Efficacy of a Non-Pharmacological Intervention in Seasonal Allergic Rhinitis Symptoms.

BACKGROUND: Patients suffering from allergic rhinitis seek for several therapeutic symptomatic options, including nonconventional treatments, to control their symptoms. OBJECTIVES: Through the present proof-of-concept study, we prospectively investigated the potential role of Puressentiel® nasal protection spray (SNPA) in patients suffering from cypress pollen allergic rhinitis. METHODS: In 15 adults, we performed two nasal provocation tests, with a cypress pollen extract, with a 15-day interval, with and without previous randomized administration of SNPA, and evaluated a nasal symptom score, the nasal inspiratory peak flow, and the concentration of inflammatory cytokines in the nasal lavage after the procedures. RESULTS: Comparing results in patients challenged with and without the SNPA spray before the nasal challenge, we found a 57% mean decrease in symptoms, and a 62% average difference in inspiratory peak flow, after the use of the spray. CONCLUSIONS: Puressentiel® SNPA is effective in reducing nasal symptoms, as assessed by nasal symptoms score and nasal inspiratory peak flow, and could be a valid natural non-pharmacological option in patients suffering from allergic rhinitis.

[Biotherapies in severe childhood asthma]. / Biothérapies dans l'asthme sévère de l'enfant.

BIOTHERAPIES IN SEVERE CHILDHOOD ASTHMA. Asthma is a chronic inflammatory disease of the lower airways and is one of the most common chronic conditions during childhood. The management of severe asthmatic patients must be multidisciplinary, personalized, and holistic, especially in pediatrics. The therapeutic approach to asthmatic patients has evolved over the last years, targeting inflammatory cells and molecules. Such treatments mainly include biotherapies, and, in children, four monoclonal antibodies are presently available to treat severe asthma: omalizumab, mepolizumab, dupilumab and tezepelumab. These biotherapies have demonstrated short- and medium-term efficacy and safety in both adults and children.

BIOTHÉRAPIES DANS L'ASTHME SÉVÈRE DE L'ENFANT. L'asthme est une maladie inflammatoire chronique des voies aériennes inférieures, et une des affections chroniques les plus fréquentes chez l'enfant. La prise en charge de l'asthme sévère doit être personnalisée, multidisciplinaire et holistique, d'autant plus en pédiatrie. Les approches thérapeutiques ont évolué au cours de ces dernières années et, dans les formes sévères, ciblent directement les acteurs de la cascade inflammatoire. Ces traitements incluent notamment les biothérapies, et, chez l'enfant, quatre molécules sont actuellement disponibles : l'omalizumab, le mépolizumab, le dupilumab et le tézépélumab. Ces biothérapies ont montré une efficacité et une sécurité d'utilisation à court et moyen terme chez l'adulte comme chez l'enfant.

Epidemiology of anaphylaxis.

PURPOSE OF REVIEW: To understand the current global epidemiological data of anaphylaxis and identify potential strategies to improve patients' care and prevention. RECENT FINDINGS: Anaphylaxis mortality and morbidity statistics (MMS) may gain new perspectives with the implementation of the International Classification of Diseases (ICD)-11 in the forthcoming years. Improving the quality of epidemiological data related to anaphylaxis should clarify some areas of uncertainty about risk factors, leading to better targeting of strategies to protect those patients at risk, and support decision-making to facilitate healthcare planning and implementation of public health measures to prevent anaphylaxis. SUMMARY: Anaphylaxis is a complex noncommunicable diseases with adverse impact on health-related quality of life of patients and their carriers and a significant proportion of deaths may be preventable. It requires an integrated holistic plan to improve quality of healthcare and gathering accurate and comparable epidemiological data is key. Morbidity related to anaphylaxis seems to be increasing worldwide whereas mortality of anaphylaxis appears to be low and stable, but this still has great challenges in capturing quality anaphylaxis MMS. Improving the quality of epidemiological data related to anaphylaxis should clarify some areas of uncertainty about risk factors, leading to better targeting of strategies to protect those patients at risk. As knowledge derived from populations is key information for more realistic decision-making, the construction of the new section addressed to anaphylaxis in the ICD-11 will allow the collection of more accurate epidemiological data to support quality management of patients, and better facilitate healthcare planning to implement public health measures to prevent and reduce the morbidity and mortality attributable to these conditions.

