Showing papers by "Josep M. Antó published in 2023"

A molecular sensitization map of European children reveals exposome‐ and climate‐dependent sensitization profiles

Abstract: Understanding differences in sensitization profiles at the molecular allergen level is important for diagnosis, personalized treatment and prevention strategies in allergy.

Digitally‐enabled, patient‐centred care in rhinitis and asthma multimorbidity: The ARIA‐MASK‐air® approach

Abstract: Abstract MASK‐air®, a validated mHealth app (Medical Device regulation Class IIa) has enabled large observational implementation studies in over 58,000 people with allergic rhinitis and/or asthma. It can help to address unmet patient needs in rhinitis and asthma care. MASK‐air® is a Good Practice of DG Santé on digitally‐enabled, patient‐centred care. It is also a candidate Good Practice of OECD (Organisation for Economic Co‐operation and Development). MASK‐air® data has enabled novel phenotype discovery and characterisation, as well as novel insights into the management of allergic rhinitis. MASK‐air® data show that most rhinitis patients (i) are not adherent and do not follow guidelines, (ii) use as‐needed treatment, (iii) do not take medication when they are well, (iv) increase their treatment based on symptoms and (v) do not use the recommended treatment. The data also show that control (symptoms, work productivity, educational performance) is not always improved by medications. A combined symptom‐medication score (ARIA‐EAACI‐CSMS) has been validated for clinical practice and trials. The implications of the novel MASK‐air® results should lead to change management in rhinitis and asthma.

Outcomes from the First European Planetary Health Hub Convening at ARTIS in Amsterdam

Abstract: A new network of over 72 organizations from 12 countries was activated during a convening at ARTIS in Amsterdam on 26–27 September 2022. Representatives are aligned with the transdisciplinary field and social movement of Planetary Health, which analyzes and addresses the impacts of human disruptions to natural systems on human health and all life on Earth. The new European Planetary Health Hub consists of organizations from various sectors, including universities, healthcare, youth, business, and civil society. The Convening, co-organized by the Planetary Health Alliance (PHA), the European Environment and Sustainable Development Advisory Councils Network (EEAC), and Natura Artis Magistra (ARTIS), aimed to develop Planetary Health Working Groups for Education, Policy Engagement, Research, and Movement Building. The Convening resulted in an outline for each of the Working Group’s aims, visions, missions, priorities, and activities, and set the framework for sustaining their activities in the future through the establishment of the European Planetary Health Hub Secretariat in the Netherlands. The Hub members shared lessons learned, built relationships, and developed artwork-inspired perspectives on Planetary Health. In conclusion, the Convening led to the establishment of a strong European foundation to contribute to the transformations needed for sustainable, just, and equitable societies that flourish within the limits of our ecosystems.

Patient‐centered digital biomarkers for allergic respiratory diseases and asthma: The ARIA‐EAACI approach – ARIA‐EAACI Task Force Report

Abstract: Biomarkers for the diagnosis, treatment and follow‐up of patients with rhinitis and/or asthma are urgently needed. Although some biologic biomarkers exist in specialist care for asthma, they cannot be largely used in primary care. There are no validated biomarkers in rhinitis or allergen immunotherapy (AIT) that can be used in clinical practice. The digital transformation of health and health care (including mHealth) places the patient at the center of the health system and is likely to optimize the practice of allergy. Allergic Rhinitis and its Impact on Asthma (ARIA) and EAACI (European Academy of Allergy and Clinical Immunology) developed a Task Force aimed at proposing patient‐reported outcome measures (PROMs) as digital biomarkers that can be easily used for different purposes in rhinitis and asthma. It first defined control digital biomarkers that should make a bridge between clinical practice, randomized controlled trials, observational real‐life studies and allergen challenges. Using the MASK‐air app as a model, a daily electronic combined symptom‐medication score for allergic diseases (CSMS) or for asthma (e‐DASTHMA), combined with a monthly control questionnaire, was embedded in a strategy similar to the diabetes approach for disease control. To mimic real‐life, it secondly proposed quality‐of‐life digital biomarkers including daily EQ‐5D visual analogue scales and the bi‐weekly RhinAsthma Patient Perspective (RAAP). The potential implications for the management of allergic respiratory diseases were proposed.

Improvement of daily allergy control by sublingual immunotherapy: A MASK-air® study.

