RESUMEN

Purpose: To provide a descriptive summary of clinical efficacy and health-related quality of life (HRQoL) measures in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and clinical features of obstructive lung disease in the Phase III dupilumab studies SINUS-24 and SINUS-52 (NCT02912468, NCT02898454). Patients and Methods: Patients met a "broad" definition of having clinical features of obstructive lung disease with any of 3 criteria: (i) pre-bronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) <0.70 and smoking history; (ii) patient-reported medical history of chronic obstructive pulmonary disease (COPD); or (iii) asthma with >10 pack-years' smoking history. A "narrow" definition including criteria (i) or (ii) was also analyzed. CRSwNP and HRQoL measures were evaluated in all patients and lung function (FEV1; FEV1/FVC ratio) was captured and analyzed only in those patients who had a self-reported history of asthma. Results: Across both studies, 131 patients met the "broad" definition, of whom 90 also had asthma, and 115 patients met the "narrow" definition, of whom 74 had asthma. CRSwNP outcomes and HRQoL were improved with dupilumab vs placebo in both the broad and narrow subgroups. Among the 90 patients who met the broad definition and had asthma, dupilumab improved pre-bronchodilator FEV1 and FEV1/FVC ratio at Week 16 (least squares mean differences vs placebo: 0.38 L [95% confidence interval: 0.17, 0.59; p = 0.0004] and 4.8% [1.7%, 7.9%; p = 0.0024], respectively) sustained through Week 24. Similar results were seen in the "narrow" subgroup with asthma. Conclusion: In a population of patients with CRSwNP and clinical features of obstructive lung disease, dupilumab improved CRSwNP and HRQoL outcomes, and, among those with a history of asthma, also improved lung function. These results support further analyses of dupilumab in patients with evidence of type 2 inflammation and obstructive lung disease such as COPD.

RESUMEN

PURPOSE: To report biomarkers present in the olfactory mucosa in chronic rhinosinusitis with nasal polyps (CRSwNP) in comparison with nasal polyps and to nasal mucosal tissues from control patients. To evaluate the kinetics of smell over 6 months in patients who underwent Reboot surgery. METHODS: Cohort study from May 2021 to May 2022. We collected samples of olfactory mucosa and nasal polyps from 16 CRSwNP patients and inferior turbinate samples from 20 control subjects. The study was not randomized for surgical and/or medical treatment. Samples were analyzed by Luminex and Unicap 100 to measure biomarkers of inflammation (IL1-ß, IL4, IL5, IL6, IL17, CCL3, CCL4, G-CSF, SE-IgE, total IgE and ECP). 12 of the CRSwNP patients underwent Extended Sniffin'tests at timepoints 1-4 days pre-surgery, and 1, 3 and 6 months after Reboot surgery. RESULTS: Type-2 markers were significantly elevated in OM and polyp tissue in CRSwNP (n = 16) vs. controls (n = 20), P < 0.05. TDI scores improved already 1 month (P < 0.05) after surgery and remained stable for 6 months. Type-2 inflammation in nasal polyps was associated with decreased sense of smell and taste before surgery, but improved after surgery (P = 0.048). Type-3 inflammation was present in the olfactory mucosa and was associated with a better sense of smell before surgery, but a smaller improvement of smell afterward. CONCLUSIONS: Type-2 inflammation is present in the olfactory mucosa in CRSwNP patients and is associated with smell loss. Reboot surgery, aiming to completely remove inflamed sinus mucosa, significantly improves the smell in this group of patients.

