Managing Allergic Rhinitis in the Pharmacy: An ARIA Guide for Implementation in Practice

The defined mapping of the MuLV integrase in previous work (10,11) has made it possible for us to design and construct molecular clones for expression of this protein in bacteria and thus easily obtain specific antisera. Our repeated inability to isolate the antigenic MuLV virion p46 protein without the use of a denaturing reagent, although preventing us from carrying out the contemplated enzymological studies, would imply that the integration function of MuLV is more stringently controlled at the virion structure level than is that of avian retroviruses. Thus, gene transfer and therapy procedures would be safer to the recipient by using the MuLV retroviral vector than the avian retroviral vector, since p46 is less likely than p32 to be aberrantly released to cause genomic damage to the cell. The apparent cytotoxity of transfection with mammalian expression vectors carrying the integrase gene is not unexpected in situations where a high level of this protein is expressed and accumulated in the nucleus. The apparently incidental emergence of neoplastic phenotypes in some stably transfected cells would cause genomic instability and gene rearrangement of the oncogenic components. This possibility is particularly noteworthy for endogenous retroviral gene elements, in which the control of integrase gene expression and function may not be as stringent as in the infectious MuLVs. 28 refs., 5 figs.

Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines—2016 revision

Allergic rhinitis is a disease underestimated by patients, and underdiagnosed and thus undertreated by physicians since most of the patients present with symptoms of moderate-to-severe disease, overall diminished quality of life, impairing sleep quality and cognitive function, and a substantial impact on work productivity, school absenteeism, and costs. The relationship between treating physician and patients is crucial in all chronic diseases. Review the main changes and innovations of recent years in the ARIA guidelines. The most recent publications of the ARIA (Allergic Rhinitis and its Impact on Asthma) guidelines were reviewed. ARIA 2016 strengthens the role of patients in the control and treatment of their symptoms by the use of technology, which improves physician-patient communication. The selection of pharmacotherapy for patients with allergic rhinitis (AR) depends on several factors, including age, prominent symptoms, symptom severity, control of AR, patient preferences, and cost. It confirms that inhaled corticosteroids are the most effective drugs for the management of seasonal or perennial allergic rhinitis, not surpassed by combination therapies with oral or topical antihistamines. On the other hand, no significant differences between the use of oral or topical antihistamines are evidenced. Allergen exposure and the resulting symptoms vary, and treatment adjustment is required. A step-up/step-down individualized approach to AR pharmacotherapy might hold the potential for optimal control of AR symptoms while minimizing side effects and costs. After choosing the best pharmacological therapy, compliance is a critical issue in the management of all chronic diseases. In order to improve compliance, it is important to consider patient preferences and views of patients and their caregivers, as ARIA guidelines remarks in the 2016 update. ARIA guideline has evolved to a technology-based implementation strategy to help rhinitis sufferers to have an active and healthy life and to reduce health and social inequalities caused by this very common disease, irrespective of their age, sex, or socio-economic status.

Allergic rhinitis (AR) represents a major challenge in primary care. The Allergic Rhinitis and its Impact on Asthma (ARIA) group proposed a new classification for AR and developed evidence-based guidelines for the management of this disease. We conducted this study to further characterize the classes of AR described by ARIA, and to evaluate whether the management of AR in general practice is in accordance with the ARIA guidelines. During the pollen season of 2003, 95 Belgian general practitioners (GPs) enrolled 804 patients who presented with symptoms of AR. For each patient, a questionnaire comprising the clinical presentation and management was completed. In 64% of the patients, AR was classified as intermittent and in 36% as persistent. Persistent rhinitis caused more discomfort than intermittent rhinitis. Only 50% of the patients had ever undergone allergy testing. Among them, 51% were allergic to both seasonal and perennial allergens. Eighty-two per cent of the persistent rhinitics were allergic to at least one seasonal allergen and 72% of the intermittent rhinitics to at least one perennial allergen. When compared strictly with the ARIA recommendations, 49% of the patients with mild and/or intermittent AR were overtreated, whereas about 30% of those with moderate/severe persistent rhinitis were undertreated. This study confirms that the previous classification of AR into 'seasonal' and 'perennial' is not satisfactory and that intermittent and persistent AR are not equivalent to seasonal and perennial AR respectively. Furthermore, persistent rhinitis has been shown to be a distinct disease entity. Further efforts are required to disseminate and implement evidence-based diagnostic and treatment guidelines for AR in primary care practice.

