Publications by authors named "J Jean Bousquet"

1,437 Publications

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Management of anaphylaxis due to COVID-19 vaccines in the elderly.

Authors:
Jean Bousquet Ioana Agache Hubert Blain Marek Jutel Maria Teresa Ventura Margitta Worm Stefano Del Giacco Athanasios Benetos M Beatrice Bilo Wienczyslawa Czarlewski Amir Hamzah Abdul Latiff Mona Al-Ahmad Elizabeth Angier Isabella Annesi-Maesano Marina Atanaskovic-Markovic Claus Bachert Annick Barbaud Anna Bedbrook Kazi S Bennoor Elena Camelia Berghea Carsten Bindslev-Jensen Sergio Bonini Sinthia Bosnic-Anticevich Knut Brockow Luisa Brussino Paulo Camargos G Walter Canonica Victoria Cardona Pedro Carreiro-Martins Ana Carriazo Thomas Casale Jean-Christoph Caubet Lorenzo Cecchi Antonio Cherubini George Christoff Derek K Chu Alvaro A Cruz Dejan Dokic Yehia El-Gamal Motohiro Ebisawa Bernadette Eberlein John Farrell Montserrat Fernandez-Rivas Wytske J Fokkens Joao A Fonseca Yadong Gao Gaëtan Gavazzi Radolslaw Gawlik Asli Gelincik Bilun Gemicioğlu Maia Gotua Olivier Guérin Tari Haahtela Karin Hoffmann-Sommergruber Hans Jürgen Hoffmann Maja Hofmann Martin Hrubisko Madda lenaIllario Carla Irani Zhanat Ispayeva Juan Carlos Ivancevich Kaja Julge Igor Kaidashev Musa Khaitov Edward Knol Helga Kraxner Piotr Kuna Violeta Kvedariene Antti Lauerma Lan Tt Le Vincent Le Moing Michael Levin Renaud Louis Olga Lourenco Vera Mahler Finbarr C Martin Andrea Matucci Branislava Milenkovic Stéphanie Miot Emma Montella Mario Morais-Almeida Charlotte G Mortz Joaquim Mullol Leyla Namazova-Baranova Hugo Neffen Kristof Nekam Marek Niedoszytko Mikaëla Odemyr Robyn E O'Hehir Yoshitaka Okamoto Markus Ollert Oscar Palomares Nikolaos G Papadopoulos Petr Panzner Gianni Passalacqua Vincenzo Patella Mirko Petrovic Oliver Pfaar Nhân Pham-Thi Davor Plavec Todor A Popov Marysia T Recto Frederico S Regateiro Jacques Reynes Regina E Roller-Winsberger Yves Rolland Antonino Romano Carmen Rondon Menachem Rottem Philip W Rouadi Nathalie Salles Boleslaw Samolinski Alexandra F Santos Faradiba Sarquis Serpa Joaquin Sastre Jos M G A Schols Nicola Scichilone Anna Sediva Mohamed H Shamji Aziz Sheikh Isabel Skypala Sylwia Smolinska Milena Sokolowska Bernardo Sousa-Pinto Milan Sova Rafael Stelmach Gunter Sturm Charlotte Suppli Ulrik Ana Maria Todo-Bom Sanna Toppila-Salmi Ioanna Tsiligianni Maria Torres Eva Untersmayr Marilyn Urrutia Pereira Arunas Valiulis Joana Vitte Alessandra Vultaggio Dana Wallace Jolanta Walusiak-Skorupa De-Yun Wang Susan Waserman Arzu Yorgancioglu Osman M Yusuf Mario Zernotti Mihaela Zidarn Tomas Chivato Cezmi A Akdis Torsten Zuberbier Ludger Klimek

Allergy 2021 Apr 2. Epub 2021 Apr 2.

Department of Otolaryngology, Head and Neck Surgery, Universitätsmedizin Mainz, Mainz, and Center for Rhinology and Allergology, Wiesbaden, Germany.

Older adults, especially men and/or those with diabetes, hypertension and/or obesity, are prone to severe COVID-19. In some countries, older adults, particularly those residing in nursing homes, have been prioritised to receive COVID-19 vaccines due to high risk of death. In very rare instances,the COVID-19 vaccines can induce anaphylaxis, and the management of anaphylaxis in older people should be considered carefully. An ARIA-EAACI-EuGMS (Allergic Rhinitis and its Impact on Asthma, European Academy of Allergy and Clinical Immunology, and European Geriatric Medicine Society)Working Group has proposed some recommendations for older adults receiving the COVID-19 vaccines. Anaphylaxis to COVID-19 vaccines is extremely rare (from 1 per 100,000 to 5 per million injections). Symptoms are similar in younger and older adults but they tend to be more severe in the older patients. Adrenaline is the mainstay treatment and should be readily available. A flowchart is proposed to manage anaphylaxis in the older patients.
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http://dx.doi.org/10.1111/all.14838DOI Listing
April 2021

Novel Graphene Electrode for Retinal Implants: An Biocompatibility Study.

Front Neurosci 2021 4;15:615256. Epub 2021 Mar 4.

INSERM, CNRS, Institut de la Vision, Sorbonne Université, Paris, France.

