Publications

Leukotriene (LT) E(4) and 8-isoprostane concentrations are elevated in exhaled breath condensate in children with asthma. The effects of leukotriene receptor antagonists (LTRAs) on exhaled leukotriene and prostanoids in children with asthma are unknown.(1) To study the effect of montelukast, a LTRA, on exhaled LTE(4), 8-isoprostane, and prostaglandin E(2) in children with asthma and atopic children; (2) to measure exhaled nitric oxide.An open-label study with oral montelukast (5 mg once daily for 4 weeks) was undertaken in 17 atopic children with asthma and 16 atopic children without asthma.Pretreatment exhaled LTE(4) (P < .0001) and 8-isoprostane (P < .0001) values were higher in atopic children with asthma than in atopic children without asthma. In atopic children with asthma, montelukast reduced exhaled LTE(4) by 33% (P < .001), and this reduction was correlated with pretreatment LTE(4) values (r = -0.90; P = .0001). Posttreatment exhaled LTE(4) levels in children with asthma were higher than pretreatment LTE(4) values in atopic children without asthma (P < .004). Montelukast had no effect on exhaled LTE(4) in atopic children without asthma (P = .74), or on exhaled 8-isoprostane (atopic children with asthma, P = .94; atopic children without asthma, P = .55) and PGE(2) (atopic children with asthma, P = .56; atopic children without asthma, P = .93) in both groups. In atopic children with asthma, exhaled nitric oxide concentrations were reduced by 27% (P < .05) after montelukast.Leukotriene receptor antagonists decrease exhaled LTE(4) in atopic children with asthma. This reduction is dependent on baseline exhaled LTE(4) values.Measurement of exhaled LTE(4) might help identify children with asthma most likely to benefit from LTRAs.

Background —Restenosis after conventional stenting is almost exclusively caused by neointimal hyperplasia. β-Particle–emitting radioactive stents decrease in-stent neointimal hyperplasia at 6-month follow-up. The purpose of this study was to evaluate the 1-year outcome of 32 P radioactive stents with an initial activity of 6 to 12 μCi using serial quantitative coronary angiography and volumetric ECG-gated 3D intravascular ultrasound (IVUS). Methods and Results —Of 40 patients undergoing initial stent implantation, 26 were event-free after the 6-month follow-up period and 22 underwent repeat catheterization and IVUS at 1 year; they comprised half of the study population. Significant luminal deterioration was observed within the stents between 6 months and 1 year, as evidenced by a decrease in the angiographic minimum lumen diameter (−0.43±0.56 mm; P =0.028) and in the mean lumen diameter in the stent (−0.55±0.63 mm; P =0.001); a significant increase in in-stent neointimal hyperplasia by IVUS (18.16±12.59 mm 3 at 6 months to 27.75±11.99 mm 3 at 1 year; P =0.001) was also observed. Target vessel revascularization was performed in 5 patients (23%). No patient experienced late occlusion, myocardial infarction, or death. By 1 year, 21 of the initial 40 patients (65%) remained event-free. Conclusions —Neointimal proliferation is delayed rather than prevented by radioactive stent implantation. Clinical outcome 1 year after the implantation of stents with an initial activity of 6 to 12 μCi is not favorable when compared with conventional stenting.

Background To date, no specific drug-eluting stent (DES) has fully proven its superiority over others in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention. Objectives The purpose of this study was to compare the safety and efficacy of coronary artery stents in STEMI patients in a patient-level network meta-analysis. Methods Eligible studies were dedicated randomized controlled trials comparing different stents in STEMI patients undergoing percutaneous coronary intervention with at least 12 months of clinical follow-up. Of 19 studies identified from the published data, individual patient data were collected in 15 studies with 10,979 patients representing 87.7% of patients in the overall network of evidence. The primary endpoint was the composite of cardiac death, reinfarction, or target lesion revascularization. Results Overall, 8,487 (77.3%) of 10,979 STEMI patients were male and the mean age was 60.7 years. At a median follow-up of 3 years, compared with bare-metal stents (BMS), patients treated with paclitaxel-, sirolimus-, everolimus-, or biolimus-eluting stents had a significantly lower risk of the primary endpoint (adjusted hazard ratios [HRs]: 0.74 [95% confidence interval (CI): 0.63 to 0.88], 0.65 [95% CI: 0.49 to 0.85], 0.70 [95% CI: 0.53 to 0.91], and 0.66 [95% CI: 0.49 to 0.88], respectively). The risk of primary endpoint was not different between patients treated with BMS and zotarolimus-eluting stents (adjusted HR: 0.83 [95% CI: 0.51 to 1.38]). Among patients treated with DES, no significant difference in the risk of the primary outcome was demonstrated. Treatment with second-generation DES was associated with significantly lower risk of definite or probable stent thrombosis compared with BMS (adjusted HR: 0.61 [95% CI: 0.42 to 0.89]) and first-generation DES (adjusted HR: 0.56 [95% CI: 0.36 to 0.88]). Conclusions In STEMI patients, DES were superior to BMS with respect to long-term efficacy. No difference in long-term efficacy and safety was observed among specific DES. Second-generation were superior to first-generation DES in reducing stent thrombosis. (Clinical Outcomes After Primary Percutaneous Coronary Intervention [PCI] Using Contemporary Drug-Eluting Stent [DES]: Evidence From the Individual Patient Data Network Meta-Analysis; CRD42018104053)

