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.

Bilastine for the treatment of allergic rhinoconjunctivitis and urticaria: results from an international Delphi study.

Background: Second-generation oral H1-antihistamines, including bilastine, represent the emerging treatments of allergic rhinitis (including rhinoconjunctivitis) and chronic urticaria in both adults and children. This study analyses available evidence supporting the use of bilastine amongst second-generation antihistamines for the symptomatic treatment of allergic rhinitis and urticaria in adults and children. Methods: Consensus amongst experts from 17 countries on the ideal treatment of rhinitis and urticaria, and the specific role of bilastine was measured by means of a modified Delphi process. A total of 12 statements were voted on by the experts using a five-point Likert scale (1 = strongly disagree; 2 = disagree; 3 = undecided; 4 = agree; 5 = strongly agree). The definition of consensus was set at a minimum of 80% concordance for 4+5 scores (agree or strongly agree). Results: All proposed statements reached consensus, with a concordance of ≥98% for five statements and ≥96% for seven. Conclusions: The wide consensus obtained for the proposed statements suggests a prominent role for bilastine in the management of allergic rhinitis and urticaria.

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.

A high-dose, depigmented polymerized birch pollen extract for subcutaneous allergen immunotherapy has a favourable efficacy/safety ratio.

BACKGROUND: Subcutaneous allergen immunotherapy (SCIT) with depigmented, polymerized (DPP) birch pollen extract has been marketed at doses of up to 1000 DPP units/mL since 2001. We sought to determine the dose-dependent efficacy of a DPP birch pollen extract formulation in patients suffering from birch-pollen-induced allergic rhinitis or rhinoconjunctivitis with or without intermittent asthma. METHODS: A titrated conjunctival provocation test (CPT) was applied as a surrogate marker. This Phase II randomized, double-blind, parallel-group, dose-ranging clinical trial was performed at 39 centres in Germany, Lithuania and Poland. After randomization to four dose-level groups (100, 1000, 5000 and 10,000 DPP units/mL) and up-dosing, participants received maintenance SCIT with five monthly subcutaneous injections. The primary endpoint was the proportion of patients in whom a higher concentration of birch pollen (vs. baseline) was needed to elicit a positive CPT. RESULTS: Three hundred forty-three patients were included (mean (range) age: 42.6 (19-70)). The highest CPT responder rates were seen in the higher dose-level groups. In the intention-to-treat analysis, the difference between the 100 and 10,000 groups was statistically significant (p = 0.0118). Although the proportion of patients with ≥1 treatment-emergent adverse events increased with the dose, almost all these events were mild (65.6%) or moderate (18.5%). CONCLUSION: Judging by the results of a CPT, the efficacy/safety ratio in SCIT appears to be favourable for a high-dose-level preparation of a DPP birch pollen extract.

Validation of AI-based software for objectification of conjunctival provocation test.

Background: Provocation tests are widely used in allergology to objectively reveal patients' sensitivity to specific allergens. The objective quantification of an allergic reaction is a crucial characteristic of these tests. Because of the absence of objective quantitative measurements, the conjunctival provocation test (CPT) is a less frequently used method despite its sensitivity and simplicity. Objective: We developed a new artificial intelligence (AI)-based method, called AllergoEye, for quantitative evaluation of conjunctival allergic reactions and validated it in a clinical study. Methods: AllergoEye was implemented as a 2-component system. The first component is based on an Android smartphone camera for screening and imaging the patient's eye, and the second is personal computer-based for image analysis and quantification. For the validation of AllergoEye, an open-label, prospective, monocentric study was carried out on 41 patients. Standardized CPT was performed with sequential titration of grass allergens in 4 dilutions, with the reaction evaluated by subjective/qualitative symptom scores and by quantitative AllergoEye scores. Results: AllergoEye demonstrated high sensitivity (98%) and specificity (90%) as compared with human estimation of allergic reaction. Tuning cutoff thresholds allowed us to increase the specificity of AllergoEye to 97%, at which point the correlation between detected sensitivity to allergen and specific IgE carrier-polymer system class becomes obvious. Strikingly, such correlation was not found with sensitivity to allergen detected on the basis of subjective and qualitative symptom scores. Conclusion: The clinical validation demonstrated that AllergoEye is a sensitive and efficient instrument for objective measurement of allergic reactions in CPT for clinical studies as well as for routine therapy control.