Abstract: Allergen immunotherapy (AIT) is an effective treatment for allergic rhinitis and has been hypothesised as rapidly effective.1 Rush subcutaneous AIT to pollen and mites reduces skin test reactivity to allergens within days, in a dose-dependent and time-independent manner.2, 3 Venom rush AIT is also effective within days. The tolerance of beekeepers to bee stings fades in some individuals and is also re-installed after a few stings in a dose-dependent and time-independent manner.4 Finally, desensitisation to drug allergy is effective within hours and there is a refractory period after tolerance.5 These short-term clinical sequences cannot be explained by an adaptive immune response (immunotherapy) but may be related to rapid and short-lasting cell downregulation responses (desensitisation).1, 6 These considerations have prompted the hypothesis that sublingual immunotherapy (SLIT) may induce a rapid relief of allergic symptoms during the pollen season.1 While previous studies have found that SLIT is effective in the same allergy season as when first introduced,7 no study has ever assessed its efficacy on a daily basis. Therefore, in this study, we aimed to assess whether days of SLIT use were associated with better allergy control during the expected pollen season. Such analyses may hint at a potential short-term effect of SLIT, to be assessed by proper studies. MASK-air® is a free mobile app available in 27 countries. The app includes a daily monitoring questionnaire which can be answered on a daily basis. The questionnaire assesses (i) the daily severity and impact of allergy symptoms (through four mandatory visual analogue scales—VASs),8 (ii) the daily rhinitis and asthma medication used on that day by the patient and (iii) whether the patient used AIT on that day. Such information allows the computation of the combined symptom-medication score (CSMS), assessing the daily control of allergic rhinitis.9 We included the daily monitoring data of European MASK-air® users (i) aged between 16 years (or lower—not below 13 years—for countries with a lower age of digital consent) and 90 years, (ii) with a self-reported diagnosis of allergic rhinitis and (iii) on SLIT for grass pollen. We analysed the data provided during the months of May and June (assuming that they corresponded to the grass pollen season in Europe) from 2015 to 2021. We performed a cross-sectional analysis, in which we studied all days reported between May and June for three different samples: (S1) all users under SLIT (of any type) for grass pollen; (S2) users taking SLIT tablets for grass pollen and (S3) users using SLIT (of any type) for grass pollen and reporting at least 1 day of AIT use during the studied period (to account for non-adherence and potential incorrect reporting of SLIT use). Sample 1 was used to assess a sufficiently-powered group. The robustness of the results of SLIT in S1 was assessed in S2 and S3, where different inclusion criteria were adopted. We performed this cross-sectional analysis by building multivariable mixed-effects regression models to assess, for each sample, whether days of AIT use were associated with a better allergic rhinitis control (with the dependent variables being either the CSMS or the VAS quantifying the impact of global allergy symptoms—‘VAS global’). In our models, we considered the clustering of observations by users, by country and by month of the year, setting these variables as random effects (i.e. we clustered observations by users, by the user's country and by the month of the year). In addition, results were further adjusted for the following independent variables which were included in our regression models: baseline domains impacted by allergic rhinitis, baseline symptoms of allergic rhinitis, patients' gender and age, self-reported diagnosis of asthma, occurrence of conjunctivitis and use of daily rhinitis or asthma medication in monotherapy or co-medication. We also performed a longitudinal analysis, in which we analysed complete periods of 2 weeks (missing at most an average of 2 days per week) of patients using SLIT for grass pollen and reporting at least 1 day of AIT use during the same period. We performed the longitudinal study in a smaller subset of users, comparing days of AIT use versus days when AIT was not used on the CSMS and VAS global. For such comparisons, we built multivariable mixed-effects regression models similar to those applied in cross-sectional analyses. When responding to the MASK-air® daily questionnaire, it is not possible to skip any of the questions and data are saved only after the final answer. This precludes missing data within each questionnaire. P-values <.05 were considered statistically significant. A Holm–Bonferroni correction was applied to account for multiple analyses. Additional information about study methods and findings is available in the following repository: