Polysensitisation is associated with more severe symptoms: The reality of patients with allergy.

BACKGROUND: Studying the sensitisation profiles of patients with allergies allows for a deeper understanding of the disease which may facilitate the selection of the best-personalised allergen immunotherapy. This observational, cross-sectional, multicentre study aimed to demonstrate the heterogeneity of the German population with allergies by analysing specific immunoglobulin E (sIgE) patterns towards aeroallergens and exploring the relationship between sensitisation and clinical symptoms. METHODS: In total, 500 patients with allergies from different regions of Germany were recruited based on their case histories, clinical allergic symptoms and skin prick test data for aeroallergens. Serum samples were analysed using ImmunoCAP assays to determine sIgE levels for 33 allergenic sources and 43 molecular allergens. RESULTS: Most patients (81%) were polysensitised. Betula verrucosa pollen was the most common cause of sensitisation (59%), followed by Phleum pratense (58%) and Dermatophagoides pteronyssinus (44%). The highest prevalence rates of molecular allergens were observed for Bet v 1 (84%) from birch pollen, Phl p 1 from grass pollen (82%), Der p 2 (69%) from mites and Fel d 1 (69%) from cat. Polysensitisation was significantly associated with the presence of asthma and the severity of rhinitis symptoms. CONCLUSIONS: Our findings show a high rate of polysensitisation and emphasise the importance of molecular diagnosis for more precise and comprehensive insights into sensitisation patterns and their association with clinical symptoms. These data may help improve personalised diagnosis and immunotherapy adapted to the needs of individual patients in the region.

A randomized, double-blind, placebo-controlled trial with mannan-conjugated birch pollen allergoids.

BACKGROUND: There is still great need to develop new strategies to improve the efficacy of allergen immunotherapies with optimal safety standards for patients. A new promising approach is to couple allergoids to mannan. The objective of this phase IIa/IIb study was to identify the optimal dose of mannan-conjugated birch pollen allergoids for the short-course treatment of birch pollen-induced allergic rhinoconjunctivitis. METHODS: For this prospective, randomized, double-blind, placebo-controlled, dose-finding study, 246 birch pollen-allergic adults received 0.5 mL placebo or 1000, 3000 or 10,000 mTU/mL of mannan-conjugated birch pollen allergoids at five pre-seasonal visits. Efficacy was assessed by comparing allergic rhinoconjunctivitis symptoms and use of anti-allergic medication during the peak of the birch pollen season 2020. Immunologic, tolerability and safety effects were also analysed. RESULTS: The highest dose of mannan-conjugated birch pollen allergoids reduced the combined symptom and medication score during the peak birch pollen season by a median of 24.7% compared to placebo. The production of Bet v 1 specific IgG4 significantly increased in a dose-dependent manner (3.6- and 4.5-fold) in the 3000 and 10,000 mTU/mL groups. The Bet v 1 specific IgE/IgG4 ratio was also strongly reduced (up to -70%). No fatalities nor serious adverse events were reported, and no adrenaline was used. In total, four systemic reactions occurred (two grade I and two grade II). CONCLUSION: All doses of mannan-conjugated birch pollen allergoids can be considered as safe. Since the application of 10,000 mTU/mL resulted in the highest efficacy, this dose qualifies for further investigation.

Digitally-enabled, person-centred care (PCC) in allergen immunotherapy: An ARIA-EAACI Position Paper.

In rhinitis and asthma, several mHealth apps have been developed but only a few have been validated. However, these apps have a high potential for improving person-centred care (PCC), especially in allergen immunotherapy (AIT). They can provide support in AIT initiation by selecting the appropriate patient and allergen shared decision-making. They can also help in (i) the evaluation of (early) efficacy, (ii) early and late stopping rules and (iii) the evaluation of (carried-over) efficacy after cessation of the treatment course. Future perspectives have been formulated in the first report of a joint task force (TF)-Allergic Rhinitis and Its Impact on Asthma (ARIA) and the European Academy of Allergy and Clinical Immunology (EAACI)-on digital biomarkers. The TF on AIT now aims to (i) outline the potential of the clinical applications of mHealth solutions, (ii) express their current limitations, (iii) make proposals regarding further developments for both clinical practice and scientific purpose and (iv) suggest which of the tools might best comply with the purpose of digitally-enabled PCC in AIT.

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

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

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.

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.

Allergen immunotherapy: The growing role of observational and randomized trial "Real-World Evidence".

