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Background: Precautionary Allergen (“may contain”) Labelling (PAL) is used by industry to communicate potential risk to food-allergic individuals posed by unintended allergen presence (UAP). In 2014, the World Allergy Organization (WAO) highlighted that PAL use was increasing, but often applied inconsistently and without regulation — which reduces its usefulness to consumers with food allergy and those purchasing food for them. WAO proposed the need for a regulated, international framework to underpin application of PAL. In 2019, the World Health Organization (WHO) and the Food and Agriculture Organization (FAO) of the United Nations convened an expert consultation to address the issue of PAL, the outputs of which are now being considered by the Codex Committee on Food Labelling (CCFL). Objectives: To summarise the latest data to inform the application of PAL in a more systematic way, for implementation into global food standards. Methods: A non-systematic review of issues surrounding precautionary labelling and food allergens in pre-packaged products. Results: Approximately, 100 countries around the world have legislation on the declaration of allergenic ingredients. Just a few have legislation on UAP. Given the risks that UAP entails, non-regulated PAL creates inconvenience in real life due to its unequal, difficult interpretation by patients. The attempts made so far to rationalize PAL present lights and shadows. Conclusions: At a time when CCFL is considering the results of the FAO/WHO Expert Consultation 2020–2023, we summarise the prospects to develop an effective and homogeneous legislation at a global level, and the areas of uncertainty that might hinder international agreement on a regulated framework for PAL of food allergens.

Abstract Patient‐reported outcome measures (PROMs) are used to assess a patient's health status at a particular point in time. They are essential in the development of person‐centred care. This paper reviews studies performed on PROMs for assessing AR and asthma control, in particular VAS scales that are included in the app MASK‐air® (Mobile Airways Sentinel networK) for asthma and rhinitis. VASs were initially developed on paper and pencil and tested for their criterion validity, cut‐offs and responsiveness. Then, a multicentric, multinational, double‐blind, placebo‐controlled, randomised control trial (DB‐PC‐RCT) using an electronic VAS form was carried out. Finally, with the development of MASK‐air® in 2015, previously validated VAS questions were adapted to the digital format and further methodologic evaluations were performed. VAS for asthma, rhinitis, conjunctivitis, work and EQ‐5D are included in the app. Additionally, two control‐medication scores for allergic symptoms of asthma (e‐DASTHMA) were validated for their criterion validity, cut‐offs and responsiveness.

In 2010, the United States Human and Health Services (US HHS) and the European Union's (EU) Directorate General for Communications Networks, Content and Technology signed a memorandum of understanding to stimulate cooperation surrounding health-related information communications technology. The key project that emerged from this agreement is the International Patient Summary (IPS), intended to provide succinct clinically relevant patient summaries, which are generalizable and condition-independent, that can be readily used by all clinicians for the care of patients. Although allergies are included in the main information required by the IPS library and framework, it is misrepresented which leads to underdiagnosis or misdiagnosis of patients suffering from allergic and hypersensitivity conditions (A/H). The French and Montpellier World Health Organization (WHO) Collaborating Centres have provided arguments for supporting representation of A/H in the IPS. These are based on the relevance of the new classification of A/H in the WHO International Classification of Diseases 11th version (ICD-11), and the need for alignment of eHealth tools with harmonized health information. We first present the A/H in the IPS initiative with the mission of producing an international information system that can be used globally in electronic health records to standardize clinical diagnoses and facilitate communication between clinicians caring for patients with A/H diseases. It is believed this initiative will provide a strong voice for the allergy community and an effective process for improving the quality of health data that will optimize medical care for our patients worldwide.

Abstract Rationale It is unclear how each individual asthma symptom is associated with asthma diagnosis or control. Objectives To assess the performance of individual asthma symptoms in the identification of patients with asthma and their association with asthma control. Methods In this cross‐sectional study, we assessed real‐world data using the MASK‐air® app. We compared the frequency of occurrence of five asthma symptoms (dyspnea, wheezing, chest tightness, fatigue and night symptoms, as assessed by the Control of Allergic Rhinitis and Asthma Test [CARAT] questionnaire) in patients with probable, possible or no current asthma. We calculated the sensitivity, specificity and predictive values of each symptom, and assessed the association between each symptom and asthma control (measured using the e‐DASTHMA score). Results were validated in a sample of patients with a physician‐established diagnosis of asthma. Measurement and Main Results We included 951 patients (2153 CARAT assessments), with 468 having probable asthma, 166 possible asthma and 317 no evidence of asthma. Wheezing displayed the highest specificity (90.5%) and positive predictive value (90.8%). In patients with probable asthma, dyspnea and chest tightness were more strongly associated with asthma control than other symptoms. Dyspnea was the symptom with the highest sensitivity (76.1%) and the one consistently associated with the control of asthma as assessed by e‐DASTHMA. Consistent results were observed when assessing patients with a physician‐made diagnosis of asthma. Conclusions Wheezing and chest tightness were the asthma symptoms with the highest specificity for asthma diagnosis, while dyspnea displayed the highest sensitivity and strongest association with asthma control.