Desloratadine treatment for intermittent and persistent allergic rhinitis: A review

The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization (WHO) workshop in 1999. The initial goals were (i) to propose a new allergic rhinitis classification, (ii) to promote the concept of multi-morbidity in asthma and rhinitis and (iii) to develop guidelines with all stakeholders for global use in all countries and populations. ARIA - disseminated and implemented in over 70 countries globally - is now focusing on the implementation of emerging technologies for individualized and predictive medicine. MASK (MACVIA (Contre les MAladies Chroniques pour un VIeillissement Actif)-ARIA Sentinel NetworK) uses mobile technology to develop care pathways in order to enable the management of rhinitis and asthma by a multi-disciplinary group or by patients themselves. An App (Android and iOS) is available in 20 countries and 15 languages. It uses a visual analogue scale to assess symptom control and work productivity as well as a clinical decision support system. It is associated with an inter-operable tablet for physicians and other health care professionals. The scaling up strategy uses the recommendations of the European Innovation Partnership on Active and Healthy Ageing. The aim of the novel ARIA approach is to provide an active and healthy life to rhinitis sufferers, whatever their age, sex or socio-economic status, in order to reduce health and social inequalities incurred by the disease. Keywords: ARIA, rhinitis, ICT, EIP on AHA, mobile technology, AIRWAYS ICPs

Background:The ARIA (Allergic Rhinitis and its Impact on Asthma) guidelines development group examined the properties of oral H1-antihistamines and made proposals about an ‘optimal’ drug. Several criteria should be met by oral H1-antihistamines in terms of their pharmacological, and clinical efficacy and safety profiles.Objective:Bilastine, a new H1-antihistamine, has been approved in 28 European countries for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria in adults and children older than 12 years. To determine its potential place in therapy in the treatment of allergic rhinitis, this manuscript examines whether bilastine meets the criteria defined in the European Academy of Allergy and Clinical Immunology (EAACI)/ARIA proposals for oral H1-antihistamines.Methods:The optimal properties of oral H1-antihistamines and current ARIA recommendations for their use in allergic rhinitis are presented, as well as relevant pharmacological and clinical data for bilastine obtained from the published literature that specifically address the defined criteria.Results:Bilastine is a potent inhibitor of the histamine H1 receptor. Data from preclinical studies have confirmed its selectivity for the histamine H1 receptor over other receptors, and demonstrated antihistaminic properties in vitro and in vivo. Bilastine does not interfere with the cytochrome P450 system and is devoid of cardiac side effects. Studies in healthy volunteers and patients have shown that bilastine does not affect driving ability, cardiac conduction or alertness. In large pivotal randomized, placebo-controlled trials (RCTs), bilastine had a favourable safety profile. Bilastine 20 mg once daily improved all nasal and ocular symptoms of allergic rhinitis with greater efficacy than placebo and comparable to that of cetirizine and desloratadine. Moreover, bilastine was shown to improve quality of life, an important outcome of RCTs in allergic diseases. There were no significant changes in laboratory tests, electrocardiograms or vital signs. A potential limitation of this assessment of bilastine is that it is a literature-based review and the findings are dependent upon the quality of the published evidence.Conclusions:Bilastine meets current EAACI/ARIA criteria for medications used in the treatment of allergic rhinitis.

