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Exposome research can improve the understanding of the mechanistic connections between exposures and health to help mitigate adverse health outcomes across the life span. The exposomic approach provides a risk profile instead of single predictors and thus is particularly applicable to allergic diseases and asthma. Under the PRACTALL collaboration between the European Academy of Allergy and Clinical Immunology (EAACI) and the American Academy of Allergy, Asthma, and Immunology (AAAAI), we evaluated the current concepts and the unmet needs on the role of the exposome in allergic diseases and asthma., (© 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline by using the best approach to integrated care pathways using mobile technology in patients with allergic rhinitis (AR) and asthma multimorbidity. The proposed next phase of ARIA is change management, with the aim of providing an active and healthy life to patients with rhinitis and to those with asthma multimorbidity across the lifecycle irrespective of their sex or socioeconomic status to reduce health and social inequities incurred by the disease. ARIA has followed the 8-step model of Kotter to assess and implement the effect of rhinitis on asthma multimorbidity and to propose multimorbid guidelines. A second change management strategy is proposed by ARIA Phase 4 to increase self-medication and shared decision making in rhinitis and asthma multimorbidity. An innovation of ARIA has been the development and validation of information technology evidence-based tools (Mobile Airways Sentinel Network [MASK]) that can inform patient decisions on the basis of a self-care plan proposed by the health care professional., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Allergic rhinitis (AR) affects 23-30% of the European population with equal prevalence reported in Belgium. Despite guidelines on the correct use of effective treatment, up to 40% of AR patients remain uncontrolled. Allergen immunotherapy (AIT) has been shown to improve the level of control up to 84% of patients being controlled by AIT. Recently, new guidelines for AIT have been published, supporting the clinical evidence for effectiveness of various subcutaneous and sublingual products for AIT in patients who are allergic to airborne allergens. AIT in AR patients not only reduces nasal and/or ocular symptoms but also induces tolerance and has preventive potential. Adoption of AIT into daily clinical practice in Belgium and other European countries is hampered primarily by reimbursement issues of each of the single products but also by several patient- and physician-related factors. Patients need to be better informed about the effectiveness of AIT and the different routes of administration of AIT. Physicians dealing with AR patients should inform patients on tolerance-inducing effects of AIT and are in the need of a harmonized and practical guide that supports them in selecting eligible patients for AIT, in choosing evidence-based AIT products and in following treatment protocols with proven efficacy. Therefore, a stepwise and holistic approach is needed for better adoption of AIT in the real-life setting in Belgium.

Background: Chronic rhinosinusitis (CRS) is a common yet under-recognised chronic inflammatory disease of the nose and paranasal sinuses that is classified according to the presence (CRSwNP) or absence (CRSsNP) of nasal polyps., Methods: This paper reports the methodology and descriptive results of the Global Allergy and Asthma European Network (GALEN) rhinosinusitis cohort. We established a large CRS cohort within the GALEN consortium (European FP6 research initiative) to identify inflammatory endotypes, the natural disease course, and its impact on health-related quality of life (HRQoL). Detailed information on the impact of CRS on HRQoL, comorbidity incidence, objective disease measures, and medical and surgical treatments were collected., Results: This multicentre cross-sectional case-control study recruited 935 adults (869 eligible for analysis: 237 CRSsNP; 445 CRSwNP; 187 controls [reference group]). Comorbidities such as asthma, allergy, eczema, food allergy, urticaria, and chronic obstructive pulmonary disease were significantly more frequent in CRS patients. Nasal corticosteroids, antibiotics, and oral corticosteroids were the most common treatments. Significantly more CRSwNP patients reported previous sinonasal surgery., Conclusions: This study provides detailed information that facilitates studying CRS and its main phenotypes. However, patient distribution of this study does not necessarily reflect disease distribution in the general population.

The 2nd Rhinology Future Debate, organized by EUFOREA (European Forum for Research and Education in Allergy and Airways diseases) was held in Brussels in December 2017. One of these debates addressed the position of MP-AzeFlu in allergic rhinitis (AR) treatment. The current article summarizes this debate; reviewing recent data, and exploring how this has been interpreted by experts and incorporated into AR management guidelines and a clinical decision support system (CDSS). The Allergic Rhinitis & its Impact on Asthma (ARIA) guideline position MP-AzeFlu firstline for the treatment of AR, and in preference to intranasal corticosteroids (INSs) during the first 2 weeks of treatment. The AR CDSS recommends MP-AzeFlu as one of the firstline treatments for patients with a visual analogue scale (VAS) score lower than 5/10 cm, and in preference (along with INS) for those with a VAS score equal or higher than5/10 cm. Panellists agreed that AR management should be kept as simple as possible, with some preferring a one treatment fits all approach, while others preferred a step-up approach. The need to change the AR management mentality was acknowledged, accepting that most patients use their medication as needed and use multiple treatments; AR medications are needed which have a very fast onset of action and which target breakthrough symptoms. Panellists agreed that MP-AzeFlu has a role to play here, since it has a 5 minute onset-of-action, provides clinically-relevant symptom relief in 15 mins and AR control in less than 3 days, targets nasal hyper-reactivity (NHR) which likely contributes to uncontrolled AR and breakthrough symptoms, and provides more effective AR symptom relief than INS monotherapy or INS + oral antihistamine. Finally, experts considered it likely that MP-AzeFlu should have a greater impact on asthma control than INS in co-morbid patients, but clinical data is required to back up existing pharmacoeconomic evidence. The next Rhinology Future Debate will be in held in Brussels in Dec 2019.

Background: Over 1 billion people suffer from chronic respiratory diseases such as asthma, COPD, rhinitis and rhinosinusitis. They cause an enormous burden and are considered as major non-communicable diseases. Many patients are still uncontrolled and the cost of inaction is unacceptable. A meeting was held in Vilnius, Lithuania (March 23, 2018) under the patronage of the Ministry of Health and several scientific societies to propose multisectoral care pathways embedding guided self-management, mHealth and air pollution in selected chronic respiratory diseases (rhinitis, chronic rhinosinusitis, asthma and COPD). The meeting resulted in the Vilnius Declaration that was developed by the participants of the EU Summit on chronic respiratory diseases under the leadership of Euforea., Conclusion: The Vilnius Declaration represents an important step for the fight against air pollution in chronic respiratory diseases globally and has a clear strategic relevance with regard to the EU Health Strategy as it will bring added value to the existing public health knowledge.