Summary: Background: Validated questionnaires are used to assess asthma control over the past 1–4 weeks from reporting. However, they do not adequately capture asthma control in patients with fluctuating symptoms. Using the Mobile Airways Sentinel Network for airway diseases (MASK-air) app, we developed and validated an electronic daily asthma control score (e-DASTHMA). Methods: We used MASK-air data (freely available to users in 27 countries) to develop and assess different daily control scores for asthma. Data-driven control scores were developed based on asthma symptoms reported by a visual analogue scale (VAS) and self-reported asthma medication use. We included the daily monitoring data from all MASK-air users aged 16–90 years (or older than 13 years to 90 years in countries with a lower age of digital consent) who had used the app in at least 3 different calendar months and had reported at least 1 day of asthma medication use. For each score, we assessed construct validity, test–retest reliability, responsiveness, and accuracy. We used VASs on dyspnoea and work disturbance, EQ-5D-VAS, Control of Allergic Rhinitis and Asthma Test (CARAT), CARAT asthma, and Work Productivity and Activity Impairment: Allergy Specific (WPAI:AS) questionnaires as comparators. We performed an internal validation using MASK-air data from Jan 1 to Oct 12, 2022, and an external validation using a cohort of patients with physician-diagnosed asthma (the INSPIRERS cohort) who had had their diagnosis and control (Global Initiative for Asthma [GINA] classification) of asthma ascertained by a physician. Findings: We studied 135 635 days of MASK-air data from 1662 users from May 21, 2015, to Dec 31, 2021. The scores were strongly correlated with VAS dyspnoea (Spearman correlation coefficient range 0·68–0·82) and moderately correlated with work comparators and quality-of-life-related comparators (for WPAI:AS work, we observed Spearman correlation coefficients of 0·59–0·68). They also displayed high test–retest reliability (intraclass correlation coefficients range 0·79–0·95) and moderate-to-high responsiveness (correlation coefficient range 0·69–0·79; effect size measures range 0·57–0·99 in the comparison with VAS dyspnoea). The best-performing score displayed a strong correlation with the effect of asthma on work and school activities in the INSPIRERS cohort (Spearman correlation coefficients 0·70; 95% CI 0·61–0·78) and good accuracy for the identification of patients with uncontrolled or partly controlled asthma according to GINA (area under the receiver operating curve 0·73; 95% CI 0·68–0·78). Interpretation: e-DASTHMA is a good tool for the daily assessment of asthma control. This tool can be used as an endpoint in clinical trials as well as in clinical practice to assess fluctuations in asthma control and guide treatment optimisation. Funding: None.

Abstract Objective The present narrative review provides a comprehensive update of the current knowledge on urticaria, both in adult and pediatric populations, and on the safety and efficacy of fexofenadine hydrochloride (HCl) as a treatment option. Data source A literature search was conducted on Embase and Medline. Study selection Clinical studies published in English and published between 1999 and 2020 were selected. Results Although the exact pathogenesis of urticaria is not fully understood, multiple pathways of mast cell activation are discussed to explain the existence of phenotypically different clinical manifestations of urticaria. An overview of the worldwide prevalence of chronic urticaria, including disease burden and patient’s quality of life is provided. The impact of urticaria on patient’s life differs on the basis of whether its form is acute or chronic, but pharmacological approaches are most often needed to control the disabling symptoms. A summary of the current management of urticaria recommended by different guidelines across countries (Global; European; American; Australian; Asian; Japanese) is presented. Non-sedating, second-generation H1-antihistamines are the preferred choice of treatment across several guidelines worldwide. Herein, the efficacy and safety of fexofenadine HCl, a representative second-generation H1-antihistamine approved for the treatment of urticaria, is discussed. The occurrence of urticaria manifestations in COVID-19 patients is also briefly presented. Conclusion The burden of acute and chronic urticaria is high for patients. Second generation anti-histamines such as fexofenadine HCl can help managing the symptoms.

Abstract MASK‐air®, a validated mHealth app (Medical Device regulation Class IIa) has enabled large observational implementation studies in over 58,000 people with allergic rhinitis and/or asthma. It can help to address unmet patient needs in rhinitis and asthma care. MASK‐air® is a Good Practice of DG Santé on digitally‐enabled, patient‐centred care. It is also a candidate Good Practice of OECD (Organisation for Economic Co‐operation and Development). MASK‐air® data has enabled novel phenotype discovery and characterisation, as well as novel insights into the management of allergic rhinitis. MASK‐air® data show that most rhinitis patients (i) are not adherent and do not follow guidelines, (ii) use as‐needed treatment, (iii) do not take medication when they are well, (iv) increase their treatment based on symptoms and (v) do not use the recommended treatment. The data also show that control (symptoms, work productivity, educational performance) is not always improved by medications. A combined symptom‐medication score (ARIA‐EAACI‐CSMS) has been validated for clinical practice and trials. The implications of the novel MASK‐air® results should lead to change management in rhinitis and asthma.

