Effect of different therapeutic strategies on olfactory outcomes in patients with chronic rhinosinusitis with nasal polyps: a systematic review.

INTRODUCTION: Olfactory impairment is one of the cardinal symptoms of chronic rhinosinusitis with nasal polyps (CRSwNP), yet the effect of the currently available therapeutic options on the recovery of the sense of smell is not well defined. The aim of this systematic review was to compile the evidence on the impact of medical, surgical, and biological therapies on the olfactory outcomes in patients with CRSwNP. METHODS: This review was conducted by two reviewers, according to the Preferred Reporting Items for Systematic Reviews and meta-Analyses (PRISMA) guidelines. The quality of evidence of all studies included in the qualitative synthesis was evaluated using the Critical Appraisal Skills Programme (CASP). RESULTS: Forty-four studies were included in the qualitative synthesis (assessing sinonasal surgery [n = 23], biologics [n =15], and conventional medical treatment [n = 6]); most had moderate-to-high methodological quality. Overall, significant improvements in the sense of smell were detected with all analyzed interventions measured by either an objective or a subjective tool (or both). However, most studies used different outcome measurements, hindering comparisons between interventions, and data on clinically relevant changes were missing. CONCLUSION: Oral corticosteroids, biologics and sinonasal surgery improve olfactory impairment associated with CRSwNP, but the high variability among existing studies does not allow accurate comparisons.

Improvement in Smell Using Monoclonal Antibodies Among Patients With Chronic Rhinosinusitis With Nasal Polyps: A Systematic Review.

BACKGROUND: Impairment of smell is more commonly related to chronic rhinosinusitis with nasal polyps (CRSwNP) than without, especially when asthma and/or NSAID-exacerbated respiratory disease and type 2 inflammation are also present. Therapeutic options include intranasal and systemic corticosteroids, surgery, and, more recently, biological therapy. We summarize current knowledge on the effect of biologics on olfaction in patients with CRSwNP. METHODS: We performed a systematic search of the PubMed and Cochrane databases from January 2001 to June 2022. The inclusion criteria were as follows: adult patients with CRS treated with dupilumab, omalizumab, mepolizumab, benralizumab, or reslizumab; and studies published in English reporting outcomes for sense of smell based on psychophysical and/or subjective tools. We excluded reports that did not assess CRSwNP, loss of smell evaluated with a method other than those accepted in the inclusion criteria, review articles, and expert opinions. No funding was received. RESULTS: Dupilumab has demonstrated rapid and sustained long-term improvement in smell in clinical trials and in real life. Omalizumab improves smell at 24 weeks. This improvement is maintained in the long-term, although it is not clinically relevant. Mepolizumab and benralizumab improved smell in the long term based on a subjective scale. No studies examining the improvement in smell in patients with CRSwNP treated with reslizumab were found. Indirect comparisons by meta-analysis consistently conclude that dupilumab is the most effective biologic for improving impaired sense of smell. CONCLUSION: Dupilumab seems to be more efficacious for improving the sense of smell than omalizumab, mepolizumab, and benralizumab.

Clinical and histological predictive factors of reclassification of prostate cancer patients on active surveillance.

INTRODUCTION AND OBJECTIVE: Active surveillance (AS) has been established as a therapeutic strategy in patients with low-risk prostate cancer. Demographic and anatomopathological factors that increase the probability of reclassifying patients have been identified. MATERIALS AND METHODS: Laboratory and histopathological data were collected from 116 patients included on AS since 2014. Univariate analysis was performed with Chi-square, t-student and Kendall's Tau, multivariate analysis according to logistic regression and Kaplan-Meier curves were calculated. RESULTS: Of the 116 patients in AS, the median age at diagnosis was 66 years and the median follow-up was 13 months (2-72). Of these, 61 (52.6%) are still on surveillance, while 55 (47.4%) have left the program, mostly due to histological progression (52 patients (45.2%)); radical prostatectomy was performed in 27 (49.1%). Prostate volume (PV)≤60cc and the number of positive cylinders >1 in diagnostic biopsy (P=.05) were associated with higher reclassification rate in univariate analysis (P<.05). Multivariate analysis showed that these two variables significantly correlated with higher reclassification rate (PV 60 cc: OR 4.39, P=.04; >1 positive cylinder at diagnostic biopsy: OR 2.48, P=.03). CONCLUSIONS: It has been shown that initial ultrasound volume and the number of positive cylinders in the diagnostic biopsy are independent risk factors for reclassification. Initial PSA, laterality of the affected cylinders and PSA density were not predictive factors of progression in our series.

