Studies on Early Allergic Sensitization in the Lithuanian Birth Cohort

Cohort studies are of great importance in defining the mechanism responsible for the development of allergy-associated diseases, such as atopic dermatitis, allergic asthma, and allergic rhinoconjunctivitis. Although these disorders share genetic and environmental risk factors, it is still under debate whether they are linked or develop sequentially along an atopic pathway. The current study was aimed to determine the pattern of allergy sensitization in the Lithuanian birth cohort “Alergemol” (n = 1558) established as a part of the multicenter European birth cohort “EuroPrevall”. Early sensitization to food allergens in the “Alergemol” birth cohort was analysed. The analysis revealed 1.3% and 2.8% of symptomatic-sensitized subjects at 6 and 12 months of age, respectively. The sensitization pattern in response to different allergens in the group of infants with food allergy symptoms was studied using allergological methods in vivo and in vitro. The impact of maternal and environmental risk factors on the early development of food allergy in at 6 and 12 months of age was evaluated. Our data showed that maternal diet, diseases, the use of antibiotics, and tobacco smoke during pregnancy had no significant impact on the early sensitization to food allergens. However, infants of atopic mothers were significantly more often sensitized to egg as compared to the infants of nonatopic mothers

Photobinding of Triflusal to Human Serum Albumin Investigated by Fluorescence, Proteomic Analysis, and Computational Studies