Allergic Rhinitis 2Basic research directed at the study of each condition separately, as well as in tandem, is needed to fully understand the pathophysiology of allergic airways disease.AR is a unique pathophysiological entity that is part of a spectrum of atopic disease including eczema and asthma.The use of relevant animal models of allergic airways disease is necessary to provide the supportive data that defines the extent and nature of AR:asthma relationships.In the last decade, research efforts that focused on animal models of AR have begun to provide a scientific framework with which to understand the role of upper airways in allergic airways disease. Insights from animal models of allergic asthmaExtensive work in susceptible rodent strains using ovalbumin as the test allergen, or environmentally-relevant allergens (e.g., house dust mite, cockroach), has helped describe both the acute and chronic immune and inflammatory responses in pulmonary airways.The strengths and limitations of laboratory animal models has been debated (Shapiro 2006;Wenzel and Holgate 2006).Studies using mice, especially transgenics and knockout strains, have been important for understanding of the role of cytokines, adhesion molecules, and cell receptors in allergic inflammatory responses.Asthma is a chronic disease of inflammation that is marked by extensive airway remodeling.By comparison, most rodent models of asthma are relatively acute, with regular exposure to allergen challenges over a few days or weeks.As such, the reproduction of the human asthma pathophysiology is not perfect.While airway hyperreactivity, eosinophilic and lymphocytic infiltration, and mucus overproduction can be induced in experimental asthma, other features such as smooth muscle cell proliferation, myofibroblast activation, subepithelial fibrosis, and epithelial proliferation and shedding are often absent in allergic rodent models.Given the limitations of acute rodent models, efforts to develop chronic asthma models that use frequent exposures to lower allergen concentrations can better portray exposure histories of allergic subjects to seasonal and episodic exacerbations.Specifically, airway remodeling in these mice include key features of human asthma, such as intraepithelial eosinophils, collagen deposition, epithelial hyperplasia and metaplasia, smooth muscle hyperplasia and hypertrophy, and increases in myofibroblasts (Lloyd and Robinson 2007;Nials and Uddin 2008;Yu et al. 2006).Regardless of the rodent model (mouse, rat or guinea pig), the method to induce allergic responses in lower airways is similar across species and allergens.Primary sensitization to the allergen is accomplished by using either systemic (e.g., intraperitoneal, subcutaneous or dermal) or airway (aerosol inhalation, or instillation in the nose, pharynx, or trachea) routes of exposure, and given as a single or multiple administrations.An adjuvant, usually alum (potassium aluminium sulfate), may also be used.Sensitized animals are then challenged with a secondary exposure by either dermal, inhalation, or airway instillation, and with varying volumes and allergen concentrations or several days or weeks.Several groups have conducted comparisons of the different protocols and determined strengths and limitations of several approaches.(

The Allergic Rhinitis and Its Impact on Asthma (ARIA) initiative started more than 20 years ago and has developed and disseminated evidence-based guidelines and projects in the field of allergic rhinitis. This initiative is currently focused on providing patient-centred guidelines that contribute to an integrated care pathway between the various levels of care and take advantage of digital solutions, and the introduction of integrated care pathways in clinical practice has been recommended. In this article we describe the adaptation for Portugal of the ARIA Integrated Care Pathways document. After a brief review of the epidemiology and impact of allergic rhinitis in Portugal and the activities carried out in Portugal within the ARIA initiative, we describe the broad knowledge base used for the development of recommendations for the pharmacological treatment of allergic rhinitis, and these recommendations are based on the GRADE methodology, real world evidence acquired by mobile technology (mHealth) and resulting from allergenic exposure chamber studies. What follows is a summary of integrated care pathways for allergen immunotherapy produced in 2019. Allergen immunotherapy is considered an example of precision medicine where the use of mHealth technologies will improve stratification for patient selection and response monitoring. These recommendations were considered as best practices of integrated patient-centred care supported by digital systems from Directorate General for Health and Food Safety of the European Union (DG Santé) and represent the ARIA Phase 4 Change Management strategy.

