those not treated with leukotriene receptor antagonists (LTRA), but not among those who were treated with LTRA, F ENO -guided treatment was associated with reduced exacerbation risk (OR 0.68, 95% CI 0.49–0.94), longer time to first exacerbation (hazard ratio (HR) 0.76, 95% CI 0.57–0.99) and borderline reduced risk for loss of control (OR 0.70, 95% CI 0.49–1.00). Nonobese children, compared to obese children, were less likely to lose asthma control when treatment was guided by F ENO (OR 0.69, 95% CI 0.48–0.99) and time to loss of control was longer (HR 0.77, 95% CI 0.61–0.99). Asthma treatment guided by F ENO may be more effective in achieving better asthma outcomes for patients who are not treated with LTRA and who are not obese, compared to standard practice.
Publisher: Dustri-Verlgag Dr. Karl Feistle
Date: 09-2019
DOI: 10.5414/ALX02096
Publisher: Stichting Nase
Date: 12-2020
DOI: 10.4193/RHIN20.246
Publisher: Wiley
Date: 03-04-2014
DOI: 10.1111/ALL.12398
Abstract: Food allergy can have significant effects on morbidity and quality of life and can be costly in terms of medical visits and treatments. There is therefore considerable interest in generating efficient approaches that may reduce the risk of developing food allergy. This guideline has been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Taskforce on Prevention and is part of the EAACI Guidelines for Food Allergy and Anaphylaxis. It aims to provide evidence-based recommendations for primary prevention of food allergy. A wide range of antenatal, perinatal, neonatal, and childhood strategies were identified and their effectiveness assessed and synthesized in a systematic review. Based on this evidence, families can be provided with evidence-based advice about preventing food allergy, particularly for infants at high risk for development of allergic disease. The advice for all mothers includes a normal diet without restrictions during pregnancy and lactation. For all infants, exclusive breastfeeding is recommended for at least first 4-6 months of life. If breastfeeding is insufficient or not possible, infants at high-risk can be recommended a hypoallergenic formula with a documented preventive effect for the first 4 months. There is no need to avoid introducing complementary foods beyond 4 months, and currently, the evidence does not justify recommendations about either withholding or encouraging exposure to potentially allergenic foods after 4 months once weaning has commenced, irrespective of atopic heredity. There is no evidence to support the use of prebiotics or probiotics for food allergy prevention.
Publisher: Wiley
Date: 10-10-2023
DOI: 10.1111/ALL.15902
Publisher: European Respiratory Society
Date: 15-09-2018
Publisher: European Respiratory Society
Date: 15-09-2018
Publisher: Wiley
Date: 19-12-2011
DOI: 10.1111/J.1365-2222.2011.03912.X
Abstract: Although adrenaline is recommended as first line treatment for anaphylaxis, it is often not utilized. There has been a debate about when adrenaline autoinjectors should be prescribed and how many should be dispensed. To see how many adrenaline autoinjectors were used during anaphylactic reactions and to determine why they were not used in situations where they were clinically indicated. Patients were recruited prospectively at 14 paediatric allergy clinics throughout UK. Participants completed a questionnaire covering demographic data, atopic status and details of allergic reactions in the previous year and reasons for using more than one device. A total of 969 patients were recruited of whom 466 (48.1%, 95% CI: 37.9-58.2) had had at least one reaction in the previous year 245 (25.3%, 95% CI: 16.2-34.4) of these reactions were anaphylaxis. An adrenaline autoinjector was used by 41 (16.7%, 95% CI: 11.7-21.3) participants experiencing anaphylaxis. Thirteen participants received more than one dose of adrenaline, for nine of these a health professional gave at least one. The commonest reasons for using more than one were severe breathing difficulties (40%), lack of improvement with first dose (20%) and miss-firing (13.3%). The commonest reasons for not using adrenaline in anaphylaxis were 'thought adrenaline unnecessary' (54.4%) and 'unsure adrenaline necessary' (19.1%). Many with wheeze did not use their autoinjector. Adrenaline is used by only a minority of patients experiencing anaphylaxis in the community. Thirteen of the 41 patients with anaphylaxis who used their autoinjector needed another dose of adrenaline. Further research is needed to consider how to best encourage the usage of adrenaline when clinically indicated in anaphylaxis.
