Recommendations for asthma monitoring in children: A PeARL document endorsed by APAPARI, EAACI, INTERASMA, REG, and WAO.

Monitoring is a major component of asthma management in children. Regular monitoring allows for diagnosis confirmation, treatment optimization, and natural history review. Numerous factors that may affect disease activity and patient well-being need to be monitored: response and adherence to treatment, disease control, disease progression, comorbidities, quality of life, medication side-effects, allergen and irritant exposures, diet and more. However, the prioritization of such factors and the selection of relevant assessment tools is an unmet need. Furthermore, rapidly developing technologies promise new opportunities for closer, or even "real-time," monitoring between visits. Following an approach that included needs assessment, evidence appraisal, and Delphi consensus, the PeARL Think Tank, in collaboration with major international professional and patient organizations, has developed a set of 24 recommendations on pediatric asthma monitoring, to support healthcare professionals in decision-making and care pathway design.

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.

IgE-Mediated and Non-IgE-Mediated Fish Allergy in Pediatric Age: A Holistic Approach-A Consensus by Diagnostic Commission of the Italian Society of Pediatric Allergy and Immunology.

Fish is one of the "big nine" foods triggering allergic reactions. For this reason, fish allergens must be accurately specified on food labels. Fish allergy affects less than 1% of the world population, but a higher prevalence is observed in pediatric cohorts, up to 7%. Parvalbumin is the main fish allergen found in the muscles. In childhood, sensitization to fish allergens occurs most frequently through the ingestion of fish, rarely transcutaneously or by inhalation. Fish allergy symptoms usually appear within two hours of the allergen contact. The diagnosis begins with the collection of the history. If it is suggestive of fish allergy, prick tests or the measurement of serum-specific IgE should be performed to confirm the suspicion. The oral food challenge is the gold standard for the diagnosis. It is not recommended in case of a severe allergic reaction. It is important to make a differential diagnosis with anisakiasis or scombroid poisoning, which have overlapping clinical features but differ in pathogenesis. Traditionally, managing fish allergy involves avoiding the triggering species (sometimes all bony fish species) and requires an action plan for accidental exposures. The present review will analyze IgE- and non-IgE-mediated fish allergy in children from epidemiology, pathogenesis to clinical features. Moreover, clinical management will be addressed with a particular focus on potential nutritional deficiencies.

Anaphylaxis management in a French pediatric emergency department: Lessons from the ANA-PED study.

BACKGROUND: Anaphylaxis is a serious systemic hypersensitivity reaction that requires immediate recognition and prompt administration of epinephrine/adrenaline. The present study aimed to assess the appropriateness of epinephrine/adrenaline use in children identified as allergic by physicians in the emergency department (ED) at the time of the reaction, and to identify factors that are possibly associated with epinephrine/adrenaline administration, auto-injector prescription, and further referral to an allergist. METHODS: We performed a retrospective cross-sectional study at the pediatric ED of the University Hospital of Montpellier, France. We included all consecutive children who attended the ED between 2016 and 2020 with an allergy-related diagnosis at discharge. RESULTS: We included 1056 allergy-related visits, including 224 (21.2%) with a diagnosis of anaphylaxis at discharge; only 17.0% of them received an epinephrine/adrenaline injection, and 57.1% consulted an allergist after the acute episode. An auto-injector was prescribed to 63 (28.1%) patients at discharge from the ED. Besides the severity of the clinical presentation, factors associated with a guidelines-based management of the anaphylactic reaction and with an increased administration rate of epinephrine/adrenaline included presence of asthma symptoms and presence of extended skin reactions. CONCLUSIONS: Our study underlines persistent gaps in the management of pediatric anaphylaxis in ED, focusing on hereby identified levers. By disseminating current knowledge and guidelines on anaphylaxis and allergies, specialists could work together with emergency physicians to establish effective management algorithms and improve anaphylaxis management and care pathways for children experiencing allergic reactions, especially anaphylaxis. TRAIL REGISTRATION: Clinical Trials, number NCT05112367.

CHOICE international survey: Clusters of allergen immunotherapy prescription from French and Spanish cohorts.