Abstract Digital health is an umbrella term which encompasses eHealth and benefits from areas such as advanced computer sciences. eHealth includes mHealth apps, which offer the potential to redesign aspects of healthcare delivery. The capacity of apps to collect large amounts of longitudinal, real‐time, real‐world data enables the progression of biomedical knowledge. Apps for rhinitis and rhinosinusitis were searched for in the Google Play and Apple App stores, via an automatic market research tool recently developed using JavaScript. Over 1500 apps for allergic rhinitis and rhinosinusitis were identified, some dealing with multimorbidity. However, only six apps for rhinitis (AirRater, AllergyMonitor, AllerSearch, Husteblume, MASK‐air and Pollen App) and one for rhinosinusitis (Galenus Health) have so far published results in the scientific literature. These apps were reviewed for their validation, discovery of novel allergy phenotypes, optimisation of identifying the pollen season, novel approaches in diagnosis and management (pharmacotherapy and allergen immunotherapy) as well as adherence to treatment. Published evidence demonstrates the potential of mobile health apps to advance in the characterisation, diagnosis and management of rhinitis and rhinosinusitis patients.

Background: Chronic cough management necessitates a clear integrated care pathway approach. Primary care physicians initially encounter the majority of chronic cough patients, yet their role in proper management can prove challenging due to limited access to advanced diagnostic testing. A multidisciplinary approach involving otolaryngologists and chest physicians, allergists, and gastroenterologists, among others, is central to the optimal diagnosis and treatment of conditions which underly or worsen cough. These include infectious and inflammatory, upper and lower airway pathologies, or gastro-esophageal reflux. Despite the wide armamentarium of ancillary testing conducted in cough multidisciplinary care, such management can improve cough but seldom resolves it completely. This can be due partly to the limited data on the role of tests (eg, spirometry, exhaled nitric oxide), as well as classical pharmacotherapy conducted in multidisciplinary specialties for chronic cough. Other important factors include presence of multiple concomitant cough trigger mechanisms and the central neuronal complexity of chronic cough. Subsequent management conducted by cough specialists aims at control of cough refractory to prior interventions and includes cough-specific behavioral counseling and pharmacotherapy with neuromodulators, among others. Preliminary data on the role of neuromodulators in a proof-of-concept manner are encouraging but lack strong evidence on efficacy and safety. Objectives: The World Allergy Organization (WAO)/Allergic Rhinitis and its Impact on Asthma (ARIA) Joint Committee on Chronic Cough reviewed the recent literature on management of chronic cough in primary, multidisciplinary, and cough-specialty care. Knowledge gaps in diagnostic testing, classical and neuromodulator pharmacotherapy, in addition to behavioral therapy of chronic cough were also analyzed. Outcomes: This third part of the WAO/ARIA consensus on chronic cough suggests a management algorithm of chronic cough in an integrated care pathway approach. Insights into the inherent limitations of multidisciplinary cough diagnostic testing, efficacy and safety of currently available antitussive pharmacotherapy, or the recently recognized behavioral therapy, can significantly improve the standards of care in patients with chronic cough.

Abstract Background Evidence regarding the effectiveness of allergen immunotherapy (AIT) on allergic rhinitis has been provided mostly by randomised controlled trials, with little data from real‐life studies. Objective To compare the reported control of allergic rhinitis symptoms in three groups of users of the MASK‐air® app: those receiving sublingual AIT (SLIT), those receiving subcutaneous AIT (SCIT), and those receiving no AIT. Methods We assessed the MASK‐air® data of European users with self‐reported grass pollen allergy, comparing the data reported by patients receiving SLIT, SCIT and no AIT. Outcome variables included the daily impact of allergy symptoms globally and on work (measured by visual analogue scales—VASs), and a combined symptom‐medication score (CSMS). We applied Bayesian mixed‐effects models, with clustering by patient, country and pollen season. Results We analysed a total of 42,756 days from 1,093 grass allergy patients, including 18,479 days of users under AIT. Compared to no AIT, SCIT was associated with similar VAS levels and CSMS. Compared to no AIT, SLIT‐tablet was associated with lower values of VAS global allergy symptoms (average difference = 7.5 units out of 100; 95% credible interval [95%CrI] = −12.1;−2.8), lower VAS Work (average difference = 5.0; 95%CrI = −8.5;−1.5), and a lower CSMS (average difference = 3.7; 95%CrI = −9.3;2.2). When compared to SCIT, SLIT‐tablet was associated with lower VAS global allergy symptoms (average difference = 10.2; 95%CrI = −17.2;−2.8), lower VAS Work (average difference = 7.8; 95%CrI = −15.1;0.2), and a lower CSMS (average difference = 9.3; 95%CrI = −18.5;0.2). Conclusion In patients with grass pollen allergy, SLIT‐tablet, when compared to no AIT and to SCIT, is associated with lower reported symptom severity. Future longitudinal studies following internationally‐harmonised standards for performing and reporting real‐world data in AIT are needed to better understand its ‘real‐world’ effectiveness.