Pollen season is reflected on symptom load for grass and birch pollen-induced allergic rhinitis in different geographic areas-An EAACI Task Force Report.

BACKGROUND: The effectiveness of allergen immunotherapy (AIT) in seasonal and perennial allergic rhinitis (AR) depends on the definition of pollen exposure intensity or time period. We recently evaluated pollen and symptom data from Germany to examine the new definitions of the European Academy of Allergy and Clinical Immunology (EAACI) on pollen season and peak pollen period start and end. Now, we aim to confirm the feasibility of these definitions to properly mirror symptom loads for grass and birch pollen-induced allergic rhinitis in other European geographical areas such as Austria, Finland and France, and therefore their suitability for AIT and clinical practice support. METHODS: Data from twenty-three pollen monitoring stations from three countries in Europe and for 3 years (2014-2016) were used to investigate the correlation between birch and grass pollen concentrations during the birch and grass pollen season defined via the EAACI criteria, and total nasal symptom and medication scores as reported with the aid of the patient's hay-fever diary (PHD). In addition, we conducted a statistical analysis, together with a graphical investigation, to reveal correlations and dependencies between the studied parameters. RESULTS: The analysis demonstrated that the definitions of pollen season as well as peak pollen period start and end as proposed by the EAACI are correlated to pollen-induced symptom loads reported by PHD users during birch and grass pollen season. A statistically significant correlation (slightly higher for birch) has been found between the Total Nasal Symptom and Medication Score (TNSMS) and the pollen concentration levels. Moreover, the maximum symptom levels occurred mostly within the peak pollen periods (PPP) following the EAACI criteria. CONCLUSIONS: Based on our analyses, we confirm the validity of the EAACI definitions on pollen season for both birch and grass and for a variety of geographical locations for the four European countries (including Germany from a previous publication) analyzed so far. On this basis, the use of the EAACI definitions is supported in future clinical trials on AIT as well as in daily routine for optimal patient care. Further evaluation of the EAACI criteria in other European regions is recommended.

Google Trends and pollen concentrations in allergy and airway diseases in France.

BACKGROUND: Google Trends (GTs) is a web-based surveillance tool that explores the searching trends of specific queries via Google. This tool proposes to reflect the real-life epidemiology of allergic rhinitis and asthma. However, the validation of GTs against pollen concentrations is missing at the country level. OBJECTIVES: In the present study, we used GTs (a) to compare the terms related to allergy in France, (b) to assess seasonal variations across the country for 5 years and (c) to compare GTs and pollen concentrations for 2016. METHODS: Google Trends queries were initially searched to investigate the terms reflecting pollen and allergic diseases. 13- and 5-year GTs were used in France. Then, 5-year GTs were assessed in all metropolitan French regions to assess the seasonality of GTs. Finally, GTs were compared with pollen concentrations (Réseau National de Surveillance en Aerobiology) for 2016 in seven regions (GTs) and corresponding cities (pollen concentrations). RESULTS: The combination of searches for "allergy" as a disease, "pollen" as a disease cause and "ragweed" as a plant was needed to fully assess the pollen season in France. "Asthma" did not show any seasonality. Using the 5-year GTs, an annual and clear seasonality of queries was found in all regions depending on the predicted pollen exposure for spring and a summer peak but not for winter peaks. The agreement between GT queries and pollen concentrations is usually poor except for spring trees and grasses. Moreover, cypress pollens are insufficiently reported by GTs. CONCLUSIONS: Google Trends cannot predict the pollen season in France.

Pru p 7 sensitization is a predominant cause of severe, cypress pollen-associated peach allergy.

