Adherence to inhaled corticosteroids and long-acting ß2-agonists in asthma: A MASK-air study.

INTRODUCTION: Adherence to controller medication is a major problem in asthma management, being difficult to assess and tackle. mHealth apps can be used to assess adherence. We aimed to assess the adherence to inhaled corticosteroids+long-acting ß2-agonists (ICS+LABA) in users of the MASK-air® app, comparing the adherence to ICS+formoterol (ICS+F) with that to ICS+other LABA. MATERIALS AND METHODS: We analysed complete weeks of MASK-air® data (2015-2022; 27 countries) from patients with self-reported asthma and ICS+LABA use. We compared patients reporting ICS+F versus ICS+other LABA on adherence levels, symptoms and symptom-medication scores. We built regression models to assess whether adherence to ICS+LABA was associated with asthma control or short-acting beta-agonist (SABA) use. Sensitivity analyses were performed considering the weeks with no more than one missing day. RESULTS: In 2598 ICS+LABA users, 621 (23.9%) reported 4824 complete weeks and 866 (33.3%) reported weeks with at most one missing day. Higher adherence (use of medication ≥80% of weekly days) was observed for ICS+other LABA (75.1%) when compared to ICS+F (59.3%), despite both groups displaying similar asthma control and work productivity. The ICS+other LABA group was associated with more days of SABA use than the ICS+F group (median=71.4% versus 57.1% days). Each additional weekly day of ICS+F use was associated with a 4.1% less risk in weekly SABA use (95%CI=-6.5;-1.6%;p=0.001). For ICS+other LABA, the percentage was 8.2 (95%CI=-11.6;-5.0%;p<0.001). CONCLUSIONS: In asthma patients adherent to the MASK-air app, adherence to ICS+LABA was high. ICS+F users reported lower adherence but also a lower SABA use and a similar level of control.

Rhinitis associated with asthma is distinct from rhinitis alone: The ARIA-MeDALL hypothesis.

Asthma, rhinitis, and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of "one-airway-one-disease," coined over 20 years ago, is a simplistic approach of the links between upper- and lower-airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitization and multimorbidity, (iii) advances in mHealth for novel phenotype definitions, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches, and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper- and lower-airway allergic diseases with skin, gut, and neuropsychiatric multimorbidities, is the "Epithelial Barrier Hypothesis." This review determined that the "one-airway-one-disease" concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme "allergic" (asthma) phenotype combining asthma, rhinitis, and conjunctivitis. Rhinitis alone and rhinitis and asthma multimorbidity represent two distinct diseases with the following differences: (i) genomic and transcriptomic background (Toll-Like Receptors and IL-17 for rhinitis alone as a local disease; IL-33 and IL-5 for allergic and non-allergic multimorbidity as a systemic disease), (ii) allergen sensitization patterns (mono- or pauci-sensitization versus polysensitization), (iii) severity of symptoms, and (iv) treatment response. In conclusion, rhinitis alone (local disease) and rhinitis with asthma multimorbidity (systemic disease) should be considered as two distinct diseases, possibly modulated by the microbiome, and may be a model for understanding the epidemics of chronic and autoimmune diseases.

Identification by cluster analysis of patients with asthma and nasal symptoms using the MASK-air® mHealth app.

BACKGROUND: The self-reporting of asthma frequently leads to patient misidentification in epidemiological studies. Strategies combining the triangulation of data sources may help to improve the identification of people with asthma. We aimed to combine information from the self-reporting of asthma, medication use and symptoms to identify asthma patterns in the users of an mHealth app. METHODS: We studied MASK-air® users who reported their daily asthma symptoms (assessed by a 0-100 visual analogue scale - "VAS Asthma") at least three times (either in three different months or in any period). K-means cluster analysis methods were applied to identify asthma patterns based on: (i) whether the user self-reported asthma; (ii) whether the user reported asthma medication use and (iii) VAS asthma. Clusters were compared by the number of medications used, VAS asthma levels and Control of Asthma and Allergic Rhinitis Test (CARAT) levels. FINDINGS: We assessed a total of 8,075 MASK-air® users. The main clustering approach resulted in the identification of seven groups. These groups were interpreted as probable: (i) severe/uncontrolled asthma despite treatment (11.9-16.1% of MASK-air® users); (ii) treated and partly-controlled asthma (6.3-9.7%); (iii) treated and controlled asthma (4.6-5.5%); (iv) untreated uncontrolled asthma (18.2-20.5%); (v) untreated partly-controlled asthma (10.1-10.7%); (vi) untreated controlled asthma (6.7-8.5%) and (vii) no evidence of asthma (33.0-40.2%). This classification was validated in a study of 192 patients enrolled by physicians. INTERPRETATION: We identified seven profiles based on the probability of having asthma and on its level of control. mHealth tools are hypothesis-generating and complement classical epidemiological approaches in identifying patients with asthma.

