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.

Co-exposure to highly allergenic airborne pollen and fungal spores in Europe.

The study is aimed at determining the potential spatiotemporal risk of the co-occurrence of airborne pollen and fungal spores high concentrations in different bio-climatic zones in Europe. Birch, grass, mugwort, ragweed, olive pollen and Alternaria and Cladosporium fungal spores were investigated at 16 sites in Europe, in 2005-2019. In Central and northern Europe, pollen and fungal spore seasons mainly overlap in June and July, while in South Europe, the highest pollen concentrations occur frequently outside of the spore seasons. In the coldest climate, no allergy thresholds were exceeded simultaneously by two spore or pollen taxa, while in the warmest climate most of the days with at least two pollen taxa exceeding threshold values were observed. The annual air temperature amplitude seems to be the main bioclimatic factor influencing the accumulation of days in which Alternaria and Cladosporium spores simultaneously exceed allergy thresholds. The phenomenon of co-occurrence of airborne allergen concentrations gets increasingly common in Europe and is proposed to be present on other continents, especially in temperate climate.

Dogmas, challenges, and promises in phase III allergen immunotherapy studies.

The concept of treatment of an allergy with the offending allergen was introduced more than a century ago. Allergen immunotherapy (AIT) is the only disease modifying treatment of allergic diseases caused by inhalational allergens and insect venoms. Despite this, only few AIT products have reached licensure in the US or an official marketing authorization status in European countries. Moreover, most of these AIT products are provided on an individual patient basis as named patient products (NPP) in Europe, while individualized preparations of (mixed) allergenic extract vials for subcutaneous administration (compounding) is common practice in the US. AIT products are generally considered safe and well tolerated, but the major practical clinical development challenge is to define the optimal dose and prove the efficacy and safety of these products using state-of-the art Phase II and pivotal Phase III studies. In planning Phase II-III AIT studies, a thorough understanding of the study challenges is essential (e.g. variability and non-validated status of subjective primary endpoints, limitations of pollen season definitions) and dogmas of these products (e.g., for sublingual immunotherapy (SLIT) trials double-blinding conditions cannot be maintained, resulting in stronger placebo responses in the active treatment group and inflated treatment effects in Phase III). There is future promise for more objective biomarker endpoints (e.g. basophil activation (CD63 and CD203c), subsets of regulatory dendritic, T and B cells, IL-10-producing group 2 innate lymphoid cells; alone or in combination) to overcome several of these dogmas and challenges; innovation in AIT clinical trials can only progress with integral biomarker research to complement the traditional endpoints in Phase II-III clinical development. The aim of this paper is to provide an overview of these dogmas, challenges and recommendations based on published data, to facilitate the design of Phase III studies and improve the evidence basis of safe and effective AIT products.

Defining Pollen Seasons: Background and Recommendations.

PURPOSE OF REVIEW: The definition of a pollen season determines the start and the end of the time period with a certain amount of pollen in the ambient air. Different pollen season definitions were used for a long time including the use of different terms for data and methods used to define a pollen season. Recently suggested pollen season definitions for clinical trials were tested and applied for the first time to more aeroallergens. RECENT FINDINGS: This is a review on pollen season definitions and the latest recommendations. Recently, proposed terminology in aerobiology is promoted here in order to support reproducibility and repeatability in research. Two pollen season definitions, one based on percentages and one based on pollen concentrations, were tested. Percentage definitions can be recommended for standard aerobiological routines and for retrospective applications, whereas pollen concentrations definitions can be recommended for prospective applications such as clinical trials.

Humoral and cellular cross-reactivity between Amb a 1, the major ragweed pollen allergen, and its mugwort homolog Art v 6.

Ragweed and mugwort are closely related weeds that represent the major cause of pollen allergy in late summer. Concomitant sensitization and clinical cross-reactivity frequently occur in subjects who are coexposed to both pollen species, and have implications for diagnosis and specific immunotherapy. Molecules involved in this cross-reactivity might be Amb a 1, the major ragweed pollen allergen, and Art v 6, a highly homologous allergen from mugwort. Therefore, we investigated the IgE and T cell response to Art v 6 of 60 weed pollen-allergic patients and assessed its immunological cross-reactivity with Amb a 1. Results of ELISA inhibition experiments suggested that both allergens are largely cross-reactive, but Amb a 1 possesses more IgE epitopes than Art v 6. In patients with IgE to both allergens, Amb a 1-induced T cell lines and clones responded weakly to Art v 6. Moreover, Art v 6-induced T cell lines responded stronger to Amb a 1. T cell epitope mapping of Art v 6 revealed that it contains only a few cross-reactive epitopes, which is opposed to the multiple T cell-activating regions present in Amb a 1. In summary, Amb a 1 can elicit more diverse allergen-specific IgE and T cell responses than Art v 6 and dominates the cross-reactivity with its homolog. Nevertheless, Art v 6 can act as a primary sensitizing allergen in areas with high mugwort pollen exposure, and consequently may facilitate sensitization to Amb a 1 by epitope cross-recognition of T and B cells.

Efficacy and safety of an oral formulation of cetirizine and prolonged-release pseudoephedrine versus budesonide nasal spray in the management of nasal congestion in allergic rhinitis.

INTRODUCTION: The aim of this study was to compare the decongestant properties and tolerability of oral cetirizine and pseudoephedrine in a prolonged release form with those of nasal (aqueous spray) budesonide. METHODS: Thirty-six individuals experiencing allergic rhinitis to house dustmites (HDM) participated in a study according to a randomized, crossover, two-period, two-treatment design with at least a 2-week washout period between treatments. In each period of 4 consecutive days, medications were taken twice daily. On day 1, immediately after the first intake of medication, individuals were exposed to HDM extract in the Vienna Challenge Chamber (VCC) for 5 hours. The primary efficacy parameter was nasal congestion, assessed by active anterior rhinomanometry and rating of nasal cavity photos. RESULTS: Rhinomanometry and nasal cavity photos both indicated that cetirizine/pseudoephedrine efficacy was statistically superior to budesonide in the management of nasal congestion during VCC sessions. The efficacy of cetirizine/pseudoephedrine was similar to that of budesonide from the end of day 1 up to day 4 when individuals were exposed to their natural environment post exposure to the aeroallergens. This study confirms the efficacy of cetirizine/pseudoephedrine and budesonide in the management of nasal congestion associated with allergic rhinitis. Both medications were well-tolerated. Cetirizine/pseudoephedrine was more effective than budesonide during HDM exposure, whereas budesonide became as effective as cetirizine/pseudoephedrine several hours post exposure to the allergens.