Effectiveness and Tolerability of Ectoin® Mouth and Throat Spray Althaea Honey (ERS09) for Sore Throat due to Acute Pharyngitis and Dry Cough: A Multicentre, Actively Controlled, Open Label Study in Germany.

Acute pharyngitis can cause sore throat. This multicentre, active-controlled, randomised, open-label, and parallel-group study, conducted according to the German Medical Devices Act, compared the effectiveness and tolerability of ERS09 mouth and throat spray with a well-established device for the treatment of sore throat caused by acute pharyngitis and dry cough. Patients were randomised 1:1 into ERS09/comparator groups (EMSER® Sore Throat Spray) for 7 ± 2 days. Patients and investigators reported effectiveness (change in total symptom score [TSS]) and safety endpoints (incidence of adverse events [AEs]; adverse device effects [ADEs]). A total of 186 patients were included (ERS09: n = 92; comparator: n = 94). The baseline-adjusted mean TSS over 7 days was -90.14 and -74.91 in the ERS09 and comparator groups, respectively (p < 0.05). The majority of patients reached a 50% reduction in symptoms by day 6 (ERS09 = 78.85; comparator = 75.8%). Most patients reported a soothing effect within five minutes (ERS09 = 82%; comparator = 71%). Improvements in individual symptoms were similar with no significant differences between groups; more patients in the ERS09 group reported an improvement in pharyngeal redness/swelling. Three AEs unrelated to medication, one ADE following ERS09, and no serious AE/ADE were reported. ERS09 was as well tolerated and effective as the established device, showing greater improvement in the management of some symptoms and greater patient preference.

Rhinosinusitis Treatment with Cineole: Patient-Reported Quality of Life Improvements from a Non-Interventional, Pharmacy-Based Survey.

BACKGROUND: Rhinosinusitis is commonly treated with decongestants, analgesics, and local corticosteroids. Phytotherapeutics are also utilised for symptomatic relief, including cineole, the main component of eucalyptus oil. METHODS: The current non-interventional, anonymised survey investigated quality of life in participants with rhinosinusitis (with or without additional symptoms of bronchitis) via the German version of a validated quality of life questionnaire (RhinoQol). Overall, 310 subjects administered a cineole preparation (Sinolpan) and 40 subjects applying nasal decongestant were recruited in German pharmacies. RESULTS: Significant improvements in frequency (64.0%), bothersomeness (52.1%), and impact (53.9%) of rhinosinusitis symptoms were reported upon treatment with cineole over a mean treatment period of seven days (p < 0.001 each). The overall treatment efficacy of cineole was evaluated as good or very good by 90.0% of the participants, and the quality of life during work or leisure time improved upon treatment. Six (non-serious) possibly related side effects were reported in four participants who were administered cineole. The tolerability of the treatment was assessed as good or very good by 93.9% of the participants. CONCLUSIONS: Cineole can be considered as a safe and well-tolerated rhinosinusitis treatment conferring a clear improvement in quality of life outcomes.

Early intervention with azelastine nasal spray may reduce viral load in SARS-CoV-2 infected patients.

With the changing epidemiology of COVID-19 and its impact on our daily lives, there is still an unmet need of COVID-19 therapies treating early infections to prevent progression. The current study was a randomized, parallel, double-blind, placebo-controlled trial. Ninety SARS-CoV-2 positive patients were randomized into 3 groups receiving placebo, 0.02% or 0.1% azelastine nasal spray for 11 days, during which viral loads were assessed by quantitative PCR. Investigators assessed patients' status throughout the trial including safety follow-ups (days 16 and 60). Symptoms were documented in patient diaries. Initial viral loads were log10 6.85 ± 1.31 (mean ± SD) copies/mL (ORF 1a/b gene). After treatment, virus load was reduced in all groups (p < 0.0001) but was greater in the 0.1% group compared to placebo (p = 0.007). In a subset of patients (initial Ct < 25) viral load was strongly reduced on day 4 in the 0.1% group compared to placebo (p = 0.005). Negative PCR results appeared earlier and more frequently in the azelastine treated groups: being 18.52% and 21.43% in the 0.1% and 0.02% groups, respectively, compared to 0% for placebo on day 8. Comparable numbers of adverse events occurred in all treatment groups with no safety concerns. The shown effects of azelastine nasal spray may thus be suggestive of azelastine's potential as an antiviral treatment.Trial registration: The study was registered in the German Clinical Trial Register (DRKS-ID: DRKS00024520; Date of Registration in DRKS: 12/02/2021). EudraCT number: 2020-005544-34.

