Jose Rodrigo-Muñoz

and 7 more

Background MicroRNAs are noncoding molecules that act both as regulators of the epigenetic landscape and as biomarkers for diseases, including asthma. In the era of personalized medicine there is a need for novel disease-associated biomarkers that can help in classifying diseases into phenotypes for treatment selection. Currently, severe eosinophilic asthma is one of the most widely studied phenotypes in clinical practice, as many patients require higher and higher doses of corticosteroids, which in some cases fail to achieve the desired outcome. Such patients may only be benefit from alternative drugs such as biologics, for which novel biomarkers are necessary. Methods MiR-144-3p was evaluated in airway biopsies and serum from asthmatics and healthy individuals. mRNA was studied in asthmatic biopsies and smooth muscle cells transfected with miR-144-3p mimic. In silico regulation of miR-144-3p was performed using miRSystem, miRDB, STRING and ShinyGO for pathway analysis. Results We found that miR-144-3p is a biomarker associated to asthma severity and corticosteroid treatment. MiR-144-3p is increased in asthmatic lungs and its presence correlates directly with blood eosinophilia and with the expression of genes involved in asthma pathophysiology in the airways. When studied in serum, this miRNA was increased in the severe asthmatics and associated with higher doses of corticosteroids, thereby making it a potential biomarker for severe asthma previously treated with higher doses of corticosteroids. Conclusion MiR-144-3p is associated with severe disease in both the airways and serum of asthmatics, and this association is related to corticosteroids treatment.
Background: Respiratory viral infections (RVIs) are frequent in preterm infants and may have long-term impact on respiratory morbidity, especially those with bronchopulmonary dysplasia (BDP). The immune response and respiratory are key defence elements, so the purpose of this study is to evaluate the immune response regulation and the respiratory epithelial barrier integrity in the preterm infants suffering RVIs during Neonatal Intensive Care Unit (NICU) admission. Materials and methods: Nasopharyngeal aspirate (NPA) was obtained, separating cells from supernatants. Viral detection was performed by RT-nested PCR, and gene expression by qPCR. Proteins were detected by western blot and ELISA or Luminex. Small airway epithelial cells (SAEC) were stimulated with Poly:IC and/or wounds. Results: Pre-infection samples from 26 preterm infants that later developed RVIs had less frequency of filaggrin gene expression and fewer protein levels compared to 23 noninfected controls. Conversely, filaggrin, IL-1β, MIP-1β, VEGF and HIF-1α levels were higher in pre-infection supernatant samples, being infection-risk biomarkers. IL-17A, RANTES, VEGF, and HIF-1α levels were higher during and post infection, while MCP-1 and amphiregulin were reduced after infection. Small airway epithelial cells (SAEC) stimulated by poly:IC reduced filaggrin gene expression and increased its levels at supernatant. Finally, poly:IC stimulation over SAEC increased TLR3 and TSLP expression, while reduced AREG. Conclusion: Filaggrin gene expression and protein quantity was reduced at cellular level of the NPA, while its secreted levels were increased in basal samples from infected newborns and in SAEC stimulated with poly:IC. Our findings highlight the importance of filaggrin as a factor facilitating RVIs.

Blanca Barroso

and 25 more

Background. Chronic rhinosinusitis with nasal polyps (CRSwNP), characterized by partial (hyposmia) or total (anosmia) loss of smell, is commonly associated with asthma and/or nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD), worsens disease severity and quality of life. The objective of this study was to determine whether, in real-life conditions, biological treatments prescribed for severe asthma can improve olfaction in patients with CRSwNP. A further objective was to compare smell improvement in N-ERD and non-N-ERD subgroups. Methods. A multicenter, non-interventional, retrospective, observational study was performed, including 206 patients with severe asthma undergoing biological treatment (omalizumab, mepolizumab, benralizumab, or reslizumab) with CRSwNP. Results. Improved olfaction was found after treatment with all monoclonal antibodies: omalizumab (35.8%), mepolizumab (35.4%), reslizumab (35.7%), and benralizumab (39.1%), with no differences between groups. Patients with atopy, greater use of short course systemic corticosteroids, and larger polyp size were more likely to experience improvement in smell. The proportion of patients experiencing smell improvement was similar between the N-ERD (37%) and non-N-ERD (35.7%) groups. Conclusions. This is the first study to compare real-life improvement in sense of smell among patients undergoing long-term treatment with omalizumab, mepolizumab, reslizumab, or benralizumab for severe asthma and associated CRSwNP. Approximately 4 out of 10 patients reported a subjective improvement in sense of smell (with non-significant differences between biologic drugs). No differences were found in smell improvement between the N-ERD and non-N-ERD group.

Marek Jutel

and 68 more