BACKGROUND: Although there is a considerable body of knowledge about allergen immunotherapy (AIT), there is a lack of data on the reliability of real-world evidence (RWE) in AIT, and consequently, a lack of information on how AIT effectively works in real life. METHODS: To address the current unmet need for an appraisal of the quality of RWE in AIT, the European Academy of Allergy and Clinical Immunology Methodology Committee recently initiated a systematic review of observational studies of AIT, which will use the RELEVANT tool and the Grading of Recommendations Assessment, Development and Evaluation approach (GRADE) to rate the quality of the evidence base as a whole. The next step will be to develop a broadly applicable, pragmatic "real-world" database using systematic data collection. Based on the current RWE base, and perspectives and recommendations of authorities and scientific societies, a hierarchy of RWE in AIT is proposed, which places pragmatic trials and registry data at the positions of highest level of evidence. KEY RESULTS: There is a need to establish more AIT registries that collect data in a cohesive way, using standardized protocols. CONCLUSIONS: This will provide an essential source of real-world data that can be easily shared, promoting evidence-based research and quality improvement in study design and clinical decision-making.

Management of patients with chronic rhinosinusitis during the COVID-19 pandemic-An EAACI position paper.

BACKGROUND: Chronic rhinosinusitis is regarded as a chronic airway disease. According to WHO recommendations, it may be a risk factor for COVID-19 patients. In most CRSwNP cases, the inflammatory changes affecting the nasal and paranasal mucous membranes are type-2 (T2) inflammation endotypes. METHODS: The current knowledge on COVID-19 and on treatment options for CRS was analyzed by a literature search in Medline, Pubmed, international guidelines, the Cochrane Library and the Internet. RESULTS: Based on international literature, on current recommendations by WHO and other international organizations as well as on previous experience, a panel of experts from EAACI and ARIA provided recommendations for the treatment of CRS during the COVID-19 pandemic. CONCLUSION: Intranasal corticosteroids remain the standard treatment for CRS in patients with SARS-CoV-2 infection. Surgical treatments should be reduced to a minimum and surgery preserved for patients with local complications and for those with no other treatment options. Systemic corticosteroids should be avoided. Treatment with biologics can be continued with careful monitoring in noninfected patients and should be temporarily interrupted during the course of the COVID-19 infection.

Personalized medicine for allergy treatment: Allergen immunotherapy still a unique and unmatched model.

The introduction of personalized medicine (PM) has been a milestone in the history of medical therapy, because it has revolutionized the previous approach of treating the disease with that of treating the patient. It is known today that diseases can occur in different genetic variants, making specific treatments of proven efficacy necessary for a given endotype. Allergic diseases are particularly suitable for PM, because they meet the therapeutic success requirements, including a known molecular mechanism of the disease, a diagnostic tool for such disease, and a treatment blocking the mechanism. The stakes of PM in allergic patients are molecular diagnostics, to detect specific IgE to single-allergen molecules and to distinguish the causative molecules from those merely cross-reactive, pursuit of patient's treatable traits addressing genetic, phenotypic, and psychosocial features, and omics, such as proteomics, epi-genomics, metabolomics, and breathomics, to forecast patient's responsiveness to therapies, to detect biomarker and mediators, and to verify the disease control. This new approach has already improved the precision of allergy diagnosis and is likely to significantly increase, through the higher performance achieved with the personalized treatment, the effectiveness of allergen immunotherapy by enhancing its already known and unique characteristics of treatment that acts on the causes.

State-of-the-art in marketed adjuvants and formulations in Allergen Immunotherapy: A position paper of the European Academy of Allergy and Clinical Immunology (EAACI).

Since the introduction of allergen immunotherapy (AIT) over 100 years ago, focus has been on standardization of allergen extracts, with reliable molecular composition of allergens receiving the highest attention. While adjuvants play a major role in European AIT, they have been less well studied. In this Position Paper, we summarize current unmet needs of adjuvants in AIT citing current evidence. Four adjuvants are used in products marketed in Europe: aluminium hydroxide (Al(OH)3 ) is the most frequently used adjuvant, with microcrystalline tyrosine (MCT), monophosphoryl lipid A (MPLA) and calcium phosphate (CaP) used less frequently. Recent studies on humans, and using mouse models, have characterized in part the mechanisms of action of adjuvants on pre-existing immune responses. AIT differs from prophylactic vaccines that provoke immunity to infectious agents, as in allergy the patient is presensitized to the antigen. The intended mode of action of adjuvants is to simultaneously enhance the immunogenicity of the allergen, while precipitating the allergen at the injection site to reduce the risk of anaphylaxis. Contrasting immune effects are seen with different adjuvants. Aluminium hydroxide initially boosts Th2 responses, while the other adjuvants utilized in AIT redirect the Th2 immune response towards Th1 immunity. After varying lengths of time, each of the adjuvants supports tolerance. Further studies of the mechanisms of action of adjuvants may advise shorter treatment periods than the current three-to-five-year regimens, enhancing patient adherence. Improved lead compounds from the adjuvant pipeline are under development and are explored for their capacity to fill this unmet need.