Background: Chronic cough can be triggered by respiratory and non-respiratory tract illnesses originating mainly from the upper and lower airways, and the GI tract (ie, reflux). Recent findings suggest it can also be a prominent feature in obstructive sleep apnea (OSA), laryngeal hyperresponsiveness, and COVID-19. The classification of chronic cough is constantly updated but lacks clear definition. Epidemiological data on the prevalence of chronic cough are informative but highly variable. The underlying mechanism of chronic cough is a neurogenic inflammation of the cough reflex which becomes hypersensitive, thus the term hypersensitive cough reflex (HCR). A current challenge is to decipher how various infectious and inflammatory airway diseases and esophageal reflux, among others, modulate HCR. Objectives: The World Allergy Organization/Allergic Rhinitis and its Impact on Asthma (WAO/ARIA) Joint Committee on Chronic Cough reviewed the current literature on classification, epidemiology, presenting features, and mechanistic pathways of chronic cough in airway- and reflux-related cough phenotypes, OSA, and COVID-19. The interplay of cough reflex sensitivity with other pathogenic mechanisms inherent to airway and reflux-related inflammatory conditions was also analyzed. Outcomes: Currently, it is difficult to clearly ascertain true prevalence rates in epidemiological studies of chronic cough phenotypes. This is likely due to lack of standardized objective measures needed for cough classification and frequent coexistence of multi-organ cough origins. Notwithstanding, we emphasize the important role of HCR as a mechanistic trigger in airway- and reflux-related cough phenotypes. Other concomitant mechanisms can also modulate HCR, including type2/Th1/Th2 inflammation, presence or absence of deep inspiration-bronchoprotective reflex (lower airways), tissue remodeling, and likely cough plasticity, among others.

Background: Cough features a complex peripheral and central neuronal network. The function of the chemosensitive and stretch (afferent) cough receptors is well described but partly understood. It is speculated that chronic cough reflects a neurogenic inflammation of the cough reflex, which becomes hypersensitive. This is mediated by neuromediators, cytokines, inflammatory cells, and a differential expression of neuronal (chemo/stretch) receptors, such as transient receptor potential (TRP) and purinergic P2X ion channels; yet the overall interaction of these mediators in neurogenic inflammation of cough pathways remains unclear. Objectives: The World Allergy Organization/Allergic Rhinitis and its Impact on Asthma (WAO/ARIA) Joint Committee on Chronic Cough reviewed the current literature on neuroanatomy and pathophysiology of chronic cough. The role of TRP ion channels in pathogenic mechanisms of the hypersensitive cough reflex was also examined. Outcomes: Chemoreceptors are better studied in cough neuronal pathways compared to stretch receptors, likely due to their anatomical overabundance in the respiratory tract, but also their distinctive functional properties. Central pathways are important in suppressive mechanisms and behavioral/affective aspects of chronic cough. Current evidence strongly suggests neurogenic inflammation induces a hypersensitive cough reflex marked by increased expression of neuromediators, mast cells, and eosinophils, among others. TRP ion channels, mainly TRP V1/A1, are important in the pathogenesis of chronic cough due to their role in mediating chemosensitivity to various endogenous and exogenous triggers, as well as a crosstalk between neurogenic and inflammatory pathways in cough-associated airways diseases.

Abstract Background In all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is a need to support the transformation of the health care system into integrated care with organizational health literacy. Main body As an example for chronic disease care, MASK (Mobile Airways Sentinel NetworK), a new project of the ARIA (Allergic Rhinitis and its Impact on Asthma) initiative, and POLLAR (Impact of Air POLLution on Asthma and Rhinitis, EIT Health), in collaboration with professional and patient organizations in the field of allergy and airway diseases, are proposing real-life ICPs centred around the patient with rhinitis, and using mHealth to monitor environmental exposure. Three aspects of care pathways are being developed: (i) Patient participation, health literacy and self-care through technology-assisted “patient activation”, (ii) Implementation of care pathways by pharmacists and (iii) Next-generation guidelines assessing the recommendations of GRADE guidelines in rhinitis and asthma using real-world evidence (RWE) obtained through mobile technology. The EU and global political agendas are of great importance in supporting the digital transformation of health and care, and MASK has been recognized by DG Santé as a Good Practice in the field of digitally-enabled, integrated, person-centred care. Conclusion In 20 years, ARIA has considerably evolved from the first multimorbidity guideline in respiratory diseases to the digital transformation of health and care with a strong political involvement.

