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  1. Article ; Online: Biologic Therapies for Severe Asthma.

    Brusselle, Guy G / Koppelman, Gerard H

    The New England journal of medicine

    2022  Volume 386, Issue 2, Page(s) 157–171

    MeSH term(s) Adolescent ; Adult ; Algorithms ; Anti-Asthmatic Agents/therapeutic use ; Antibodies, Monoclonal/therapeutic use ; Asthma/immunology ; Asthma/physiopathology ; Asthma/therapy ; Biological Therapy ; Biomarkers/blood ; Child ; Humans ; Interleukin-4 Receptor alpha Subunit/antagonists & inhibitors ; Interleukin-5/antagonists & inhibitors ; Lung/physiopathology ; Patient Acuity
    Chemical Substances Anti-Asthmatic Agents ; Antibodies, Monoclonal ; Biomarkers ; Interleukin-4 Receptor alpha Subunit ; Interleukin-5
    Language English
    Publishing date 2022-01-12
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 207154-x
    ISSN 1533-4406 ; 0028-4793
    ISSN (online) 1533-4406
    ISSN 0028-4793
    DOI 10.1056/NEJMra2032506
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  2. Article ; Online: Genetics of preschool wheeze and its progression to childhood asthma.

    Wolters, Alba A B / Kersten, Elin T G / Koppelman, Gerard H

    Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology

    2024  Volume 35, Issue 1, Page(s) e14067

    Abstract: Wheezing is a common and heterogeneous condition in preschool children. In some countries, the prevalence can be as high as 30% and up to 50% of all children experience wheezing before the age of 6. Asthma often starts with preschool wheeze, but not all ... ...

    Abstract Wheezing is a common and heterogeneous condition in preschool children. In some countries, the prevalence can be as high as 30% and up to 50% of all children experience wheezing before the age of 6. Asthma often starts with preschool wheeze, but not all wheezing children will develop asthma at school age. At this moment, it is not possible to accurately predict which wheezing children will develop asthma. Recently, studying the genetics of wheeze and the childhood-onset of asthma have grown in interest. Childhood-onset asthma has a stronger heritability in comparison with adult-onset asthma. In early childhood asthma exacerbations, CDHR3, which encodes the receptor for Rhinovirus C, was identified, as well as IL33, and the 17q locus that includes GSDMB and ORMDL3 genes. The 17q locus is the strongest wheeze and childhood-onset asthma locus, and was shown to interact with many environmental factors, including smoking and infections. Finally, ANXA1 was recently associated with early-onset, persistent wheeze. ANXA1 may help resolve eosinophilic inflammation. Overall, despite its complexities, genetic approaches to unravel the early-onset of wheeze and asthma are promising, since these shed more light on mechanisms of childhood asthma-onset. Implicated genes point toward airway epithelium and its response to external factors, such as viral infections. However, the heterogeneity of wheeze phenotypes complicates genetic studies. It is therefore important to define accurate wheezing phenotypes and forge larger international collaborations to gain a better understanding of the pathways underlying early-onset asthma.
    MeSH term(s) Adult ; Child, Preschool ; Humans ; Respiratory Sounds/genetics ; Schools ; Asthma/epidemiology ; Asthma/genetics ; Neoplasm Proteins ; Phenotype ; Cadherin Related Proteins ; Membrane Proteins
    Chemical Substances Neoplasm Proteins ; CDHR3 protein, human ; Cadherin Related Proteins ; Membrane Proteins
    Language English
    Publishing date 2024-01-29
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1057059-7
    ISSN 1399-3038 ; 0905-6157 ; 0906-5784
    ISSN (online) 1399-3038
    ISSN 0905-6157 ; 0906-5784
    DOI 10.1111/pai.14067
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  3. Article ; Online: Epigenome-wide association studies of allergic disease and the environment.

    Cardenas, Andres / Fadadu, Raj P / Koppelman, Gerard H

    The Journal of allergy and clinical immunology

    2023  Volume 152, Issue 3, Page(s) 582–590

    Abstract: The epigenome is at the intersection of the environment, genotype, and cellular response. DNA methylation of cytosine nucleotides, the most studied epigenetic modification, has been systematically evaluated in human studies by using untargeted epigenome- ... ...

