Spotlight on a Short-Time Treatment with the IL-4/IL-13 Receptor Blocker in Patients with CRSwNP: microRNAs Modulations and Preliminary Clinical Evidence

Mimmi, Selena; Lombardo, Nicola; Maisano, Domenico; Piazzetta, Giovanna; Pelaia, Corrado; Pelaia, Girolamo; Greco, Marta; Foti, Daniela; Dattilo, Vincenzo; Iaccino, Enrico

doi:10.3390/genes13122366

Cited by 6 publications

(5 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Other pathways investigated or identified in these studies include those related to T cells and cytokines ( 40 , 43 , 48 , 55 , 60 , 66 ), eosinophil trafficking ( 59 ), PI3K/AKT signaling ( 40 , 56 , 58 , 65 , 75 ), Ras–MAPK signaling ( 47 , 66 , 69 , 75 ), Wnt signaling ( 47 , 57 ), ECM ( 83 , 84 ), adherens junctions ( 65 , 83 , 84 ), focal adhesions ( 47 , 65 , 84 ), matrix metalloproteinases ( 77 ), vascular permeability ( 45 , 78 ), cell cycle and apoptosis ( 64 , 85 ), EGF ( 74 ), ROR alpha (on exposure to pollution) ( 61 ), and IRF4 ( 42 ).…”

Section: Resultsmentioning

confidence: 99%

“…These include involvement of the mucin type-O-glycan biosynthesis pathway ( 44 , 62 , 65 , 66 , 81 ), mucin secretion ( 76 ), and identification of GALNT7 through a lncRNA study ( 44 ). Impairment of pathways and implication of genes involved in structural integrity include COL18A1 ( 28 ), integrin genes ( ITGB2 , ITGAL , and ITGAM ) ( 31 ), KRT19 ( 26 ), alpha-SMA , fibronectin , and collagen type 1 ( 32 , 33 ), and miRNA studies have found pathways involving adherens junctions ( 65 , 83 , 84 ) and focal adhesions ( 47 , 65 , 84 ). An impaired epithelial barrier is a commonly accepted pathophysiological mechanism in CRS, and whether the epigenetic modifications in genes involved in the nasal epithelial structure is a cause or consequence of the inflammatory process is yet to be discerned.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Insights into the epigenetics of chronic rhinosinusitis with and without nasal polyps: a systematic review

2023

View full text Add to dashboard Cite

BackgroundEpigenetics facilitates insights on the impact of host environment on the genesis of chronic rhinosinusitis (CRS) through modulations of host gene expression and activity. Epigenetic mechanisms such as DNA methylation cause reversible but heritable changes in gene expression over generations of progeny, without altering the DNA base-pair sequences. These studies offer a critical understanding of the environment-induced changes that result in host predisposition to disease and may help in developing novel biomarkers and therapeutics. The goal of this systematic review is to summarize the current evidence on epigenetics of CRS with a focus on chronic rhinosinusitis with nasal polyps (CRSwNP) and highlight gaps that merit further research.MethodsA systematic review of the English language literature was performed to identify investigations related to epigenetic studies in subjects with CRS.ResultsThe review identified 65 studies. These have focused on DNA methylation and non-coding RNAs, with only a few on histone deacetylation, alternative polyadenylation, and chromatin accessibility. Studies include those investigating in vivo and in vitro changes or both. Studies also include animal models of CRS. Almost all have been conducted in Asia. The genome-wide studies of DNA methylation found differences in global methylation between CRSwNP and controls, while others specifically found significant differences in methylation of the CpG sites of the thymic stromal lymphopoietin (TSLP), IL-8, and PLAT. In addition, DNA methyltransferase inhibitors and histone deacetylase inhibitors were studied as potential therapeutic agents. Majority of the studies investigating non-coding RNAs focused on micro-RNAs (miRNA) and found differences in global expression of miRNA levels. These studies also revealed some previously known as well as novel targets and pathways such as tumor necrosis factor alpha, TGF beta-1, IL-10, EGR2, aryl hydrocarbon receptor, PI3K/AKT pathway, mucin secretion, and vascular permeability. Overall, the studies have found a dysregulation in pathways/genes involving inflammation, immune regulation, tissue remodeling, structural proteins, mucin secretion, arachidonic acid metabolism, and transcription.ConclusionsEpigenetic studies in CRS subjects suggest that there is likely a major impact of the environment. However, these are association studies and do not directly imply pathogenesis. Longitudinal studies in geographically and racially diverse population cohorts are necessary to quantify genetic vs. environmental risks for CRSwNP and CRS without nasal polyps and assess heritability risk, as well as develop novel biomarkers and therapeutic agents.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Insights into the epigenetics of chronic rhinosinusitis with and without nasal polyps: a systematic review

