The understanding of asthma pathogenesis in the era of precision medicine

Hizawa, Nobuyuki

doi:10.1016/j.alit.2022.09.001

Cited by 17 publications

(12 citation statements)

References 87 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, well‐powered and ethnically diverse studies also have the potential to improve the power of common variants to identify individuals at risk of developing asthma via polygenic risk scores, which can be used in the clinic for patient stratification and precision medicine approaches 179,180 . Through such approaches, GWAS/EWAS findings may also prove valuable as biomarkers in a clinical context, for example, by supporting patient phenotyping or for predicting risk of developing exacerbations and therapy response 33,181,182 . Given that cost of (epi)genotyping assays have been rapidly decreasing, we envision that well‐curated sets of (epi)genetic variants could in the future be employed in various clinical settings.…”

Section: Discussionmentioning

confidence: 99%

“…179,180 Through such approaches, GWAS/EWAS findings may also prove valuable as biomarkers in a clinical context, for example, by supporting patient phenotyping or for predicting risk of developing exacerbations and therapy response. 33,181,182 Given that cost of (epi)genotyping assays have been rapidly decreasing, we envision that well-curated sets of (epi)genetic variants could in the future be employed in various clinical settings. Regarding EWAS findings, it should be noted that replication of these associations has remained challenging, likely due to relatively small cohort sizes and differences in the investigated cell types or tissues.…”

Section: Con Clus I On S and Future Direc Tionsmentioning

confidence: 99%

See 1 more Smart Citation

Decoding the genetic and epigenetic basis of asthma

Stikker

Hendriks

Stadhouders

2023

Allergy

View full text Add to dashboard Cite

Asthma is a complex and heterogeneous chronic inflammatory disease of the airways. Alongside environmental factors, asthma susceptibility is strongly influenced by genetics. Given its high prevalence and our incomplete understanding of the mechanisms underlying disease susceptibility, asthma is frequently studied in genome‐wide association studies (GWAS), which have identified thousands of genetic variants associated with asthma development. Virtually all these genetic variants reside in non‐coding genomic regions, which has obscured the functional impact of asthma‐associated variants and their translation into disease‐relevant mechanisms. Recent advances in genomics technology and epigenetics now offer methods to link genetic variants to gene regulatory elements embedded within non‐coding regions, which have started to unravel the molecular mechanisms underlying the complex (epi)genetics of asthma. Here, we provide an integrated overview of (epi)genetic variants associated with asthma, focusing on efforts to link these disease associations to biological insight into asthma pathophysiology using state‐of‐the‐art genomics methodology. Finally, we provide a perspective as to how decoding the genetic and epigenetic basis of asthma has the potential to transform clinical management of asthma and to predict the risk of asthma development.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Con Clus I On S and Future Direc Tionsmentioning

confidence: 99%

Decoding the genetic and epigenetic basis of asthma

Stikker

Hendriks

Stadhouders

2023

Allergy

View full text Add to dashboard Cite

show abstract

“…The microbial flora colonizing the intestine are important factors that maintain the overall immune function and immune defense of the host [ 48 ]. Living environment and antibiotic abuse can trigger intestinal flora disorders and mediate the development of various diseases [ 49 ]. The “hygiene hypothesis” was the first to suggest a relationship between the absence and presence of microbial exposure during early childhood and chronic inflammatory diseases such as asthma [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

Integrated Network Pharmacology and Gut Microbiota Analysis to Explore the Mechanism of Sijunzi Decoction Involved in Alleviating Airway Inflammation in a Mouse Model of Asthma

