Publications by authors named "Jean Bousquet"

507 Publications

Allergen Immunotherapy: A Long Way Gone and a Long Way to Go.

J Allergy Clin Immunol Pract 2021 May;9(5):1839-1840

University Hospital Montpellier, Montpellier, France.

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http://dx.doi.org/10.1016/j.jaip.2021.03.003DOI Listing
May 2021

The Finnish Allergy Program 2008-2018: Society-wide proactive program for change of management to mitigate allergy burden.

J Allergy Clin Immunol 2021 May 5. Epub 2021 May 5.

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

A 10-year national program to improve prevention and management of allergic diseases and asthma was implemented in Finland (population 5.5. million) in 2008-2018. The main aim was to reduce the long-term burden of these conditions. The strategy was changed from traditional avoidance to tolerance and resilience of the population. Health was endorsed instead of medicalization of mild symptoms. Disease severity was reevaluated, and disabling clinical manifestations were given high priority. For health care, 5 quantitative goals and 1 qualitative goal were set. For each of the goals, specific tasks, tools, and outcome evaluation were stipulated. During the program, 376 educational sessions gathered 24,000 health care participants. An information campaign targeted the lay public, and social media was used to contact people. In the 10 years of the program, the prevalence of allergic diseases and asthma leveled off. Asthma caused fewer symptoms and less disability, and 50% fewer hospital days. Food allergy diets in day care and schools decreased by half. Occupational allergies were reduced by 45%. In 2018, the direct and indirect costs of allergic diseases and asthma ranged from €1.5 million to €1.8 million, with the 2018 figures being 30% less than in the respective figures in 2007. The Finnish proactive and real-world intervention markedly reduced the public health burden of allergic disorders. The allergy paradigm was revisited to improve management with systematic education.
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http://dx.doi.org/10.1016/j.jaci.2021.03.037DOI Listing
May 2021

Heterogeneity of the pharmacologic treatment of allergic rhinitis in Europe based on MIDAS and OTCims platforms.

Clin Exp Allergy 2021 Apr 20. Epub 2021 Apr 20.

Charité Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.

Background: The practice of allergology varies widely between countries, and the costs and sales for the treatment of rhinitis differ depending on practices and health systems. To understand these differences and their implications, the rhinitis market was studied in some of the EU countries.

Methods: We conducted a pharmaco-epidemiological database analysis to assess the medications that were being prescribed for allergic rhinitis in the years 2016, 2017 and 2018. We used the IQVIA platforms for prescribed medicines (MIDAS Meaningful Integration of Data, Analytics and Services) and for OTC medicines (OTC International Market Tracking-OTCims). We selected the five most important markets in the EU (France, Germany, Italy, Poland and Spain).

Results: Intranasal decongestants were excluded from the analyses because they are rarely prescribed for allergic rhinitis. For both Standard Units (SU) and costs, France is leading the other countries. In terms of SU, the four other countries are similar. For costs, Poland is lower than the three others. However, medication use differs largely. For 2018, in SU, intranasal corticosteroid is the first treatment in Poland (70.0%), France (51.3%), Spain (51.1%) and Germany (50.3%), whereas the Italian market is dominated by systemic antihistamines (41.4%) followed by intranasal corticosteroids (30.1%). Results of other years were similar.

Discussion: There are major differences between countries in terms of rhinoconjunctivitis medication usage.
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http://dx.doi.org/10.1111/cea.13884DOI Listing
April 2021

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

Allergy 2021 Apr 2. Epub 2021 Apr 2.

Regional Ministry of Health of Andalusia, Seville, Spain.

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

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

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

Allergy 2021 Mar 17. Epub 2021 Mar 17.

Division of Allergy, Department of Pediatric Medicine, The Bambino Gesù Children's Research Hospital Holy see, IRCCS, Rome, Italy.

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 with the common cold or allergic rhinitis. An ARIA-EAACI study group attempted to differentiate upper respiratory symptoms between the three diseases.

