Updates in biologic therapy for chronic rhinosinusitis with nasal polyps and NSAID-exacerbated respiratory disease.

Chronic rhinosinusitis with nasal polyps (CRSwNP) associated with type 2 inflammation and non-steroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (N-ERD) can be difficult to control with standard medical therapy and sinus surgery. In this group, biologicals are potentially promising treatment options. The phase III clinical trials for omalizumab, dupilumab, mepolizumab and benralizumab in CRSwNP have demonstrated favourable outcomes. Moving forward, direct comparisons among biologicals, refining patient selection criteria for specific biologicals, determining optimal treatment duration and monitoring long-term outcomes are areas of emerging interest. This review summarizes the clinical evidence from the recent 2 years on the role of biologicals in severe CRSwNP and N-ERD, and proposes an approach towards decision-making in their use.

A Comparison of International Guidelines for Rhinosinusitis.

The European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS), latest version EPOS2020, and the International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR-RS), latest version ICAR-RS-2021, assimilate thousands of articles on the topic of rhinosinusitis. Encompassing scores of subtopics and relying on the perspectives of many international experts, EPOS2020 and ICAR-RS-2021 reduce the existing data into consumable formats and create evidence-based recommendations. The approaches and findings are similar in many respects but have significant differences. This clinical commentary, authored by some of the principal authors of these documents, compares and contrasts EPOS2020 and ICAR-RS-2021, examining methodology, diagnostic and treatment recommendations, and each document's emphases. This commentary demonstrates that, through somewhat differing methodologies, the 2 documents arrive at largely similar conclusions. Those who care for patients suffering from rhinosinusitis will find the documents complementary and valuable in their differences as much as in their similarities.

Induction of IL-10-producing type 2 innate lymphoid cells by allergen immunotherapy is associated with clinical response.

The role of innate immune cells in allergen immunotherapy that confers immune tolerance to the sensitizing allergen is unclear. Here, we report a role of interleukin-10-producing type 2 innate lymphoid cells (IL-10+ ILC2s) in modulating grass-pollen allergy. We demonstrate that KLRG1+ but not KLRG1- ILC2 produced IL-10 upon activation with IL-33 and retinoic acid. These cells attenuated Th responses and maintained epithelial cell integrity. IL-10+ KLRG1+ ILC2s were lower in patients with grass-pollen allergy when compared to healthy subjects. In a prospective, double-blind, placebo-controlled trial, we demonstrated that the competence of ILC2 to produce IL-10 was restored in patients who received grass-pollen sublingual immunotherapy. The underpinning mechanisms were associated with the modification of retinol metabolic pathway, cytokine-cytokine receptor interaction, and JAK-STAT signaling pathways in the ILCs. Altogether, our findings underscore the contribution of IL-10+ ILC2s in the disease-modifying effect by allergen immunotherapy.

[Executive Summary of ARIA 2019: Integrated care pathways for allergic rhinitis in Argentina, Spain and Mexico]. / Resumen ejecutivo de ARIA 2019: Vías integradas de atención para la rinitis alérgica en Argentina, España y México.

The health and economic impact of allergic diseases are increasing rapidly, and changes in management strategies are required. Its influence reduces the capacity of work and school performance by at least a third. The ICPs of the airways (integrated care pathways for respiratory diseases) are structured multidisciplinary healthcare plans, promoting the recommendations of the guidelines in local protocols and their application to clinical practice. This document presents an executive summary for Argentina, Mexico, and Spain. Next-generation ARIA guidelines are being developed for the pharmacological treatment of allergic rhinitis (AR), using the GRADE-based guidelines for AR, tested with real-life evidence provided by mobile technology with visual analogue scales. It is concluded that in the AR treatment, H1-antihistamines are less effective than intranasal corticosteroids (INCS), in severe AR the INCS represent the first line of treatment, and intranasal combination INCS + anti-H1 is more effective than monotherapy. However, according to the MASK real-life observational study, patients have poor adherence to treatment and often self-medicate, according to their needs.

