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

INTRODUCTION: Clinical 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 ANALYSIS: Standard 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 DISSEMINATION: Ethics 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.

The Hidden Burden of Severe Asthma: From Patient Perspective to New Opportunities for Clinicians.

Severe asthma is an important topic in respiratory diseases, due to its high impact on morbidity and mortality as well as on health-care resources. The many challenges that still exist in the management of the most difficult-to-treat forms of the disease, and the acknowledgement of the existence of unexplored areas in the pathophysiological mechanisms and the therapeutic targets represent an opportunity to gather experts in the field with the immediate goals to summarize current understanding about the natural history of severe asthma and to identify gaps in knowledge and research opportunities, with the aim to contribute to improved medical care and health outcomes. This article is a consensus document from the "International Course on Severe Asthma" that took place in Palermo, Italy, on May 10-11, 2019. Emerging topics in severe asthma were addressed and discussed among experts, with special focus on patient's needs and research opportunities, with the aim to highlight the unanswered questions in the diagnostic process and therapeutic approach.

Research Priorities in Pediatric Asthma: Results of a Global Survey of Multiple Stakeholder Groups by the Pediatric Asthma in Real Life (PeARL) Think Tank.

BACKGROUND: Pediatric asthma remains a public health challenge with enormous impact worldwide. OBJECTIVE: The aim of this study was to identify and prioritize unmet clinical needs in pediatric asthma, which could be used to guide future research and policy activities. METHODS: We first identified unmet needs through an open-question survey administered to international experts in pediatric asthma who were members of the Pediatric Asthma in Real Life Think Tank. Prioritization of topics was then achieved through a second, extensive survey with global reach, of multiple stakeholders (leading experts, researchers, clinicians, patients, policy makers, and the pharmaceutical industry). Differences across responder groups were compared. RESULTS: A total of 57 unmet clinical need topics identified by international experts were prioritized by 412 participants from 5 continents and 60 countries. Prevention of disease progression and prediction of future risk, including persistence into adulthood, emerged as the most urgent research questions. Stratified care, based on biomarkers, clinical phenotypes, the children's age, and demographics were also highly rated. The identification of minimum diagnostic criteria in different age groups, cultural perceptions of asthma, and best treatment by age group were priorities for responders from low-middle-income countries. There was good agreement across different stakeholder groups in all domains with some notable exceptions that highlight the importance of involving the whole range of stakeholders in formulation of recommendations. CONCLUSIONS: Different stakeholders agree in the majority of research and strategic (eg, prevention, personalized approach) priorities for pediatric asthma. Stakeholder diversity is crucial for highlighting divergent issues that future guidelines should consider.

Out-of-pocket Costs for Individuals with Atopic Eczema: A Cross-sectional Study in Nine European Countries.

Atopic eczema (AE) is one of the most common non-communicable inflammatory skin diseases, and has a huge socioeconomic impact. Studies on the everyday economic impact of AE on patients, however, are limited. To estimate the annual extra out-of-pocket spending due to AE among patients in Europe, a cross-sectional study using computer-assisted phone interviewing of patients with AE was performed in 9 European countries. A total of 1,189 patients (56% women) with AE, who were either eligible for, or on, systemic treatment, participated in the study between October 2017 and March 2018. Mean extra spending on everyday necessities was €927 per patient per year for healthcare expenses, and this figure was slightly, but not statistically significantly, influenced by the severity of AE. Emollients and moisturizers accounted for the highest monthly costs, followed by medication that was not reimbursed, doctors' and hospital costs. AE-related out-of-pocket costs pose a substantial burden for affected individuals, are higher than in other chronic diseases, and should always be included in economic assessments of the impact of this disease.

Allergic Rhinitis and its Impact on Asthma (ARIA) Phase 4 (2018): Change management in allergic rhinitis and asthma multimorbidity using mobile technology.

Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline by using the best approach to integrated care pathways using mobile technology in patients with allergic rhinitis (AR) and asthma multimorbidity. The proposed next phase of ARIA is change management, with the aim of providing an active and healthy life to patients with rhinitis and to those with asthma multimorbidity across the lifecycle irrespective of their sex or socioeconomic status to reduce health and social inequities incurred by the disease. ARIA has followed the 8-step model of Kotter to assess and implement the effect of rhinitis on asthma multimorbidity and to propose multimorbid guidelines. A second change management strategy is proposed by ARIA Phase 4 to increase self-medication and shared decision making in rhinitis and asthma multimorbidity. An innovation of ARIA has been the development and validation of information technology evidence-based tools (Mobile Airways Sentinel Network [MASK]) that can inform patient decisions on the basis of a self-care plan proposed by the health care professional.

ARIA pharmacy 2018 "Allergic rhinitis care pathways for community pharmacy": AIRWAYS ICPs initiative (European Innovation Partnership on Active and Healthy Ageing, DG CONNECT and DG Santé) POLLAR (Impact of Air POLLution on Asthma and Rhinitis) GARD Demonstration project.

Pharmacists are trusted health care professionals. Many patients use over-the-counter (OTC) medications and are seen by pharmacists who are the initial point of contact for allergic rhinitis management in most countries. The role of pharmacists in integrated care pathways (ICPs) for allergic diseases is important. This paper builds on existing studies and provides tools intended to help pharmacists provide optimal advice/interventions/strategies to patients with rhinitis. The Allergic Rhinitis and its Impact on Asthma (ARIA)-pharmacy ICP includes a diagnostic questionnaire specifically focusing attention on key symptoms and markers of the disease, a systematic Diagnosis Guide (including differential diagnoses), and a simple flowchart with proposed treatment for rhinitis and asthma multimorbidity. Key prompts for referral within the ICP are included. The use of technology is critical to enhance the management of allergic rhinitis. However, the ARIA-pharmacy ICP should be adapted to local healthcare environments/situations as regional (national) differences exist in pharmacy care.

