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.

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.

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.

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.

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.

Treatment of allergic rhinitis using mobile technology with real-world data: The MASK observational pilot study.

BACKGROUND: Large observational implementation studies are needed to triangulate the findings from randomized control trials as they reflect "real-world" everyday practice. In a pilot study, we attempted to provide additional and complementary insights on the real-life treatment of allergic rhinitis (AR) using mobile technology. METHODS: A mobile phone app (Allergy Diary, freely available in Google Play and Apple App stores) collects the data of daily visual analog scales (VAS) for (i) overall allergic symptoms, (ii) nasal, ocular, and asthma symptoms, (iii) work, as well as (iv) medication use using a treatment scroll list including all medications (prescribed and over the counter (OTC)) for rhinitis customized for 15 countries. RESULTS: A total of 2871 users filled in 17 091 days of VAS in 2015 and 2016. Medications were reported for 9634 days. The assessment of days appeared to be more informative than the course of the treatment as, in real life, patients do not necessarily use treatment on a daily basis; rather, they appear to increase treatment use with the loss of symptom control. The Allergy Diary allowed differentiation between treatments within or between classes (intranasal corticosteroid use containing medications and oral H1-antihistamines). The control of days differed between no [best control], single, or multiple treatments (worst control). CONCLUSIONS: This study confirms the usefulness of the Allergy Diary in accessing and assessing everyday use and practice in AR. This pilot observational study uses a very simple assessment (VAS) on a mobile phone, shows novel findings, and generates new hypotheses.

Daily allergic multimorbidity in rhinitis using mobile technology: A novel concept of the MASK study.

BACKGROUND: Multimorbidity in allergic airway diseases is well known, but no data exist about the daily dynamics of symptoms and their impact on work. To better understand this, we aimed to assess the presence and control of daily allergic multimorbidity (asthma, conjunctivitis, rhinitis) and its impact on work productivity using a mobile technology, the Allergy Diary. METHODS: We undertook a 1-year prospective observational study in which 4 210 users and 32 585 days were monitored in 19 countries. Five visual analogue scales (VAS) assessed the daily burden of the disease (i.e., global evaluation, nose, eyes, asthma and work). Visual analogue scale levels <20/100 were categorized as "Low" burden and VAS levels ≥50/100 as "High" burden. RESULTS: Visual analogue scales global measured levels assessing the global control of the allergic disease were significantly associated with allergic multimorbidity. Eight hypothesis-driven patterns were defined based on "Low" and "High" VAS levels. There were <0.2% days of Rhinitis Low and Asthma High or Conjunctivitis High patterns. There were 5.9% days with a Rhinitis High-Asthma Low pattern. There were 1.7% days with a Rhinitis High-Asthma High-Conjunctivitis Low pattern. A novel Rhinitis High-Asthma High-Conjunctivitis High pattern was identified in 2.9% days and had the greatest impact on uncontrolled VAS global measured and impaired work productivity. Work productivity was significantly correlated with VAS global measured levels. CONCLUSIONS: In a novel approach examining daily symptoms with mobile technology, we found considerable intra-individual variability of allergic multimorbidity including a previously unrecognized extreme pattern of uncontrolled multimorbidity.

The Allergic Rhinitis and its Impact on Asthma (ARIA) score of allergic rhinitis using mobile technology correlates with quality of life: The MASK study.

Mobile technology has been used to appraise allergic rhinitis control, but more data are needed. To better assess the importance of mobile technologies in rhinitis control, the ARIA (Allergic Rhinitis and its Impact on Asthma) score ranging from 0 to 4 of the Allergy Diary was compared with EQ-5D (EuroQuol) and WPAI-AS (Work Productivity and Activity Impairment in allergy) in 1288 users in 18 countries. This study showed that quality-of-life data (EQ-5D visual analogue scale and WPA-IS Question 9) are similar in users without rhinitis and in those with mild rhinitis (scores 0-2). Users with a score of 3 or 4 had a significant impairment in quality-of-life questionnaires.