The role of mobile health technologies in allergy care: An EAACI position paper.

Mobile health (mHealth) uses mobile communication devices such as smartphones and tablet computers to support and improve health-related services, data and information flow, patient self-management, surveillance, and disease management from the moment of first diagnosis to an optimized treatment. The European Academy of Allergy and Clinical Immunology created a task force to assess the state of the art and future potential of mHealth in allergology. The task force endorsed the "Be He@lthy, Be Mobile" WHO initiative and debated the quality, usability, efficiency, advantages, limitations, and risks of mobile solutions for allergic diseases. The results are summarized in this position paper, analyzing also the regulatory background with regard to the "General Data Protection Regulation" and Medical Directives of the European Community. The task force assessed the design, user engagement, content, potential of inducing behavioral change, credibility/accountability, and privacy policies of mHealth products. The perspectives of healthcare professionals and allergic patients are discussed, underlining the need of thorough investigation for an effective design of mHealth technologies as auxiliary tools to improve quality of care. Within the context of precision medicine, these could facilitate the change in perspective from clinician- to patient-centered care. The current and future potential of mHealth is then examined for specific areas of allergology, including allergic rhinitis, aerobiology, allergen immunotherapy, asthma, dermatological diseases, food allergies, anaphylaxis, insect venom, and drug allergy. The impact of mobile technologies and associated big data sets are outlined. Facts and recommendations for future mHealth initiatives within EAACI are listed.

Immunologic mechanisms of a short-course of Lolium perenne peptide immunotherapy: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: A 3-week short-course of adjuvant-free hydrolysates of Lolium perenne peptide (LPP) immunotherapy for rhinoconjunctivitis with or without asthma over 4 physician visits is safe, well tolerated, and effective. OBJECTIVE: We sought to investigate immunologic mechanisms of LPP immunotherapy in a subset of patients who participated in a phase III, multicenter, randomized, double-blind, placebo-controlled trial (clinical.govNCT02560948). METHODS: Participants were randomized to receive LPP (n = 21) or placebo (n = 11) for 3 weeks over 4 visits. Grass pollen-induced basophil, T-cell, and B-cell responses were evaluated before treatment (visit [V] 2), at the end of treatment (V6), and after the pollen season (V8). RESULTS: Combined symptom and rescue medication scores (CSMS) were lower during the peak pollen season (-35.1%, P = .03) and throughout the pollen season (-53.7%, P = .03) in the LPP-treated group compared with those in the placebo-treated group. Proportions of CD63+ and CD203cbrightCRTH2+ basophils were decreased following LPP treatment at V6 (10 ng/mL, P < .0001) and V8 (10 ng/mL, P < .001) compared to V2. No change in the placebo-treated group was observed. Blunting of seasonal increases in levels of grass pollen-specific IgE was observed in LPP-treated but not placebo-treated group. LPP immunotherapy, but not placebo, was associated with a reduction in proportions of IL-4+ TH2 (V6, P = .02), IL-4+ (V6, P = .003; V8, P = .004), and IL-21+ (V6, P = .003; V8, P = .002) follicular helper T cells. Induction of FoxP3+, follicular regulatory T, and IL-10+ regulatory B cells were observed at V6 (all P < .05) and V8 (all P < .05) in LPP-treated group. Induction of regulatory B cells was associated with allergen-neutralizing IgG4-blocking antibodies. CONCLUSION: For the first time, we demonstrate that the immunologic mechanisms of LPP immunotherapy are underscored by immune modulation in the T- and B-cell compartments, which is necessary for its effect.

Mobile technology offers novel insights into the control and treatment of allergic rhinitis: The MASK study.