Evaluating biocompatibility is a core essential step to introducing a new material as a candidate for brain-machine interfaces. Foreign body reactions often result in glial scars that can impede the performance of the interface. Having a high conductivity and large electrochemical window, graphene is a candidate material for electrical stimulation with retinal prosthesis. In this study, non-functional devices consisting of chemical vapor deposition (CVD) graphene embedded onto polyimide/SU-8 substrates were fabricated for a biocompatibility study. The devices were implanted beneath the retina of blind P23H rats. Implants were monitored by optical coherence tomography (OCT) and eye fundus which indicated a high stability up to 3 months before histology studies were done. Microglial reconstruction through confocal imaging illustrates that the presence of graphene on polyimide reduced the number of microglial cells in the retina compared to polyimide alone, thereby indicating a high biocompatibility. This study highlights an interesting approach to assess material biocompatibility in a tissue model of central nervous system, the retina, which is easily accessed optically and surgically.
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http://dx.doi.org/10.3389/fnins.2021.615256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969870PMC
March 2021

Associations between specific IgE sensitization to 26 respiratory allergen molecules and HLA class II alleles in the EGEA cohort.

Allergy 2021 Mar 19. Epub 2021 Mar 19.

Inserm, CNRS, IAB, Team of Environmental Epidemiology Applied to Reproduction and Respiratory Health, University Grenoble Alpes, Grenoble, France.

Background: Allergy, the most frequent immune disorder affecting 30% of the world's population, is the consequence of immunoglobin E (IgE) sensitization to allergens. Among the genetic factors suspected to be involved in allergy, the HLA class-II genomic region is a strong candidate.

Objective: To assess the association between HLA class-II alleles and specific IgE (sIgE) sensitization to a large number of respiratory allergen molecules.

Methods: The analysis relied on 927 participants of the EGEA cohort, including 497 asthmatics. The study focuses on 26 aeroallergens recognized by sIgE in at least 5% of the study population (determined with the MEDALL chip with sIgE ≥ 0.3 ISU) and 23 imputed HLA class-II alleles. For each sIgE sensitization and HLA class-II allele, we fitted a logistic regression model accounting for familial dependence and adjusted for gender, age, and genetic principal components. p-values were corrected for multiple comparisons (False Discovery Rate).

Results: Most of the 19 statistically significant associations observed regard pollen allergens (mugwort Art v 1, olive tree Ole e 1, timothy grass Phl p 2, Phl p 5 and plantain Pla l 1), three were mold allergen (Alternaria Alt a 1), and a single one regards house dust mite allergen (Der p 7). No association was observed with pet allergens. The strongest associations were found with mugwort Art v 1 (OR = 5.42 (95%CI, 3.30; 8.88), 4.14 (2.65; 6.47), 3.16 (1.88; 5.31) with DQB1*05:01, DQA1*01:01 and DRB1*01:01, respectively).

Conclusion: Our results support the important role of HLA class-II alleles as immune response genes predisposing their carriers for sensitization to various major pollen allergens.
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http://dx.doi.org/10.1111/all.14820DOI Listing
March 2021

[Dupilumab has an additional benefit in treatment of chronic rhinosinusitis with nasal polyps].

HNO 2021 Mar 18. Epub 2021 Mar 18.

Klinik für Hals‑, Nasen- und Ohrenheilkunde, Universitätsklinikum Gent, Gent, Belgien.

Background: For patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP) which cannot be controlled by continuous therapy with intranasal corticosteroids (INCS) and systemic corticosteroids and/or surgical treatment, there were no approved curative options for a long time. For CRSwNP treatment with T2-addressing biologics is possible. On October 24, 2019, the European Commission granted extended approval for dupilumab as the first biological agent for treatment of insufficiently controlled severe CRSwNP. The Federal Joint Committee (G‑BA) evaluates the benefits of reimbursable drugs with new active ingredients. This includes assessment of the additional benefit and its therapeutic relevance.

Methods: A meta-analysis was performed using individual patient data based on two phase III studies. Both studies examined the safety and efficacy of dupilumab as an add-on therapy to INCS for treatment of CRSwNP in adults inadequately controlled with systemic corticosteroids and/or surgery compared to INCS alone.

Results: Based on the present data, the G‑BA decided that there is an indication of a considerable additional benefit of dupilumab compared to mometasone furoate.

Conclusion: For patients with severe CRSwNP inadequately controlled with INCS and systemic corticosteroids and/or surgery, there is an indication of a considerable additional benefit for the administration of dupilumab as an add-on therapy to INCS compared to mometasone furoate alone.
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http://dx.doi.org/10.1007/s00106-021-01018-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971351PMC
March 2021

Differentiation of COVID-19 signs and symptoms from allergic rhinitis and common cold- An ARIA-EAACI-GA LENconsensus.

Authors:
Jan Hagemann Gabrielle L Onorato Marek Jutel Cezmi A Akdis Ioana Agache Torsten Zuberbier Wienczyslawa Czarlewski Joaquim Mullol Anna Bedbrook Claus Bachert Kazi S Bennoor Karl-Christian Bergmann Fulvio Braido Paulo Camargos Luis Caraballo Victoria Cardona Thomas Casale Lorenzo Cecchi Tomas Chivato Derek K Chu Cemal Cingi Jaime Correia-de-Sousa Stefano Del Giacco Dejan Dokic Mark Dykewicz Motohiro Ebisawa Yehia El-Gamal Regina Emuzyte Jean-Luc Fauquert Alessandro Fiocchi Wytske J Fokkens Joao A Fonseca Bilun Gemicioglu Maximiliano Gomez Gotua Maia Tari Haahtela Eckard Hamelmann Tomohisa Iinuma Juan Carlos Ivancevich Ewa Jassem Omer Kalayci Przemyslaw Kardas Musa Khaitov Piotr Kuna Violeta Kvedariene Desiree E Larenas-Linnemann Brian Lipworth Michael Makris Jorge F Maspero Neven Miculinic Florin Mihaltan Yousser Mohammad Stephen Montefort Mario Morais-Almeida Ralph Mösges Robert Naclerio Hugo Neffen Marek Niedoszytko Robyn E O'Hehir Ken Ohta Yoshitaka Okamoto Kimi Okubo Petr Panzner Nikolaos G Papadopoulos Giovanni Passalacqua Vincenzo Patella Ana Pereira Oliver Pfaar Davor Plavec Todor A Popov Emmanuel P Prokopakis Francesca Puggioni Filip Raciborski Jere Reijula Frederico S Regateiro Sietze Reitsma Antonino Romano Nelson Rosario Menachem Rottem Dermot Ryan Boleslaw Samolinski Joaquin Sastre Dirceu Solé Milan Sova Cristiana Stellato Charlotte Suppli-Ulrik Ioanna Tsiligianni Antonio Valero Arunas Valiulis Erkka Valovirta Tuula Vasankari Maria Teresa Ventura Dana Wallace De Yun Wang Iân Williams Arzu Yorgancioglu Osman M Yusuf Mario Zernotti Jean Bousquet Ludger Klimek