Respiratory disease mortality in the United Kingdom compared with EU15+ countries in 1985-2015: observational study.

OBJECTIVE: To compare age standardised death rates for respiratory disease mortality between the United Kingdom and other countries with similar health system performance. DESIGN: Observational study. SETTING: World Health Organization Mortality Database, 1985-2015. PARTICIPANTS: Residents of the UK, Austria, Belgium, Denmark, Finland, France, Germany, Greece, Ireland, Italy, Luxembourg, the Netherlands, Portugal, Spain, Sweden, Australia, Canada, the United States, and Norway (also known as EU15+ countries). MAIN OUTCOME MEASURES: Mortality from all respiratory disease and infectious, neoplastic, interstitial, obstructive, and other respiratory disease. Differences between countries were tested over time by mixed effect regression models, and trends in subcategories of respiratory related diseases assessed by a locally weighted scatter plot smoother. RESULTS: Between 1985 and 2015, overall mortality from respiratory disease in the UK and EU15+ countries decreased for men and remained static for women. In the UK, the age standardised death rate (deaths per 100 000 people) for respiratory disease mortality in the UK fell from 151 to 89 for men and changed from 67 to 68 for women. In EU15+ countries, the corresponding changes were from 108 to 69 for men and from 35 to 37 in women. The UK had higher mortality than most EU15+ countries for obstructive, interstitial, and infectious subcategories of respiratory disease in both men and women. CONCLUSION: Mortality from overall respiratory disease was higher in the UK than in EU15+ countries between 1985 and 2015. Mortality was reduced in men, but remained the same in women. Mortality from obstructive, interstitial, and infectious respiratory disease was higher in the UK than in EU15+ countries.

Mechanisms of the Development of Allergy (MeDALL): Introducing novel concepts in allergy phenotypes.

Asthma, rhinitis, and eczema are complex diseases with multiple genetic and environmental factors interlinked through IgE-associated and non-IgE-associated mechanisms. Mechanisms of the Development of ALLergy (MeDALL; EU FP7-CP-IP; project no: 261357; 2010-2015) studied the complex links of allergic diseases at the clinical and mechanistic levels by linking epidemiologic, clinical, and mechanistic research, including in vivo and in vitro models. MeDALL integrated 14 European birth cohorts, including 44,010 participants and 160 cohort follow-ups between pregnancy and age 20 years. Thirteen thousand children were prospectively followed after puberty by using a newly standardized MeDALL Core Questionnaire. A microarray developed for allergen molecules with increased IgE sensitivity was obtained for 3,292 children. Estimates of air pollution exposure from previous studies were available for 10,000 children. Omics data included those from historical genome-wide association studies (23,000 children) and DNA methylation (2,173), targeted multiplex biomarker (1,427), and transcriptomic (723) studies. Using classical epidemiology and machine-learning methods in 16,147 children aged 4 years and 11,080 children aged 8 years, MeDALL showed the multimorbidity of eczema, rhinitis, and asthma and estimated that only 38% of multimorbidity was attributable to IgE sensitization. MeDALL has proposed a new vision of multimorbidity independent of IgE sensitization, and has shown that monosensitization and polysensitization represent 2 distinct phenotypes. The translational component of MeDALL is shown by the identification of a novel allergic phenotype characterized by polysensitization and multimorbidity, which is associated with the frequency, persistence, and severity of allergic symptoms. The results of MeDALL will help integrate personalized, predictive, preventative, and participatory approaches in allergic diseases.

MACVIA clinical decision algorithm in adolescents and adults with allergic rhinitis.

The selection of pharmacotherapy for patients with allergic rhinitis (AR) depends on several factors, including age, prominent symptoms, symptom severity, control of AR, patient preferences, and cost. Allergen exposure and the resulting symptoms vary, and treatment adjustment is required. Clinical decision support systems (CDSSs) might be beneficial for the assessment of disease control. CDSSs should be based on the best evidence and algorithms to aid patients and health care professionals to jointly determine treatment and its step-up or step-down strategy depending on AR control. Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR [fighting chronic diseases for active and healthy ageing]), one of the reference sites of the European Innovation Partnership on Active and Healthy Ageing, has initiated an allergy sentinel network (the MACVIA-ARIA Sentinel Network). A CDSS is currently being developed to optimize AR control. An algorithm developed by consensus is presented in this article. This algorithm should be confirmed by appropriate trials.

Integrated Allergy and Asthma Prevention and Care: Report of the MeDALL/AIRWAYS ICPs Meeting at the Ministry of Health and Care Services, Oslo, Norway.

Allergic diseases and asthma are increasing in prevalence globally. They can start early in life and many persist. It is important to prevent, detect and control these diseases early on and throughout life, so as to promote active and healthy ageing. The translational activities of MeDALL (Mechanisms of the Development of Allergy; EU FP7) are of great importance and include the deployment of successful allergy programmes. The Finnish Allergy Plan is a prototype for the prevention and control of severe allergic diseases. It has been considered for deployment to Norway by the Ministry of Health and Care Services in the frame of AIRWAYS ICPs (Integrated Care Pathways for Airway Diseases), a programme of Action Plan B3 of the EIP on AHA (European Innovation Partnership on Active and Healthy Ageing). Deployment of the Finnish and Norwegian Plans will make use of the scaling-up strategy of the EIP on AHA in regions in the European Union, and the WHO GARD (Global Alliance against Chronic Respiratory Diseases) globally. The regional deployment in Norway serves as a model of a national plan for the use of the EIP on AHA scaling-up strategy in other regions.