Managing the allergy and asthma epidemic in 2020s-Lessons from the Finnish experience.

In Finland, a systematic public health programme was implemented from 2008 to 2018 to mitigate the burden of allergic disorders by revisiting the prevention strategy. Allergy health and contacts with natural environment were emphasized to promote immunological and psychological resilience instead of poorly justified avoidance. Allergy management practices were improved and low-valued recommendations for care, for example for food allergy, were revised. Patients and families were empowered to use guided self-management to proactively stop symptom exacerbations. A professional non-governmental organization implemented the nationwide education for healthcare and patient NGOs for patients, families and lay public. In healthcare, the work supporting allergic patients and families was organized towards common goals and integrated into everyday work without extra costs. Reaching the predefined goals was followed by employing the national healthcare registers and questionnaire surveys. Governmental bodies contributed with kick-off funding, which was supplemented by private funding. International collaboration, for example with the European patient organization (EFA), increased awareness of the Finnish action and predisposed it for peer review. The 10-year results are favourable, patients are less disabled, practices and attitudes in healthcare have changed, and major cost savings have been obtained. Views of the lay public and patients are slow to move, however. Local multidisciplinary allergy teams were set up to continue the activities also after the Programme. Changes in environment and lifestyle in the last 50 years are the main reasons for the allergy rise. The Finnish experience may help to manage allergic diseases, improve nature relatedness in the fast-urbanizing world, combat nature loss and reduce the disease burden.

The Finnish Allergy Program 2008-2018: Society-wide proactive program for change of management to mitigate allergy burden.

A 10-year national program to improve prevention and management of allergic diseases and asthma was implemented in Finland (population 5.5. million) in 2008-2018. The main aim was to reduce the long-term burden of these conditions. The strategy was changed from traditional avoidance to tolerance and resilience of the population. Health was endorsed instead of medicalization of mild symptoms. Disease severity was reevaluated, and disabling clinical manifestations were given high priority. For health care, 5 quantitative goals and 1 qualitative goal were set. For each of the goals, specific tasks, tools, and outcome evaluation were stipulated. During the program, 376 educational sessions gathered 24,000 health care participants. An information campaign targeted the lay public, and social media was used to contact people. In the 10 years of the program, the prevalence of allergic diseases and asthma leveled off. Asthma caused fewer symptoms and less disability, and 50% fewer hospital days. Food allergy diets in day care and schools decreased by half. Occupational allergies were reduced by 45%. In 2018, the direct and indirect costs of allergic diseases and asthma ranged from €1.5 billion to €1.8 billion, with the 2018 figures being 30% less than in the respective figures in 2007. The Finnish proactive and real-world intervention markedly reduced the public health burden of allergic disorders. The allergy paradigm was revisited to improve management with systematic education.

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.

The SQ tree SLIT-tablet is highly effective and well tolerated: Results from a randomized, double-blind, placebo-controlled phase III trial.

BACKGROUND: The SQ tree sublingual immunotherapy (SLIT)-tablet (ALK-Abelló, Hørsholm, Denmark) is developed for treatment of tree pollen-induced allergic rhinoconjunctivitis (ARC). OBJECTIVE: The aim of this pivotal phase III trial was to demonstrate the efficacy and safety of the SQ tree SLIT-tablet. METHODS: This was a randomized, double-blind, placebo-controlled trial with 634 subjects (12-65 years) with moderate-to-severe ARC despite use of symptom-relieving medication. Eligible subjects were randomized 1:1 to active or placebo treatment. The primary end point was the average daily ARC total combined score (TCS) during the birch pollen season (BPS) analyzed for subjects with diary data during the BPS. Secondary end points included average daily symptom scores (DSS) during the BPS, average TCS and DSS during the tree pollen season (TPS), and average daily medication scores (DMS) in the BPS and TPS. RESULTS: The primary and key secondary end points demonstrated statistically significant and clinically relevant effects of the SQ tree SLIT-tablet compared with placebo. For the BPS, absolute (relative) differences from placebo were 3.02 (40%) for TCS, 1.32 (37%) for DSS, and 1.58 (49%) for DMS (all P < .0001). For the TPS, absolute (relative) differences from placebo were 2.27 (37%) for TCS, 0.99 (33%) for DSS, and 1.20 (47%) for DMS (all P < .0001). Treatment was well tolerated. The most frequently reported treatment-related adverse events were mild or moderate local reactions related to sublingual administration. CONCLUSION: The trial demonstrated the efficacy and safety of the SQ tree SLIT-tablet compared with placebo during the BPS and TPS in adolescents and adults with birch pollen-induced ARC (EudraCT 2015-004821-15).