https://github.com/BernardoSousaPinto/Improvement-of-daily-allergy-control-by-sublingual-immunotherapy-A-MASK-air-study MASK-air® is CE1-registered and complies with the General Data Protection Regulation. All data were anonymised prior to the study. Users agreed to having their data analysed for scientific purposes in the Terms of Use. An independent review board approval was not required for this study. In the cross-sectional analysis, we studied 3968 days from 171 patients in S1. Immunotherapy was reported in 2380 (60.0%) days. There were 111 users (N = 2311 days; S2) using SLIT tablets for grass pollen. Finally, 113 users (N = 3098 days; S3) indicated that they were under SLIT for grass pollen allergy and reported the use of AIT for at least 1 day. In the longitudinal analysis, we studied 2615 days from 45 patients. Immunotherapy was reported in 2026 (77.5%) days. The baseline characteristics of the users were not similar in all samples. The median CSMS and VAS global levels tended to be lower in days with SLIT. In days of MASK-air® use, the average adherence to SLIT was 54.8%. Considering only users reporting at least 1 day of SLIT use, the average adherence was 83.0%. In S1, SLIT days were associated with improved CSMS (regression coefficient = −2.2; 95%CI = −3.1; −1.3; p < .001) and VAS global (regression coefficient = −3.0; 95%CI = −4.5; −1.5; p < .001) (Table 1; Figure 1). SLIT days were also associated with decreased CSMS and VAS global in S2 and S3 (Table 1; Figure 1). Higher adherence to the MASK-air® app was found to be associated with lower CSMS and VAS global. Ancillary analyses were performed (i) in grass pollen SLIT users reporting at least 4 days of MASK-air® use, (ii) comparing patients with high/variable median CSMS versus those with low median CSMS and (iii) considering the effect of SLIT given on the previous day. Similar results were observed in all these analyses, except when, for days without SLIT, we compared days when SLIT had been used on the previous day versus days on which this had not occurred. Results of the longitudinal study were comparable to those of the cross-sectional study (Figure 1), with SLIT days being associated with lower CSMS (regression coefficient = −2.6; 95%CI = −3.6; −1.6) and VAS global (regression coefficient = −4.0; 95%CI = −5.6; −2.3). This study using MASK-air® real-world data suggests that in patients under SLIT during the pollen season, AIT may have a very short-term effect. In particular, in patients under SLIT, days with AIT were associated with better allergy control than those without AIT. However, real-world data are only hypothesis-generating (considering the study design, we should be particularly careful when dealing with temporality) and such hypotheses require confirmation by future well-designed and sufficiently-powered trials. This study has several strengths, including its multinational scope and the large volume of data analysed. In addition, the CSMS and MASK-air® VASs display medium-high validity, reliability and responsiveness.8, 9 Finally, we analysed three samples in cross-sectional analyses and performed a longitudinal analysis, observing robust results. This study also has limitations of which some are common to other mHealth observational studies (e.g. selection biases resulting from overrepresentation of younger users and information biases related to the self-reported nature of the data).8 In addition, there are specific limitations: (i) This is mostly a cross-sectional study, impairing the establishment of causality or of temporal relationships, and therefore being capable only of generating new hypotheses. Although we performed a longitudinal analysis, it encompassed only 45 patients. (ii) We do not have information on the date each patient started using SLIT. We are therefore unable to distinguish patients who have been on SLIT for a period long enough to allow reaching an optimal control versus those who have just started using SLIT. (iii) The grass pollen season has been roughly estimated, considering the period of May–June. (iv) We did not consider the different SLIT products in this study. These different products display highly variable standardisation, allergen content and clinical documentation of efficacy and safety. Such a limitation, however, has been partly overcome by the assessment of S2, as, in Europe, there are only a limited set of available products for grass pollen SLIT tablets. The results of this study raise the hypothesis that SLIT may have a short-term effectiveness. If confirmed in future studies, this may provide a novel strategy in patients allergic to pollens who are uncontrolled despite optimal pharmacotherapy. However, several limitations of the study should be considered and its results should be understood as hypothesis-generating, building the basis for future studies. Jean Bousquet proposed the concept of the paper, analysed