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.

Transcriptional analysis of nasal polyps fibroblasts reveals a new source of pro-inflammatory signaling in CRSwNP.

BACKGROUND: Fibroblasts and others mesenchymal cells have recently been identified as critical cells triggering tissue-specific inflammatory responses. Persistent activation of fibroblasts inflammatory program has been suggested as an underlying cause of chronic inflammation in a wide range of tissues and pathologies. Nevertheless, the role of fibroblasts in the emergence of chronic inflammation in the upper airway has not been previously addressed. We aimed to elucidate whether fibroblasts could have a role in the inflammatory response in chronic rhinosinusitis with nasal polyps (CRSwNP). METHODOLOGY: We performed whole-transcriptome microarray in fibroblast cultured from CRSwNP samples and confirmed our results by qRT-PCR. We selected patients without other associated diseases in upper airway. To investigate shifts in transcriptional profile we used fibroblasts from nasal polyps and uncinate mucosae from patient with CRSwNP, and fibroblasts from uncinate mucosae from healthy subjects as controls. RESULTS: This study exposes activation of a pro-inflammatory and pro-fibrotic transcriptional program in nasal polyps and CRSwNP fibroblasts when compared to controls. Our Gene-set Enrichment Analysis (GSEA) pointed to common up-regulation of several pro-inflammatory pathways in patients-derived fibroblasts, along with higher mRNA expression levels of cytokines, growth factors and extracellular matrix components. CONCLUSIONS: Our work reveals a potential new source of inflammatory signaling in CRSwNP. Furthermore, our results suggest that deregulated inflammatory signaling in tissue-resident fibroblasts could support a Type-2 inflammatory response. Further investigations will be necessary to demonstrate the functionality of these novel results.

Severity and duration of allergic conjunctivitis: are they associated with severity and duration of allergic rhinitis and asthma?

Summary: Objective. The association of allergic conjunctivitis (AC) with rhinitis and/or asthma is poorly understood. The objective of this study was to apply the Consensus Document for Allergic Conjunctivitis (DECA) criteria for the classification of AC to a population of patients with AC to assess the association between the severity and duration of AC and rhinitis and/or asthma. Methods. Patients with ocular symptoms of AC who participated in the 'Alergológica 2015' study were included. The demographics, classification according to the DECA criteria, etiology, and comorbidities were evaluated by age groups (less or equal than 14 and greater than 14 years). Results. A total of 2,914 patients (age range, 1-90 years) were included in the "Alergológica 2015" study. Of these, 965 patients (33.1%) were diagnosed with AC (77.5% > 14 years). AC was classified as severe, moderate, or mild in 1.8%, 46.4%, and 51.8%, respectively; and as intermittent or persistent in 51.6% and 48.4% of the patients. AC alone occurred in 4% of patients. AC was mainly associated with rhinitis (88.4%), asthma (38.2%), food allergy (8.3%) and atopic dermatitis (3.5%). In allergic respiratory disease rhinitis preceded AC and asthma developed later. The severity and duration of AC was significantly associated with severity and duration of rhinitis (p less than 0.001 for both age groups) and asthma (p less than 0.001 only in adults). Conclusions. The application of the new DECA classification for AC reveals a direct relationship between AC, rhinitis and asthma respect to severity and duration. These relationships suggest that AC should be considered an integral part of the "one airway, one disease" hypothesis.

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.

Smell and Taste Dysfunction in COVID-19 Is Associated With Younger Age in Ambulatory Settings: A Multicenter Cross-Sectional Study.

BACKGROUND AND OBJECTIVE: Since the initial anecdotal reports of coronavirus disease 2019 (COVID-19) from China, a growing number of studies have reported on smell and/or taste dysfunction (STD). Objective: The aim of our study was to investigate the frequency and severity of STD in COVID-19 patients and to evaluate the association with demographic characteristics, hospital admission, symptoms, comorbidities, and blood biomarkers. METHODS: We performed a multicenter cross-sectional study on patients who were positive for SARS-CoV-2 (n=846) and controls (n=143) from 15 Spanish hospitals. Data on STD were collected prospectively using an in-person survey. The severity of STD was categorized using a visual analog scale. We analyzed time to onset, recovery rate, time to recovery, hospital admission, pneumonia, comorbidities, smoking, and symptoms. RESULTS: STD was at least 2-fold more common in COVID-19-positive patients than in controls. COVID-19-positive hospitalized patients were older, with a lower frequency of STD, and recovered earlier than outpatients. Analysis stratified by severity of STD showed that more than half of COVID-19 patients presented severe loss of smell (53.7%) or taste (52.2%); both senses were impaired in >90%. In the multivariate analysis, older age (>60 years), being hospitalized, and increased C-reactive protein were associated with a better sense of smell and/or taste. COVID-19-positive patients reported improvement in smell (45.6%) and taste (46.1%) at the time of the survey; in 90.6% this was within 2 weeks of infection. CONCLUSION: STD is a common symptom in COVID-19 and presents mainly in young and nonhospitalized patients. More studies are needed to evaluate follow-up of chemosensory impairment.

