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.

Prevalence of chronic rhinosinusitis without/with nasal polyps according to severity in Spain.

BACKGROUND: The worldwide prevalence range of chronic rhinosinusitis (CRS) is 5-12%; from this, 20 % have nasal polyps. Due to the little epidemiological data about CRS in the Spanish population, this study analyses the prevalence and severity of CRS with (CRSwNP) or without (CRSsNP) nasal polyps, and their connection with other coexisting type 2 inflammatory diseases in Spain. METHODOLOGY: This is a retrospective, large-scale, nationwide, epidemiological study based on the electronic medical records from the BIG-PAC® database. Patients diagnosed of CRSsNP and CRSwNP were identified using specific disease codes. The severe form of the disease was defined as patients who received at least a long course of antibiotics in CRSsNP or ≥2 short courses of systemic corticosteroids in CRSwNP in ≤12 months during the last 2 years, and/or had previous sinus surgery. Physician-diagnosed prevalence, sociodemographic and clinical characteristics, and disease severity were assessed. RESULTS: Out of a cohort of 1,012,257 patients (≥18 years old), 42,863 and 7,550 patients with diagnosed CRSsNP and CRSwNP, respectively, were analysed. The overall prevalence of diagnosed CRS was 5.1%, being 4.3% and 0.8% for CRSsNP and CRSwNP, respectively. Patients with CRSwNP and severe forms of the disease were older and had higher levels of type 2 inflammatory biomarkers than CRSsNP patients and non-severe disease. CONCLUSIONS: Although CRSsNP was more prevalent than CRSwNP, the severe forms of CRS were more frequent in patients with CRSwNP. In addition, CRSwNP patients had a higher incidence of coexisting type 2 inflammatory diseases.

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.

Spanish Consensus on the Management of Chronic Rhinosinusitis With Nasal Polyps (POLIposis NAsal/POLINA 2.0).

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a highly prevalent and burdensome disease for both individuals and health systems. Its management involves many specialties, including otorhinolaryngology, allergology, pulmonology, primary care, pharmacy, and pediatrics. A multidisciplinary approach and the participation of the patient in decision-making are essential, both for diagnosis and for therapy. The authors of the consensus aim to translate current knowledge into an easy-to-read practical guide and emphasize those aspects requiring further discussion or with unmet needs owing to the lack of appropriate scientific evidence. An iterative approach for the development of an evidence-based systematic review with recommendations was followed using a standard quality assessment approach (Scottish Intercollegiate Guidelines Network [SIGN] and National Institute for Health and Care Excellence [NICE]). The guideline was critically evaluated using the Appraisal of Guidelines for Research and Evaluation (AGREE II) and Recommendation Excellence (AGREE REX) instruments. Consequently, POLINA has been considered a high-quality guideline by an independent agency. The POLINA consensus provides new definitions of control, therapeutic management (including surgery and evaluation of severity), indications for use of biologics, and response. Finally, this guideline focuses on unmet research needs in CRSwNP.

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.

Eosinophilia Induced by Blocking the IL-4/IL-13 Pathway: Potential Mechanisms and Clinical Outcomes.

Five biological drugs are currently marketed for treatment of uncontrolled severe asthma. They all block type 2 inflammatory pathways by targeting IgE (omalizumab), the IL-5 pathway (mepolizumab, reslizumab, benralizumab), or the IL-4/IL-13 pathway (dupilumab). Hypereosinophilia has been observed in 4%-25% of patients treated with dupilumab and is transient in most cases, although there have been reports of persistent cases of symptomatic hypereosinophilia consistent with eosinophilic granulomatosis with polyangiitis (EGPA), eosinophilic pneumonia, eosinophilic vasculitis, and sudden worsening of asthma symptoms. Cases of EGPA have been reported with all biologics, including anti-IL-5 agents, and with leukotriene receptor antagonists in publications or in the EudraVigilance database. In many cases, EGPA appears during tapering of systemic corticosteroids or after switching from an anti-IL-5 biologic to dupilumab, suggesting that systemic corticosteroids or the anti-IL-5 agent were masking vasculitis. This review investigates plausible mechanisms of dupilumab-induced hypereosinophilia and review cases of symptomatic hypereosinophilia associated with dupilumab. Blockade of the IL-4/IL-13 pathway reduces eosinophil migration and accumulation of blood by inhibiting eotaxin-3, VCAM-1, and TARC without simultaneously inhibiting eosinophilopoiesis in bone marrow. When choosing the optimal biologic, it seems necessary to consider the presence of hypereosinophilia (>1500/µL), in which case an anti-IL-5/IL-5R agent is preferable. Furthermore, when switching from an anti-IL-5/5R to an anti-IL-4/13R agent, blood eosinophils and clinical progress should be closely monitored. Nevertheless, dual therapy with anti-IL-5/5R and anti-IL4/IL-13R agents may be needed for optimal control, since both the IL-5 and the IL-4/IL-13 pathways can simultaneously contribute to airway inflammation. This approach can prevent the development of EGPA and other types of symptomatic hypereosinophilia while maintaining control of nasal polyposis. In the near future, it will be possible to use a new generation of biological therapies for the treatment of severe asthma. These act at a higher level of the inflammatory cascade, as is the case of the antialarmins tezepelumab and itepekimab.