[EN] Triflusal is a platelet antiaggregant employed for the treatment and prevention of thromboembolic diseases. After administration, it is biotransformed into its active metabolite, the 2-hydroxy-4-trifluoromethylbenzoic acid (HTB). We present here an investigation on HTB photobinding to human serum albumin (HSA), the most abundant protein in plasma, using an approach that combines fluorescence, MS/MS, and peptide fingerprint analysis as well as theoretical calculations (docking and molecular dynamics simulation studies). The proteomic analysis of HTB/HSA photolysates shows that HTB addition takes place at the epsilon-amino groups of the Lys137, Lys199, Lys205, Lys351, Lys432, Lys525, Lys541 and Lys545 residues and involves replacement of the trifluoromethyl moiety of HTB with a new amide function. Only Lys199 is located in an internal pocket of the protein, and the remaining modified residues are placed in the external part. Docking and molecular dynamic simulation studies reveal that HTB supramolecular binding to HSA occurs in the "V-cleft" region and that the process is assisted by the presence of Glu/Asp residues in the neighborhood of the external Lys, in agreement with the experimentally observed modifications. In principle, photobinding can occur with other trifluoroaromatic compounds and may be responsible for the appearance of undesired photoallergic side effects.We gratefully acknowledge financial support from the Spanish Government (CTQ2016-78875-P, SAF2016-75638-R, BES-2014-069404, and RETICS network ARADyAL RD16/0006/0030), the Generalitat Valenciana (PROMETEO/2017/075 and CIDEGENT/2018/044), the Xunta de Galicia [Centro Singular de Investigacion de Galicia accreditation 2016-2019 (ED431G/09), ED431B 2018/04 and post-doctoral fellowship to EL], and the European Union (European Regional Development Fund-ERDF). The proteomic analysis was performed in the proteomics facility of SCSIE University of Valencia that belongs to ProteoRed PRB3 and is supported by grant PT17/0019, of the PE I+D+i 2013-2016, funded by ISCIII and ERDF. We are grateful to the Centro de Supercomputacion de Galicia (CESGA) for use of the Finis Terrae computer.Molins-Molina, O.; Pérez Ruiz, R.; Lence, E.; González-Bello, C.; Miranda Alonso, MÁ.; Jiménez Molero, MC. (2019). Photobinding of Triflusal to Human Serum Albumin Investigated by Fluorescence, Proteomic Analysis, and Computational Studies. Frontiers in Pharmacology. 10:1-9. https://doi.org/10.3389/fphar.2019.01028S1910Cuquerella, M. C., Lhiaubet-Vallet, V., Cadet, J., & Miranda, M. A. (2012). Benzophenone Photosensitized DNA Damage. Accounts of Chemical Research, 45(9), 1558-1570. doi:10.1021/ar300054eDarden, T., York, D., & Pedersen, L. (1993). Particle mesh Ewald: AnN⋅log(N) method for Ewald sums in large systems. 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Journal of Photochemistry and Photobiology B: Biology, 63(1-3), 103-113. doi:10.1016/s1011-1344(01)00207-xGordon, J. C., Myers, J. B., Folta, T., Shoja, V., Heath, L. S., & Onufriev, A. (2005). H++: a server for estimating pKas and adding missing hydrogens to macromolecules. Nucleic Acids Research, 33(Web Server), W368-W371. doi:10.1093/nar/gki464Honari, G. (2014). Photoallergy. Reviews on Environmental Health, 29(3). doi:10.1515/reveh-2014-0067Le Grand, S., Götz, A. W., & Walker, R. C. (2013). SPFP: Speed without compromise—A mixed precision model for GPU accelerated molecular dynamics simulations. Computer Physics Communications, 184(2), 374-380. doi:10.1016/j.cpc.2012.09.022Lee, A.-Y., Joo, H.-J., Chey, W.-Y., & Kim, Y.-G. (2001). Photopatch Testing in Seven Cases of Photosensitive Drug Eruptions. Annals of Pharmacotherapy, 35(12), 1584-1587. doi:10.1345/aph.1a007Lee, A.-Y., Yoo, S.-H., & Lee, K.-H. (1999). A case of photoallergic drug eruption caused by triflusal (Disgren®). 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Frontiers in Pharmacology, 7. doi:10.3389/fphar.2016.00277Onoue, S., Ohtake, H., Suzuki, G., Seto, Y., Nishida, H., Hirota, M., … Kouzuki, H. (2016). Comparative study on prediction performance of photosafety testing tools on photoallergens. Toxicology in Vitro, 33, 147-152. doi:10.1016/j.tiv.2016.03.003Onoue, S., Seto, Y., Gandy, G., & Yamada, S. (2009). Drug-Induced Phototoxicity; An Early In Vitro Identification of Phototoxic Potential of New Drug Entities in Drug Discovery and Development. Current Drug Safety, 4(2), 123-136. doi:10.2174/157488609788173044Onoue, S., Seto, Y., Sato, H., Nishida, H., Hirota, M., Ashikaga, T., … Tokura, Y. (2017). Chemical photoallergy: photobiochemical mechanisms, classification, and risk assessments. Journal of Dermatological Science, 85(1), 4-11. doi:10.1016/j.jdermsci.2016.08.005Onoue, S., Suzuki, G., Kato, M., Hirota, M., Nishida, H., Kitagaki, M., … Yamada, S. (2013). Non-animal photosafety assessment approaches for cosmetics based on the photochemical and photobiochemical properties. Toxicology in Vitro, 27(8), 2316-2324. doi:10.1016/j.tiv.2013.10.003Pérez-Ruiz, R., Molins-Molina, O., Lence, E., González-Bello, C., Miranda, M. A., & Jiménez, M. C. (2018). Photogeneration of Quinone Methides as Latent Electrophiles for Lysine Targeting. The Journal of Organic Chemistry, 83(21), 13019-13029. doi:10.1021/acs.joc.8b01559Ryckaert, J.-P., Ciccotti, G., & Berendsen, H. J. . (1977). Numerical integration of the cartesian equations of motion of a system with constraints: molecular dynamics of n-alkanes. Journal of Computational Physics, 23(3), 327-341. doi:10.1016/0021-9991(77)90098-5Schothorst, A. A., Van Steveninck, J., Went, L. N., & Suurmond, D. (1972). Photodynamic damage of the erythrocyte membrane caused by protoporphyrin in protoporphyria and in normal red blood cells. Clinica Chimica Acta, 39(1), 161-170. doi:10.1016/0009-8981(72)90312-9Stein, K. 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Treatment of allergic rhinitis during and outside the pollen season using mobile technology. A MASK study