Anaphylaxis: A Decade of a Nationwide Allergy Society Registry

Background: Anaphylaxis is an acute, life-threatening, multiorgan hypersensitivity reaction.Objective: The aim of this study was to identify the causes of anaphylaxis in Portugal in order to improve our knowledge of epidemiology and management.Methods: We implemented a nationwide notification system for anaphylaxis over a 10-year period, with voluntary reporting by allergists. Data on 1783 patients with anaphylaxis were included. Etiopathogenesis, manifestations, and clinical management were characterized in detail for both children and adults.Results: The mean age was 32.7 (20.3) years, and 30% were under 18 years of age; 58% were female. The mean age at the first anaphylaxis episode was 27.5 (20.4) years (ranging from 1 month to 88 years). The main culprits of anaphylaxis were foods (48%), drugs (37%) (main trigger in adults, 48%), and hymenoptera venom (7%). The main culprit foods were shellfish (27%), fresh fruit (17%), cow’s milk (16%), tree nuts (15%), fish (8%), egg (7%), and peanut (7%). The main drugs were nonsteroidal anti-inflammatory drugs (43%), antibiotics (39%), and anesthetic agents (6%). Other causes included exercise (3%), latex (2%), cold-induced anaphylaxis (2%), and idiopathic anaphylaxis (2%). Most patients (80%) were admitted to the emergency department; only 43% received adrenaline. Anaphylaxis recurred in 41% of patients (21% with ≥3 anaphylactic episodes); 7% used an adrenaline autoinjector device.Conclusions: Food is the leading cause of anaphylaxis in Portugal, while drugs were the main elicitors in adults. We emphasize undertreatment with adrenaline and recurrent episodes, highlighting the need to improve diagnostic and therapeutic approaches to anaphylaxis (AU)

Antecedentes: La anafilaxia es una reacción de hipersensibilidad sistémica potencialmente mortal.Objetivo: El objetivo de este estudio fue el identificar las causas de la anafilaxia en Portugal para mejorar el conocimiento de la epidemiologíay del manejo de la enfermedad.Métodos: Durante un período de 10 años, se implementó un sistema nacional de notificación de anafilaxia, por parte de los alergólogos,mediante la emisión de informes voluntarios. Se recogieron datos de 1.783 pacientes con anafilaxia, pediátricos y adultos, relativos a laetiopatogenia, las manifestaciones clínicas y el manejo clínico de la misma.Resultados: La edad media fue de 32,7 ± 20,3 años, siendo el 30% de los pacientes menores de 18 años. El 58% fueron mujeres. Laedad media del primer episodio de anafilaxia fue de 27,5 ± 20,4 años (desde 1 mes hasta 88 años). Los principales agentes responsablesde anafilaxia fueron los alimentos (48%), los medicamentos (37%), que fue el principal desencadenante en los pacientes adultos, y losvenenos de himenópteros (7%). Los principales alimentos responsables fueron: mariscos (27%), frutas frescas (17%), leche de vaca (16%),nueces (15%), pescado (8%), huevo (7%) y cacahuete (7%). Los principales fármacos, fueron los antiinflamatorios no esteroideos (43%),antibióticos (39%) y anestésicos (6%). Entre otras causas implicadas se incluyó: ejercicio físico (3%), látex (2%), frío (2%) e idiopática (2%). La mayoría de los pacientes fueron atendidos en el servicio de urgencias (80%), y solo el 43% recibió tratamiento con adrenalina.La recurrencia de la anafilaxia ocurrió en el 41% de los pacientes (21% con ≥3 episodios anafilácticos). El 7% utilizó un dispositivoautoinyector de adrenalina.Conclusiones: Los alimentos son la principal causa de anafilaxia en Portugal y en el subgrupo de pacientes adultos, lo son los medicamentos

Biologics and global burden of asthma: A worldwide portrait and a call for action.

