EUFOREA/EPOS2020 statement on the clinical considerations for chronic rhinosinusitis with nasal polyps care.

Following the European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) treatment algorithm for chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP), patients suffering from severe uncontrolled CRSwNP are recommended to receive oral corticosteroids, (revision) sinus surgery, systemic biologicals and/or aspirin treatment after desensitization (ATAD). Given the major differences in indications, outcomes, practical considerations, risks and costs of these key pillars of treatment, there is a growing need to define criteria for each treatment option and list the clinically relevant and major considerations for them. This EUFOREA document therefore provides an expert panel overview of the expected outcomes, specific considerations and (contra)indications of the five major treatment arms of severe uncontrolled CRSwNP: oral corticosteroids, primary and revision sinus surgery, biological treatment and ATAD. This overview of treatment considerations is needed to allow physicians and patients to consider the different options in the context of providing optimal and personalized care for severe uncontrolled CRSwNP. In conclusion, the five major treatment options for severe uncontrolled CRSwNP have intrinsic advantages, specific indications and considerations that are of importance to the patient, the physician and the society. This EUFOREA statement supports the unmet need to define criteria for the indication of every treatment pillar of CRSwNP.

EUFOREUM Berlin 2023: Optimizing care for type 2 inflammatory diseases from clinic to AI: A pediatric focus.

The European Forum for Research and Education in Allergy and Airways diseases (EUFOREA) organized its bi-annual forum EUFOREUM in Berlin in November 2023. The aim of EUFOREUM 2023 was to highlight pediatric action plans for prevention and optimizing care for type 2 inflammatory conditions starting in childhood, with a focus on early-stage diagnosis, ensuring neither under- nor overdiagnosis, optimal care, and suggestions for improvement of care. EUFOREA is an international not-for-profit organization forming an alliance of all stakeholders dedicated to reducing the prevalence and burden of chronic respiratory diseases through the implementation of optimal patient care via educational, research, and advocacy activities. The inclusive and multidisciplinary approach of EUFOREA was reflected in the keynote lectures and faculty of the virtual EUFOREUM 2023 (www.euforea.eu/euforeum) coming from the pediatric, allergology, pulmonology, ENT, dermatology, primary health care fields and patients around the central theme of type 2 inflammation. As most type 2 inflammatory conditions may start in childhood or adolescence, and most children have type 2 inflammation when suffering from a respiratory or skin disease, the moment has come to raise the bar of ambitions of care, including prevention, remission and disease modification at an early stage. The current report provides a comprehensive overview of key statements by the faculty of the EUFOREUM 2023 and the ambitions of EUFOREA allowing all stakeholders in the respiratory field to be updated and ready to join forces in Europe and beyond.

European Academy of Allergy and Clinical Immunology position paper on endoscopic scoring of nasal polyposis.

Nasal endoscopy is not only used for the diagnosis of chronic rhinosinusitis with nasal polyps (CRSwNP), but also for monitoring the response to therapy playing an important role in both daily practice and research. In contrast to patient-reported outcomes, endoscopic nasal polyp scoring by independent blinded readers is an objective measurement, not influenced by the placebo effect. It is safer and cheaper compared with computed tomography imaging and therefore, better suited for regular assessments of the extent of the disease. Since the early 90s, a variety of endoscopic staging methods have been proposed and used in clinical research, making it hard to compare results from different studies. This paper resulted from a task force with experts in the field of CRSwNP, originated by the Ear, Nose and Throat section of the European Academy of Allergy and Clinical Immunology and aims to provide a unified endoscopic NP scoring system that can serve as a reference standard for researchers, but also as a useful tool for practitioners involved in the management of CRSwNP.

A retrospective study on long-term efficacy of intranasal lysine-aspirin in controlling NSAID-exacerbated respiratory disease.