Allergy 2021 Mar 17. Epub 2021 Mar 17.

Department of Otolaryngology, Head and Neck Surgery, Universitätsmedizin Mainz, Mainz, Germany.

Background: Although there are many asymptomatic patients, one of the problems of COVID-19 is early recognition of the disease. COVID-19 symptoms are polymorphic and may include upper respiratory symptoms. However, COVID-19 symptoms may be mistaken withthe common cold or allergic rhinitis. An ARIA-EAACI study group attempted to differentiate upper respiratory symptoms betweenthe three diseases.

Methods: A modified Delphi process was used and ARIA members who were seeing COVID-19 patients were asked to fill in a questionnaire on the upper airway symptoms of COVID-19, common cold andallergic rhinitis.

Results: Among the 192 ARIA members who were invited to respond to the questionnaire, 89 responded. 87 questionnaires were analysed. The consensus was then reported.A two-way ANOVA analysis revealed significant differences inthe symptom intensity between the three diseases (p<0.001).

Conclusions: This modified Delphi approach enabled thedifferentiationof upper respiratory symptoms betweenCOVID-19, common cold and allergic rhinitis. An electronic algorithm will be devised using the questionnaire.
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http://dx.doi.org/10.1111/all.14815DOI Listing
March 2021

Questionnaire as an alternative of skin prick tests to differentiate allergic from non-allergic rhinitis in epidemiological studies.

Allergy 2021 Mar 12. Epub 2021 Mar 12.

Université Paris-Saclay, UVSQ, Univ. Paris-Sud, Inserm, Equipe d'Epidémiologie Respiratoire Intégrative, CESP, Villejuif, France.

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http://dx.doi.org/10.1111/all.14812DOI Listing
March 2021

The Debate: Regular Versus As-Needed Use of Intranasal Corticosteroids for a Patient-Centered Approach.

J Allergy Clin Immunol Pract 2021 Mar;9(3):1374-1375

Skin and Allergy Hospital, Helsinki University Hospital, and University of Helsinki, Helsinki, Finland.

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http://dx.doi.org/10.1016/j.jaip.2020.11.019DOI Listing
March 2021

Reply to "Cabbage and COVID-19".

Allergy 2021 03;76(3):968

Department of Dermatology and Allergy, Berlin Institute of Health, Comprehensive Allergy Center, Charité, Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.

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http://dx.doi.org/10.1111/all.14653DOI Listing
March 2021

The role of mobile health technologies in stratifying patients for AIT and its cessation. The ARIA-EAACI perspective.

J Allergy Clin Immunol Pract 2021 Mar 1. Epub 2021 Mar 1.

Charité, Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Comprehensive Allergy Center, Department of Dermatology and Allergy, Berlin, Germany.

Allergen immunotherapy (AIT) is a proven therapeutic option for the treatment of allergic rhinitis and/or asthma. Many international or national practice guidelines have been produced, but the evidence-based method varies and they do not usually propose care pathways. The present paper considers the possible role of mHealth in AIT for allergic rhinitis/asthma. There are no currently available validated biologic biomarkers that can predict AIT success, and mHealth biomarkers have some relevance. In the current paper, the following aspects will be discussed: patient stratification for AIT, symptom medication scores for the follow-up of patients, clinical trials as well as the approach of the European Academy of Allergy and Clinical Immunology.
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http://dx.doi.org/10.1016/j.jaip.2021.02.035DOI Listing
March 2021

Allergenic components of the mRNA-1273 vaccine for COVID-19: possible involvement of polyethylene glycol and IgG-mediated complement activation.

Allergy 2021 Mar 3. Epub 2021 Mar 3.

Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.

Following the emergency use authorization of the mRNA-1273 vaccine on the 18 of December2020,two mRNAvaccinesare in current use for the prevention of coronavirus disease 2019 (COVID-19). For both mRNA vaccines, the phase IIIpivotal trials excluded individuals with a history of allergy tovaccine components.Immediately after the initiation of vaccination in the United Kingdom, Canada, and the US, anaphylactic reactions were reported. While the culprit trigger requires investigation, initial reports suggested the excipient polyethylene glycol 2000 (PEG-2000) -contained in both vaccines as the PEG-micellar carrier system - as the potentialculprit. Surface PEG chains form a hydrate shell to increasestability and prevent opsonization. Allergic reactions to such PEGylated lipids can be IgE-mediated,but may alsoresult from complement activation-related pseudoallergy (CARPA) that has been described insimilar liposomes. In addition, mRNA-1273 also contains tromethamine (trometamol), which has been reported to cause anaphylaxis to substances such asgadolinium-based contrast media. Skin prick, intradermal and epicutaneoustests, in vitro sIgE assessment, evaluation ofsIgG/IgM,as well as basophil activation tests are being used to demonstrate allergic reactions to various components of the vaccines.
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http://dx.doi.org/10.1111/all.14794DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013891PMC
March 2021

New Insights into Wine Taste: Impact of Dietary Lipids on Sensory Perceptions of Grape Tannins.

