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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 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.

BackgroundReliance on short-acting β-2 agonists and nonadherence to maintenance medication are associated with poor clinical outcomes in asthma. Digital health solutions could support optimal medication use and therefore disease control in patients with asthma; however, their use in community settings has not been determined. ObjectiveThe primary objective of this study is to investigate community implementation of the Turbu+ program designed to support asthma self-management, including adherence to budesonide and formoterol (Symbicort) Turbuhaler, a combination inhaler for both maintenance therapy or maintenance and reliever therapy. The secondary objective is to provide health care professionals with insights into how patients were using their medication in real life. MethodsPatients with physician-diagnosed asthma were prescribed budesonide and formoterol as maintenance therapy, at a dose of either 1 inhalation twice daily (1-BID) or 2 inhalations twice daily (2-BID), or as maintenance and reliever therapy (1-BID and reliever or 2-BID and reliever in a single inhaler), and they received training on Turbu+ in secondary care centers across Italy. An electronic device attached to the patients’ inhaler for ≥90 days (data cutoff) securely uploaded medication use data to a smartphone app and provided reminders, visualized medication use, and motivational nudge messages. Average medication adherence was defined as the proportion of daily maintenance inhalations taken as prescribed (number of recorded maintenance actuations per day or maintenance inhalations prescribed per day) averaged over the monitoring period. The proportion of adherent days was defined as the proportion of days when all prescribed maintenance inhalations were taken on a given day. The Wilcoxon test was used to compare the proportion of adherent days between patients in the maintenance regimen and patients in the maintenance and reliever regimen of a given dose. ResultsIn 661 patients, the mean (SD) number of days monitored was 217.2 (SD 109.0) days. The average medication adherence (maintenance doses taken/doses prescribed) was 70.2% (108,040/153,820) overall and was similar across the groups (1-BID: 6332/9520, 66.5%; 1‑BID and reliever: 43,578/61,360, 71.0%; 2-BID: 10,088/14,960, 67.4%; 2-BID and reliever: 48,042/67,980, 70.7%). The proportion of adherent days (prescribed maintenance doses/doses taken in a given day) was 56.6% (31,812/56,175) overall and was higher with maintenance and reliever therapy (1-BID and reliever vs 1-BID: 18,413/30,680, 60.0% vs 2510/4760, 52.7%; P

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.

Abstract Background Allergic rhinitis (AR) management requires a coordinated effort from healthcare providers and patients. Pharmacists are key members of these integrated care pathways resolving medication‐related problems, optimizing regimens, improving adherence and recommending therapies while establishing liaisons between patients and physicians. Methods Allergic Rhinitis and its Impact on Asthma (ARIA) first published a reference document on the pharmacist's role in allergic rhinitis management in 2004. Several guidelines were developed over the past 20 years improving the care of allergic rhinitis patients through an evidence‐based, integrated care approach. Results This ARIA/EAACI/FIP Position Paper is based on the latest ARIA in the Pharmacy guidelines and provides: (a) a structured approach to pharmacists identifying people with AR and/or allergic conjunctivitis as well as those at risk of poor disease control; (b) an evidence‐based clinical decision support tool for optimising the management of allergic rhinitis in the community pharmacy; and (c) a framework of referral to the physician. Conclusion This document is not intended to be a mandatory standard of care but is provided as a basis for pharmacists and their staff to develop relevant local standards of care for their patients, within their local practice environment. Pharmacy care varies between countries, and the guide should be adapted to the local situation.

Abstract Background In asthma, persistent airflow limitation (PAL) is associated with poorer control, lung function decline and exacerbations. Using post‐hoc analyses we evaluated: the relationship between post‐salbutamol PAL at screening, airflow limitation (AL) during 52 weeks treatment with extrafine beclometasone dipropionate/formoterol fumarate/glycopyrronium (BDP/FF/G) versus BDP/FF and the risk of moderate/severe asthma exacerbations. Methods TRIMARAN and TRIGGER were double‐blind studies comparing BDP/FF/G with BDP/FF (TRIMARAN medium‐dose ICS; TRIGGER high‐dose) in adults with uncontrolled asthma. Patients were subgrouped according to post‐salbutamol PAL status at screening, and AL over the 52‐week treatment period. Results Most patients with post‐salbutamol PAL at screening had AL at all on‐treatment visits (TRIMARAN 62.8%; TRIGGER 66.8%). A significantly higher proportion of patients had normalised airflow on ≥1 follow‐up visit when receiving BDP/FF/G than BDP/FF (TRIMARAN 44.1 vs. 33.1% [p = 0.003]; TRIGGER 40.1 vs. 26.0% [p

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.

