Omalizumab in patients with NSAIDs-exacerbated respiratory disease.

BACKGROUND: The association of acetylsalicylic acid (ASA) intolerance, chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, or chronic urticaria is known as NSAID-exacerbated respiratory disease (N-ERD). N-ERD patients often suffer from recurrent nasal polyps, severe asthma or also from urticaria. The aim of the present study was to retrospectively analyze the clinical efficacy of anti-IgE antibody treatment with omalizumab in patients with confirmed N-ERD. METHODS: In the open trial with patients receiving verum patients with CRSwNP, confirmed N-ERD by oral or nasal ASA challenges, asthma or chronic urticaria were included in the study. Rhinological and pulmonary parameters were evaluated before and after 3, 6 and 9 months of therapy by rhinological questionnaires (CRS VAS-scores and RSOM-31), nasal polyp (NP)-, ACT-scores and FEV1 values. Urticaria activity was monitored clinically. N-ERD patients with aspirin desensitization were included as control group (follow-up 9 months). RESULTS: In the omalizumab group 16 patients were included (10 female, 6 male, mean age 51 yrs). CRS symptoms, RSOM-31- and NP-score decreased significantly following omalizumab therapy compared to baseline. The ACT-score (MV 16.5 to 20.6) and FEV1values (MV 80 % to 89 %) improved significantly. No urticaria symptoms were reported after 3 months. Oral prednisolone therapy was required in one case and a repeated nasal sinus surgery in an additional case due to progression of NP. In the control group (8 female, 8 male, mean age 45 yrs) the NP-score was unchanged. CONCLUSIONS: Omalizumab is an effective therapy option in N-ERD patients in a 9 month study period.

New European Academy of Allergy and Clinical Immunology definition on pollen season mirrors symptom load for grass and birch pollen-induced allergic rhinitis.

BACKGROUND: The use of allergen immunotherapy (AIT) for allergic rhinitis and its clinical efficacy in clinical trials depends on the effective determination of pollen allergen exposure time periods. We evaluate pollen data from Germany to examine the new definitions on pollen season and peak pollen period start and end as proposed by the European Academy of Allergy and Clinical Immunology (EAACI) in a recently published Position Paper. The aim was to demonstrate the ability of these definitions to mirror symptom loads for grass and birch pollen-induced allergic rhinitis based on real-life data. METHODS: Data coming from four pollen monitoring stations in the Berlin and Brandenburg area in Germany and for 3 years (2014-2016) were used to investigate the correlation of season definitions, birch and grass pollen counts and total nasal symptom and mediation scores as reported by patients in "Patients Hay fever Diaries" (PHDs). After the identification of pollen periods on the basis of the EACCI criteria, a statistical analysis was employed, followed by a detailed graphical investigation. RESULTS: The analysis revealed that the definitions of pollen season as well as peak pollen period start and end as proposed by the EAACI are correlated to symptom loads for grass and birch pollen-induced allergic rhinitis reported by patients in PHDs. CONCLUSION: Based on our analysis, the validity of the EAACI definitions on pollen season is confirmed. Their use is recommended in future clinical trials on AIT as well as in daily routine for optimal patient care.

Treatment of allergic rhinitis using mobile technology with real-world data: The MASK observational pilot study.

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.

Daily allergic multimorbidity in rhinitis using mobile technology: A novel concept of the MASK study.

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.

The Allergic Rhinitis and its Impact on Asthma (ARIA) score of allergic rhinitis using mobile technology correlates with quality of life: The MASK study.

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.

Transfer of innovation on allergic rhinitis and asthma multimorbidity in the elderly (MACVIA-ARIA) - EIP on AHA Twinning Reference Site (GARD research demonstration project).

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.

Validation of the MASK-rhinitis visual analogue scale on smartphone screens to assess allergic rhinitis control.

BACKGROUND: Visual Analogue Scale (VAS) is a validated tool to assess control in allergic rhinitis patients. OBJECTIVE: The aim of this study was to validate the use of VAS in the MASK-rhinitis (MACVIA-ARIA Sentinel NetworK for allergic rhinitis) app (Allergy Diary) on smartphones screens to evaluate allergic rhinitis symptoms and disease control. METHODS: Each user filled 4 different VAS measuring overall, nasal, ocular, and asthma symptoms at least once. Following COSMIN guidelines, we evaluated internal consistency, (Cronbach's alpha coefficient and test-retest), reliability (intraclass correlation coefficients), sensitivity, and acceptability of the MASK-Rhinitis VAS. RESULTS: Between 1 August 2015 and 31 July 2016, the app was used 14 612 times in 15 countries. A total of 1225 users used it more than once, during the evaluated period. The tool resulted to be statistically satisfactory, showing excellent internal consistency (Cronbach's test > 0.84, test-retest > 0.7), reliability (>0.9), and acceptability. In addition, the tool had a good sensitivity when users (n = 521) answered the VAS twice in less than 3 hours. CONCLUSIONS AND CLINICAL RELEVANCE: The MASK-rhinitis VAS is a reliable and valid tool to assess allergic control on smartphone screens, at the population level.

Defining pollen exposure times for clinical trials of allergen immunotherapy for pollen-induced rhinoconjunctivitis - an EAACI position paper.