BACKGROUND: Peach is a common elicitor of food allergic reactions. Peach-induced immediate reactions may occur as benign pollen-food syndromes, usually due to birch pollen-related PR-10 cross-reactivity in temperate climates, and as potentially severe primary food allergies, predominantly related to nsLTP Pru p 3 in Mediterranean regions. The newly described peach allergen Pru p 7 has gained recent attention as a potential peach allergy severity marker. Sensitization to Pru p 7 and its allergenic homologues of the gibberellin-regulated protein family occurs in areas with high Cupressaceae tree pollen exposure. OBJECTIVE: We sought to investigate the distribution, clinical characteristics and molecular associations of Pru p 7 sensitization among subjects with suspected peach allergy in different regions of France. METHODS: Subjects with suspected peach allergy (n = 316) were included. Diagnostic work-up was performed according to current guidelines, including open food challenge when required. IgE antibody measurements and competition experiments were performed using the ImmunoCAP assay platform. RESULTS: Sensitization to Pru p 7 was present in 171 (54%) of all subjects in the study and in 123 of 198 (62%) diagnosed as peach allergic, more than half of whom were sensitized to no other peach allergen. Frequency and magnitude of Pru p 7 sensitization were associated with the presence of peach allergy, the clinical severity of peach-induced allergic reactions and the level of cypress pollen exposure. Cypress pollen extract completely outcompeted IgE binding to Pru p 7. Pru p 7 was extremely potent in basophil activation tests. CONCLUSION AND CLINICAL RELEVANCE: A subtype of Cupressaceae pollinosis, characterized by Pru p 7 sensitization, can be an underlying cause of severe peach allergy.

Immunotherapy with grass pollen tablets reduces medication dispensing for allergic rhinitis and asthma: A retrospective database study in France.

BACKGROUND: Moderate-to-severe allergic rhinitis (AR) may increase the risk of developing or worsening asthma, whereas treatment of AR with subcutaneously or sublingual allergen immunotherapy (SLIT) may slow this progression. METHODS: In a retrospective real-world analysis, prescription fulfilment data were gathered from French retail pharmacies between 1 March 2012 and 31 December 2016. Using linear regression analyses, patients having received at least two prescriptions of grass pollen SLIT tablets over at least 2 successive years were compared with control patients having received symptomatic medications only. RESULTS: A total of 1099 SLIT patients and 27 475 control patients were included in the main analysis. With regard to symptomatic AR medication dispensing, we observed a 50% decrease in the pre-index/follow-up ratio in the SLIT group, a 30% increase in the control group without age matching (P < 0.0001 vs SLIT) and a 20% increase in the control group with age matching (P < 0.0001 vs SLIT). During the follow-up, 11 (1.8%) and 782 (5.3%) patients initiated asthma treatment in the SLIT and control groups, respectively. The relative risk of medication dispensing for new asthma was lower in the SLIT group (by 62.5% [29.1%-80.1%] without age matching (P = 0.0025) and by 63.7% [31.5%-80.7%] with age matching; P = 0.0018). SLIT was also associated with slower progression of asthma medication dispensing during the follow-up period, relative to the control group (regression coefficient: -0.58 [-0.74 to 0.42] without age matching (P < 0.0001) and -0.61 [-0.76 to -0.46] with age matching; P < 0.0001). CONCLUSION: Prescription of grass pollen SLIT tablets reduced the dispensing of AR and asthma medications in real life.

Globalization and anaphylaxis.

PURPOSE OF REVIEW: To understand the impact of globalization in the management of anaphylaxis and identify potential strategies to improve patients' care and prevention. RECENT FINDINGS: Developments in the field of anaphylaxis have been consistently following these globalization trends offering possibilities of collaborations of the allergy community and integrated international initiatives to reach quality care of allergic patients worldwide. SUMMARY: Globalization is the process of interaction and integration between people, companies, and governments worldwide. Developments in the field of anaphylaxis have been following these globalization trends offering possibilities of collaborations and integrated international initiatives to reach quality care of allergic patients worldwide. Complex disorders, such as anaphylaxis, have called for complex integrative strategies, leading to a new acceptance of outside traditions. Allergy is encouraging us to accept holistic and integrative medical practices as viable options. With the dissolution of multinational boundaries and the universal free access to information, the notion of holistic and global-based care is emerging as the new reality of the medicine. We strongly believe that the integrated action plan to the management and prevention of anaphylaxis, just possible through the globalization, is a key health, political and economical move that advocates for the best practice of allergology.