Methods: A modified Delphi process was used. The 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 and allergic rhinitis.

Results: Among the 192 ARIA members who were invited to respond to the questionnaire, 89 responded and 87 questionnaires were analysed. The consensus was then reported. A two-way ANOVA revealed significant differences in the symptom intensity between the three diseases (p < .001).

Conclusions: This modified Delphi approach enabled the differentiation of upper respiratory symptoms between COVID-19, the 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 May 1;9(5):1805-1812. Epub 2021 Mar 1.

Charité, Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, Berlin, Germany; 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 article considers the possible role of mobile health in AIT for allergic rhinitis/asthma. There are no currently available validated biologic biomarkers that can predict AIT success, and mobile health biomarkers have some relevance. In the current article, 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
May 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

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 immunisation rates in 456 residents from eight nursing homes facing a COVID-19 outbreak.

Age Ageing 2021 05;50(3):641-648

Charité, Univeersitätsmedizin 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 coronavirus disease 2019 (COVID-19). The value of real-time reverse-transcriptase polymerase chain reaction (rRT-PCR) testing for identifying severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nursing homes (NHs) residents is not known.

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

Design: A retrospective longitudinal study.

Setting: Eight NHs with at least 10 rRT-PCR-positive residents.

Subjects: A total of 456 residents.

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

Results: A total of 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
May 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.

Division of Infection, Immunity & Respiratory Medicine, Royal Manchester Children's Hospital, University of Manchester, Manchester, United Kingdom.

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 06;21(3):229-244

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
June 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.

Maladies Infectieuses et Tropicales, CHU, Montpellier, France.

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.

Centre for Individualized Infection Medicine, CiiM, a joint venture between Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany; TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany; Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, 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 02 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

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

Anomalous asthma and chronic obstructive pulmonary disease Google Trends patterns during the COVID-19 pandemic.

Clin Transl Allergy 2020 Nov 2;10(1):47. Epub 2020 Nov 2.

MACVIA-France, Montpellier, France.

Background: An increase in online searches on health topics may either mirror epidemiological changes or reflect media coverage. In the context of COVID-19, this is particularly relevant, as COVID-19 symptoms may be mistaken for those of respiratory disease exacerbations. Therefore, we aimed to assess Internet search patterns on asthma and chronic obstructive pulmonary disease (COPD) in the context of COVID-19, as compared to searches on other chronic diseases.

Methods: We retrieved Google Trends (GTs) data on two respiratory (asthma and COPD) and three non-respiratory (diabetes, hypertension, and Crohn's disease) chronic diseases over the past 5 years (up to May 31, 2020). For 54 countries, and for each disease, we built autoregressive integrated moving average (ARIMA) models to predict GTs for 2020 based on 2015-2019 search patterns. In addition, we estimated the proportion of searches in which COVID-19-related terms were used. To assess the potential impact of media coverage on online searches, we assessed whether weekly "asthma" GTs correlated with the number of Google News items on asthma.

Results: Over the past 5 years, worldwide search volumes for asthma and COPD reached their maximum values in March 2020. Such was not observed for diabetes, hypertension and Crohn's disease. In 38 (70%) countries, GTs on asthma were higher in March 2020 than the respective maximum predicted values. This compares to 19 countries for COPD, 23 for hypertension, 11 for Crohn's disease, and 9 for diabetes. Queries with COVID-19-related terms represented up to 47.8% of the monthly searches on asthma, and up to 21.3% of COPD searches. In most of the assessed countries, moderate-strong correlations were observed between "asthma" GTs and the number of news items on asthma.

Conclusions: During March 2020, there was a peak in searches on asthma and COPD, which was probably mostly driven by media coverage, as suggested by their simultaneity in several countries with different epidemiological situations.
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http://dx.doi.org/10.1186/s13601-020-00352-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604916PMC
November 2020

Genomics of asthma, allergy and chronic rhinosinusitis: novel concepts and relevance in airway mucosa.