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.

Cutoff Values of MASK-air Patient-Reported Outcome Measures.

BACKGROUND: In clinical and epidemiological studies, cutoffs of patient-reported outcome measures can be used to classify patients into groups of statistical and clinical relevance. However, visual analog scale (VAS) cutoffs in MASK-air have not been tested. OBJECTIVE: To calculate cutoffs for VAS global, nasal, ocular, and asthma symptoms. METHODS: In a cross-sectional study design of all MASK-air participants, we compared (1) approaches based on the percentiles (tertiles or quartiles) of VAS distributions and (2) data-driven approaches based on clusters of data from 2 comparators (VAS work and VAS sleep). We then performed sensitivity analyses for individual countries and for VAS levels corresponding to full allergy control. Finally, we tested the different approaches using MASK-air real-world cross-sectional and longitudinal data to assess the most relevant cutoffs. RESULTS: We assessed 395,223 days from 23,201 MASK-air users with self-reported allergic rhinitis. The percentile-oriented approach resulted in lower cutoff values than the data-driven approach. We obtained consistent results in the data-driven approach. Following the latter, the proposed cutoff differentiating "controlled" and "partly-controlled" patients was similar to the cutoff value that had been arbitrarily used (20/100). However, a lower cutoff was obtained to differentiate between "partly-controlled" and "uncontrolled" patients (35 vs the arbitrarily-used value of 50/100). CONCLUSIONS: Using a data-driven approach, we were able to define cutoff values for MASK-air VASs on allergy and asthma symptoms. This may allow for a better classification of patients with rhinitis and asthma according to different levels of control, supporting improved disease management.

International Delphi-based consensus on the appropriate use and effect of Benzydamine hydrochloride in the treatment of sore throat.

BACKGROUND: Benzydamine hydrochloride is a locally-acting Non-Steroidal Anti-Inflammatory Drug (NSAID) with combined local anesthetic and analgesic properties, indicated for the symptomatic relief of pain in acute sore throat. The aim of this study was to obtain an European Consensus among pharmacists, general practitioners and pediatricians on the appropriate use of benzydamine hydrochloride in the treatment of sore throat. METHODS: The authors developed a Delphi questionnaire organized into 15 statements focused on 4 topics: the mechanism of action of benzydamine, the benzydamine treatment in an adult patient and in a pediatric patient, and the advantages of benzydamine over other topical treatments. The survey was administered to a panel of to 320 participants including general practitioners, pediatricians, and pharmacists from 6 European countries (Italy, Germany, Portugal, Romania, Russia, and Spain), who rated their level of agreement or disagreement with each statement on a 6-point Likert scale. Consensus was predefined as more than 66% of the panel agreeing/disagreeing with each statement. RESULTS: Panelists' agreement on statements was very high. Consensus was reached for all 15 statements in the Delphi survey, with more than 98% positive agreement on topic 4, suggesting a shared view among European healthcare professionals (HCPs) about the advantages of benzydamine over other topical treatments. A strong consensus (> 99%) was reached for all the statements of topic 1 regarding the mechanism of action of benzydamine, except for its anesthetic properties (79%). Strong agreement was reached for all statements in topics 2 and 3 regarding the treatment of acute sore throat symptoms in the adult and pediatric patient, except for one on the efficacy of benzydamine in preventing post-operative sore throat, for which it was 67%. CONCLUSION: Because all relevant publications on benzydamine are dated and there are no recommendations on its use for the symptomatic treatment of sore throat in European guidelines, this Delphi-based international consensus may be important in reinforcing the appropriate use and effect of benzydamine in the treatment of sore throat among health care professionals.