Objective: To assess the relationship between mouth breathing and growth disorders among children and teenagers. Data source: Search on MEDLINE database, over the last 10 years, by using the following terms: “mouth breathing”, “adenotonsilar hypertrophy”, “allergic rhinitis”, “sleep disturbance” AND “growth impairment”, “growth hormone”, “failure to thrive”, “short stature”, or “failure to thrive”. Data summary: A total of 247 articles were identified and, after reading the headings, this number was reduced to 45 articles, whose abstracts were read and, of these, 20 were deemed important and were included in the review. In addition of these articles, references mentioned in them and specific books on mouth breathing deemed important were included. Hypertrophy of palatine and/or pharyngeal tonsils, whether associated with allergic rhinitis, as well as poorly controlled allergic rhinitis, are the main causes of mouth breathing in children. Respiratory sleep disorders are frequent among these patients. Several studies associate mouth breathing with reduced growth, as well as with reduced growth hormone release, which are reestablished after effective treatment of mouth breathing (clinical and/or surgical). Conclusions: Mouth breathing should be considered as a potential cause of growth retardation in children; pediatricians should assess these patients in a broad manner. Resumo: Objetivo: Avaliar a relação entre respiração oral e distúrbios do crescimento entre crianças e adolescentes. Fonte de dados: Busca na base de dados do MEDLINE, nos últimos 10 anos, com o emprego dos seguintes termos: “mouth breathing” ou “adenotonsilar hypertrophy”, ou “allergic rhinitis” ou sleep disturbance” AND “growth impairment” ou “growth hormone” ou “failure to thrive” ou “short stature” ou “failure to thrive”. Síntese dos dados: Foram identificados 247 artigos, que após a leitura dos títulos foram reduzidos a 45, cujos resumos foram lidos e desses 20 foram considerados de importância e integraram a revisão. Além desses, referências por eles citadas e livros‐texto específicos sobre respiração oral considerados importantes foram incluídos. A hipertrofia de tonsilas palatinas e/ou faríngeas, associada ou não à rinite alérgica, assim como a rinite alérgica mal controlada, é a principal causa de respiração oral na criança. Distúrbios respiratórios do sono são frequentes entre esses pacientes. Vários estudos associam a respiração oral à redução do crescimento, bem como à redução de liberação de hormônio do crescimento, que são restabelecidos após o tratamento efetivo da respiração oral (clínico e/ou cirúrgico). Conclusões: A respiração oral deve ser cogitada como possível causa de retardo de crescimento em crianças e cabe ao pediatra a tarefa de investigar esses pacientes de forma mais abrangente. Keywords: Allergic rhinitis, Adenoid hypertrophy, Tonsillar hypertrophy, Mouth breather, Growth, Palavras‐chave: Rinite alérgica, Hipertrofia de adenoide, Hipertrofia de amígdala, Respirador oral, Crescimento

Background: The COVID-19 outbreak brought an unprecedented challenge to the world. Knowledge in the field has been increasing exponentially and the main allergy societies have produced guidance documents for better management of allergic patients during this period. However, few publications so far have provided real-life data from the allergy community concerning allergy practice during the COVID-19 outbreak. Therefore, we proposed an international survey on the management of allergic patients during the current pandemic. Methods: We performed an online survey undertaken to reach out the worldwide allergy community by e-mail and social media. The web-based questionnaire contained 24 questions covering demographic data from the participants, clinical practice during this period, and questions related to the new international classification and coding tools addressed for COVID-19. It was circulated for 8 weeks and had anonymous and volunteer context. Results: Data are presented for 635 participants from 78 countries of all continents. Allergists with long-term professional experience were the main audience. As expected, we received many responses as “I have no data” or “I don't know” to the questions of the survey. However, most with more experience on managing allergic patients during the pandemic agreed that patients suffering from allergic or hypersensitivity conditions have no increased risk of contracting COVID-19 or developing SARS CoV-2. Also, participants mentioned that none of the allergy treatments (inhaled corticosteroids, allergen immunotherapy, biological agents) increased the risk of contracting COVID-19 infection including severe presentations. Conclusion: The data presented are a starting point in the process of getting feedback on all the recommendations provided by the allergy societies; it could also be the basis of new strategies to support health professionals while new COVID-19 specific treatments and vaccines are being explored. The information here presented intends to be helpful to the community but represents a course of action in a highly specific situation due to the state of emergency, and it should be helpful to health systems.