J Agric Food Chem 2021 Mar 3;69(10):3165-3174. Epub 2021 Mar 3.

Univ. Bordeaux, CNRS, CBMN UMR 5348, IECB, F-33600 Pessac, France.

Wine is very often consumed with a meal. However, although it is well known to tasters that the taste of wine changes in the presence of food, the influence of dietary lipids on wine astringency and bitterness caused by grape tannins is not well established from a molecular point of view. In this context, we investigated wine tannin-lipid interactions by combining biophysical techniques to sensory analysis. Nuclear magnetic resonance and optical and electron microscopy showed an interaction between catechin, a majority component of grape tannins, and lipid droplets from a phospholipid-stabilized oil-in-water emulsion, characterized by (a) an increase in the droplet size in the presence of catechin, (b) slowing of their size growth over time, and (c) an increase in lipid dynamics in the droplet interfacial layer. Those results were strengthened by sensory analysis, which demonstrated that dietary oils decrease the perception of astringency of grape tannin solutions. Our results highlight that dietary lipids are crucial molecular agents impacting our sensory perception during wine consumption.
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http://dx.doi.org/10.1021/acs.jafc.0c06589DOI Listing
March 2021

SNP-based analysis reveals unexpected features of genetic diversity, parental contributions and pollen contamination in a white spruce breeding program.

Sci Rep 2021 Mar 2;11(1):4990. Epub 2021 Mar 2.

Department of Renewable Resources, 442 Earth Sciences Building, University of Alberta, Edmonton, AB, T6G 2E3, Canada.

Accurate monitoring of genetic diversity levels of seedlots and mating patterns of parents from seed orchards are crucial to ensure that tree breeding programs are long-lasting and will deliver anticipated genetic gains. We used SNP genotyping to characterize founder trees, five bulk seed orchard seedlots, and trees from progeny trials to assess pollen contamination and the impact of severe roguing on genetic diversity and parental contributions in a first-generation open-pollinated white spruce clonal seed orchard. After severe roguing (eliminating 65% of the seed orchard trees), we found a slight reduction in the Shannon Index and a slightly negative inbreeding coefficient, but a sharp decrease in effective population size (eightfold) concomitant with sharp increase in coancestry (eightfold). Pedigree reconstruction showed unequal parental contributions across years with pollen contamination levels between 12 and 51% (average 27%) among seedlots, and 7-68% (average 30%) among individual genotypes within a seedlot. These contamination levels were not correlated with estimates obtained using pollen flight traps. Levels of pollen contamination also showed a Pearson's correlation of 0.92 with wind direction, likely from a pollen source 1 km away from the orchard under study. The achievement of 5% genetic gain in height at rotation through eliminating two-thirds of the orchard thus generated a loss in genetic diversity as determined by the reduction in effective population size. The use of genomic profiles revealed the considerable impact of roguing on genetic diversity, and pedigree reconstruction of full-sib families showed the unanticipated impact of pollen contamination from a previously unconsidered source.
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http://dx.doi.org/10.1038/s41598-021-84566-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925517PMC
March 2021

Atypical symptoms, SARS-CoV-2 test results, and immunization rates in 456 residents from eight nursing homes facing a COVID-19 outbreak.

Age Ageing 2021 Feb 23. Epub 2021 Feb 23.

Charité, Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Comprehensive Allergy Center, Department of Dermatology and Allergy, Berlin, Germany.

Background: Frail older persons may have an atypical presentation of COVID-19. The value of rRT-PCR testing for identifying SARS-CoV-2 nursing homes (NH) residents is not known.

Objective: To determine whether (i) atypical symptoms may predict rRT-PCR results and (ii) rRT-PCR results may predict immunization against SARS-CoV-2 in NH residents.

Design: A retrospective longitudinal study.

Setting: eight NHs with at least ten rRT-PCR-positive residents.

Subjects: 456 residents.

Methods: Typical and atypical symptoms recorded in residents' files during the 14 days before and after rRT-PCR testing were analyzed. Residents underwent blood testing for IgG-SARS-CoV-2 nucleocapsid protein 6 to 8 weeks after testing. Univariate and multivariate analyses compared symptoms and immunization rates in rRT-PCR-positive and negative residents.

Results: 161 residents had a positive rRT-PCR (35.3%), 17.4% of whom were asymptomatic before testing. Temperature > 37.8°C, oxygen saturation < 90%, unexplained anorexia, behavioural change, exhaustion, malaise, and falls before testing were independent predictors of a further positive rRT-PCR. Among the rRT-PCR-positive residents, 95.2% developed SARS-CoV-2 antibodies vs 7.6% in the rRT-PCR-negative residents. Among the residents with a negative rRT-PCR, those who developed SARS-CoV-2 antibodies more often had typical or atypical symptoms (p = 0.02 and < 0.01, respectively).

Conclusion: This study supports a strategy based on (i) testing residents with typical or unexplained atypical symptoms for an early identification of the first SARS-CoV-2 cases, (ii) rT-PCR testing for identifying COVID-19 residents, (iii) repeated wide-facility testing (including asymptomatic cases) as soon as a resident is tested positive for SARS-CoV-2, and (iv) implementing SARS-CoV-2 infection control measures in rRT-PCR-negative residents when they have unexplained typical or atypical symptoms.
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http://dx.doi.org/10.1093/ageing/afab050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7929417PMC
February 2021

Connecting tree-ring phenotypes, genetic associations and transcriptomics to decipher the genomic architecture of drought adaptation in a widespread conifer.

