Conectar
by Aditya Sri Listyoko, Ryota Okazaki, Tomoya Harada, Genki Inui, Hiroki Kohno, Miyu Nishigami, Miki Takata, Masato Morita, Akira Yamasaki
BackgroundThe interaction between viral components and type 1 or type 2 cytokines during asthma exacerbations in the airway epithelium may contribute to worsening inflammation. However, these interactions in the small airway epithelium—particularly those involving alarmins (TSLP, IL-25, and IL-33) and IL-8—remain unclear. Dupilumab, a biologic agent used in severe asthma, blocks IL-4 receptor alpha (IL-4Rα) and may offer therapeutic benefits in virus-induced asthma exacerbations. In this study, we evaluate the effects of double-stranded RNA (dsRNA), in combination with various cytokines and dupilumab, on the Human Small Airway Epithelial Cells (HSAECs) line.
MethodsPrimary HSAECs were preincubated with dsRNA to induce the gene and protein expression of alarmins and IL-8. To evaluate the effects of cytokines on dsRNA-induced alarmin and IL-8 expression, various type 1 and type 2 cytokines were co-stimulated with dsRNA. Dupilumab was used as a pretreatment prior to co-stimulation with dsRNA and IL-4 or IL-13. Gene expression of TSLP, IL-25, IL-33, and IL-8 was assessed by quantitative PCR, and protein expression was evaluated by Western Blotting.
ResultsdsRNA significantly increased the expression of TSLP and IL-8. IL-4 and IL-13 further enhanced dsRNA-induced TSLP and IL-8 gene and protein expression. In contrast, TNF-α reduced dsRNA-induced TSLP expression but enhanced IL-8 gene and protein expression. Dupilumab attenuated the expression of TSLP and IL-8 induced by co-stimulation with dsRNA and IL-4 or IL-13 in HSAECs.
ConclusionIn the microenvironment of small airway epithelial cells, particularly during viral infections, the presence of IL-4 or IL-13 may enhance the expression of TSLP and IL-8. Dupilumab attenuates this expression, potentially offering additional benefits in the treatment of asthma, especially during virus-induced asthma exacerbations.
To investigate the relationship between a quality of life (QOL) score and clinical parameters in patients with hypertrophic cardiomyopathy (HCM).
A multicentre cross-sectional study.
We analysed data from the Searching for Atrial Fibrillation and Early Recruitment of Heart Failure in HCM registry, collected between 2018 and 2023.
Patients with HCM (n=499) aged ≥18 years from 12 institutions (Shizuoka Prefecture, Japan) were consecutively enrolled.
Clinical parameters, along with data from a short form of the Kansas City Cardiomyopathy Questionnaire (KCCQ-12), were collected. The association between each clinical parameter and the KCCQ-12 score was analysed. Clinical parameters with a significant univariable association (p
In the univariable analysis, KCCQ-12 scores exhibited significant associations with 21 clinical parameters, including sex, left ventricular morphology and the Pittsburgh Sleep Quality Index (PSQI). The multiple regression model with 12 parameters that had a significant univariable association exhibited an adjusted R2 of 0.48. In this model, the PSQI (standardised coefficient –0.39; p
In patients with HCM, we investigated the association between the KCCQ-12 score and various clinical parameters. PSQI, as well as known heart failure-related clinical parameters, was significantly associated with the KCCQ-12 score. Visualising the associations of various clinical parameters with the KCCQ-12 score will help physicians to consider factors linked to the decline in QOL in patients with HCM.
Hypertension is a major health challenge imposing substantial economic and health burdens worldwide. This study compared treatment outcomes and costs between cost-intensive and non-cost-intensive pharmacotherapies, defined by prescribing intervals and the type of drugs, using electronic health record (EHR) data from multiple healthcare facilities, focusing on the type of antihypertensive drug and prescribing patterns.
A retrospective cohort study. A mixed-effects Cox proportional hazards model was used to investigate the association between cardiovascular events and healthcare resource use.
EHRs from 34 primary care facilities in Japan.
Patients prescribed either angiotensin receptor blockers (ARBs) alone or calcium channel blockers (CCBs) alone were included.
During 6629 person-years of follow-up, 71 events were observed. Model diagnostics confirmed the proportional hazards assumption and substantial inter-clinic heterogeneity. The type of drug (ARBs or CCBs) had no statistically significant impact on the incidence of cardiovascular events (HR 0.999, 95% CI 0.603 to 1.655). Similarly, shorter prescribing intervals (less than 36 days) were not significantly associated with the outcome (HR 1.724, 95% CI 0.906 to 3.279). The mean annual medical cost per patient for the cost-intensive (ARB with short prescribing intervals) and non-cost-intensive (CCB with long prescribing intervals) groups was Japanese yen (JPY) 137 023 and JPY 85 911, respectively. Sensitivity analysis using different time windows yielded similar results, confirming the robustness of the findings.
No apparent reduction in cardiovascular events associated with the use of ARBs or shorter prescribing intervals was observed despite the elevated cost caused by intensive pharmacotherapy and frequent clinic visits.
FreshRSS 