Background: The current COVID-19 pandemic has changed many medical practices in order to provide additional protection to both our patients and healthcare providers. In many cases this includes seeing patients through electronic means such as telehealth or telephone rather than seeing them in person. Asthma exacerbations cannot always be treated in this way. Problem: Current emergency unit asthma guidelines recommend bronchodilators be administered by metered dose inhaler (MDI) and spacer for mild-moderate asthma and include it as a choice even in severe asthma, but many emergency units continue to prefer nebulised therapy for patients who urgently require beta-agonists. The utilization of nebulised therapy potentially increases the risk of aerosolization of the coronavirus. Since nosocomial transmission of respiratory pathogens is a major threat in the context of the SARS-CoV-2 pandemic, use of nebulised therapy is of even greater concern due to the potential increased risk of infection spread to nearby patients and healthcare workers. Practical implications: We propose a risk stratification plan that aims to avoid nebulised therapy, when possible, by providing an algorithm to help better delineate those who require nebulised therapy. Protocols that include strategies to allow flexibility in using MDIs rather than nebulisers in all but the most severe patients should help mitigate this risk of aerosolised infection transmission to patients and health care providers. Furthermore, expedient treatment of patients with high dose MDI therapy augmented with more rapid initiation of systemic therapy may help ensure patients are less likely to deteriorate to the stage where nebulisers are required.

We conducted a large global survey, Still Fighting for Breath, in patients with severe persistent asthma, 10 years after the Fighting for Breath survey to assess the impact of disease on patients' lives and to determine if control and management have changed in recent years. Data were collected from 1333 adults (aged >18 years) and caregivers of children (aged 6–17 years) with severe persistent asthma from nine countries through an online survey conducted in 2016 by GfK. A decade after the first survey, our results showed that the impact of severe asthma has not changed significantly and a high proportion of patients with severe asthma remain inadequately controlled. A large discrepancy was observed between the proportion of patients who perceived their asthma to be well controlled (42%) and the proportion of patients who reported to be well controlled as per the Global Initiative for Asthma (GINA) assessment (6%). Although most patients perceived their asthma to be controlled, many experienced frequent symptoms that affected their daily lives. Thus, there is a need for improved management (support and strategies) of patients with severe persistent asthma and improved coordination of efforts that would enable these patients to achieve better disease control.

Real-world data on the range and impact of comorbid health conditions that affect pediatric asthma are scant, especially from developing countries. Lack of data hinders effective diagnosis, treatment, and overall management of these complex cases. We, hereby, describe the common pediatric asthma comorbid conditions in terms of evidence for association, potential mechanisms of impact on asthma control, and treatment benefit. Obesity, upper airway allergies, dysfunctional breathing, multiple sensitizations, depressive disorders, food allergy, and gastro-esophageal reflux are common associations with difficult-to-treat asthma. On the other hand, asthma symptoms and/or management may negatively impact the well-being of children through drug adverse effects, worsening of anaphylaxis symptoms, and disturbing mental health.Awareness of these ailments may be crucial for designing the optimum care for each asthmatic child individually and may ultimately improve the quality of life of patients and their families. A multidisciplinary team of physicians is required to identify and manage such comorbidities aiming to mitigate the over-use of asthma pharmacotherapy. Asthma research should target relevant real-world difficulties encountered at clinical practice and focus on interventions that would mitigate the impact of such comorbidities. Finally, policymakers and global healthcare organizations are urged to recognize pediatric asthma control as a healthcare priority and allocate resources for research and clinical interventions. In other words, global asthma control needs support by compassionate scientific partnership.

There is a lack of consensus over the description and severity assignment of allergic adverse reactions to immunotherapy, although there seems to be a consensus at least in terms of using the World Allergy Organization (WAO) grading systems to describe local adverse events for Sublingual Immunotherapy (SLIT) and Systemic Allergic Reactions (SARs) to Subcutaneous Immunotherapy (SCIT) amongst the major national/regional allergy societies. In this manuscript, we propose a modification of the previous WAO Grading system for SARs, which aligns with the newly-proposed Consortium for Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions in Food Allergy (version 3.0). We hope this can facilitate a unified grading system appropriate to SARs due to allergen immunotherapy, independent of allergen and route of administration, and across clinical and research practice.

The emergence of biologic therapies for the management of asthma has been a revolutionary change in our capacity to manage this disease.Since the launch of omalizumab, several other biologics have been marketed or are close to being marketed, suggesting that a plethora of monoclonal antibodies can be expected in the coming years. This will facilitate the transition to the paradigm of personalized medicine, but on the other hand will decisively further complicate the choice of the most appropriate treatment, in the absence of reliable enough biological markers.For these reasons, along with the relatively short time of use with these treatments, there are recurrently arising questions for which there are not even moderately documented answers, and for which the only solution must be based, with all reservations, on the combination of indirect evidence and expertise. In this paper, we attempt to address such questions, providing relevant commentaries and considering the whole width of the evidence base.

