24 research outputs found

    Management of asthma in childhood: study protocol of a systematic evidence update by the Paediatric Asthma in Real Life (PeARL) Think Tank

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    IntroductionClinical recommendations for childhood asthma are often based on data extrapolated from studies conducted in adults, despite significant differences in mechanisms and response to treatments. The Paediatric Asthma in Real Life (PeARL) Think Tank aspires to develop recommendations based on the best available evidence from studies in children. An overview of systematic reviews (SRs) on paediatric asthma maintenance management and an SR of treatments for acute asthma attacks in children, requiring an emergency presentation with/without hospital admission will be conducted.Methods and analysisStandard methodology recommended by Cochrane will be followed. Maintenance pharmacotherapy of childhood asthma will be evaluated in an overview of SRs published after 2005 and including clinical trials or real-life studies. For evaluating pharmacotherapy of acute asthma attacks leading to an emergency presentation with/without hospital admission, we opted to conduct de novo synthesis in the absence of adequate up-to-date published SRs. For the SR of acute asthma pharmacotherapy, we will consider eligible SRs, clinical trials or real-life studies without time restrictions. Our evidence updates will be based on broad searches of Pubmed/Medline and the Cochrane Library. We will use A MeaSurement Tool to Assess systematic Reviews, V.2, Cochrane risk of bias 2 and REal Life EVidence AssessmeNt Tool to evaluate the methodological quality of SRs, controlled clinical trials and real-life studies, respectively. Next, we will further assess interventions for acute severe asthma attacks with positive clinical results in meta-analyses. We will include both controlled clinical trials and observational studies and will assess their quality using the previously mentioned tools. We will employ random effect models for conducting meta-analyses, and Grading of Recommendations Assessment, Development and Evaluation methodology to assess certainty in the body of evidence.Ethics and disseminationEthics approval is not required for SRs. Our findings will be published in peer reviewed journals and will inform clinical recommendations being developed by the PeARL Think Tank.PROSPERO registration numbers CRD42020132990, CRD42020171624.</p

    Genetic and environmental interplay in asthma severity and its underlying airway pathology

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    Astma is een chronische inflammatoire aandoening van de luchtwegen, die kinderen en volwassenen van alle leeftijden treft. De WHO schat dat wereldwijd 400 miljoen patiënten astma hebben in 2025. Astma wordt veroorzaakt door een combinatie van genetische en omgevingsfactoren. Astmapatiënten hebben terugkerende aanvallen van piepen, kortademigheid, beklemming op de borst en hoesten, vooral 's nachts of in de vroege ochtend. De klinische ernst van astma is geassocieerd met ontsteking van de luchtwegwand, een verstoorde barrière in het epitheel dat de luchtwegwand bekleedt en een veranderde eiwitsamenstelling van de luchtwegwand (remodellering). Inhalatiecorticosteroïden vormen de basis van de behandeling van astma. De therapie met inhalatiecorticosteroïden leidt tot onderdrukking van ontsteking in de luchtwegen en vermindering van de astmasymptomen en gevoeligheid van de luchtwegen voor ingeademde prikkels zoasl allergenen, mist, koude lucht en sigarettenrook (hyperreactiviteit). Dit proefschrift toont aan dat genetische variatie mede de epitheliale integriteit bepaalt en ook de uitgebreidheid van de luchtwegwandontsteking en remodellering en daaraan gerelateerde ernst van astma op volwassen leeftijd. Daarnaast aan bleek een interactie tussen bepaalde genen en inhalatiesteroïden, en tussen bepaalde genen en roken, de klinische en pathologische expressie van astma te beïnvloeden. Bij kinderen met astma bleek er een verband te bestaan tussen langdurige blootstelling aan luchtverontreiniging en de ernst van luchtwegvernauwing en hyperreactiviteit ( gevoeligheid van luchtwegen). We vonden geen sterk bewijs dat inhalatiecorticosteroïden, die in de studie werd onderzocht, de effecten van luchtverontreiniging kon veranderen, maar wel dat de genetische factoren een rol spelen bij de respons van kinderen met astma op luchtverontreiniging. Asthma is a chronic inflammatory disorder of the airways that affects children and adults of all ages. With this thesis we aimed to understand better the underlying mechanisms of asthma severity. We investigated the role of genes encoding proteins involved in epithelial integrity, chronic airway inflammation and airway remodeling in asthma and showed that genetic variation determines epithelial integrity, the extent of the airway inflammation and remodeling, as well as the subsequent clinical severity (i.e. airway hyperresponsiveness, lung function level and decline over time) of adult individuals with asthma. We showed that gene by inhaled corticosteroids and gene by smoking interactions also play a role in the clinicopathological expression of the disease. We further focused on the susceptibility of asthmatic children to ambient air pollution, an unavoidable environmental exposure of the modern world. We showed associations of long-term air pollution (carbon monoxide and nitrogen dioxide) exposure with severity of airflow obstruction and airway hyperresponsiveness in children with asthma. We did not find strong evidence of modification of pollution effects by controller medication used in a clinical trial. However, we showed that genetics play a role in the respiratory response of asthmatic children to air pollution by potentially regulating oxidant/anti-oxidant cellular mechanisms and inflammation. Understanding the underlying mechanisms of asthma severity and adding to the current knowledge of asthma pathophysiology may ultimately offer better targets for drug development for either prevention or cure of asthma.

