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

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

Differentiation of COVID-19 signs and symptoms from allergic rhinitis and common cold: An ARIA-EAACI-GA2 LEN consensus.

BACKGROUND: Although there are many asymptomatic patients, one of the problems of COVID-19 is early recognition of the disease. COVID-19 symptoms are polymorphic and may include upper respiratory symptoms. However, COVID-19 symptoms may be mistaken with the common cold or allergic rhinitis. An ARIA-EAACI study group attempted to differentiate upper respiratory symptoms between the three diseases. METHODS: A modified Delphi process was used. The ARIA members who were seeing COVID-19 patients were asked to fill in a questionnaire on the upper airway symptoms of COVID-19, common cold and allergic rhinitis. RESULTS: Among the 192 ARIA members who were invited to respond to the questionnaire, 89 responded and 87 questionnaires were analysed. The consensus was then reported. A two-way ANOVA revealed significant differences in the symptom intensity between the three diseases (p < .001). CONCLUSIONS: This modified Delphi approach enabled the differentiation of upper respiratory symptoms between COVID-19, the common cold and allergic rhinitis. An electronic algorithm will be devised using the questionnaire.

Why fexofenadine is considered as a truly non-sedating antihistamine with no brain penetration: a systematic review.

OBJECTIVE: Fexofenadine is a second-generation inverse agonist of H1-receptor of histamine which is highly selective with proven efficacy in relieving symptoms associated with allergic conditions. It has an additional benefit of not penetrating the blood-brain barrier and therefore do not induce sedation and not impair the cognitive function/psychomotor performance. This review aimed at providing evidence based on available controlled studies to reinforce the non-sedative property of fexofenadine for treating patients with allergic rhinitis and urticaria. METHODS: We performed an electronic literature search using keywords such as fexofenadine, drowsiness, somnolence, sedation, fatigue, cognitive, impairment, psychomotor, driving performances, sleep, rapid eye movement, alertness, clinical study, in vitro study, in vivo study, and pharmacodynamics in the Embase search engine. The review included randomized controlled trials, review articles, systematic reviews, and meta-analyses, together with post-marketing analysis conducted in healthy subjects and patients with allergy and were focused on comparing the antihistaminic potential or safety of fexofenadine with other antihistamines or placebo. RESULTS: Positron emission tomography (PET) and proportional impairment ratio (PIR) data along with other objective tests from various studies confirmed the non-sedative property of fexofenadine. Results of brain H1-receptor occupancy (H1RO) obtained from PET showed no H1RO by fexofenadine, the receptor which is known to cause sedation of H1 antihistamines. Most studies calculating PIR value as 0 showed fexofenadine to be a non-impairing oral antihistamine regardless of dose. Clinical trials in adults and children showed fexofenadine to be well tolerated without sedative effect or impairment of cognitive/psychomotor function even at higher than recommended doses. CONCLUSION: Published literature based on various parameters and clinical trials conducted for evaluating the effect of fexofenadine on sedation and central nervous system shows fexofenadine is both clinically effective and non-sedating.

Update meta-analysis on the efficacy and safety issues of fexofenadine.

Background: Fexofenadine emerged as one of the most representative second generation histamine H1 antagonist drugs since the 1990s, with an outstanding efficacy and appreciable safety for the treatment of allergic patients. While allergic rhino-conjunctivitis represents the most frequent atopic disease globally, an update of fexofenadine efficacy and safety on this entity was proposed as a surrogate of allergic condition. Methods: Double blind, placebo controlled, randomized clinical trials investigating the efficacy and safety of fexofenadine for the treatment of Allergic Rhinitis were searched in 5 major global databases. Eligibility criteria and characteristics, risk of bias, and validity assessment, data extraction and heterogeneity evaluation are described. Primary outcome selected corresponded to 12-reflective and instantaneous total symptom scores (TSS), besides morning instantaneous TSS and the frequency of reported adverse events (AEs); analysis was planned on the intention-to-treat population.Standardized mean differences of scoring systems were analyzed, and Cochran's Q statistic test and the I2 test were assessed for heterogeneity. Results: From the initial 83 identified records, 12 eligible studies were selected. In the evaluated patients, individuals receiving fexofenadine (1910) showed a significant reduction of TSS compared with those who received placebo (1777), change from baseline: standardized mean difference (SMD) -0.33; 95% CI-0.47 to -0.18, p < 0.0001. Morning instantaneous TSS also demonstrated lower symptoms (change from baseline: SMS -1.42; 95% CI -2.22 to -0.62, p = 0.0005). Heterogeneity was found across selected studies.Frequency of AEs was similar compared to placebo (OR = 1.04; 0.88-1.21), with no detection of heterogeneity across these 12 studies. Conclusions: According to this new evidence, fexofenadine maintains its beneficial profile on signs and symptoms of patients with allergic conditions, as well as its attributes as one of the major candidates for an ideal antihistamine medication (including special conditions such as pregnancy and pre-school age), providing support to its over-the-counter condition in several countries.