Publisher: Wiley
Date: 20-01-2022
DOI: 10.1002/ASE.2137
Abstract: The transition from secondary to tertiary education can be challenging, as students must adapt to independent learning. For students in the allied health and nursing disciplines, this transition may coincide with compulsory first-year courses in anatomy, which are traditionally difficult to master. Students' agency-their capacity to make intentional choices to alter the path of their learning-may play a role in their successful completion of first-year anatomy courses. This study aimed to develop a measure for agency and to determine whether agency is associated with academic achievement. First-year students (n = 131) completed open-ended questions measuring each aspect of agency. Student responses were quantified using rubrics and then combined to create an overall agency score. Three factors of agency were determined: action, metacognition, and self-efficacy. Students with higher agency scores were significantly more likely to have higher academic achievement in anatomy compared to students with lower agency scores. The relationship between agency and academic achievement was strongest for action. These results suggest that encouraging students to be active participants in their learning may help them to achieve at university.
Publisher: Wiley
Date: 17-06-2018
DOI: 10.1111/ALL.13408
Abstract: The accurate assessment and communication of the severity of acute allergic reactions are important to patients, clinicians, researchers, the food industry, and public health and regulatory authorities. Severity has different meanings to different stakeholders with patients and clinicians rating the significance of particular symptoms very differently. Many severity scoring systems have been generated, most focusing on the severity of reactions following exposure to a limited group of allergens. They are heterogeneous in format, none has used an accepted developmental approach, and none has been validated. Their wide range of outcome formats has led to difficulties with interpretation and application. Therefore, there is a persisting need for an appropriately developed and validated severity scoring system for allergic reactions that work across the range of allergenic triggers and address the needs of different stakeholder groups. We propose a novel approach to develop and then validate a harmonized scoring system for acute allergic reactions, based on a data-driven method that is informed by clinical and patient experience and other stakeholders' perspectives. We envisage two formats: (i) a numerical score giving a continuum from mild to severe reactions that are clinically meaningful and are useful for allergy healthcare professionals and researchers, and (ii) a three-grade-based ordinal format that is simple enough to be used and understood by other professionals and patients. Testing of reliability and validity of the new approach in a range of settings and populations will allow eventual implementation of a standardized scoring system in clinical studies and routine practice.
Publisher: Wiley
Date: 15-07-2019
DOI: 10.1111/ALL.13805
Abstract: Allergen immunotherapy (AIT) is a proven therapeutic option for the treatment of allergic rhinitis and/or asthma. Many guidelines or national practice guidelines have been produced but the evidence-based method varies, many are complex and none propose care pathways. This paper reviews care pathways for AIT using strict criteria and provides simple recommendations that can be used by all stakeholders including healthcare professionals. The decision to prescribe AIT for the patient should be in idualized and based on the relevance of the allergens, the persistence of symptoms despite appropriate medications according to guidelines as well as the availability of good-quality and efficacious extracts. Allergen extracts cannot be regarded as generics. Immunotherapy is selected by specialists for stratified patients. There are no currently available validated biomarkers that can predict AIT success. In adolescents and adults, AIT should be reserved for patients with moderate/severe rhinitis or for those with moderate asthma who, despite appropriate pharmacotherapy and adherence, continue to exhibit exacerbations that appear to be related to allergen exposure, except in some specific cases. Immunotherapy may be even more advantageous in patients with multimorbidity. In children, AIT may prevent asthma onset in patients with rhinitis. mHealth tools are promising for the stratification and follow-up of patients.
