Urokinase plasminogen activator receptor polymorphisms and airway remodelling in asthma

PLAUR polymorphisms and levels are associated with markers of airway remodelling in lung biopsies of asthma patients http://ow.ly/X5Sr

Increase in anaphylaxis-related hospitalizations but no increase in fatalities: An analysis of United Kingdom national anaphylaxis data, 1992-2012

BackgroundThe incidence of anaphylaxis might be increasing. Data for fatal anaphylaxis are limited because of the rarity of this outcome.ObjectiveWe sought to document trends in anaphylaxis admissions and fatalities by age, sex, and cause in England and Wales over a 20-year period.MethodsWe extracted data from national databases that record hospital admissions and fatalities caused by anaphylaxis in England and Wales (1992-2012) and crosschecked fatalities against a prospective fatal anaphylaxis registry. We examined time trends and age distribution for fatal anaphylaxis caused by food, drugs, and insect stings.ResultsHospital admissions from all-cause anaphylaxis increased by 615% over the time period studied, but annual fatality rates remained stable at 0.047 cases (95% CI, 0.042-0.052 cases) per 100,000 population. Admission and fatality rates for drug- and insect sting–induced anaphylaxis were highest in the group aged 60 years and older. In contrast, admissions because of food-triggered anaphylaxis were most common in young people, with a marked peak in the incidence of fatal food reactions during the second and third decades of life. These findings are not explained by age-related differences in rates of hospitalization.ConclusionsHospitalizations for anaphylaxis increased between 1992 and 2012, but the incidence of fatal anaphylaxis did not. This might be due to increasing awareness of the diagnosis, shifting patterns of behavior in patients and health care providers, or both. The age distribution of fatal anaphylaxis varies significantly according to the nature of the eliciting agent, which suggests a specific vulnerability to severe outcomes from food-induced allergic reactions in the second and third decades

Diet during pregnancy and infancy, and risk of allergic or autoimmune disease: a systematic review and meta-analysis

Background: There is uncertainty about the influence of diet during pregnancy and infancy on a child’s immune development. We assessed whether variations in maternal or infant diet can influence risk of allergic or autoimmune disease. Methods and findings: Two authors selected studies, extracted data, and assessed risk of bias. Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to assess certainty of findings. We searched Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica dataBASE (EMBASE), Web of Science, Central Register of Controlled Trials (CENTRAL), and Literatura Latino Americana em Ciências da Saúde (LILACS) between January 1946 and July 2013 for observational studies and until December 2017 for intervention studies that evaluated the relationship between diet during pregnancy, lactation, or the first year of life and future risk of allergic or autoimmune disease. We identified 260 original studies (964,143 participants) of milk feeding, including 1 intervention trial of breastfeeding promotion, and 173 original studies (542,672 participants) of other maternal or infant dietary exposures, including 80 trials of maternal (n = 26), infant (n = 32), or combined (n = 22) interventions. Risk of bias was high in 125 (48%) milk feeding studies and 44 (25%) studies of other dietary exposures. Evidence from 19 intervention trials suggests that oral supplementation with nonpathogenic micro-organisms (probiotics) during late pregnancy and lactation may reduce risk of eczema (Risk Ratio [RR] 0.78; 95% CI 0.68–0.90; I2 = 61%; Absolute Risk Reduction 44 cases per 1,000; 95% CI 20–64), and 6 trials suggest that fish oil supplementation during pregnancy and lactation may reduce risk of allergic sensitisation to egg (RR 0.69, 95% CI 0.53–0.90; I2 = 15%; Absolute Risk Reduction 31 cases per 1,000; 95% CI 10–47). GRADE certainty of these findings was moderate. We found weaker support for the hypotheses that breastfeeding promotion reduces risk of eczema during infancy (1 intervention trial), that longer exclusive breastfeeding is associated with reduced type 1 diabetes mellitus (28 observational studies), and that probiotics reduce risk of allergic sensitisation to cow’s milk (9 intervention trials), where GRADE certainty of findings was low. We did not find that other dietary exposures—including prebiotic supplements, maternal allergenic food avoidance, and vitamin, mineral, fruit, and vegetable intake—influence risk of allergic or autoimmune disease. For many dietary exposures, data were inconclusive or inconsistent, such that we were unable to exclude the possibility of important beneficial or harmful effects. In this comprehensive systematic review, we were not able to include more recent observational studies or verify data via direct contact with authors, and we did not evaluate measures of food diversity during infancy. Conclusions: Our findings support a relationship between maternal diet and risk of immune-mediated diseases in the child. Maternal probiotic and fish oil supplementation may reduce risk of eczema and allergic sensitisation to food, respectively

2019 ARIA Care pathways for allergen immunotherapy

Allergen immunotherapy (AIT) is a proven therapeutic option for the treatment of allergic rhinitis and/or asthma. Many guidelines or national practice guidelines have been produced but the evidence-based method varies, many are complex and none propose care pathways. This paper reviews care pathways for AIT using strict criteria and provides simple recommendations that can be used by all stakeholders including healthcare professionals. The decision to prescribe AIT for the patient should be individualized and based on the relevance of the allergens, the persistence of symptoms despite appropriate medications according to guidelines as well as the availability of good-quality and efficacious extracts. Allergen extracts cannot be regarded as generics. Immunotherapy is selected by specialists for stratified patients. There are no currently available validated biomarkers that can predict AIT success. In adolescents and adults, AIT should be reserved for patients with moderate/severe rhinitis or for those with moderate asthma who, despite appropriate pharmacotherapy and adherence, continue to exhibit exacerbations that appear to be related to allergen exposure, except in some specific cases. Immunotherapy may be even more advantageous in patients with multimorbidity. In children, AIT may prevent asthma onset in patients with rhinitis. mHealth tools are promising for the stratification and follow-up of patients.Peer reviewe

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

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

ARIA digital anamorphosis : Digital transformation of health and care in airway diseases from research to practice

Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.Peer reviewe

ARIA digital anamorphosis: Digital transformation of health and care in airway diseases from research to practice

Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed

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

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.