Unanswered questions on the use of biologics in pediatric asthma.

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.

Utility of biomarkers in the diagnosis and monitoring of asthmatic children.

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.

The role of environmental allergen control in the management of asthma.

Allergen exposure may exacerbate asthma symptoms in sensitized patients. Allergen reduction or avoidance measures have been widely utilized; however, there is ongoing controversy on the effectiveness of specific allergen control measures in the management of children with asthma. Often, allergen avoidance strategies are not recommended by guidelines because they can be complex or burdensome, although individual patients may benefit. Here we explore the potential for intervention against exposure to the major allergens implicated in asthma (ie, house dust mites, indoor molds, rodents, cockroaches, furry pets, and outdoor molds and pollens), and subsequent effects on asthma symptoms. We critically assess the available evidence regarding the clinical benefits of specific environmental control measures for each allergen. Finally, we underscore the need for standardized and multifaceted approaches in research and real-life settings, which would result in the identification of more personalized and beneficial prevention strategies.

Active smoking effect in allergic rhinitis.

BACKGROUND: Tobacco smoke has been described as causing increased prevalence of rhinitis symptoms and decreased atopy. Furthermore, these nasal symptoms and quality of life in smokers with Allergic Rhinitis (AR) were not significantly different to non-smokers. As a result of this duality, a comparison study between the quality of life and inflammatory markers of atopy among active smokers and non-smokers having AR was put forward. MATERIAL AND METHODS: Cross-sectional study in adult smokers and non-smokers, with a clinical diagnosis of AR and positive Skin Prick Test (SPT). Smoking status was confirmed by salivary cotinine measurements. Functional respiratory evaluation was performed, and quality of life between groups was compared using Mini-RQLQ questionnaire. Immunological markers in serum and nasal washes (IgE, IL-4, IL 5, IL 13, IL 17, IL 33) were evaluated, while samples from a third group of passive smokers was incorporated for serological comparison exclusively. The statistical analysis included Student T test, x2, Mann Whitney U (Anova 2-way), and Kruskal Wallis for 3 groups analysis. Values of P < 0.05 were considered significant. RESULTS: Twenty-two patients per group with similar demographics and allergen sensitivity were studied. Regarding inflammatory markers, a reduction of IL 33 in the serum of smokers (P < 0.001) was the only statistically significant different parameter revealed, showing a remarkable trend in nasal lavage. Salivary cotinine levels were absolutely different (P < 0.0001), but pulmonary function evaluations were not statistically significant after multiple adjusting. There were no significant differences in quality of life parameters. CONCLUSIONS: In our study of AR, active smokers do not demonstrate impaired nasal related quality of life or impact on atopic inflammatory parameters, compared to non-smokers. Reduced levels of IL33 could explain a lack of symptoms alerting smokers of the harmful consequences of smoking.

"Chronic urticaria and obstructive sleep apnea: Is there a significant association?"

BACKGROUND: Few studies have explored the association between obstructive sleep apnea (OSA) and chronic urticaria (CU). Our study aims to fill this gap by determining the frequency of the risk categories for OSA and how they might correlate with the specific CU patient reported outcome measures urticaria activity score (UAS7), urticaria control test (UCT) and CU quality of life questionnaire (CU-Q2oL). METHODS: We conducted a cross-sectional study involving a cohort of 171 Latin American CU patients. Descriptive statistics were used to determine frequency and proportions for demographic and clinical variables, while a chi-squared test for association between STOP-Bang OSA questionnaire categories and both UAS7 and UCT categories was performed to analyze how such variables interact. To further assess the strength of the correlation a Cramer's V coefficient was reported. Finally, a Kendall-Tau b correlation coefficient was performed to measure the correlation between the STOP-Bang score and other independent continuous variables. RESULTS: The average STOP-Bang score was 2.5, with 24% and 21% of patients falling into the intermediate and high-risk category for moderate-to-severe OSA, respectively. There was a strong statistically significant association (Cramer's V = 0.263; p = .000) between UAS-7 categories and STOP-Bang risk categories. A similar pattern of strong significant association (Cramer's V = .269; p = .002) was observed between UCT categories and STOP-Bang risk categories. A weak positive correlation between the STOP-Bang score and the CU-Q2oL average score (τb = 0.188, p = .001) was identified. Overall, 72.5% patients reported limitations with respect to sleep in a varied degree according to the CU-Q2oL. CONCLUSIONS: Our results suggest that a considerable proportion of patients with CU are at intermediate to high risk for OSA. Higher disease activity, poor CU control, and worse quality of life were all found to be associated with an increased risk. Additional studies are needed to determine the exact link between these conditions, and to determine whether screening and treatment for OSA might benefit patients with CU.