Mol Ecol 2021 Feb 15. Epub 2021 Feb 15.

Canada Research Chair in Forest Genomics, Institute for Systems and Integrative Biology, Université Laval, Québec, QC, Canada.

As boreal forests face significant threats from climate change, understanding evolutionary trajectories of coniferous species has become fundamental to adapting management and conservation to a drying climate. We examined the genomic architecture underlying adaptive variation related to drought tolerance in 43 populations of a widespread boreal conifer, white spruce (Picea glauca [Moench] Voss), by combining genotype-environment associations, genotype-phenotype associations, and transcriptomics. Adaptive genetic variation was identified by correlating allele frequencies for 6,153 single nucleotide polymorphisms from 2,606 candidate genes with temperature, precipitation and aridity gradients, and testing for significant associations between genotypes and 11 dendrometric and drought-related traits (i.e., anatomical, growth response and climate-sensitivity traits) using a polygenic model. We identified a set of 285 genes significantly associated with a climatic factor or a phenotypic trait, including 110 that were differentially expressed in response to drought under greenhouse-controlled conditions. The interlinked phenotype-genotype-environment network revealed eight high-confidence genes involved in white spruce adaptation to drought, of which four were drought-responsive in the expression analysis. Our findings represent a significant step toward the characterization of the genomic basis of drought tolerance and adaptation to climate in conifers, which is essential to enable the establishment of resilient forests in view of new climate conditions.
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http://dx.doi.org/10.1111/mec.15846DOI Listing
February 2021

Potential Interplay between Nrf2, TRPA1, and TRPV1 in Nutrients for the Control of COVID-19.

Int Arch Allergy Immunol 2021 10;182(4):324-338. Epub 2021 Feb 10.

IMIM (Hospital del Mar Research Institute), Barcelona, Spain.

In this article, we propose that differences in COVID-19 morbidity may be associated with transient receptor potential ankyrin 1 (TRPA1) and/or transient receptor potential vanilloid 1 (TRPV1) activation as well as desensitization. TRPA1 and TRPV1 induce inflammation and play a key role in the physiology of almost all organs. They may augment sensory or vagal nerve discharges to evoke pain and several symptoms of COVID-19, including cough, nasal obstruction, vomiting, diarrhea, and, at least partly, sudden and severe loss of smell and taste. TRPA1 can be activated by reactive oxygen species and may therefore be up-regulated in COVID-19. TRPA1 and TRPV1 channels can be activated by pungent compounds including many nuclear factor (erythroid-derived 2) (Nrf2)-interacting foods leading to channel desensitization. Interactions between Nrf2-associated nutrients and TRPA1/TRPV1 may be partly responsible for the severity of some of the COVID-19 symptoms. The regulation by Nrf2 of TRPA1/TRPV1 is still unclear, but suggested from very limited clinical evidence. In COVID-19, it is proposed that rapid desensitization of TRAP1/TRPV1 by some ingredients in foods could reduce symptom severity and provide new therapeutic strategies.
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http://dx.doi.org/10.1159/000514204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018185PMC
April 2021

Olfactory and taste dysfunctions in COVID-19.

Curr Opin Allergy Clin Immunol 2021 Feb 3. Epub 2021 Feb 3.

Department of Otolaryngology-Head and Neck Surgery, Holy Spirit University of Kaslik, Eye and Ear University Hospital, Beirut, Lebanon Department of Audiology and Neurotology, Edouard Herriot Hospital, Lyon, France Charité, Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Comprehensive Allergy Center, Department of Dermatology and Allergy, Berlin, Germany.

Purpose Of Review: Olfactory dysfunction (OD) can be a single and early prominent symptom of severe acute respiratory syndrome (SARS)-COV-2 infection unlike middle east respiratory syndrome (MERS) and SARS. OD data are very informative but many are not peer-reviewed, often inconclusive and may reveal variable and sometimes contradictory results. This is often due to incongruent data of subjective and objective OD testing. Mechanistic pathways of OD and taste dysfunction (TD) are slowly unveiling, not infrequently extrapolated from historical models of SARS and MERS and are still partly unclear.

Recent Findings: We reviewed the literature on OD and TD during the COVID-19 pandemic analyzing current data on pathogenesis and clinical correlates including prevalence, recovery rates, risk factors, and predictive power. Also, we evaluated various methods of subjective and objective olfactory testing and discussed challenges in management of patients with OD and rhinitis during the pandemic.

Summary: Subjective evaluation of smell disturbances during COVID-19 pandemic likely underestimates true prevalence, severity, and recovery rates of OD when compared to objective testing. OD is predictive of COVID-19 infection, more so when associated with TD. Recognizing inherent limitations of both subjective and objective OD and TD testing enables us better to manage chemosensory dysfunction in COVID-19 patients. Besides, current mechanistic data suggest neurotropism of COVID-19 for olfactory neuro-epithelium and a potential role of transient receptor potential (TRP) channels. Future studies are needed to explore further the neurogenic inflammation in COVID-19.
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http://dx.doi.org/10.1097/ACI.0000000000000735DOI Listing
February 2021

News Beyond Our Pages.

J Allergy Clin Immunol 2021 Jan 5;147(1):43-44. Epub 2021 Jan 5.