Following allergen exposure, sensitized Brown–Norway rats develop airway hyperresponsiveness (AHR) and eosinophilic inflammation together with an increase in activated T cells (CD25 + ) in the airways. We tested the hypothesis that CD4 + T cells are involved directly in the acquisition of AHR. Spleen T cells from animals that were injected intraperitoneally on three consecutive days with ovalbumin/Al(OH) 3 , showed a dose‐dependent proliferative response in vitr o to ovalbumin, but not to bovine serum albumin, as measured by []&gt; 3 H]thymidine uptake. For total T‐cell transfer, spleen cells obtained from donor rats 4 days after sensitization were depleted of adherent cells by a nylon wool column separation. CD4 + and CD8 + T cells were purified by immunomagnetic beads cell separation. Recipient naive rats were injected intravenously with 50×10 6 total T cells, 20×10 6 and 5×10 6 CD4 + cells, and 5×10 6 CD8 + cells, and were exposed to ovalbumin aerosol 24 hr afterwards. After a further 24 hr, airway responsiveness to acetylcholine (ACh) was measured and provocative concentration (PC) values (PC 100 , PC 200 andPC 300 ) (the ACh concentration needed to achieve 100, 200 and 300% increase in lung resistance above baseline) were calculated. Airway responsiveness was significantly increased in recipients of sensitized total T cells compared with recipients of cells from saline‐injected donor rats ( P &lt;0·05). There were significantly increased eosinophil major basic protein (MBP) + cell counts/mm 2 in airway submucosal tissue in the hyperreactive rats and a significant correlation was found between the number of MBP + cells and PC 100 ( r = 0·75; P &lt;0·03) in recipients of sensitized total T cells. Purified CD4 + T cells from sensitized donors induced AHR in naive recipients ( P &lt;0·05), while sensitized CD8 + and naive CD4 + cells failed to do so. Our data indicate that T cells may induce AHR through an eosinophilic airway inflammation and that CD4 + T cells may have a direct effect in this process in Brown–Norway rats.

No abstract is provided for this article.

OBJECTIVETo assess whether incomplete revascularization by percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) has an effect on long-term outcomes.

Objectives This study sought to compare the clinical outcomes of everolimus-eluting stents (EES) versus paclitaxel-eluting stents (PES) in patients with acute coronary syndromes (ACS) and stable coronary artery disease (CAD). Background Although randomized trials have shown superiority of EES to PES, the safety and efficacy of EES in ACS is unknown. Methods We performed a patient-level pooled analysis from the prospective, randomized SPIRIT (Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System) II, III, IV, and COMPARE (A Trial of Everolimus-Eluting Stents and Paclitaxel-Eluting Stents for Coronary Revascularization in Daily Practice) trials in which 2,381 patients with ACS and 4,404 patients with stable CAD were randomized to EES or to PES. Kaplan-Meier estimates of death, myocardial infarction (MI), ischemia-driven target lesion revascularization, and stent thrombosis were assessed at 2 years and stratified by clinical presentation (ACS vs. stable CAD). Results At 2 years, patients with ACS compared with stable CAD had higher rates of death (3.2% vs. 2.4%, hazard ratio [HR]: 1.37 [95% confidence interval (CI): 1.02 to 1.85], p = 0.04) and MI (4.9% vs. 3.4%, HR: 1.45 [95% CI: 1.14 to 1.85], p = 0.02). In patients with ACS, EES versus PES reduced the rate of death or MI (6.6% vs. 9.3%, HR: 0.70 [95% CI: 0.52 to 0.94], p = 0.02), stent thrombosis (0.7% vs. 2.9%, HR: 0.25 [95% CI: 0.12 to 0.52], p = 0.0002), and ischemia-driven target lesion revascularization (4.7% vs. 6.2%, HR: 0.69 [95% CI: 0.48 to 0.99], p = 0.04). In patients with stable CAD, EES reduced the rate of death or MI (4.5% vs. 7.1%, HR: 0.62 [95% CI: 0.48 to 0.80], p = 0.0002), stent thrombosis (0.7% vs. 1.8%, HR: 0.34 [95% CI: 0.19 to 0.62], p = 0.0002), and ischemia-driven target lesion revascularization (3.9% vs. 6.9%, HR: 0.55 [95% CI: 0.42 to 0.73], p < 0.0001). Conclusions Treatment with EES versus PES provides enhanced safety and efficacy regardless of the acuity of the clinical syndrome being treated and appears to mitigate the increased risk of stent thrombosis associated with ACS. (A Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System in the Treatment of Patients With de Novo Native Coronary Artery Lesions [SPIRIT II]; NCT00180310; SPIRIT III: A Clinical Evaluation of the Investigational Device XIENCE V Everolimus Eluting Coronary Stent System [EECSS] in the Treatment of Subjects With de Novo Native Coronary Artery Lesions [SPIRIT III]; NCT00180479; SPIRIT IV Clinical Trial: Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System in the Treatment of Subjects With de Novo Native Coronary Artery Lesions [SPIRIT IV]; NCT00307047; A Trial of Everolimus-Eluting Stents and Paclitaxel-Eluting Stents for Coronary Revascularization in Daily Practice: the COMPARE Trial [COMPARE]; NCT01016041)