Background: The analysis of mobile health (mHealth) data has generated innovative insights into improving allergic rhinitis control, but additive information is needed. A cross-sectional real-world observational study was undertaken in 17 European countries during and outside the estimated pollen season. The aim was to collect novel information including the phenotypic characteristics of the users. Methods: The Allergy Diary–MASK-air–mobile phone app, freely available via Google Play and App, was used to collect the data of daily visual analogue scales (VASs) for overall allergic symptoms and medication use. Fluticasone Furoate (FF), Mometasone Furoate (MF), Azelastine Fluticasone Proprionate combination (MPAzeFlu) and eight oral H1-antihistamines were studied. Phenotypic characteristics were recorded at entry. The ARIA severity score was derived from entry data. This was an a priori planned analysis. Results: 9037 users filled in 70,286 days of VAS in 2016, 2017 and 2018. The ARIA severity score was lower outside than during the pollen season. Severity was similar for all treatment groups during the pollen season, and lower in the MPAzeFlu group outside the pollen season. Days with MPAzeFlu had lower VAS levels and a higher frequency of monotherapy than the other treatments during the season. Outside the season, days with MPAzeFlu also had a higher frequency of monotherapy. The number of reported days was significantly higher with MPAzeFlu during and outside the season than with MF, FF or oral H1-antihistamines. Conclusions: This study shows that the overall efficacy of treatments is similar during and outside the pollen season and indicates that medications are similarly effective during the year

A concept for integrated care pathways for atopic dermatitis-A GA2 LEN ADCARE initiative

INTRODUCTION: The integrated care pathways for atopic dermatitis (AD-ICPs) aim to bridge the gap between existing AD treatment evidence-based guidelines and expert opinion based on daily practice by offering a structured multidisciplinary plan for patient management of AD. ICPs have the potential to enhance guideline recommendations by combining interventions and aspects from different guidelines, integrating quality assurance, and describing co-ordination of care. Most importantly, patients can enter the ICPs at any level depending on AD severity, resources available in their country, and economic factors such as differences in insurance reimbursement systems. METHODS: The GA2 LEN ADCARE network and partners as well as all stakeholders, abbreviated as the AD-ICPs working group, were involved in the discussion and preparation of the AD ICPs during a series of subgroup workshops and meetings in years 2020 and 2021, after which the document was circulated within all GAL2 EN ADCARE centres. RESULTS: The AD-ICPs outline the diagnostic procedures, possible co-morbidities, different available treatment options including differential approaches for the pediatric population, and the role of the pharmacists and other stakeholders, as well as remaining unmet needs in the management of AD. CONCLUSION: The AD-ICPs provide a multidisciplinary plan for improved diagnosis, treatment, and patient feedback in AD management, as well as addressing critical unmet needs, including improved access to care, training specialists, implementation of educational programs, assessment on the impact of climate change, and fostering a personalised treatment approach. By focusing on these key areas, the initiative aims to pave the way for a brighter future in the management of AD

A concept for integrated care pathways for atopic dermatitis—A GA2LEN ADCARE initiative

Introduction: The integrated care pathways for atopic dermatitis (AD-ICPs) aim to bridge the gap between existing AD treatment evidence-based guidelines and expert opinion based on daily practice by offering a structured multidisciplinary plan for patient management of AD. ICPs have the potential to enhance guideline recommendations by combining interventions and aspects from different guidelines, integrating quality assurance, and describing co-ordination of care. Most importantly, patients can enter the ICPs at any level depending on AD severity, resources available in their country, and economic factors such as differences in insurance reimbursement systems. Methods: The GA2LEN ADCARE network and partners as well as all stakeholders, abbreviated as the AD-ICPs working group, were involved in the discussion and preparation of the AD ICPs during a series of subgroup workshops and meetings in years 2020 and 2021, after which the document was circulated within all GAL2EN ADCARE centres. Results: The AD-ICPs outline the diagnostic procedures, possible co-morbidities, different available treatment options including differential approaches for the pediatric population, and the role of the pharmacists and other stakeholders, as well as remaining unmet needs in the management of AD. Conclusion: The AD-ICPs provide a multidisciplinary plan for improved diagnosis, treatment, and patient feedback in AD management, as well as addressing critical unmet needs, including improved access to care, training specialists, implementation of educational programs, assessment on the impact of climate change, and fostering a personalised treatment approach. By focusing on these key areas, the initiative aims to pave the way for a brighter future in the management of AD

Scaling up strategies of the chronic respiratory disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3: Area 5)