Drug-induced anaphylaxis: seven-year single-center survey.

Summary: Background and Objective. Drug-induced anaphylaxis (DIA) is the most common cause of fatal anaphylaxis. We aimed to characterize patients with DIA and their allergological workup. Methods. Systematic review of patients with history of DIA referred to our center over 7 years. Results. Included 125 patients (10% pediatric age), being 36 years the median age of first episode (from 1 to 74 years). The main culprits were nonsteroidal anti-inflammatory drugs (NSAIDs) (43%), antibiotics (42%) and anesthetic agents (6%). In 24% the reactions occurred in hospital setting and 14% perioperative. The etiology was confirmed in 75% through allergological workup. Conclusions. NSAIDs and antibiotics were responsible for most of DIA. The heterogeneity of mechanisms, the severity of the reactions and the lack of standardized in vivo and/or in vitro tests for some drugs do not allow to confirm the diagnosis in all cases. Patients with DIA should be evaluated in specialized centers to perform accurate diagnosis, to prevent recurrence and to find safe alternatives.

Lower airway flow influences peak nasal inspiratory flow in school-aged children.

BACKGROUND: Rhinitis and asthma frequently coexist. Peak nasal inspiratory flow (PNIF) objectively evaluates nasal obstruction. Lower airway flow's impact on PNIF has seldom been analysed in children. We aimed to study the associations between PNIF and: 1)forced expiratory volume in one second (FEV1) and peak expiratory flow (PEF) in children with allergic rhinitis and asthma and healthy controls; 2)allergic rhinitis and asthma control subjective evaluation. METHODS: Sequential assessments of PNIF before and after nasal decongestion and spirometry with bronchodilation test were performed in 65 children (6-12 years) with allergic rhinitis and asthma, and 24 gender, age-matched healthy controls. The Control of Allergic Rhinitis and Asthma Test in children (CARATkids) was used for control assessment. Associations were investigated by multiple linear regression models. RESULTS: Baseline and decongested PNIF correlated with baseline and post-bronchodilation FEV1 and PEF, observed independently of rhinitis and asthma diagnosis. The best model for PNIF included PEF, age and gender. No association was found between PNIF and CARATkids scores, except for nasal obstruction self-report. CONCLUSION: In school-aged children, besides age and gender, PEF values should ideally be known to interpret PNIF values. PNIF can be complementary to subjective control assessment in children with allergic rhinitis and asthma.

Pilot study of mobile phone technology in allergic rhinitis in European countries: the MASK-rhinitis study.

BACKGROUND: The use of Apps running on smartphones and tablets profoundly affects medicine. The MASK-rhinitis (MACVIA-ARIA Sentinel NetworK for allergic rhinitis) App (Allergy Diary) assesses allergic rhinitis symptoms, disease control and impact on patients' lives. It is freely available in 20 countries (iOS and Android platforms). AIMS: To assess in a pilot study whether (i) Allergy Diary users were able to properly provide baseline characteristics (ii) simple phenotypic characteristics based upon data captured by the Allergy Diary could be identified and (iii) information gathered by this study could suggest novel research questions. METHODS: The Allergy Diary users were classified into six groups according to the baseline data that they entered into the App: (i) asymptomatic; (ii) nasal symptoms excluding rhinorrhea; (iii) rhinorrhea; (iv) rhinorrhea plus 1-2 nasal/ocular symptoms; (v) rhinorrhea plus ≥3 nasal/ocular symptoms; and (vi) rhinorrhea plus all nasal/ocular symptoms. RESULTS: By 1 June 2016, 3260 users had registered with the Allergy Diary and 2710 had completed the baseline questionnaire. Troublesome symptoms were found mainly in the users with the most symptoms. Around 50% of users with troublesome rhinitis and/or ocular symptoms suffered work impairment. Sleep was impaired by troublesome symptoms and nasal obstruction. CONCLUSIONS: This is the first App (iOS and Android) to have tested for allergic rhinitis and conjunctivitis. A simple questionnaire administered by cell phones enables the identification of phenotypic differences between a priori defined rhinitis groups. The results suggest novel concepts and research questions in allergic rhinitis that may not be identified using classical methods.