    Abstract The epigenome is at the intersection of the environment, genotype, and cellular response. DNA methylation of cytosine nucleotides, the most studied epigenetic modification, has been systematically evaluated in human studies by using untargeted epigenome-wide association studies (EWASs) and shown to be both sensitive to environmental exposures and associated with allergic diseases. In this narrative review, we summarize findings from key EWASs previously conducted on this topic; interpret results from recent studies; and discuss the strengths, challenges, and opportunities regarding epigenetics research on the environment-allergy relationship. The majority of these EWASs have systematically investigated select environmental exposures during the prenatal and early childhood periods and allergy-associated epigenetic changes in leukocyte-isolated DNA and more recently in nasal cells. Overall, many studies have found consistent DNA methylation associations across cohorts for certain exposures, such as smoking (eg, aryl hydrocarbon receptor repressor gene [AHRR] gene), and allergic diseases (eg, EPX gene). We recommend the integration of both environmental exposures and allergy or asthma within long-term prospective designs to strengthen causality as well as biomarker development. Future studies should collect paired target tissues to examine compartment-specific epigenetic responses, incorporate genetic influences in DNA methylation (methylation quantitative trait locus), replicate findings across diverse populations, and carefully interpret epigenetic signatures from bulk, target tissue or isolated cells.
    MeSH term(s) Pregnancy ; Female ; Humans ; Child, Preschool ; Epigenome ; Genome-Wide Association Study ; Epigenesis, Genetic ; Hypersensitivity/genetics ; DNA Methylation
    Language English
    Publishing date 2023-06-07
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 121011-7
    ISSN 1097-6825 ; 1085-8725 ; 0091-6749
    ISSN (online) 1097-6825 ; 1085-8725
    ISSN 0091-6749
    DOI 10.1016/j.jaci.2023.05.020
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  4. Article ; Online: T2-low asthma in school-aged children: unacknowledged and understudied.

    Mishra, Pooja E / Melén, Erik / Koppelman, Gerard H / Celedón, Juan C

    The Lancet. Respiratory medicine

    2023  Volume 11, Issue 12, Page(s) 1044–1045

    MeSH term(s) Humans ; Child ; Asthma ; Schools
    Language English
    Publishing date 2023-10-12
    Publishing country England
    Document type Journal Article
    ZDB-ID 2686754-0
    ISSN 2213-2619 ; 2213-2600
    ISSN (online) 2213-2619
    ISSN 2213-2600
    DOI 10.1016/S2213-2600(23)00369-7
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  5. Article ; Online: Asthma susceptibility: Learning from genetic diversity.

    Sun, Yidan / Kersten, Elin T G / Qi, Cancan / Koppelman, Gerard H

    The Journal of allergy and clinical immunology

    2023  Volume 151, Issue 4, Page(s) 904–906

    MeSH term(s) Humans ; Genetic Predisposition to Disease ; Genotype ; Asthma/genetics ; Genetic Variation ; Genome-Wide Association Study ; Polymorphism, Single Nucleotide
    Language English
    Publishing date 2023-02-21
    Publishing country United States
    Document type Editorial ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 121011-7
    ISSN 1097-6825 ; 1085-8725 ; 0091-6749
    ISSN (online) 1097-6825 ; 1085-8725
    ISSN 0091-6749
    DOI 10.1016/j.jaci.2023.01.034
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  6. Article ; Online: Predicting the course of asthma from childhood until early adulthood.

    Koefoed, Hans Jacob L / Vonk, Judith M / Koppelman, Gerard H

    Current opinion in allergy and clinical immunology

    2022  Volume 22, Issue 2, Page(s) 115–122

    Abstract: Purpose of review: To communicate recent insights about the natural history of childhood asthma, with a focus on prediction of persistence and remission of childhood asthma, up to early adulthood.: Recent findings: Lung function around the age of 8-9  ...

    Abstract Purpose of review: To communicate recent insights about the natural history of childhood asthma, with a focus on prediction of persistence and remission of childhood asthma, up to early adulthood.
    Recent findings: Lung function around the age of 8-9 years is the strongest predictor: obstructive lung function predicts asthma persistence up to early adulthood, whereas normal lung function predicts remission. The ability to predict asthma remission improves when lung function is combined with blood eosinophil levels and degree of bronchial hyperresponsiveness. Interventions, such as inhaled corticosteroids and immunotherapy do not appear to alter the course of asthma. Epigenetic studies have revealed potential novel biomarkers of asthma remission, such as micro-RNA patterns in blood. Specifically, lower serum levels of mi-R221-5p, which is associated with lower IL-6 release and eosinophilic inflammation, predict remission. Higher levels of blood DNA-methylation of a CpG site in Peroxisomal Biogenesis Factor 11 Beta were associated with asthma remission.
    Summary: Lung function, allergic comorbidity and polysensitization in childhood predict the course of asthma. Recent epigenetic studies have provided a better understanding of underlying pathological processes in asthma remission, which may be used to improve prediction or develop novel treatments aimed at altering the course of asthma.
    MeSH term(s) Adult ; Asthma/therapy ; Biomarkers ; Bronchial Hyperreactivity ; Child ; Eosinophils ; Humans ; Hypersensitivity
    Chemical Substances Biomarkers
    Language English
    Publishing date 2022-02-18
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2088710-3
    ISSN 1473-6322 ; 1528-4050
    ISSN (online) 1473-6322
    ISSN 1528-4050
    DOI 10.1097/ACI.0000000000000810
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  7. Article ; Online: Grandmaternal smoking, asthma and lung function in the offspring: the Lifelines cohort study.