<b>Introduction:</b> Few population-based studies have described allergic rhinitis (AR) according to the Allergic Rhinitis and its Impact on Asthma (ARIA) classification. <b>Aims:</b> To describe AR according to its severity and duration and taking asthma multimorbidity into account among adults from the population-based cohort Constances. <b>Methods:</b> Cross-sectional analyses were performed using data from the 2014 annual follow-up questionnaire. AR was defined by sneezing, runny or blocked nose in the last 12 months and the report of nasal allergies. Following ARIA recommendations, rhinitis was considered according to its severity (mild or moderate-severe) and duration (intermittent or persistent). Asthma ever was self-reported on questionnaire. <b>Results:</b> Among the 4675 participants with AR (57% women, mean age 50.2±12.7 years), 44% were classified as mild/intermittent, 16% mild/persistent, 25% moderate-severe/intermittent, and 15% moderate-severe/persistent. Within each of the four ARIA classes, compared to participants with rhinitis alone, participants with rhinitis and asthma had significantly more severe symptoms, more conjunctivitis, higher levels of eosinophils and more common treatments with intra-nasal corticosteroids and oral antihistamines co-medication (all p &lt;0.05). <b>Conclusion:</b> This is a paradigm changing study as, for the first time we show how taking asthma status into account modify ARIA classification. Moreover, it was done in a large population-based study in adults. This study confirms that rhinitis alone and rhinitis and asthma represent two entirely different phenotypes. This new classification should be used for new guidelines.

Allergic rhinitis (AR) symptom phenotypes have been described, and two different classifications exist. The former classification, seasonal versus perennial AR (SAR-PAR), and the Allergic Rhinitis and Its Impact on Asthma (ARIA) classifications, intermittent (INT) versus persistent (PER; ≥4 days/wk and ≥4 consecutive weeks) and mild versus moderate/severe. ARIA cataloging of INT-PER is based on the patient's description of the frequency of symptoms. This study was designed to (1) describe the epidemiology of these two AR classifications and relate them to one another and to a visual analog severity scale (VAS) and (2) describe how the cataloging of these classifications differs between patients and allergists. Skin-prick test-positive AR patients seen nationwide by Mexican allergists completed a validated questionnaire cataloging AR. They recorded demographic data and AR severity on a VAS. The patients' physicians were also asked to classify the AR phenotypes. Of the patients, 56.5% had INT and 82.2% had PAR and moderate-severe (84.7%) AR. However, 57% of the INT-PAR patients were misdiagnosed as PER-PAR by their physicians. PER patients had more severe disease with a longer clinical history, more PAR, nose and eye symptoms, and a higher VAS score, and only 7% had mild symptoms. VAS values ≥7.45 relate to PER (sensitivity, 68%; specificity, 65%). VAS ≤6.2 indicated mild and ≥6.4 indicated moderate-severe AR. Similar to the adults, in the 2- to 11 year and 12- to 17-year age groups perennial, INT, and moderate-severe AR was the most frequent finding, but the children had more INT (p < 0.01) and mild (p < 0.03) symptoms, less SAR (p = 0.03), and more physician-diagnosed asthma (p < 0.05). Public health care (PHC) patients had more INT (p = 0.016). In the PAR group, the physicians' classification of INT-PER often goes astray. PER overdiagnoses might affect treatment decisions because PER is a more severe phenotype. VAS is useful to evaluate severity. In Mexican AR patients, rhinitis symptom phenotypes differ according to age and between private and PHC system patients.

Clinical Practice Guidelines for allergic rhinitis have been developed over the past 15 years and have been found to improve the care for patients with allergic rhinitis. The ARIA (allergic rhinitis and its impact on asthma) guideline was the first of these evidenced-based guidelines, developed with primary care physicians. Subsequent guidelines include those by the IPCRG, BSACI, the AAAAI/ACAAI Practice Parameters for the diagnosis and management of rhinitis, and the ARIA 2008 Update. These guidelines were based on various evidencebased models, but the first to use GRADE methodology (Grading of Recommendations Assessment, Development and Evaluation) is the ARIA 2009 Revision. Since primary care physicians treat the majority of patients with allergic rhinitis it is essential that they are involved in the development and implementation of guidelines for allergic rhinitis. Prior to their implementation, guidelines should be evaluated for their accuracy and user friendliness - specifically for primary care physicians - but such validation is rarely performed. This is of great importance, in particular as regards evaluating the applicability of evidence from high quality randomised controlled trials (RCTs) which are often based on highly selected patients not representing the population of patients seen in day-to-day practice.