Publisher: Elsevier BV
Date: 03-2021
Publisher: Elsevier BV
Date: 02-2019
Publisher: Wiley
Date: 18-06-2020
DOI: 10.1111/PAI.13273
Publisher: American Thoracic Society
Date: 15-05-2017
Publisher: Elsevier BV
Date: 07-2021
Publisher: European Respiratory Society (ERS)
Date: 22-12-2022
DOI: 10.1183/13993003.01231-2022
Abstract: Valid outcome measures are imperative to evaluate treatment response, yet the suitability of existing end-points for severe asthma is unclear. This review aimed to identify outcome measures for severe asthma and appraise the quality of their measurement properties. A literature search was performed to identify “candidate” outcome measures published between 2018 and 2020. A modified Delphi exercise was conducted to select “key” outcome measures within healthcare professional, patient, pharmaceutical and regulatory stakeholder groups. Initial validation studies for “key” measures were rated against modified quality criteria from COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN). The evidence was discussed at multi-stakeholder meetings to ratify “priority” outcome measures. Subsequently, four bibliographic databases were searched from inception to 20 July 2020 to identify development and validation studies for these end-points. Two reviewers screened records, extracted data, assessed their methodological quality and graded the evidence according to COSMIN. 96 outcome measures were identified as “candidates”, 55 as “key” and 24 as “priority” for severe asthma, including clinical, healthcare utilisation, quality of life, asthma control and composite. 32 studies reported measurement properties of 17 “priority” end-points from the latter three domains. Only the Severe Asthma Questionnaire and Childhood Asthma Control Test were developed with input from severe asthma patients. The certainty of evidence was “low” to “very low” for most “priority” end-points across all measurement properties and none fulfilled all quality standards. Only two outcome measures had robust developmental data for severe asthma. This review informed development of core outcome measures sets for severe asthma.
Publisher: Wiley
Date: 15-02-2011
DOI: 10.1111/J.1365-2702.2010.03480.X
Abstract: Aim and objective. To explore why innovations in service and delivery are adopted and how they are then successfully implemented and eventually assimilated into routine nursing practice. Background. The ‘Productive Ward’ is a national quality improvement programme that aims to engage nursing staff in the implementation of change at ward level. Design. Mixed methods (analysis of routine data, online survey, interviews) to apply an evidence‐based diffusion of innovations framework. Method. (1) Broad and narrow indicators of the timing of ‘decisions to adopt’ the Productive Ward were applied. (2) An online survey explored the perceptions of 150 respondents involved with local implementation. (3) Fifty‐eight interviews in five organisational case studies to explore the process of assimilation in each context. Results. Since the launch of the programme in May 2008 staff in approximately 85% of NHS acute hospitals had either downloaded Productive Ward materials or formally purchased a support package (as of March 2009). On a narrower measure, 40% (140) of all NHS hospitals had adopted the programme (i.e. purchased a support package) with large variation between geographical regions. Four key interactions in the diffusion of innovations framework appeared central to the rapid adoption of the programme. Despite widespread perception of significant benefits, frontline nursing staff report that more needs to be carried out to ensure that impact can be demonstrated in quantifiable terms and include patient perspectives. Conclusions. The programme has been rapidly adopted by NHS hospitals in England. A variety of implementation approaches are being employed, which are likely to have implications for the successful assimilation of the programme into routine nursing practice. Relevance to clinical practice. This paper summarises the perceived benefits of the Productive Ward programme and highlights important lessons for nurse leaders who are designing (or adapting) and then implementing quality improvement programmes locally, particularly in terms of how to frame such initiatives – and provide support to – ward‐level staff.
