1,720,989 research outputs found
Exhaled volatile organic compounds as biomarkers for airway biology in severe asthma
No full textBreathomics, the measurement of exhaled volatile organic compounds (VOCs), is an exciting new biomarker medium for airways disease. The greatest unmet need for biomarkers in severe asthma is in T2 low disease and so, in this thesis, I sought to identify a T2 low phenotype and assess whether breathomics could be used as a biomarker for this patient group.A cohort of severe asthma patients was recruited and clinically characterised in parallel to sputum induction and exhaled breath collection. Though the T2 high phenotype was easy to recognise, T2 low disease was poorly defined by inflammatory cell counts alone. Measures of inflammatory cell activation provided were insufficient to describe new phenotypes. 16s rRNA sequencing of sputum samples identified a cohort of T2 low patients, characterised by airway colonisation with Haemophilus, sputum neutrophilia and ongoing disease burden. However, none of the clinically available biomarkers were able to identify this cohort of patents. The exhaled VOC samples from this severe asthma cohort demonstrate a clear structure to the exhaled VOC matrix, however, sensitivity to underlying airway inflammation was weak. Repeated breath sampling identified heterogeneity in the stability of VOCs during an otherwise clinically stable state. Exclusion of VOCs with a high degree of within-subject variability resulted in less model overfitting and AUC an of 0.643 for predicting sputum eosinophilia (>2%). 2-pentanone, was identified as having the strongest feature importance. This ketone is thought to be generated in the airway epithelium. Applying this newly established analytical framework, a model was built to predict the cluster of patients with heavy Haemophilus colonisation, potentially amenable to Azithromycin therapy. A model built on non-erratic VOCs predicting Haemophilus with an AUC of 0.857. Decane was identified as a possible biomarker, however further validation is required. The findings from this thesis demonstrate sensitivity of exhaled VOCs to the airway biology of severe asthma patients but require validation
Exhaled volatile organic compounds in adult asthma: a systematic review
No full textThe search for biomarkers that can guide precision medicine in asthma, particularly those that can be translated to the clinic, has seen recent interest in exhaled volatile organic compounds (VOCs). Given the number of studies reporting "breathomics" findings and its growing integration in clinical trials, we performed a systematic review of the literature to summarise current evidence and understanding of breathomics technology in asthma.A PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses)-oriented systematic search was performed (CRD42017084145) of MEDLINE, Embase and the Cochrane databases to search for any reports that assessed exhaled VOCs in adult asthma patients, using the following terms (asthma AND (volatile organic compounds AND exhaled) OR breathomics).Two authors independently determined the eligibility of 2957 unique records, of which 66 underwent full-text review. Data extraction and risk of bias assessment was performed on the 22 studies deemed to fulfil the search criteria. The studies are described in terms of methodology and the evidence narratively summarised under the following clinical headings: diagnostics, phenotyping, treatment stratification, treatment monitoring and exacerbation prediction/assessment.Our review found that most studies were designed to assess diagnostic potential rather than focus on underlying biology or treatable traits. Results are generally limited by a lack of methodological standardisation and external validation and by insufficiently powered studies, but there is consistency across the literature that exhaled VOCs are sensitive to underlying inflammation. Modern studies are applying robust breath analysis workflows to large multi-centre study designs, which should unlock the full potential of measurement of exhaled volatile organic compounds in airways diseases such as asthma.</p
Severe acute respiratory syndrome coronavirus 2 infection in those on mepolizumab therapy
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Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Validation and further insight into the International Severe Asthma Registry (ISAR) eosinophil gradient algorithm in the Wessex AsThma CoHort of difficult asthma (WATCH) using historical blood eosinophil counts and induced sputum
No full textPeripheral airways type 2 inflammation, neutrophilia and microbial dysbiosis in severe asthma
No full textBackground: IL-13 is considered an archetypal T2 cytokine central to the clinical disease expression of asthma. The IL-13 response genes, which are upregulated in central airway bronchial epithelial of asthma patients, can be normalized by high-dose inhaled steroid therapy in severe asthma. However, this is not the case within the peripheral airways. We have sought to further understand IL-13 in the peripheral airways in severe asthma through bronchoalveolar analysis. Methods: bronchoalveolar lavage samples were collected from 203 asthmatic and healthy volunteers, including 78 with severe asthma. Inflammatory mediators were measured using a multiple cytokine immunoassay platform. This analysis was replicated in a further 59 volunteers, in whom 16S rRNA analysis of BAL samples was undertaken by terminal restriction fragment length polymorphism. Results: severe asthma patients with high BAL IL-13, despite treatment with high-dose inhaled corticosteroids, had more severe lung function and significantly higher BAL neutrophil percentages, but not BAL eosinophils than those with normal BAL-13 concentrations. This finding was replicated in the second cohort, which further associated BAL IL-13 and neutrophilia with a greater abundance of potentially pathogenic bacteria in the peripheral airways. Conclusion: our findings demonstrate a steroid unresponsive source of IL-13 that is associated with BAL neutrophilia and bacterial dysbiosis in severe asthma. Our findings highlight the biological complexity of severe asthma and the importance of a greater understanding of the innate and adaptive immune responses in the peripheral airways in this disease.</p
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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