BACKGROUND: Mobile health can be used to generate innovative insights into optimizing treatment to improve allergic rhinitis (AR) control. OBJECTIVES: A cross-sectional real-world observational study was undertaken in 22 countries to complement a pilot study and provide novel information on medication use, disease control, and work productivity in the everyday life of patients with AR. METHODS: A mobile phone app (Allergy Diary, which is freely available on Google Play and Apple stores) was used to collect the data of daily visual analogue scale (VAS) scores for (1) overall allergic symptoms; (2) nasal, ocular, and asthma symptoms; (3) work; and (4) medication use by using a treatment scroll list including all allergy medications (prescribed and over-the-counter) customized for 22 countries. The 4 most common intranasal medications containing intranasal corticosteroids and 8 oral H1-antihistamines were studied. RESULTS: Nine thousand one hundred twenty-two users filled in 112,054 days of VASs in 2016 and 2017. Assessment of days was informative. Control of days with rhinitis differed between no (best control), single (good control for intranasal corticosteroid-treated days), or multiple (worst control) treatments. Users with the worst control increased the range of treatments being used. The same trend was found for asthma, eye symptoms, and work productivity. Differences between oral H1-antihistamines were found. CONCLUSIONS: This study confirms the usefulness of the Allergy Diary in accessing and assessing behavior in patients with AR. This observational study using a very simple assessment tool (VAS) on a mobile phone had the potential to answer questions previously thought infeasible.

[Therapy of Allergies and Allergy Immunotherapy in Children]. / Allergietherapie und Allergie-Immuntherapie im Kindesalter.

Adequate diagnostical workup for respiratory allergies and consequent therapy in children determine the individual course of disease. Therapy consists first of symptomatic treatment and includes in the next step the important option of allergy immunotherapy (AIT) as a causative treatment of disease. Children are an important target group for AIT, since AIT offers a proven longterm effect including secondary preventive properties with not only transiently reduced symptoms but moreover longstanding and beneficial disease modification.New strategies with AIT as primary and secondary preventive interventions are being evaluated with the aim to reduce clinical appearance and the amount and extent of sensitizations to allergens in high-risk children. Until implementation of such potentially preventive strategies the currently more attractive early intervention is the early adoption of AIT within the first 12 to 24 months of onset of symptoms as a first-line treatment of allergic rhinitis.Simplified treatment protocols can improve the willingness to perform an AIT and the adherence and compliance of children and their parents. The overall goal is to make AIT as the most important treatment modality available to more affected children.

Adherence to treatment in allergic rhinitis using mobile technology. The MASK Study.

BACKGROUND: Mobile technology may help to better understand the adherence to treatment. MASK-rhinitis (Mobile Airways Sentinel NetworK for allergic rhinitis) is a patient-centred ICT system. A mobile phone app (the Allergy Diary) central to MASK is available in 22 countries. OBJECTIVES: To assess the adherence to treatment in allergic rhinitis patients using the Allergy Diary App. METHODS: An observational cross-sectional study was carried out on all users who filled in the Allergy Diary from 1 January 2016 to 1 August 2017. Secondary adherence was assessed by using the modified Medication Possession Ratio (MPR) and the Proportion of days covered (PDC) approach. RESULTS: A total of 12 143 users were registered. A total of 6 949 users reported at least one VAS data recording. Among them, 1 887 users reported ≥7 VAS data. About 1 195 subjects were included in the analysis of adherence. One hundred and thirty-six (11.28%) users were adherent (MPR ≥70% and PDC ≤1.25), 51 (4.23%) were partly adherent (MPR ≥70% and PDC = 1.50) and 176 (14.60%) were switchers. On the other hand, 832 (69.05%) users were non-adherent to medications (MPR <70%). Of those, the largest group was non-adherent to medications and the time interval was increased in 442 (36.68%) users. CONCLUSION AND CLINICAL RELEVANCE: Adherence to treatment is low. The relative efficacy of continuous vs on-demand treatment for allergic rhinitis symptoms is still a matter of debate. This study shows an approach for measuring retrospective adherence based on a mobile app. This also represents a novel approach for analysing medication-taking behaviour in a real-world setting.

EAACI Guidelines on Allergen Immunotherapy: House dust mite-driven allergic asthma.

