Publications by authors named "Louise J Fleming"

Article Synopsis
  • Early identification of poorly controlled asthma in children is crucial for improving treatment methods, and analyzing exhaled volatile organic compounds (VOCs) shows promise for this task.
  • A study evaluated the effectiveness of gas chromatography-mass spectrometry to distinguish between controlled and uncontrolled pediatric asthma, using data from multiple research phases.
  • Key findings revealed that specific VOCs, such as acetophenone and ethylbenzene, could differentiate asthma control levels, achieving strong accuracy in predicting outcomes based on the collected data from 196 children.
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Article Synopsis
  • Children with preschool wheezing or school-age asthma have different microbial profiles in their airways, which can affect their condition and treatment outcomes.
  • A study of oropharyngeal samples from 241 children identified four distinct clusters based on microbial composition, with significant differences in associated allergies and asthma severity.
  • The findings suggest that understanding these microbial clusters could offer new insights into asthma management and lead to innovative treatment strategies.
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Background: Asthma is a chronic respiratory disease with significant heterogeneity in its clinical presentation and pathobiology. There is need for improved understanding of respiratory lipid metabolism in asthma patients and its relation to observable clinical features.

Objective: We performed a comprehensive, prospective, cross-sectional analysis of the lipid composition of induced sputum supernatant obtained from asthma patients with a range of disease severities, as well as from healthy controls.

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Background: Exacerbation-prone asthma is a feature of severe disease. However, the basis for its persistency remains unclear.

Objectives: To determine the clinical and transcriptomic features of frequent exacerbators (FEs) and persistent FEs (PFEs) in the U-BIOPRED cohort.

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Article Synopsis
  • - GINA's 2021 Strategy Report gives updated, evidence-based recommendations for asthma treatment, emphasizing the need for inhaled corticosteroids (ICS) instead of relying solely on short-acting β-agonists (SABA), due to risks associated with SABA overuse.
  • - The report introduces two treatment tracks for adults and adolescents: Track 1 recommends low-dose ICS-formoterol as the reliever, while Track 2 opts for as-needed SABA, with specific guidance for different steps based on asthma severity.
  • - It also emphasizes the importance of personalized assessment and management across age groups, highlighting the need for ongoing education and adaptation of treatment plans to improve asthma outcomes.
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The Global Initiative for Asthma (GINA) Strategy Report provides clinicians with an annually updated evidence-based strategy for asthma management and prevention, which can be adapted for local circumstances (e.g., medication availability).

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Article Synopsis
  • The GINA Strategy Report offers an updated, evidence-based approach for asthma management that is flexible enough to suit local conditions, advising against SABA-only treatments due to associated risks.
  • Key recommendations from GINA 2021 include using combination inhaled corticosteroids (ICS) with formoterol for better control of asthma, and categorizing treatments for adults/adolescents into two main tracks, with a preference for low-dose ICS-formoterol.
  • For managing asthma in various age groups and severities, the report stresses personalized assessments, addressing modifiable risk factors, and educating patients on self-management as critical for improving health outcomes.
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The Global Initiative for Asthma (GINA) Strategy Report provides clinicians with an annually updated evidence-based strategy for asthma management and prevention, which can be adapted for local circumstances (e.g., medication availability).

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Background: Transcriptomic changes in patients who respond clinically to biological therapies may identify responses in other tissues or diseases.

Objective: We sought to determine whether a disease signature identified in atopic dermatitis (AD) is seen in adults with severe asthma and whether a transcriptomic signature for patients with AD who respond clinically to anti-IL-22 (fezakinumab [FZ]) is enriched in severe asthma.

Methods: An AD disease signature was obtained from analysis of differentially expressed genes between AD lesional and nonlesional skin biopsies.

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Background: Although estimates of suboptimal adherence to oral corticosteroids in asthma range from 30% to 50%, no ideal method for measurement exists; the impact of poor adherence in severe asthma is likely to be particularly high.

Research Questions: What is the prevalence of suboptimal adherence detected by self-reporting and direct measures? Is suboptimal adherence associated with disease activity?