PURPOSE: Aspirin treatment after desensitization (ATAD) represents an effective therapeutic option suitable for NSAID-exacerbated respiratory disease (N-ERD) patients with recalcitrant disease. Intranasal administration of lysine-aspirin (LAS) has been suggested as a safer and faster route than oral ATAD but evidence for its use is less strong. We investigated nasal LAS therapy long-term efficacy based on objective outcomes, smell function, polyp recurrence and need for surgery or rescue therapy. Clinical biomarkers predicting response to intranasal LAS, long-term side effects and consequences of discontinuing treatment have been evaluated. METHODS: A retrospective analysis of a database of 60 N-ERD patients seen between 2012 and 2020 was performed in March 2021. They were followed up at 3-months, 1-, 2- and 3-years with upper and lower airway functions assessed at each follow-up. RESULTS: Higher nasal airflow and smell scores were found at each follow-up in patients taking LAS (p < 0.001 and p = 0.048 respectively). No influence of LAS on pulmonary function measurements was observed. Patient on intranasal LAS showed a lower rate of revision sinus surgery when compared to those who discontinued the treatment (p < 0.001). None of the variables studied was found to influence LAS treatment response. CONCLUSION: Our study demonstrates the clinical effectiveness of long-term intranasal LAS in the management of N-ERD in terms of improved nasal airflow and olfaction and a reduced need for revision sinus surgery. Intranasal LAS is safe, being associated with a lower rate of side effects when compared to oral ATAD. However, discontinuation of the treatment at any stage is associated with a loss of clinical benefit.

Heterogeneity of the pharmacologic treatment of allergic rhinitis in Europe based on MIDAS and OTCims platforms.

BACKGROUND: The practice of allergology varies widely between countries, and the costs and sales for the treatment of rhinitis differ depending on practices and health systems. To understand these differences and their implications, the rhinitis market was studied in some of the EU countries. METHODS: We conducted a pharmaco-epidemiological database analysis to assess the medications that were being prescribed for allergic rhinitis in the years 2016, 2017 and 2018. We used the IQVIA platforms for prescribed medicines (MIDAS®- Meaningful Integration of Data, Analytics and Services) and for OTC medicines (OTC International Market Tracking-OTCims). We selected the five most important markets in the EU (France, Germany, Italy, Poland and Spain). RESULTS: Intranasal decongestants were excluded from the analyses because they are rarely prescribed for allergic rhinitis. For both Standard Units (SU) and costs, France is leading the other countries. In terms of SU, the four other countries are similar. For costs, Poland is lower than the three others. However, medication use differs largely. For 2018, in SU, intranasal corticosteroid is the first treatment in Poland (70.0%), France (51.3%), Spain (51.1%) and Germany (50.3%), whereas the Italian market is dominated by systemic antihistamines (41.4%) followed by intranasal corticosteroids (30.1%). Results of other years were similar. DISCUSSION: There are major differences between countries in terms of rhinoconjunctivitis medication usage.

Placebo effects in allergen immunotherapy-An EAACI Task Force Position Paper.

The placebo (Latin "I will please") effect commonly occurs in clinical trials. The psychological and physiological factors associated with patients' expectations about a treatment's positive and negative effects have yet to be well characterized, although a functional prefrontal cortex and intense bidirectional communication between the central nervous system and the immune system appear to be prerequisites for a placebo effect. The use of placebo raises certain ethical issues, especially if patients in a placebo group are denied an effective treatment for a long period of time. The placebo effect appears to be relatively large (up to 77%, relative to pretreatment scores) in controlled clinical trials of allergen immunotherapy (AIT), such as the pivotal, double-blind, placebo-controlled (DBPC) randomized clinical trials currently required by regulatory authorities worldwide. The European Academy of Allergy and Clinical Immunology (EAACI) therefore initiated a Task Force, in order to better understand the placebo effect in AIT and its specific role in comorbidities, blinding issues, adherence, measurement time points, variability and the natural course of the disease. In this Position Paper, the EAACI Task Force highlights several important topics regarding the placebo effect in AIT such as a) regulatory aspects, b) neuroimmunological and psychological mechanisms, c) placebo effect sizes in AIT trials, d) methodological limitations in AIT trial design and e) potential solutions in future AIT trial design. In conclusion, this Position Paper aims to examine the methodological problem of placebo in AIT from different aspects and also to highlight unmet needs and possible solutions for future trials.

MP-AzeFlu in Moderate-to-Severe Allergic Rhinitis: A Literature Review.