Ivy leaves extract EA 575 in the treatment of cough during acute respiratory tract infections: meta-analysis of double-blind, randomized, placebo-controlled trials.

Ivy leaves extracts have been used successfully to treat acute cough, and data from well-controlled trials is accumulating. We present a meta-analysis of two double-blind, randomized, placebo-controlled trials. Patients with acute respiratory tract infection (ARTI) received ivy leaves dry extract EA 575 (n = 228) or placebo (n = 162) for 7 days, followed by a 7-day period without treatment. The main efficacy outcome was the Bronchitis Severity Score (BSS). Individual patient data meta-analyses were performed using mixed models for repeated measures, analysis of covariance and logistic ordinal regression. Significant BSS differences between EA 575 and placebo occurred already after 2 days and increased until treatment end, with BSS reductions of 8.6 ± 0.2 and 6.2 ± 0.2 (marginal means ± SEM; p < 0.001). The score reduction for placebo after 7 days was comparable to that for EA 575 after 4 days. In the EA 575 group, the proportion of cough-free patients was 18.1% at treatment end and 56.2% at end of follow-up, compared to 9.3% and 25.6% for placebo, respectively. Adverse event rates for EA 575 and placebo were comparable. EA 575 reduces effectively the intensity of acute cough associated with ARTIs and leads to a significant acceleration of recovery. No safety signals were observed.

Correlation of the combined symptom and medication score with quality of life, symptom severity and symptom control in allergic rhinoconjunctivitis.

Background: The European Academy of Allergy and Clinical Immunology recommended the Combined Symptom and Medication Score (CSMS) as primary endpoint in clinical trials on allergen-specific immunotherapy (AIT) in allergic rhinoconjunctivitis. Here, the correlation between the CSMS and the validated standardised Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ(S)), Rhinitis Control Assessment Test (RCAT) and Visual Analogue Scale (VAS) was analysed. Methods: Two prospective, multicentre, non-interventional studies on tree pollen, grass pollen and house dust mite allergic patients were performed. The first study comprised 167 patients receiving AIT (AIT population), and the second included 56 patients treated with symptomatic medication only (control population). For up to two seasons (pollen)/exposure periods (house dust mites), participants documented their symptoms and medication intake in a CSMS diary, including VAS. In addition, the standardised RQLQ(S) and the RCAT were completed during study visits. Results: Comparison between CSMS and RQLQ(S) revealed a positive correlation in the AIT population (r = 0.426) and in the control population (r = 0.569). For CSMS and RCAT, a negative correlation with r = -0.409 (AIT) and r = -0.547 (control) was shown. Positive correlation between CSMS and VAS was also demonstrated with r = 0.585 (AIT) and r = 0.563 (control). Conclusion: These results support the assumption that the CSMS correlates with quality of life, symptom severity and symptom control on the one hand, while the moderate strength of correlations on the other hand mirrors distinctions of the CSMS compared to the assessments used here.

Pharmacometric Modeling of the Impact of Azelastine Nasal Spray on SARS-CoV-2 Viral Load and Related Symptoms in COVID-19 Patients.

The histamine-1 receptor antagonist azelastine was recently found to impact SARS-CoV-2 viral kinetics in a Phase 2 clinical trial (CARVIN). Thus, we investigated the relationship between intranasal azelastine administrations and viral load, as well as symptom severity in COVID-19 patients and analyzed the impact of covariates using non-linear mixed-effects modeling. For this, we developed a pharmacokinetic (PK) model for the oral and intranasal administration of azelastine. A one-compartment model with parallel absorption after intranasal administration described the PK best, covering both the intranasal and the gastro-intestinal absorption pathways. For virus kinetic and symptoms modeling, viral load and symptom records were gathered from the CARVIN study that included data of 82 COVID-19 patients receiving placebo or intranasal azelastine. The effect of azelastine on viral load was described by a dose-effect model targeting the virus elimination rate. An extension of the model revealed a relationship between COVID-19 symptoms severity and the number of infected cells. The analysis revealed that the intranasal administration of azelastine led to a faster decline in viral load and symptoms severity compared to placebo. Moreover, older patients showed a slower decline in viral load compared to younger patients and male patients experienced higher peak viral loads than females.