El impacto sanitario y económico de las enfermedades alérgicas está aumentando rápidamente y se necesitan cambios en las estrategias para su manejo. Su influencia reduce al menos en un tercio la capacidad de desempeño laboral y escolar. Los ICP (Vías Integradas de Atención) de las enfermedades de las vías respiratorias son planes de atención estructurados y multidisciplinarios, que promueven las recomendaciones de las guías en protocolos locales y su aplicación a la práctica clínica. En este documento se presenta un resumen ejecutivo para Argentina, México y España. Se desarrollan las guías ARIA de próxima generación para el tratamiento farmacológico de la rinitis alérgica (RA) utilizando las pautas basadas en GRADE para RA, probadas con evidencia de la vida real proporcionada por tecnología móvil basada en escalas visuales analógicas. Se concluye que en el tratamiento de la RA, los antihistamínicos anti-H1 son menos efectivos que los corticoides intranasales (CINS), que en la rinitis gravelos CINS representan la primera línea de tratamiento, y que la combinación intranasal de CINS + anti-H1 es más eficaz que la monoterapia. Sin embargo, según el estudio MASK observacional en vida real, los pacientes tienen pobre adherencia al tratamiento y frecuentemente se automedican de acuerdo con sus necesidades.

International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis.

BACKGROUND: Critical examination of the quality and validity of available allergic rhinitis (AR) literature is necessary to improve understanding and to appropriately translate this knowledge to clinical care of the AR patient. To evaluate the existing AR literature, international multidisciplinary experts with an interest in AR have produced the International Consensus statement on Allergy and Rhinology: Allergic Rhinitis (ICAR:AR). METHODS: Using previously described methodology, specific topics were developed relating to AR. Each topic was assigned a literature review, evidence-based review (EBR), or evidence-based review with recommendations (EBRR) format as dictated by available evidence and purpose within the ICAR:AR document. Following iterative reviews of each topic, the ICAR:AR document was synthesized and reviewed by all authors for consensus. RESULTS: The ICAR:AR document addresses over 100 individual topics related to AR, including diagnosis, pathophysiology, epidemiology, disease burden, risk factors for the development of AR, allergy testing modalities, treatment, and other conditions/comorbidities associated with AR. CONCLUSION: This critical review of the AR literature has identified several strengths; providers can be confident that treatment decisions are supported by rigorous studies. However, there are also substantial gaps in the AR literature. These knowledge gaps should be viewed as opportunities for improvement, as often the things that we teach and the medicine that we practice are not based on the best quality evidence. This document aims to highlight the strengths and weaknesses of the AR literature to identify areas for future AR research and improved understanding.

[ARIA 2016 executive summary: Integrated care pathways for predictive medicine throughout the life cycle in Argentina]. / Resumen ejecutivo de ARIA 2016: vías integradas de atención para la medicina predictiva a lo largo del ciclo de vida en Argentina.

The ARIA initiative was started during a World Health Organization workshop in 1999. The initial goals were to propose a new classification for allergic rhinitis, to promote the concept of multi-morbidity in asthma and rhinitis and to develop guidelines with stakeholders for world-wide use. ARIA is now focused on the implementation of emerging technologies for individualized and predictive medicine. MASK: MACVIA-Aria Sentinel Network uses mobile technology to develop care pathways that enable management by a multidisciplinary group or by patients themselves. An App for iOS and Android 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 interoperable tablet for health professionals. The escalation strategy uses recommendations of the European Innovation Partnership on Active and Healthy Ageing. The aim of ARIA's new approach is to provide an active and healthy life to people affected by rhinitis, regardless of age, gender or socioeconomic status, in order to reduce social and health inequalities caused by the disease.

La iniciativa ARIA (Rinitis Alérgica y su Impacto en el Asma) se inició durante un taller de la Organización Mundial de la Salud en 1999. Los objetivos iniciales fueron proponer una nueva clasificación de rinitis alérgica, promover el concepto de multimorbilidad en asma y rinitis y desarrollar guías con todas las partes interesadas para su en todos los países y poblaciones. ARIA, difundida e implementada en más de 70 naciones, ahora se centra en la implementación de tecnologías emergentes para la medicina individualizada y predictiva. MASK (MACVIA [Contre les Maladies Chroniques pour un Vieillissement Actif] Aria Sentinel Network) utiliza la tecnología móvil para desarrollar vías de atención que permitan el manejo de la rinitis y del asma por un grupo multidisciplinario o por los propios pacientes. Una aplicación (app) para iOS y Android está disponible en 20 países y 15 idiomas; utiliza una escala analógica visual para evaluar el control de los síntomas y la productividad del trabajo, así como un sistema de apoyo para las decisiones clínicas. Se asocia con una tabla interoperable (que permite intercambiar información) para médicos y otros profesionales de la salud. La estrategia de escalamiento utiliza las recomendaciones de la Asociación Europea de Innovación para el Envejecimiento Activo y Saludable. El objetivo del nuevo enfoque ARIA es proporcionar una vida activa y saludable a las personas afectadas por la rinitis, cualquiera que sea su edad, sexo o condición socioeconómica, con el fin de reducir las desigualdades sociales y de salud causadas por la enfermedad.