Allergic rhinitis (AR) is prevalent, and many patients present with moderate-to-severe symptomatic disease. The majority of patients are not satisfied with their AR treatment, despite the use of concurrent medications. These gaps underscore the need for treatment with more effective options for moderate-to-severe AR. The authors' objective was to review systematically the efficacy and safety of MP-AzeFlu for the treatment of AR. The primary outcomes studied were nasal, ocular, and total symptoms. Other outcomes included time to onset and of AR control, quality of life, and safety. Searches of PubMed and Cochrane databases were conducted on May 14, 2020, with no date restrictions, to identify publications reporting data on MP-AzeFlu. Clinical studies of any phase were included. Studies were excluded if they were not in English, were review articles, did not discuss the safety and efficacy of MP-AzeFlu for AR symptoms. Treatment of AR with MP-AzeFlu results in effective, sustained relief of nasal and ocular symptoms, and faster onset and time to control compared with intranasal azelastine or fluticasone propionate. Long-term use of MP-AzeFlu was safe, with benefits in children, adults, and adults aged ≥65 years. Other treatment options, including fluticasone propionate and azelastine alone or the combination of intranasal corticosteroids and oral antihistamine, do not provide the same level of efficacy as MP-AzeFlu in terms of rapid and sustained relief of the entire AR symptom complex. Furthermore, MP-AzeFlu significantly improves patient quality of life. MP-AzeFlu is a currently available combination that may satisfy all these patient needs and expectations.

Effect of Specific Immunoglobulin E Response and Comorbidities on Effectiveness of MP-AzeFlu in a Real-Life Study.

INTRODUCTION: Phenotyping allergic rhinitis (AR) by immunoglobulin E (IgE) sensitivity and comorbidities may help characterize AR and provide a framework for treatment decisions. METHODS: This prospective, noninterventional study evaluated the effectiveness of MP-AzeFlu (azelastine hydrochloride plus fluticasone propionate intranasal spray formulation) across AR phenotypes. Patients with moderate-to--severe seasonal or perennial AR for whom MP-AzeFlu was prescribed were enrolled. AR subpopulations (ARPs) were assigned based on the classification of IgE response and comorbidities. AR symptoms over the previous 24 h were documented using an AR visual analog scale (AR-VAS), with ratings from "not at all bothersome" (0 mm) to "extremely bothersome" (100 mm), at the inclusion visit and on days 1, 3, 7, and the last day of the study (approximately day 14). AR quality-of-life measures were recorded using a VAS. RESULTS: A total of 1,103 patients with AR were included. Mean baseline AR-VAS scores ranged from 70.3 to 75.1 mm (severe) across ARPs. In the overall population, 86.6% of patients responded to treatment (AR-VAS score <50 mm on ≥1 days). In the ARPs, response rates ranged from 79.3 to 89.6%. Mean reduction in AR-VAS scores ranged from 47.9 to 40.9 mm, a decrease from severe to mild across all ARPs. Quality-of-life VAS scores were similarly reduced in the total population and ARPs. DISCUSSION/CONCLUSION: MP-AzeFlu treatment reduced VAS severity and quality-of-life scores from baseline in the total population and ARPs, supporting MP-AzeFlu as an effective treatment for all patients with moderate-to-severe AR, regardless of AR phenotype or comorbidities.

Allergic rhinitis and asthma symptoms in a real-life study of MP-AzeFlu to treat multimorbid allergic rhinitis and asthma.