Background: The evolving literature on 3D surface imaging demonstrates that this technology is becoming the preferred simulation technique in hospitals and research centers. However, no study has demonstrated before the superiority of this facility over standard 2D simulation during preoperative evaluation in rhinoplasty., Methods: One hundred seventy-two consecutive patients requesting rhinoplasty were included. Patients answered a questionnaire following a 2D simulation and subsequently experienced 3D morphing. A single question was answered regarding the added value of the latter by patients and surgeons, respectively., Results: In our survey, satisfaction with 2D morphing reached 61%. Ninety-five percentage of the same group considered 3D simulation an added value over 2D. Additionally, 84% of patients requesting revision rhinoplasty admitted that 3D computer simulation has helped them understand the aims of surgery, in contrast to 61% of patients from the primary group. Furthermore, patients unsatisfied with their 2D simulation got reassured following 3D simulation to undergo surgery at a higher percentage (67%), compared with the group initially satisfied with 2D (48%). Women appeared reassured by 3D imaging in higher percentage (63%) compared with men (42%). The 2 surgeons, however, found 3D simulations to be an added value in 66% and 74% of all patients., Conclusions: The overwhelming majority of our patients considered 3D simulation an added value over 2D. Patients initially unsatisfied with 2D morphing, revision rhinoplasty patients, and women seemed to be the groups that appreciated more 3D than 2D computer simulation. In contrast, surgeons considered the facility of 3D an added value in two-thirds of the patients.

This review highlights research advances and important achievements in food allergy, anaphylaxis, and drug allergy that were published in the Journals of the European Academy of Allergy and Clinical Immunology (EAACI) in 2017. Food allergy and anaphylaxis research have continued to rapidly accelerate, with increasing numbers of outstanding developments in 2017. We saw new studies on the mechanisms, diagnosis, prevention of food allergy, and novel food allergens. Drug hypersensitivity, as well as hereditary angioedema, has been highlighted in the present review as the focus of recent developments. The EAACI owns three journals: Allergy, Pediatric Allergy and Immunology (PAI), and Clinical and Translational Allergy (CTA). One of the major goals of the EAACI is to support health promotion in which prevention of allergy and asthma plays a critical role and to disseminate the knowledge of allergy to all stakeholders including the EAACI junior members. This paper summarizes the achievements of 2017 in anaphylaxis, and food and drug allergy., (© 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Prevention of chronicity of disease and minimising its impact with individualized treatment is a fundamental tenet of precision medicine. A review of the literature has been undertaken to explore how this may apply to chronic rhinosinusitis (CRS). Prevention may be thought of across 3 main domains. Primary prevention of CRS focuses on the avoidance of exposure to environmental factors associated with increased incidence of disease. This includes avoidance of tobacco smoke and occupational toxins. Although allergic rhinitis, respiratory infections and gastro-oesophageal reflux have been shown to be risk factors, there is no evidence as yet that treatment of these conditions is associated with reduced incidence of CRS. Secondary prevention of CRS is concerned with detecting a disease in its earliest stages, intervening to achieve disease and symptom control and preventing future exacerbations. Evidence based guidelines facilitate early diagnosis and appropriate use of medical and surgical interventions. In the future the use of endotypes to direct optimal is like to allow more clinically and cost-effective use of current and emerging treatments, such as monoclonal antibodies. Tertiary prevention aims to minimise the impact of an ongoing illness or injury that has lasting effects. Anxiety and depression have been shown to be associated with symptom amplification and may require treatment. The role of disease-related factors such as the role of the microbiome and osteo-neogenesis in the development of chronicity, and the development of severe combined upper airway disease needs further research.

Prevention of chronic rhinosinusitis remains a true societal challenge, as prevention of this highly prevalent non-communicable disease will significantly reduce socio-economic costs and improve the overall well-being of the large group of affected individuals. In alignment with the health priorities of national governments, prevention and cost-effective health care should be embraced by the Rhinologic community.

The European Academy of Allergy and Clinical Immunology (EAACI) owns three journals: Allergy, Pediatric Allergy and Immunology and Clinical and Translational Allergy. One of the major goals of EAACI is to support health promotion in which prevention of allergy and asthma plays a critical role and to disseminate the knowledge of allergy to all stakeholders including the EAACI junior members. There was substantial progress in 2017 in the identification of basic mechanisms of allergic and respiratory disease and the translation of these mechanisms into clinics. Better understanding of molecular and cellular mechanisms, efforts for the development of biomarkers for disease prediction, novel prevention and intervention studies, elucidation of mechanisms of multimorbidies, entrance of new drugs in the clinics as well as recently completed phase three clinical studies and publication of a large number of allergen immunotherapy studies and metaanalyses have been the highlights of the last year.

Nonsyndromic orofacial clefting is one of the most frequently occurring congenital conditions. The aim of the study was to investigate the prevalence and nature of reduced olfactory function in patients with nonsyndromic cleft lip and/or cleft palate (NSCL/P) and their unaffected first-degree relatives. Olfactory function was tested using the Sniffin' Sticks identification test in patients with NSCL/P, in their unaffected relatives, and in control subjects. MR imaging was performed to measure olfactory bulb (OB) volumes and olfactory sulcus (OS) depths. A reduced olfactory function was seen in significantly more patients with NSCL/P (p = .002) than in control subjects, regardless of the cleft type. Strikingly, unaffected relatives of patients with NSCL/P also had a higher rate of hyposmia (p = .001). In hyposmic patients, the OB volumes (left: p = .01 and right: p = .003) and the depth of the left OS (p = .02) were significantly smaller than in controls. In hyposmic relatives, both OS depths (left: p = .02 and right: p = .03) were significantly smaller. Patients with NSCL/P and their unaffected relatives have an increased prevalence of reduced olfactory function, associated with changes in the central olfactory structures., (© 2018 Wiley Periodicals, Inc.)

Probiotics are live microorganisms that, when administered in adequate amounts, confer health benefit on the host. The therapeutic effects of probiotics have been mostly studied in the gastrointestinal tract, but recent evidence points toward the potential of these bacteria to prevent and/or treat chronic airway diseases. In this review, possible mechanisms of action of probiotics in the airways are described, with a particular focus on their capacity to modulate the epithelial barrier function and their mode of interaction with the immune system. Indeed, probiotic bacteria, mostly lactobacilli, can promote the expression and regulation of tight junctions and adherence junctions, resulting in the restoration of a defective epithelial barrier. These bacteria interact with the epithelial barrier and immune cells through pattern recognition receptors, such as Toll-like receptors, which upon activation can stimulate or suppress various immune responses. Finally, the clinical potential of probiotics to treat inflammatory diseases of the upper and lower respiratory tract, and the difference between their mode of application (eg, oral or nasal) are discussed here., (© 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Epithelial cell lines are often used to evaluate the effect of exogenous/endogenous stimuli on epithelial barrier function and innate immune responses in allergic airway diseases, without clear view on differences between epithelial cell lines and primary nasal epithelial cell responses. In this observational study, we compared the response of Calu-3 and primary nasal epithelial cells to two relevant exogenous stimuli: i.e. Staphylococcus aureus enterotoxin B (SEB) and house dust mite (HDM). Stimulation of Calu-3 cells with SEB decreased epithelial integrity in a dose dependent manner, which was associated with a significant increase in IL-6 and IL-8 production. In contrast, no alteration in barrier integrity or IL-6 and IL-8 production was seen when primary nasal epithelial cells were stimulated with SEB. HDM extract altered the integrity of primary nasal epithelial cells, but not of Calu-3 epithelial cells. Increased IL-8 production was seen after stimulation with HDM in primary nasal epithelial cells and not in Calu-3 epithelial cells. In conclusion, immune and barrier function differ between different epithelial cell types studied. As a consequence, care must be taken when interpreting data using different epithelial cell types.