Efficacy and safety of birch pollen allergoid subcutaneous immunotherapy: A 2-year double-blind, placebo-controlled, randomized trial plus 1-year open-label extension.

BACKGROUND: Previous clinical trials with birch pollen subcutaneous immunotherapy have been conducted over a 1- to 2-year treatment period and involved mostly a single geographic location. OBJECTIVE: This study (EudraCT-Number: 2005-000025-35) intended to evaluate the effect of subcutaneous immunotherapy with high-dose hypoallergenic birch pollen allergoid in patients with confirmed moderate to severe seasonal allergic rhinitis/rhinoconjunctivitis over a 3-year course in 19 European centres. METHODS: Adults with confirmed birch pollen allergy (n = 253) were randomized to preseasonal placebo (n = 129) or active treatment (n = 124). Primary endpoint was change in Symptom Medication Score after 2 years treatment (2007). RESULTS: The change in Symptom Medication Score of active- vs placebo-treated patients for the Full Analysis Set (n = 227, 15.2% reduction, P = 0.0710) and Per-Protocol Set (n = 216, 16.7% reduction, P = 0.0523) showed a positive trend, although significance was not achieved. The primary endpoint, assessed in 2007, coincided with the lowest pollination during the study period. In a subgroup analysis of patients in the north-eastern region (n = 102), where birch is the major tree and consequently patients' exposure is higher, changes in Symptom Medication Score (32.7% reduction, P = 0.0034) and median number of well days (P = 0.0232) were highly significant in favour of the active group. During the open-label third year of treatment, the mean Symptom Medication Score of active-treated patients was further reduced despite an increased pollen count. Subcutaneous immunotherapy was well tolerated and consistent with the known safety profile. CONCLUSIONS AND CLINICAL RELEVANCE: Although the primary endpoint was not reached for the Full Analysis Set, a significant and clinically relevant effect on Symptom Medication Score was clearly demonstrated for the subgroup of patients in the north-eastern region of Europe, where birch is the predominant tree species. Proving efficacy of birch allergen subcutaneous immunotherapy is challenging due to the numerous factors influencing birch pollen allergen exposure in field studies.

Results from the 5-year SQ grass sublingual immunotherapy tablet asthma prevention (GAP) trial in children with grass pollen allergy.

BACKGROUND: Allergy immunotherapy targets the immunological cause of allergic rhinoconjunctivitis and allergic asthma and has the potential to alter the natural course of allergic disease. OBJECTIVE: The primary objective was to investigate the effect of the SQ grass sublingual immunotherapy tablet compared with placebo on the risk of developing asthma. METHODS: A total of 812 children (5-12 years), with a clinically relevant history of grass pollen allergic rhinoconjunctivitis and no medical history or signs of asthma, were included in the randomized, double-blind, placebo-controlled trial, comprising 3 years of treatment and 2 years of follow-up. RESULTS: There was no difference in time to onset of asthma, defined by prespecified asthma criteria relying on documented reversible impairment of lung function (primary endpoint). Treatment with the SQ grass sublingual immunotherapy tablet significantly reduced the risk of experiencing asthma symptoms or using asthma medication at the end of trial (odds ratio = 0.66, P < .036), during the 2-year posttreatment follow-up, and during the entire 5-year trial period. Also, grass allergic rhinoconjunctivitis symptoms were 22% to 30% reduced (P < .005 for all 5 years). At the end of the trial, the use of allergic rhinoconjunctivitis pharmacotherapy was significantly less (27% relative difference to placebo, P < .001). Total IgE, grass pollen-specific IgE, and skin prick test reactivity to grass pollen were all reduced compared to placebo. CONCLUSIONS: Treatment with the SQ grass sublingual immunotherapy tablet reduced the risk of experiencing asthma symptoms and using asthma medication, and had a positive, long-term clinical effect on rhinoconjunctivitis symptoms and medication use but did not show an effect on the time to onset of asthma.