BACKGROUND: Asthma affects up to nearly 40% of patients with allergic rhinitis (AR). Poor control of AR symptoms is associated with poor asthma control. The goal of this study was to evaluate the effect of AR treatment with MP-AzeFlu on symptoms of AR as well as symptoms of asthma. METHODS: This prospective study used a visual analog scale (VAS) to assess symptoms of AR and asthma before and after treatment with MP-AzeFlu (Dymista®; azelastine hydrochloride plus fluticasone propionate; 1 spray in each nostril twice daily for 2 weeks). Participants suffered from moderate-to-severe AR according to Allergic Rhinitis and its Impact on Asthma criteria, with acute AR symptoms (AR-VAS scores ≥ 50 mm) on inclusion day. In addition to symptom assessment, patients recorded the impact of AR symptoms on quality-of-life measures before, during, and at the conclusion of the treatment period (approximately 14 days). Patients self-reported change in frequency of their usage of asthma reliever medication on the last day of treatment. RESULTS: Of 1103 study participants, 267 (24.2%) had comorbid asthma. These participants reported using a mean of 5.1 puffs of asthma reliever medication in the week before treatment with MP-AzeFlu. A total of 81.8% of patients with comorbid asthma responded to AR therapy (AR-VAS < 50 mm on at least 1 study day). Among patients with AR and comorbid asthma, MP-AzeFlu was associated with improved VAS scores across all study parameters, including AR symptom severity, asthma symptom severity, sleep quality, daily work or school activities, daily social activities, and daily outdoor activities. Asthma symptom severity decreased from a mean of 48.9 mm to 24.1 mm on the VAS. Self-reported frequency of asthma reliever medication use was reduced for 57.6% of participants (n = 139/241). CONCLUSION: MP-AzeFlu used to relieve AR symptoms was associated with reduced asthma symptom VAS scores and frequency of asthma reliever medication usage. Changes in overall symptoms of AR and asthma were correlated.

Diagnosis and management of NSAID-Exacerbated Respiratory Disease (N-ERD)-a EAACI position paper.

NSAID-exacerbated respiratory disease (N-ERD) is a chronic eosinophilic, inflammatory disorder of the respiratory tract occurring in patients with asthma and/or chronic rhinosinusitis with nasal polyps (CRSwNP), symptoms of which are exacerbated by NSAIDs, including aspirin. Despite some progress in understanding of the pathophysiology of the syndrome, which affects 1/10 of patients with asthma and rhinosinusitis, it remains a diagnostic and therapeutic challenge. In order to provide evidence-based recommendations for the diagnosis and management of N-ERD, a panel of international experts was called by the EAACI Asthma Section. The document summarizes current knowledge on the pathophysiology and clinical presentation of N-ERD pointing at significant heterogeneity of this syndrome. Critically evaluating the usefulness of diagnostic tools available, the paper offers practical algorithm for the diagnosis of N-ERD. Recommendations for the most effective management of a patient with N-ERD stressing the potential high morbidity and severity of the underlying asthma and rhinosinusitis are discussed and proposed. Newly described sub-phenotypes and emerging sub-endotypes of N-ERD are potentially relevant for new and more specific (eg, biological) treatment modalities. Finally, the document defines major gaps in our knowledge on N-ERD and unmet needs, which should be addressed in the future.

Cluster Analysis of Chronic Rhinosinusitis Suggests Gender-Based Differences.

PURPOSE: We aimed to evaluate the interaction between the overall severity of chronic rhinosinusitis (CRS) before treatment and subjective improvement following surgical or medical treatment. PROCEDURES: A group of 97 patients with CRS completed the visual analog scale (VAS) symptom score and the Sino-Nasal Outcome Test 22 (SNOT-22) questionnaire in the moment of their sinus computerized tomography (CT) scan. Data were analyzed via a 2-step cluster analysis based on gender, polyp presence, CT scan, and VAS scores for symptoms. RESULTS: There were 3 clusters: the first cluster comprised 37 female patients with CRS without nasal polyps (CRSsNP), the second cluster comprised 30 patients with CRS and NP (CRSwNP; 15 males and 15 females); and third cluster had 30 male patients with CRS without NP (CRSsNP). Different symptom patterns between clusters were identified. After adjustment for polyp presence, gender, eosinophilia (p = 0.021), and the SNOT-22 score (p = 0.005) were found to be better outcome predictors than the CT score (p = 0.26). CONCLUSION: Long-term patient satisfaction is significantly associated with the subjective symptom severity prior to treatment, i.e., postnasal drip and overall disease severity (SNOT-22 score), but not with the objective severity of the disease (CT score and inflammation).

Saline irrigation for allergic rhinitis.