Background: There is no description of the drivers of prescription for allergen immunotherapy (AIT) for respiratory allergic diseases. Methods: A prospective, multicentre, observational, non-interventional real-life study was performed in France and Spain for 20 months. Data were gathered using 2 different questionnaires, anonymously collected in an online platform. No names of AIT products were recorded. Multivariate analysis and unsupervised cluster analysis were performed. Results: One hundred and three physicians (50.5% from Spain and 49.5% from France) reported 1735 patients (433 in France and 1302 in Spain), 47.9% males, 64.8% adults with a mean age 26.2 years old. They suffered from allergic rhinitis (99%), allergic conjunctivitis (70.4%), allergic asthma (51.8%), atopic dermatitis (13.9%), and food allergy (9.9%). A clustering analysis based on 13 predefined relevant variables for AIT-prescription identified 5 different clusters, each of them including information regarding doctor's profile and patient demographics, baseline disease characteristics, and main AIT indication: 1) Looking at the future: focusing on asthma prevention (n = 355), 2) Efficacy after discontinuation of AIT (n = 293), 3) Fighting severe allergic disease (n = 322), 4) Looking at the present, facing current symptoms (n = 265) and 5) Doctor's own clinical experience (n = 500). Each one of these clusters have specific patients' and doctors' characteristics, representing distinctive AIT prescription drivers. Conclusion: Using data-driven analysis, we identified for the first time some reasons and patterns of AIT prescriptions in real-life clinical settings. There is no uniform indication for prescribing AIT, which varies amongst patients and doctors with multiple but specific drivers, taking into account several relevant parameters.

Deciphering Differential Behavior of Immune Responses as the Foundation for Precision Dosing in Allergen Immunotherapy.

Like in many fields of medicine, the concept of precision dosing has re-emerged in routine practice in allergology. Only one retrospective study on French physicians' practice has addressed this topic so far and generated preliminary data supporting dose adaptation, mainly based on experience, patient profile understanding and response to treatment. Both intrinsic and extrinsic factors shape the individual immune system response to allergen immunotherapy (AIT). Herein, we focus on key immune cells (i.e., dendritic cells, innate lymphoid cells, B and T cells, basophils and mast cells) involved in allergic disease and its resolution to further understand the effect of AIT on the phenotype, frequency or polarization of these cells. We strive to discriminate differences in immune responses between responders and non-responders to AIT, and discuss the eligibility of a non/low-responder subset for dose adaptation. A differential behavior in immune cells is clearly observed in responders, highlighting the importance of conducting clinical trials with large cohorts of well-characterized subjects to decipher the immune mechanism of AIT. We conclude that there is a need for designing new clinical and mechanistic studies to support the scientific rationale of dose adaptation in the interest of patients who do not properly respond to AIT.

Criteria used by health professionals on the selection of allergen immunotherapy in real clinical practice: Methodology.

Background: Allergen immunotherapy (AIT) is today the only etiological therapy for respiratory allergic diseases, including allergic rhinitis, allergic conjunctivitis, and allergic asthma. Even though interest in real-world data has recently increased, publications mainly focus on short-term and long-term efficacy and safety of AIT. Indeed, information is still lacking regarding the "key parameters" or "drivers of prescription" used by doctors to prescribe AIT or by the patients to accept AIT as treatment for their respiratory allergic disease. Examining these factors is therefore the main goal of the CHOICE-Global Survey: "Criteria Used by Health Professionals on the Selection of Allergen Immunotherapy in Real Clinical Practice: An international academic electronic survey". Methods: We present the methodology of the CHOICE-Global Survey, an academic, prospective, multicenter, observational, transversal, web-based e-survey, conducted in real-life clinical settings designed to collect data from 31 countries representing 9 global different socio-economic and demographic regions. In the present document, we describe the survey, how it was conceived and developed, how data are stored and analyzed, and the different steps that will provide this information to the allergy community. Conclusions: The CHOICE-Global Survey will be able to provide, from an academic point of view, information on the drivers of prescription of AIT in real-life practice and improve understanding regarding the key parameters considered by doctors and patients for such therapy.

Symptom control and health-related quality of life in allergic rhinitis with and without comorbid asthma: A multicentre European study.

BACKGROUND: Allergic rhinitis (AR) is a major non-communicable disease that affects the health-related quality of life (HRQoL) of patients. However, data on HRQoL and symptom control in AR patients with comorbid asthma (AR + asthma) are lacking. METHODS: In this multicentre, cross-sectional study, patients with AR were screened and administered questionnaires of demographic characteristics and health conditions (symptoms/diagnosis of AR and asthma, disease severity level, and allergic conditions). HRQoL was assessed using a modified version of the RHINASTHMA questionnaire (30, 'not at all bothered' - 150 'very much bothered') and symptom control was evaluated by a modified version of the Control of Allergic Rhinitis/Asthma Test (CARAT) (0, 'no control' - 30, 'very high control'). RESULTS: Out of 643 patients with AR, 500 (78%) had asthma as a comorbidity, and 54% had moderate-severe intermittent AR, followed by moderate-severe persistent AR (34%). Compared to the patients with AR alone, patients with AR + asthma had significantly higher RHINASTHMA (e.g., median RHINASTHMA-total score 48.5 vs. 84, respectively) and a significantly lower CARAT score (median CARAT-total score 23 vs. 16.5, respectively). Upon stratifying asthma based on severity, AR patients with severe persistent asthma had worse HRQoL and control than those with mild persistent asthma. The association was significantly higher among non-obese participants compared to obese ones, with RHINASTHMA-upper symptoms score but not with CARAT. CONCLUSIONS: Our observation of poorer HRQoL and symptoms control in AR patients with comorbid asthma supports the importance of a comprehensive approach for the management of AR in case of a comorbid allergic condition.