The influence of BMI in asthma. Which traits are due to obesity and which to asthma and obesity phenotype?

BACKGROUND AND OBJECTIVES: Characteristics of the asthma and obesity phenotype have been described by cluster studies, but they have not been subsequently confirmed. Specific characteristics of this phenotype have not been differentiated from those inherent to the patient's body mass index (BMI). This study aims to assess the effect of BMI on asthma. This will allow to identify which traits could define the asthma and obesity phenotype, and which are inherent to the patient´s BMI. METHODS: A real-life retrospective observational study was conducted with a 2,514 patients database. Data was collected on the first visit to the Allergy clinic of all patients who underwent a correct spirometry maneuver due to suspected asthma between November 2014 and November 2017. All BMI, sex and age groups were represented. RESULTS: BMI influence over asthma differed in different age groups and genders. All spirometric results and FeNO were influenced by BMI. Concerning asthma characteristics only a later asthma onset with higher BMI values was observed. No other differences were found between different BMI groups. CONCLUSIONS: The effect of BMI on asthma is age dependent, so it should be corrected for age. The most important variations are on FeNO and spirometric results. The specific characteristics of the asthma and obesity phenotype are a greater perception of symptoms with fewer alterations in respiratory function tests and a lower prevalence of atopy, rhinitis and allergy, including allergic asthma. Other characteristics of this phenotype, such as a higher women prevalence or being late-onset or non-eosinophilic asthma, are non-specific for this phenotype.

Clinical and Immunologic Changes due to Subcutaneous Immunotherapy With Cat and Dog Extracts Using an Ultrarush Up-Dosing Phase: A Real-Life Study.

OBJECTIVES: We aimed to evaluate the efficacy of and immunologic changes caused by subcutaneous immunotherapy (SCIT) in patients with allergy to cat and dog. METHODS: The study population comprised patients with rhinitis and/or asthma and allergy to cat or dog from a previous safety study. All patients had specific IgE to cat and/or dog. The SCIT maintenance dose was administered using an infusion pump over a single 4-hour session, followed by monthly administration over 6 months. Data were gathered on clinical outcomes, pulmonary function, FeNO, rhinitis and asthma symptoms, quality of life (QOL), and scores for the Asthma Control Test and symptom visual analog scale were recorded at baseline and then at 1, 3, and 6 months. Specific IgE and IgG antibody responses to cat and dog allergens were determined. RESULTS: The study population comprised 61 patients with a mean age of 35.6 (9.7) years, of whom 40 underwent SCIT for at allergy. A significant improvement was observed in rhinitis and asthma symptoms and in QOL, use of medication, visual analog scale score, and Asthma Control Test score at 1 month; these improvements persisted at month 6. The clinical improvement with cat extract was significantly more marked than with dog extract. Nearly half of the patients (49.09%) had an increase of >0.9 in the ESPRINT-15 QOL in allergic rhinitis questionnaire, and 58.18% had an increase of >0.5 in the Asthma Quality of Life Questionnaire score at month 6. Both differences represent the minimal clinical important difference. A significant increase was observed in specific IgG and IgE to different allergens at 3 and/or 6 months. CONCLUSION: Ultrarush SCIT with cat and dog extracts has substantial clinical value for many patients.

Consensus on the Definition of Control and Remission in Chronic Urticaria.