2023

View full text Add to dashboard Cite

show abstract

“…At the end of the treatment, a decrease in the expression of miRNAs-25-3p and -185-5p was shown in the blood. As was proven, they are involved in the inflammatory process, T lymphocyte regulation, and drug resistance, thanks to which we note a significant clinical improvement among the subjects after using the drug [52]. Currently, no studies show the relationship between Dupilumab and miRNAs in asthmatics.…”

Section: Mirnas and Individual Groups Of Drugs Used In Asthma (Glucoc...mentioning

confidence: 59%

miRNAs as Modern Biomarkers in Asthma Therapy

Kierbiedź-Guzik¹,

Sozańska

2023

IJMS

View full text Add to dashboard Cite

Asthma is a chronic inflammatory disease of the airways characterized by shortness of breath, chest tightness, coughing, and wheezing. For several decades (approximately 30 years), miRNAs and their role in asthma have been of constant interest among scientists. These small, non-coding RNA fragments, 18–25 nucleotides long, regulate gene expression at the post-transcriptional level by binding to the target mRNA. In this way, they affect several biological processes, e.g., shaping airway structures, producing cytokines and immune mediators, and controlling defense mechanisms. Publications confirm their potential role in the diagnosis and monitoring of the disease, but only some articles address the use of miRNAs in the treatment of asthma. The following paper reviews the latest available studies and presents miRNAs as a useful tool for predicting the effectiveness of the included treatment, early diagnosis of exacerbations, and in assessing patient compliance for different groups of drugs used in asthma. The latest known pathways underlying the pathogenesis of the disease, which are associated with a change in miRNA expression, may be precise targets of therapeutic activity in the future.

show abstract

“…The inhibition of the IL-4/IL-13 axis by dupilumab should be recognized as a multisystemic effect ( 30 , 31 ). Our results showed the overall improvement of the clinical picture that dupilumab offers for patients with severe AD and persistent allergic asthma of any severity.…”

Section: Discussionmentioning

confidence: 99%

Asthma improvement in patients treated with dupilumab for severe atopic dermatitis

Dubini,

Benzecry,

Rivolta

et al. 2023

Front. Allergy

View full text Add to dashboard Cite

IntroductionAtopic dermatitis (AD) is considered a systemic type 2 immune driven disease, and it is associated to many atopic comorbidities including asthma. The aim of our study was to prospectively evaluate the respiratory outcomes in patients with persistent allergic asthma treated with dupilumab due to severe AD (sAD).MethodsWe enrolled eligible patients with sAD for dupilumab treatment from September 2018 to December 2020. We then selected the subgroup of patients sensitized to perennial allergens. Dupilumab's efficacy and safety on AD and comorbid asthma were assessed at baseline, one month, four months, and then every 4 months up to one year.ResultsA total of 437 patients with sAD were enrolled for dupilumab treatment due to sAD, and 273 reached 48 weeks of therapy. Respiratory outcomes were evaluated in the 85 asthmatic patients with positivity only to perennial allergens. Our patients showed statistically and clinically significant improvement in asthma control (Asthma Control Test and Asthma Control Questionnaire) and airway obstruction parameters (FEV1), in addition to the expected AD-related skin outcomes. Specifically, a significant improvement was achieved at the fourth month of dupilumab therapy, and this trend was maintained up to twelve months, regardless of asthma severity.ConclusionsOur results showed the overall improvement of the clinical picture that dupilumab offers for patients with severe AD and persistent allergic asthma of any severity, highlighting the importance of a global multidisciplinary approach of type 2 driven disease.

show abstract

Spotlight on a Short-Time Treatment with the IL-4/IL-13 Receptor Blocker in Patients with CRSwNP: microRNAs Modulations and Preliminary Clinical Evidence

Cited by 6 publications

References 40 publications

Insights into the epigenetics of chronic rhinosinusitis with and without nasal polyps: a systematic review

Insights into the epigenetics of chronic rhinosinusitis with and without nasal polyps: a systematic review

miRNAs as Modern Biomarkers in Asthma Therapy

Asthma improvement in patients treated with dupilumab for severe atopic dermatitis

Contact Info

Product

Resources

About