Publisher: American Thoracic Society
Date: 15-07-2023
Publisher: Springer Science and Business Media LLC
Date: 19-05-2023
DOI: 10.1038/S41467-023-38588-1
Abstract: Regulation of cutaneous immunity is severely compromised in inflammatory skin disease. To investigate the molecular crosstalk underpinning tolerance versus inflammation in atopic dermatitis, we utilise a human in vivo allergen challenge study, exposing atopic dermatitis patients to house dust mite. Here we analyse transcriptional programmes at the population and single cell levels in parallel with immunophenotyping of cutaneous immunocytes revealed a distinct dichotomy in atopic dermatitis patient responsiveness to house dust mite challenge. Our study shows that reactivity to house dust mite was associated with high basal levels of TNF-expressing cutaneous Th17 T cells, and documents the presence of hub structures where Langerhans cells and T cells co-localised. Mechanistically, we identify expression of metallothioneins and transcriptional programmes encoding antioxidant defences across all skin cell types, that appear to protect against allergen-induced inflammation. Furthermore, single nucleotide polymorphisms in the MTIX gene are associated with patients who did not react to house dust mite, opening up possibilities for therapeutic interventions modulating metallothionein expression in atopic dermatitis.
Publisher: Springer Science and Business Media LLC
Date: 03-08-2015
Publisher: Wiley
Date: 29-03-2021
DOI: 10.1111/PAI.13503
Abstract: There are limited data describing lung function changes in children after an asthma exacerbation. Our hypothesis was that lung function does not fully recover in children in the months following an asthma exacerbation. We used a data set of children with asthma where lung function (including FEV 1 , FEV 1 /FVC ratio and FEF 25‐75 ) was measured at 3‐month intervals over a year. Mixed‐level models compared spirometry measured on two occasions 3 months apart before a single exacerbation (assessments 1 and 2) with measurements made on two occasions after the exacerbation (assessments 3 and 4), with adjustment for covariates. Changes in spirometry over a year were also analysed across those with exacerbations in no, one or more than one 3‐month periods. For the 113 children who had a single exacerbation, spirometry measured at assessments 1 or 2 did not differ from measurements at assessments 3 or 4 when the whole population was considered. When stratified into tertiles by change in %FEV 1 between assessments 2 and 3, those with the greater reduction were more likely to be treated with long‐acting beta‐agonist, but in this category, %FEV 1 at assessment 4 had returned to the value at assessment 1. %FEV 1 did not change over a 12‐month period within and between the three exacerbation categories (n = 809). One or more asthma exacerbation was not associated with a fall in lung function for the whole population. In a subset of in iduals, lung function does fall after an exacerbation but returns to pre‐exacerbation values after a period of months.
Publisher: Public Library of Science (PLoS)
Date: 29-08-2012
Publisher: Elsevier BV
Date: 02-2020
Publisher: Elsevier BV
Date: 08-2015
DOI: 10.1016/J.ANAI.2015.06.001
Abstract: The purpose of this brief communication is to highlight emerging evidence to existing guidelines regarding potential benefits of supporting early, rather than delayed, peanut introduction during the period of complementary food introduction in infants. This document should be considered as interim guidance based on consensus among the following organizations: American Academy of Allergy, Asthma & Immunology, American Academy of Pediatrics, American College of Allergy, Asthma & Immunology, Australasian Society of Clinical Immunology and Allergy, Canadian Society of Allergy and Clinical Immunology, European Academy of Allergy and Clinical Immunology, Israel Association of Allergy and Clinical Immunology, Japanese Society for Allergology, Society for Pediatric Dermatology, and World Allergy Organization. More formal guidelines regarding early-life, complementary feeding practices and the risk of allergy development will follow in the next year from the National Institute of Allergy and Infectious Diseases-sponsored Working Group and the European Academy of Allergy and Clinical Immunology.