Allergen immunotherapy (AIT) has been in use for the treatment of allergic disease for more than 100 years. Asthma treatment relies mainly on corticosteroids and other controllers recommended to achieve and maintain asthma control, prevent exacerbations, and improve quality of life. AIT is underused in asthma, both in children and in adults. Notably, patients with allergic asthma not adequately controlled on pharmacotherapy (including biologics) represent an unmet health need. The European Academy of Allergy and Clinical Immunology has developed a clinical practice guideline providing evidence-based recommendations for the use of house dust mites (HDM) AIT as add-on treatment for HDM-driven allergic asthma. This guideline was developed by a multi-disciplinary working group using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. HDM AIT was separately evaluated by route of administration and children and adults: subcutaneous (SCIT) and sublingual AIT (SLIT), drops, and tablets. Recommendations were formulated for each. The important prerequisites for successful treatment with HDM AIT are (a) selection of patients most likely to respond to AIT and (b) use of allergen extracts and desensitization protocols of proven efficacy. To date, only AIT with HDM SLIT-tablet has demonstrated a robust effect in adults for critical end points (exacerbations, asthma control, and safety). Thus, it is recommended as an add-on to regular asthma therapy for adults with controlled or partially controlled HDM-driven allergic asthma (conditional recommendation, moderate-quality evidence). HDM SCIT is recommended for adults and children, and SLIT drops are recommended for children with controlled HDM-driven allergic asthma as the add-on to regular asthma therapy to decrease symptoms and medication needs (conditional recommendation, low-quality evidence).

Liposomal Eye Spray Is as Effective as Antihistamine Eye Drops in Patients with Allergic Rhinoconjunctivitis Induced by Conjunctival Provocation Testing.

BACKGROUND: Liposomal eye spray (LS) has been introduced for the treatment of dry eye. Whether LS can also relieve symptoms due to allergic rhinoconjunctivitis (ARC) has not yet been sufficiently investigated. OBJECTIVES: The aim of this study was to assess the onset of action, the reduction of allergy symptoms, and the safety of LS - a nonpharmacological treatment option - compared with those of antihistamine eye drops (AD). METHODS: In this open, prospective, controlled, monocenter noninterventional study, adults with ARC received either LS or AD for the relief of eye irritation after a positive conjunctival provocation test (CPT). All patients completed a questionnaire before and after the CPT. Eye irritation was rated on a visual analogue scale (VAS) at 6 time points. Conjunctival redness was analyzed using objective digital analysis based on images taken during the study visit. RESULTS: Data were collected from 40 patients (20 per group). In both groups, 80% of patients perceived an onset of action within 0-2 min after application of LS or AD following the CPT. Relief of eye irritation (as determined by VAS) increased throughout the visit for both groups. In the digital analysis, the mean proportion of redness of the eye decreased from 10.3 to 7.0% for LS and from 10.4 to 6.5% for AD, with the largest difference observed 10 min after application (LS: 8.9%; AD: 6.0%; p = 0.094). CONCLUSIONS: LS is a nonpharmacological treatment option for ARC, showing no significant difference or relevant numerical inferiority to AD in any parameter studied. It was generally safe and well tolerated.

Ectoine lozenges in the treatment of acute viral pharyngitis: a prospective, active-controlled clinical study.

PURPOSE: Acute pharyngitis is an uncomfortable disorder mostly caused by viruses and for which antibiotics are unwarranted. This study compared lozenges containing ectoine, a natural extremolyte, with hyaluronic acid lozenges and hypertonic saline gargle for symptomatic treatment of acute viral pharyngitis. METHODS: This prospective, controlled clinical study, recruited 90 patients with moderate-to-severe pharyngitis symptoms who chose to use either ectoine (n = 35), hyaluronic acid (n = 35), or saline gargle (n = 20). Patients applied their 7-day treatment from the inclusion visit (V1) until the end-of-study visit (V2). Patients' pharyngitis symptoms, general health, general treatment effectiveness and tolerability, and patient compliance were assessed by investigators and patients. RESULTS: The sum score for three primary symptoms (pain on swallowing, urge to cough, and hoarseness) decreased by 79.5% (ectoine), 72.2% (hyaluronic acid), and 44.8% (saline gargle). Both lozenges were significantly superior to saline gargle (P < 0.05). Regarding general health improvement, ectoine was significantly superior to saline gargle (72.5% vs. 45.2%, P < 0.05), but hyaluronic acid (63.3%) was not. At V2, 65.7% of patients receiving ectoine reported "very good" general health vs. 48.6% of those receiving hyaluronic acid and 20.0% using saline gargle. Ectoine was significantly superior (P < 0.05) to both hyaluronic acid and saline gargle in terms of tolerability and patient compliance. No patients taking ectoine reported unpleasant sensations while applying their treatment, whereas almost half of patients using hyaluronic acid lozenges and saline gargle did. CONCLUSION: Treatment with ectoine lozenges significantly relieves moderate-to-severe symptoms of acute viral pharyngitis and is more effective and tolerable than treatments with hyaluronic acid lozenges and hypertonic saline gargle.