Factores clínicos e histológicos predictores de reclasificación en pacientes incluidos en programa de vigilancia activa de cáncer de próstata / Clinical and histological predictive factors of reclassification of prostate cancer patients on active surveillance

Introducción y objetivo La vigilancia activa (VA) se ha establecido como estrategia terapéutica en pacientes con cáncer de próstata de bajo riesgo. Se han identificado factores demográficos y anatomopatológicos que aumentan la probabilidad de reclasificar a los enfermos. Materiales y métodos Se han recogido datos analíticos e histopatológicos de 116 pacientes incluidos en VA desde 2014. Se ha realizado un análisis univariante con X2, t de Student y Tau de Kendall, un análisis multivariante según regresión logística y se han calculado las curvas de Kaplan-Meier. Resultados De los 116 pacientes en VA, la mediana de edad al diagnóstico fue 66 años y la mediana de seguimiento fueron 13 meses (2-72). De todos ellos, 61 (52,6%) siguen en vigilancia mientras que 55 (47,4%) han salido del programa, la mayoría por progresión histológica (52 pacientes [45,2%]), realizándose prostatectomía radical en 27 (49,1%). El volumen prostático (Vp) ≤ 60cc y el número de cilindros positivos >1 en la biopsia diagnóstica (p = 0,05) se asociaron con mayor tasa de reclasificación en el análisis univariante (p < 0,05). En el análisis multivariante, estas dos variables se correlacionaron significativamente con una mayor tasa de reclasificación (Vp ≤ 60 cc: OR 4,39, p = 0,04; >1 cilindro positivo en la biopsia diagnóstica: OR 2,48, p = 0,03). Conclusiones Se ha objetivado que el volumen ecográfico inicial y el número de cilindros positivos en la biopsia diagnóstica son factores de riesgo independientes para la reclasificación. El antígeno prostático específico (PSA) inicial, la lateralidad de los cilindros afectos y la densidad de PSA no fueron elementos predictores de progresión en nuestra serie (AU)

Introduction and Objective Active surveillance (AS) has been established as a therapeutic strategy in patients with low-risk prostate cancer. Demographic and anatomopathological factors that increase the probability of reclassifying patients have been identified. Materials and Methods Laboratory and histopathological data were collected from 116 patients included on AS since 2014. Univariate analysis was performed with Chi-square, t-student and Kendall's Tau, multivariate analysis according to logistic regression and Kaplan-Meier curves were calculated. Results Of the 116 patients in AS, the median age at diagnosis was 66 years and the median follow-up was 13 months (2-72). Of these, 61 (52.6%) are still on surveillance, while 55 (47.4%) have left the program, mostly due to histological progression (52 patients (45.2%)); radical prostatectomy was performed in 27 (49.1%). Prostate volume (PV) ≤ 60cc and the number of positive cylinders > 1 in diagnostic biopsy (p = 0.05) were associated with higher reclassification rate in univariate analysis (p < 0.05). Multivariate analysis showed that these two variables significantly correlated with higher reclassification rate (PV 60 cc: OR 4.39, p = 0.04; > 1 positive cylinder at diagnostic biopsy: OR 2.48, p = 0.03). Conclusions It has been shown that initial ultrasound volume and the number of positive cylinders in the diagnostic biopsy are independent risk factors for reclassification. Initial PSA, laterality of the affected cylinders and PSA density were not predictive factors of progression in our series (AU)

Exacerbations Among Patients With Asthma Are Largely Dependent on the Presence of Multimorbidity.