Position paper on nasal obstruction: evaluation and treatment.

Nasal obstruction (NO) is defined as the subjective perception of discomfort or difficulty in the passage of air through the nostrils. It is a common reason for consultation in primary and specialized care and may affect up to 30%-40% of the population. It affects quality of life (especially sleep) and lowers work efficiency. The aim of this document is to agree on how to treat NO, establish a methodology for evaluating and diagnosing it, and define an individualized approach to its treatment. NO can be unilateral or bilateral, intermittent or persistent and may be caused by local or systemic factors, which may be anatomical, inflammatory, neurological, hormonal, functional, environmental, or pharmacological in origin. Directed study of the medical history and physical examination are key for diagnosing the specific cause. NO may be evaluated using subjective assessment tools (visual analog scale, symptom score, standardized questionnaires) or by objective estimation (active anterior rhinomanometry, acoustic rhinometry, peak nasal inspiratory flow). Although there is little correlation between the results, they may be considered complementary and not exclusive. Assessing the impact on quality of life through questionnaires standardized according to the underlying disease is also advisable. NO is treated according to its cause. Treatment is fundamentally pharmacological (topical and/or systemic) when the etiology is inflammatory or functional. Surgery may be necessary when medical treatment fails to complement or improve medical treatment or when other therapeutic approaches are not possible. Combinations of surgical techniques and medical treatment may be necessary.

Allergy rhinitis: similarities and differences between children and adults.

BACKGROUND: Allergic rhinitis (AR) is a highly prevalent disease worldwide. Although a number of studies have described AR, no studies compared children and adult AR populations. The objective was to compare the AR characteristics between two AR cohorts of children and adults. METHODS: Two AR cohorts (children and adults) from Spain were studied through observational cross-sectional multicentre studies. AR was classified based on classical (allergen exposure), original (o-ARIA), and modified (m-ARIA) ARIA criteria. AR was evaluated by Total 4-Symptoms Score (T4SS), and disease severity by Visual Analogue Scale (VAS, 0-100 mm). AR comorbidities were also evaluated. RESULTS: A total of 5,405 patients (1,275 children, 4,130 adults) were studied. According to symptoms duration, intermittent AR was more frequent in children than in adults. Using o-ARIA severity, more children than adults had moderate/severe AR while, using m-ARIA, more children than adults had severe AR. T4SS was higher in adults than in children. Moreover, VAS was also higher in adults than in children. In addition, asthma atopic dermatitis and conjunctivitis were more associated to children than adults with AR, the frequency of this comorbidities increasing according to higher severity. CONCLUSIONS: AR in children was more intermittent, severe, with less symptoms but with more comorbidities than in adults. These results suggest AR has similarities but also significant differences between children and adults.

Allergic rhinitis severity can be assessed using a visual analogue scale in mild, moderate and severe.

BACKGROUND: Allergic rhinitis is a global healthcare problem due to its high prevalence, impact on individuals and socioeconomic burden for the nations. Allergic rhinitis severity evaluation is the key to a correct treatment, prevention of comorbidities and improving the quality of life of patients. This evaluation should be made with a simple, easy, fast but accurate and reliable methodology, both in a primary care and specialist setting. The visual analogue scale (VAS) meets all requirements to be the ideal tool to assess allergic rhinitis severity and has already been validated by using a single cut-off point, but this classification in two degrees of severity suffer from not allocating the patients uniformly and from giving a blind interval to classify the patients when the score is between 5 to 6 cm. METHODOLOGY: The main objective of our study is to describe the optimal cut-off points by using a VAS to discriminate between three degrees of allergic rhinitis severity (mild, moderate, and severe) following the ARIA modified severity criteria that has been previously validated. Sensitivity, specificity, positive and negative predictive values just like receiver operating characteristic curves were used to select the best cut-off values. RESULTS: In a cross-sectional multicentre study with 3,572 patients included we have found that VAS has a significant correlation with nasal symptom score and quality of life and that the best cut-off points to differentiate between mild, moderate an severe allergic rhinitis are a VAS score of 4 and 7, respectively. CONCLUSIONS: Allergic rhinitis severity could be assessed in three degrees by using VAS in a simple, easy, and accurate method.