Sensitivity of FEV1 and Clinical Parameters in Children With a Suspected Asthma Diagnosis.

BACKGROUND: Asthma is the most common chronic disease in children and a robust diagnosis is crucial to optimize patient care and reduce its burden. To diagnose asthma in children, the Global Initiative for Asthma (GINA) recommendations propose a 12% improvement in forced expiratory volume in 1 second (FEV1) after a bronchodilation test. Nevertheless, such a criterion is rarely confirmed in these patients in clinical practice. OBJECTIVE: The objective of this study was to evaluate the sensitivity of spirometric and clinical parameters in identifying children with possible asthma. METHODS: The VERI-VEMS Study is a multicenter international retrospective cohort study. Data were collected, from January 2008 until January 2019, for all consecutive children (aged 5-18 years), with a diagnosis of asthma, who performed a spirometry at the time of the diagnosis. We compared the sensitivity of the reversibility criterion proposed by GINA guidelines, with other spirometric and clinical variables, using physician-diagnosed asthma and response to treatment as the standard. RESULTS: The study included 871 children. The reversibility criterion of 12% of FEV1 showed a sensitivity of 30.4%. The 3 best spirometric or clinical criteria were the presence of dry cough, or wheezing or atopy and dry cough, or wheezing or exercise-induced dyspnea, with a sensitivity reaching 99.5%, with no added value of the spirometric parameters in the calculation of the cumulated sensitivity for the diagnosis of pediatric asthma. CONCLUSIONS: Postbronchodilator reversibility of 12%, although essential for patients' follow-up, has an insufficient low sensitivity in reaching a diagnosis of asthma in pediatric patients, compared with a combination of clinical symptoms, that show a better sensitivity. Further studies on specificity will help clarify the role of this change in the diagnostic paradigm in formally diagnosing children with asthma.

Hypersensitivity reactions to biologics in children.

INTRODUCTION: Hypersensitivity reactions (HSRs) have been observed with the use of biologics in children. The management of HSRs in children is mainly based on experiences from the adult population. Recently, data from different centers experienced in managing these reactions, including desensitization in children, have been published, allowing clinicians to have an appropriate global overview and compare results. AREAS COVERED: This review highlights the published data on hypersensitivity reactions to biologics in children and drug desensitization protocols adapted to the pediatric population. EXPERT OPINION: With regard to HSRs to biologics in children, few data are available. Compared with the adult population, there is a lack of knowledge in the endophenotypes, management and the standardization of protocols including premedication regimens in children. An international consensus is needed to provide clinicians with new insight on how to apply personalized management and to perform tailored desensitization protocols in pediatric populations. Various specialists including allergists, pediatricians, oncologists, hematologists, rheumatologists, and pharmacists, should build a multidisciplinary management team to keep pediatric patients on their best treatment options in the safest manner.

Amikacin Liposomal Inhalation Suspension in the Treatment of Mycobacterium abscessus Lung Infection: A French Observational Experience.

Background: Mycobacterium abscessus infections remain difficult to manage in both cystic fibrosis (CF) and non-CF patients and reported clinical outcomes are largely unsatisfactory. Clinical trial data are limited and no approved therapies are currently available for the management of M abscessus lung diseases. As an alternative, cohort studies may provide insightful information into the management of M abscessus pulmonary disease. Methods: Based on a retrospective observational cohort study, we investigated the safety and efficacy of amikacin liposome inhaled suspension (ALIS) as an adjunct to a standard antibiotic regimen for M abscessus lung infection in both CF and non-CF patients. We also assessed the association of patient drug compliance with culture conversion and clinical outcomes. Results: Twenty-six patients had long-term follow-up data available. Culture conversion was achieved in 54% (14/26) of the patients with no difference between CF and non-CF patients after an average treatment duration of 10 months. Patient treatment compliance was significantly better in the converter group compared to nonconverters with an odds ratio of 44.78 associated with good compared to poor patient compliance. Overall, 9 patients (35%) experienced an adverse event that led to treatment discontinuation. Conclusions: ALIS appears beneficial in both CF and non-CF populations with M abscessus lung disease.

Fungal exposome, human health, and unmet needs: A 2022 update with special focus on allergy.