WAO-ARIA consensus on chronic cough - Part II: Phenotypes and mechanisms of abnormal cough presentation - Updates in COVID-19.

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.

Impact of COVID-19 on Pediatric Asthma: Practice Adjustments and Disease Burden.

BACKGROUND: It is unclear whether asthma may affect susceptibility or severity of coronavirus disease 2019 (COVID-19) in children and how pediatric asthma services worldwide have responded to the pandemic. OBJECTIVE: To describe the impact of the COVID-19 pandemic on pediatric asthma services and on disease burden in their patients. METHODS: An online survey was sent to members of the Pediatric Asthma in Real Life think tank and the World Allergy Organization Pediatric Asthma Committee. It included questions on service provision, disease burden, and the clinical course of confirmed cases of COVID-19 infection among children with asthma. RESULTS: Ninety-one respondents, caring for an estimated population of more than 133,000 children with asthma, completed the survey. COVID-19 significantly impacted pediatric asthma services: 39% ceased physical appointments, 47% stopped accepting new patients, and 75% limited patients' visits. Consultations were almost halved to a median of 20 (interquartile range, 10-25) patients per week. Virtual clinics and helplines were launched in most centers. Better than expected disease control was reported in 20% (10%-40%) of patients, whereas control was negatively affected in only 10% (7.5%-12.5%). Adherence also appeared to increase. Only 15 confirmed cases of COVID-19 were reported among the population; the estimated incidence is not apparently different from the reports of general pediatric cohorts. CONCLUSIONS: Children with asthma do not appear to be disproportionately affected by COVID-19. Outcomes may even have improved, possibly through increased adherence and/or reduced exposures. Clinical services have rapidly responded to the pandemic by limiting and replacing physical appointments with virtual encounters.

Will precision medicine be available for all patients in the near future?

PURPOSE OF REVIEW: Evidence-based medicine and guidelines directing the diagnosis and treatment of patients are changing. General recommendations are moving towards an individual focus, where technology evolution allows identification of specific patterns and where 'one size fits all' no longer has a place. RECENT FINDINGS: Emerging innovations on health technology include useful tools for individualizing patients' specific conditions and follow-up. There are several preventive initiatives that aim to reduce allergic disease development, but they have no generalizable and definitive results as yet. Both omics and molecular diagnosis have provided the basis for differentiating clusters of patients, both allowing prediction of severity and also indicating appropriate management. Here we discuss examples contributing to some specific conditions we are now facing. SUMMARY: Precision medicine encompasses a personalized care of the patient, the prediction of a successful treatment, the potential prevention of a disease and its progression when present and the important active participation of the patient in the planning and guidance of the approach and management. Technology and medical innovations like omics and molecular diagnosis help for discriminating specific phenotypes/endotypes and the correct individualized interventions. The great challenge for implementing precision medicine will be the possibility of providing those advances to everyone at affordable costs. CONCLUSION: Technology and innovations in medicine are aimed to help all patients globally, providing evidence for particular conditions that need to be personally considered, involving the patient's decision while treating, predicting and preventing disease. Our aim should be to have precision medicine available everywhere at any time.

Latin American chronic urticaria registry (CUR) contribution to the understanding and knowledge of the disease in the region.

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.

Challenges and choices in the pharmacological treatment of non-severe pediatric asthma: A commentary for the practicing physician.

In recent years, asthma research has focused intensely on the severe part of the disease spectrum, leading to new treatments, mostly therapeutic monoclonal antibodies. However, severe asthma accounts for not more than 2% of asthma in the pediatric population. Therefore, non-severe asthma remains a major health problem in children, not only for patients and parents but also for healthcare professionals such as general practitioners, pediatricians and allergists who take care of these patients. It is thus essential to identify and put in context novel concepts, applicable to the treatment of these patients. Recent evidence suggests benefits from using anti-inflammatory treatment even for the mildest cases, for whom until now only symptomatic bronchodilation was recommended. Likewise, "reliever" medication may be better combined with an inhaled corticosteroid (ICS). Among "new" treatments (for children), ICS formulation in ultrafine particles has showed promise and tiotropium is gaining access to the pediatric population. Maintenance and reliever therapy (MART) is an option for moderate disease. Most importantly, personalized response to medications appears to be considerable, therefore, it may need to be taken into account. Overall, these new options provide opportunities for multiple new management strategies. The deployment of such strategies in different populations remains to be evaluated.

