Phl p 5 levels more strongly associated than grass pollen counts with allergic respiratory health.

BACKGROUND: Studies have linked daily pollen counts to respiratory allergic health outcomes, but few have considered allergen levels. OBJECTIVE: We sought to assess associations of grass pollen counts and grass allergen levels (Phl p 5) with respiratory allergic health symptoms in a panel of 93 adults with moderate-severe allergic rhinitis and daily asthma hospital admissions in London, United Kingdom. METHODS: Daily symptom and medication scores were collected from adult participants in an allergy clinical trial. Daily counts of asthma hospital admissions in the London general population were obtained from Hospital Episode Statistics data. Daily grass pollen counts were measured using a volumetric air sampler, and novel Phl p 5 levels were measured using a ChemVol High Volume Cascade Impactor and ELISA analyses (May through August). Associations between the 2 pollen variables and daily health scores (dichotomized based on within-person 75th percentiles) were assessed using generalized estimating equation logistic models and with asthma hospital admissions using Poisson regression models. RESULTS: Daily pollen counts and Phl p 5 levels were each positively associated with reporting a high combined symptom and medication health score in separate models. However, in mutually adjusted models including terms for both pollen counts and Phl p 5 levels, associations remained for Phl p 5 levels (odds ratio [95% CI]: 1.18 [1.12, 1.24]), but were heavily attenuated for pollen counts (odds ratio [95% CI]: 1.00 [0.93, 1.07]). Similar trends were not observed for asthma hospital admissions in London. CONCLUSIONS: Grass allergen (Phl p 5) levels are more consistently associated with allergic respiratory symptoms than grass pollen counts.

EAACI guidelines on environmental science for allergy and asthma: The impact of short-term exposure to outdoor air pollutants on asthma-related outcomes and recommendations for mitigation measures.

The EAACI Guidelines on the impact of short-term exposure to outdoor pollutants on asthma-related outcomes provide recommendations for prevention, patient care and mitigation in a framework supporting rational decisions for healthcare professionals and patients to individualize and improve asthma management and for policymakers and regulators as an evidence-informed reference to help setting legally binding standards and goals for outdoor air quality at international, national and local levels. The Guideline was developed using the GRADE approach and evaluated outdoor pollutants referenced in the current Air Quality Guideline of the World Health Organization as single or mixed pollutants and outdoor pesticides. Short-term exposure to all pollutants evaluated increases the risk of asthma-related adverse outcomes, especially hospital admissions and emergency department visits (moderate certainty of evidence at specific lag days). There is limited evidence for the impact of traffic-related air pollution and outdoor pesticides exposure as well as for the interventions to reduce emissions. Due to the quality of evidence, conditional recommendations were formulated for all pollutants and for the interventions reducing outdoor air pollution. Asthma management counselled by the current EAACI guidelines can improve asthma-related outcomes but global measures for clean air are needed to achieve significant impact.

The impact of outdoor pollution and extreme temperatures on asthma-related outcomes: A systematic review for the EAACI guidelines on environmental science for allergic diseases and asthma.

Air pollution is one of the biggest environmental threats for asthma. Its impact is augmented by climate change. To inform the recommendations of the EAACI Guidelines on the environmental science for allergic diseases and asthma, a systematic review (SR) evaluated the impact on asthma-related outcomes of short-term exposure to outdoor air pollutants (PM2.5, PM10, NO2 , SO2 , O3 , and CO), heavy traffic, outdoor pesticides, and extreme temperatures. Additionally, the SR evaluated the impact of the efficacy of interventions reducing outdoor pollutants. The risk of bias was assessed using ROBINS-E tools and the certainty of the evidence by using GRADE. Short-term exposure to PM2.5, PM10, and NO2 probably increases the risk of asthma-related hospital admissions (HA) and emergency department (ED) visits (moderate certainty evidence). Exposure to heavy traffic may increase HA and deteriorate asthma control (low certainty evidence). Interventions reducing outdoor pollutants may reduce asthma exacerbations (low to very low certainty evidence). Exposure to fumigants may increase the risk of new-onset asthma in agricultural workers, while exposure to 1,3-dichloropropene may increase the risk of asthma-related ED visits (low certainty evidence). Heatwaves and cold spells may increase the risk of asthma-related ED visits and HA and asthma mortality (low certainty evidence).

