ORCID Profile
0000-0002-2220-7745
Current Organisations
Université Laval
,
University of Southampton
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Publisher: Wiley
Date: 02-06-2019
DOI: 10.1111/CEA.13409
Abstract: Human milk (HM) transforming growth factor beta (TGF-β) is critical for inflammation regulation and oral tolerance promotion. Previous reports suggested that variations in HM TGF-β levels are associated with allergic outcomes. We undertook a systematic review (PROSPERO 2017 CRD42017069920) to reassess the evidence on the relationships between HM TGF-β and allergic outcomes in children. Electronic bibliographic databases (MEDLINE, EMBASE and Cochrane Library) were systematically searched. Two independent reviewers screened reference lists, extracted the data and assessed risk of bias using the National Institute for Clinical Excellence methodological checklist. A total of 21 studies were identified. Sixteen studies assessed relationships between HM TGF-β and risk of eczema 14, allergic sensitization nine, wheezing/asthma six, food allergy three, allergic rhinitis/conjunctivitis. Five cohorts (5/18, 28%) reported a protective effect of TGF-β1, while 3 (3/10, 30%) suggested increased risk of allergic outcomes development and 1 (1/10, 10%), a protective effect of TGF-β2 on eczema. Meta-analysis was not possible due to significant heterogeneity in methodology, age of outcome assessment and differing statistical approaches. 71% (15/21) of studies carried a high risk of bias. In contrast with previous findings, we did not find strong evidence of associations between HM TGF-β and allergic outcomes. Differences in studies' methodology and outcomes do not allow unconditional rejection or acceptance of the hypothesis that HM TGF-β influences the risk of allergy development. Future studies on erse populations employing standardized methods, accurate phenotyping of outcomes and evaluation of the effect of TGF-β in combination with other HM immune markers, microbiome and oligosaccharides are required.
Publisher: Wiley
Date: 18-06-2020
DOI: 10.1111/PAI.13273
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: The Endocrine Society
Date: 09-2014
DOI: 10.1210/EN.2014-1341
Abstract: The initial segment (IS) of the epididymis plays an essential role in male fertility. The IS epithelium is undifferentiated and nonfunctional at birth. Prior to puberty, the epithelium undergoes differentiation that leads to the formation of a fully functional organ. However, the mechanistic details of this program are not well understood. To explore this further, we used genetic engineering to create a kinase dead allele of the ROS1 receptor tyrosine kinase in mice and studied the effects of ROS1 tyrosine kinase activity on the differentiation of the IS epithelium. We show that the expression and activation of ROS1 coincides with the onset of differentiation and is exclusively located in the IS of the maturing and adult mouse epididymides. Here we demonstrate that the differentiation of the IS is dependent on the kinase activity of ROS1 and its downstream effector MEK1/2-ERK1/2 signaling axis. Using genetic engineering, we show that germ line ablation of ROS1 kinase activity leads to a failure of the IS epithelium to differentiate, and as a consequence sperm maturation and infertility were dramatically perturbed. Pharmacological inhibition of ROS1 kinase activity in the developing epididymis, however, only delayed differentiation transiently and did not result in infertility. Our results demonstrate that ROS1 kinase activity and the ensuing MEK1/2-ERK1/2 signaling are necessary for the postnatal development of the IS epithelium and that a sustained ablation of ROS1 kinase activity within the critical window of terminal differentiation abrogate the function of the epididymis and leads to sterility.
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: Oxford University Press (OUP)
Date: 21-05-2019
Abstract: A large number of biologically active components have been found in human milk (HM), and in both human and animal models, studies have provided some evidence suggesting that HM composition can be altered by maternal exposures, subsequently influencing health outcomes for the breastfed child. Evidence varies from the research studies on whether breastfeeding protects the offspring from noncommunicable diseases, including those associated with immunological dysfunction. It has been hypothesized that the conflicting evidence results from HM composition variations, which contain many immune active molecules, oligosaccharides, lactoferrin, and lysozyme in differing concentrations, along with a erse microbiome. Determining the components that influence infant health outcomes in terms of both short- and long-term sequelae is complicated by a lack of understanding of the environmental factors that modify HM constituents and thereby offspring outcomes. Variations in HM immune and microbial composition (and the differing infantile responses) may in part explain the controversies that are evidenced in studies that aim to evaluate the prevalence of allergy by prolonged and exclusive breastfeeding. HM is a “mixture” of immune active factors, oligosaccharides, and microbes, which all may influence early immunological outcomes. This comprehensive review provides an in-depth overview of existing evidence on the studied relationships between maternal exposures, HM composition, vaccine responses, and immunological outcomes.
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: Oxford University Press (OUP)
Date: 05-2014
Location: United States of America
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Ekaterina Khaleva.