Abstract Background An increase in online searches on health topics may either mirror epidemiological changes or reflect media coverage. In the context of COVID-19, this is particularly relevant, as COVID-19 symptoms may be mistaken for those of respiratory disease exacerbations. Therefore, we aimed to assess Internet search patterns on asthma and chronic obstructive pulmonary disease (COPD) in the context of COVID-19, as compared to searches on other chronic diseases. Methods We retrieved Google Trends (GTs) data on two respiratory (asthma and COPD) and three non-respiratory (diabetes, hypertension, and Crohn’s disease) chronic diseases over the past 5 years (up to May 31, 2020). For 54 countries, and for each disease, we built autoregressive integrated moving average (ARIMA) models to predict GTs for 2020 based on 2015–2019 search patterns. In addition, we estimated the proportion of searches in which COVID-19-related terms were used. To assess the potential impact of media coverage on online searches, we assessed whether weekly “asthma” GTs correlated with the number of Google News items on asthma. Results Over the past 5 years, worldwide search volumes for asthma and COPD reached their maximum values in March 2020. Such was not observed for diabetes, hypertension and Crohn’s disease. In 38 (70%) countries, GTs on asthma were higher in March 2020 than the respective maximum predicted values. This compares to 19 countries for COPD, 23 for hypertension, 11 for Crohn’s disease, and 9 for diabetes. Queries with COVID-19-related terms represented up to 47.8% of the monthly searches on asthma, and up to 21.3% of COPD searches. In most of the assessed countries, moderate-strong correlations were observed between “asthma” GTs and the number of news items on asthma. Conclusions During March 2020, there was a peak in searches on asthma and COPD, which was probably mostly driven by media coverage, as suggested by their simultaneity in several countries with different epidemiological situations.

Abstract Reported COVID-19 deaths in Germany are relatively low as compared to many European countries. Among the several explanations proposed, an early and large testing of the population was put forward. Most current debates on COVID-19 focus on the differences among countries, but little attention has been given to regional differences and diet. The low-death rate European countries (e.g. Austria, Baltic States, Czech Republic, Finland, Norway, Poland, Slovakia) have used different quarantine and/or confinement times and methods and none have performed as many early tests as Germany. Among other factors that may be significant are the dietary habits. It seems that some foods largely used in these countries may reduce angiotensin-converting enzyme activity or are anti-oxidants. Among the many possible areas of research, it might be important to understand diet and angiotensin-converting enzyme-2 (ACE2) levels in populations with different COVID-19 death rates since dietary interventions may be of great benefit.

Allergen immunotherapy (AIT) is a very useful therapy for allergic rhinitis. However, some patients do not achieve the expected results. The aim of the study was to investigate the potential factors that could affect the result, either good or poor, from AIT. Methods: A retrospective analysis of 1624 patients with allergic rhinitis who underwent AIT and 1519 matched patients who underwent only symptomatic therapy (without AIT) was performed. Symptoms, medications scores and quality of life related to allergic diseases before and after therapy were recorded. Cluster analysis on all of the patients was performed to find any associations between responsiveness to therapy and the analyzed parameters. Responsiveness to therapy was assessed by the Mailing criteria. Results: A total of 1266 (77.8%) patients from the AIT group met the criterion of 30% or greater improvement, and 1061 (65.2%) of these patients met the threshold of 60% or greater improvement according to the Mailing criteria. Patients who had a frequently better response to AIT were highly represented in the two clusters. There were subjects with a short history of allergic rhinitis and concomitant allergy to grass pollen or house dust mites. Patients with a prolonged duration of allergic rhinitis before therapy and with polysensitization were more frequently worse responders to AIT. Conclusion: Responsiveness to therapy, including that to AIT, is difficult to assess. However, there were associations suggesting that short-term allergic rhinitis and monovalent allergies to grass pollen or mites could correspond to a better response to AIT.

An amendment to this paper has been published and can be accessed via the original article.