Publisher: European Respiratory Society
Date: 15-09-2018
Publisher: American Thoracic Society
Date: 15-10-2022
Publisher: Elsevier BV
Date: 11-2020
Publisher: Wiley
Date: 15-06-2012
Publisher: European Respiratory Society (ERS)
Date: 29-09-2021
DOI: 10.1183/23120541.00457-2021
Abstract: The prevalences of obstructive and restrictive spirometric phenotypes, and their relation to early-life risk factors from childhood to young adulthood remain poorly understood. The aim was to explore these phenotypes and associations with well-known respiratory risk factors across ages and populations in European cohorts. We studied 49 334 participants from 14 population-based cohorts in different age groups (≤10, –15, –20, –25 years, and overall, 5–25 years). The obstructive phenotype was defined as forced expiratory volume in 1 s (FEV 1 )/forced vital capacity (FVC) z-score less than the lower limit of normal (LLN), whereas the restrictive phenotype was defined as FEV 1 /FVC z-score ≥LLN, and FVC z-score LLN. The prevalence of obstructive and restrictive phenotypes varied from 3.2–10.9% and 1.8–7.7%, respectively, without clear age trends. A diagnosis of asthma (adjusted odds ratio (aOR=2.55, 95% CI 2.14–3.04), preterm birth (aOR=1.84, 1.27–2.66), maternal smoking during pregnancy (aOR=1.16, 95% CI 1.01–1.35) and family history of asthma (aOR=1.44, 95% CI 1.25–1.66) were associated with a higher prevalence of obstructive, but not restrictive, phenotype across ages (5–25 years). A higher current body mass index (BMI was more often observed in those with the obstructive phenotype but less in those with the restrictive phenotype (aOR=1.05, 95% CI 1.03–1.06 and aOR=0.81, 95% CI 0.78–0.85, per kg·m −2 increase in BMI, respectively). Current smoking was associated with the obstructive phenotype in participants older than 10 years (aOR=1.24, 95% CI 1.05–1.46). Obstructive and restrictive phenotypes were found to be relatively prevalent during childhood, which supports the early origins concept. Several well-known respiratory risk factors were associated with the obstructive phenotype, whereas only low BMI was associated with the restrictive phenotype, suggesting different underlying pathobiology of these two phenotypes.
Publisher: European Respiratory Society
Date: 09-2017
Publisher: Wiley
Date: 06-2021
DOI: 10.1002/CLT2.12014
Publisher: Springer Science and Business Media LLC
Date: 07-01-2021
DOI: 10.1186/S12931-020-01605-8
Abstract: Patients with severe asthma may have a greater risk of dying from COVID-19 disease. Angiotensin converting enzyme-2 (ACE2) and the enzyme proteases, transmembrane protease serine 2 (TMPRSS2) and FURIN, are needed for viral attachment and invasion into host cells. We examined microarray mRNA expression of ACE2, TMPRSS2 and FURIN in sputum, bronchial brushing and bronchial biopsies of the European U-BIOPRED cohort. Clinical parameters and molecular phenotypes, including asthma severity, sputum inflammatory cells, lung functions, oral corticosteroid (OCS) use, and transcriptomic-associated clusters, were examined in relation to gene expression levels. ACE2 levels were significantly increased in sputum of severe asthma compared to mild-moderate asthma. In multivariate analyses, sputum ACE2 levels were positively associated with OCS use and male gender. Sputum FURIN levels were significantly related to neutrophils (%) and the presence of severe asthma. In bronchial brushing s les, TMPRSS2 levels were positively associated with male gender and body mass index, whereas FURIN levels with male gender and blood neutrophils. In bronchial biopsies, TMPRSS2 levels were positively related to blood neutrophils. The neutrophilic molecular phenotype characterised by high inflammasome activation expressed significantly higher FURIN levels in sputum than the eosinophilic Type 2-high or the pauci-granulocytic oxidative phosphorylation phenotypes. Levels of ACE2 and FURIN may differ by clinical or molecular phenotypes of asthma. Sputum FURIN expression levels were strongly associated with neutrophilic inflammation and with inflammasome activation. This might indicate the potential for a greater morbidity and mortality outcome from SARS-CoV-2 infection in neutrophilic severe asthma.