Electronic Clinical Decision Support System for allergic rhinitis management: MASK e-CDSS.

BACKGROUND: Allergic rhinitis (AR) management has changed in recent years following the switch from the concept of disease severity to the concept of disease control, publication of the AR clinical decision support system (CDSS) and development of mobile health (m-health) tools for patients (eg Allergy Diary). The Allergy Diary Companion app for healthcare providers is currently being developed and will be launched in 2018. It incorporates the AR CDSS to provide evidence-based treatment recommendations, linking all key stakeholders in AR management. OBJECTIVE: To produce an electronic version of the AR CDSS (e-CDSS) for incorporation into the Allergy Diary Companion, to describe the app interfaces used to collect information necessary to inform the e-CDSS and to summarize some key features of the Allergy Diary Companion. METHODS: The steps involved in producing the e-CDSS and incorporating it into the Allergy Diary Companion were (a) generation of treatment management scenarios; (b) expert consensus on treatment recommendations; (c) generation of electronic decisional algorithms to describe all AR CDSS scenarios; (d) digitization of these algorithms to form the e-CDSS; and (e) embedding the e-CDSS into the app to permit easy user e-CDSS interfacing. RESULTS: Key experts in the AR field agreed on the AR CDSS approach to AR management and on specific treatment recommendations provided by Allergy Diary Companion. Based on this consensus, decision processes were developed and programmed into the Allergy Diary Companion using Titanium Appcelerator (JavaScript) for IOS tablets. To our knowledge, this is the first time the development of any m-health tool has been described in this transparent and detailed way, providing confidence, not only in the app, but also in the provided management recommendations. CONCLUSION: The Allergy Diary Companion for providers provides guideline and expert-endorsed AR management recommendations. [MASK paper No 32].

Current state and future of pediatric allergology in Europe: A road map.

The history of pediatric allergology (PA) in Europe is relatively youthful, dating back to 1984, when a small group of pediatricians founded the European Working Group on Pediatric Allergy and Immunology-later giving rise to ESPACI (European Society on Pediatric Allergology and Clinical Immunology). In 1990, the first dedicated journal, Pediatric Allergy and Immunology (PAI), was founded. There are striking differences across Europe, and even within European countries, in relation to the training pathways for doctors seeing children with allergic disease(s). In 2016, the EAACIClemens von Pirquet Foundation (CvP) organized and sponsored a workshop with the European Academy of Allergy and Clinical Immunology (EAACI) Pediatric Section. This collaboration focussed on the future of PA and specifically on education, research, and networking/ advocacy. The delegates representing many countries across Europe have endorsed the concept that optimal care of children with allergic diseases is delivered by pediatricians who have received dedicated training in allergy, or allergists who have received dedicated training in pediatrics. In order to meet the needs of children and families with allergic disease(s), the pediatric allergist is highly encouraged to develop several networks. Our challenge is to reinforce a clear strategic approach to scientific excellence to across our member base and to ensure and enhance the relevance of European pediatric research in allergy. With research opportunities in basic, translational, clinical, and epidemiologic trials, more trainees and trained specialists are needed and it is an exciting time to be a pediatric allergologist.

Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines-2016 revision.