The impact of indoor pollution on asthma-related outcomes: A systematic review for the EAACI guidelines on environmental science for allergic diseases and asthma.

Systematic review using GRADE of the impact of exposure to volatile organic compounds (VOCs), cleaning agents, mould/damp, pesticides on the risk of (i) new-onset asthma (incidence) and (ii) adverse asthma-related outcomes (impact). MEDLINE, EMBASE and Web of Science were searched for indoor pollutant exposure studies reporting on new-onset asthma and critical and important asthma-related outcomes. Ninety four studies were included: 11 for VOCs (7 for incidenceand 4 for impact), 25 for cleaning agents (7 for incidenceand 8 for impact), 48 for damp/mould (26 for incidence and 22 for impact) and 10 for pesticides (8 for incidence and 2 for impact). Exposure to damp/mould increases the risk of new-onset wheeze (moderate certainty evidence). Exposure to cleaning agents may be associated with a higher risk of new-onset asthma and with asthma severity (low level of certainty). Exposure to pesticides and VOCs may increase the risk of new-onset asthma (very low certainty evidence). The impact on asthma-related outcomes of all major indoor pollutants is uncertain. As the level of certainty is low or very low for most of the available evidence on the impact of indoor pollutants on asthma-related outcomes more rigorous research in the field is warranted.

The impact of exposure to tobacco smoke and e-cigarettes on asthma-related outcomes: Systematic review informing the EAACI guidelines on environmental science for allergic diseases and asthma.

To inform the clinical practice guidelines' recommendations developed by the European Academy of Allergy and Clinical Immunology systematic reviews (SR) assessed using GRADE on the impact of environmental tobacco smoke (ETS) and active smoking on the risk of new-onset asthma/recurrent wheezing (RW)/low lung function (LF), and on asthma-related outcomes. Only longitudinal studies were included, almost all on combustion cigarettes, only one assessing e-cigarettes and LF. According to the first SR (67 studies), prenatal ETS increases the risk of RW (moderate certainty evidence) and may increase the risk of new-onset asthma and of low LF (low certainty evidence). Postnatal ETS increases the risk of new-onset asthma and of RW (moderate certainty evidence) and may impact LF (low certainty evidence). Combined in utero and postnatal ETS may increase the risk of new-onset asthma (low certainty evidence) and increases the risk of RW (moderate certainty evidence). According to the second SR (24 studies), ETS increases the risk of severe asthma exacerbations and impairs asthma control and LF (moderate certainty evidence). According to the third SR (25 studies), active smoking increases the risk of severe asthma exacerbations and of suboptimal asthma control (moderate certainty evidence) and may impact asthma-related quality-of-life and LF (low certainty evidence).

Optimization of the diagnosis and characterization of gibberellin-regulated protein sensitization: An Italian cohort study.

BACKGROUND: Pru p 7 was the first gibberellin-regulated protein (GRP) to be identified as a food allergen as the basis of a pollen food allergy syndrome. OBJECTIVE: To clinically and biologically characterize a group of patients with suspected allergy to Pru p 7 to optimize the diagnostic workup of GRP sensitization. METHODS: Allergy to Pru p 7 was suspected in the presence of a systemic allergic reaction to plant food, positive skin prick test results for cypress pollen and lipid-transfer protein-enriched peach extract, and absence of Pru p 3-specific immunoglobulin E. Controls were patients with food allergies, patients sensitized to Pru p 3, and patients with cypress allergy without food allergy. Diagnostic workup included skin tests, basophil activation test, Western blot, and single and multiplex assays. RESULTS: In total, 23 patients and 14 controls were enrolled. The most implicated food was peach (91.3%). Approximately 70% of patients reacted to multiple foods. Mueller 4 reactions were 8.7%. In 26.1% of cases, a cofactor triggered the reaction. The basophil activation test results were positive for rPru p 7 in 87% of the patients. Specific immunoglobulin E to Pru p 7 was detected in 95.7% by singleplex and in 73.9% by multiplex assays in patients with suspected allergies; 73.9% of them also reacted to cypress pollen GRP (Cup s 7) in Western blot analysis. CONCLUSION: Patients with Pru p 7-Cup s 7 allergy in our cohort confirm a mild-to-severe clinical syndrome characterized by pollen and food allergy. The diagnosis may benefit from the proposed selection criteria that can be used as preliminary steps to further characterize the cross-reactive GRP sensitization.