The terms control and remission and other key terms used in chronic urticaria (CU) such as flare-up, relapse, exacerbation, and recurrence have not been fully defined in the literature. Disease monitoring and treatment goals in clinical practice are not well established. After a qualitative appraisal of available evidence, we aimed to find a consensus definition of control and remission, clarify key terminology, provide guidance on how to monitor the disease, and establish treatment goals in clinical practice. A modified Delphi consensus approach was used. Based on a literature review, a scientific committee provided 137 statements addressing controversial definitions and terms, available patient-reported outcomes (PROs), and recommendations on how to measure therapeutic objectives in CU. The questionnaire was evaluated by 138 expert allergists and dermatologists. A consensus was reached on 105 out of the 137 proposed items (76.6%). The experts agreed that complete control and remission of CU could be defined as the absence of signs or symptoms while on treatment and in the absence of treatment, respectively. Consensus was not reached on the definition of other key terms such as flare-up, exacerbation, and recurrence. The panel agreed that the objective of therapy in CU should be to achieve complete control. PROs that define the degree of control (complete, good, partial, or absence) were established. An algorithm for disease assessment is provided. In conclusion, this work offers consensus definitions and tools that may be useful in the management of patients with CU.

Serum microRNAs Catalog Asthma Patients by Phenotype.

BACKGROUND AND OBJECTIVES: Asthma is a chronic inflammatory condition of the airways with a complex pathophysiology. Stratification of asthma subtypes into phenotypes and endotypes should move the field forward, making treatment more effective and personalized. Eosinophils are the key inflammatory cells involved in severe eosinophilic asthma. Given the health threat posed by eosinophilic asthma, there is a need for reliable biomarkers to identify affected patients and treat them properly with novel biologics. microRNAs (miRNAs) are a promising diagnostic tool. The aim of this study was to identify serum miRNAs that can phenotype asthma patients. METHODS: Serum miRNAs of patients with eosinophilic asthma (N=40) and patients with noneosinophilic asthma (N=36) were evaluated using next-generation sequencing, specifically miRNAs-seq, and selected miRNAs were validated using RT-qPCR. Pathway enrichment analysis of deregulated miRNAs was performed. RESULTS: Next-generation sequencing revealed 15 miRNAs that were expressed differentially between eosinophilic and noneosinophilic asthma patients, although no differences were observed in the miRNome between atopic and nonatopic asthma patients. Of the 15 miRNAs expressed differentially between eosinophilic and noneosinophilic asthma patients, hsa-miR-26a-1-3p and hsa-miR-376a-3p were validated by RT-qPCR. Expression levels of these 2 miRNAs were higher in eosinophilic than in noneosinophilic asthma patients. Furthermore, expression values of hsa-miR-26a-1-3p correlated inversely with peripheral blood eosinophil count, and hsa-miR-376a-3p expression values correlated with FeNO values and the number of exacerbations. Additionally, in silico pathway enrichment analysis revealed that these 2 miRNAs regulate signaling pathways associated with the pathogenesis of asthma. CONCLUSIONS: hsa-miR-26a-1-3p and hsa-miR-376a-3p could be used to differentiate between eosinophilic and noneosinophilic asthma.

Sputum Inflammatory Patterns are Associated with Distinct Clinical Characteristics in Subjects with Occupational Asthma Independently from the Causal Agent.

BACKGROUND AND OBJECTIVES: Clinical heterogeneity in sensitizer-induced occupational asthma (OA) and its relationship to airway inflammatory profiles remain poorly elucidated. To further characterize the interactions between induced sputum inflammatory patterns, asthma-related outcomes and the high- or low-molecular-weight category of causal agents in a large cohort of subjects with OA. METHODS: This multicenter, retrospective, cross-sectional study was conducted among 296 subjects with OA ascertained by a positive specific inhalation challenge who completed induced sputum assessment before and 24 hours after challenge exposure. RESULTS: Multivariate logistic regression analysis revealed that sputum eosinophilia ≥3% was significantly associated with a high dose of inhaled corticosteroid (odds ratio [95% confidence interval], 1.31 [1.11-1.55] for each 250-µg increment in daily dose), short-acting b2-agonist use less than once a day (3.54 [1.82-7.00]), and the level of baseline nonspecific bronchial hyperresponsiveness (mild: 2.48 [1.21-5.08]); moderate/severe: 3.40 [1.44-8.29]). Sputum neutrophilia ≥76% was associated with age (1.06 [1.01-1.11]), male gender (3.34 [1.29-9.99]), absence of corticosteroid use (5.47 [2.09-15.16]), short-acting b2-agonist use once or more a day (4.09 [1.71-10.01]), ≥2 severe exacerbations during the last 12 months at work (4.22 [1.14-14.99]), and isolated early reactions during the SIC (4.45 [1.85-11.59]). CONCLUSIONS: The findings indicate that sputum inflammatory patterns in subjects with OA are associated with distinct phenotypic characteristics and further highlight the differential effects of neutrophils and eosinophils on asthma-related outcomes. These associations between inflammatory patterns and clinical characteristics share broad similarities with what has been reported in nonoccupational asthma and are not related to the type of causal agent.