Capsaicin for Rhinitis.

Rhinitis is a multifactorial disease characterized by symptoms of sneezing, rhinorrhea, postnasal drip, and nasal congestion. Non-allergic rhinitis is characterized by rhinitis symptoms without systemic sensitization of infectious etiology. Based on endotypes, we can categorize non-allergic rhinitis into an inflammatory endotype with usually eosinophilic inflammation encompassing at least NARES and LAR and part of the drug induced rhinitis (e.g., aspirin intolerance) and a neurogenic endotype encompassing idiopathic rhinitis, gustatory rhinitis, and rhinitis of the elderly. Patients with idiopathic rhinitis have a higher baseline TRPV1 expression in the nasal mucosa than healthy controls. Capsaicin (8-methyl-N-vanillyl-6-nonenamide) is the active component of chili peppers, plants of the genus Capsicum. Capsaicin is unique among naturally occurring irritant compounds because the initial neuronal excitation evoked by it is followed by a long-lasting refractory period, during which the previously excited neurons are no longer responsive to a broad range of stimuli. Patients with idiopathic rhinitis benefit from intranasal treatment with capsaicin. Expression of TRPV1 is reduced in patients with idiopathic rhinitis after capsaicin treatment. Recently, in a Cochrane review, the effectiveness of capsaicin in the management of idiopathic rhinitis was evaluated and the authors concluded that given that many other options do not work well in non-allergic rhinitis, capsaicin is a reasonable option to try under physician supervision. Capsaicin has not been shown to be effective in allergic rhinitis nor in other forms of non-allergic rhinitis like the inflammatory endotypes or other neurogenic endotypes like rhinitis of the elderly or smoking induced rhinitis.

Novel, Alternative, and Controversial Therapies of Rhinitis.

Rhinitis is a multifactorial disease characterized by sneezing, rhinorrhea, postnasal drip, and nasal congestion. This condition affects 10% to 40% of the population and is responsible for billions of spent health care dollars and impairment in quality of life for those affected. Currently available medical and vaccine therapies are effective for a large segment of this population; however, a subset of patients still has difficult-to-control rhinitis. This article reviews the current progress being made in novel drug and vaccine development and delves into alternative medical, surgical, and homeopathic strategies that may be promising adjunctive treatments for the difficult-to-treat rhinitis patient.

Capsaicin for non-allergic rhinitis.