Multidisciplinary Decision-Making-ITAlian Consensus After Two Years of Real Practice on the Management of Severe Uncontrolled CRSwNP by Biologics (ITACA Study).

PURPOSE OF REVIEW: We aimed to reach an Italian multidisciplinary consensus on some crucial aspects of treatment decision making in CRSwNP, following 2 years of clinical experience in order to support specialists in the management of CRSwNP in clinical practice. We addressed issues relating to therapeutic decision-making and shared criteria for the treatment choice, as well as appropriate timing and criteria for evaluating treatment response, and highlighted the need for repeated multidisciplinary assessments. RECENT FINDINGS: A national survey has been conducted recently to understand how rhinology practice has changed in Italy with the advent of biologics and how this affects patients with uncontrolled, severe CRSwNP. Despite the many published consensus documents, practical recommendations, and protocols on the use of biologics in CRSwNP, heterogenous behaviors in practice are still observed mainly conditioned by the novelty of the topic. The consensus procedure followed a modified Delphi approach. The scientific board included 18 otorhinolaryngologists and 8 allergists, who selected the 4 main topics to be addressed and developed overall 20 statements. Consensus on these statements was sought by a larger group of 48 additional experts, through two rounds of voting, the first web-based, the second in presence with discussion and possible refinement of the statements. The statements reaching an average score ≥ 7 at the second voting round were approved. Five statements were proposed for each of the following topics: baseline evaluation of patients eligible for biologic therapy; choice between different therapeutic options; assessment of the response to biologic treatment; multidisciplinary management. At the first voting round, 19 out of the 20 statements reached a mean score ≥ 7. Following the discussion and a few consequent amendments, at the second round of voting all the 20 statements were approved.

Chemical Data and Relationships for a Scoring Algorithm of Extra Virgin Olive Oil's Nutritional Value.

Extra virgin olive oil (EVOO) is a valuable product and is highly appreciated by consumers for its great nutritional value. However, to date, there has been a lack of uniform systems capable of ranking the nutritional value of EVOO based on its chemical composition in terms of macro- and micronutrients (including phenolic compounds and tocopherols). The aim of this study was to propose a scoring algorithm to rank the nutritional value of EVOO samples, considering their chemical composition in macro- and micronutrients and their sensitivity to oxidation phenomena. Data from more than 1000 EVOO samples were used to assess the variability of the data, considering the selected negative parameters (free acidity, peroxide value, spectrophotometric indices) and positive components (composition in tocopherols via HPLC-DAD, phenolic compounds via HPLC-DAD, and fatty acids via GC-MS) so as to ensure the universal validity of the scoring algorithm. The dataset included samples from the main producing countries worldwide, in addition to Australia, across several production years; data were selected to represent different production realities. A mathematical model was set up for each chemical component, resulting in six variable values. By combining these values with a dimensionless constant value, the algorithm for computing the nutritional value score (NVS) was defined. It allows the nutritional value of an oil to be ranked on a scale of 0 to 100 based on its chemical composition. The algorithm was then successfully tested using chemical data from about 300 EVOO samples obtained from laboratories from different Italian regions. The proposed NVS is a simple and objective tool for scoring the nutritional value of an EVOO, easy to understand for both producers and consumers.

Can a Fraction of Flour and Sugar Be Replaced with Fruit By-Product Extracts in a Gluten-Free and Vegan Cookie Recipe?