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http://dx.doi.org/10.1016/j.jaci.2020.11.009DOI Listing
January 2021

Real-World Effectiveness of Omalizumab in Severe Allergic Asthma: A Meta-Analysis of Observational Studies.

J Allergy Clin Immunol Pract 2021 Jan 21. Epub 2021 Jan 21.

Novartis Pharma AG, Basel, Switzerland.

Background: Assessment of clinical outcomes in the real-world corroborates findings from randomized controlled trials (RCTs).

Objective: This meta-analysis evaluated real-world data of omalizumab on treatment response, lung function, exacerbations, oral corticosteroid (OCS) use, patient-reported outcomes (PROs), health care resource utilization (HCRU), and school/work absenteeism at 4, 6, and 12 months after treatment.

Methods: Observational studies in patients with severe allergic asthma (≥6 years) treated with omalizumab for ≥16 weeks, published from January 2005 to October 2018, were retrieved from PubMed, Embase, and Cochrane. A random-effects model was used to assess heterogeneity.

Results: In total, 86 publications were included. Global evaluation of treatment effectiveness (GETE) was good/excellent in 77% patients at 16 weeks (risk difference: 0.77; 95% confidence interval [CI]: 0.70-0.84; I = 96%) and in 82% patients at 12 months (0.82, 0.73-0.91; 97%). The mean improvement in forced expiratory volume in 1 second was 160, 220, and 250 mL at 16 weeks, 6 months, and 12 months, respectively. There was a decrease in Asthma Control Questionnaire score at 16 weeks (-1.14), 6 months (-1.56), and 12 months (-1.13) after omalizumab therapy. Omalizumab significantly reduced annualized rate of severe exacerbations (risk ratio [RR]: 0.41, 95% CI: 0.30-0.56; I = 96%), proportion of patients receiving OCS (RR: 0.59, 95% CI: 0.47-0.75; I = 96%), and number of unscheduled physician visits (mean difference: -2.34, 95% CI: -3.54 to -1.13; I = 98%) at 12 months versus baseline.

Conclusion: The consistent improvements in GETE, lung function, and PROs, and reductions in asthma exacerbations, OCS use, and HCRU with add-on omalizumab in real-life confirm and complement the efficacy data of RCTs.
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http://dx.doi.org/10.1016/j.jaip.2021.01.011DOI Listing
January 2021

Efficacy of broccoli and glucoraphanin in COVID-19: From hypothesis to proof-of-concept with three experimental clinical cases.

World Allergy Organ J 2021 Jan 9;14(1):100498. Epub 2020 Dec 9.

IMIM (Hospital del Mar Research Institute), Barcelona, Spain.

COVID-19 is described in a clinical case involving a patient who proposed the hypothesis that Nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-interacting nutrients may help to prevent severe COVID-19 symptoms. Capsules of broccoli seeds containing glucoraphanin were being taken before the onset of SARS-CoV-2 infection and were continued daily for over a month after the first COVID-19 symptoms. They were found to reduce many of the symptoms rapidly and for a duration of 6-12 h by repeated dosing. When the patient was stable but still suffering from cough and nasal obstruction when not taking the broccoli capsules, a double-blind induced cough challenge confirmed the speed of onset of the capsules (less than 10 min). A second clinical case with lower broccoli doses carried out during the cytokine storm confirmed the clinical benefits already observed. A third clinical case showed similar effects at the onset of symptoms. In the first clinical trial, we used a dose of under 600 μmol per day of glucoraphanin. However, such a high dose may induce pharmacologic effects that require careful examination before the performance of any study. It is likely that the fast onset of action is mediated through the TRPA1 channel. These experimental clinical cases represent a proof-of-concept confirming the hypothesis that Nrf2-interacting nutrients are effective in COVID-19. However, this cannot be used in practice before the availability of further safety data, and confirmation is necessary through proper trials on efficacy and safety.
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http://dx.doi.org/10.1016/j.waojou.2020.100498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770975PMC
January 2021

Next-Generation Allergic Rhinitis Care in Singapore: 2019 ARIA Care Pathways.

Ann Acad Med Singap 2020 11;49(11):885-896

Department of Otolaryngology, Head and Neck Surgery, Sengkang General Hospital, Singapore.

Allergic rhinitis (AR) is prevalent in Singapore, with a significant disease burden. Afflicting up to 13% of the population, AR impairs quality of life, leads to reduced work productivity and is an independent risk factor for asthma. In the last 2 decades, local studies have identified patient and physician behaviours leading to suboptimal control of the disease. Yet, there is an overall lack of attention to address this important health issue. Allergic Rhinitis and its Impact on Asthma (ARIA) is a European organisation aimed at implementing evidence-based management for AR worldwide. Recent focus in Europe has been directed towards empowering patients for self-management, exploring the complementary role of mobile health, and establishing healthcare system-based integrated care pathways. Consolidation of these ongoing efforts has led to the release of the 2019 ARIA care pathways. This review summarises the ARIA update with particular emphasis on the current status of adult AR in Singapore. In addition, we identify unmet needs and future opportunities for research and clinical care of AR in the local context.
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November 2020

ARIA-EAACI statement on severe allergic reactions to COVID-19 vaccines - an EAACI-ARIA position paper.

Allergy 2020 Dec 30. Epub 2020 Dec 30.

Charité Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Comprehensive Allergy Center, Department of Dermatology and Allergy, Berlin, Germany.