BACKGROUND AND OBJECTIVE: Comorbidities can influence asthma control and promote asthma exacerbations (AEs). However, the impact of multimorbidity in AEs, assessed based on long-term follow-up of patients with asthma of different degrees of severity, has received little attention in real-life conditions. To describe the epidemiological and clinical characteristics and predictors of AEs in patients who had presented at least 1 AE in the previous year in the MEchanism of Genesis and Evolution of Asthma (MEGA) cohort. METHODS: The work-up included a detailed clinical examination, pulmonary function testing, fractional exhaled nitric oxide (FeNO), blood counts, induced sputum, skin prick-tests, asthma questionnaires, and assessment of multimorbidity. The number of moderate-severe AEs in the preceding year was registered for each patient. RESULTS: The study population comprised 486 patients with asthma (23.7% mild, 35% moderate, 41.3% severe). Disease remained uncontrolled in 41.9%, and 47.3% presented ≥1 moderate-severe AE, with a mean (SD) annual exacerbation rate of 0.47 (0.91) vs 2.11 (2.82) in mild and severe asthma, respectively. Comorbidity was detected in 56.4% (66.6% among those with severe asthma). Bronchiectasis, chronic rhinosinusitis with nasal polyps, atopy, psychiatric illnesses, hyperlipidemia, and hypertension were significantly associated with AEs. No associations were found for FeNO, blood eosinophils, or total serum IgE. Sputum eosinophilia and a high-T2 inflammatory pattern were significantly associated with AEs. Multivariable regression analysis showed a significant association with asthma severity, uncontrolled disease, and low prebronchodilator FEV1/FVC. CONCLUSION: Our study revealed a high frequency of AE in the MEGA cohort. This was strongly associated with multimorbidity, asthma severity, poor asthma control, airflow obstruction, higher sputum eosinophils, and a very high-T2 inflammatory pattern.

Improvement in Olfaction in Patients With CRSwNP and Severe Asthma Taking Anti-IgE and Anti-IL-5 Biologics: A Real-Life Study.

BACKGROUND AND OBJECTIVES: Chronic rhinosinusitis with nasal polyps (CRSwNP), which is characterized by partial loss of smell (hyposmia) or total loss of smell (anosmia), is commonly associated with asthma and/or nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD). CRSwNP worsens disease severity and quality of life. The objective of this real-world study was to determine whether biological treatments prescribed for severe asthma can improve olfaction in patients with CRSwNP. A further objective was to compare the improvement in in olfaction in N-ERD and non-N-ERD subgroups. METHODS: We performed a multicenter, noninterventional, retrospective, observational study of 206 patients with severe asthma and CRSwNP undergoing biological treatment (omalizumab, mepolizumab, benralizumab, or reslizumab). RESULTS: Olfaction improved after treatment with all 4 monoclonal antibodies (omalizumab [35.8%], mepolizumab [35.4%], reslizumab [35.7%], and benralizumab [39.1%]), with no differences between the groups. Olfaction was more likely to improve in patients with atopy, more frequent use of short-course systemic corticosteroids, and larger polyp size. The proportion of patients whose olfaction improved was similar between the N-ERD (37%) and non-N-ERD (35.7%) groups. CONCLUSIONS: This is the first real-world study to compare improvement in olfaction among patients undergoing long-term treatment with omalizumab, mepolizumab, reslizumab, or benralizumab for severe asthma and associated CRSwNP. Approximately 4 out of 10 patients reported a subjective improvement in olfaction (with nonsignificant differences between biologic drugs). No differences were found for improved olfaction between the N-ERD and non-N-ERD groups.

Improvement in Olfaction in Patients With CRSwNP and Severe Asthma Taking Anti-IgE and Anti–IL-5 Biologics: A Real-Life Study