Certain food by-products, including not-good-for-sale apples and pomegranate peels, are rich in bioactive molecules that can be collected and reused in food formulations. Their extracts, rich in pectin and antioxidant compounds, were obtained using hydrodynamic cavitation (HC), a green, efficient, and scalable extraction technique. The extracts were chemically and physically characterized and used in gluten-free and vegan cookie formulations to replace part of the flour and sugar to study whether they can mimic the role of these ingredients. The amount of flour + sugar removed and replaced with extracts was 5% and 10% of the total. Physical (dimensions, color, hardness, moisture content, water activity), chemical (total phenolic content, DPPH radical-scavenging activity), and sensory characteristics of cookie samples were studied. Cookies supplemented with the apple extract were endowed with similar or better characteristics compared to control cookies: high spread ratio, similar color, and similar sensory characteristics. In contrast, the pomegranate peel extract enriched the cookies in antioxidant molecules but significantly changed their physical and sensory characteristics: high hardness value, different color, and a bitter and astringent taste. HC emerged as a feasible technique to enable the biofortification of consumer products at a real scale with extracts from agri-food by-products.

EAACI guidelines on environmental science in allergic diseases and asthma - Leveraging artificial intelligence and machine learning to develop a causality model in exposomics.

Allergic diseases and asthma are intrinsically linked to the environment we live in and to patterns of exposure. The integrated approach to understanding the effects of exposures on the immune system includes the ongoing collection of large-scale and complex data. This requires sophisticated methods to take full advantage of what this data can offer. Here we discuss the progress and further promise of applying artificial intelligence and machine-learning approaches to help unlock the power of complex environmental data sets toward providing causality models of exposure and intervention. We discuss a range of relevant machine-learning paradigms and models including the way such models are trained and validated together with examples of machine learning applied to allergic disease in the context of specific environmental exposures as well as attempts to tie these environmental data streams to the full representative exposome. We also discuss the promise of artificial intelligence in personalized medicine and the methodological approaches to healthcare with the final AI to improve public health.

Is exposure to pollen a risk factor for moderate and severe asthma exacerbations?

Limited number of studies have focused on the impact of pollen exposure on asthma. As a part of the EAACI Guidelines on Environment Science, this first systematic review on the relationship of pollen exposure to asthma exacerbations aimed to bridge this knowledge gap in view of implementing recommendations of prevention. We searched electronic iPubMed, Embase, and Web of Science databases using a set of MeSH terms and related synonyms and identified 73 eligible studies that were included for systemic review. When possible, meta-analyses were conducted. Overall meta-analysis suggests that outdoor pollen exposure may have an effect on asthma exacerbation, but caution is needed due to the low number of studies and their heterogeneity. The strongest associations were found between asthma attacks, asthma-related ED admissions or hospitalizations, and an increase in grass pollen concentration in the previous 2-day overall in children aged less than 18 years of age. Tree pollen may increase asthma-related ED visits or admissions lagged up to 7-day overall in individuals younger than 18 years. Rare data show that among subjects under 18 years of age, an exposure to grass pollen lagged up to 3 days may lower lung function. Further research considering effect modifiers of pollen sensitization, hay fever, asthma, air pollution, green spaces, and pre-existing medications is urgently warranted to better evaluate the impacts of pollen on asthma exacerbation. Preventive measures in relation to pollen exposure should be integrated in asthma control as pollen increase continues due to climate change.

Consistent trajectories of rhinitis control and treatment in 16,177 weeks: The MASK-air® longitudinal study.