Although nasal hyperreactivity (NHR) is a common feature in patients suffering from allergic and nonallergic rhinitis, it is widely neglected during history taking, underdiagnosed in the majority of patients with rhinitis and rhinosinusitis, not considered as an outcome parameter in clinical trials on novel treatments for rhinitis and rhinosinusitis, and no target for routine treatment. In contrast to the simple nature of diagnosing NHR by a history of nasal symptoms induced by nonspecific exogenous and/or endogenous triggers, quantification is hardly performed in routine clinic given the lack of a simple tool for its diagnosis. So far, limited efforts have been invested into gaining better insight in the underlying pathophysiology of NHR, helping us to explain why some patients with inflammation develop NHR and others not. Of note, environmental and microbial factors have been reported to influence NHR, contributing to the complex nature of understanding the development of NHR. As a consequence of the neglect of NHR as a key clinical feature of rhinitis and chronic rhinosinusitis (CRS), patients with NHR might be suboptimally controlled and/or dissatisfied with current treatment. We here aim to provide a comprehensive overview of current knowledge on the pathophysiology, and the available tools to diagnose and treat NHR., (© 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Mobile health technology is emerging to take a prominent position in the management of chronic diseases. These technologies aim at enhancing patient empowerment via education and self-management. To date, of all the different apps available for patients with sinus disease, none were developed by medical experts dealing with chronic rhinosinusitis (CRS). The European Forum for Research and Education in Allergy and Airway diseases (EUFOREA) has undertaken a multi-stakeholder approach for designing, developing and implementing a tool to support CRS patients in monitoring their symptoms and to provide patients with a digital support platform containing reliable medical information about their disease and treatment options. mySinusitisCoach has been developed by medical experts dealing with CRS in close collaboration with patients, primary care physicians and community pharmacists, meeting the needs of both patients and health care providers. From a research perspective, the generation of real life data will help to validate clinical studies, patient stratification and improve understanding of the socio-economic impact of CRS, thereby paving the way for better treatment strategies.

Background: A high burden of lower airway symptoms is found in elite swimmers. To what extent elite swimmers suffer from upper airway symptoms and how these associate with nasal inflammation is less clear. We here aimed to evaluate upper airway symptoms and nasal inflammation in elite athletes., Methodology: Elite swimmers, indoor athletes and age-matched controls were recruited. Upper airway symptoms were assessed by sino-nasal outcome test (SNOT)-22 questionnaire. Visual Analogue score (VAS) for nasal symptoms as well as neurogenic and inflammatory mediators in nasal fluid were assessed at baseline, immediately and 24-hours after sport-specific training. The effect of hypochlorite on nasal epithelial cells was evaluated in vitro., Results: Baseline SNOT-22 and VAS for nasal itch and impaired smell were significantly higher in swimmers compared to controls. Nasal substance P and uric acid levels were increased in elite swimmers 24-hours after swimming compared to baseline. In elite swimmers, uric acid levels 24-hours post-exercise correlated with baseline SNOT-22. As increased symptoms and inflammation were found in swimmers but not in indoor athletes, we hypothesized that hypochlorite exposure might be the underlying mechanism. In vitro, the highest dose of hypochlorite decreased nasal epithelial cell integrity and induced release of uric acid., Conclusion: Upper airway symptoms are frequently reported in elite swimmers. Intensive swimming resulted in a delayed increase of epithelial injury and neurogenic inflammation.