Biologics for severe asthma can significantly impact on the burden of disease and also have the potential to reduce asthma mortality. By reviewing the literature and contacting the pharmaceutical companies, the present paper aims at providing a worldwide snapshot of biologic drugs availability, related with the trend of asthma mortality rate, as a marker of the burden of the disease. A decline in the global rate of annual asthma mortality was observed until the 1980s, but overall no further reduction occurred, and the current mortality estimation is 0.19 deaths per 100.000 people. A higher mortality rate has been registered in low and middle-income countries (LMICs), where poor socioeconomic conditions and lack of access to the medical resources are more relevant. The availability of monoclonal antibodies is mainly limited to the developed and high-income countries. Furthermore the overall "asthma management system" in LMICs suffers from a number of restrictions that hamper the widespread availability of biologics besides their costs. The availability of generic drugs in the field of biologics for severe asthma could contribute to facilitate their widespread accessibility. But before that, awareness and expertise regarding severe asthma, and proper tools to assess and manage it, deserve to be shared worldwide. Collaboration projects involving physicians from all the countries through the scientific Academies network and with the support of the Companies active in the field may provide an initial concrete opportunity.

What do asthmatic patients think about telemedicine visits?

Summary: Introduction. Due to the Coronavirus disease 2019 (COVID-19) outbreak and the national emergency state, virtual visits were implemented as an alternative to in-person visits. With this study we aimed to establish asthma patients' general satisfaction with the quality of health care provided by virtual visits (phone or video calls). Materials and methods. A questionnaire (9 questions) was published on the Facebook page of the Portuguese Association of Asthmatics. It was available online for general self-reported asthmatic patients to answer during one month, starting on 11st May 2020. The survey only allowed one answer per registered user. Results. Fifty-five responses were obtained. Patients were satisfied with communication with providers (> 88%); nevertheless, one-half evaluated the virtual visit as inferior when compared to in-person visits. About one third attributed a classification of 6 or less (0-10 scale, 0 being the worst and 10 the best consultation possible), but still most of the patients would either recommend it or use this kind of medical visits in the future, even outside the actual pandemic context. Patients also referred some important limitations, as lack of physical examination and the fact that the medical visit was more impersonal. Only 27% had technical issues accessing virtual visits. Positive aspects were also named, such as virtual visits being practical and avoiding the need to move to the hospital. Discussion and conclusions. Our survey revealed that small changes could further increase patients' satisfaction, adherence and confidence in telemedicine. Although presenting some limitations, virtual visits seem to be generally well accepted by asthmatic patients and it might be a good alternative for in-person visits, at leastin such difficult times when social distancing is recommended.

Anaphylaxis: A Decade of a Nationwide Allergy Society Registry.