INTRODUCTION: Data from mHealth apps can provide valuable information on rhinitis control and treatment patterns. However, in MASK-air®, these data have only been analyzed cross-sectionally, without considering the changes of symptoms over time. We analyzed data from MASK-air® longitudinally, clustering weeks according to reported rhinitis symptoms. METHODS: We analyzed MASK-air® data, assessing the weeks for which patients had answered a rhinitis daily questionnaire on all 7 days. We firstly used k-means clustering algorithms for longitudinal data to define clusters of weeks according to the trajectories of reported daily rhinitis symptoms. Clustering was applied separately for weeks when medication was reported or not. We compared obtained clusters on symptoms and rhinitis medication patterns. We then used the latent class mixture model to assess the robustness of results. RESULTS: We analyzed 113,239 days (16,177 complete weeks) from 2590 patients (mean age ± SD = 39.1 ± 13.7 years). The first clustering algorithm identified ten clusters among weeks with medication use: seven with low variability in rhinitis control during the week and three with highly-variable control. Clusters with poorly-controlled rhinitis displayed a higher frequency of rhinitis co-medication, a more frequent change of medication schemes and more pronounced seasonal patterns. Six clusters were identified in weeks when no rhinitis medication was used, displaying similar control patterns. The second clustering method provided similar results. Moreover, patients displayed consistent levels of rhinitis control, reporting several weeks with similar levels of control. CONCLUSIONS: We identified 16 patterns of weekly rhinitis control. Co-medication and medication change schemes were common in uncontrolled weeks, reinforcing the hypothesis that patients treat themselves according to their symptoms.

Patient-centered digital biomarkers for allergic respiratory diseases and asthma: The ARIA-EAACI approach - ARIA-EAACI Task Force Report.

Biomarkers for the diagnosis, treatment and follow-up of patients with rhinitis and/or asthma are urgently needed. Although some biologic biomarkers exist in specialist care for asthma, they cannot be largely used in primary care. There are no validated biomarkers in rhinitis or allergen immunotherapy (AIT) that can be used in clinical practice. The digital transformation of health and health care (including mHealth) places the patient at the center of the health system and is likely to optimize the practice of allergy. Allergic Rhinitis and its Impact on Asthma (ARIA) and EAACI (European Academy of Allergy and Clinical Immunology) developed a Task Force aimed at proposing patient-reported outcome measures (PROMs) as digital biomarkers that can be easily used for different purposes in rhinitis and asthma. It first defined control digital biomarkers that should make a bridge between clinical practice, randomized controlled trials, observational real-life studies and allergen challenges. Using the MASK-air app as a model, a daily electronic combined symptom-medication score for allergic diseases (CSMS) or for asthma (e-DASTHMA), combined with a monthly control questionnaire, was embedded in a strategy similar to the diabetes approach for disease control. To mimic real-life, it secondly proposed quality-of-life digital biomarkers including daily EQ-5D visual analogue scales and the bi-weekly RhinAsthma Patient Perspective (RAAP). The potential implications for the management of allergic respiratory diseases were proposed.

Environmental influences on childhood asthma: Climate change.

Climate change is a key environmental factor for allergic respiratory diseases, especially in childhood. This review describes the influences of climate change on childhood asthma considering the factors acting directly, indirectly and with their amplifying interactions. Recent findings on the direct effects of temperature and weather changes, as well as the influences of climate change on air pollution, allergens, biocontaminants and their interplays, are discussed herein. The review also focusses on the impact of climate change on biodiversity loss and on migration status as a model to study environmental effects on childhood asthma onset and progression. Adaptation and mitigation strategies are urgently needed to prevent further respiratory diseases and human health damage in general, especially in younger and future generations.

Virgin Olive Oil By-Products: Biological Activity of Phenolic Extract of Pâté on AGS Gastric Cells.

Pâté is a by-product of olive oil production which represents an abundant source of phenolic compounds and can be used for food formulation, reducing its environmental impact and promoting a circular economy. In this context, the effects of a hydroalcoholic extract of pâté were evaluated for the first time in an AGS human cell line commonly used as model of gastric mucosa. Pâté was obtained from Tuscan olives; the total phenolic content was 16.6 mg/g dried extract, with verbascoside and secoiridoid derivatives as the most abundant phenols. The phenolic pâté extract did not alter viability, distribution of cell cycle phases or proliferation and migration of AGS cells at the tested concentrations. Seven enzymes were chosen to investigate the metabolic effect of the pâté extract in the context of oxidative stress. Pâté produced a statistically significant increase in the activity of key enzymes of some metabolic pathways: Lactate dehydrogenase, Enolase, Pyruvate kinase, Glucose 6-phosphate dehydrogenase, Citrate synthase, 3-Hydroxyacyl-CoA dehydrogenase and Hexokinase. Pre-treatments with the extract of pâté at 100 µg/mL or 200 µg/mL, as observed through PCA analysis, appeared able to counteract the enzymatic activity alterations due to oxidative stress induced by H2O2 1 mM and 2 mM. The results indicate that dried pâté, due to its phenolic components, can be proposed as a new functional food ingredient.