Jia

Zhao

et al. 2023

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

Background. Asthma is a chronic inflammatory disease of the airways with recurrent attacks, which seriously affects the patients’ quality of life and even threatens their lives. The disease can even threaten the lives of patients. Sijunzi decoction (SJZD), a classical Chinese medicine formula with a long history of administration, is a basic formula used for the treatment of asthma and demonstrates remarkable efficacy. However, the underlying mechanism has not been elucidated. Materials and Methods. We aimed to integrate network pharmacology and intestinal flora sequencing analysis to study the mechanism of SJZD in the treatment of allergic asthmatic mice. The active compounds of SJZD and their asthma-related targets were predicted by various databases. We performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses to identify potentially relevant pathways for target genes. Furthermore, the active compound-target and target-signaling pathway network maps were constructed by using Cytoscape 3.8.2. These results were combined with those of the intestinal flora sequencing analysis to study the influence of SJZD on airway inflammation in allergic asthmatic mice. Result. We obtained 137 active compounds from SJZD and associated them with 1445 asthma-related targets acquired from the databases. A total of 109 common targets were identified. We visualized active compound-target and target-signaling pathway network maps. The pathological analysis and inflammation score results suggested that SJZD could alleviate airway inflammation in asthmatic mice. Sequencing analysis of intestinal flora showed that SJZD could increase the relevant abundance of beneficial bacterial genus and maintain the balance of the intestinal flora. The core toll-like receptor (TLR) signaling pathway was identified based on network pharmacology analysis, and the important role TLRs play in intestinal flora and organismal immunity was also recognized. The analysis of the correlation between environmental factors and intestinal flora revealed that beneficial bacterial genera were negatively correlated with TLR2 and positively correlated with the TLR7 expression. Furthermore, they were positively correlated with IFN-γ and IL-10 levels and negatively correlated with IL-4 and IL-17 levels. Conclusion. SJZD alleviated the airway inflammation state in asthmatic mice. The findings suggest that increasing the relevant abundance of beneficial intestinal bacteria in mice with asthma, regulating intestinal flora, interfering with the level of TLR2 and TLR7 expression to adjust the secretion of inflammatory factors, and alleviating asthmatic airway inflammation may be the possible mechanism involved in the treatment of asthma by SJZD, providing a basis for further studies on SJZD.

show abstract

“…ns-not significant. ns Hizawa, 2022). We hypothesize that ICS can alter gut microbiomes in asthma patients who are resistant to ICS therapy and subsequently alter their immune responses, potentially contributing to poor outcomes in difficult-totreat patients suffering from asthma.…”

Section: Discussionmentioning

confidence: 99%

A steroid‐resistant cockroach allergen model is associated with lung and cecal microbiome changes

Asai

Ethridge

Fonseca

et al. 2023

Physiological Reports

View full text Add to dashboard Cite

The pathogenesis of asthma has been partially linked to lung and gut microbiome. We utilized a steroid‐resistant chronic model of cockroach antigen‐induced (CRA) asthma with corticosteroid (fluticasone) treatment to examine lung and gut microbiome during disease. The pathophysiology assessment demonstrated that mucus and airway hyperresponsiveness were increased in the chronic CRA with no alteration in the fluticasone (Flut)‐treated group, demonstrating steroid resistance. Analysis of mRNA from lungs showed no decrease of MUC5AC or Gob5 in the Flut‐treated group. Furthermore, flow‐cytometry in lung tissue showed eosinophils and neutrophils were not significantly reduced in the Flut‐treated group compared to the chronic CRA group. When the microbiome profiles were assessed, data showed that only the Flut‐treated animals were significantly different in the gut microbiome. Finally, a functional analysis of cecal microbiome metabolites using PiCRUSt showed several biosynthetic pathways were significantly enriched in the Flut‐treated group, with tryptophan pathway verified by ELISA with increased kynurenine in homogenized cecum samples. While the implications of these data are unclear, they may suggest a significant impact of steroid treatment on future disease pathogenesis through microbiome and associated metabolite pathway changes.

show abstract

The understanding of asthma pathogenesis in the era of precision medicine

Cited by 17 publications

References 87 publications

Decoding the genetic and epigenetic basis of asthma

Decoding the genetic and epigenetic basis of asthma

Integrated Network Pharmacology and Gut Microbiota Analysis to Explore the Mechanism of Sijunzi Decoction Involved in Alleviating Airway Inflammation in a Mouse Model of Asthma

A steroid‐resistant cockroach allergen model is associated with lung and cecal microbiome changes

Contact Info

Product

Resources

About