BACKGROUND:The fatality rate of pulmonary arterial hypertension (PAH) is high. This study aimed to determine the correlation between ACE2 and monocrotaline (MCT)-induced PAH in rats. METHODS:Rats were randomly divided into 4 groups: control group; MCT group; resorcinolnaphthalein (Rec) group; and Rec + A779 (Mas receptor antagonist) group. Rats in the control group received a single subcutaneous injection of normal saline on the 1st d, and an osmotic pump capsule combining normal saline subcutaneously since the 2nd d. The rats in the other 3 groups received a single subcutaneous injection of MCT on the 1st d. An osmotic minipumps containing normal saline, Rec, and Rec + A779 were implanted in rats in the MCT, Rec, and Rec + A779 groups, respectively. RESULTS:The PAH rat model was successfully constructed with MCT. ACE2 reduced the mPAP, right ventricular hypertrophy index, and pulmonary artery media in the PAH rats (p < 0.05). Rec activated ACE2 expression and significantly increased the Mas levels, phospho-Akt (P-Akt), and phospho-eNOS (P-eNOS) in lung tissues of PAH rats (p < 0.05). The mPAP, right ventricular hypertrophy index, and pulmonary artery media in the Rec + A779 group were significantly increased compared to the blank and Rec groups (p < 0.05). The Mas level, P-Akt, and P-eNOS in rat lung tissues were significantly decreased in the Rec + A779 group compared to the Rec group (p < 0.05). CONCLUSION:Rec upregulates ACE2 expression, and this elevated ACE2 expression may be associated with amelioration of MCT‑induced PAH in rats, likely through the downstream Akt/eNOS signaling pathway.
Background:No randomised controlled trials (RCTs) have compared inhaled corticosteroid (ICS)/formoterol reliever-based stepwise algorithms with short-acting β-agonist (SABA) reliever-based stepwise algorithms, titrated to levels of asthma control and exacerbations. Knowledge gaps remain in understanding ICS exposure over time, transitions between treatment steps, efficacy and participant satisfaction with different algorithm approaches. Objective:The aim of the study is to determine the exposure to ICS in adults and adolescents aged 16 to 75 years treated with a budesonide/formoterol reliever-based algorithm (Algorithm 1) compared to a salbutamol reliever-based algorithm (Algorithm 2) across the spectrum of asthma severity. Methods:This is an investigator-initiated, 52-week, single-site, open-label, parallel-groups, 2-arm RCT of 152 adults and adolescents with mild, moderate and moderate-severe asthma (ACTRN12624001488594). Participants will be randomly allocated in a 1:1 ratio to a budesonide/formoterol reliever-based or a salbutamol reliever-based algorithm. Global Initiative for Asthma (GINA) treatment step at enrolment according to the 2024 GINA Guidelines will be used to allocate participants to the corresponding steps of each algorithm. Treatment step transition will be in response to asthma exacerbations and level of asthma control. Those experiencing exacerbations or poorly controlled asthma will be stepped up, and those well controlled stepped down. The primary outcome is ICS exposure. Important secondary outcomes include composite systemic corticosteroid exposure, rates of asthma exacerbations, asthma control, T-helper 2 biomarkers, spirometry and participants' treatment perceptions and satisfaction. Conclusion:This is the first RCT to compare ICS/formoterol- and SABA-based reliever stepwise algorithmic approaches in asthma, with treatment adjusted according to asthma control and exacerbations.
Adopting race-neutral GLI 2022 reclassified 12.9% of Korean COPD patients from trial-eligible to ineligible mild disease, and these reclassified patients demonstrated significantly lower risks of exacerbations and mortality https://bit.ly/4cG1OZt.
Both moderate and severe exacerbations of COPD follow patient-specific, predictable patterns rather than occurring as random events of chance https://bit.ly/4d6TkMS.
Transitioning from selexipag to parenteral prostacyclin analogues yielded haemodynamic improvement. Outcomes are poor among those within this population who do not achieve a low-risk status after the transition. https://bit.ly/4sMY3aF.
