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Sökning: WFRF:(Haughney J.)

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  • Östling, Jörgen, et al. (författare)
  • IL-17-high asthma with features of a psoriasis immunophenotype
  • 2019
  • Ingår i: Journal of Allergy and Clinical Immunology. - Elsevier. - 0091-6749 .- 1097-6825. ; 144:5, s. 1198-1213
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The role of IL-17 immunity is well established in patients with inflammatory diseases, such as psoriasis and inflammatory bowel disease, but not in asthmatic patients, in whom further study is required.Objective: We sought to undertake a deep phenotyping study of asthmatic patients with upregulated IL-17 immunity.Methods: Whole-genome transcriptomic analysis was performed by using epithelial brushings, bronchial biopsy specimens (91 asthmatic patients and 46 healthy control subjects), and whole blood samples (n = 498) from the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) cohort. Gene signatures induced in vitro by IL-17 and IL-13 in bronchial epithelial cells were used to identify patients with IL-17–high and IL-13–high asthma phenotypes.Results: Twenty-two of 91 patients were identified with IL-17, and 9 patients were identified with IL-13 gene signatures. The patients with IL-17–high asthma were characterized by risk of frequent exacerbations, airway (sputum and mucosal) neutrophilia, decreased lung microbiota diversity, and urinary biomarker evidence of activation of the thromboxane B2 pathway. In pathway analysis the differentially expressed genes in patients with IL-17-high asthma were shared with those reported as altered in psoriasis lesions and included genes regulating epithelial barrier function and defense mechanisms, such as IL1B, IL6, IL8, and β-defensin.Conclusion: The IL-17–high asthma phenotype, characterized by bronchial epithelial dysfunction and upregulated antimicrobial and inflammatory response, resembles the immunophenotype of psoriasis, including activation of the thromboxane B2 pathway, which should be considered a biomarker for this phenotype in further studies, including clinical trials targeting IL-17.
  • Bousquet, Jean, et al. (författare)
  • Development and implementation of guidelines in allergic rhinitis – an ARIA-GA2LEN paper.
  • 2010
  • Ingår i: Allergy. - 1398-9995. ; 65:10, s. 1212-21
  • Tidskriftsartikel (refereegranskat)abstract
    • The links between asthma and rhinitis are well characterized. The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines stress the importance of these links and provide guidance for their prevention and treatment. Despite effective treatments being available, too few patients receive appropriate medical care for both diseases. Most patients with rhinitis and asthma consult primary care physicians and therefore these physicians are encouraged to understand and use ARIA guidelines. Patients should also be informed about these guidelines to raise their awareness of optimal care and increase control of the two related diseases. To apply these guidelines, clinicians and patients need to understand how and why the recommendations were made. The goal of the ARIA guidelines is to provide recommendations about the best management options for most patients in most situations. These recommendations should be based on the best available evidence. Making recommendations requires the assessment of the quality of available evidence, deciding on the balance between benefits and downsides, consideration of patients’ values and preferences, and, if applicable, resource implications. Guidelines must be updated as new management options become available or important new evidence emerges. Transparent reporting of guidelines facilitates understanding and acceptance, but implementation strategies need to be improved.
  • Schofield, James P. R., et al. (författare)
  • Stratification of asthma phenotypes by airway proteomic signatures
  • 2019
  • Ingår i: Journal of Allergy and Clinical Immunology. - Elsevier. - 0091-6749 .- 1097-6825. ; 144:1, s. 70-82
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Stratification by eosinophil and neutrophil counts increases our understanding of asthma and helps target therapy, but there is room for improvement in our accuracy in prediction of treatment responses and a need for better understanding of the underlying mechanisms. Objective: We sought to identify molecular subphenotypes of asthma defined by proteomic signatures for improved stratification. Methods: Unbiased label-free quantitative mass spectrometry and topological data analysis were used to analyze the proteomes of sputum supernatants from 246 participants (206 asthmatic patients) as a novel means of asthma stratification. Microarray analysis of sputum cells provided transcriptomics data additionally to inform on underlying mechanisms. Results: Analysis of the sputum proteome resulted in 10 clusters (ie, proteotypes) based on similarity in proteomic features, representing discrete molecular subphenotypes of asthma. Overlaying granulocyte counts onto the 10 clusters as metadata further defined 3 of these as highly eosinophilic, 3 as highly neutrophilic, and 2 as highly atopic with relatively low granulocytic inflammation. For each of these 3 phenotypes, logistic regression analysis identified candidate protein biomarkers, and matched transcriptomic data pointed to differentially activated underlying mechanisms. Conclusion: This study provides further stratification of asthma currently classified based on quantification of granulocytic inflammation and provided additional insight into their underlying mechanisms, which could become targets for novel therapies.