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP), which is characterized by partial loss of smell (hyposmia) or total loss of smell (anosmia), is commonly associated with asthma and/or nonsteroidal anti-inflammatory drug–exacerbated respiratory disease (N-ERD). CRSwNP worsens disease severity and quality of life. Objectives: The objective of this real-world study was to determine whether biological treatments prescribed for severe asthma can improve olfaction in patients with CRSwNP. A further objective was to compare the improvement in in olfaction in N-ERD and non–N-ERD subgroups.Methods: We performed a multicenter, noninterventional, retrospective, observational study of 206 patients with severe asthma and CRSwNP undergoing biological treatment (omalizumab, mepolizumab, benralizumab, or reslizumab). Results: Olfaction improved after treatment with all 4 monoclonal antibodies (omalizumab [35.8%], mepolizumab [35.4%], reslizumab [35.7%], and benralizumab [39.1%]), with no differences between the groups. Olfaction was more likely to improve in patients with atopy, more frequent use of short-course systemic corticosteroids, and larger polyp size. The proportion of patients whose olfaction improved was similar between the N-ERD (37%) and non–N-ERD (35.7%) groups. Conclusions: This is the first real-world study to compare improvement in olfaction among patients undergoing long-term treatment with omalizumab, mepolizumab, reslizumab, or benralizumab for severe asthma and associated CRSwNP. Approximately 4 out of 10 patients reported a subjective improvement in olfaction (with nonsignificant differences between biologic drugs). No differences were found for improved olfaction between the N-ERD and non–N-ERD groups (AU)

La rinosinusitis crónica con poliposis nasal (PN), caracterizada por la pérdida parcial o completa del olfato (hiposmia o anosmia, respectivamente), se asocia frecuentemente a asma y a enfermedad respiratoria exacerbada por ácido acetilsalicílico (EREA), lo cual implica una mayor gravedad y un deterioro adicional de la calidad de vida del paciente. Objetivos: El objetivo principal de este estudio fue determinar, en condiciones de vida real, si los tratamientos biológicos prescritos para asma grave mejoraban el olfato en aquellos pacientes que asociaban PN. Como objetivo secundario, se comparó la mejoría del olfato entre los subgrupos EREA y no EREA. Métodos: Se llevó a cabo un estudio multicéntrico, observacional, retrospectivo, que incluyó 206 pacientes con PN y asma grave en tratamiento con algún biológico (omalizumab, mepolizumab, benralizumab oreslizumab). Resultados: Se encontró mejoría del olfato con todos los biológicos: omalizumab (35,8%), mepolizumab (35,4%), reslizumab (35,7%) y benralizumab (39,1%), sin diferencias estadísticamente significativas entre ellos. Los pacientes con atopia, mayor uso de corticoides sistémicos y mayor tamaño de PN inicial, presentaron mayor mejoría. La proporción de pacientes que presentaron mejoría en el olfato fue similar entre el grupo EREA (37%) y no EREA (35,7%). Conclusiones: Se trata del primer estudio que compara, en condiciones de vida real, la mejoría del olfato en pacientes en tratamiento con omalizumab, mepolizumab, reslizumab o benralizumab indicados por asma grave que asociaban PN. Aproximadamente, 4 de cada 10 pacientes refirió mejoría subjetiva en el olfato (sin diferencias estadísticamente significativas entre los distintos biológicos). No se encontraron diferencias entre el grupo EREA y no EREA (AU)

Improvement in Smell Using Monoclonal Antibodies Among Patients With Chronic Rhinosinusitis With Nasal Polyps: A Systematic Review

Background: Impairment of smell is more commonly related to chronic rhinosinusitis with nasal polyps (CRSwNP) than without, especially when asthma and/or NSAID-exacerbated respiratory disease and type 2 inflammation are also present. Therapeutic options include intranasal and systemic corticosteroids, surgery, and, more recently, biological therapy. We summarize current knowledge on the effect of biologics on olfaction in patients with CRSwNP.Methods: We performed a systematic search of the PubMed and Cochrane databases from January 2001 to June 2022. The inclusion criteria were as follows: adult patients with CRS treated with dupilumab, omalizumab, mepolizumab, benralizumab, or reslizumab; and studies published in English reporting outcomes for sense of smell based on psychophysical and/or subjective tools. We excluded reports that did not assess CRSwNP, loss of smell evaluated with a method other than those accepted in the inclusion criteria, review articles, and expert opinions. No funding was received.Results: Dupilumab has demonstrated rapid and sustained long-term improvement in smell in clinical trials and in real life. Omalizumab improves smell at 24 weeks. This improvement is maintained in the long-term, although it is not clinically relevant. Mepolizumab and benralizumab improved smell in the long term based on a subjective scale. No studies examining the improvement in smell in patients with CRSwNP treated with reslizumab were found. Indirect comparisons by meta-analysis consistently conclude that dupilumab is the most effective biologic for improving impaired sense of smell.Conclusion: Dupilumab seems to be more efficacious for improving the sense of smell than omalizumab, mepolizumab, and benralizumab. (AU)