Background: Large observational implementation studies are needed to triangulate the findings from randomized control trials as they reflect "real-world" everyday practice. In a pilot study, we attempted to provide additional and complementary insights on the real-life treatment of allergic rhinitis (AR) using mobile technology., Methods: A mobile phone app (Allergy Diary, freely available in Google Play and Apple App stores) collects the data of daily visual analog scales (VAS) for (i) overall allergic symptoms, (ii) nasal, ocular, and asthma symptoms, (iii) work, as well as (iv) medication use using a treatment scroll list including all medications (prescribed and over the counter (OTC)) for rhinitis customized for 15 countries., Results: A total of 2871 users filled in 17 091 days of VAS in 2015 and 2016. Medications were reported for 9634 days. The assessment of days appeared to be more informative than the course of the treatment as, in real life, patients do not necessarily use treatment on a daily basis; rather, they appear to increase treatment use with the loss of symptom control. The Allergy Diary allowed differentiation between treatments within or between classes (intranasal corticosteroid use containing medications and oral H1-antihistamines). The control of days differed between no [best control], single, or multiple treatments (worst control)., Conclusions: This study confirms the usefulness of the Allergy Diary in accessing and assessing everyday use and practice in AR. This pilot observational study uses a very simple assessment (VAS) on a mobile phone, shows novel findings, and generates new hypotheses., (© 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Multimorbidity in allergic airway diseases is well known, but no data exist about the daily dynamics of symptoms and their impact on work. To better understand this, we aimed to assess the presence and control of daily allergic multimorbidity (asthma, conjunctivitis, rhinitis) and its impact on work productivity using a mobile technology, the Allergy Diary., Methods: We undertook a 1-year prospective observational study in which 4 210 users and 32 585 days were monitored in 19 countries. Five visual analogue scales (VAS) assessed the daily burden of the disease (i.e., global evaluation, nose, eyes, asthma and work). Visual analogue scale levels <20/100 were categorized as "Low" burden and VAS levels ≥50/100 as "High" burden., Results: Visual analogue scales global measured levels assessing the global control of the allergic disease were significantly associated with allergic multimorbidity. Eight hypothesis-driven patterns were defined based on "Low" and "High" VAS levels. There were <0.2% days of Rhinitis Low and Asthma High or Conjunctivitis High patterns. There were 5.9% days with a Rhinitis High-Asthma Low pattern. There were 1.7% days with a Rhinitis High-Asthma High-Conjunctivitis Low pattern. A novel Rhinitis High-Asthma High-Conjunctivitis High pattern was identified in 2.9% days and had the greatest impact on uncontrolled VAS global measured and impaired work productivity. Work productivity was significantly correlated with VAS global measured levels., Conclusions: In a novel approach examining daily symptoms with mobile technology, we found considerable intra-individual variability of allergic multimorbidity including a previously unrecognized extreme pattern of uncontrolled multimorbidity., (© 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Collecting data on the localization of users is a key issue for the MASK (Mobile Airways Sentinel networK: the Allergy Diary) App. Data anonymization is a method of sanitization for privacy. The European Commission's Article 29 Working Party stated that geolocation information is personal data.To assess geolocation using the MASK method and to compare two anonymization methods in the MASK database to find an optimal privacy method., Methods: Geolocation was studied for all people who used the Allergy Diary App from December 2015 to November 2017 and who reported medical outcomes. Two different anonymization methods have been evaluated: Noise addition (randomization) and k-anonymity (generalization)., Results: Ninety-three thousand one hundred and sixteen days of VAS were collected from 8535 users and 54,500 (58.5%) were geolocalized, corresponding to 5428 users. Noise addition was found to be less accurate than k-anonymity using MASK data to protect the users' life privacy., Discussion: k-anonymity is an acceptable method for the anonymization of MASK data and results can be used for other databases., Competing Interests: No ethical committee was required for the study.Not needed. JB reports personal fees and other from Chiesi, Cipla, Hikma, Menarini, Mundipharma, Mylan, Novartis, Sanofi-Aventis, Takeda, Teva, Uriach, other from Kyomed, outside the submitted work.RA reports grants from North Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL2020 Partnership Agreement and through the European Regional Development Fund (ERDF), during the conduct of the study.AC reports grants and personal fees from GlaxoSmithKline, personal fees from Boehringer Ingelheim, MEDA Pharma, CHIESI, AstraZeneca, om Merck, Sharp & Dohme, Novartis EUROFARMA outside the submitted work.H reports personal fees from Munidpharma, Novartis, OrionPharma, outside the submitted work. PK reports personal fees from Adamed, Boehringer Ingelheim, AstraZeneca, Chiesi, FAES, Berlin Chemie, Novartis, Polpharma, Allergopharma, outside the submitted work.V.K has received payment for consultancy from GSK and for lectures from StallergensGreer, Berlin-CHemie outsaide the submitted work.LL reports personal fees from MSD, Pfizer, GSK, Astrazeneca, MEDA, Boehringer Ingelheim, Novartis, Grunenthal, UCB, TEVA, Amstrong, Siegfried, DBV Technologies, grants from Sanofi, Pfizer, Astrazeneca, Novartis, UCB, outside the submitted work.RM reports personal fees from ALK, allergopharma, Allergy Therapeutics, Bayer, Friulchem, FAES, GSK, Hexal, Servier, Klosterfrau, MSD, Johnson&Johnson, Meda, Stada, UCB, Nuvo; grants and personal fees from Bencard, Stallergenes; grants from Leti, Optima, ASIT biotech, BitopAG, Hulka, Ursapharm; grants, personal fees and non-financial support from Lofarma; non-financial support from Atmos, Roxall, Bionorica, Otonomy, Ferrero; personal fees and non-financial support from Novartis; outside the submitted work.NGP reports personal fees from Abbvie Novartis, Faes Farma, BIOMAY, HAL, Nutricia Research, Menarini, Novartis, MEDA, MSD, Omega Pharma, Danone, grants from Menarini, outside the submitted work.0P reports grants and personal fees from ALK-Abelló, Allergopharma, Stallergenes Greer, HAL Allergy Holding B.V./HAL Allergie GmbH, Bencard Allergie GmbH/Allergy Therapeutics, Lofarma, Biotech Tools S.A., Laboratorios LETI/LETI Pharma, Anergis S.A., grants from Biomay, Nuvo, Circassia, Glaxo Smith Kline, personal fees from Novartis Pharma, MEDA Pharma, Mobile Chamber Experts (a GA2LEN Partner), Pohl-Boskamp, Indoor Biotechnologies, grants from, outside the submitted work.RS reports grants from São Paulo Research Foundation, MSD, grants and personal fees from Novartis, grants, personal fees and non-financial support from AstraZeneca, Chiesi, personal fees and non-financial support from Boheringer Ingelheim, outside the submitted work.TBAM reports grants and personal fees from Novartis, Boehringer Ingelheim, Mundipharma, GSK (GlaxoSmithKline), personal fees from Teva Pharma, AstraZeneca, grants from Leti, outside the submitted work. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background: Allergic rhinitis (AR) is increasingly acknowledged as having a substantial socioeconomic impact associated with impaired work productivity, although available information remains fragmented., Objective: This systematic review summarizes recently available information to provide a quantitative estimate of the burden of AR on work productivity including lost work time (ie, absenteeism) and reduced performance while working (ie, presenteeism)., Methods: A Medline search retrieved original studies from 2005 to 2015 pertaining to the impact of AR on work productivity. A pooled analysis of results was carried out with studies reporting data collected through the validated Work Productivity and Activity Impairment (WPAI) questionnaire., Results: The search identified 19 observational surveys and 9 interventional studies. Six studies reported economic evaluations. Pooled analysis of WPAI-based studies found an estimated 3.6% (95% confidence interval [CI], 2.4; 4.8%) missed work time and 35.9% (95% CI, 29.7; 42.1%) had impairment in at-work performance due to AR. Economic evaluations indicated that indirect costs associated with lost work productivity are the principal contributor to the total AR costs and result mainly from impaired presenteeism. The severity of AR symptoms was the most consistent disease-related factor associated with a greater impact of AR on work productivity, although ocular symptoms and sleep disturbances may independently affect work productivity. Overall, the pharmacologic treatment of AR showed a beneficial effect on work productivity., Conclusions: This systematic review provides summary estimates of the magnitude of work productivity impairment due to AR and identifies its main determinant factors. This information may help guide both clinicians and health policy makers., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Chronic rhinosinusitis (CRS) has been differentiated clinically into CRS without nasal polyps and CRS with nasal polyps, with both forms subjected to glucocorticosteroid and antibiotic treatments and, if not successful, to nasal and sinus surgery tailored to endoscopic and computed tomographic scan findings. The elaboration of endotypes based on pathomechanisms involving different immune responses offers new possibilities in terms of prediction of prognosis and risks and sophisticated guidance in personalized pharmacotherapy, surgical approaches, and innovative treatment approaches in the CRS field with various biologics. Surgical approaches can vary from classical functional endoscopic sinus surgery to extended and "reboot" approaches, with the idea to completely remove the dysfunctional and inflamed mucosa and replace it with a newly grown healthy mucosa. Biologics in this field are targeting the type 2 cytokines IL-4, IL-5, and IL-13, as well as IgE. Phase I and II study results are promising, and phase III studies are currently being performed. The development of endotype-driven integrated care pathways appreciating these innovations are now needed for the management of CRS., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Nasal hyperreactivity (NHR) is an important clinical feature of allergic rhinitis (AR). The efficacy of MP29-02 (azelastine hydrochloride (AZE) and fluticasone propionate [FP]) nasal spray on local inflammatory mediators and NHR in AR is unknown. We tested if MP29-02 decreases inflammatory mediators and NHR in AR and if this effect is due to restoration of nasal epithelial barrier function., Methods: A 4-week double-blinded placebo-controlled trial with MP29-02 treatment was conducted in 28 patients with house dust mite (HDM) AR. The presence of NHR was evaluated by measuring reduction in nasal flow upon cold dry air exposure. The effects of AZE ± FP on barrier integrity and airway inflammation were studied in a murine model of HDM-induced NHR and on reduced activation of murine sensory neurons and human mast cells., Results: MP29-02 but not placebo reduced NHR (P < .0001 vs P = .21), levels of substance P (P = .026 vs P = .941), and β-hexosaminidase (P = .036 vs P = .632) in human nasal secretions. In wild-type C57BL6 mice, the reduction in β-hexosaminidase levels (P < .0001) by AZE + FP treatment upon HDM challenge was found in parallel with a decreased transmucosal passage (P = .0012) and completely reversed eosinophilic inflammation (P = .0013). In vitro, repeated applications of AZE + FP desensitized sensory neurons expressing the transient receptor potential channels TRPA1 and TRPV1. AZE + FP reduced MC degranulation to the same extent as AZE alone., Conclusion: MP29-02 treatment reduces inflammatory mediators and NHR in AR. The effects of AZE + FP on MC degranulation, nasal epithelial barrier integrity, and TRP channels provide novel insights into the pathophysiology of allergic rhinitis., (© 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: In contrast to the well-known significant impairment of quality of life (QoL) in allergic rhinitis (AR), the degree of impairment in QoL in nonallergic rhinitis (NAR) remained unknown for a long time, due to a lack of a validated questionnaire to assess QoL in the NAR patient group. In this study, a validation of the mini-RQLQ questionnaire in NAR patients was performed, followed by an assessment of QoL in NAR patients compared to AR and healthy controls. Secondly, use of medication and treatment satisfaction in AR and NAR was assessed., Methods: The study was an observational cohort study in 287 AR and 160 NAR patients. Patients with symptoms of rhinitis were recruited from a tertiary care outpatient clinic of the Otorhinolaryngology Department. Allergic rhinitis (AR) was defined as one or more positive results on skin prick testing and clinically relevant symptoms of rhinitis related to their sensitization. Nonallergic rhinitis (NAR) was defined as clinically relevant symptoms of rhinitis but without positive results on skin prick testing. The mini-RQLQ was successfully validated in this study for NAR patients., Results: Quality of life (QoL) in NAR patients was equally-and for some aspects even more-impaired compared to AR. More than half of both AR and NAR patients were unsatisfied with treatment., Conclusion: These results demonstrate a significant impairment in both AR and NAR patients in their QoL combined with a low treatment satisfaction, emphasizing the need for adequate treatment, especially in the NAR patient group., (© 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Physical exercise requires proper function of the upper and lower airways in order to meet exertional ventilatory requirements. Athletes performing frequent intensive exercise experience more sino-nasal symptoms and demonstrate objective decreases in sino-nasal function when compared with the general population. Sino-nasal dysfunction is known to interfere with sport performance. Nasal epithelial injury, neutrophilic influx, and decreased mucociliary clearance have been associated with intensive training. In this review, the authors provide a comprehensive overview of the prevalence of sino-nasal disease in athletes, the possible underlying pathophysiologic mechanisms, and a summary of diagnostic and treatment options., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Competing Interests: Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Statement of Problem: Evaluating the effectiveness of treatments in chronic rhinosinusitis (CRS) have been limited by both a paucity of high quality randomised trials, and the heterogeneity of outcomes in those that have been reported. Core outcome sets (COS) are an agreed, standardized set of outcomes that should be measured and reported by future trials as a minimum and will facilitate future meta-analysis of trial results in systematic reviews (SRs). We set out to develop a core outcome set for interventions for adults with CRS., Method(s) of Study: A long-list of potential outcomes was identified by a steering group utilising a literature review, thematic analysis of a wide range of stakeholders' views and systematic analysis of currently available Patient Reported Outcome Measures (PROMs). A subsequent e-Delphi process allowed 110 patients and healthcare practitioners to individually rate the outcomes in terms of importance, on a Likert scale., Main Results: After 2 rounds of the iterative Delphi process, the 54 initial outcomes were distilled down to a final core-outcome set of 15 items, over 4 domains., Principal Conclusions: The authors hope inclusion of these core outcomes in future trials will increase the value of research on interventions for CRS in adults. It was felt important to make recommendations regarding how these outcomes should be measured, although additional work is now required to further develop and revalidate existing outcome measures.