BACKGROUND: There are many forms of rhinitis. Patients are diagnosed with non-allergic rhinitis when anatomic, infectious and allergic aetiologies have been excluded. The symptoms, including nasal congestion, blockage or obstruction, clear rhinorrhoea, sneezing and, less frequently, nasal itching, can range from mild to debilitating. It affects between 25% and 50% of patients with rhinitis. Several medications are widely used in the treatment of non-allergic rhinitis, including oral and topical nasal antihistamines, intranasal and (rarely) systemic corticosteroids, and anticholinergics. Capsaicin, the active component of chili peppers, delivered intranasally, is considered a treatment option for non-allergic rhinitis. OBJECTIVES: To assess the effectiveness of capsaicin in the management of non-allergic rhinitis compared with no therapy, placebo or other topical or systemic medications, or two or more of the above therapies in combination, or different capsaicin regimens. SEARCH METHODS: We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 5); PubMed; EMBASE; CINAHL; Web of Science; Cambridge Scientific Abstracts; ICTRP and additional sources for published and unpublished trials. The date of the search was 24 June 2015. SELECTION CRITERIA: Randomised controlled trials in adult patients with non-allergic rhinitis comparing intranasal capsaicin with no therapy, placebo or other topical or systemic medications, or their combinations. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by The Cochrane Collaboration. MAIN RESULTS: We included four studies (five publications) involving 302 participants with idiopathic non-allergic rhinitis. All the included studies described patients with moderately severe, idiopathic non-allergic rhinitis who were between the ages of 16 and 65. Studies had follow-up periods ranging from four to 38 weeks. The overall risk of bias in the studies was either high or unclear (two studies had overall high risk of bias, while two others had low to unclear risk of bias). Using the GRADE system we assessed the evidence as being of low to moderate quality. A meta-analysis was not possible, given lack of similarity of the reported outcomes.Two studies compared capsaicin with placebo. One study reported that capsaicin resulted in an improvement of overall nasal symptoms (a primary outcome) measured on a visual analogue scale (VAS) of 0 to 10. There was a mean difference (MD) of -3.34 (95% confidence interval (CI) -5.24 to -1.44), MD -3.73 (95% CI -5.45 to -2.01) and MD -3.52 (95% CI -5.55 to -1.48) at two, 12 and 36 weeks post-treatment, respectively. Another study reported that, compared to placebo, capsaicin (at 4 µg/puff) was more likely to produce overall symptom resolution (reduction in nasal blockage, sneezing/itching/coughing and nasal secretion measured with a daily record chart) at four weeks post-treatment (a primary outcome). The risk ratio (RR) was 3.17 (95% CI 1.38 to 7.29).One study compared capsaicin to budesonide (an intranasal corticosteroid). This study found that patients treated with capsaicin had a better overall symptom score compared to those treated with budesonide (MD 2.50, 95% CI 1.06 to 3.94, VAS of 0 to 10). However, there were no differences in the individual symptom scores for headache, postnasal drip, rhinorrhoea, nasal blockage, sneezing and sore throat assessed during the last three days of a four-week treatment.One study compared two different regimens of capsaicin administration: five treatments in one day versus five treatments given every two to three days during two weeks. Using daily record charts, the study reported significant improvement of individual symptom scores for rhinorrhoea in patients treated five times per day, however numerical data were not presented. There were no improvements in the other outcomes: rhinorrhoea, nasal obstruction, sneezing and overall nasal symptoms, measured on a VAS.Finally, one of these studies also compared three doses of capsaicin (to placebo). Patients treated with a 1 µg versus 4 µg per puff dose of capsaicin had a worse daily record chart overall symptom score resolution (RR 0.63, 95% CI 0.34 to 1.16).Only one study attempted to measure adverse effects (a primary outcome), however due to methodological issues with the assessment we are unable to draw any conclusions.We sought to include other secondary outcomes (e.g. quality of life measures, treatment dropouts, endoscopic scores, turbinate or mucosal size, cost of therapy), but none of these were measured or reported in the included studies. AUTHORS' CONCLUSIONS: Capsaicin may be an option in the treatment of idiopathic non-allergic rhinitis. It is given in the form of brief treatments, usually during the same day. It appears to have beneficial effects on overall nasal symptoms up to 36 weeks after treatment, based on a few, small studies (low-quality evidence). Well-conducted randomised controlled trials are required to further advance our understanding of the effectiveness of capsaicin in non-allergic rhinitis, especially in patients with non-allergic rhinitis of different types and severity, and using different methods of capsaicin application.

Current management of allergic rhinitis in children.

Over the last 20 years, there has been significant progress in our understanding of the pathophysiology of allergic rhinitis, including the discovery of new inflammatory mediators, the link between asthma and allergic rhinitis ('one airway-one disease' concept) and the introduction of novel therapeutic modalities. These new insights have been documented in the Allergic Rhinitis and its Impact on Asthma guidelines and have led to the creation of evidence-based management algorithms. We now understand the importance of a common strategy for treating allergic inflammation of the upper and lower airway as a way of improving outcome, reducing hospital admissions, providing better quality of life and perhaps, altering the natural course of the 'allergic march'. A therapeutic ladder is suggested: Whereas for mild intermittent allergic rhinitis, allergen avoidance should be the first line of treatment with subsequent addition of a second generation topical or oral antihistamine, nasal saline or cromoglycate, in cases of moderate to severe allergic rhinitis, a nasal steroid is the treatment of choice. If a patient with moderate/severe persistent allergic rhinitis fails to improve after 4 wk of adequate treatment, patient compliance or the diagnosis must be re-assessed. In such cases, when the diagnosis is in doubt, a careful clinical examination including nasal endoscopy is mandatory to assess for other potential causes of nasal obstruction. In children who suffer from concomitant allergic rhinitis and asthma, a management algorithm that addresses concurrently asthma and allergic rhinitis is vital, both from a theoretical and from a practical point of view: Parents overwhelmingly prefer a single strategy for the treatment of their child's upper and lower airway symptoms; however, the overall quality of life in children with severe asthma can be significantly improved if rhinitis is adequately addressed.

An integrated analysis of the efficacy of fluticasone furoate nasal spray on individual nasal and ocular symptoms of seasonal allergic rhinitis.