BACKGROUND: Allergic rhinitis is a common condition affecting both adults and children. Patients experience symptoms of nasal obstruction, rhinorrhoea, sneezing and nasal itching, which may affect their quality of life.Nasal irrigation with saline (salty water), also known as nasal douching, washing or lavage, is a procedure that rinses the nasal cavity with isotonic or hypertonic saline solutions. It can be performed with low positive pressure from a spray, pump or squirt bottle, with a nebuliser or with gravity-based pressure in which the person instils saline into one nostril and allows it to drain out of the other. Saline solutions are available over the counter and can be used alone or as an adjunct to other therapies. OBJECTIVES: To evaluate the effects of nasal saline irrigation in people with allergic rhinitis. SEARCH METHODS: The Cochrane ENT Information Specialist searched the ENT Trials Register; CENTRAL; Ovid MEDLINE; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 23 November 2017. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing nasal saline irrigation, delivered by any means and with any volume, tonicity and alkalinity, with (a) no nasal saline irrigation or (b) other pharmacological treatments in adults and children with allergic rhinitis. We included studies comparing nasal saline versus no saline, where all participants also received pharmacological treatment (intranasal corticosteroids or oral antihistamines). DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. Primary outcomes were patient-reported disease severity and a common adverse effect - epistaxis. Secondary outcomes were disease-specific health-related quality of life (HRQL), individual symptom scores, general HRQL, the adverse effects of local irritation or discomfort, ear symptoms (pain or pressure) and nasal endoscopy scores. We used GRADE to assess the quality of the evidence for each outcome; this is indicated in italics. MAIN RESULTS: We included 14 studies (747 participants). The studies included children (seven studies, 499 participants) and adults (seven studies, 248 participants). No studies reported outcomes beyond three months follow-up. Saline volumes ranged from 'very low' to 'high' volume. Where stated, studies used either hypertonic or isotonic saline solution.Nasal saline versus no saline treatmentAll seven studies (112 adults; 332 children) evaluating this comparison used different scoring systems for patient-reported disease severity, so we pooled the data using the standardised mean difference (SMD). Saline irrigation may improve patient-reported disease severity compared with no saline at up to four weeks (SMD -1.32, 95% confidence interval (CI) -1.84 to -0.81; 407 participants; 6 studies; low quality) and between four weeks and three months (SMD -1.44, 95% CI -2.39 to -0.48; 167 participants; 5 studies; low quality). Although the evidence was low quality the SMD values at both time points are considered large effect sizes. Subgroup analysis showed the improvement in both adults and children. Subgroup analyses for volume and tonicity were inconclusive due to heterogeneity.Two studies reported methods for recording adverse effects and five studies mentioned them. Two studies (240 children) reported no adverse effects (epistaxis or local discomfort) in either group and three only reported no adverse effects in the saline group.One study (48 children) reported disease-specific HRQL using a modified RCQ-36 scale. It was uncertain whether there was a difference between the groups at any of the specified time points (very low quality). No other secondary outcomes were reported.Nasal saline versus no saline with adjuvant use of intranasal steroids or oral antihistamines Three studies (40 adults; 79 children) compared saline with intranasal steroids versus intranasal steroids alone; one study (14 adults) compared saline with oral antihistamines versus oral antihistamines alone. It is uncertain if there is a difference in patient-reported disease severity at up to four weeks (SMD -0.60, 95% CI -1.34 to 0.15; 32 participants; 2 studies; very low quality) or from four weeks to three months (SMD -0.32, 95% CI -0.85 to 0.21; 58 participants; 2 studies; very low quality). Although none of the studies reported methods for recording adverse effects, three mentioned them: one study (40 adults; adjuvant intranasal steroids) reported no adverse effects (epistaxis or local discomfort) in either group; the other two only reported no adverse effects in the saline group.It is uncertain if saline irrigation in addition to pharmacological treatment improved disease-specific HRQL at four weeks to three months, compared with pharmacological treatment alone (SMD -1.26, 95% CI -2.47 to -0.05; 54 participants; 2 studies; very low quality). No other secondary outcomes were reported.Nasal saline versus intranasal steroidsIt is uncertain if there was a difference in patient-reported disease severity between nasal saline and intranasal steroids at up to four weeks (MD 1.06, 95% CI -1.65 to 3.77; 14 participants; 1 study), or between four weeks and three months (SMD 1.26, 95% CI -0.92 to 3.43; 97 participants; 3 studies), or indisease-specific HRQL between four weeks and three months (SMD 0.01, 95% CI -0.73 to 0.75; 83 participants; 2 studies). Only one study reported methods for recording adverse effects although three studies mentioned them. One (21 participants) reported two withdrawals due to adverse effects but did not describe these or state which group. Three studies reported no adverse effects (epistaxis or local discomfort) with saline, although one study reported that 27% of participants experienced local discomfort with steroid use. No other secondary outcomes were reported. AUTHORS' CONCLUSIONS: Saline irrigation may reduce patient-reported disease severity compared with no saline irrigation at up to three months in both adults and children with allergic rhinitis, with no reported adverse effects. No data were available for any outcomes beyond three months. The overall quality of evidence was low or very low. The included studies were generally small and used a range of different outcome measures to report disease severity scores, with unclear validation. This review did not include direct comparisons of saline types (e.g. different volume, tonicity).Since saline irrigation could provide a cheap, safe and acceptable alternative to intranasal steroids and antihistamines further high-quality, adequately powered research in this area is warranted.