the results and wrote the paper. Bernardo Sousa-Pinto made the statistical plan, performed the analysis and wrote the paper. Josep M Anto, G Walter Canonica, Wienczyslawa Czarlewski, Philippe Devillier, Tari Haahtela, Daniel Laune, Joaquim Mullol, Marek Jutel, Piotr Kuna, Mohamed H Shamji, Erkka Valovirta, Torsten Zuberbier and Joao A Fonseca represented the think tank and participated in the analysis and in the writing of the paper. Ludger Klimek, Luisa Brussino, Lorenzo Cecchi, Violeta Kvedariene, Mario Morais-Almeida, Ralph Mösges, Marek Niedoszytko, Nikolaos G Papadopoulos, Vincenzo Patella, Nhân Pham-Thi, Boleslaw Samolinski, Luis Taborda-Barata31, Sanna Toppila-Salmi, Joaquin Sastre, Arunas Valiulis and Maria Teresa Ventura proposed the MASK-air app to their patients. Oliver Pfaar participated in the concept of the study and wrote the paper. All authors have read the paper and given their final approval for submission. JB reports personal fees from Cipla, Menarini, Mylan, Novartis, Purina, Sanofi-Aventis, Teva, Uriach, other from KYomed-Innov, other from Mask-air-SAS, outside the submitted work. LC reports personal fees from Thermofisher, personal fees from Sanofi, personal fees from Astra Zeneca, personal fees from Novartis, outside the submitted work. PD reports personal fees from ALK Abello, personal fees and non-financial support from Boehringer Ingelheim, personal fees from Chiesi, personal fees and non-financial support from Astra Zeneca, personal fees from GlaxoSmithKline, personal fees from Menarini, personal fees from Novartis, personal fees and non-financial support from Stallergenes, personal fees from Sanofi, outside the submitted work. JAF reports being co-founder of an SME that develops mHealth technologies, such as digital biomarkers and has the copyright of the CARAT and a CARATkids PROM. TH reports personal fees from Orion Pharma, outside the submitted work. MJ reports personal fees from ALK-Abello, personal fees from Allergopharma, personal fees from Stallergenes, personal fees from Anergis, personal fees from Allergy Therapeutics, personal fees from Leti, personal fees from HAL, during the conduct of the study; personal fees from GSK, personal fees from Novartis, personal fees from Teva, personal fees from Takeda, personal fees from Chiesi, outside the submitted work. LK reports grants and personal fees from Allergopharma, grants and personal fees from Viatris, personal fees from HAL Allergie, personal fees from ALK Abelló, grants and personal fees from LETI Pharma, grants and personal fees from Stallergenes, grants from Quintiles, grants and personal fees from Sanofi, grants from ASIT biotech, grants from Lofarma, personal fees from Allergy Therapeut., grants from AstraZeneca, grants and personal fees from GSK, grants from Inmunotek, personal fees from Cassella med, personal fees from Novartis, personal fees from Regeneron Pharmaceuticals, personal fees from ROXALL Medizin GmbH, outside the submitted work; and Membership: AeDA DGHNO Deutsche Akademie für Allergologie und klinische Immunologie HNO-BV GPA EAACI. PK reports personal fees from Adamed, personal fees from Berlin Chemie Menarini, personal fees from AstraZeneca, personal fees from Boehringer Ingelheim, personal fees from Celon Pharma, personal fees from Polpharma, personal fees from Teva, personal fees from Novartis, personal fees from Glenmark, personal fees from Zentiva, outside the submitted work. VK reports other from NORAMEDA, outside the submitted work. RM reports personal fees from ALK, grants from ASIT biotech, personal fees from allergopharma, personal fees from Allergy Therapeutics, grants and personal fees from Bencard, grants from Leti, grants, personal fees and non-financial support from Lofarma, non-financial support from Roxall, grants and personal fees from Stallergenes, grants from Optima, personal fees from Friulchem, personal fees from Hexal, personal fees from Servier, personal fees from Klosterfrau, non-financial support from Atmos, personal fees from Bayer, non-financial support from Bionorica, personal fees from FAES, personal fees from GSK, personal fees from MSD, personal fees from Johnson&Johnson, personal fees from Meda, personal fees and non-financial support from Novartis, non-financial support from Otonomy, personal fees from Stada, personal fees from UCB, non-financial support from Ferrero, grants from BitopAG, grants from Hulka, personal fees from Nuvo, grants and personal fees from Ursapharm, personal fees from Menarini, personal fees from Mundipharma, personal fees from Pohl-Boskamp, grants from Inmunotek, grants from Cassella-med GmbH & Co. KG, personal fees from Laboratoire de la Mer, personal fees from Sidroga, grants and personal fees from HAL BV, personal fees from Lek, personal fees from PRO-AdWise, personal fees from Angelini Pharma, grants and non-financial support from JGL, outside the submitted work. JM