A review on the pathophysiology of asthma remission

Carpaij, Orestes A; Burgess, Janette K.; Kerstjens, Huib; Nawijn, Martijn C.; Berge, Maarten van den

doi:10.1016/j.pharmthera.2019.05.002

Cited by 48 publications

(40 citation statements)

References 145 publications

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“…Another important characteristic of persistent airflow obstruction in asthma is airway remodeling, including GCM, EMT, subepithelial collagen deposition, airway smooth muscle hyperplasia, and increased vascularity [5,6]. Increasing evidence suggests the involvement of EMT in the bronchial remodeling of asthmatic patients [43][44][45][46].…”

Section: Discussionmentioning

confidence: 99%

“…Asthma is characterized by reversible airflow obstruction [1,2]. Airway remodeling is one crucial part of the reversible airflow obstruction of asthma [3], including goblet cell metaplasia (GCM), epithelial-tomesenchymal transition (EMT), excessive subepithelial collagen deposition, airway smooth muscle hyperplasia, and increased vascularity [4,5]. Although the prevailing thought is that remodeling is an abnormal response to persistent airway inflammation, recent evidence, especially from studies of remodeling in asthmatic children, suggests that the two processes occur in parallel [6,7].…”

Section: Introductionmentioning

confidence: 99%

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ZDHXB-101 (3′,5-Diallyl-2, 4′-dihydroxy-[1,1′-biphen-yl]-3,5′-dicarbaldehyde) protects against airway remodeling and hyperresponsiveness via inhibiting both the activation of the mitogen-activated protein kinase and the signal transducer and activator of transcription-3 signaling pathways

et al. 2020

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Airway remodeling consists of the structural changes of airway walls, which is often considered the result of longstanding airway inflammation, but it may be present to an equivalent degree in the airways of children with asthma, raising the need for early and specific therapeutic interventions. The arachidonic acid cytochrome P-450 (CYP) pathway has thus far received relatively little attention in its relation to asthma. In this study, we studied the inhibition of soluble epoxide hydrolase (sEH) on airway remodeling and hyperresponsiveness (AHR) in a chronic asthmatic model which long-term exposure to antigen over a period of 12 weeks. The expression of sEH and CYP2J2, the level of 14, 15-epoxyeicosatrienoic acids (EETs), airway remodeling, hyperresponsiveness and inflammation were analyzed to determine the inhibition of sEH. The intragastric administration of 3 or 10 mg/kg ZDHXB-101, which is a structural derivative of natural product honokiol and a novel soluble epoxide hydrolase (sEH) inhibitor, daily for 9 weeks significantly increased the level of 14, 15-EETs by inhibiting the expression of sEH and increasing the expression of CYP2J2 in lung tissues. ZDHXB-101 reduced the expression of remodeling-related markers such as interleukin (IL)-13, IL-17, MMP-9 N-cadherin, α-smooth muscle actin, S100A4, Twist, goblet cell metaplasia, and collagen deposition in the lung tissue or in bronchoalveolar lavage fluid. Moreover, ZDHXB-101 alleviated AHR, which is an indicator that is used to evaluate the airway remodeling function. The inhibitory effects of ZDHXB-101 were demonstrated to be related to its direct inhibition of the extracellular signal-regulated kinase

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

ZDHXB-101 (3′,5-Diallyl-2, 4′-dihydroxy-[1,1′-biphen-yl]-3,5′-dicarbaldehyde) protects against airway remodeling and hyperresponsiveness via inhibiting both the activation of the mitogen-activated protein kinase and the signal transducer and activator of transcription-3 signaling pathways

et al. 2020

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“…Asthma remission is more common in patients with childhood onset asthma, and the proportions of remission differ in different age groups at follow-up (33–53% in adolescence, 6–33% in young adulthood and 11–52% in adulthood) [ 1 , 2 ]. There are two types of asthma remission, one is defined by absence of asthma symptoms and medication for at least one year, which is called “clinical remission” (ClinR).…”

Section: Introductionmentioning

confidence: 99%

“…In addition to criteria of ClinR, ComR has to meet additional criteria of normal lung function and absence of AHR. This is a more rare phenomenon, that takes place in 5–22% of asthmatics [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Epigenome-wide association study identifies DNA methylation markers for asthma remission in whole blood and nasal epithelium