Reduced need for surgery in severe nasal polyposis with mepolizumab: Randomized trial.

BACKGROUND: Patients with eosinophilic nasal polyposis frequently require surgery, and recurrence rates are high. OBJECTIVE: We sought to assess the efficacy and safety of mepolizumab versus placebo for severe bilateral nasal polyposis. METHODS: This randomized, double-blind, placebo-controlled trial recruited patients aged 18 to 70 years with recurrent nasal polyposis requiring surgery. Patients received 750 mg of intravenous mepolizumab or placebo every 4 weeks for a total of 6 doses in addition to daily topical corticosteroid treatment. The primary end point was the number of patients no longer requiring surgery at Week 25 based on a composite end point of endoscopic nasal polyp score and nasal polyposis severity visual analog scale (VAS) score. Secondary end points included change in nasal polyposis severity VAS score, endoscopic nasal polyp score, improvement in individual VAS symptoms (rhinorrhea, mucus in throat, nasal blockage, and sense of smell), patient-reported outcomes, and safety. RESULTS: One hundred five patients received mepolizumab (n = 54) or placebo (n = 51). A significantly greater proportion of patients in the mepolizumab group compared with the placebo group no longer required surgery at Week 25 (16 [30%] vs 5 [10%], respectively; P = .006). There was a significant improvement in nasal polyposis severity VAS score, endoscopic nasal polyp score, all individual VAS symptom scores, and Sino-Nasal Outcome Test patient-reported outcome score in the mepolizumab compared with placebo groups. Mepolizumab's safety profile was comparable with that of placebo. CONCLUSION: In patients with recurrent nasal polyposis receiving topical corticosteroids who required surgery, mepolizumab treatment led to a greater reduction in the need for surgery and a greater improvement in symptoms than placebo.

Inflammatory endotypes of chronic rhinosinusitis based on cluster analysis of biomarkers.

BACKGROUND: Current phenotyping of chronic rhinosinusitis (CRS) into chronic rhinosinusitis with nasal polyps (CRSwNP) and chronic rhinosinusitis without nasal polyps (CRSsNP) might not adequately reflect the pathophysiologic diversity within patients with CRS. OBJECTIVE: We sought to identify inflammatory endotypes of CRS. Therefore we aimed to cluster patients with CRS based solely on immune markers in a phenotype-free approach. Secondarily, we aimed to match clusters to phenotypes. METHODS: In this multicenter case-control study patients with CRS and control subjects underwent surgery, and tissue was analyzed for IL-5, IFN-γ, IL-17A, TNF-α, IL-22, IL-1ß, IL-6, IL-8, eosinophilic cationic protein, myeloperoxidase, TGF-ß1, IgE, Staphylococcus aureus enterotoxin-specific IgE, and albumin. We used partition-based clustering. RESULTS: Clustering of 173 cases resulted in 10 clusters, of which 4 clusters with low or undetectable IL-5, eosinophilic cationic protein, IgE, and albumin concentrations, and 6 clusters with high concentrations of those markers. The group of IL-5-negative clusters, 3 clusters clinically resembled a predominant chronic rhinosinusitis without nasal polyps (CRSsNP) phenotype without increased asthma prevalence, and 1 cluster had a TH17 profile and had mixed CRSsNP/CRSwNP. The IL-5-positive clusters were divided into a group with moderate IL-5 concentrations, a mixed CRSsNP/CRSwNP and increased asthma phenotype, and a group with high IL-5 levels, an almost exclusive nasal polyp phenotype with strongly increased asthma prevalence. In the latter group, 2 clusters demonstrated the highest concentrations of IgE and asthma prevalence, with all samples expressing Staphylococcus aureus enterotoxin-specific IgE. CONCLUSION: Distinct CRS clusters with diverse inflammatory mechanisms largely correlated with phenotypes and further differentiated them and provided a more accurate description of the inflammatory mechanisms involved than phenotype information only.