Antecedentes: La pérdida de olfato de la rinosinusitis crónica se relaciona principalmente con el fenotipo que presenta poliposis nasal (RSCcPN), especialmente si asocia asma y/o EREA, e inflamación tipo 2. Los corticoides intranasales y sistémicos, la cirugía y, de forma más reciente, los fármacos biológicos, constituyen las principales estrategias terapéuticas. Este documento contiene una revisión sistemática del efecto de los fármacos biológicos en el olfato de pacientes con RSCcPN. Métodos: Se realizó una búsqueda sistemática en las bases de datos PubMed y Cochrane desde enero de 2001 hasta junio de 2022. Los criterios de inclusión fueron: pacientes adultos con RSC tratados con dupilumab, omalizumab, mepolizumab, benralizumab o reslizumab; estudios publicados en inglés, con datos sobre la mejoría del olfato utilizando test psicofísicos y/o subjetivos. Los criterios de exclusión fueron: publicaciones que no incluían pacientes con poliposis nasal, la pérdida del olfato evaluada con un método diferente de los criterios de inclusión mencionados, los artículos de revisión y la opinión de expertos. No se empleó ningún recurso de financiación. Resultados: Dupilumab ha demostrado una mejora del olfato rápida y mantenida a largo plazo en ensayos clínicos y en la práctica clínica habitual. Omalizumab mejora el olfato en la 24ª semana y lo mantiene a largo plazo, pero no alcanza una mejoría clínicamente relevante. Mepolizumab y benralizumab mejoran el olfato a largo plazo, evaluado mediante un test subjetivo. No se encontraron estudios respecto a la mejoría del olfato en pacientes con RSCcPN tratados con reslizumab. Las comparaciones indirectas mediante metaanálisis concluyen de forma consistente que dupilumab es el biológico más eficaz para mejorar el sentido del olfato. Conclusión: Dupilumab es el biológico más eficaz en la mejoría del olfato en RSCcPN, en comparación con omalizumab, mepolizumab y benralizumab. (AU)

Exacerbations Among Patients With Asthma Are Largely Dependent on the Presence of Multimorbidity

Introduction: Comorbidities can influence asthma control and promote asthma exacerbations (AEs). However, the impact of multimorbidity in AEs, assessed based on long-term follow-up of patients with asthma of different degrees of severity, has received little attention in real-life conditions. Objective: To describe the epidemiological and clinical characteristics and predictors of AEs in patients who had presented at least 1 AE in the previous year in the MEchanism of Genesis and Evolution of Asthma (MEGA) cohort. Methods: The work-up included a detailed clinical examination, pulmonary function testing, fractional exhaled nitric oxide (FeNO), blood counts, induced sputum, skin prick-tests, asthma questionnaires, and assessment of multimorbidity. The number of moderate-severe AEs in the preceding year was registered for each patient. Results: The study population comprised 486 patients with asthma (23.7% mild, 35% moderate, 41.3% severe). Disease remained uncontrolled in 41.9%, and 47.3% presented ≥1 moderate-severe AE, with a mean (SD) annual exacerbation rate of 0.47 (0.91) vs 2.11 (2.82) in mild and severe asthma, respectively. Comorbidity was detected in 56.4% (66.6% among those with severe asthma). Bronchiectasis, chronic rhinosinusitis with nasal polyps, atopy, psychiatric illnesses, hyperlipidemia, and hypertension were significantly associated with AEs. No associations were found for FeNO, blood eosinophils, or total serum IgE. Sputum eosinophilia and a high-T2 inflammatory pattern were significantly associated with AEs. Multivariable regression analysis showed a significant association with asthma severity, uncontrolled disease, and low prebronchodilator FEV1/FVC.Conclusions: Our study revealed a high frequency of AE in the MEGA cohort. This was strongly associated with multimorbidity, asthma severity, poor asthma control, airflow obstruction, higher sputum eosinophils, and a very high-T2 inflammatory pattern (AU)