LAUSR

To the editor, Allergic rhinitis (AR) is a common disease resulting in nasal, ocular and potentially oropharyngeal symptoms. Up to 70% of pollen allergy patients also suffer from the “oral allergy syndrome” (OAS), manifesting in itching and swelling of the oropharynx. Antihistamines are the first choice of drugs to treat allergic oropharyngeal symptoms, but reservation against use of drugs and side effects may limit patient compliance. In addition to pharmacotherapies against AR, guidelines recommend allergen‐specific immunotherapy (SIT), comprising subcutaneous (SCIT) or sublingual (SLIT) forms. However, in more than 50% of patients, SLIT preparations cause side effects, resulting in oropharyngeal itching, swelling, discomfort or irritation. These side effects often begin upon initiation of SLIT and last for 30–60 min. Therapy of these side effects includes antihistamines. Here, Ectoin containing lozenges (CE‐marked medical device Ectoin Allergy Lozenges), a non‐pharmacological treatment option for allergic oropharyngeal symptoms, was investigated. Ectoin is a compatible solute with membrane‐protecting and inflammation‐ reducing properties, whose clinical efficacy in AR has already been reported. The current study investigated therapeutic and preventive effects of Ectoin lozenges on oropharyngeal allergic symptoms using the initiation of SLIT as a study model. The multi‐center, prospective, randomized, controlled study was performed according to §23b German Medical Devices Act (MPG), registered with ClinTrials.gov database (NCT03975257) and approved by the responsible ethics committees. Eligibility criteria are described in Table S1. Treatment (one lozenge) was administered 5 min before (preventive) or 5 min after (therapeutic) the first SLIT dose. No lozenge was administered in the control group. SLIT was carried out in accordance with the guidelines; Fexofenadine was available as on‐ demand rescue medication. Patients' oropharyngeal symptoms were assessed in a patient questionnaire 30 min after SLIT initiation, determining the perception of allergic symptoms (swelling, itching, and irritation) in mouth, on the lips and in the throat/pharynx. Symptom intensity was evaluated as 0 = “no symptoms”, 1 = “mild symptoms, 2 = “moderate symptoms,” or 3 = “severe symptoms.” The sum score of individual allergic symptoms of an organ resulted in the organ‐specific symptom score, and the sum of organ‐specific symptoms in the oropharyngeal symptom score (OPSS; min = 0, max = 27). Tolerability and safety of treatments were assessed on the occurrence of (serious) adverse events. Eighty‐nine patients aged 19–75 years with equal distribution into preventive, therapeutic, or control group were enrolled in seven study sites (Figure S1, Table S2). Treatment groups were balanced regarding gender, age, and type(s) of treated allergy (Table S3). No serious adverse event and one mild adverse event occurred in the study (Table S3). Preventive and therapeutic treatment with Ectoin lozenges resulted in reduction of oropharyngeal symptoms compared to the control group, reaching significant differences regarding mouth symptoms and OPSS (Figure 1). The most pronounced symptom in the mouth was itching. Preventive treatment with Ectoin lozenges resulted in 66% lower itching scores (p = 0.002), and patients treated therapeutically showed 77% lower values (p = 0.000) compared to control. In line with this, sum scores of the mouth were statistically significantly lower in patients treated with Ectoin lozenges compared to control (Figure 1). Swelling and itching of the lips were lower upon preventive and therapeutic treatment compared to control, whereas symptom scores for lip irritation were lower upon preventive treatment but higher upon therapeutic treatment compared to control. Overall, symptoms of the lips were not significantly different between groups (Figure 1). Pharynx/throat symptoms were lower in patients treated preventively or therapeutically compared to control without significant differences between groups (Figure 1). Differences in the OPSS were significant (p < 0.017) comparing preventive treatment (2.72), therapeutic treatment (2.14) and the control group (4.61; Figure 1). A subgroup analysis of patients with seasonal allergy demonstrated significantly lower values reflecting itching of the mouth, sum scores of the mouth and OPSS upon preventive and therapeutic