BACKGROUND: Clinical efficacy of pollen allergen immunotherapy (AIT) has been broadly documented in randomized controlled trials. The underlying clinical endpoints are analysed in seasonal time periods predefined based on the background pollen concentration. However, any validated or generally accepted definition from academia or regulatory authorities for this relevant pollen exposure intensity or period of time (season) is currently not available. Therefore, this Task Force initiative of the European Academy of Allergy and Clinical Immunology (EAACI) aimed to propose definitions based on expert consensus. METHODS: A Task Force of the Immunotherapy and Aerobiology and Pollution Interest Groups of the EAACI reviewed the literature on pollen exposure in the context of defining relevant time intervals for evaluation of efficacy in AIT trials. Underlying principles in measuring pollen exposure and associated methodological problems and limitations were considered to achieve a consensus. RESULTS: The Task Force achieved a comprehensive position in defining pollen exposure times for different pollen types. Definitions are presented for 'pollen season', 'high pollen season' (or 'peak pollen period') and 'high pollen days'. CONCLUSION: This EAACI position paper provides definitions of pollen exposures for different pollen types for use in AIT trials. Their validity as standards remains to be tested in future studies.

Allergen exposure chambers: harmonizing current concepts and projecting the needs for the future - an EAACI Position Paper.

BACKGROUND: Allergen exposure chambers (AECs) are clinical facilities allowing for controlled exposure of subjects to allergens in an enclosed environment. AECs have contributed towards characterizing the pathophysiology of respiratory allergic diseases and the pharmacological properties of new therapies. In addition, they are complementary to and offer some advantages over traditional multicentre field trials for evaluation of novel therapeutics. To date, AEC studies conducted have been monocentric and have followed protocols unique to each centre. Because there are technical differences among AECs, it may be necessary to define parameters to standardize the AECs so that studies may be extrapolated for driving basic immunological research and for marketing authorization purposes by regulatory authorities. METHODS: For this task force initiative of the European Academy of Allergy and Clinical Immunology (EAACI), experts from academia and regulatory agencies met with chamber operators to list technical, clinical and regulatory unmet needs as well as the prerequisites for clinical validation. RESULTS: The latter covered the validation process, standardization of challenges and outcomes, intra- and interchamber variability and reproducibility, in addition to comparability with field trials and specifics of paediatric trials and regulatory issues. CONCLUSION: This EAACI Position Paper aims to harmonize current concepts in AECs and to project unmet needs with the intent to enhance progress towards use of these facilities in determining safety and efficacy of new therapeutics in the future.

Google Trends terms reporting rhinitis and related topics differ in European countries.

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).

Pilot study of mobile phone technology in allergic rhinitis in European countries: the MASK-rhinitis study.

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.

Work productivity in rhinitis using cell phones: The MASK pilot study.

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.

[IgE and Anti-IgE in Asthma: A Chequered History]. / IgE und Anti-IgE bei Asthma: eine wechselvolle Geschichte.

A long and winding road led to the discovery of immunoglobulin E (IgE) in 1966 and 1967. We are currently on a long and winding road to understand the immunologic basis of the clinical effects of the anti-IgE antibody omalizumab in asthma. It is possible that patients with asthma (as patients with chronic spontaneous urticaria) benefit in different immunologic ways from omalizumab treatment. This article reviews the history of IgE discovery and current concepts of anti-IgE therapy in asthma.

MACVIA-ARIA Sentinel NetworK for allergic rhinitis (MASK-rhinitis): the new generation guideline implementation.

Several unmet needs have been identified in allergic rhinitis: identification of the time of onset of the pollen season, optimal control of rhinitis and comorbidities, patient stratification, multidisciplinary team for integrated care pathways, innovation in clinical trials and, above all, patient empowerment. MASK-rhinitis (MACVIA-ARIA Sentinel NetworK for allergic rhinitis) is a simple system centred around the patient which was devised to fill many of these gaps using Information and Communications Technology (ICT) tools and a clinical decision support system (CDSS) based on the most widely used guideline in allergic rhinitis and its asthma comorbidity (ARIA 2015 revision). It is one of the implementation systems of Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA). Three tools are used for the electronic monitoring of allergic diseases: a cell phone-based daily visual analogue scale (VAS) assessment of disease control, CARAT (Control of Allergic Rhinitis and Asthma Test) and e-Allergy screening (premedical system of early diagnosis of allergy and asthma based on online tools). These tools are combined with a clinical decision support system (CDSS) and are available in many languages. An e-CRF and an e-learning tool complete MASK. MASK is flexible and other tools can be added. It appears to be an advanced, global and integrated ICT answer for many unmet needs in allergic diseases which will improve policies and standards.

Personalized symptoms forecasting for pollen-induced allergic rhinitis sufferers.

Hay fever is a pollen-induced allergic reaction that strongly affects the overall quality of life of many individuals. The disorder may vary in severity and symptoms depending on patient-specific factors such as genetic disposition, individual threshold of pollen concentration levels, medication, former immunotherapy, and others. Thus, information services that improve the quality of life of hay fever sufferers must address the needs of each individual separately. In this paper, we demonstrate the development of information services that offer personalized pollen-induced symptoms forecasts. The backbone of these services consists of data of allergic symptoms reported by the users of the Personal Hay Fever Diary system and pollen concentration levels (European Aeroallergen Network) in several sampling sites. Data were analyzed using computational intelligence methods, resulting in highly customizable forecasting models that offer personalized warnings to users of the Patient Hay Fever Diary system. The overall system performance for the pilot area (Vienna and Lower Austria) reached a correlation coefficient of r = 0.71 ± 0.17 (average ± standard deviation) in a sample of 219 users with major contribution to the Pollen Hay Fever Diary system and an overall performance of r = 0.66 ± 0.18 in a second sample of 393 users, with minor contribution to the system. These findings provide an example of combining data from different sources using advanced data engineering in order to develop innovative e-health services with the capacity to provide more direct and personalized information to allergic rhinitis sufferers.