Background: Allergic rhinitis (AR) is characterized by mucosal inflammation, driven by activated immune cells. Mast cells and T H 2 cells might decrease epithelial barrier integrity in AR, maintaining a leaky epithelial barrier., Objective: We sought to investigate the role of histamine and T H 2 cells in driving epithelial barrier dysfunction in AR., Methods: Air-liquid interface cultures of primary nasal epithelial cells were used to measure transepithelial electrical resistance, paracellular flux of fluorescein isothiocyanate-dextran 4 kDa, and mRNA expression of tight junctions. Nasal secretions were collected from healthy control subjects, AR patients, and idiopathic rhinitis patients and were tested in vitro. In addition, the effect of activated T H 1 and T H 2 cells, mast cells, and neurons was tested in vitro. The effect of IL-4, IL-13, IFN-γ, and TNF-α on mucosal permeability was tested in vivo., Results: Histamine as well as nasal secretions of AR but not idiopathic rhinitis patients rapidly decreased epithelial barrier integrity in vitro. Pretreatment with histamine receptor-1 antagonist, azelastine prevented the early effect of nasal secretions of AR patients on epithelial integrity. Supernatant of activated T H 1 and T H 2 cells impaired epithelial integrity, while treatment with anti-TNF-α or anti-IL-4Rα monoclonal antibodies restored the T H 1- and T H 2-induced epithelial barrier dysfunction, respectively. IL-4, IFN-γ, and TNF-α enhanced mucosal permeability in mice. Antagonizing IL-4 prevented mucosal barrier disruption and tight junction downregulation in a mouse model of house dust mite allergic airway inflammation., Conclusions: Our data indicate a key role for allergic inflammatory mediators in modulating nasal epithelial barrier integrity in the pathophysiology in AR., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Mobile technology has been used to appraise allergic rhinitis control, but more data are needed. To better assess the importance of mobile technologies in rhinitis control, the ARIA (Allergic Rhinitis and its Impact on Asthma) score ranging from 0 to 4 of the Allergy Diary was compared with EQ-5D (EuroQuol) and WPAI-AS (Work Productivity and Activity Impairment in allergy) in 1288 users in 18 countries. This study showed that quality-of-life data (EQ-5D visual analogue scale and WPA-IS Question 9) are similar in users without rhinitis and in those with mild rhinitis (scores 0-2). Users with a score of 3 or 4 had a significant impairment in quality-of-life questionnaires., (© 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Literature is convincing regarding the efficacy of capsaicin nasal treatment in idiopathic rhinitis (IR). However, up to 50% of IR patients do not meet the strict inclusion criteria of the trials conducted so far. As a consequence, the efficacy of capsaicin is unknown in a significant number of IR patients that do not meet the strict inclusion/exclusion criteria (J Allergy Clin Immunol. 2014;133:1332, J Allergy Clin Immunol. 2017; [Epub ahead of print]). "Mixed rhinitis" (MR) patients have more than one major etiologic factor involved in the mucosal pathology. We have no idea about the efficacy of capsaicin nasal spray in these patients nor about the time interval to seek a second application. We report here that capsaicin nasal spray is effective in a broader group of IR than the purely selected ones described before, that subjective nasal hyper-reactivity is a good predictor of positive outcome, and that the time interval for seeking a second treatment is likely to be shorter in MR patients than in the strictly selected IR patients., (© 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