Humans inhale, ingest, and touch thousands of fungi each day. The ubiquity and diversity of the fungal kingdom, reflected by its complex taxonomy, are in sharp contrast with our scarce knowledge about its distribution, pathogenic effects, and effective interventions at the environmental and individual levels. Here, we present an overview of salient features of fungi as permanent players of the human exposome and key determinants of human health, through the lens of fungal allergy and other fungal hypersensitivity reactions. Improved understanding of the fungal exposome sheds new light on the epidemiology of fungal-related hypersensitivity diseases, their immunological substratum, the currently available methods, and biomarkers for environmental and medical fungi. Unmet needs are described and potential approaches are highlighted as perspectives.

A review of allergen immunotherapy in asthma.

Asthma is one of the most common chronic diseases worldwide. Besides symptomatic treatments, allergen immunotherapy (AIT) is a possible add-on treatment for asthmatic patients. In case of an immunologically proven allergen-driven mechanism of asthma, AIT represents the only etiologic treatment for allergic symptoms. AIT has proven both its efficacy and effectiveness in reducing asthma symptoms and asthma medications. It is still debated whether its prescription in severe asthmatic patients is allowed and safe. As for uncontrolled asthma, such a condition should be considered temporary, and AIT may be started as asthma becomes at least partially controlled after treatment adjustment. Finally, randomized trials and real-life studies in recent years have proven that AIT could be administered as a preventive strategy to reduce the risk of developing asthma in patients suffering from allergic rhinitis. More studies are needed to provide more precise indications on the role in clinical practice of AIT in asthmatic patients. Nevertheless, present data are already strong enough to highlight its role as a therapeutic option for allergic asthma and as a preventive strategy to stop or at least decelerate the allergic march.

Phenotypes and Endotypes of Peach Allergy: What Is New?

Peach allergy is emerging as a common type of fresh-fruit allergy in Europe, especially in the Mediterranean area. The clinical manifestations of peach allergy tend to have a peculiar geographical distribution and can range from mild oral symptoms to anaphylaxis, depending on the allergic sensitization profile. The peach allergen Pru p 7, also known as peamaclein, has recently been identified as a marker of peach allergy severity and as being responsible for peculiar clinical features in areas with high exposure to cypress pollen. This review addresses the latest findings on molecular allergens for the diagnosis of peach allergy, the clinical phenotypes and endotypes of peach allergy in adults and children, and management strategies, including immunotherapy, for peach allergy.

Food immunotherapy practice: Nation differences across Europe, the FIND project.

BACKGROUND: Food allergen immunotherapy (FA-AIT) practice is known to vary globally. This project aims to identify and characterize European centres performing FA-AIT. METHODS: An EAACI task force conducted an online survey to gather relevant information regarding FA-AIT practice and setting-specific resources after reviewing the published literature and congress abstracts throughout Europe. RESULTS: We identified 102 FA-AIT centres in 18 countries; only Spain (n = 39) and France (n = 16) had ≥10 such centres. Overall, most facilities were hospital-based (77.5%), publicly funded (80.4%) and delivered FA-AIT as routine clinical care (80.4%). On average, departments had 3 allergists/paediatric allergists and 2 nurses. Surveyed centres had provided FA-AIT for a median of 9 years [1-24] to a median of 105 [5-2415] patients. The estimated total number of treated patients was 24875, of whom 41.3% received AIT for milk, 34.2% egg, 12.8% peanut and 11.7% other foods. Anaphylaxis to AIT doses requiring over 4-6 h of observation was reported by 70.6% of centres, ICU admissions by 10.8% and eosinophilic esophagitis by 45.1%. Quality of life and sustained unresponsiveness were evaluated in 20.6% and 54.9% of centres, respectively. The main contraindications for food AIT were severe asthma (57%-63%), eosinophilic esophagitis (56%-48%) and age below 5 years (47%-41%). CONCLUSIONS: In Europe, FA-AIT is provided mostly in clinical practice. Significant variation is seen in the number of centres per country, facility characteristics and inclusion/exclusion criteria, and in certain aspects of protocols. Potential inequality in access to AIT has been identified as well as the need for education and guidance for treatment standardization.

Food allergy in primary care.

Prevalence of food allergy has been increasing over the last decades. It may appear as an immediate or a delayed reaction. The disease has a major impact on the quality of life of patients and their families, and it is associated to elevated costs. Primary care physicians are the first healthcare providers who assist children with food allergy, especially in mild to moderate forms. Through the present review, we examine the steps that should be followed in primary care to manage food allergy, and to promptly prescribe an elimination diet and an emergency kit in case of accidental exposure to the allergen. We also focus on the special management of IgE and non-IgE mediated cow's milk allergy, and on management and prevention of egg and peanuts allergy.