Functional Examination of the Upper and Lower Airways in Asthma and Respiratory Allergic Diseases: Considerations in the Post-SARS-CoV-2 Era.

Airway examination procedures can potentially transmit infectious diseases to patients and to the health care professionals who perform them via various mechanisms. The COVID-19 pandemic has halted most of the activity of the clinics and laboratories involved in assessment of lung and nasal function, and clear recommendations in this regard have been made. Today, we still do not know for sure what its consequences will be in the short or long term, since important gaps remain in our knowledge of aspects as fundamental as virus transmission mechanisms, pathophysiology, immune response, and diagnosis. In this review, we study the examination techniques used to assess patients with respiratory allergy, asthma, and associated diseases during this period and highlight their possible advantages and disadvantages. Therefore, we focus on exploring the entire upper and lower airways, from the perspective of the safety of both health professionals and patients and their specific characteristics. We also analyze the intrinsic value of these interventions in terms of diagnosis and patient management. The changing situation of COVID-19 may mean that some of the assertions presented in this review will have to be modified in the future. While we seek to ensure a consistently broad approach, some differences in operational details may apply owing to local regulations.

SEAIC Specialty Forum: Analysis of the Current Situation of Allergology in Spain and Outlook for the Future.

BACKGROUND AND OBJECTIVES: Allergology has been a recognized medical specialty in Spain, with fully defined aims and competencies for more than 4 decades. However, in recent years, its visibility seems to have decreased somewhat. Objectives: To identify which specific factors have contributed to the waning of the importance of the specialty and find tangible solutions to consolidate its place as a front-line medical specialty. MATERIAL AND METHODS: An online population survey comprising 60 items of interest was prepared. The degree of agreement and the level of satisfaction with each item were assessed, and implementable initiatives in the short, medium, and long terms were defined in order to provide solutions to the issues identified. RESULTS: The survey was completed by a total of 167 specialists with an average of 18 years' experience. Most were from public reference hospitals, and 29.3% were heads of department. The line of action for which a good degree of agreement was achieved was to promote the inclusion of an allergist in multidisciplinary teams. The priority lines of action were to improve undergraduate and graduate training in allergology and specialized nursing, to identify curricula in Spain, and to develop robust teaching projects. CONCLUSIONS: The results revealed a high degree of homogeneity between professionals. The basic pillars highlighted were as follows: quality training, knowledge, and research in immunotherapy; an innovative portfolio of services endorsed by clinical practice guidelines; and presence in multidisciplinary teams and relevant hospital committees.

Ebastine in the Treatment of Allergic Rhinitis and Urticaria: 30 Years of Clinical Studies and Real-World Experience.

Histamine, acting predominantly via the H1-receptor, is an important mediator of the symptoms of allergy. H1-antihistamines, which stabilize the receptor in its inactive form, are the treatment of choice for some chronic allergic conditions. Ebastine is a well-established secondgeneration oral H1-antihistamine that is administered once daily at a dose of 10-20 mg and is available both as a standard tablet and as a fast-dissolving tablet that disintegrates in the mouth. Ebastine has been shown to relieve symptoms in patients with allergic rhinitis or urticaria in multiple clinical trials. In addition to its antihistamine effects, the drug has modulating effects on the allergic inflammatory process, thus potentially explaining its beneficial effect on nasal obstruction in some patients. Ebastine is generally well tolerated at recommended doses and is one of the lowest-risk antihistamines with respect to adverse cognitive/psychomotor effects, as confirmed by decades of pharmacovigilance. New long-term data confirm its efficacy and tolerability during up to 1 year of treatment in patients with chronic urticaria.

Subcutaneous Immunotherapy With High-Dose Cat and Dog Extracts: A Real-life Study.