Work productivity in rhinitis using cell phones: The MASK pilot study.

Allergic rhinitis often impairs social life and performance. The aim of this cross-sectional study was to use cell phone data to assess the impact on work productivity of uncontrolled rhinitis assessed by visual analogue scale (VAS). A mobile phone app (Allergy Diary, Google Play Store and Apple App Store) collects data from daily visual analogue scales (VAS) for overall allergic symptoms (VAS-global measured), nasal (VAS-nasal), ocular (VAS-ocular) and asthma symptoms (VAS-asthma) as well as work (VAS-work). A combined nasal-ocular score is calculated. The Allergy Diary is available in 21 countries. The app includes the Work Productivity and Activity Impairment Allergic Specific Questionnaire (WPAI:AS) in six EU countries. All consecutive users who completed the VAS-work from 1 June to 31 October 2016 were included in the study. A total of 1136 users filled in 5818 days of VAS-work. Symptoms of allergic rhinitis were controlled (VAS-global <20) in approximately 60% of the days. In users with uncontrolled rhinitis, approximately 90% had some work impairment and over 50% had severe work impairment (VAS-work >50). There was a significant correlation between VAS-global calculated and VAS-work (Rho=0.83, P<0.00001, Spearman's rank test). In 144 users, there was a significant correlation between VAS-work and WPAI:AS (Rho=0.53, P<0.0001). This pilot study provides not only proof-of-concept data on the work impairment collected with the app but also data on the app itself, especially the distribution of responses for the VAS. This supports the interpretation that persons with rhinitis report both the presence and the absence of symptoms.

Hypersensitivity to beta-lactam antibiotics: a three-year study.

BACKGROUND: Beta-lactams antibiotics (BL) are the most frequent elicitors of allergic drug reactions. The aim of our study was to characterize the patients referred with suspected hypersensitivity (HS) to BL. METHODS: Over a three-year period (2011-2013), a total of 234 adult and paediatric patients (pts) with suspected HS to BL were investigated according to the European Network for Drug Allergy guidelines. RESULTS: HS to BL was confirmed in 43 pts (18%), without differences between adult and paediatric pts; anaphylaxis was reported by 20 pts. Diagnosis was ascertained by: serum-specific IgE antibodies in 5 pts (12%), skin prick tests in 5 (12%), intradermal tests in 25 (58%), 3 with delayed reading, and the remaining 8 (18%) by drug provocation tests. Penicillins / derivatives were the culprit drugs in 39 pts, mainly amoxicillin, and cephalosporins in 4. CONCLUSION: In most of these patients with suspected HS to BL, allergological work-up was negative and HS was excluded. One fourth of confirmed cases had a plausible non-IgE mediated mechanism.

Trends of asthma hospitalization and hospital mortality in mainland Portugal.

AIM: To evaluate nationwide asthma hospitalizations and hospital mortality from the year 2000 to 2010. METHODS: Data from the Health Services Central Administration of the Portuguese Ministry of Health on hospital admissions and hospital mortality in the National Health Service in mainland Portugal, from January 1st 2000 to December 31st 2010, were analysed. Cases with bronchial asthma as a main diagnosis were selected. RESULTS: We found a mean frequency of asthma hospitalizations of 2.5 / 1000 hospital admissions, 28.1 / 100,000 inhabitants (66.6/100,000 in < 19 years old). The global frequency of hospital admissions decreased 18.6% from 2000 to 2010 (r = -0.85, p = 0.002), and 47.0% in those aged 0 to 2 years old (r = -0.77, p = 0.008). There were 261 hospital deaths attributed to asthma (68.5% > 65 years old), accounting for an in-hospital mortality of 8.0 / 1000 asthma hospitalizations and 2.4 / 1,000,000 inhabitants, with no change throughout the years. CONCLUSION: Asthma hospitalization rates have decreased, especially in younger children. Mortality remained unchanged, particularly in the elderly; this might be explained by deficient control in this age group.