MicroCrystalline Tyrosine-adsorbed immunotherapy.

PURPOSE OF REVIEW: The purpose of this article is to provide an overview of the literature pertaining to the use of MicroCrystalline Tyrosine (MCT) in the immunotherapy with an emphasis on recent developments. RECENT FINDINGS: In addition to significant effectiveness and safety profiles, additional aspects of interest such as booster immunotherapy concepts, sustained clinical effects, long-term efficacy and disease-modifying effects are being focused on in the recently published studies. The depot adjuvant MCT also shows potential in promising disease-challenge models such as for malaria and melanoma. SUMMARY: MCT-adsorbed immunotherapy products have been shown to provide convincing overall safety, tolerability and efficacy outcomes, as well in vulnerable groups such as children and asthmatic patients.

Pharmacological Management of Allergic Rhinitis: A Consensus Statement from the Malaysian Society of Allergy and Immunology.

The goal of allergic rhinitis (AR) management is to achieve satisfactory symptom control to ensure good quality of life. Most patients with AR are currently treated with pharmacotherapy. However, knowledge gaps on the use of pharmacotherapy still exist among physicians, particularly in the primary care setting, despite the availability of guideline recommendations. Furthermore, it is common for physicians in the secondary care setting to express uncertainty regarding the use of new combination therapies like intranasal corticosteroid plus antihistamine combinations. Inadequate treatment leads to significant reduction of quality of life that affects daily activities at home, work, and school. With these concerns in mind, a practical consensus statement was developed to complement existing guidelines on the rational use of pharmacotherapy in both the primary and secondary care settings.

Benzydamine hydrochloride for the treatment of sore throat and irritative/inflammatory conditions of the oropharynx: a cross-national survey among pharmacists and general practitioners.

BACKGROUND: Benzydamine for oromucosal use is indicated in the relief of pain and irritation of the mouth and throat. It is an indazole derivative, non-steroidal anti-inflammatory drug, with combined local anesthetic and analgesic properties, and antiseptic activity, marketed under the brand name "Tantum Verde". The aim of this study was to explore knowledge and prescriptive/advising attitudes among general practitioners (GPs) and pharmacists (PHs) with regard to the topical treatment of sore throat and other irritative/inflammatory conditions of the oropharynx, with a focus on benzydamine. These findings could be important to increase awareness on benzydamine efficacy in sore throat and stomatological conditions, and to reinforce knowledge on the characteristics of benzydamine and its mechanisms of action among healthcare professionals (pediatricians, otolaryngologists, oncologists, etc.). MATERIALS AND METHODS: An online questionnaire survey was performed among PHs and GPs in four European countries (Italy, Germany, Russia and Poland). RESULTS: Both GPs and PHs proved to have an excellent knowledge and mastery of the constituents effective against oral symptoms. Among all the principles, benzydamine hydrochloride is the most recognized as certainly suitable for the topical treatment of sore throat symptoms and various inflammatory/irritative conditions of the oral cavity. It is recommended by about 90% of PHs and prescribed by 80% of GPs, mainly to solve the ailments caused by sore throats and stomatitis, especially for its anti-inflammatory, analgesic and anesthetic characteristics. Also in the pediatric field, benzydamine hydrochloride is recommended: among GPs, a high percentage (about 40%) prescribes it like the remedies based on dichlorobenzyl alcohol-sodium benzoate, which are instead more often recommended by PHs (44% against 37%). CONCLUSION: Although the public has a lot of confidence in this treatment, GPs and PHs do not recommend/prescribe benzydamine as a first-line treatment of sore throat and other irritative/inflammatory conditions of the oropharynx. To increase the knowledge of benzydamine among these healthcare professionals, it would be important to emphasize its characteristics and the different irritative/inflammatory conditions of the oropharynx in which it can be used.