BACKGROUND: Allergic rhinitis (AR) affects 10% to 40% of the population. It reduces quality of life and school and work performance and is a frequent reason for office visits in general practice. Medical costs are large, but avoidable costs associated with lost work productivity are even larger than those incurred by asthma. New evidence has accumulated since the last revision of the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines in 2010, prompting its update. OBJECTIVE: We sought to provide a targeted update of the ARIA guidelines. METHODS: The ARIA guideline panel identified new clinical questions and selected questions requiring an update. We performed systematic reviews of health effects and the evidence about patients' values and preferences and resource requirements (up to June 2016). We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence-to-decision frameworks to develop recommendations. RESULTS: The 2016 revision of the ARIA guidelines provides both updated and new recommendations about the pharmacologic treatment of AR. Specifically, it addresses the relative merits of using oral H1-antihistamines, intranasal H1-antihistamines, intranasal corticosteroids, and leukotriene receptor antagonists either alone or in combination. The ARIA guideline panel provides specific recommendations for the choice of treatment and the rationale for the choice and discusses specific considerations that clinicians and patients might want to review to choose the management most appropriate for an individual patient. CONCLUSIONS: Appropriate treatment of AR might improve patients' quality of life and school and work productivity. ARIA recommendations support patients, their caregivers, and health care providers in choosing the optimal treatment.

Physicians' experience and opinion on contraindications to allergen immunotherapy: The CONSIT survey.

BACKGROUND: Allergen immunotherapy (AIT) is the only disease-modifying treatment in allergy but several contraindications limit its use. OBJECTIVE: To collect the outcome of using AIT in theoretically contraindicated situations in real patients in the Contraindications to Specific ImmunoTherapy (CONSIT) survey. METHODS: The CONSIT is an electronic European Academy of Allergy and Clinical Immunology survey conducted to gather the safety outcomes of patients undergoing subcutaneous, sublingual, or venom AIT and the opinions of physicians on each of 17 selected conditions: children younger than 5 years; starting AIT during pregnancy; controlled severe asthma; arrhythmias; coronary disease; cancer; autoimmune disease; bone marrow and solid organ transplantation; human immunodeficiency virus and acquired immunodeficiency syndrome; previous anaphylaxis during AIT; use of ß-blockers, angiotensin-converting inhibitors, cyclosporine, and methotrexate; and inability to communicate. Safety using AIT was reported in a 3-point scale: 1, "no problems"; 2, "minor problems" (requiring only dose modifications); and 3, "major problems" (AIT not tolerated). Each physician was asked about the degree of contraindication that each condition should have: no contraindication (score 1), relative contraindication (score 2), or absolute contraindication (score 3). RESULTS: Five hundred twenty physicians (75% Europeans, 89% allergists) reported on approximately 45,000 patients undergoing AIT with any of these conditions. Major problems were infrequent, occurring more frequently in patients with asthma (9.9%) and with previous anaphylaxis from AIT (9.5%). Regarding opinions, experienced physicians scored a significantly lower mean for all conditions than non-experienced physicians for all routes. CONCLUSION: Major problems were infrequent and experienced physicians were less likely to be restrictive in the use of AIT.

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.

Efficacy of MP-AzeFlu in children with seasonal allergic rhinitis: Importance of paediatric symptom assessment.