Real-life clinical practice and management of polysensitized patients with respiratory allergies: a large, global survey of clinicians prescribing allergen immunotherapy.

BACKGROUND: The allermix survey was conducted to gain insights into the most frequently diagnosed allergies worldwide, the use of allergen immunotherapy (AIT) in clinical practice, and to identify current clinical approaches for the management of polyallergic patients. METHODS: The survey was conducted in 19 countries worldwide during 2016. Clinicians currently prescribing AIT completed an online questionnaire, designed to gather data on their daily clinical practice, most commonly diagnosed and treated allergies among their patients, awareness and adherence to recommendations and guidelines on AIT, the AIT format(s) that they choose to prescribe, and management of polyallergic patients. RESULTS: Respondents (N = 1029) considered a clinical demonstration of safety and effectiveness, and quality and standardization of allergen extract, as key factors influencing their choice of which AIT formulation to prescribe. 98% of respondents reported managing polyallergic patients; 58% were treated with single-allergen AIT and 42% with multiple-allergen AIT. 74% of respondents were aware of latest AIT practice guidelines, while 67% had an awareness of recent recommendations for pharmaceutical manufacturers. CONCLUSION: These findings highlight the need for high-quality AIT products that are supported by robust efficacy and safety data, and address the treatment habits of allergy specialists in their real-life clinical practice.

The European Survey on Adverse Systemic Reactions in Allergen Immunotherapy (EASSI): A paediatric assessment.

BACKGROUND: Safety data on 'real-life' allergen immunotherapy (AIT) in children and adolescents is usually extrapolated from studies in adults. METHODS: Patients aged 18 or under initiating aeroallergen AIT were evaluated in a prospective European survey. Patient profiles and systemic reactions (SRs) were recorded. Descriptive, univariate and multivariate analyses were used to identify risk factors for SRs. RESULTS: A total of 1563 patients (mean ± SD age: 11.7 ± 3.9 years; rhinitis: 93.7%; asthma: 61.5%; polysensitization: 62.5%) and 1578 courses of AIT were assessed. Single-allergen AIT was administered in 89.5% of cases (n = 1412; mites: 49%; grass pollen: 25.8%; tree pollen: 8.7%; Alternaria: 4.6%; dander: 0.8%; weed pollen: 0.6%). Subcutaneous AIT (SCIT) was used in 71.4% (n = 1127) of the treatments, including 574 (50.9%) with natural extracts. Sublingual AIT (SLIT) was used for the remaining 451 treatments (drops: 73.8%; tablets: 26.2%). The mean ± SD follow-up period was 12.9 ± 3.3 months. The estimated total number of doses was 19,669 for SCIT and 131,550 for SLIT. Twenty-four patients (1.53%) experienced 29 SRs. Respiratory (55.7%) and skin symptoms (37.9%) were most frequent. Anaphylaxis was diagnosed in 3 SRs (10.3%), and adrenaline was administered in 2 of these cases. In a univariate analysis, the risk of SRs was lower in mite-sensitized patients and higher in cases of pollen polysensitization (>3), grass pollen extracts and the use of natural extracts (vs. allergoids). CONCLUSIONS: In a real-life paediatric setting, AIT is safe. SRs are infrequent and generally not severe. Pollen polysensitization, grass pollen extracts and natural extracts (vs. allergoids) were risk factors for AIT-associated SRs.

Comparison of allergenic extracts from different origins: the value of the FDA's bioequivalent allergy unit (BAU).

INTRODUCTION: Allergy immunotherapy (AIT) is the only disease-modifying intervention for the treatment of allergic diseases. The clinical effectiveness of AIT is clearly dose-dependent, so it is important that clinicians can assess and compare the potency of the various products available. However, this is not possible in practice, because manufacturers use different methods to determine potency. Therefore, a clear need exists for adoption of a 'gold-standard' measure of allergenicity. The bioequivalent allergy unit (BAU) is thus far the only allergen unit approved by a regulatory agency (the US Food and Drug Administration), with European regulatory authorities yet to adopt a common unit. AREAS COVERED: Using PubMed, we performed a review of the literature on measures of allergen extract potency, use of the BAU, and BAU assessment for grass pollen tablets. Expert commentary: There is an obvious benefit to allergists and patients for having a single, comparable unit across products, and we strongly support the adoption of a single, 'gold-standard' unit of measurement for all products. Use of the BAU allows a clear comparison of the potency of allergen products from different manufacturers, and enables better understanding of the potential reasons for any differences in administration and dosing protocols between these products.