Asthma imposes a heavy morbidity burden during childhood; it affects over 10% of children in Europe and North America and it is estimated to exceed 400 million people worldwide by the year 2025. In clinical practice, diagnosis of asthma in children is mostly based on clinical criteria; nevertheless, assessment of both physiological and pathological processes through biomarkers, support asthma diagnosis, aid monitoring, and further lead to better treatment outcomes and reduced morbidity. Recently, identification and validation of biomarkers in pediatric asthma has emerged as a top priority across leading experts, researchers, and clinicians. Moreover, the implementation of non-invasive biomarkers for the assessment and monitoring of paediatric patients with asthma, has been prioritized; however, only a proportion of them are currently included in the clinical practise. Although, the use of non-invasive biomarkers is highly supported in recent asthma guidelines for documenting diagnosis and supporting monitoring of asthmatic patients, data on the Pediatric population are limited.In the present report, the Pediatric Asthma Committee of the World Allergy Organization (WAO), aims to summarize and discuss available data for the implementation of non-invasive biomarkers in the diagnosis and monitoring in children with asthma. Information on the most studied biomarkers, including spirometry, oscillometry, markers of allergic sensitization, fractional exhaled nitric oxide, and the most recent exhaled breath markers and “omic” approaches, will be reviewed. Practical limitations and considerations based on both experts' opinion and critical review of the literature, on the utility of all “well-known” and newly introduced non-invasive biomarkers will be presented. A critical commentary on biomarkers’ use in diagnosing and monitoring asthma during the COVID-19 pandemic, cost and availability of biomarkers in different settings and in developing countries, the differences on the biomarkers use between Primary Practitioners, Pediatricians, and Specialists and their role on the longitudinal aspect of asthma is provided.

Abstract Background Asthma affects the lives of hundred million people around the World. Despite notable progresses in disease management, asthma control remains largely insufficient worldwide, influencing patients’ wellbeing and quality of life. Poor patient handling of inhaling devices has been identified as a major persistent problem that significantly reduces inhaled drugs’ efficacy and is associated with poor adherence to treatment, impairing clinical results such as asthma control and increasing disease-related costs. We herein review key research and development (R&D) innovation in inhaler devices, highlighting major real-world critical errors in the handling and inhalation technique with current devices and considering potential solutions. Furthermore, we discuss current evidence regarding breath-triggered inhalers (BTI). Main body The two most common significant problems with inhalers are coordinating actuation and inhalation with pressurized metered-dose inhalers (pMDIs), and the need to inhale forcibly with a dry powder inhaler. BTI R&D plans were designed to overcome these problems. Its newest device k-haler® has several other important features, generating a less forceful aerosol plume than previous pMDIs, with efficient drug delivery and lung deposition, even in patients with low inspiratory flow. The local and systemic bioavailability of fluticasone propionate and formoterol (FP/FORM) administered via k-haler® has been shown to be therapeutically equivalent when administered via the previous FP/FORM pMDI. This device requires very few steps and has been considered easy to use (even at first attempt) and preferred by the patients in a randomized crossover study. In our country, FP/FORM k-haler is available without additional costs compared to FP/FORM pMDI. All devices continue to require education and regular checking of the correct inhalation technique. Conclusion BTI R&D can bring advantage over current available inhalers, avoiding the two most common identified critical errors in inhalation technique. K-haler® BTI is currently available, without an increased cost, and approved for adolescents and adults with asthma in whom treatment with inhaled combined therapy with long-acting beta2-agonists and corticosteroids is indicated. Its attractive and practical design to facilitate its use has been awarded. K-haler® represents added value through innovation to fulfill actual asthma patient needs, thus with potential relevant impact in asthma management and effective control.

Dyspnea is reported in a minority of patients affected by coronavirus disease 2019 (COVID-19). Even patients with pneumonia can present hypoxemia without any respiratory distress, a phenomenon known as “silent” or “happy hypoxemia”. During the current pandemic there were only a few studies conducted on this subject and these were quite heterogeneous. Therefore, the prevalence of “silent hypoxemia” varied substantially. While studies did not show a clear tendency of “silent hypoxemia” to poorer outcomes compared to hypoxemia presenting with dyspnea, several showed that patients with “silent hypoxemia” are not protected from poor outcomes either. There is a need for a uniform definition of “silent hypoxemia”, in order to better guide clinicians and investigators. More studies are needed to shed light on the mechanisms of “silent hypoxemia”, as well as its presentation and influence in the disease's progression and outcomes, so as to better assist physicians in the care of COVID-19 patients.

