Epidemiology of sensitization to perennial aeroallergens in adults with severe asthma in Belgium. The BEIgE study.

The evaluation of the atopic (allergic) status is an integral part of asthma assessment.1, 2 There are no global guidelines on which allergens to test, and there are geographical variations.3 The limited number of tests performed in clinical practice often complicates the management of patients with severe asthma (SA). By testing a panel of 43 perennial aeroallergens (PAAs) in 176 adult SA patients (Tables S1 and S2), this prospective study aimed at providing a detailed description of the epidemiology of sensitization to PAAs in SA. The individual PAAs were selected based on their relevance for Belgium, in concertation with academic experts. The analyses were performed in a central laboratory with a singleplex ImmunoCAP® assay using a Phadia 1000 analyzer (Thermo Scientific, serial number N10066) and commercially available ImmunoCAP® tests (ThermoFisher Scientific, Phadia AB, Uppsala, Sweden). In our population (of whom 53% had a previously reported sensitization to a PAA), 68% tested positive for ≥1 PAA, 43% for ≥4, and 13% for >10 PAAs (Figure 1A). A higher number of prospective positive tests was associated with increased total serum IgE levels, reaching an 18-fold increase in patients with >10 positive tests versus nonpositive (p < .0001, Figure 1B). The most prevalent sensitizations were to the three house dust mites (HDMs) Dermatophagoides pteronyssinus, Dermatophagoides farinae, and Dermatophagoides microceras, and to Aspergillus fumigatus, Staphylococcus aureus Toxic Shock Syndrome Toxin (TSST), and Candida albicans, using two different sIgE cutoff levels (Figure 1C). Thus, this study provides evidence that the number of sensitizations to PAAs is underestimated in SA patients, being in line with previous data.4 Strikingly, our data indicate a high prevalence of sensitization to S. aureus toxins,5 especially to TSST. The prevalence ranking in patients previously considered non-sensitized to PAAs but with at least one positive test in the prospective laboratory results, highlights the interest of evaluating sensitizations to these PAAs in patients suffering from severe asthma (Table S3). Interestingly, patients living in an urban area had overall a higher mean (±SEM) number of prospective positive tests compared to those living in a rural area (5.2 ± 0.6 vs 3.3 ± 0.4 tests, respectively, p < .05; Figure S1A), as well as an increase in total serum IgE (Figure S1B), a difference in the level of some sIgE (Figure S1C) and in the ranking of the most prevalent sensitizations (Figure S1D), despite similar clinical characteristics (not shown). We also compared the ranking of sensitizations between patients with early versus adult-onset asthma (<18 years of age vs ≥18, respectively),6 the latter representing the majority of patients included in this study (68.9%, mean ± SEM; age of onset 30.3 ± 1.5 years, Table S1). We found a marked difference in sensitization profiles between both groups (Table S3). There was a high prevalence of sensitization to 10 PAAs in patients with early onset asthma (n = 52); each of these 10 PAAs were positive in at least 25% of this population, whereas the prevalence did not exceed 25% in patients with adult-onset asthma (n = 115). The four most prevalent sensitizations were to the 4 HDMs in patients with early onset asthma, in contrast to S. aureus-TSST, D. pteronyssinus, A. fumigatus, and C. albicans in adult-onset asthma (Table S3). We propose a diagnostic workup guideline (Table 1) to select and prioritize specific IgEs for testing in daily practice in countries with a PAA profile comparable to Belgium. We suggest omitting D. farinae and D. microceras given the redundancy (all patients sensitized to D. farinae and D. microceras were also sensitized to D. pteronyssinus). No other redundant tests were identified in the PAA test panel. Testing for sensitizations to PAAs “beyond the usual suspects” should be considered by physicians managing patients with SA. In particular, S. aureus toxins should be added to the test panels for patients with SA, especially in those previously considered as “non-atopic.” Jan Van Schoor, Sandra Gurdain, and Mieke Jansen are accountable for study concept and design, Jan Van Schoor and Sandra Gurdain for data collection, Eléonore Maury for data analysis, and Eléonore Maury and Jan Van Schoor for the interpretation of data. Eléonore Maury and Jan Van Schoor drafted the article. Florence Schleich, Claus Bachert, Shane Hanon, and Olivier Michel performed critical revision of the article for important intellectual content. Jan Van Schoor supervised, initiated, and guided the entire project. All authors gave final approval of the version to be published. We thank Ann Verdonck, Karolien Claes, Sofie Vanmechelen, Gertjan Gysembergt, Glynis Frans, and the laboratory technicians (department Allergy) from the Central Laboratory of the University Hospital Gasthuisberg Leuven, Belgium, for performing the total and specific IgE measurements. We also thank Wim Claeys (consultant) for the expert administrative support throughout all phases of the study. List of BEIgE Study Investigators (in alphabetical order): Gwenaëlle Brui, CHWAPI Notre-Dame, Tournai; Alain Delobbe, Private Practice; Solange de Lovinfosse, Hôpital de Jolimont, La Louvière; Itte Dobbeleir, St Elisabeth Hospital, Herentals; Lieven Dupont, University Hospital Gasthuisberg, Leuven; Shane Hanon, University Hospital VUB, Brussel; Sofie Maddens, AZ Groeninge, Kortrijk; Olivier Michel, University Hospital ULB Brugmann, Brussel; Vicky Nowé, St Vincentius Hospital, Antwerpen; Rudi Peché, University Hospital Vésale, Charleroi; Linda Remels, AZ St Elisabeth, Zottegem; Anna Sadowska, ZOL, Maaseik; Florence Schleich, University Hospital Sart-Tilman, Liège; Hélène Simonis, CHR La Citadelle, Liège; François Spirlet, University Hospital UCL Dinant-Godinne, campus Dinant; Joël Thimpont, CH EpiCURA, Baudour; Bram Vandenberge, AZ St Jan, campus Henri Serruys, Oostende*; Luc Vanmaele, AZ Zeno, Knokke*; *Centers (2) not able to recruit due to the COVID sanitary crisis. FS reports grants and research support from GSK, Chiesi, and AstraZeneca, and honoraria or consultation fees from GSK, Chiesi, Novartis, AstraZeneca, TEVA, and Amgen. CB is an Advisory Board member and speaker for Novartis, GSK, AstraZeneca, Sanofi, ALK, and Mylan. SH reports consultancy fees from GSK, AstraZeneca, Teva, Sanofi, MSD and Novartis, as well as research grants and personal fees from Chiesi, outside the submitted work. OM has no conflicts of interest to declare for this article. This research was sponsored by Novartis Pharma. The data that supports the findings of this study are available in the supplementary material of this article. Data S1. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.