Comparison of outcome measures in allergic rhinitis in children, adolescents and adults.

BACKGROUND: Grass pollen-induced allergic rhinoconjunctivitis (AR) is very common worldwide. However, its symptoms may vary with the patient's age. The present study compared symptom profiles and quality of life (QoL) in children, adolescents and adults with grass pollen-induced AR. METHODS: This was a four-week, multicentre, observational study of children (aged 6-11), adolescents (12-17) and adults (18-65) consulting specialist physicians in France. The management of AR was at the physicians' discretion. Participants regularly rated their symptoms (the rhinoconjunctivitis total symptom score (RTSS) and a visual analogue scale (VAS)) and QoL (the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). RESULTS: A total of 806 patients (253 children, 250 adolescents and 303 adults, of whom 83.5% suffered from moderate-to-severe, persistent AR) provided data for at least the first 2 weeks of the study. Ocular pruritus (the most bothersome symptom in children (35%), adolescents (22%) and adults (16%)) was associated with poor QoL in all groups, whereas nasal obstruction and pruritus were associated with poor QoL in adolescents and children. Over 4 weeks, the weekly mean RTSS and VAS scores fell by around half. This change was associated with an improvement in the RQLQ scores. In all age groups, the VAS score was well correlated with the weekly mean RTSS score (Pearson's r: 0.79-0.88) and moderately correlated with the weekly mean RQLQ score (Pearson's r: 0.64-0.80). CONCLUSIONS: In moderate-to-severe grass pollen-induced AR, symptom perception differs in children vs. older patients. However, the assessments of treatment outcomes (using the RTSS, VAS and RQLQ) were similar in all age groups.

MASK-rhinitis, a single tool for integrated care pathways in allergic rhinitis.

Allergic rhinitis (AR) is among the most common diseases globally. MASK-rhinitis is a simple ICT tool to implement care pathways for allergic rhinitis from patients to health care providers using a common language and a clinical decision support system. This is based on the assessment of the control of allergic rhinitis by a visual analogue scale on and App and a tablet. MASK-rhinitis will allow (i) the patients to screen for allergic disease, (ii) the pharmacists, to guide them in the prescription of OTC medications and direct the uncontrolled patients to physicians, (iii) the primary care physician, to prescribe appropriate treatment and to follow-up with the patient according to the physician's instructions (CDSS) and assessment of control and (vi) the specialist and outpatient clinics in allergology, if there is failure to gain control by the primary physician. MASK-rhinitis will be important for establishing care pathways across the life cycle, stratify patients with severe uncontrolled rhinitis and to perform clinical trials.

A meta-analysis of sublingual allergen immunotherapy and pharmacotherapy in pollen-induced seasonal allergic rhinoconjunctivitis.