Vonk

Plaat

et al. 2020

Clin Transl Allergy

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Background Asthma is a chronic respiratory disease which is not curable, yet some patients experience spontaneous remission. We hypothesized that epigenetic mechanisms may be involved in asthma remission. Methods Clinical remission (ClinR) was defined as the absence of asthma symptoms and medication for at least 12 months, and complete remission (ComR) was defined as ClinR with normal lung function and absence of airway hyperresponsiveness. We analyzed differential DNA methylation of ClinR and ComR comparing to persistent asthma (PersA) in whole blood samples (n = 72) and nasal brushing samples (n = 97) in a longitudinal cohort of well characterized asthma patients. Significant findings of whole blood DNA methylation were tested for replication in two independent cohorts, Lifelines and Epidemiological study on the Genetics and Environment of Asthma (EGEA). Results We identified differentially methylated CpG sites associated with ClinR (7 CpG sites) and ComR (129 CpG sites) in whole blood. One CpG (cg13378519, Chr1) associated with ClinR was replicated and annotated to PEX11 (Peroxisomal Biogenesis Factor 11 Beta). The whole blood DNA methylation levels of this CpG were also different between ClinR and healthy subjects. One ComR-associated CpG (cg24788483, Chr10) that annotated to TCF7L2 (Transcription Factor 7 Like 2) was replicated and associated with expression of TCF7L2 gene. One out of seven ClinR-associated CpG sites and 8 out of 129 ComR-associated CpG sites identified from whole blood samples showed nominal significance (P < 0.05) and the same direction of effect in nasal brushes. Conclusion We identified DNA methylation markers possibly associated with clinical and complete asthma remission in nasal brushes and whole blood, and two CpG sites identified from whole blood can be replicated in independent cohorts and may play a role in peroxisome proliferation and Wnt signaling pathway.

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“…In addition to criteria of ClinR, ComR has to meet additional criteria of normal lung function and absence of AHR. This is a more rare phenomenon, that takes place in 5%-22% of asthmatics 3 .…”

Section: Introductionmentioning

confidence: 99%

Epigenome-wide association study identifies DNA methylation markers for asthma remission in blood and nasal epithelium

Vonk

Plaat

et al. 2020

Preprint

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Background: Asthma is a chronic respiratory disease which is not curable, yet some patients experience spontaneous remission. We hypothesized that epigenetic mechanisms may be involved in asthma remission. Methods: Clinical remission (ClinR) was defined as the absence of asthma symptoms and medication for at least 12 months, and complete remission (ComR) was defined as ClinR with normal lung function and absence of airway hyperresponsiveness. We analyzed differential DNA methylation of ClinR and ComR comparing to persistent asthma (PersA) in whole blood samples (n=72) and nasal brushing samples (n=97) in a longitudinal cohort of well characterized asthma patients. Significant findings of whole blood DNA methylation were tested for replication in two independent cohorts, Lifelines and EGEA. Results: We identified differentially methylated CpG sites associated with ClinR (7 CpG sites) and ComR (129 CpG sites) in whole blood. One CpG (cg13378519, Chr1) associated with ClinR was replicated and annotated to PEX11 (Peroxisomal Biogenesis Factor 11 Beta). The whole blood DNA methylation levels of this CpG were also different between ClinR and healthy subjects. One ComR-associated CpG (cg24788483, Chr10) that annotated to TCF7L2 (Transcription Factor 7 Like 2) was replicated and associated with expression of TCF7L2 gene. One out of seven ClinR-associated CpG sites and 8 out of 129 ComR-associated CpG sites identified from whole blood samples showed nominal significance (P<0.05) and the same direction of effect in nasal brushes. Conclusion: We identified DNA methylation markers possibly associated with clinical and complete asthma remission in nasal brushes and whole blood.

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A review on the pathophysiology of asthma remission

Cited by 48 publications

References 145 publications

ZDHXB-101 (3′,5-Diallyl-2, 4′-dihydroxy-[1,1′-biphen-yl]-3,5′-dicarbaldehyde) protects against airway remodeling and hyperresponsiveness via inhibiting both the activation of the mitogen-activated protein kinase and the signal transducer and activator of transcription-3 signaling pathways

ZDHXB-101 (3′,5-Diallyl-2, 4′-dihydroxy-[1,1′-biphen-yl]-3,5′-dicarbaldehyde) protects against airway remodeling and hyperresponsiveness via inhibiting both the activation of the mitogen-activated protein kinase and the signal transducer and activator of transcription-3 signaling pathways

Epigenome-wide association study identifies DNA methylation markers for asthma remission in whole blood and nasal epithelium

Epigenome-wide association study identifies DNA methylation markers for asthma remission in blood and nasal epithelium

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