reports personal fees and other from SANOFI-GENZYME & REGENERON, personal fees and other from NOVARTIS, grants and personal fees from VIATRIS, grants and personal fees from URIACH Group, personal fees from Mitsubishi-Tanabe, personal fees from Menarini, personal fees from UCB, personal fees from AstraZeneca, grants and personal fees from GSK, personal fees from MSD, outside the submitted work. NGP reports personal fees from NOVARTIS, personal fees from NUTRICIA, personal fees from HAL, personal fees from MENARINI/FAES FARMA, personal fees from SANOFI/REGENERON, personal fees from MYLAN, personal fees from ASTRA ZENECA, personal fees from GSK, grants from VIANEX, grants from REG, grants from CAPRICARE, grants from NESTLE, grants from NUMIL, personal fees from ABBOTT, personal fees from ABBVIE, personal fees from OM PHARMA, personal fees from MEDSCAPE, outside the submitted work. OP reports grants and personal fees from ALK-Abelló, grants and personal fees from Allergopharma, grants and personal fees from Stallergenes Greer, grants and personal fees from HAL Allergy Holding B.V./HAL Allergie GmbH, grants and personal fees from Bencard Allergie GmbH/Allergy Therapeutics, grants and personal fees from Lofarma, grants from Biomay, grants from Circassia, grants and personal fees from ASIT Biotech Tools S.A., grants and personal fees from Laboratorios LETI/LETI Pharma, personal fees from MEDA Pharma/MYLAN, grants and personal fees from Anergis S.A., personal fees from Mobile Chamber Experts (a GA2LEN Partner), personal fees from Indoor Biotechnologies, grants and personal fees from GlaxoSmithKline, personal fees from Astellas Pharma Global, personal fees from EUFOREA, personal fees from ROXALL Medizin, personal fees from Novartis, personal fees from Sanofi-Aventis and Sanofi-Genzyme, personal fees from Med Update Europe GmbH, personal fees from streamedup. GmbH, grants from Pohl-Boskamp, grants from Inmunotek S.L., personal fees from John Wiley and Sons, AS, personal fees from Paul-Martini-Stiftung (PMS), personal fees from Regeneron Pharmaceuticals Inc., personal fees from RG Aerztefortbildung, personal fees from Institut für Disease Management, personal fees from Springer GmbH, grants and personal fees from AstraZeneca, personal fees from IQVIA Commercial, personal fees from Ingress Health, personal fees from Wort&Bild Verlag, personal fees from Verlag ME, personal fees from Procter&Gamble, personal fees from Alfried-Krupp Krankenhaus, Essen, outside the submitted work; and member of EAACI Excom, member of ext. board of directors DGAKI; coordinator, main- or co-author of different position papers and guidelines in rhinology, allergology and allergen-immunotherapy. BS reports personal fees from Polpharma, personal fees from Viatris, grants and personal fees from AstraZeneca, personal fees from TEVA, personal fees from patient ombudsman, personal fees from Polish Allergology Society, grants from GSK, outside the submitted work. JS reports grants and personal fees from SANOFI, personal fees from GSK, personal fees from NOVARTIS, personal fees from ASTRA ZENECA, personal fees from MUNDIPHARMA, personal fees from FAES FARMA, outside the submitted work. LTB reports other from LETI, other from Vitoria Laboratories, other from Novartis, other from Diater Laboratories, during the conduct of the study. STS reports other from ERT, from Novartis, from Sanofi Pharma, from Roche Products, grants from GSK, outside the submitted work. TZ reports grants and personal fees from Novartis, grants and personal fees from Henkel, personal fees from Bayer, personal fees from FAES, personal fees from Astra Zeneca, personal fees from AbbVie, personal fees from ALK, personal fees from Almirall, personal fees from Astellas, personal fees from Bayer, personal fees from Bencard, personal fees from Berlin Chemie, personal fees from FAES, personal fees from Hal, personal fees from Leti, personal fees from Mesa, personal fees from Menarini, personal fees from Merck, personal fees from MSD, personal fees from Novartis, personal fees from Pfizer, personal fees from Sanofi, personal fees from Stallergenes, personal fees from Takeda, personal fees from Teva, personal fees from UCB, personal fees from Henkel, personal fees from Kryolan, personal fees from L'Oreal, outside the submitted work and Organizational affiliations: Committee member: WHO-Initiative ‘Allergic Rhinitis and Its Impact on Asthma’ (ARIA); Member of the Board: German Society for Allergy and Clinical Immunology (DGAKI); Head: European Centre for Allergy Research Foundation (ECARF); President: Global Allergy and Asthma European Network (GA2LEN);Member: Committee on Allergy Diagnosis and Molecular Allergology, World Allergy Organization (WAO). The other authors have no COIs to disclose, outside the submitted work. Data sharing is not applicable to this article as no new data were created or analyzed in this study.