Study Design And Methods: Data were included from individuals with severe asthma taking part in the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes) study and prescribed daily oral corticosteroids. Participants completed the Medication Adherence Report Scale, a five-item questionnaire used to grade adherence on a scale from 1 to 5, and provided a urine sample for analysis of prednisolone and metabolites by liquid chromatography-mass spectrometry.

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New biologics are being continually developed for paediatric asthma, but it is unclear whether there are sufficient numbers of children in Europe with severe asthma and poor control to recruit to trials needed for registration. To address these questions, the European Respiratory Society funded the Severe Paediatric Asthma Collaborative in Europe (SPACE), a severe asthma registry. We report the first analysis of the SPACE registry, which includes data from 10 paediatric respiratory centres across Europe.

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Serial peak expiratory flow (PEF) measurements can identify phenotypes in severe adult asthma, enabling more targeted treatment. The feasibility of this approach in children has not been investigated. Overall, 105 children (67% male, median age 12.

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Background: Electronic noses (eNoses) are emerging point-of-care tools that may help in the subphenotyping of chronic respiratory diseases such as asthma.

Objective: We aimed to investigate whether eNoses can classify atopy in pediatric and adult patients with asthma.

Methods: Participants with asthma and/or wheezing from 4 independent cohorts were included; BreathCloud participants (n = 429), Unbiased Biomarkers in Prediction of Respiratory Disease Outcomes adults (n = 96), Unbiased Biomarkers in Prediction of Respiratory Disease Outcomes pediatric participants (n = 100), and Pharmacogenetics of Asthma Medication in Children: Medication with Anti-Inflammatory Effects 2 participants (n = 30).

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Background: Allergic sensitization is associated with severe asthma, but assessment of sensitization is not recommended by most guidelines.

Objective: We hypothesized that patterns of IgE responses to multiple allergenic proteins differ between sensitized participants with mild/moderate and severe asthma.

Methods: IgE to 112 allergenic molecules (components, c-sIgE) was measured using multiplex array among 509 adults and 140 school-age and 131 preschool children with asthma/wheeze from the Unbiased BIOmarkers for the PREDiction of respiratory diseases outcomes cohort, of whom 595 had severe disease.

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Background: Lung epithelial lining fluid (ELF)-sampled through sputum induction-is a medium rich in cells, proteins and lipids. However, despite its key role in maintaining lung function, homeostasis and defences, the composition and biology of ELF, especially in respect of lipids, remain incompletely understood.

Objectives: To characterise the induced sputum lipidome of healthy adult individuals, and to examine associations between different ELF lipid phenotypes and the demographic characteristics within the study cohort.

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Type-2 (T2) immune responses in airway epithelial cells (AECs) classifies mild-moderate asthma into a T2-high phenotype. We examined whether currently available clinical biomarkers can predict AEC-defined T2-high phenotype within the U-BIOPRED cohort.The transcriptomic profile of AECs obtained from brushings of 103 patients with asthma and 44 healthy controls was obtained and gene set variation analysis used to determine the relative expression score of T2 asthma using a signature from interleukin (IL)-13-exposed AECs.

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Article Synopsis
  • Oxidative stress is linked to inflammation in people with severe asthma, especially those who smoke or have smoked.
  • The U-BIOPRED project studied a group of asthma patients, separating them into current smokers, ex-smokers, and non-smokers to see how smoking affects their condition.
  • Results showed that current and ex-smokers had higher levels of a specific substance in their urine linked to oxidative stress, and certain genes related to oxidative stress were more active in their lungs compared to non-smokers.
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The development of new asthma biologics and receptor blockers for the treatment of paediatric severe asthma raises challenges. It is unclear whether there are sufficient children in Europe to recruit into randomised placebo-controlled trials to establish efficacy and safety in this age group. In February 2016, the European Respiratory Society funded a clinical research collaboration entitled "Severe Paediatric Asthma Collaborative in Europe" (SPACE).

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Severe asthma patients with a significant smoking history have airflow obstruction with reported neutrophilia. We hypothesise that multi-omic analysis will enable the definition of smoking and ex-smoking severe asthma molecular phenotypes.The U-BIOPRED cohort of severe asthma patients, containing current-smokers (CSA), ex-smokers (ESA), nonsmokers and healthy nonsmokers was examined.

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