BACKGROUND: This study aimed to assess the efficacy of MP-AzeFlu (a novel intranasal formulation of azelastine hydrochloride and fluticasone propionate in a single spray) in children with seasonal allergic rhinitis (SAR) and explore the importance of child symptom severity assessment in paediatric allergic rhinitis (AR) trials. METHODS: A total of 348 children (4-11 years) with moderate/severe SAR were randomized into a double-blind, placebo-controlled, 14-day, parallel-group trial. Efficacy was assessed by changes from baseline in reflective total nasal symptom score (rTNSS), reflective total ocular symptom score (rTOSS) and individual symptom scores over 14 days (children 6-11 years; n = 304), recorded by either children or caregivers. To determine whether a by-proxy effect existed, efficacy outcomes were assessed according to degree of child/caregiver rating. Moreover, total Paediatric Rhinitis Quality of Life Questionnaire (PRQLQ) score was compared between the groups. RESULTS: A statistically superior, clinically relevant efficacy signal of MP-AzeFlu versus placebo was apparent for PRQLQ overall score (diff: -0.29, 95% CI -0.55, -0.03; p = 0.027), but not for rTNSS (diff: -0.80; 95% CI: -1.75; 0.15; p = 0.099). However, as the extent of children's self-rating increased, so too did the treatment difference between MP-AzeFlu and placebo; MP-AzeFlu provided significantly better relief than placebo for rTNSS (p = 0.002), rTOSS (p = 0.009) and each individual nasal and ocular symptom assessed (except rhinorrhoea; p = 0.064) when children mostly rated their own symptoms. CONCLUSIONS: MP-AzeFlu is an effective treatment for AR in childhood. Caregivers are less able than children to accurately assess response to treatment with available tools. A simple paediatric-specific tool to assess efficacy in AR trials in children is needed.

Allergy and asthma prevention 2014.

Asthma and allergic diseases have become one of the epidemics of the 21st century in developed countries. Much of the success of other areas of medicine, such as infectious diseases, lies on preventive measures. Thus, much effort is also being placed lately in the prevention of asthma and allergy. This manuscript reviews the current evidence, divided into four areas of activity. Interventions modifying environmental exposure to allergens have provided inconsistent results, with multifaceted interventions being more effective in the prevention of asthma. Regarding nutrition, the use of hydrolyzed formulas in high-risk infants reduces the incidence of atopic dermatitis, while there is for now not enough evidence to recommend other dietary modifications, prebiotics, probiotics, or other microbial products. Pharmacologic agents used until now for prevention have not proved useful, while there is hope that antiviral vaccines could be useful in the future. Allergen-specific immunotherapy is effective for the treatment of allergic patients with symptoms; the study of its value for primary and secondary prevention of asthma and allergy is in its very preliminary phases. The lack of success in the prevention of these disorders lies on their complexity, which involves many genetic, epigenetic, and environmental interactions. There is a need to identify target populations, involved mechanisms and interactions, and the best interventions. These must be effective, feasible, implementable, and affordable.

Diagnosing new-onset asthma in a paediatric clinical trial setting in school-age children.

Asthma is a common chronic disease in children. It is a dynamic condition-symptoms change over time, and the outcome of diagnostic tests can vary. Consequently, evaluating the onset of asthma at a single point in time, perhaps when patients are asymptomatic with limited impairment of the lung function, may result in false diagnostic conclusions. The absence of consistent gold-standard diagnostic criteria in children challenges the ability of any study to ascertain an effect of treatment on asthma prevention. A comprehensive review of the diagnostic criteria used for new-onset asthma in school-age children was conducted based on existing recommendations from published clinical guidance, alongside evidence from paediatric asthma prevention trials. Findings from the review were used to propose suggestions for diagnosing new-onset asthma in future asthma prevention trials. Despite an overall lack of consensus in the published clinical guidance, there are similarities between the various recommendations for diagnosing asthma in children, which typically involve assessing the variable symptoms and supplementing the medical history with objective measures of lung function. For future paediatric asthma prevention trials, we suggest that paediatric clinical trials should use a new-onset asthma definition that incorporates the concepts of "possible", "probable" and "confirmed" asthma. "Possible" asthma would capture self-reported features of chronic symptoms and symptom relief with ß2-agonist bronchodilator (suggesting reversibility). "Probable" asthma would include symptom chronicity, self-reported symptom relief with ß2-agonist bronchodilator, and objective features of asthma (reversibility or bronchial hyper-responsiveness). A "confirmed" diagnosis would be made only if there is a positive response to controller therapy. These suggestions aim to improve the diagnosis of new-onset childhood asthma in clinical trials, which will be useful in the design and conduct of future paediatric asthma prevention trials.