Abstract Background MASK‐air® is an app that supports allergic rhinitis patients in disease control. Users register daily allergy symptoms and their impact on activities using visual analog scales (VASs). We aimed to assess the concurrent validity, reliability, and responsiveness of these daily VASs. Methods Daily monitoring VAS data were assessed in MASK‐air® users with allergic rhinitis. Concurrent validity was assessed by correlating daily VAS values with those of the EuroQol‐5 Dimensions (EQ‐5D) VAS, the Control of Allergic Rhinitis and Asthma Test (CARAT) score, and the Work Productivity and Activity Impairment Allergic Specific (WPAI‐AS) Questionnaire (work and activity impairment scores). Intra‐rater reliability was assessed in users providing multiple daily VASs within the same day. Test–retest reliability was tested in clinically stable users, as defined by the EQ‐5D VAS, CARAT, or “VAS Work” (i.e., VAS assessing the impact of allergy on work). Responsiveness was determined in users with two consecutive measurements of EQ‐5D‐VAS or “VAS Work” indicating clinical change. Results A total of 17,780 MASK‐air® users, with 317,176 VAS days, were assessed. Concurrent validity was moderate–high (Spearman correlation coefficient range: 0.437–0.716). Intra‐rater reliability intraclass correlation coefficients (ICCs) ranged between 0.870 (VAS assessing global allergy symptoms) and 0.937 (VAS assessing allergy symptoms on sleep). Test–retest reliability ICCs ranged between 0.604 and 0.878—“VAS Work” and “VAS asthma” presented the highest ICCs. Moderate/large responsiveness effect sizes were observed—the sleep VAS was associated with lower responsiveness, while the global allergy symptoms VAS demonstrated higher responsiveness. Conclusion In MASK‐air®, daily monitoring VASs have high intra‐rater reliability and moderate–high validity, reliability, and responsiveness, pointing to a reliable measure of symptom loads.

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.

This is Part 1 of an updated follow-up review of a World Allergy Organization (WAO) position paper published in 2012 on the diagnosis and treatment of urticaria and angioedema. Since 2012, there have been advances in the understanding of the pathogenesis of chronic urticaria, and greater experience with the use of biologics, such as omalizumab, in patients with severe refractory disease. For these reasons, the WAO decided to initiate an update targeted to general practitioners around the world, incorporating the most recent information on epidemiology, immunopathogenesis, comorbidities, quality of life, clinical case presentations, and the management of chronic spontaneous and chronic inducible urticaria, including urticaria in special situations such as childhood and pregnancy. A special task force of WAO experts was invited to write the different sections of the manuscript, and the final document was approved by the WAO Board of Directors. This paper is not intended to be a substitute for current national and international guidelines on the management of urticaria and angioedema but to provide an updated, simplified guidance for physicians around the world who manage patients with this common ailment.

A iniciativa Allergic Rhinitis and Its Impact on Asthma (ARIA) teve início há mais de 20 anos e tem elaborado e disseminado orientações baseadas em evidência, e desenvolvido projetos na área da rinite alérgica. Esta iniciativa está atualmente focada em proporcionar orientações centradas no doente que contribuam para um percurso integrado entre os vários níveis de cuidados e que tirem partido de soluções digitais, tendo sido recomendada a introdução na prática clínica de percursos assistenciais integrados. Neste artigo descrevemos a adaptação para Portugal do documento ARIA Integrated Care Pathways. Após breve revisão sobre a epidemiologia e o impacto da rinite alérgica em Portugal e das atividades realizadas em Portugal no âmbito da iniciativa ARIA, é descrito o conjunto alargado de conhecimento utilizado para o desenvolvimento das recomendações para o tratamento farmacológico da rinite alérgica, recomendações essas baseadas na metodologia GRADE, evidência do mundo real adquirida por tecnologia móvel (mHealth) e resultante de estudos de câmara de exposição alergénica. Em seguida, são resumidos os percursos assistenciais integrados para imunoterapia com alergénios produzidas em 2019. Considera-se a imunoterapia com alergénios um exemplo de medicina de precisão e em que a utilização de tecnologias mHealth permitirá melhorar a estratificação para seleção dos doentes e monitorização da resposta. Estas recomendações foram consideradas como ‘boas práticas’ dos cuidados integrados centrados no doente apoiados por sistemas digitais da DG Santé (Direção Geral de Saúde e de Segurança Alimentar da União Europeia) e representam a estratégia de gestão da mudança da fase 4 do ARIA.

Medical devices provide people with some health benefits in terms of diagnosis, prevention, treatment, and monitoring of disease processes. Different medical specialties use varieties of medical devices more or less specific for them. Allergology is an interdisciplinary field of medical science and teaches that allergic reactions are of systemic nature but can express themselves at the level of different organs across the life cycle of an individual. Subsequently, medical devices used in allergology could be regarded as: 1) general, servicing the integral diagnostic and management principles and features of allergology, and 2) organ specific, which are shared by organ specific disciplines like pulmonology, otorhinolaryngology, dermatology, and others. The present position paper of the World Allergy Organization (WAO) is meant to be the first integral document providing structured information on medical devices in allergology used in daily routine but also needed for sophisticated diagnostic purposes and modern disease management. It is supposed to contribute to the transformation of the health care system into integrated care pathways for interrelated comorbidities.