BACKGROUND AND OBJECTIVES: Anaphylaxis is an acute, life-threatening, multiorgan hypersensitivity reaction. Objective: The aim of this study was to identify the causes of anaphylaxis in Portugal in order to improve our knowledge of epidemiology and management. METHODS: We implemented a nationwide notification system for anaphylaxis over a 10-year period, with voluntary reporting by allergists. Data on 1783 patients with anaphylaxis were included. Etiopathogenesis, manifestations, and clinical management were characterized in detail for both children and adults. RESULTS: The mean age was 32.7 (20.3) years, and 30% were under 18 years of age; 58% were female. The mean age at the first anaphylaxis episode was 27.5 (20.4) years (ranging from 1 month to 88 years). The main culprits of anaphylaxis were foods (48%), drugs (37%) (main trigger in adults, 48%), and hymenoptera venom (7%). The main culprit foods were shellfish (27%), fresh fruit (17%), cow's milk (16%), tree nuts (15%), fish (8%), egg (7%), and peanut (7%). The main drugs were nonsteroidal anti-inflammatory drugs (43%), antibiotics (39%), and anesthetic agents (6%). Other causes included exercise (3%), latex (2%), cold-induced anaphylaxis (2%), and idiopathic anaphylaxis (2%). Most patients (80%) were admitted to the emergency department; only 43% received adrenaline. Anaphylaxis recurred in 41% of patients (21% with ≥3 anaphylactic episodes); 7% used an adrenaline autoinjector device. CONCLUSION: Food is the leading cause of anaphylaxis in Portugal, while drugs were the main elicitors in adults. We emphasize undertreatment with adrenaline and recurrent episodes, highlighting the need to improve diagnostic and therapeutic approaches to anaphylaxis.

Treatment of allergic rhinitis during and outside the pollen season using mobile technology. A MASK study.

BACKGROUND: The analysis of mobile health (mHealth) data has generated innovative insights into improving allergic rhinitis control, but additive information is needed. A cross-sectional real-world observational study was undertaken in 17 European countries during and outside the estimated pollen season. The aim was to collect novel information including the phenotypic characteristics of the users. METHODS: The Allergy Diary-MASK-air-mobile phone app, freely available via Google Play and App, was used to collect the data of daily visual analogue scales (VASs) for overall allergic symptoms and medication use. Fluticasone Furoate (FF), Mometasone Furoate (MF), Azelastine Fluticasone Proprionate combination (MPAzeFlu) and eight oral H1-antihistamines were studied. Phenotypic characteristics were recorded at entry. The ARIA severity score was derived from entry data. This was an a priori planned analysis. RESULTS: 9037 users filled in 70,286 days of VAS in 2016, 2017 and 2018. The ARIA severity score was lower outside than during the pollen season. Severity was similar for all treatment groups during the pollen season, and lower in the MPAzeFlu group outside the pollen season. Days with MPAzeFlu had lower VAS levels and a higher frequency of monotherapy than the other treatments during the season. Outside the season, days with MPAzeFlu also had a higher frequency of monotherapy. The number of reported days was significantly higher with MPAzeFlu during and outside the season than with MF, FF or oral H1-antihistamines. CONCLUSIONS: This study shows that the overall efficacy of treatments is similar during and outside the pollen season and indicates that medications are similarly effective during the year.

Tree Nuts Anaphylaxis in Preschool Age Children.

Summary: Introduction. The incidence of food-induced anaphylaxis (FIA) is increasing in young children. Although the commonest culprits are cow's milk and egg, FIA to tree nuts (TNs) have been increasing. Objective. Characterization of children referred to our allergy department due to TNs-induced anaphylaxis (TNs-FIA) during preschool age. Materials and methods. We have retrospectively included 25 children with clinical history of preschool TNs-FIA, proven by allergological work-up. TNs sensitization was assessed by skin prick tests and/or specific IgE. Results. The mean age of the first anaphylactic episode was 3.1±1.2 years. The majority (92%) had an allergic disease (52% asthma). The implicated TNs were cashew (11 children), walnut (8), pine nut (5), hazelnut (2) and almond (1). The reaction occurred after the first known ingestion in 68%. In 92%, symptoms appeared within 30 minutes after exposure. The most frequent clinical symptoms were mucocutaneous (96%), respiratory (80%) and gastrointestinal (52%). Twenty-one children were admitted to the emergency department, although only 48% were treated with epinephrine. An underneath IgE-mediated mechanism was proven in all cases. Immunologic cross-reactivity with other TNs was identified in 84%, and with peanut in 36%. Overall, in our center, TNs-FIA represents 18% of all causes of FIA. Conclusions. In preschool age children with TNs-FIA, cashew and walnut were the commonest implicated nuts. Most reactions occurred briefly after exposure to minimal amounts of TNs, demonstrating the high potency of these allergens. About one-third also had peanut sensitization. Potentially life-threatening TNs allergy can occur early in childhood and adequate management should be undertaken.