Coronavirus disease 2019 (COVID-19) vaccine BNT162b2 received approval and within the first few days of public vaccination several severe anaphylaxis cases occurred. An investigation is taking place to understand the cases and their triggers. The vaccine will be administered to a large number of individuals worldwide and concerns raised for severe adverse events might occur. With the current information, the European Academy of Allergy and Clinical Immunology (EAACI) states its position for the following preliminary recommendations that are to be revised as soon as more data emerges. To minimize the risk of severe allergic reactions in vaccinated individuals, it is urgently required to understand the specific nature of the reported severe allergic reactions, including the background medical history of the individuals affected and the mechanisms involved. To achieve this goal all clinical and laboratory information should be collected and reported. Mild and moderate allergic patients should not be excluded from the vaccine as the exclusion of all these patients from vaccination may have a significant impact on reaching the goal of population immunity. Health care practitioners vaccinating against COVID-19 are required to be sufficiently prepared to recognise and treat anaphylaxis properly with the ability to administer adrenaline. A mandatory observation period after vaccine administration of at least 15 minutes for all individuals should be followed. The current data has not shown any higher risk for patients suffering from allergic rhinitis or asthma and this message should be clearly stated by physicians to give our patients trust. The benefit of the vaccination clearly outweighs the risk of severe COVID-19 development including the more than 30% of the population suffering from allergic diseases.
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http://dx.doi.org/10.1111/all.14726DOI Listing
December 2020

Spices to Control COVID-19 Symptoms: Yes, but Not Only….

Int Arch Allergy Immunol 2020 Dec 22:1-7. Epub 2020 Dec 22.

IMIM (Hospital del Mar Research Institute), Barcelona, Spain.

There are large country variations in COVID-19 death rates that may be partly explained by diet. Many countries with low COVID-19 death rates have a common feature of eating large quantities of fermented vegetables such as cabbage and, in some continents, various spices. Fermented vegetables and spices are agonists of the antioxidant transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and spices are transient receptor potential ankyrin 1 and vanillin 1 (TRPA1/V1) agonists. These mechanisms may explain many COVID-19 symptoms and severity. It appears that there is a synergy between Nrf2 and TRPA1/V1 foods that may explain the role of diet in COVID-19. One of the mechanisms of COVID-19 appears to be an oxygen species (ROS)-mediated process in synergy with TRP channels, modulated by Nrf2 pathways. Spicy foods are likely to desensitize TRP channels and act in synergy with exogenous antioxidants that activate the Nrf2 pathway.
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http://dx.doi.org/10.1159/000513538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900475PMC
December 2020

Shared DNA methylation signatures in childhood allergy: The MeDALL study.

J Allergy Clin Immunol 2021 Mar 15;147(3):1031-1040. Epub 2020 Dec 15.

Department of Pediatric Pulmonology and Pediatric Allergy, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; GRIAC Research Institute, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Background: Differential DNA methylation associated with allergy might provide novel insights into the shared or unique etiology of asthma, rhinitis, and eczema.

Objective: We sought to identify DNA methylation profiles associated with childhood allergy.

Methods: Within the European Mechanisms of the Development of Allergy (MeDALL) consortium, we performed an epigenome-wide association study of whole blood DNA methylation by using a cross-sectional design. Allergy was defined as having symptoms from at least 1 allergic disease (asthma, rhinitis, or eczema) and positive serum-specific IgE to common aeroallergens. The discovery study included 219 case patients and 417 controls at age 4 years and 228 case patients and 593 controls at age 8 years from 3 birth cohorts, with replication analyses in 325 case patients and 1111 controls. We performed additional analyses on 21 replicated sites in 785 case patients and 2124 controls by allergic symptoms only from 8 cohorts, 3 of which were not previously included in analyses.

Results: We identified 80 differentially methylated CpG sites that showed a 1% to 3% methylation difference in the discovery phase, of which 21 (including 5 novel CpG sites) passed genome-wide significance after meta-analysis. All 21 CpG sites were also significantly differentially methylated with allergic symptoms and shared between asthma, rhinitis, and eczema. The 21 CpG sites mapped to relevant genes, including ACOT7, LMAN3, and CLDN23. All 21 CpG sties were differently methylated in asthma in isolated eosinophils, and 10 were replicated in respiratory epithelium.

Conclusion: Reduced whole blood DNA methylation at 21 CpG sites was significantly associated with childhood allergy. The findings provide novel insights into the shared molecular mechanisms underlying asthma, rhinitis, and eczema.
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http://dx.doi.org/10.1016/j.jaci.2020.11.044DOI Listing
March 2021

A call for urgent action to safeguard our planet and our health in line with the helsinki declaration.

Environ Res 2021 Feb 9;193:110600. Epub 2020 Dec 9.

ISGlobal, Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain. Electronic address:

In 2015, the Rockefeller Foundation-Lancet Commission launched a report introducing a novel approach called Planetary Health and proposed a concept, a strategy and a course of action. To discuss the concept of Planetary Health in the context of Europe, a conference entitled: "Europe That Protects: Safeguarding Our Planet, Safeguarding Our Health" was held in Helsinki in December 2019. The conference participants concluded with a need for action to support Planetary Health during the 2020s. The Helsinki Declaration emphasizes the urgency to act as scientific evidence shows that human activities are causing climate change, biodiversity loss, land degradation, overuse of natural resources and pollution. They threaten the health and safety of human kind. Global, regional, national, local and individual initiatives are called for and multidisciplinary and multisectorial actions and measures are needed. A framework for an action plan is suggested that can be modified for local needs. Accordingly, a shift from fragmented approaches to policy and practice towards systematic actions will promote human health and health of the planet. Systems thinking will feed into conserving nature and biodiversity, and into halting climate change. The Planetary Health paradigm ‒ the health of human civilization and the state of natural systems on which it depends ‒ must become the driver for all policies.
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http://dx.doi.org/10.1016/j.envres.2020.110600DOI Listing
February 2021

Discovery of , a Novel Broad-Spectrum Serine β-Lactamase Inhibitor of the Diazabicyclooctane Class, Which Strongly Potentiates Meropenem Activity against Carbapenem-Resistant Enterobacterales and .