    Mediterranean Spotted Fever: Current Knowledge and Recent Advances

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    Mediterranean spotted fever (MSF) is an emerging tick-borne rickettsiosis of the spotted fever group (SFG), endemic in the Mediterranean basin. By virtue of technological innovations in molecular genetics, it has been determined that the causative agent of MSF is Rickettsia conorii subspecies conorii. The arthropod vector of this bacterium is the brown dog tick Rhipicephalus sanguineus. The true nature of the reservoir of R. conorii conorii has not been completely deciphered yet, although many authors theorize that the canine population, other mammals, and the ticks themselves could potentially contribute as reservoirs. Typical symptoms of MSF include fever, maculopapular rash, and a characteristic eschar (“tache noire”). Atypical clinical features and severe multi-organ complications may also be present. All of these manifestations arise from the disseminated infection of the endothelium by R. conorii conorii. Several methods exist for the diagnosis of MSF. Serological tests are widely used and molecular techniques have become increasingly available. Doxycycline remains the treatment of choice, while preventive measures are focused on modification of human behavior and vector control strategies. The purpose of this review is to summarize the current knowledge on the epidemiology, pathogenesis, clinical features, diagnosis, and treatment of MSF

    Mediterranean Spotted Fever: Current Knowledge and Recent Advances

    No full text
    Mediterranean spotted fever (MSF) is an emerging tick-borne rickettsiosis of the spotted fever group (SFG), endemic in the Mediterranean basin. By virtue of technological innovations in molecular genetics, it has been determined that the causative agent of MSF is Rickettsia conorii subspecies conorii. The arthropod vector of this bacterium is the brown dog tick Rhipicephalus sanguineus. The true nature of the reservoir of R. conorii conorii has not been completely deciphered yet, although many authors theorize that the canine population, other mammals, and the ticks themselves could potentially contribute as reservoirs. Typical symptoms of MSF include fever, maculopapular rash, and a characteristic eschar (“tache noire”). Atypical clinical features and severe multi-organ complications may also be present. All of these manifestations arise from the disseminated infection of the endothelium by R. conorii conorii. Several methods exist for the diagnosis of MSF. Serological tests are widely used and molecular techniques have become increasingly available. Doxycycline remains the treatment of choice, while preventive measures are focused on modification of human behavior and vector control strategies. The purpose of this review is to summarize the current knowledge on the epidemiology, pathogenesis, clinical features, diagnosis, and treatment of MSF

    Timing of allergenic food introduction and risk of IgE-mediated food allergy: systematic review and meta-analysis

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    Importance: Earlier egg and peanut introduction probably reduce risk of egg or peanut allergy, but it is uncertain whether food allergy as a whole can be prevented using earlier allergenic food introduction.Objective: This study is a systematic review on timing of allergenic food introduction to the infant diet and risk of food allergy.Data Sources: Medline, Embase and CENTRAL were searched to December 2022.Study Selection: Randomized controlled trials evaluating timing of allergenic food introduction during infancy were included.Data Extraction and Synthesis: Data were extracted in duplicate and synthesized using a random-effects model. GRADE was used to assess certainty of evidence.Main Outcomes and Measures: Primary outcomes were risk of allergy to any food and withdrawal from the intervention. Secondary outcomes included allergy to specific foods.Results: Of 9283 titles screened, data were extracted from 23 eligible trials (56 reports, 13749 randomized participants). There was moderate-certainty evidence from 4 trials (3295 participants) that earlier introduction of multiple allergenic foods at 2 to 12 months (median 3 to 4 months) was associated with reduced food allergy (risk ratio [RR], 0.49; 95% CI, 0.33-0.74; I2=49%). Absolute risk reduction for a population with 5% incidence of food allergy was 26 cases (95% CI, 13-34 cases) per 1000 population. There was moderate-certainty evidence from 5 trials (4703 participants) that earlier introduction of multiple allergenic foods at 2 to 12 months was associated with increased withdrawal from the intervention ([RR], 2.29; 95% CI, 1.45-3.63; I2=89%). Absolute risk difference for a population with 20% withdrawal from the intervention was 258 cases (95% CI, 90-526 cases) per 1000 population. There was high-certainty evidence from 9 trials (4811 participants) that earlier introduction of egg at 3 to 6 months was associated with reduced egg allergy (RR, 0.60; 95% CI, 0.46-0.77; I2=0%); and high-certainty evidence from 4 trials (3796 participants) that earlier introduction of peanut at 3 to 10 months was associated with reduced peanut allergy (RR, 0.31; 95% CI, 0.19-0.51; I2=21%). Evidence for timing of introduction of cow's milk and risk of milk allergy was very low certainty.Conclusions and Relevance: Earlier introduction of multiple allergenic foods was associated with lower risk of developing food allergy, but a high rate of withdrawal from the intervention
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