    Mahon, Gillian M / Koppelman, Gerard H / Vonk, Judith M

    Thorax

    2021  Volume 76, Issue 5, Page(s) 441–447

    Abstract: Background/objective: Limited research exists regarding the association between grandmaternal smoking during pregnancy and the risk for asthma and altered lung function in grandchildren. This study aimed to investigate this association in a three- ... ...

    Abstract Background/objective: Limited research exists regarding the association between grandmaternal smoking during pregnancy and the risk for asthma and altered lung function in grandchildren. This study aimed to investigate this association in a three-generation design.
    Methods: 37 291 participants (25 747 adults and 11 544 children) were included from the Lifelines study, a prospective longitudinal three generation cohort study in The Netherlands. Spirometry was available in 69.5% and 61.1% of the included adults and children. Logistic and linear regression were used to analyse the association between grandmaternal smoking during pregnancy and (1) asthma, (2) early childhood asthma (ie, onset before 6 years) and (3) lung function level. Maternal and paternal grandmaternal smoking were studied separately and the analyses were stratified by adult/child and by gender. The analyses were adjusted for gender, current smoking, birth variables and socioeconomic status.
    Results: In the adult population, maternal grandmaternal smoking during pregnancy was associated with a higher risk for asthma (OR (95% CI): 1.38 (1.06 to 1.79)), early childhood asthma (1.49 (95% CI 1.06 to 2.11)) and a lower FEV1/FVC% predicted (B (95% CI): -1.04 (-1.91 to -0.16) in men. These findings were not observed in a separate analysis of children that participated in this study. There was also no significant association between paternal grandmaternal smoking and asthma/lung function.
    Conclusion: Maternal grandmaternal smoking during pregnancy is associated with higher asthma risk and lower lung function in male grandchildren and a reverse effect in male grandchildren of subsequent generations. Our study highlights the deep-rooted effects of tobacco smoking across generations.
    Language English
    Publishing date 2021-02-04
    Publishing country England
    Document type Journal Article
    ZDB-ID 204353-1
    ISSN 1468-3296 ; 0040-6376
    ISSN (online) 1468-3296
    ISSN 0040-6376
    DOI 10.1136/thoraxjnl-2020-215232
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  8. Article ; Online: Improvements in air quality: whose lungs benefit?

    Gehring, Ulrike / Koppelman, Gerard H

    The European respiratory journal

    2019  Volume 53, Issue 4

    MeSH term(s) Aging ; Air Pollutants/analysis ; Air Pollution ; Humans ; Lung/chemistry ; Obesity
    Chemical Substances Air Pollutants
    Language English
    Publishing date 2019-04-25
    Publishing country England
    Document type Editorial ; Comment
    ZDB-ID 639359-7
    ISSN 1399-3003 ; 0903-1936
    ISSN (online) 1399-3003
    ISSN 0903-1936
    DOI 10.1183/13993003.00365-2019
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  9. Article ; Online: Towards diversity in asthma pharmacogenetics.

    Kersten, Elin T G / Koppelman, Gerard H

    The Lancet. Child & adolescent health

    2021  Volume 5, Issue 12, Page(s) 838–839

    MeSH term(s) Anti-Asthmatic Agents/therapeutic use ; Asthma/drug therapy ; Humans ; Pharmacogenetics
    Chemical Substances Anti-Asthmatic Agents
    Language English
    Publishing date 2021-11-09
    Publishing country England
    Document type Journal Article ; Comment
    ISSN 2352-4650
    ISSN (online) 2352-4650
    DOI 10.1016/S2352-4642(21)00330-8
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  10. Article ; Online: Understanding How Asthma Starts: Longitudinal Patterns of Wheeze and the Chromosome 17q Locus.

    Koppelman, Gerard H / Kersten, Elin T G

    American journal of respiratory and critical care medicine

    2021  Volume 203, Issue 7, Page(s) 793–795

    MeSH term(s) Asthma/genetics ; Child ; Chromosomes, Human, Pair 21 ; Humans ; Phenotype ; Respiratory Sounds/genetics
    Language English
    Publishing date 2021-04-09
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 1180953-x
    ISSN 1535-4970 ; 0003-0805 ; 1073-449X
    ISSN (online) 1535-4970
    ISSN 0003-0805 ; 1073-449X
    DOI 10.1164/rccm.202102-0443ED
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