BACKGROUND AND OBJECTIVE: Background: Data on the efficacy of immunotherapy administered to patients with cat or dog allergy are scarce. Objective: We aimed to evaluate the safety and efficacy of subcutaneous immunotherapy (SCIT) in patients with allergy to cat and dog dander. METHODS: Consecutive patients with rhinitis and/or asthma related to sensitization to cat or dog dander were included in a pragmatic, real-life, prospective, observational study. All patients had specific IgE to cat, dog, or both. SCIT was administered using an infusion pump over 3 sessions as part of a rush protocol, followed by monthly administration over 12 months. We recorded adverse events, clinical outcomes, pulmonary function, FeNO, symptoms of rhinitis and asthma, quality of life (QoL), Asthma Control Test (ACT) score, and visual analog scale (VAS) score at baseline, 6 months, and 12 months. RESULTS: The study population comprised 66 patients (38 females, 46 allergic to cat and 20 to dog), with ages ranging from 9 to 59 years. During the up-dosing phase, in which the infusion pump was used, 8.1% of doses elicited a systemic reaction and 5.4% caused a local reaction, while 9.3% of doses administered during the maintenance phase (ie, without an infusion pump) induced a systemic reaction. No local reactions were recorded. A significant improvement in FEV1, symptoms of rhinitis and asthma, QoL, use of medication, VAS score, and ACT score was observed at 6 months and continued at 12 months. Clinical improvement with cat extract was significantly better than with dog extract. CONCLUSIONS: High-dose SCIT has substantial clinical value in many cat- and dog-allergic patients.

Adaptation to Spanish and Validation of the Rhinitis Control Assessment Test questionnaire.

BACKGROUND AND OBJECTIVE: The Rhinitis Control Assessment Test (RCAT) is a patient-based questionnaire that is widely used to evaluate control of rhinitis. Objective: To develop and validate a Spanish version of the RCAT (RCATe). METHODS: After translation and cultural adaptation of the original RCAT, this multicenter, observational, prospective study evaluated the properties/attributes of the RCATe by assessing its validity, reliability, responsiveness, effect size, minimal important difference and cut point. RESULTS: The recruited sample comprised 252 allergic rhinitis (AR) patients from 27 allergy and otolaryngology departments in hospitals throughout Spain. Significant and strong correlations were found between the RCATe and the total nasal symptom score and the visual analog scale (-0.79 and -0.77, respectively; P<.0001). The RCATe revealed significant differences between patients grouped in the different categories of severity or duration of AR (P<.001). The internal consistency (Cronbach α) was good (0.84), and the test-retest reliability was moderate (0.54 evaluated by the physician and 0.49 by the patient). The responsiveness to change was high and significant for RCATe (P<.0001) and correlated linearly with the improvement in AR. The overall effect size was 1.62. The cut-off point to identify patients with adequate control of AR was >20 (area under the receiver operating characteristic curve, 0.746; sensitivity, 58.3%; specificity, 90.9%). CONCLUSION: The psychometric evaluation and validation of the RCATe indicated good reliability, validity, and responsiveness, thus suggesting that it is effective for measuring control of AR symptoms by Spanish-speaking patients.

Treatment and Outcome of Patients with Stage IS Testicular Cancer: A Retrospective Study from the Spanish Germ Cell Cancer Group.

PURPOSE: Stage IS testicular cancer is defined by the persistence of elevated serum tumor markers, including α-fetoprotein and/or ß-human chorionic gonadotropin, after orchiectomy without radiological evidence of metastatic disease. Current treatment recommendations include cisplatin based chemotherapy up front but the recommendations are based on limited single center series. MATERIALS AND METHODS: We retrospectively analyzed clinical and pathological characteristics, and long-term outcomes in 110 patients uniformly treated with primary chemotherapy between 1994 and 2016. The primary objective was to evaluate long-term disease-free survival. We also explored factors associated with the need for additional treatment. RESULTS: The elevated prechemotherapy tumor markers were α-fetoprotein in 48% of cases, ß-human chorionic gonadotropin in 14%, and α-fetoprotein and ß-human chorionic gonadotropin in 38%. Median α-fetoprotein and ß-human chorionic gonadotropin values were 71 ng/ml and 80 mIU/ml, respectively. The IGCCCG (International Germ Cell Cancer Collaborative Group) prognostic classification was good in 94% of cases. Mixed nonseminomatous germ cell tumor was found in 78% of cases. Of the patients 103 achieved a complete response to chemotherapy. In 6 patients radiological signs of progressive disease developed during chemotherapy, while 8 experienced relapse after an initial complete response. At a median followup of 108 months 108 patients were alive and disease-free. Five and 10-year disease-free survival rates were 87% and 85%, respectively. The predominance of embryonal carcinoma in the primary tumor was the only factor associated with the probability of needing additional therapy. CONCLUSIONS: Stage IS testicular cancer is more commonly associated with elevated α-fetoprotein, an IGCCCG good prognosis and mixed nonseminomatous germ cell tumor. Treatment with cisplatin based chemotherapy leads to cure in most cases. However, a proportion of patients require the integration of additional therapies, including more frequently when embryonal carcinoma is not predominant.