J Med Chem 2020 12 11;63(24):15802-15820. Epub 2020 Dec 11.

Antabio SAS, 436 rue Pierre et Marie Curie, 31670 Labège, France.

The diazabicyclooctanes (DBOs) are a class of serine β-lactamase (SBL) inhibitors that use a strained urea moiety as the warhead to react with the active serine residue in the active site of SBLs. The first in-class drug, avibactam, as well as several other recently approved DBOs (e.g., relebactam) or those in clinical development (e.g., nacubactam and zidebactam) potentiate activity of β-lactam antibiotics, to various extents, against carbapenem-resistant Enterobacterales (CRE) carrying class A, C, and D SBLs; however, none of these are able to rescue the activity of β-lactam antibiotics against carbapenem-resistant (CRAB), a WHO "critical priority pathogen" producing class D OXA-type SBLs. Herein, we describe the chemical optimization and resulting structure-activity relationship, leading to the discovery of a novel DBO, , which uniquely has a fluorine atom replacing the carboxamide and stands apart from the current DBOs in restoring carbapenem activity against OXA-CRAB as well as SBL-carrying CRE pathogens.
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http://dx.doi.org/10.1021/acs.jmedchem.0c01535DOI Listing
December 2020

Treatment of allergic rhinitis during and outside the pollen season using mobile technology. A MASK study.

Clin Transl Allergy 2020 Dec 9;10(1):62. Epub 2020 Dec 9.

CHU de Montpellier, Montpellier, France.

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.
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http://dx.doi.org/10.1186/s13601-020-00342-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726888PMC
December 2020

Genomic selection for resistance to spruce budworm in white spruce and relationships with growth and wood quality traits.

Evol Appl 2020 Dec 11;13(10):2704-2722. Epub 2020 Aug 11.

Canada Research Chair in Forest Genomics Institute of Systems and Integrative Biology and Systems, and Centre for Forest Research Université Laval Québec QC Canada.

With climate change, the pressure on tree breeding to provide varieties with improved resilience to biotic and abiotic stress is increasing. As such, pest resistance is of high priority but has been neglected in most tree breeding programs, given the complexity of phenotyping for these traits and delays to assess mature trees. In addition, the existing genetic variation of resistance and its relationship with productivity should be better understood for their consideration in multitrait breeding. In this study, we evaluated the prospects for genetic improvement of the levels of acetophenone aglycones (AAs) in white spruce needles, which have been shown to be tightly linked to resistance to spruce budworm. Furthermore, we estimated the accuracy of genomic selection (GS) for these traits, allowing selection at a very early stage to accelerate breeding. A total of 1,516 progeny trees established on five sites and belonging to 136 full-sib families from a mature breeding population in New Brunswick were measured for height growth and genotyped for 4,148 high-quality SNPs belonging to as many genes along the white spruce genome. In addition, 598 trees were assessed for levels of AAs piceol and pungenol in needles, and 578 for wood stiffness. GS models were developed with the phenotyped trees and then applied to predict the trait values of unphenotyped trees. AAs were under moderate-to-high genetic control (: 0.43-0.57) with null or marginally negative genetic correlations with other traits. The prediction accuracy of GS models (GBLUP) for AAs was high (: 0.63-0.67) and comparable or slightly higher than pedigree-based (ABLUP) or BayesCπ models. We show that AA traits can be improved and that GS speeds up the selection of improved trees for insect resistance and for growth and wood quality traits. Various selection strategies were tested to optimize multitrait gains.
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http://dx.doi.org/10.1111/eva.13076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691460PMC
December 2020

Nrf2-interacting nutrients and COVID-19: time for research to develop adaptation strategies.

Clin Transl Allergy 2020 Dec 3;10(1):58. Epub 2020 Dec 3.

Department of Dermatology and Allergy, Charité, Universitätsmedizin Berlin, Humboldt-Universität Zu Berlin, Berlin Institute of Health, Comprehensive Allergy Center, Berlin, Germany.

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPARγ:Peroxisome proliferator-activated receptor, NFκB: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2α:Elongation initiation factor 2α). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-ATR axis (ATR) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity.
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http://dx.doi.org/10.1186/s13601-020-00362-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711617PMC
December 2020

Highlights and recent developments in allergic diseases in EAACI journals (2019).

Clin Transl Allergy 2020 Dec 3;10(1):56. Epub 2020 Dec 3.

Department of Clinical Immunology, Wrocław Medical University, Wrocław, Poland.

The European Academy of Allergy and Clinical Immunology (EAACI) owns three journals: Allergy, Pediatric Allergy and Immunology and Clinical and Translational Allergy. One of the major goals of EAACI is to support health promotion in which prevention of allergy and asthma plays a critical role and to disseminate the knowledge of allergy to all stakeholders including the EAACI junior members. There was substantial progress in 2019 in the identification of basic mechanisms of allergic and respiratory disease and the translation of these mechanisms into clinics. Better understanding of molecular and cellular mechanisms, efforts for the development of biomarkers for disease prediction, novel prevention and intervention studies, elucidation of mechanisms of multimorbidities, entrance of new drugs in the clinics as well as recently completed phase three clinical studies and publication of a large number of allergen immunotherapy studies and meta-analyses have been the highlights of the last year.
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http://dx.doi.org/10.1186/s13601-020-00366-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712618PMC
December 2020