Anaphylaxis to beta-lactam antibiotics at pediatric age: Six-year survey

Introduction: Beta-lactams are the most frequently used antibiotics in pediatric age. Anaphylactic reactions may occur and need to be properly studied, but studies in children are scarce. Objective: Characterization of case reports of anaphylaxis in children referred to an allergy department with suspected beta-lactams hypersensitivity. Materials and methods: Retrospective analysis of all children referred to our Drug Allergy Center with suspected beta-lactams hypersensitivity between January 2011 and December 2016. Description of the drug allergy work-up performed studied according to standardized diagnostic procedures of ENDA/EAACI, including specific-IgE assay, skin prick and intradermal tests and diagnostic/alternative drug challenge tests. Results: 146 children with suspected beta-lactams hypersensitivity were studied, and in 21 (14.4%) the diagnosis was confirmed. In all of them, except for three children, an alternative beta-lactam was found. In seven children (33.3% of those with confirmed beta-lactams hypersensitivity) anaphylaxis was confirmed, and all of them described reactions with cutaneous and respiratory or gastrointestinal involvement. The culprit drug was amoxicillin in six and flucloxacillin in one. In this sample, we also performed oral challenge with cefuroxime, being negative in all cases. Almost all cases of confirmed anaphylaxis (six from seven cases) were IgE mediated, with positive skin tests despite negative serum specific-IgE. Conclusions: Allergic reactions to beta-lactams, although rare in children, require a detailed clinical history and a specialized drug allergy work-up to allow a correct diagnosis as well as to avoid the possibility of a potential life-threatening reaction and provide alternative drugs

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Successful oral desensitization in children with cow's milk anaphylaxis: Clinical and laboratory evaluation up to nine-years follow-up

Introduction: Cow's milk protein allergy (CMPA) is the most common food allergy in children worldwide. Some children have severe and persistent CMPA, with near-fatal reactions after exposure to trace amounts of cow's milk-proteins (CMP). Strict avoidance diet is difficult, negatively affects quality of life and represents a conservative approach. Therefore, different therapeutic strategies are necessary. Objective: We aimed to assess long-term efficacy and safety of oral immunotherapy (OIT) in children with severe and long-lasting IgE-mediated CMPA. Materials and methods: The authors present four case reports of patients with CMPA who underwent CMP-OIT, that have been under long-term follow-up up to nine years. We provide information about the clinical and laboratory evaluation. Skin prick tests (SPT), specific IgE and IgG4 were performed before, during, and after OIT. Immune profile after OIT was assessed by flow cytometry (lymphocyte subsets, regulatory T and B cells). Results: The success rate was 100%, and all patients currently have a free diet with minimal diary ingestion of 200mL CMP or equivalent. Specific IgE levels and SPT to CMP have progressively decreased, and specific IgG4 levels have increased. CD4+CD25+CD127/dim regulatory T cells were increased after OIT. Conclusions: OIT ensured a clinical tolerance state after up to nine years, confirmed by both clinical and immune profile, allowing a diet without restrictions, with high satisfaction from patients and caregivers. We emphasize that OIT should be performed only by allergy experts in the hospital setting, and that only motivated families should be enrolled, since it is essential to ensure CMP daily intake at home

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Guidance to 2018 good practice: ARIA digitally-enabled, integrated, person-centred care for rhinitis and asthma.