Translation to Portuguese and cultural adaptation of Food Allergy Quality of Life Questionnaire - Parent Form (FAQLQ-PF).

Food allergy is a health problem with significant negative impact in Quality of Life (QoL). We aimed to translate into Portuguese and culturally adapt to our population the Food Allergy Quality of Life Questionnaire - Parent Form (FAQLQ-PF). Cross-cultural translation was performed according to guidelines. Linguistic validation consisted in 3 steps: forward translation, backward translation and comprehensibility testing. A consensual version was obtained and tested in parents of food allergic children by cognitive debriefing. Twelve questionnaires were fulfilled, all completed in ≤ 15 min. No comments, doubts or suggestions were posed, except for 2 parents regarding a question about the number of food their children had to avoid. Two gave special positive feedback about the utility of FAQLQ-PF. Changes have been included after this pre-test in accordance to doubts and suggestions of participants, and the Portuguese version is now able to be used in clinics and research.

Can esophageal dilation be avoided in the treatment of severe esophageal stricture caused by eosinophilic esophagitis?

Eosinophilic esophagitis (EoE) is an inflammatory immune-mediated disease with predominant eosinophilic inflammation characterized by the presence of esophageal dysfunction symptoms. Treatment delay can be associated with disease complications, like esophageal strictures, that can justify the use of invasive procedures which are not deprived of side effects. We present a case report of a 14 year old child with severe esophageal stricture secondary to EoE, that was treated with topical and systemic corticosteroid before any invasive procedure was considered. After 26 weeks of medical treatment, significant improvement of esophageal dysfunction occurred with histological remission and stricture resolution. In patients with severe esophageal strictures secondary to EoE, the need for esophageal dilation procedures should be considered only after anti-inflammatory treatment.

One-year survey of paediatric anaphylaxis in an allergy department.

AIM: To determine the frequency of anaphylaxis in an allergy outpatient department, allowing a better understanding regarding aetiology, clinical manifestations and management, in children and adolescents. METHODS: From among 3646 patients up to 18 years old observed during one-year period, we included those with history of anaphylaxis reported by allergists. RESULTS: Sixty-four children had history of anaphylaxis (prevalence of 1.8%), with mean age 8.1±5.5 years, 61% being male. Median age of the first anaphylactic episode was 3 years (1 month-17 years). The majority of patients had food-induced anaphylaxis (84%): milk 22, egg 7, peanut 6, tree nuts 6, fresh fruits 6, crustaceans 4, fish 4 and wheat 2. Food-associated exercise-induced anaphylaxis was reported in 2 adolescents. Drug-induced anaphylaxis occurred in 8%: 4 non-steroidal anti-inflammatory drugs and 1 amoxicillin. Three children had cold-induced anaphylaxis, one adolescent had anaphylaxis to latex and one child had anaphylaxis to insect sting. The majority (73%) had no previous diagnosis of the etiologic factor. Symptoms reported were mainly mucocutaneous (94%) and respiratory (84%), followed by gastrointestinal (42%) and cardiovascular (25%). Fifty-one patients were admitted to the emergency department, although only 33% were treated with epinephrine. Recurrence of anaphylaxis occurred in 26 patients (3 or more episodes in 14). CONCLUSIONS: In our paediatric population, the main triggering agent of anaphylaxis was IgE-mediated food allergy. Epinephrine is underused, as reported by others. Often, children have several episodes before being assessed by an allergist. We stress the importance of systematic notification and improvement of educational programmes in order to achieve a better preventive and therapeutic management of this life-threatening entity.