Relationship between respiratory and food allergy and evaluation of preventive measures.

Food allergy and respiratory allergy are two frequently associated diseases and with an increasing prevalence. Several reports show the presence of respiratory symptoms in patients with food allergy, while certain foods may be related to the development or exacerbation of allergic rhinitis and asthma. The present update focuses on this relationship, revealing a pathogenic and clinical association between food and respiratory allergy. This association is even more intense when the food hypersensitivity is persistent or starts in the early years of life. Food allergy usually precedes respiratory allergy and may be a risk factor for allergic rhinitis and asthma, becoming a relevant clinical marker for severe atopic asthma. Furthermore, the presence of co-existing asthma may enhance life-threatening symptoms occurring during a food allergic reaction. Recommendations for dietary restrictions during pregnancy and breastfeeding to prevent the development of respiratory allergy are controversial and not supported by consistent scientific data. Current recommendations from medical societies propose exclusive breastfeeding during the first four months of life, with the introduction of solid food in the fourth to the seventh month period of life. A delayed introduction of solid food after this period may increase the risk of developing subsequent allergic conditions. Further studies are encouraged to avoid unjustified recommendations involving useless dietary restrictions.

Consensus document on allergic conjunctivitis (DECA).

Allergic conjunctivitis (AC) is an inflammatory disease of the conjunctiva caused mainly by an IgE-mediated mechanism. It is the most common type of ocular allergy. Despite being the most benign form of conjunctivitis, AC has a considerable effect on patient quality of life, reduces work productivity, and increases health care costs. No consensus has been reached on its classification, diagnosis, or treatment. Consequently, the literature provides little information on its natural history, epidemiological data are scarce, and it is often difficult to ascertain its true morbidity. The main objective of the Consensus Document on Allergic Conjunctivitis (Documento dE Consenso sobre Conjuntivitis Alérgica [DECA]), which was drafted by an expert panel from the Spanish Society of Allergology and Spanish Society of Ophthalmology, was to reach agreement on basic criteria that could prove useful for both specialists and primary care physicians and facilitate the diagnosis, classification, and treatment of AC. This document is the first of its kind to describe and analyze aspects of AC that could make it possible to control symptoms.

Specialist-based treatment reduces the severity of allergic rhinitis.

BACKGROUND: Although the treatment of allergic rhinitis (AR) is now well established, its impact on severity has not yet been evaluated. OBJECTIVE: The aim was to analyse specialist-based treatment on AR severity, nasal symptoms and quality of life. METHODS: A longitudinal observational, prospective, multi-centre study with 4 weeks of follow-up was carried out by 141 allergologists and ENT specialists in Spain. Selection criteria were adult patients with AR, clinically diagnosed at least 2 years before, with a total nasal symptom score (TNSS) ≥5, not receiving either antihistamines within the previous week or nasal corticosteroids during the 2 previous weeks. Disease severity using both original Allergic Rhinitis and its Impact on Asthma (o-ARIA) and modified (m-ARIA) classifications, nasal symptoms, and Quality of Life (ESPRINT-15), were measured at baseline and after 4 weeks of treatment. RESULTS: Among the recruited AR patients (n = 707, 58% women), 39.3% were intermittent and 60.7% persistent, 40.2% had asthma and 61.4% conjunctivitis. Most patients were treated with second generation antihistamines in monotherapy (63.2%) or in combination with intranasal corticosteroids (31.5%). While using o-ARIA, 96.9% of patients had 'moderate/severe' AR, the m-ARIA discriminated between 'moderate' (55.4%) and severe (41.5%) AR, at baseline. After 4 weeks of treatment, improvement was found on disease severity (P < 0.0001), TNSS (8.2 ± 1.8 vs. 3.5 ± 2.3, P < 0.0001) and Quality of Life (ESPRINT-15 global score: 3.0 ± 1.2 vs. 1.1 ± 1.0, P < 0.0001). CONCLUSIONS: Specialist-based treatment reduces AR severity, evaluated using the m-ARIA classification for the first time, in addition to the improvement of nasal symptoms and quality of life. CLINICAL RELEVANCE: Specialist-based treatment improves AR severity, in addition to nasal symptoms and quality of life. However, no matter the treatment option some AR patients remain severe and need further follow-up.