Abstract Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) focuses on the integrated care of chronic diseases. Area 5 (Care Pathways) was initiated using chronic respiratory diseases as a model. The chronic respiratory disease action plan includes (1) AIRWAYS integrated care pathways (ICPs), (2) the joint initiative between the Reference site MACVIA-LR (Contre les MAladies Chroniques pour un VIeillissement Actif) and ARIA (Allergic Rhinitis and its Impact on Asthma), (3) Commitments for Action to the European Innovation Partnership on Active and Healthy Ageing and the AIRWAYS ICPs network. It is deployed in collaboration with the World Health Organization Global Alliance against Chronic Respiratory Diseases (GARD). The European Innovation Partnership on Active and Healthy Ageing has proposed a 5-step framework for developing an individual scaling up strategy: (1) what to scale up: (1-a) databases of good practices, (1-b) assessment of viability of the scaling up of good practices, (1-c) classification of good practices for local replication and (2) how to scale up: (2-a) facilitating partnerships for scaling up, (2-b) implementation of key success factors and lessons learnt, including emerging technologies for individualised and predictive medicine. This strategy has already been applied to the chronic respiratory disease action plan of the European Innovation Partnership on Active and Healthy Ageing

ARIA 2016: Care pathways implementing emerging technologies for predictive medicine in rhinitis and asthma across the life cycle

Abstract The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma and rhinitis and (3) to develop guidelines with all stakeholders that could be used globally for all countries and populations. ARIA—disseminated and implemented in over 70 countries globally—is now focusing on the implementation of emerging technologies for individualized and predictive medicine. MASK [MACVIA (Contre les Maladies Chroniques pour un Vieillissement Actif)-ARIA Sentinel NetworK] uses mobile technology to develop care pathways for the management of rhinitis and asthma by a multi-disciplinary group and by patients themselves. An app (Android and iOS) is available in 20 countries and 15 languages. It uses a visual analogue scale to assess symptom control and work productivity as well as a clinical decision support system. It is associated with an inter-operable tablet for physicians and other health care professionals. The scaling up strategy uses the recommendations of the European Innovation Partnership on Active and Healthy Ageing. The aim of the novel ARIA approach is to provide an active and healthy life to rhinitis sufferers, whatever their age, sex or socio-economic status, in order to reduce health and social inequalities incurred by the disease

BUILDING BRIDGES FOR INNOVATION IN AGEING : SYNERGIES BETWEEN ACTION GROUPS OF THE EIP ON AHA

The Strategic Implementation Plan of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) proposed six Action Groups. After almost three years of activity, many achievements have been obtained through commitments or collaborative work of the Action Groups. However, they have often worked in silos and, consequently, synergies between Action Groups have been proposed to strengthen the triple win of the EIP on AHA. The paper presents the methodology and current status of the Task Force on EIP on AHA synergies. Synergies are in line with the Action Groups' new Renovated Action Plan (2016-2018) to ensure that their future objectives are coherent and fully connected. The outcomes and impact of synergies are using the Monitoring and Assessment Framework for the EIP on AHA (MAFEIP). Eight proposals for synergies have been approved by the Task Force: Five cross-cutting synergies which can be used for all current and future synergies as they consider overarching domains (appropriate polypharmacy, citizen empowerment, teaching and coaching on AHA, deployment of synergies to EU regions, Responsible Research and Innovation), and three cross-cutting synergies focussing on current Action Group activities (falls, frailty, integrated care and chronic respiratory diseases).Peer reviewe

ARIA 2016:Care pathways implementing emerging technologies for predictive medicine in rhinitis and asthma across the life cycle

The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma and rhinitis and (3) to develop guidelines with all stakeholders that could be used globally for all countries and populations. ARIA-disseminated and implemented in over 70 countries globally-is now focusing on the implementation of emerging technologies for individualized and predictive medicine. MASK [MACVIA (Contre les Maladies Chroniques pour un Vieillissement Actif)-ARIA Sentinel NetworK] uses mobile technology to develop care pathways for the management of rhinitis and asthma by a multi-disciplinary group and by patients themselves. An app (Android and iOS) is available in 20 countries and 15 languages. It uses a visual analogue scale to assess symptom control and work productivity as well as a clinical decision support system. It is associated with an inter-operable tablet for physicians and other health care professionals. The scaling up strategy uses the recommendations of the European Innovation Partnership on Active and Healthy Ageing. The aim of the novel ARIA approach is to provide an active and healthy life to rhinitis sufferers, whatever their age, sex or socio-economic status, in order to reduce health and social inequalities incurred by the disease