MACVIA clinical decision algorithm in adolescents and adults with allergic rhinitis.

The selection of pharmacotherapy for patients with allergic rhinitis (AR) depends on several factors, including age, prominent symptoms, symptom severity, control of AR, patient preferences, and cost. Allergen exposure and the resulting symptoms vary, and treatment adjustment is required. Clinical decision support systems (CDSSs) might be beneficial for the assessment of disease control. CDSSs should be based on the best evidence and algorithms to aid patients and health care professionals to jointly determine treatment and its step-up or step-down strategy depending on AR control. Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR [fighting chronic diseases for active and healthy ageing]), one of the reference sites of the European Innovation Partnership on Active and Healthy Ageing, has initiated an allergy sentinel network (the MACVIA-ARIA Sentinel Network). A CDSS is currently being developed to optimize AR control. An algorithm developed by consensus is presented in this article. This algorithm should be confirmed by appropriate trials.

Saline irrigation for chronic rhinosinusitis.

BACKGROUND: This review is one of six looking at the primary medical management options for patients with chronic rhinosinusitis.Chronic rhinosinusitis is common and is characterised by inflammation of the lining of the nose and paranasal sinuses leading to nasal blockage, nasal discharge, facial pressure/pain and loss of sense of smell. The condition can occur with or without nasal polyps. Nasal saline irrigation is commonly used to improve patient symptoms. OBJECTIVES: To evaluate the effects of saline irrigation in patients with chronic rhinosinusitis. SEARCH METHODS: The Cochrane ENT Information Specialist searched the ENT Trials Register; Central Register of Controlled Trials (CENTRAL 2015, Issue 9); MEDLINE; EMBASE; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 30 October 2015. SELECTION CRITERIA: Randomised controlled trials (RCTs) with a follow-up period of at least three months comparing saline delivered to the nose by any means (douche, irrigation, drops, spray or nebuliser) with (a) placebo, (b) no treatment or (c) other pharmacological interventions. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. Our primary outcomes were disease-specific health-related quality of life (HRQL), patient-reported disease severity and the commonest adverse event - epistaxis. Secondary outcomes included general HRQL, endoscopic nasal polyp score, computerised tomography (CT) scan score and the adverse events of local irritation and discomfort. We used GRADE to assess the quality of the evidence for each outcome; this is indicated in italics. MAIN RESULTS: We included two RCTs (116 adult participants). One compared large-volume (150 ml) hypertonic (2%) saline irrigation with usual treatment over a six-month period; the other compared 5 ml nebulised saline twice a day with intranasal corticosteroids, treating participants for three months and evaluating them on completion of treatment and three months later. Large-volume, hypertonic nasal saline versus usual care One trial included 76 adult participants (52 intervention, 24 control) with or without polyps.Disease-specific HRQL was reported using the Rhinosinusitis Disability Index (RSDI; 0 to 100, 100 = best quality of life). At the end of three months of treatment, patients in the saline group were better than those in the placebo group (mean difference (MD) 6.3 points, 95% confidence interval (CI) 0.89 to 11.71) and at six months there was a greater effect (MD 13.5 points, 95% CI 9.63 to 17.37). We assessed the evidence to be of low quality for the three months follow-up and very low quality for the six months follow-up. Patient-reported disease severity was evaluated using a "single-item sinus symptom severity assessment" but the range of scores is not stated, making it impossible for us to determine the meaning of the data presented.No adverse effects data were collected in the control group but 23% of participants in the saline group experienced side effects including epistaxis. General HRQL was measured using SF-12 (0 to 100, 100 = best quality of life). No difference was found after three months of treatment (low quality evidence) but at six months there was a small difference favouring the saline group, which may not be of clinical significance and has high uncertainty (MD 10.5 points, 95% CI 0.66 to 20.34) (very low quality evidence). Low-volume, nebulised saline versus intranasal corticosteroids One trial included 40 adult participants with polyps. Our primary outcome of disease-specific HRQL was not reported. At the end of treatment (three months) the patients who had intranasal corticosteroids had less severe symptoms (MD -13.50, 95% CI -14.44 to -12.56); this corresponds to a large effect size. We assessed the evidence to be of very low quality. AUTHORS' CONCLUSIONS: The two studies were very different in terms of included populations, interventions and comparisons and so it is therefore difficult to draw conclusions for practice. The evidence suggests that there is no benefit of a low-volume (5 ml) nebulised saline spray over intranasal steroids. There is some benefit of daily, large-volume (150 ml) saline irrigation with a hypertonic solution when compared with placebo, but the quality of the evidence is low for three months and very low for six months of treatment.