BACKGROUND: The capacity of sublingual allergen immunotherapy (SLIT) to provide effective symptom relief in pollen-induced seasonal allergic rhinitis is often questioned, despite evidence of clinical efficacy from meta-analyses and well-powered, double-blind, placebo-controlled randomized clinical trials. In the absence of direct, head-to-head, comparative trials of SLIT and symptomatic medication, only indirect comparisons are possible. METHODS: We performed a meta-analysis of classes of products (second-generation H1-antihistamines, nasal corticosteroids and grass pollen SLIT tablet formulations) and single products (the azelastine-fluticasone combination MP29-02, and the leukotriene receptor antagonist montelukast) for the treatment of seasonal allergic rhinitis in adults, adolescents and/or children. We searched the literature for large (n >100 in the smallest treatment arm) double-blind, placebo-controlled randomized clinical trials. For each drug or drug class, we performed a meta-analysis of the effect on symptom scores. For each selected trial, we calculated the relative clinical impact (according to a previously published method) on the basis of the reported post-treatment or season-long nasal or total symptom scores: 100 × (scorePlacebo - scoreActive)/scorePlacebo. RESULTS: Twenty-eight publications on symptomatic medication trials and ten on SLIT trials met our selection criteria (total number of patients: n = 21,223). The Hedges' g values from the meta-analyses confirmed the presence of a treatment effect for all drug classes. In an indirect comparison, the weighted mean (range) relative clinical impacts were -29.6% (-23% to -37%) for five-grass pollen SLIT tablets, -19.2% (-6% to -29%) for timothy pollen SLIT tablets, -23.5% (-7% to -54%) for nasal corticosteroids, -17.1% (-15% to -20%) for MP29-02, -15.0% (-3% to -26%) for H1-antihistamines and -6.5% (-3% to -10%) for montelukast. CONCLUSIONS: In an indirect comparison, grass pollen SLIT tablets had a greater mean relative clinical impact than second-generation antihistamines and montelukast and much the same mean relative clinical impact as nasal corticosteroids. This result was obtained despite the presence of methodological factors that mask the clinical efficacy of SLIT for the treatment of seasonal allergic rhinitis.

Systems medicine approaches for the definition of complex phenotypes in chronic diseases and ageing. From concept to implementation and policies.

Chronic diseases are diseases of long duration and slow progression. Major NCDs (cardiovascular diseases, cancer, chronic respiratory diseases, diabetes, rheumatologic diseases and mental health) represent the predominant health problem of the Century. The prevention and control of NCDs are the priority of the World Health Organization 2008 Action Plan, the United Nations 2010 Resolution and the European Union 2010 Council. The novel trend for the management of NCDs is evolving towards integrative, holistic approaches. NCDs are intertwined with ageing. The European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) has prioritised NCDs. To tackle them in their totality in order to reduce their burden and societal impact, it is proposed that NCDs should be considered as a single expression of disease with different risk factors and entities. An innovative integrated health system built around systems medicine and strategic partnerships is proposed to combat NCDs. It includes (i) understanding the social, economic, environmental, genetic determinants, as well as the molecular and cellular mechanisms underlying NCDs; (ii) primary care and practice-based interprofessional collaboration; (iii) carefully phenotyped patients; (iv) development of unbiased and accurate biomarkers for comorbidities, severity and follow up of patients; (v) socio-economic science; (vi) development of guidelines; (vii) training; and (viii) policy decisions. The results could be applicable to all countries and adapted to local needs, economy and health systems. This paper reviews the complexity of NCDs intertwined with ageing. It gives an overview of the problem and proposes two practical examples of systems medicine (MeDALL) applied to allergy and to NCD co-morbidities (MACVIA-LR, Reference Site of the European Innovation Partnership on Active and Healthy Ageing).

Grass pollen counts, air pollution levels and allergic rhinitis severity.

BACKGROUND: Little is known about the relation between allergic rhinitis severity and airborne pollen in combination with air pollutants. OBJECTIVE: To model the risk of suffering from severe seasonal allergic rhinitis (SAR) as a function of both pollen count and air pollution levels in a large nationwide sample of patients whose SAR was diagnosed by a physician and confirmed by skin prick test positivity or specific immunolglobulin E to common aeroallergens. METHODS: The severity of SAR symptoms was estimated with the Symptomatic Global Score (SGS) among 36,397 patients suffering from an untreated and uncomplicated SAR between May and August 2004 in metropolitan France. Patients who had an SGS in the upper third quartile were classified as suffering from severe SAR. A multilevel model relating SAR severity, pollen and air pollution was used to take into account the hierarchical data structure. RESULTS: 18.9% of the 17,567 urban patients retained for the analysis suffered from severe rhinitis. At the Lag0 (day of the visit), a rise of 60 grass pollen grains/m(3) increased the risk of suffering from a severe SAR form by 8% in the multileveled model after adjusting for potential confounders and air pollution levels. Results were also confirmed in the subsample of individuals with documented sensitization to grass pollen. CONCLUSION: Grass pollen count aggravated SAR in terms of symptoms in our nationwide sample. These findings confirm the need for proper treatment and preventive measures in SAR patients sensitized to grass pollen.