[Update on current care guidelines: asthma]. / Astma.

Asthma is an inflammatory disease of the lower airways. The typical symptoms of asthma are cough, wheezing and shortness of breath. Asthma is diagnosed based on measures of pulmonary function showing variable or reversible airways obstruction. The basic pharmacological treatment consists of alleviating the asthmatic inflammation with regular inhaled glucocorticoids and relieving sudden obstructions with as-needed inhaled beta2-agonists. The treatment is adjusted based on asthma control. If good control of asthma is not achieved with low to medium doses of inhaled glucocorticoids, additional control medication (inhaled long acting beta2-agonists, antileukotrienes, in adults also theophylline or tiotrohium) should be introduced.

A short history from Karelia study to biodiversity and public health interventions.

Contact with natural environments enriches the human microbiome, promotes immune balance and protects against allergies and inflammatory disorders. In Finland, the allergy & asthma epidemic became slowly visible in mid 1960s. After the World War II, Karelia was split into Finnish and Soviet Union (now Russia) territories. This led to more marked environmental and lifestyle changes in the Finnish compared with Russian Karelia. The Karelia Allergy Study 2002-2022 showed that allergic conditions were much more common on the Finnish side. The Russians had richer gene-microbe network and interaction than the Finns, which associated with better balanced immune regulatory circuits and lower allergy prevalence. In the Finnish adolescents, a biodiverse natural environment around the homes associated with lower occurrence of allergies. Overall, the plausible explanation of the allergy disparity was the prominent change in environment and lifestyle in the Finnish Karelia from 1940s to 1980s. The nationwide Finnish Allergy Programme 2008-2018 implemented the biodiversity hypothesis into practice by endorsing immune tolerance, nature contacts, and allergy health with favorable results. A regional health and environment programme, Nature Step to Health 2022-2032, has been initiated in the City of Lahti, EU Green Capital 2021. The programme integrates prevention of chronic diseases (asthma, diabetes, obesity, depression), nature loss, and climate crisis in the spirit of Planetary Health. Allergic diseases exemplify inappropriate immunological responses to natural environment. Successful management of the epidemics of allergy and other non-communicable diseases may pave the way to improve human and environmental health.

Nocturnal temperature controlled laminar airflow for treating atopic asthma: a randomised controlled trial.

OBJECTIVE: To determine whether environmental control using nocturnal temperature controlled laminar airflow (TLA) treatment could improve the quality of life of patients with persistent atopic asthma. DESIGN: Randomised, double-blind, placebo-controlled, parallel-group trial. Setting Nineteen European asthma clinics. PARTICIPANTS: 312 patients aged 7-70 with inadequately controlled persistent atopic asthma. MAIN OUTCOME MEASURE: Proportion of patients with an increase of ≥0.5 points in asthma quality of life score after 1 year of treatment. RESULTS: TLA devices were successfully installed in the bedrooms of 282 (90%) patients included in the primary efficacy analysis. There was a difference in treatment response rate between active (143 of 189, 76%) and placebo (56 of 92, 61%) groups, difference 14.8% (95% CI 3.1 to 26.5, p=0.02).3 In patients aged ≥12, on whom the study was powered, the difference in response rate was similar-active 106 of 143 (74%), placebo 42 of 70 (60%), difference 14.1% (0.6 to 27.7, p=0.059). There was a difference between groups in fractional exhaled nitric oxide change of -7.1 ppb (-13.6 to -0.7, p=0.03). Active treatment was associated with less increase in cat-specific IgE than placebo. There was no difference in adverse event rates between treatment groups. CONCLUSION: Inhalant exposure reduction with TLA improves quality of life, airway inflammation and systemic allergy in patients with persistent atopic asthma. TLA may be a treatment option for patients with inadequately controlled persistent atopic asthma. Trial registration number Clinical Trials NCT00986323.