AIMS: Mobile Airways Sentinel NetworK (MASK) belongs to the Fondation Partenariale MACVIA-LR of Montpellier, France and aims to provide an active and healthy life to rhinitis sufferers and to those with asthma multimorbidity across the life cycle, whatever their gender or socio-economic status, in order to reduce health and social inequities incurred by the disease and to improve the digital transformation of health and care. The ultimate goal is to change the management strategy in chronic diseases. METHODS: MASK implements ICT technologies for individualized and predictive medicine to develop novel care pathways by a multi-disciplinary group centred around the patients. STAKEHOLDERS: Include patients, health care professionals (pharmacists and physicians), authorities, patient's associations, private and public sectors. RESULTS: MASK is deployed in 23 countries and 17 languages. 26,000 users have registered. EU GRANTS 2018: MASK is participating in EU projects (POLLAR: impact of air POLLution in Asthma and Rhinitis, EIT Health, DigitalHealthEurope, Euriphi and Vigour). LESSONS LEARNT: (i) Adherence to treatment is the major problem of allergic disease, (ii) Self-management strategies should be considerably expanded (behavioural), (iii) Change management is essential in allergic diseases, (iv) Education strategies should be reconsidered using a patient-centred approach and (v) Lessons learnt for allergic diseases can be expanded to chronic diseases.

Successful oral desensitization in children with cow's milk anaphylaxis: Clinical and laboratory evaluation up to nine-years follow-up.

INTRODUCTION: Cow's milk protein allergy (CMPA) is the most common food allergy in children worldwide. Some children have severe and persistent CMPA, with near-fatal reactions after exposure to trace amounts of cow's milk-proteins (CMP). Strict avoidance diet is difficult, negatively affects quality of life and represents a conservative approach. Therefore, different therapeutic strategies are necessary. OBJECTIVE: We aimed to assess long-term efficacy and safety of oral immunotherapy (OIT) in children with severe and long-lasting IgE-mediated CMPA. MATERIALS AND METHODS: The authors present four case reports of patients with CMPA who underwent CMP-OIT, that have been under long-term follow-up up to nine years. We provide information about the clinical and laboratory evaluation. Skin prick tests (SPT), specific IgE and IgG4 were performed before, during, and after OIT. Immune profile after OIT was assessed by flow cytometry (lymphocyte subsets, regulatory T and B cells). RESULTS: The success rate was 100%, and all patients currently have a free diet with minimal diary ingestion of 200mL CMP or equivalent. Specific IgE levels and SPT to CMP have progressively decreased, and specific IgG4 levels have increased. CD4+CD25+CD127-/dim regulatory T cells were increased after OIT. CONCLUSIONS: OIT ensured a clinical tolerance state after up to nine years, confirmed by both clinical and immune profile, allowing a diet without restrictions, with high satisfaction from patients and caregivers. We emphasize that OIT should be performed only by allergy experts in the hospital setting, and that only motivated families should be enrolled, since it is essential to ensure CMP daily intake at home.

Anaphylaxis to beta-lactam antibiotics at pediatric age: Six-year survey.

INTRODUCTION: Beta-lactams are the most frequently used antibiotics in pediatric age. Anaphylactic reactions may occur and need to be properly studied, but studies in children are scarce. OBJECTIVE: Characterization of case reports of anaphylaxis in children referred to an allergy department with suspected beta-lactams hypersensitivity. MATERIALS AND METHODS: Retrospective analysis of all children referred to our Drug Allergy Center with suspected beta-lactams hypersensitivity between January 2011 and December 2016. Description of the drug allergy work-up performed studied according to standardized diagnostic procedures of ENDA/EAACI, including specific-IgE assay, skin prick and intradermal tests and diagnostic/alternative drug challenge tests. RESULTS: 146 children with suspected beta-lactams hypersensitivity were studied, and in 21 (14.4%) the diagnosis was confirmed. In all of them, except for three children, an alternative beta-lactam was found. In seven children (33.3% of those with confirmed beta-lactams hypersensitivity) anaphylaxis was confirmed, and all of them described reactions with cutaneous and respiratory or gastrointestinal involvement. The culprit drug was amoxicillin in six and flucloxacillin in one. In this sample, we also performed oral challenge with cefuroxime, being negative in all cases. Almost all cases of confirmed anaphylaxis (six from seven cases) were IgE mediated, with positive skin tests despite negative serum specific-IgE. CONCLUSIONS: Allergic reactions to beta-lactams, although rare in children, require a detailed clinical history and a specialized drug allergy work-up to allow a correct diagnosis as well as to avoid the possibility of a potential life-threatening reaction and provide alternative drugs.

Anaphylaxis to clavulanic acid: a 7-year survey

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