The overarching goals of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) are to enable European citizens to lead healthy, active and independent lives whilst ageing. The EIP on AHA includes 74 Reference Sites. The aim of this study was to transfer innovation from an app developed by the MACVIA-France EIP on AHA reference site (Allergy Diary) to other reference sites. The phenotypic characteristics of rhinitis and asthma multimorbidity in adults and the elderly will be compared using validated information and communication technology (ICT) tools (i.e. the Allergy Diary and CARAT: Control of Allergic Rhinitis and Asthma Test) in 22 Reference Sites or regions across Europe. This will improve the understanding, assessment of burden, diagnosis and management of rhinitis in the elderly by comparison with an adult population. Specific objectives will be: (i) to assess the percentage of adults and elderly who are able to use the Allergy Diary, (ii) to study the phenotypic characteristics and treatment over a 1-year period of rhinitis and asthma multimorbidity at baseline (cross-sectional study) and (iii) to follow-up using visual analogue scale (VAS). This part of the study may provide some insight into the differences between the elderly and adults in terms of response to treatment and practice. Finally (iv) work productivity will be examined in adults., (© 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

On March 29, 2017, a European Summit on the Prevention and Self-Management of Chronic Respiratory Diseases (CRD) was organized by the European Forum for Research and Education in Allergy and Airway Diseases. The event took place in the European Parliament of Brussels and was hosted by MEP David Borrelli and MEP Sirpa Pietikainen. The aim of the Summit was to correspond to the needs of the European Commission and of patients suffering from CRD to join forces in Europe for the prevention and self-management. Delegates of the European Rhinologic Society, European Respiratory Society, European Academy of Allergy and Clinical Immunology, European Academy of Paediatrics, and European Patients Organization EFA all lectured on their vision and action plan to join forces in achieving adequate prevention and self-management of CRD in the context of Precision Medicine. Recent data highlight the preventive capacity of education on optimal care pathways for CRD. Self-management and patient empowerment can be achieved by novel educational on-line materials and by novel mobile health tools enabling patients and doctors to monitor and optimally treat CRDs based on the level of control. This report summarizes the contributions of the representatives of different European academic stakeholders in the field of CRD.

The European Academy of Allergy and Clinical Immunology (EAACI) owns three journals: Allergy, Pediatric Allergy and Immunology and Clinical and Translational Allergy. One of the major goals of EAACI is to support health promotion in which prevention of allergy and asthma plays a critical role and to disseminate the knowledge of allergy to all stakeholders including the EAACI junior members.

The first Rhinology Future Debates was held in Brussels in December 2016, organized by EUFOREA (European Forum for Research and Education in Allergy and Airways diseases). The purpose of these debates is to bring novel developments in the field of Rhinology to the attention of the medical, paramedical and patient community, in a highly credible and balanced context. For the first time in Rhinology, a peer to peer scientific exchange with key experts in the field of rhinology and key medical colleagues from leading industries let to a brainstorming and discussion event on a number of hot issues in Rhinology. Novel developments are presented by key experts from industry and/or key thought leaders in Rhinology, and then followed by a lively debate on the potential positioning of new developments in care pathways, the strengths and weaknesses of the novel development(s), and comparisons with existing and/or competing products, devices, and/or molecules. As all debates are recorded and distributed on-line with limited editing (www.rhinology-future.com), EUFOREA aims at maximizing the education of the target groups on novel developments, allowing a critical appraisal of the future and a more rapid implementation of promising novel tools, techniques and/or molecules in clinical practise in Europe. The next Rhinology Future debate will be held in Brussels in December 2017.

Since its discovery, the understanding of stem/progenitor cells raised dramatically in the last decade. Their regenerative potential is important to develop new therapeutic applications, but the identification advanced much faster than our understanding of stem/progenitor cells. In nasal polyposis, little is known about stem cells/progenitor cells and their ability. However, the further characterization of stem cells/progenitor cells may provide new treatment options for combating nasal polyposis. This review highlights the knowledge of the current literature about stem cells/progenitor cells in nasal polyposis and how this may be exploited in the development of novel treatment strategies., (© 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

This EAACI position paper aims at providing a state-of-the-art overview on nonallergic rhinitis (NAR). A significant number of patients suffering from persistent rhinitis are defined as nonallergic noninfectious rhinitis (NANIR) patients, often denominated in short as having NAR. NAR is defined as a symptomatic inflammation of the nasal mucosa with the presence of a minimum of two nasal symptoms such as nasal obstruction, rhinorrhea, sneezing, and/or itchy nose, without clinical evidence of endonasal infection and without systemic signs of sensitization to inhalant allergens. Symptoms of NAR may have a wide range of severity and be either continuously present and/or induced by exposure to unspecific triggers, also called nasal hyperresponsiveness (NHR). NHR represents a clinical feature of both AR and NAR patients. NAR involves different subgroups: drug-induced rhinitis, (nonallergic) occupational rhinitis, hormonal rhinitis (including pregnancy rhinitis), gustatory rhinitis, senile rhinitis, and idiopathic rhinitis (IR). NAR should be distinguished from those rhinitis patients with an allergic reaction confined to the nasal mucosa, also called "entopy" or local allergic rhinitis (LAR). We here provide an overview of the current consensus on phenotypes of NAR, recommendations for diagnosis, a treatment algorithm, and defining the unmet needs in this neglected area of research., (© 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

A Good Practice is a practice that works well, produces good results, and is recommended as a model. MACVIA-ARIA Sentinel Network (MASK), the new Allergic Rhinitis and its Impact on Asthma (ARIA) initiative, is an example of a Good Practice focusing on the implementation of multi-sectoral care pathways using emerging technologies with real life data in rhinitis and asthma multi-morbidity. The European Union Joint Action on Chronic Diseases and Promoting Healthy Ageing across the Life Cycle (JA-CHRODIS) has developed a checklist of 28 items for the evaluation of Good Practices. SUNFRAIL (Reference Sites Network for Prevention and Care of Frailty and Chronic Conditions in community dwelling persons of EU Countries), a European Union project, assessed whether MASK is in line with the 28 items of JA-CHRODIS. A short summary was proposed for each item and 18 experts, all members of ARIA and SUNFRAIL from 12 countries, assessed the 28 items using a Survey Monkey-based questionnaire. A visual analogue scale (VAS) from 0 (strongly disagree) to 100 (strongly agree) was used. Agreement equal or over 75% was observed for 14 items (50%). MASK is following the JA-CHRODIS recommendations for the evaluation of Good Practices.

