Atopic dermatitis is an important comorbidity in severe asthma

Lee, Jason K.; Han, Duhyun

doi:10.1016/j.anai.2018.02.026

Cited by 9 publications

(7 citation statements)

References 10 publications

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“…Finally, asthma is a complex disease involving both genetic and environmental influences and we have not formally assessed the role of the environment, which could be critical for the development of more severe asthma. Accumulating data suggest a role for several factors in the development of severe disease (eg, comorbidities such as atopic dermatitis in severe asthma 68 and environmental or epigenetic mechanisms 69 ) but further work is needed.…”

Section: Discussionmentioning

confidence: 99%

Moderate-to-severe asthma in individuals of European ancestry: a genome-wide association study

Shrine

Portelli

John

et al. 2019

The Lancet Respiratory Medicine

209

246

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SummaryBackgroundFew genetic studies that focus on moderate-to-severe asthma exist. We aimed to identity novel genetic variants associated with moderate-to-severe asthma, see whether previously identified genetic variants for all types of asthma contribute to moderate-to-severe asthma, and provide novel mechanistic insights using expression analyses in patients with asthma.MethodsIn this genome-wide association study, we used a two-stage case-control design. In stage 1, we genotyped patient-level data from two UK cohorts (the Genetics of Asthma Severity and Phenotypes [GASP] initiative and the Unbiased BIOmarkers in PREDiction of respiratory disease outcomes [U-BIOPRED] project) and used data from the UK Biobank to collect patient-level genomic data for cases and controls of European ancestry in a 1:5 ratio. Cases were defined as having moderate-to-severe asthma if they were taking appropriate medication or had been diagnosed by a doctor. Controls were defined as not having asthma, rhinitis, eczema, allergy, emphysema, or chronic bronchitis as diagnosed by a doctor. For stage 2, an independent cohort of cases and controls (1:5) was selected from the UK Biobank only, with no overlap with stage 1 samples. In stage 1 we undertook a genome-wide association study of moderate-to-severe asthma, and in stage 2 we followed up independent variants that reached the significance threshold of p less than 1 × 10−6 in stage 1. We set genome-wide significance at p less than 5 × 10−8. For novel signals, we investigated their effect on all types of asthma (mild, moderate, and severe). For all signals meeting genome-wide significance, we investigated their effect on gene expression in patients with asthma and controls.FindingsWe included 5135 cases and 25 675 controls for stage 1, and 5414 cases and 21 471 controls for stage 2. We identified 24 genome-wide significant signals of association with moderate-to-severe asthma, including several signals in innate or adaptive immune-response genes. Three novel signals were identified: rs10905284 in GATA3 (coded allele A, odds ratio [OR] 0·90, 95% CI 0·88–0·93; p=1·76 × 10−10), rs11603634 in the MUC5AC region (coded allele G, OR 1·09, 1·06–1·12; p=2·32 × 10−8), and rs560026225 near KIAA1109 (coded allele GATT, OR 1·12, 1·08–1·16; p=3·06 × 10−9). The MUC5AC signal was not associated with asthma when analyses included mild asthma. The rs11603634 G allele was associated with increased expression of MUC5AC mRNA in bronchial epithelial brush samples via proxy SNP rs11602802; (p=2·50 × 10−5) and MUC5AC mRNA was increased in bronchial epithelial samples from patients with severe asthma (in two independent analyses, p=0·039 and p=0·022).InterpretationWe found substantial shared genetic architecture between mild and moderate-to-severe asthma. We also report for the first time genetic variants associated with the risk of developing moderate-to-severe asthma that regulate mucin production. Finally, we identify candidate causal genes in these loci and provide increased insight into this difficult to tr...

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Section: Discussionmentioning

confidence: 99%

Moderate-to-severe asthma in individuals of European ancestry: a genome-wide association study

Shrine

Portelli

John

et al. 2019

The Lancet Respiratory Medicine

209

246

View full text Add to dashboard Cite

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“…Relevante Einflussfaktoren sind der frühe Beginn einer atopischen Dermatitis, ihr höherer Schweregrad, eine familiäre Atopieanamnese und ein männliches Geschlecht [483,484]. Die atopische Dermatitis als Komorbidität geht mit einem höheren Schweregrad des Asthma einher [485]. 9.9 Asthma und Psyche 9.9.1 Bedeutung psychosozialer Belastungsfaktoren Psychosoziale Belastungsfaktoren sind für Genese, Exazerbationen und Prognose des Asthma relevant: Eine Metaanalyse bestätigte den bidirektionalen Zusammenhang zwischen psychologischen Faktoren und Asthma [486].…”

Section: Atopische Dermatitisunclassified

S2k-Leitlinie zur fachärztlichen Diagnostik und Therapie von Asthma 2023

et al. 2023

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ZusammenfassungDas Management von Asthma hat sich in den letzten Jahrzehnten fundamental gewandelt. Die vorliegende Leitlinie zur Diagnostik und Therapie von Asthma wurde für pneumologisch tätige Fachärztinnen und Fachärzte entwickelt, welche detaillierte und evidenzbasierte Informationen zu den neuen diagnostischen und therapeutischen Optionen von Asthma benötigen. Die Leitlinie zeigt die neue Bedeutung der Biomarker, insbesondere der Bluteosinophilen und des exhalierten NO (FeNO), in den diagnostischen Algorithmen von Asthma. Als erste Asthma-Leitlinie weltweit benennt die vorliegende Leitlinie die nachhaltige Symptomprävention und die Asthma-Remission als Asthma-Therapieziele, welche durch den Einsatz individuell angepasster, krankheitsmodifizierender Medikamente (wie inhalative Steroide, Allergenimmuntherapie oder Biologika) erreicht werden können. Die zentrale Bedeutung der Behandlung von typischen Asthma-Komorbiditäten wird zudem betont. Schließlich wird auch auf besondere Herausforderungen im Asthma-Management eingegangen, wie bspw. die Therapie von Asthma in der Schwangerschaft, die Behandlung von schwerem Asthma oder die Diagnostik und Therapie von arbeitsbedingten Asthma-Formen.

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“…Several studies reported that family history of atopy, early onset AD, higher initial severity of atopic eczema, hens' egg sensitization and male sex are associated with an increased risk of asthma in childhood (33). Furthermore, the percentage of patients with severe asthma and concomitant eczema is greater than expected and close relationship between asthma and atopic dermatitis severity has been reported (34).…”

Section: Allergic Comorbiditiesmentioning

confidence: 97%

Severe Asthma and Allergy: A Pediatric Perspective

et al. 2019

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Severe asthma in children is associated with significant morbidity and lung function decline. It represents a highly heterogeneous disorder with multiple clinical phenotypes. As its management is demanding, the social and economic burden are impressive. Several co-morbidities may contribute to worsen asthma control and complicate diagnostic and therapeutic management of severe asthmatic patients. Allergen sensitization and/or allergy symptoms may predict asthma onset and severity. A better framing of “allergen sensitization” and understanding of mechanisms underlying progression of atopic march could improve the management and the long-term outcomes of pediatric severe asthma. This review focuses on the current knowledge about interactions between severe asthma and allergies.

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Atopic dermatitis is an important comorbidity in severe asthma

Cited by 9 publications

References 10 publications

Moderate-to-severe asthma in individuals of European ancestry: a genome-wide association study

Moderate-to-severe asthma in individuals of European ancestry: a genome-wide association study

S2k-Leitlinie zur fachärztlichen Diagnostik und Therapie von Asthma 2023

Severe Asthma and Allergy: A Pediatric Perspective

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