Diretriz Latino-americana sobre o Diagnóstico e Tratamento da Alergia Ocular ­ Em nome da Sociedade Latinoamericana de Alergia, Asma e Imunologia (SLAAI) / Latin American Guideline on the Diagnosis and Treatment of Ocular Allergy ­ On behalf of the Latin American Society of Allergy, Asthma and Immunology (SLAAI)

A alergia ocular, também conhecida como conjuntivite alérgica (CA), é uma reação de hipersensibilidade mediada por imunoglobulina E (IgE) do olho desencadeada por aeroalérgenos, principalmente ácaros da poeira doméstica e pólen de gramíneas. Os sintomas geralmente consistem em prurido ocular ou periocular, lacrimejamento e olhos vermelhos que podem estar presentes durante todo o ano ou sazonalmente. A alergia ocular tem frequência elevada, é subdiagnosticada e pode ser debilitante para o paciente. É potencialmente danosa para a visão, nos casos em que ocasiona cicatrização corneana grave, e na maioria dos pacientes associa-se a outros quadros alérgicos, principalmente rinite, asma e dermatite atópica. É classificada em conjuntivite alérgica perene, conjuntivite alérgica sazonal, ceratoconjuntivite atópica e ceratoconjuntivite vernal. O diagnóstico procura evidenciar o agente etiológico e a confirmação se dá pela realização do teste de provocação conjuntival. O tratamento baseia-se em evitar o contato com os desencadeantes, lubrificação, anti-histamínicos tópicos, estabilizadores de mastócitos, imunossupressores e imunoterapia específica com o objetivo de obter o controle e prevenir as complicações da doença.

Ocular allergy, also known as allergic conjunctivitis, is an immunoglobulin E-mediated hypersensitivity reaction of the eye triggered by airborne allergens, primarily house dust mites and grass pollen. Symptoms usually consist of ocular or periocular itching, watery eyes, and red eyes that may be present year-round or seasonally. Ocular allergy has a high frequency, is underdiagnosed, and can be debilitating for the patient. It is potentially harmful to vision in cases of severe corneal scarring, and in most patients, it is associated with other allergic conditions, especially rhinitis, asthma, and atopic dermatitis. It is classified as perennial allergic conjunctivitis, seasonal allergic conjunctivitis, atopic keratoconjunctivitis, and vernal keratoconjunctivitis. Diagnosis seeks to identify the etiologic agent, and confirmation is given by conjunctival provocation testing. Treatment is based on avoiding contact with triggers, lubrication, topical antihistamines, mast cell stabilizers, immunosuppressants, and specific immunotherapy with the aim of achieving control and preventing disease complications.

The international survey on the management of allergic rhinitis by physicians and patients (ISMAR).

Epidemiologic studies suggest that the prevalence of allergic rhinitis (AR) is rising worldwide. Several reports, in fact, indicate increasing trends in the prevalence of AR especially in developing countries, likely related to the environment and climate changes and the adoption of an urbanized Western lifestyle. The primary objective of the present study was to collect information about management in real-life settings, including a characterization of typical patients' profile referring to physicians, the disease features, the common approaches to diagnostic assessments and therapeutic decisions. This was an international, multicenter, cross-sectional study conducted in adults or children (≥6 years) suffering from rhinitis confirmed by physician's diagnosis for at least one year. The 234 physicians who participated in the study included a total of 2778 patients in Egypt, Mexico, Brazil, Colombia, Guatemala, Iran, Venezuela, Argentina, Israel, Kuwait and United Arab Emirates. It was found that clinical history was the selected tool to diagnose and categorize AR patients (97.1%), with less than half of patients undergoing allergy testing, may be explaining the scarce use of immunotherapy on management of disease. Out of 2776 patients, 93.4% had somehow received a recommendation to avoid allergens and irritant agent exposure. Notably, 91.4% were receiving at least one treatment at the time of the survey, mostly oral antihistamines (79.7%) and intranasal corticosteroids (66.3%). Oral antihistamines, intranasal steroids and decongestants were considered both safe and effective by patients and physicians, preferring oral and nasal route of administration. The ISMAR registry was designed according to the most accepted epidemiological recommendations, and provides interesting information regarding the management of rhinitis from a patient and physician points of view, with many similarities between the participating countries. Further efforts are required to better manage AR and its comorbidities.