The holo beta-lactoglobulin lozenge reduces symptoms in cat allergy-Evaluation in an allergen exposure chamber and by titrated nasal allergen challenge

Abstract

Background: The allergists´ tool box in cat allergy management is limited. Clinical studies have shown that holo beta-lactoglobulin (holoBLG) can restore micronutritional deficits in atopic immune cells and alleviate allergic symptoms in a completely allergen-nonspecific manner. With this study, we aimed to provide proof of principle in cat allergy.

Methods: A novel challenge protocol for cat allergy in a standardized ECARF allergen exposure chamber (AEC) was developed. In an open pilot study (NCT05455749), patients with clinically relevant cat allergy were provoked with cat allergen for 120 min in the AEC before and after a 3-month intervention phase (holoBLG lozenge 2x daily). Nasal, conjunctival, bronchial, and pruritus symptoms were scored every 10 min- constituting the total symptom score (TSS). Peak nasal inspiratory flow (PNIF) was measured every 30 min. In addition, a titrated nasal provocation test (NPT) was performed before and after the intervention. Primary endpoint was change in TSS at the end of final exposure compared to baseline. Secondary endpoints included changes in PNIF, NPT, and occurrence of late reactions up to 24 h after exposure.

Results: 35 patients (mean age: 40 years) completed the study. Compared to baseline, holoBLG supplementation resulted in significant improvement in median TSS of 50% (p < 0.001), as well as in median nasal flow by 20 L/min (p = 0.0035). 20% of patients reported late reactions after baseline exposure, but 0% after the final exposure.

Conclusions: Cat allergic patients profited from targeted micronutrition with the holoBLG lozenge. As previously seen in other allergies, holoBLG supplementation also induced immune resilience in cat allergies, resulting in significant symptom amelioration.

Keywords: allergen exposure chamber; allergic rhinoconjunctivitis; cat allergy; immune resilience; targeted micronutrition.

Conflict of interest statement

Franziska Roth‐Walter and Erika Jensen‐Jarolim declare inventorship of the patent EP 14150965.3, Year: 01/2014; US 14/204,570 (Method and means for diagnosing and treating allergy; owned by Biomedical International R + D GmbH, Vienna, Austria), underlying the immunoBON® lozenge. Erika Jensen‐Jarolim is a shareholder of Biomedical Int. R + D GmbH, Vienna, Austria and collaborates with Bencard Allergie GmbH in projects and studies on holoBLG. Franziska Roth‐Walter received research funding from Biomedical International R + D GmbH, Vienna, Austria and lecture honoraria by Bencard Allergie GmbH, Munich, Germany and Vienna, Austria, and Allergy Therapeutics, Worthing, UK. Jennifer Raab, Anke Graessel, Thomas Zwingers and Matthias F. Kramer are employees of Allergy Therapeutics/Bencard Allergie GmbH. Karl–Christian Bergmann received honoraria for lectures from ALK, AstraZeneca, Bencard, GSK, HAL, LETI Novartis, Sanofi during last 2 years, works for the German Pollen Information Service Foundation and is member of ECARF‐Institute GmbH. Torsten Zuberbier reports lecture honoraria from AstraZeneca, ALK, AbbVie, Almirall, Astellas, Bayer health Care, Bencard, Berlin Chemie, FAES, HAL, Leti, Meda, menarini, Merck, MSD, Novartis, Pfizer, Sanofi, Stallergenes, Takeda, Teva, UCB, Henkel, Kryolan and LÓreal. Sylvia Becker and Sebastian Kugler report no competing interests.

© 2023 The Authors. Clinical and Translational Allergy published by John Wiley and Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.

Figures

FIGURE 1

Individual changes (median) in symptom scores and well‐being at 120 min in the AEC at baseline (V2) and after intervention (V5). A: The primary endpoint TSS (total symptom score) was reduced by −50% (p = 0.0006). B: Reduction of the total eye symptom score (TESS) by −33% (p = 0.0118). C: Reduction in total nasal symptom score (TNSS) by −50% (p = 0.0066). D: No reduction in total bronchial symptom score (TBSS). E: Reduction in pruritus symptoms (TOSS: itching skin and palate) by −50% (p < 0.0001). F: Improvement in personal well‐being, determined by visual analog scale (VAS), by 42% (p = 0.0238), which is reflected in a reduction of median VAS score.

FIGURE 2

Temporal evolution of the sum of all symptoms (TSS) and the single symptom scores for nose (TNSS), bronchial (TBSS), eye (TESS) and pruritus (TOSS) over time of cat allergen exposure in the AEC at baseline (V2) and after intervention (V5). A: Increase and respective confidence intervals (CI) of all symptom scores over time analyzed by the linear mixed effects models. The smaller slope increases during V5 describe decreased symptoms during this exposure compared to V2. B: Summary table of linear mixed effects model results, which analyzed the symptom scores for their linear evolution over time. p‐values represent a descriptive summary measure.

FIGURE 3

Development of peak nasal inspiratory flow (PNIF) during the exposure in the AEC at baseline (V2) and after intervention (V5). Median improvement in PNIF at 120 min by 20 L/min (p = 0.0035) at V5 compared to V2.

FIGURE 4

Change in parameters of the nasal provocation test (NPT). A: Change in TSSNPT (total symptom score of all symptoms assessed during the NPT) after intervention (V4) at the concentration that led to a positive NPT at baseline (V1): median reduction of −1 (p = 0.0091). B: Change in peak nasal inspiratory flow during NPT (PNIFNPT) after intervention (V4) at the concentration, that led to a positive NPT at baseline (V1): median improvement of 25 L/min (p = 0.0004). C: Individual change of required concentration in titrated NPT after intervention (V4) compared to baseline: 12 patients remained negative despite the highest allergen concentration, 8 patients required a higher concentration for a positive NPT, 12 patients the same and 3 patients a lower concentration (p = 0.0203).

FIGURE 5

Late phase reactions (LPR) reported during the follow‐up call 24 h after exposure in the AEC at baseline (V3) and after intervention (V6): 20% of patients reported LPRs after the first exposure in the AEC at V3, while this was described by 0% of patients after the final exposure (V6).