Intranasal steroids have been shown to affect ocular symptoms of allergic rhinitis (AR). The results of the published literature, however, are not uniform across all products. This study was designed to evaluate whether the effects of fluticasone furoate nasal spray (FFNS) are consistent across different allergy seasons and different geographic regions for individual nasal and ocular symptoms of seasonal allergic rhinitis (SAR). An integrated analysis was performed on data from four randomized, double-blind, placebo-controlled, parallel-group, multicenter trials, designed to evaluate the efficacy and safety of FFNS, 110 micrograms, once daily for 14 days in 1141 adult and adolescent SAR patients exposed to mountain cedar, ragweed, or grass pollen allergen. All patients evaluated severity of seven individual nasal and ocular symptoms on a 4-point categorical scale. The main efficacy measures included change from baseline in daily reflective, morning (A.M.) predose instantaneous, and daily A.M. and evening (P.M.) reflective score for each nasal/ocular symptom. FFNS significantly improved daily mean reflective, A.M. predose instantaneous, and daily A.M. and P.M. reflective scores for nasal itching, sneezing, congestion, rhinorrhea, and ocular itching/burning, tearing/watering, and redness, compared with placebo (p < 0.001 for all versus placebo). The least square (LS) mean treatment differences ranged from -0.44 to -0.33 (p < 0.0001) for the individual nasal symptoms and from -0.22 to -0.19 (p < 0.0001) for the individual ocular symptoms. FFNS also significantly improved daily reflective total nasal symptom scores (TNSS)/reflective total ocular symptom scores (TOSS), and A.M. predose instantaneous TNSS and instantaneous TOSS, compared with placebo (LS mean treatment differences = -1.47, -0.65, -1.49, and -0.63, respectively; p < 0.001 for all). FFNS, 110 micrograms, once daily consistently relieved all nasal and ocular symptoms of SAR across different allergy seasons and geographical locations.

Diminished response to grass pollen allergen challenge in subjects with concurrent house dust mite allergy.

INTRODUCTION: The clinical manifestation of allergic rhinitis is influenced by many factors; while different subpopulations are not well defined. Different combinations of allergic sensitization may lead to different clinical manifestations of allergic disease. METHODS: In a nasal allergen challenge model we compared allergic rhinitis symptoms between subjects mono-sensitized to grass pollen or house dust mite, poly-sensitized subjects, and healthy controls. We measured visual analogue scales of symptoms and peak nasal inspiratory flow. We also compared serum total IgE, allergen-specific IgE and IgG4, and basophil histamine release. RESULTS: Nasal challenge with grass pollen extract led to a significantly larger increase in subjective (p = 0.031) and objective (p = 0.001) nasal symptoms in grass pollen mono-sensitized subjects than in poly-sensitized subjects. No differences were found in serum levels of allergen-specific IgE and IgG4 or in biological activity of IgE (basophil histamine release) between mono-sensitized and poly-sensitized subjects. We found a strong inverse correlation between serum allergen-specific IgE and basophil histamine release (-0.789, p = 0.001). CONCLUSIONS: Grass pollen mono-sensitized subjects have a more severe clinical response to nasal challenge than poly-sensitized subjects. This cannot be explained by serum levels of IgE or its biological activity. The continuous allergen exposure in poly-sensitized subjects may alter local immuno-regulatory processes, leading to a reduced clinical response to allergen challenge.

Use of neuromuscular electrostimulation in the treatment of dysphagia in patients with multiple sclerosis.

OBJECTIVES: We explored the possible effects of neuromuscular electrostimulation on the swallowing function of patients with multiple sclerosis and swallowing problems. METHODS: Twenty-five patients (average age, 53.1 years; SD, 9.8 years) with multiple sclerosis and swallowing problems were treated for 3 weeks with 2 sessions per week of neuromuscular electrostimulation. The average time since the onset of multiple sclerosis was 16.5 years (SD, 10.2 years). Seventeen patients were examined with transnasal flexible endoscopy 1 week before treatment and 1 week after treatment. RESULTS: After treatment, a significant decrease in pooling of saliva in the pyriform sinuses was seen in 6 patients (p = 0.03), and significantly less aspiration during swallowing of thin liquids (p <0.01) was seen in 9 patients. Overall, the 25 patients reported that their swallowing had improved (p <0.01), and in 20% of the patients,it had become less strenuous. No adverse effects of the treatment were reported. CONCLUSIONS: Our study showed that the treatment of swallowing problems with neuromuscular electrostimulation in patients with multiple sclerosis in this sample was successful in the reduction of pooling of saliva and in the reduction of aspiration.