Lipopolysaccharides (LPS), the major components of the wall of gram-negative bacteria, trigger powerful defensive responses in the airways via mechanisms thought to rely solely on the Toll-like receptor 4 (TLR4) immune pathway. Here we show that airway epithelial cells display an increase in intracellular Ca 2+ concentration within seconds of LPS application. This response occurs in a TLR4-independent manner, via activation of the transient receptor potential vanilloid 4 cation channel (TRPV4). We found that TRPV4 mediates immediate LPS-induced increases in ciliary beat frequency and the production of bactericidal nitric oxide. Upon LPS challenge TRPV4-deficient mice display exacerbated ventilatory changes and recruitment of polymorphonuclear leukocytes into the airways. We conclude that LPS-induced activation of TRPV4 triggers signaling mechanisms that operate faster and independently from the canonical TLR4 immune pathway, leading to immediate protective responses such as direct antimicrobial action, increase in airway clearance, and the regulation of the inflammatory innate immune reaction.

Background: Allergic rhinitis (AR) affects 10% to 40% of the population. It reduces quality of life and school and work performance and is a frequent reason for office visits in general practice. Medical costs are large, but avoidable costs associated with lost work productivity are even larger than those incurred by asthma. New evidence has accumulated since the last revision of the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines in 2010, prompting its update., Objective: We sought to provide a targeted update of the ARIA guidelines., Methods: The ARIA guideline panel identified new clinical questions and selected questions requiring an update. We performed systematic reviews of health effects and the evidence about patients' values and preferences and resource requirements (up to June 2016). We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence-to-decision frameworks to develop recommendations., Results: The 2016 revision of the ARIA guidelines provides both updated and new recommendations about the pharmacologic treatment of AR. Specifically, it addresses the relative merits of using oral H 1 -antihistamines, intranasal H 1 -antihistamines, intranasal corticosteroids, and leukotriene receptor antagonists either alone or in combination. The ARIA guideline panel provides specific recommendations for the choice of treatment and the rationale for the choice and discusses specific considerations that clinicians and patients might want to review to choose the management most appropriate for an individual patient., Conclusions: Appropriate treatment of AR might improve patients' quality of life and school and work productivity. ARIA recommendations support patients, their caregivers, and health care providers in choosing the optimal treatment., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Allergic rhinitis often impairs social life and performance. The aim of this cross-sectional study was to use cell phone data to assess the impact on work productivity of uncontrolled rhinitis assessed by visual analogue scale (VAS). A mobile phone app (Allergy Diary, Google Play Store and Apple App Store) collects data from daily visual analogue scales (VAS) for overall allergic symptoms (VAS-global measured), nasal (VAS-nasal), ocular (VAS-ocular) and asthma symptoms (VAS-asthma) as well as work (VAS-work). A combined nasal-ocular score is calculated. The Allergy Diary is available in 21 countries. The app includes the Work Productivity and Activity Impairment Allergic Specific Questionnaire (WPAI:AS) in six EU countries. All consecutive users who completed the VAS-work from 1 June to 31 October 2016 were included in the study. A total of 1136 users filled in 5818 days of VAS-work. Symptoms of allergic rhinitis were controlled (VAS-global <20) in approximately 60% of the days. In users with uncontrolled rhinitis, approximately 90% had some work impairment and over 50% had severe work impairment (VAS-work >50). There was a significant correlation between VAS-global calculated and VAS-work (Rho=0.83, P<0.00001, Spearman's rank test). In 144 users, there was a significant correlation between VAS-work and WPAI:AS (Rho=0.53, P<0.0001). This pilot study provides not only proof-of-concept data on the work impairment collected with the app but also data on the app itself, especially the distribution of responses for the VAS. This supports the interpretation that persons with rhinitis report both the presence and the absence of symptoms., (© 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

The first European Rhinology Research Forum organized by the European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) was held in the Royal Academy of Medicine in Brussels on 17th and 18th November 2016, in collaboration with the European Rhinologic Society (ERS) and the Global Allergy and Asthma European Network (GA2LEN). One hundred and thirty participants (medical doctors from different specialties, researchers, as well as patients and industry representatives) from 27 countries took part in the multiple perspective discussions including brainstorming sessions on care pathways and research needs in rhinitis and rhinosinusitis. The debates started with an overview of the current state of the art, including weaknesses and strengths of the current practices, followed by the identification of essential research needs, thoroughly integrated in the context of Precision Medicine (PM), with personalized care, prediction of success of treatment, participation of the patient and prevention of disease as key principles for improving current clinical practices. This report provides a concise summary of the outcomes of the brainstorming sessions of the European Rhinology Research Forum 2016.

Google Trends (GT) searches trends of specific queries in Google and reflects the real-life epidemiology of allergic rhinitis. We compared Google Trends terms related to allergy and rhinitis in all European Union countries, Norway and Switzerland from 1 January 2011 to 20 December 2016. The aim was to assess whether the same terms could be used to report the seasonal variations of allergic diseases. Using the Google Trend 5-year graph, an annual and clear seasonality of queries was found in all countries apart from Cyprus, Estonia, Latvia, Lithuania and Malta. Different terms were found to demonstrate seasonality depending on the country - namely 'hay fever', 'allergy' and 'pollen' - showing cultural differences. A single set of terms cannot be used across all European countries, but allergy seasonality can be compared across Europe providing the above three terms are used. Using longitudinal data in different countries and multiple terms, we identified an awareness-related spike of searches (December 2016)., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The therapeutic action of capsaicin treatment in patients with idiopathic rhinitis (IR) is based on ablation of the transient receptor potential cation channel subfamily V, receptor 1 (TRPV1)-substance P nociceptive signaling pathway. However, the functional consequences of capsaicin treatment on nasal nerve activation and the association between the reduction in nasal hyperreactivity (NHR) and response to capsaicin treatment remain unknown., Objective: We sought to study the effects of capsaicin nasal spray on the afferent innervation of the nasal mucosa by monitoring trigeminal nerve activity in patients with IR and healthy control (HC) subjects., Methods: A double-blind, placebo-controlled randomized trial with capsaicin nasal spray was performed involving 33 patients with IR and 12 HC subjects. Before and at 4, 12, and 26 weeks after treatment, nasal mucosal potentials (NMPs) were measured while exposing the nasal mucosa of patients with IR and HC subjects to aerosols with increasing doses of the chemical irritants allyl isothiocyanate (AITC; also known as mustard oil) or capsaicin. The threshold for each compound was determined for each subject. The results of the NMP measurements were evaluated in parallel with the therapeutic response, visual analog scale scores for nasal symptoms, self-reported NHR, and mRNA expression of PGP9.5; TRPV1; transient receptor potential cation channel subfamily A, receptor 1 (TRPA1); TRPV4; transient receptor potential cation channel subfamily M, member 8 (TRPM8); and nerve growth factor (NGF) in nasal biopsy specimens., Results: AITC turned out to be the best stimulus because the coughing induced by capsaicin interfered with measurements. At baseline, the threshold for evoking changes in NMPs based on AITC was significantly lower for patients with IR compared with HC subjects (P = .0423). Capsaicin treatment of IR patients increased the threshold for the response to AITC at 4 and 12 weeks compared with placebo (P = .0406 and P = .0325, respectively), which returned to baseline by week 26 (P = .0611). This increase correlated with changes in visual analog scale major symptom (P = .0004) and total symptom (P = .0018) scores. IR patients with self-reported NHR at baseline showed a trend to being better responders to capsaicin treatment compared with patients with IR but without NHR (P = .10)., Conclusion: The lower threshold for AITC based on NMPs in patients with IR compared with HC subjects and the increased threshold for AITC after capsaicin treatment in patients with IR demonstrate the crucial role of TRPA1 and TRPV1 in IR pathophysiology. The strong correlation between the increase in AITC threshold in patients with IR and symptom reduction after capsaicin treatment demonstrates the clinical relevance of these findings., (Copyright © 2017. Published by Elsevier Inc.)