Clin Transl Allergy 2020 Oct 28;10(1):45. Epub 2020 Oct 28.

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

Genome wide association studies (GWASs) have revealed several airway disease-associated risk loci. Their role in the onset of asthma, allergic rhinitis (AR) or chronic rhinosinusitis (CRS), however, is not yet fully understood. The aim of this review is to evaluate the airway relevance of loci and genes identified in GWAS studies. GWASs were searched from databases, and a list of loci associating significantly (p < 10) with asthma, AR and CRS was created. This yielded a total of 267 significantly asthma/AR-associated loci from 31 GWASs. No significant CRS -associated loci were found in this search. A total of 170 protein coding genes were connected to these loci. Of these, 76/170 (44%) showed bronchial epithelial protein expression in stained microscopic figures of Human Protein Atlas (HPA), and 61/170 (36%) had a literature report of having airway epithelial function. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation analyses were performed, and 19 functional protein categories were found as significantly (p < 0.05) enriched among these genes. These were related to cytokine production, cell activation and adaptive immune response, and all were strongly connected in network analysis. We also identified 15 protein pathways that were significantly (p < 0.05) enriched in these genes, related to T-helper cell differentiation, virus infection, JAK-STAT signaling pathway, and asthma. A third of GWAS-level risk loci genes of asthma or AR seemed to have airway epithelial functions according to our database and literature searches. In addition, many of the risk loci genes were immunity related. Some risk loci genes also related to metabolism, neuro-musculoskeletal or other functions. Functions overlapped and formed a strong network in our pathway analyses and are worth future studies of biomarker and therapeutics.
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http://dx.doi.org/10.1186/s13601-020-00347-6DOI Listing
October 2020

Physicians' prescribing behaviour and clinical practice patterns for allergic rhinitis management in Italy.

Clin Mol Allergy 2020 Nov 3;18(1):20. Epub 2020 Nov 3.

Asthma & Allergy Clinic-Humanitas University & Research Hospital Milan, Milan, Italy.

Background: Despite availability of clinical guidelines, underdiagnosis, undertreatment, and poor adherence are still significant concerns in allergic rhinitis (AR) therapeutic management. We investigated clinical practice patterns and prescribing behavior of Italian healthcare professionals (HCPs) specialized in AR.

Methods: One-hundred allergologists, 100 ear, nose and throat (ENT) specialists, and 150 general practitioners (GPs) were recruited. The survey assessed: socio-demographic, work experience, monthly caseload, prescription drivers. Next, HCPs were invited to retrospectively recover patients' clinical data to investigate: AR clinical characteristics, therapy management, prescription patterns, patient adherence. Descriptive statistics, Chi square, One-Way analysis of variance, and Two-Way Analysis of Variance were performed.

Results: Allergologists visited more AR patients (31% of monthly caseload) than ENTs (21%, p < 0.001), while GPs' caseload was the lowest (6%). Clinical information of 2823 patients were retrieved of whom 1906 (67.5%) suffered from moderate/severe AR (discomfort score: 7.7 ± 1.3) and 917 (32.4%) from mild AR (5.7 ± 1.9). About one-third of mild patients had a discomfort score ≥ 7. Main prescription drivers were "effective on all symptoms" (54.3% patients) and "quick symptom relief" (47.8%), whereas minor drivers were "affordable price" (13.4%) and "refundable" (8.7%). The most prescribed drugs were antihistamines and intranasal corticosteroids (79% and 55% prescriptions), followed by fixed-dose-combination of intranasal azelastine/fluticasone (19%). Polytherapy was the most common treatment strategy (59.6%). HCPs' believe that the majority of the patients was adherent to treatment (88% with score > 7).

Conclusions: This survey describes the therapeutic approach adopted by Italian physicians to cope with AR and shows that HCPs underestimated AR severity and had a non-realistic perception of patients' adherence. These findings suggest that further efforts are required to improve AR clinical management in Italy.
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http://dx.doi.org/10.1186/s12948-020-00135-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7640419PMC
November 2020