Allergic rhinitis affects the quality of life of millions of people worldwide. Air pollution not only causes morbidity, but nearly 3 million people per year die from unhealthy indoor air exposure. Furthermore, allergic rhinitis and air pollution interact. This report summarizes the discussion of an International Expert Consensus on the management of allergic rhinitis aggravated by air pollution. The report begins with a review of indoor and outdoor air pollutants followed by epidemiologic evidence showing the impact of air pollution and climate change on the upper airway and allergic rhinitis. Mechanisms, particularly oxidative stress, potentially explaining the interactions between air pollution and allergic rhinitis are discussed. Treatment for the management of allergic rhinitis aggravated by air pollution primarily involves treating allergic rhinitis by guidelines and reducing exposure to pollutants. Fexofenadine a non-sedating oral antihistamine improves AR symptoms aggravated by air pollution. However, more efficacy studies on other pharmacological therapy of coexisting AR and air pollution are currently lacking. Keywords: Allergic rhinitis, Occupational rhinitis, Air pollution, Climate change, Air pollutants, Indoor air quality, Oxidative stress, Antioxidant enzymes

Chronic urticaria (CU) has a widespread spectrum on causal or exacerbating factors, clinical manifestations, therapeutic response and quality of life affectation. Registries are useful tools in several real-life diagnosis and management approach.We aimed to evaluate the characteristics of CU patients living in Latin America through an original cross-sectional registry with data entered by regional allergologists. Results: Three hundred patients were included, being 72% female, with median age of 36 years (1–85) and 20 months of CU median evolution time. The cause of CU was reported as unknown in 72% of them.Thirty-nine percent of suspected cases presented positive serology for Mycoplasma, positive autologous serum skin test (ASST) was reported in 47%, and occasional presence of thyroid or antinuclear autoantibodies and parasites. The impact of pruritus in their quality of life was moderate to severe in 60% of patients, with almost 3 out of four patients having partial or lack of urticaria control with anti-histamines. Conclusions: Our registry provides retrospective data on the real-life assistance of a large number of patients from the region. Continuous search for associated conditions and better treatment possibilities are needed, in order to control the significant impact on quality of life and the length of disease. Keywords: Chronic urticaria, Registry, Latin America, Evaluations, Management

Abstract Evidence that enables us to identify, assess, and access the small airways in asthma and chronic obstructive pulmonary disease (COPD) has led INTERASMA (Global Asthma Association) and WAO to take a position on the role of the small airways in these diseases. Starting from an extensive literature review, both organizations developed, discussed, and approved the manifesto, which was subsequently approved and endorsed by the chairs of ARIA and GA2LEN. The manifesto describes the evidence gathered to date and defines and proposes issues on small airway involvement and management in asthma and COPD with the aim of challenging assumptions, fostering commitment, and bringing about change. The small airways (defined as those with an internal diameter

Abstract One of the major concerns in the practice of allergy is related to the safety of procedures for the diagnosis and treatment of allergic disease. Management (diagnosis and treatment) of hypersensitivity disorders involves often intentional exposure to potentially allergenic substances (during skin testing), deliberate induction in the office of allergic symptoms to offending compounds (provocation tests) or intentional application of potentially dangerous substances (allergy vaccine) to sensitized patients. These situations may be associated with a significant risk of unwanted, excessive or even dangerous reactions, which in many instances cannot be completely avoided. However, adverse reactions can be minimized or even avoided if a physician is fully aware of potential risk and is prepared to appropriately handle the situation. Information on the risk of diagnostic and therapeutic procedures in allergic diseases has been accumulated in the medical literature for decades; however, except for allergen specific immunotherapy, it has never been presented in a systematic fashion. Up to now no single document addressed the risk of the most commonly used medical procedures in the allergy office nor attempted to present general requirements necessary to assure the safety of these procedures. Following review of available literature a group of allergy experts within the World Allergy Organization (WAO), representing various continents and areas of allergy expertise, presents this report on risk associated with diagnostic and therapeutic procedures in allergology and proposes a consensus on safety requirements for performing procedures in allergy offices. Optimal safety measures including appropriate location, type and required time of supervision, availability of safety equipment, access to specialized emergency services, etc. for various procedures have been recommended. This document should be useful for allergists with already established practices and experience as well as to other specialists taking care of patients with allergies.