Asunto(s)

RESUMEN

OBJECTIVE: To evaluate the time for recovery of the sense of smell in patients with CRSwNP who underwent Reboot surgery compared to patients undergoing ESS in a long-term follow-up study. METHODS: Data were collected retrospectively from 168 patients with severe uncontrolled CRSwNP, who underwent revision surgery, either as Extended Endoscopic Sinus Surgery (Reboot, 140 patients) or as regular Endoscopic Sinus Surgery (ESS, 28 patients) between January 1, 2014, and December 31, 2015, aiming to compare the outcome of surgeries after 2 years of follow-up. Sense of smell was scored as judged by the patient using scores 0 to 3 reflecting a percentage estimate of remaining smell. RESULTS: Smell improved similarly in the Reboot and ESS groups over the first 9 months, which was maintained over 24 months in the Reboot, but not the ESS group (p = 0.007 after 18 months, p = 0.001 after 24 months). Furthermore, polyp recurrence rates were significantly lower in the Reboot group. CONCLUSION: Reboot surgery significantly improved olfactory function and significantly reduced nasal polyp recurrence rates over 2 years post-operatively. Therefore, Reboot should be considered for patients with uncontrolled severe CRSwNP, specifically when ESS failed, to offer long-term smell and a polyp-free status. LEVEL OF EVIDENCE: 3b.

Asunto(s)

RESUMEN

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.

Asunto(s)

RESUMEN

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.

Asunto(s)

Asunto(s)

Asunto(s)

RESUMEN

BACKGROUND: Systemic reactions are related to the pathogenesis of Aspirin Exacerbated Respiratory Disease (AERD). With this work we wanted to study the changes in the systemic levels of inflammatory mediators in both baseline and after oral aspirin challenge in patients with and without AERD. METHODS: Patients with nasal polyposis and asthma with AERD (n=20) and without (n=18) were orally challenged with aspirin in a single-blind placebo controlled study. Serum samples and urine were collected before and 6h after placebo and aspirin oral challenges. Serum levels of inflammatory mediators were assayed by using the Luminex technology and ELISA. The concentrations of 9-alpha, 11-beta prostaglandin F2, and leukotriene E4 (uLTE4) were measured in urine samples by ELISA. The expression of T-cell surface markers was analyzed in peripheral blood mononuclear cells isolated before and after the challenges. RESULTS: AERD patients showed significantly higher baseline levels of s-IL-5R-alpha, uLTE4 and percentage of CD4(+)CD25(+)CD127(pos) and CD4(+)CD45RA(-)CD45RO(+) but decreased levels of TGF-ß1 and number of CD4(+)CD25(+)CD127(neg) cells. Aspirin challenge induced the release of uLTE4, IL-6 and increased the number of CD4(+)CD45RA(-)CD45RO(+) memory T-cells only in AERD patients but failed to reduce the levels of sCD40L as observed in non-AERD subjects. Further, IL-8 and sIL-5R-alpha levels directly correlated with the PD20ASA and the effects of aspirin on IL-6 and number of memory T-cells was more pronounced in subjects showing more strong reaction (bronchial and nasal). CONCLUSIONS: AERD patients have a differential baseline inflammatory pattern that supports the role inflammation as underlying mechanism of the disease. Systemic response to oral aspirin challenge was related to an increase in serum IL-6 and the number of circulating memory T-cells in AERD patients.

Asunto(s)

RESUMEN

In the past, asthma was considered mainly as a childhood disease. However, asthma is an important cause of morbidity and mortality in the elderly nowadays. In addition, the burden of asthma is more significant in the elderly than in their younger counterparts, particularly with regard to mortality, hospitalization, medical costs or health-related quality of life. Nevertheless, asthma in the elderly is still been underdiagnosed and undertreated. Therefore, it is an imperative task to recognize our current challenges and to set future directions. This project aims to review the current literature and identify unmet needs in the fields of research and practice for asthma in the elderly. This will enable us to find new research directions, propose new therapeutic strategies, and ultimately improve outcomes for elderly people with asthma. There are data to suggest that asthma in older adults is phenotypically different from young patients, with potential impact on the diagnosis, assessment and management in this population. The diagnosis of AIE in older populations relies on the same clinical findings and diagnostic tests used in younger populations, but the interpretation of the clinical data is more difficult. The challenge today is to encourage new research in AIE but to use the existing knowledge we have to make the diagnosis of AIE, educate the patient, develop a therapeutic approach to control the disease, and ultimately provide a better quality of life to our elderly patients.