  • Bousquet, Jean, et al. (författare)
  • Inhaled Corticosteroid/Long-Acting beta(2)-Agonist Combination Therapy for Asthma: Attitudes of Specialists in Europe
  • 2012
  • Ingår i: International Archives of Allergy and Immunology. - Karger. - 1423-0097. ; 157:3, s. 303-310
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: As new combinations of inhaled corticosteroids (ICSs) and long-acting beta(2)-agonists (LABAs) become available for the treatment of asthma, it will be important to determine criteria against which they can be evaluated. The aim of this study was to assess which attributes of combination therapy physicians consider most important. Methods: Primary and secondary care asthma specialists (n = 32) were recruited for an expert Delphi process that was performed over three rounds to determine attributes perceived to be important in the selection of combination therapy. A pan-European survey was carried out to assess the attitudes, perceptions and prescribing behaviour of a larger population (n = 1,861) of physicians with a specialist interest in asthma treatment. Results: The expert Delphi panel (response rate 59.4%) agreed that the availability of a range of doses (88% agreement in the final round), the efficacy of the combination (81%) and the safety and tolerability of the therapy (81%) were important attributes of ICS/LABA combination treatment. The potency of the ICS (69%) and the speed of onset of the LABA (69%) were also prioritized. The results of the attitudinal survey (eligibility rate 54.1%) showed that the same factors were considered important in everyday clinical practice. Conclusions: These studies identified which attributes of an ICS/LABA treatment are considered most important by an expert panel and a broader group of physicians; further research is warranted to better understand the influences that drive physician opinions. Copyright (C) 2011 S. Karger AG, Basel
  • Haughney, J, et al. (författare)
  • Exacerbations of COPD: quantifying the patient's perspective using discrete choice modelling
  • 2005
  • Ingår i: European Respiratory Journal. - Eur Respiratory Soc. - 1399-3003. ; 26:4, s. 623-629
  • Tidskriftsartikel (refereegranskat)abstract
    • Patient-centred care is the current vogue in chronic obstructive pulmonary disease (COPD), but it is only recently that robust techniques have become available to determine patients' values and preferences. In this international cross-sectional study, patients' concerns and expectations regarding COPD exacerbations were explored using discrete choice modelling. A fractional factorial design was used to develop scenarios comprising a combination of levels for nine different attributes. In face-to-face interviews, patients were presented with paired scenarios and asked to choose the least preferable. Multinomial logit (with hierarchical Bayes) methods were used to estimate utilities. A total of 125 patients (82 males; mean age 66 yrs; 4.6 mean exacerbations(.)yr(-1)) were recruited. The attributes of exacerbations considered most important were impact on everyday life (20%) need for medical care (16%), number of future attacks (12%) and breathlessness (11 %). The next most important attributes were speed of recovery, productive cough and social impact (all 9%), followed by sleep disturbance and impact on mood (both 7%). Importantly, analysis of utility shifts showed that patients most feared being hospitalised, housebound or bedridden. These issues were more important than symptom improvement. Strategies for the clinical management of chronic obstructive pulmonary disease should clearly address patients' concerns and focus on preventing and treating exacerbations to avoid these feared outcomes.
  • Holgate, S., et al. (författare)
  • The Brussels Declaration: the need for change in asthma management
  • 2008
  • Ingår i: European Respiratory Journal. - Eur Respiratory Soc. - 1399-3003. ; 32:6, s. 1433-1442
  • Tidskriftsartikel (refereegranskat)abstract
    • Asthma is a highly prevalent condition across Europe and numerous guidelines have been developed to optimise management. However, asthma can be neither cured nor prevented, treatment choices are limited and many patients have poorly controlled or uncontrolled asthma. The Brussels Declaration on Asthma, sponsored by The Asthma, Allergy and Inflammation Research Charity, was developed to call attention to the shortfalls in asthma management and to urge European policy makers to recognise that asthma is a public health problem that should be a political priority. The Declaration urges recognition and action on the following points: the systemic Inflammatory component of asthma should be better understood and considered in assessments of treatment efficacy; current research must be communicated and responded to quickly; the European Medicines Agency guidance note on asthma should be updated; "real world" studies should be funded and results used to Inform guidelines; variations in care across Europe should be addressed; people with asthma should participate in their own care; the impact of environmental factors should be understood; and targets should be set for improvement. The present paper reviews the evidence supporting the need for change in asthma management and summarises the ten key points contained In the Brussels Declaration.
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