Use of second generation H1 antihistamines in special situations.

Antihistamine drugs are one of the therapeutic classes most used at world level, at all ages and in multiple situations. Although in general they have a good safety profile, only the more recent drugs (second generation antihistamines) have been studied specifically with regard to the more important safety aspects. Given the variety of antihistamine drugs, they cannot all be considered equivalent in application to various special clinical situations, so that the documented clinical experience must be assessed in each case or, in the absence of such, the particular pharmacological characteristics of each molecule for the purpose of recommendation in these special situations. In general, there are few clinical studies published for groups of patients with kidney or liver failure, with concomitant multiple pathologies (such as cardiac pathology), in extremes of age (paediatrics or geriatrics) and in natural stages such as pregnancy or lactation, but these are normal situations and it is more and more frequent (among the elderly) for antihistamine drugs to be recommended. This review sets out the more relevant details compiled on the use of antihistamines in these special situations.

H1 antihistamines and benzodiazepines. Pharmacological interactions and their impact on cerebral function.

Antihistamines (AH) have been classified into first and second generation according to their pharmacokinetic properties, structural characteristics and adverse effects. The effects on the central nervous system (CNS) are determined basically by their capacity to cross the hematoencephalic barrier and attach to central H1 receptors. Benzodiazepines (BZD) are drugs with effects on the CNS following their union to the specific location of GABA receptors type A. At low doses, the BZD have sedative and anticonvulsive effects, and as the dose increases it leads to sedation, amnesia and finally unconsciousness. Various studies have been made on the possible interaction between the BZD and the AH H1 with special attention to their effect on the CNS. In some cases these were studies to assess the safety of this association and in others, the aim was different: to see if their joint administration gives a better therapeutic result in pathology related with anxiety syndrome or insomnia. In general it can be said that first generation AH interact with the BZD increasing the sedative effects of the latter. However, second generation AH do not increase these sedative effects, which makes them the chosen drugs to treat allergic rhinitis/rhino-conjunctivitis and urticaria in patients also receiving BZD.

Antihistamines in drivers, aircrew and occupations of risk.

The most commonly occurring allergic diseases can involve a daytime drowsiness associated with the condition itself. The antihistamines used in their treatment can also have central effects and affect certain occupations concerned with risk, road safety and maritime and air navigation. Cognitive tests, experimental studies and epidemiological data recommend avoiding 1st generation antihistamines for people who must drive regularly and/or professions concerned with safety. Although there are no comparative studies on real driving between 1st and 2nd generation antihistamines, in this type of patients there should be a preference for prescribing those with least possible central effect, especially those which are a good substrate for transmembrane transporter pumps such as P-glycoprotein and therefore have a low capacity for crossing the hematoencephalic barrier, thus allowing a broader window for therapy. In this sense, bilastine is a good P-glycoprotein substrate and shows good tolerance at CNS level, in both psychometric trials and real driving test protocols, even at double the dose recommended in the technical file.

ESPRINT-15 questionnaire (Spanish version): reference values according to disease severity using both the original and the modified ARIA classifications.

OBJECTIVE: ESPRINT-15 is a specific and validated instrument to measure health-related quality of life in adults with allergic rhinitis. The aim of this study was to obtain new reference values based on disease severity using both the original and the modified versions of the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines. METHODS: ESPRINT-15 was administered to a representative sample of adults with allergic rhinitis in Spain. As in a previous study by our group, means and percentiles were analyzed for 16 quotas based on gender, allergic rhinitis type (intermittent vs persistent), and 4 symptom intensity groups according to the total symptom score (TSS4). The novel aspect of the present study was our application the severity criteria proposed by both the original and the modified ARIA classifications. RESULTS: Of the 2756 patients in our previous dataset, 2580 were included in the present analysis. In terms of symptom severity, women ha relatively more intense symptoms than men with both ARIA classifications. In fact, using only the modified ARIA classification, we were abl to determine that severe rhinitis is moderately more frequent in women (27% vs 23%), although the difference is not statistically significant. CONCLUSIONS: The new set of reference values enables the ESPRINT-15 questionnaire to be adapted to the current severity classification Consequently, this quality of life tool (http://www.seaic.org/inicio/esprint) can be easily used and better interpreted in daily clinical practice.