MP-AzeFlu provides rapid and effective allergic rhinitis control in real life: A pan-European study.

BACKGROUND: The European Union has prioritized allergic rhinitis (AR) control. Contre les Maladies Chronique pour un Vieillissement Actif Allergic Rhinitis and its Impact on Asthma has endorsed the visual analog scale (VAS) as the AR control language and incorporated it into a new AR treatment algorithm. Concurrently, the Respiratory Effectiveness Group and the European Academy of Allergy and Clinical Immunology are striving to improve the quality of published real-life AR research. Our aim was to assess the effectiveness of MP-AzeFlu by using a VAS in a well-designed, real-life, pan-European study. METHODS: A total of 2988 patients (aged ≥ 12 years) with Allergic Rhinitis and its Impact on Asthma defined moderate-to-severe AR from Germany, Sweden, Romania, United Kingdom, Denmark, and Norway were included. Patients (except from the United Kingdom) assessed symptom severity by using a VAS from 0 mm (not at all bothersome) to 100 mm (very bothersome) on days 0, 1, 3, 7, and the last visit (∼day 14) in the morning before MP-AzeFlu use. Patients' perceived level of disease control was assessed on day 3. A VAS score cutoff on day 3 for "well controlled" was determined, and the proportion of patients who achieved this response was calculated. RESULTS: MP-AzeFlu was associated with a mean VAS score reduction from 73.7 mm at baseline to 23.4 mm by the last visit. This reduction was significant (p < 0.001) compared with baseline from day 1 and sustained until the last day of the study. By day 3, 50.3% of patients considered their symptoms well controlled; 18.2, 40.0, 66.6, and 75.9% of the patients achieved the ≤38 mm well-controlled VAS score cutoff on days 1, 3, 7 and the last day, respectively. The results were consistent across countries, age, phenotype, and severity. CONCLUSION: MP-AzeFlu provided effective and rapid symptom control in a real-life pan-European setting and aligned with the European Union, Contre les Maladies Chronique pour un Vieillissement Actif Allergic Rhinitis and its Impact on Asthma, the Respiratory Effectiveness Group, and the European Academy of Allergy and Clinical Immunology objectives, supporting MP-AzeFlu as the drug of choice for the treatment of moderate-to-severe AR.

Peak nasal inspiratory flow and peak expiratory flow. Upright and sitting values in an adult population.

BACKGROUND: Nasal obstruction is correlated with a decreased quality of life . An easy way to evaluate nasal patency is the peak nasal inspiratory flow (PNIF) measurement. Normal PNIF values have been published by many authors. However, some authors evaluated volunteers in a sitting position, while others have measured PNIF values in standing volunteers. Body position has been shown to influence pulmonary function, with differences between sitting and upright positions. As nasal and pulmonary flows are strictly related, the present pilot study tried to establish whether PNIF/PEF changed with body position in adults. METHODOLOGY: PNIF and PEF were measured in sitting and standing positions with the order of testing randomized in 76 healthy volunteers, 30 male (40 ± 16 years). RESULTS: In the group as a whole between sitting and upright position, PEF was significantly different (p=0.009), while PNIF showed a trend towards a significant difference (p=0.10). CONCLUSIONS: The present study, although showing a generally positive effect of the standing position on PEF values, does not show a clear effect on PNIF.