Rhinitis and rhinosinusitis are the two major clinical entities of chronic upper airway disease. Chronic rhinosinusitis (CRS) and allergic rhinitis (AR) affect respectively up to 10 and 30% of the total population, hence being associated with an important socio-economic burden. Different phenotypes of rhinitis and CRS have been described based on symptom severity and duration, atopy status, level of control, comorbidities and presence or absence of nasal polyps in CRS. The underlying pathophysiological mechanisms are diverse, with different, and sometimes overlapping, endotypes being recognized. Type 2 inflammation is well characterized in both AR and CRS with nasal polyps (CRSwNP), whereas type 1 inflammation is found in infectious rhinitis and CRS without nasal polyps (CRSsNP). The neurogenic endotype has been demonstrated in some forms of non-allergic rhinitis. Epithelial barrier dysfunction is shown in AR and CRSwNP. Emerging therapies are targeting one specific pathophysiological pathway or endotype. This endotype-driven treatment approach requires careful selection of the patient population who might benefit from a specific treatment. Personalized medicine is addressing the issue of providing targeted treatment for the right patient and should be seen as one aspect of the promising trend towards precision medicine. This review provides a comprehensive overview of the current state of endotypes, biomarkers and targeted treatments in chronic inflammatory conditions of the nose and paranasal sinuses.

The ARIA initiative was started during a World Health Organization workshop in 1999. The initial goals were to propose a new classification for allergic rhinitis, to promote the concept of multi-morbidity in asthma and rhinitis and to develop guidelines with stakeholders for world-wide use. ARIA is now focused on the implementation of emerging technologies for individualized and predictive medicine. MASK: MACVIA-Aria Sentinel Network uses mobile technology to develop care pathways that enable management by a multidisciplinary group or by patients themselves. An App for iOS and Android uses a visual analogue scale to assess symptom control and work productivity, as well as a clinical decision support system; it is associated with an interoperable tablet for health professionals. The escalation strategy uses recommendations of the European Innovation Partnership on Active and Healthy Ageing. The aim of ARIA's new approach is to provide an active and healthy life to people affected by rhinitis, regardless of age, gender or socioeconomic status, in order to reduce social and health inequalities caused by the disease.

Background: Programmed cell death-1 (PD-1) is a negative regulator of T-cell responses. Expression of PD-1 and its ligands PD-L1 and PD-L2 in chronic rhinosinusitis with nasal polyps (CRSwNP) is poorly studied., Methods: Expression of PD-1, PD-L1, PD-L2, TGF-β, IL-5, and IL-10 mRNA was measured by real-time quantitative PCR on tissue homogenates of patients with CRSwNP (n = 21) and healthy controls (n = 21) and on primary epithelial cells. Disease severity was scored using the Lund-Mackay scores of maxillofacial computed tomography (CT) scans. Expression of PD-1 and PD-L1/L2 was evaluated at the cellular and tissue levels (n = 6) by flow cytometry and immunohistochemistry., Results: Programmed cell death-1 mRNA expression was increased in tissue homogenates from patients with CRSwNP compared with controls, irrespective of the atopy status. Importantly, expression of PD-1 correlated with the total CT scan scores (r = 0.5, P = 0.02). Additionally, a significant association was found between PD-1 mRNA and expression of IL-5 mRNA in control nasal tissue (r = 0.95, P < 0.0001) and in CRSwNP (r = 0.63, P = 0.002). PD-1 was expressed on different subsets of T cells and CD11b - dendritic cells. Both PD-1 and its ligands were expressed on primary epithelial cells from control nasal tissue and nasal polyp tissue., Conclusions: Higher PD-1 expression was found in CRSwNP than in nasal tissue from controls. This was associated with disease severity and tissue IL-5 expression but unrelated to the patients' atopy status., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The use of Apps running on smartphones and tablets profoundly affects medicine. The MASK-rhinitis (MACVIA-ARIA Sentinel NetworK for allergic rhinitis) App (Allergy Diary) assesses allergic rhinitis symptoms, disease control and impact on patients' lives. It is freely available in 20 countries (iOS and Android platforms)., Aims: To assess in a pilot study whether (i) Allergy Diary users were able to properly provide baseline characteristics (ii) simple phenotypic characteristics based upon data captured by the Allergy Diary could be identified and (iii) information gathered by this study could suggest novel research questions., Methods: The Allergy Diary users were classified into six groups according to the baseline data that they entered into the App: (i) asymptomatic; (ii) nasal symptoms excluding rhinorrhea; (iii) rhinorrhea; (iv) rhinorrhea plus 1-2 nasal/ocular symptoms; (v) rhinorrhea plus ≥3 nasal/ocular symptoms; and (vi) rhinorrhea plus all nasal/ocular symptoms., Results: By 1 June 2016, 3260 users had registered with the Allergy Diary and 2710 had completed the baseline questionnaire. Troublesome symptoms were found mainly in the users with the most symptoms. Around 50% of users with troublesome rhinitis and/or ocular symptoms suffered work impairment. Sleep was impaired by troublesome symptoms and nasal obstruction., Conclusions: This is the first App (iOS and Android) to have tested for allergic rhinitis and conjunctivitis. A simple questionnaire administered by cell phones enables the identification of phenotypic differences between a priori defined rhinitis groups. The results suggest novel concepts and research questions in allergic rhinitis that may not be identified using classical methods., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)