The paradigm of how we manage allergic rhinitis is shifting with a growing understanding that it is a complex process, requiring a coordinated effort from healthcare providers and patients. Pharmacists are key members of these integrated care pathways resolving medication-related problems, optimizing regimens, improving adherence and recommending therapies while establishing liaisons between patients and physicians. Community pharmacists are the most accessible healthcare professionals to the public and allergic rhinitis is one of the most common diseases managed by pharmacists. Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines developed over the past 20 years have improved the care of allergic rhinitis patients through an evidence-based, integrated care approach. In this paper, we propose an integrated approach to allergic rhinitis management in community pharmacy following the 2019 ARIA in the pharmacy guidelines.

Urticaria and angioedema are common clinical conditions representing a major concern for physicians and patients alike. The World Allergy Organization (WAO), recognizing the importance of these diseases, has contributed to previous guidelines for the diagnosis and management of urticaria. The Scientific and Clinical Issues Council of WAO proposed the development of this global Position Paper to further enhance the clinical management of these disorders through the participation of renowned experts from all WAO regions of the world. Sections on definition and classification, prevalence, etiology and pathogenesis, diagnosis, treatment, and prognosis are based on the best scientific evidence presently available. Additional sections devoted to urticaria and angioedema in children and pregnant women, quality of life and patient-reported outcomes, and physical urticarias have been incorporated into this document. It is expected that this article will supplement recent international guidelines with the contribution of an expert panel designated by the WAO, increasing awareness of the importance of urticaria and angioedema in medical practice and will become a useful source of information for optimum patient management worldwide. Keywords: urticaria, angioedema

The allergy cascade presents widespread inflammatory and proinflammatory activation, robust cytokine and chemokine signaling, and heterogeneous immune and endothelial responses that lead ultimately to the manifestations of allergic reaction. Histamine, a small peptide with inherent vasoactive properties, is released from granules contained within mast cells, basophils, lymphocytes, and other reservoirs and interacts with histamine receptors to regulate numerous cellular functions involved in allergic inflammation and immune modulation. Of the known histamine receptors, the H1-receptor is most clearly associated with potentiation of proinflammatory immune cell activity and enhanced effector function and is the prime focus of suppressive therapy. Second-generation oral H1-antihistamines, such as cetirizine, desloratadine, fexofenadine, levocetirizine, and loratadine, are mainstays of allergy treatment, acting as highly specific, long-acting H1-receptor agonists at its unique receptor. The ongoing identification of immune effector cells and mediators involved in the allergic cascade indicates that further research is necessary to define the role of antihistamines such as desloratadine in anti-inflammatory therapy. Keywords: allergic rhinitis, antihistamine, anti-inflammatory, desloratadine, second-generation antihistamines, urticaria

Despite positive clinical experience and the published clinical benefits of monotherapy with low-or medium-dose inhaled corticosteroids or combination therapy with ICS + long-acting beta-agonist to treat asthma, many patients remain suboptimally controlled. Alternative approaches are needed, and 3 options that have had some success are: 1) using the patient's level of inflammation by established biomarkers to set treatment; 2) self-management incorporating flexible dosing; and 3) using a single inhaler for rescue and maintenance therapy. Which strategy for which patient depends ultimately on the individual patient's disease burden, life-style, comorbidities, preferences, and his or her ability to self-manage the disease, including assessing symptoms and adhering with therapy. Keywords: asthma, inhaled corticosteroid, flexible dosing, combination therapy, long-acting beta-agonist

Background Allergic rhinitis (AR) is a common, costly, and troublesome condition, impairing patients' quality of life (QoL), cognitive function, and productivity. Patients with AR report disturbed sleep, fatigue, irritability, and a range of practical problems. However, there is a relative lack of data on how patients with AR perceive their QoL.Objective To better understand how patients perceive AR and their attitudes toward this condition (including QoL) and its treatment options.Methods An online and telephone survey of 3635 people identified as having outdoor and indoor allergies, urticaria, and/or pet allergies was performed in 6 countries.Results The survey confirmed that patients with allergies perceive their symptoms as causing significant disruptions to their daily lives. Respondents were affected for a considerable part of each day, with the most severe symptoms occurring in the morning. The most important desired effect of medication was the restoration of normal breathing, and the most highly rated attributes of the ''ideal'' AR drug were efficacy, safety, and freedom from undesirable side effects.Conclusions The information gathered from allergy sufferers who participated in this survey sheds light on the degree to which people with allergies are affected by their disease and the limitations imposed by associated symptoms. Keywords: allergic rhinitis, nonallergic rhinitis, quality of life