Polysaccharides and Phenolic Compounds Recovered from Red Bell Pepper, Tomato and Basil By-Products Using a Green Extraction by Extractor Timatic®.

Fruits and vegetables processing produces significant amounts of by-products rich in valuable bioactive compounds such as polyphenols and dietary fiber. Food by-product re-use promotes the eco-sustainability of several crops. This study aimed to apply green extractions of bioactive compounds from by-products of basil, tomato, and red bell pepper production. Tests were performed by applying extraction procedures both at laboratory scale and using the Timatic® extractor. Water and ethanol 10% and 20% were used for extraction of red bell pepper and tomato, testing different temperatures (30, 50, and 90 °C; water at 90 °C and ethanol 20% were applied for basil. The obtained phenolic extracts were analyzed by HPLC-DAD-MS. Polysaccharides of tomato and red bell pepper were extracted at laboratory scale and chemically characterized using 1H-NMR to define the methylation and acylation degree, and DLS to estimate the hydrodynamic volume. Laboratory extraction tests allowed efficient scaling-up of the process on the Timatic® extractor. Phenolic content in the dried extracts (DE) ranged 8.0-11.2 mg/g for tomato and red bell pepper and reached 240 mg/g for basil extracts. Polysaccharide yields (w/w on DM) reached 6.0 and 10.4% for dried tomato and red bell pepper, respectively. Dry extracts obtained using the Timatic® extractor and water can be useful sources of bioactive phenols. The study provided new data on tomato and red bell pepper polysaccharides that may be useful for future applications.

Virgin Olive Oil By-Product Valorization: An Insight into the Phenolic Composition of Olive Seed Extracts from Three Cultivars as Sources of Bioactive Molecules.

Olives are very rich in phenolic compounds with important health-promoting properties. The profile and content of phenols in olive pulp and virgin olive oil are strongly influenced by the fruit ripening degree, but little is known concerning the evolution of phenolic compounds in the seed. In this work, the phenolic composition of seed from Tuscan cultivars (Frantoio, Moraiolo, Leccino) was studied over maturation. Starting from each seed sample, a phenolic extract was prepared and analyzed by HPLC-DAD-MS. Nüzhenide and nüzhenide 11-methyl oleoside were by far the most abundant phenolic compounds; their content reached up to 46 g/kg in dry seeds, although this diminished in the final stage of fruit maturation. At the same time, the phenolic composition of the pulp was also characterized over the course of maturation, showing that oleuropein was by far the most abundant compound, with concentrations comparable to those of nüzhenide and nüzhenide 11-methyl oleoside in the seeds. Overall, the total amount of phenols in seed dry extracts was significant, reaching approx. 100 g/kg. The chemically characterized dry phenolic extracts from seeds could be used for future biological assays aimed at evaluating the potential bioactivities of these phytocomplexes.

Comparison of rhinitis treatments using MASK-air® data and considering the minimal important difference.

BACKGROUND: Different treatments exist for allergic rhinitis (AR), including pharmacotherapy and allergen immunotherapy (AIT), but they have not been compared using direct patient data (i.e., "real-world data"). We aimed to compare AR pharmacological treatments on (i) daily symptoms, (ii) frequency of use in co-medication, (iii) visual analogue scales (VASs) on allergy symptom control considering the minimal important difference (MID) and (iv) the effect of AIT. METHODS: We assessed the MASK-air® app data (May 2015-December 2020) by users self-reporting AR (16-90 years). We compared eight AR medication schemes on reported VAS of allergy symptoms, clustering data by the patient and controlling for confounding factors. We compared (i) allergy symptoms between patients with and without AIT and (ii) different drug classes used in co-medication. RESULTS: We analysed 269,837 days from 10,860 users. Most days (52.7%) involved medication use. Median VAS levels were significantly higher in co-medication than in monotherapy (including the fixed combination azelastine-fluticasone) schemes. In adjusted models, azelastine-fluticasone was associated with lower average VAS global allergy symptoms than all other medication schemes, while the contrary was observed for oral corticosteroids. AIT was associated with a decrease in allergy symptoms in some medication schemes. A difference larger than the MID compared to no treatment was observed for oral steroids. Azelastine-fluticasone was the drug class with the lowest chance of being used in co-medication (adjusted OR = 0.75; 95% CI = 0.71-0.80). CONCLUSION: Median VAS levels were higher in co-medication than in monotherapy. Patients with more severe symptoms report a higher treatment, which is currently not reflected in guidelines.