Validation of the modified allergic rhinitis and its impact on asthma (ARIA) severity classification in allergic rhinitis children: the PEDRIAL study.

BACKGROUND: A modified allergic rhinitis and its impact on asthma (ARIA) (m-ARIA) criterion to classify the severity of allergic rhinitis (AR) has recently been validated in both treated and untreated adult patients; however, such information in children is lacking. The aim of this study was to validate this m-ARIA severity criterion, which allows for discrimination between moderate and severe AR, in a large pediatric patient sample population. METHODS: The m-ARIA classification categorizes AR severity into mild (no affected items), moderate (1-3 affected items), and severe (all four affected items). We applied this modified criterion to untreated AR pediatric patients aged 6-12 years, through an observational, cross-sectional, and multicenter study. AR symptoms were assessed using the Total Four Symptom Score (T4SS), and the severity was evaluated by both ARIA severity items and visual analogue scale (VAS). RESULTS: Allergic rhinitis pediatric patients (N = 1269) from 271 centers were included. Among them, 59.5% had intermittent and 40.5% persistent disease; 89.9% had moderate/severe AR using the original ARIA (o-ARIA) classification and 59.5% had moderate, while 30.5% had severe AR using the m-ARIA criterion. Using the m-ARIA, significantly higher T4SS and VAS scores were obtained when comparing severe with moderate AR. CONCLUSIONS: The m-ARIA severity classification is a useful clinical tool to discriminate moderate from severe AR among untreated pediatric patients.

Rupatadine improves nasal symptoms, quality of life (ESPRINT-15) and severity in a subanalysis of a cohort of Spanish allergic rhinitis patients.

BACKGROUND: According to current guidelines, new second-generation oral Hi-antihistamines, as well as intranasal corticosteroids (ICSs), are recommended for the treatment of allergic rhinitis (AR) in adults and children. OBJECTIVE: To assess changes in AR severity, in addition to nasal symptoms and health-related quality of life (HRQoL), after 4 weeks of treatment with rupatadine in a cohort of AR patients. METHODS: A subanalysis of a longitudinal, observational, prospective, multicenter Spanish study was carried out in spring-summer 2007. Enrolled patients had a clinical diagnosis of AR of at least 2 years' evolution, a total nasal symptom score (TNSS) of at least 5, and had not received antihistamines in the previous week or ICSs in the previous 2 weeks. HRQoL (ESPRINT-15 questionnaire), disease severity (using both the original and modified Allergic Rhinitis and its Impact on Asthma [ARIA] classifications), and nasal symptoms (TNSS) were measured at baseline and after 4 weeks of rupatadine treatment. RESULTS: Data from a cohort of 360 patients treated with rupatadine were analyzed (57.2% women, 42.5% with intermittent AR, 36.4% with asthma, and 61.7% with conjunctivitis). After 4 weeks of treatment, the patients showed a significantly lower mean (SD) TNSS (8.2 [1.9] vs 3.1 [2.1], P < .001), a significant improvement in HRQoL (3.0 [1.2] vs 1.0 [0.9], P < .001) and significantly reduced AR severity (P < .0001). CONCLUSIONS: In addition to an improvement in nasal symptoms and HRQoL, rupatadine reduced AR severity after 4 weeks of treatment.

Effect of bilastine upon nasal obstruction.

H1 antihistamines constitute one of the main references for the treatment of allergic rhinitis. Classically, these drugs have been considered effective in controlling sneezing, rhinorrhea and itching, though they have not been regarded as particularly effective in application to nasal obstruction. The most recent studies, involving second-generation H1 antihistamines (desloratadine, fexofenadine, levocetirizine, rupatadine), have shown these drugs to offer effects upon nasal obstruction significantly superior to those of placebo. The present review examines the effect of bilastine, a new, potent and highly specific H1 antihistamine without sedative effects or cardiac toxicity, upon nasal obstruction. The analysis of the data from the different clinical trials indicates that in patients with allergic rhinitis, the effect of bilastine upon nasal obstruction is superior to that of placebo and similar to that of other second-generation H1 antihistamines, manifesting within 24 hours after the start of treatment.