RESUMEN

OBJECTIVE: To evaluate TGF-ß1 expression in polypoid mucosa (epithelium and stroma) of patients with chronic rhinosinusitis with nasal polyposis (CRSwNP). METHODS: Cross-sectional study with two groups: 17 patients with nasal polyposis and 11 controls. Polyps and normal nasal mucosa were processed by immunohistochemical methods for TGF-ß1 visualization. Then, the percentage of TGF-ß1 expression in stroma and epithelium was objectively quantified using UT Morph software. RESULTS: A lower percentage of positive expression was found in the epithelium of CRSwNP patients (32.44%) versus normal controls (55.91%) (p < 0.05), and a higher percentage of positive expression in the stroma of CRSwNP patients (23.24%) versus controls (5.88%) (p < 0.05). CONCLUSION: The lower percentage of TGF-ß1 expression in the nasal epithelium of CRSwNP patients may have an impact on epithelium-directed topical treatments employed in this patient population.

Asunto(s)

RESUMEN

Allergic rhinitis and asthma represent global problems of public health affecting all age groups; asthma and allergic rhinitis frequently coexist in the same patients. In Latin American prevalence of allergic rhinitis, although variable, is very high. Allergic rhinitis and its Impact on Asthma (ARIA) started during a workshop of the World Health Organization performed in 1999 and was published in 2001. ARIA proposed a new classification of allergic rhinitis in intermittent or persistent and mild or moderate-severe. This approach of classification reflects more nearly the impact of allergic rhinitis in patients. In its review of 2010 ARIA developed guidelines for diagnosis and treatment of allergic rhinitis and of clinical practices for management of comorbidities of allergic rhinitis and asthma based on GRADE (Grading of Recommendations, Development and Evaluation). ARIA has been spread and implemented in more than 50 countries. In Latin American an intense activity has been developed to spread these recommendations in almost all the countries of the region and it is important to record the obtained goals in the diffusion and implementation of ARIA, as well as to identify the unsatisfied needs from the clinical, research and implementation points of view. Final objective is to reinforce the priority that allergy and asthma should have, especially in children, in the programs of public health, as they have been prioritized in European Union in 2011.

La rinitis alérgica y el asma representan problemas globales de salud pública que afectan a todos los grupos etarios; el asma y la rinitis alérgica frecuentemente coexisten en los mismos pacientes. En América Latina la prevalencia de rinitis alérgica, aunque variable, es muy elevada. La iniciativa Rinitis Alérgica y su Impacto en Asma (globalmente conocida como ARIA, de su nombre en inglés Allergic Rhinitis and its Impact on Asthma) comenzó durante un taller de la Organización Mundial de la Salud (OMS) realizado en 1999 que se publicó en el año 2001. ARIA propuso una nueva clasificación de rinitis alérgica en intermitente o persistente y leve o moderada-severa. Este esquema de clasificación refleja más estrechamente el impacto de la rinitis alérgica en los pacientes. En su revisión de 2010, la guía ARIA desarrolló pautas para el diagnóstico y tratamiento de la rinitis alérgica y de prácticas clínicas para el manejo de las comorbilidades de la rinitis alérgica y el asma basadas en GRADE (Gradación de Recomendaciones, Desarrollo y Evaluación). ARIA se ha diseminado e implantado en más de 50 países. En América Latina se ha desarrollado una intensa actividad para diseminar estas recomendaciones en casi todos los países de la región y es importante llevar un registro de los logros obtenidos en la difusión e implantación de ARIA, además de identificar las necesidades insatisfechas desde el punto de vista clínico, de la investigación y de la implantación. El objetivo final es reforzar la prioridad que deben tener la alergia y el asma ­especialmente en niños­ en los programas de Salud Pública, tal como los priorizó la Unión Europea en 2011.

Asunto(s)