Behavioural patterns in allergic rhinitis medication in Europe: A study using MASK-air® real-world data.

BACKGROUND: Co-medication is common among patients with allergic rhinitis (AR), but its dimension and patterns are unknown. This is particularly relevant since AR is understood differently across European countries, as reflected by rhinitis-related search patterns in Google Trends. This study aims to assess AR co-medication and its regional patterns in Europe, using real-world data. METHODS: We analysed 2015-2020 MASK-air® European data. We compared days under no medication, monotherapy and co-medication using the visual analogue scale (VAS) levels for overall allergic symptoms ('VAS Global Symptoms') and impact of AR on work. We assessed the monthly use of different medication schemes, performing separate analyses by region (defined geographically or by Google Trends patterns). We estimated the average number of different drugs reported per patient within 1 year. RESULTS: We analysed 222,024 days (13,122 users), including 63,887 days (28.8%) under monotherapy and 38,315 (17.3%) under co-medication. The median 'VAS Global Symptoms' was 7 for no medication days, 14 for monotherapy and 21 for co-medication (p < .001). Medication use peaked during the spring, with similar patterns across different European regions (defined geographically or by Google Trends). Oral H1 -antihistamines were the most common medication in single and co-medication. Each patient reported using an annual average of 2.7 drugs, with 80% reporting two or more. CONCLUSIONS: Allergic rhinitis medication patterns are similar across European regions. One third of treatment days involved co-medication. These findings suggest that patients treat themselves according to their symptoms (irrespective of how they understand AR) and that co-medication use is driven by symptom severity.

Development and validation of combined symptom-medication scores for allergic rhinitis.

BACKGROUND: Validated combined symptom-medication scores (CSMSs) are needed to investigate the effects of allergic rhinitis treatments. This study aimed to use real-life data from the MASK-air® app to generate and validate hypothesis- and data-driven CSMSs. METHODS: We used MASK-air® data to assess the concurrent validity, test-retest reliability and responsiveness of one hypothesis-driven CSMS (modified CSMS: mCSMS), one mixed hypothesis- and data-driven score (mixed score), and several data-driven CSMSs. The latter were generated with MASK-air® data following cluster analysis and regression models or factor analysis. These CSMSs were compared with scales measuring (i) the impact of rhinitis on work productivity (visual analogue scale [VAS] of work of MASK-air® , and Work Productivity and Activity Impairment: Allergy Specific [WPAI-AS]), (ii) quality-of-life (EQ-5D VAS) and (iii) control of allergic diseases (Control of Allergic Rhinitis and Asthma Test [CARAT]). RESULTS: We assessed 317,176 days of MASK-air® use from 17,780 users aged 16-90 years, in 25 countries. The mCSMS and the factor analyses-based CSMSs displayed poorer validity and responsiveness compared to the remaining CSMSs. The latter displayed moderate-to-strong correlations with the tested comparators, high test-retest reliability and moderate-to-large responsiveness. Among data-driven CSMSs, a better performance was observed for cluster analyses-based CSMSs. High accuracy (capacity of discriminating different levels of rhinitis control) was observed for the latter (AUC-ROC = 0.904) and for the mixed CSMS (AUC-ROC = 0.820). CONCLUSION: The mixed CSMS and the cluster-based CSMSs presented medium-high validity, reliability and accuracy, rendering them as candidates for primary endpoints in future rhinitis trials.