Allergic rhinitis and its impact on asthma (ARIA) has been the most preferred reference for national guidelines. The ARIA 2010 revision is the first evidence-based clinical guideline in the field of allergies, which has great influence in the world. The ARIA 2016 revision continues the basic framework of the 2010 revision, which focuses on six controversial clinical issues in the treatment of allergic rhinitis.It aimed to provide clear informationand systematic treatment for patients, clinicians and health policy makers. The interpretation of the ARIA 2016 revision will help domestic otolaryngologist, respiratory doctors, and allergy practitioners understand the latest guidelines for AR drug treatment in the world.

In this article, we review the impact and the treatment of sleep disturbance caused by allergic rhinitis (AR) in adult and pediatric patients. Although intranasal corticosteroids (INS) remain the mainstay treatments for AR-induced sleep disturbance, allergen immunotherapy (AIT) has been suggested to be effective in altering the course and progression of moderate-to-severe AR that is refractory to pharmacotherapy. MP-AzeFlu is a recently developed formulation containing azelastine, an intranasal antihistamine (INAH), and fluticasone propionate, an INS. MP-AzeFlu has been reported to have a fast onset of action thanks to the effect of the INAH. AR is one of the most common chronic inflammatory diseases in the USA with symptoms that can severely affect patients’ quality of life. Sleep disturbance is a serious consequence of AR-induced symptoms that can lead to daytime somnolence, impaired cognitive functions, and decreased work/school performance. Nasal congestion and rhinorrhea have been suggested to be the primary causes of sleep disturbance in patients with AR. There is a lack of adequate assessment method for AR-induced sleep disturbance and its consequences in the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines and the Sino-Nasal Outcome Test-22 (SNOT-22). The NIH-developed Patient Reported Outcome Measurement Information System (PROMIS) has measures for these symptoms. Although more research is needed to develop more pediatric-specific questionnaires, PROMIS is a good start. In terms of treatment for AR-induced sleep disturbance, therapy should be aimed at treating the nasal congestion and rhinorrhea caused by AR. INS are the mainstay treatments for moderate-to-severe AR. The newer INS have low systemic bioavailability and are well tolerated. For adults, fluticasone propionate is an effective treatment. For children from 2 to 4 years old, mometasone and fluticasone furoate are recommended. Fluticasone propionate should be used in children age 4 or older. Budesonide is the only category B safety drug as classified by the FDA, making it recommended treatment for pregnant and breastfeeding women.

BackgroundAn important subpopulation in allergic rhinitis is represented by patients with severe form of disease that is not responsive to drug treatment. It has been reported that grass pollen subcutaneous immunotherapy is effective in drug-resistant patients. In a real-life study, we evaluated the efficacy of 5-grass pollen tablets in patients with grass pollen-induced allergic rhinitis not responsive to drug therapy.MethodsWe carried out this multicenter observational study in adults and adolescents with grass-induced allergic rhinitis not responsive to drug therapy who were treated for a year with 5-grass pollen tablets. Clinical data collected before and after sublingual immunotherapy (SLIT) included Allergic Rhinitis and its Impact on Asthma (ARIA) classification of allergic rhinitis, response to therapy, and patient satisfaction.ResultsForty-seven patients entered the study. By ARIA classification, three patients had moderate to severe intermittent allergic rhinitis, ten had mild persistent allergic rhinitis, and 34 had moderate to severe persistent allergic rhinitis. There were no cases of mild intermittent allergic rhinitis before SLIT. After SLIT, 33 patients had mild intermittent allergic rhinitis, none had moderate to severe intermittent allergic rhinitis, seven had mild persistent allergic rhinitis, and seven had moderate to severe persistent allergic rhinitis. The mean medication score decreased from 4.2±1.3 before to 2.4±2.0 after SLIT (P<0.01), representing a reduction of 42%. The response to treatment before SLIT was judged as poor by 70% of patients and very poor by 30%. Patient satisfaction was significantly increased after SLIT (P<0.01).ConclusionIn real life, most patients with grass pollen-induced allergic rhinitis not responsive to drug treatment can achieve control of the condition with one season of treatment using 5-grass pollen tablets.