Publisher: Springer Science and Business Media LLC
Date: 21-02-2022
DOI: 10.1186/S40168-021-01201-Y
Abstract: There is increasing evidence that the airway microbiome plays a key role in the establishment of respiratory health by interacting with the developing immune system early in life. While it has become clear that bacteria are involved in this process, there is a knowledge gap concerning the role of fungi. Moreover, the inter-kingdom interactions that influence immune development remain unknown. In this prospective exploratory human study, we aimed to determine early post-natal microbial and immunological features of the upper airways in 121 healthy newborns. We found that the oropharynx and nasal cavity represent distinct ecological niches for bacteria and fungi. Breastfeeding correlated with changes in microbiota composition of oropharyngeal s les with the greatest impact upon the relative abundance of Streptococcus species and Candida . Host transcriptome profiling revealed that genes with the highest expression variation were immunological in nature. Multi-omics factor analysis of host and microbial data revealed unique co-variation patterns. These data provide evidence of a erse multi-kingdom microbiota linked with local immunological characteristics in the first week of life that could represent distinct trajectories for future respiratory health. NHS Health Research Authority, IRAS ID 199053. Registered 5 Oct 2016. www.hra.nhs.uk lanning-and-improving-research/application-summaries/research-summaries/breathing-together/
Publisher: Elsevier BV
Date: 06-2017
DOI: 10.1016/J.JACI.2016.08.048
Abstract: 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. We stratified patients with moderate-to-severe asthma based on clinicophysiologic parameters and performed an omics analysis of sputum. Partition-around-medoids clustering was applied to a training set of 266 asthmatic participants from the European Unbiased Biomarkers for the Prediction of Respiratory Diseases Outcomes (U-BIOPRED) adult cohort using 8 prespecified clinic-physiologic variables. This was repeated in a separate validation set of 152 asthmatic patients. The clusters were compared based on sputum proteomics and transcriptomics data. Four reproducible and stable clusters of asthmatic patients were identified. The training set cluster T1 consists of patients with well-controlled moderate-to-severe asthma, whereas cluster T2 is a group of patients with late-onset severe asthma with a history of smoking and chronic airflow obstruction. Cluster T3 is similar to cluster T2 in terms of chronic airflow obstruction but is composed of nonsmokers. Cluster T4 is predominantly composed of obese female patients with uncontrolled severe asthma with increased exacerbations but with normal lung function. The validation set exhibited similar clusters, demonstrating reproducibility of the classification. There were significant differences in sputum proteomics and transcriptomics between the clusters. The severe asthma clusters (T2, T3, and T4) had higher sputum eosinophilia than cluster T1, with no differences in sputum neutrophil counts and exhaled nitric oxide and serum IgE levels. Clustering based on clinicophysiologic parameters yielded 4 stable and reproducible clusters that associate with different pathobiological pathways.
Publisher: European Respiratory Society
Date: 15-09-2018
Publisher: Elsevier BV
Date: 12-2021
DOI: 10.1016/J.JACI.2021.10.018
Abstract: The prevalence of food allergy (FA) is increasing in some areas of the globe, highlighting the need for better strategies for prevention, diagnosis, and therapy. In the last few decades, we have made great strides in understanding the causes and mechanisms underlying FAs, prompting guideline updates. Earlier guidelines recommended avoidance of common food allergens during pregnancy and lactation and delaying the introduction of allergenic foods in children aged between 1 and 3 years. Recent guidelines for allergy prevention recommend consumption of a healthy and erse diet without eliminating or increasing the consumption of allergenic foods during pregnancy or breast-feeding. Early introduction of allergenic foods is recommended by most guidelines for allergy prevention after a period of exclusive breast-feedng (6 months [World Health Organization] or 4 months [European Academy of Allergy and Clinical Immunology]). New diagnostics for FA have been developed with varied availability of these tests in different countries. Finally, the first oral immunotherapy drug for FA was approved by the US Food and Drug Administration and European Medicines Agency in 2020. In this review, we will address the global prevalence of FA, our current understanding of the causes of FA, and the latest guidelines for preventing, diagnosing, and treating FA. We will also discuss similarities and differences between FA guidelines.
Publisher: Wiley
Date: 12-11-2018
DOI: 10.1111/ALL.13629
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Graham Roberts.