Chronic intermittent hypoxia (CIH) and chronic hypoxia (CH) are associated with high-altitude pulmonary hypertension (HAPH). Asymmetric dimethylarginine (ADMA), a NO synthase (NOS) inhibitor, may contribute to HAPH. This study assessed changes in the ADMA/NO pathway and the underlying mechanisms in rat lungs following exposure to CIH or CH simulated in a hypobaric chamber at 428 Torr. Twenty-four adult Wistar rats were randomly assigned to three groups: CIH2x2 (2 days of hypoxia/2 days of normoxia), CH, and NX (permanent normoxia), for 30 days. All analyses were performed in whole lung tissue. L-Arginine and ADMA were analyzed using LC-MS/MS. Under both hypoxic conditions right ventricular hypertrophy was observed (p < 0.01) and endothelial NOS mRNA increased (p < 0.001), but the phosphorylated/nonphosphorylated vasodilator-stimulated phosphoprotein (VASP) ratio was unchanged. ADMA increased (p < 0.001), whereas dimethylarginine dimethylaminohydrolase (DDAH) activity decreased only under CH (p < 0.05). Although arginase activity increased (p < 0.001) and L-arginine exhibited no changes, the L-arginine/ADMA ratio decreased significantly (p < 0.001). Moreover, NOX4 expression increased only under CH (p < 0.01), but malondialdehyde (MDA) increased (up to 2-fold) equally in CIH2x2 and CH (p < 0.001). Our results suggest that ADMA and oxidative stress likely reduce NO bioavailability under altitude hypoxia, which implies greater pulmonary vascular reactivity and tone, despite the more subdued effects observed under CIH.
Objectives: Delivery of warmed, humidified air via nasal high flow therapy could potentially reduce replication of temperature-sensitive viruses in the upper respiratory tract. This study investigates whether nasal high flow therapy is well tolerated by healthy adults at 37°C and 41°C.
Methods: In this randomised, double-blind, controlled crossover pilot trial, nasal high flow therapy was used to deliver humidified air at 35 L/min, at either 37°C or 41°C, for three one-hour sessions of use over one day. The alternative was delivered at least 14 days later. Ten healthy, nonsmoking adults were asked, via questionnaire after each day's use, whether they would use nasal high flow therapy while being unwell with a cold or flu if it was demonstrated to improve symptoms.
Results: All participants completed both interventions. Eighty percent responded "yes" to future use of nasal high flow therapy, for both 37°C and 41°C. There was no significant change from baseline in saccharin times following either intervention or in the following morning.
Conclusions: Delivering humidified air via nasal high flow therapy at both 37°C and 41°C is well tolerated by healthy adults. This supports investigation into the potential use of nasal high flow therapy as treatment in viral upper respiratory tract infections. Trial Registration. This trial is registered with ACTRN12614000183684 (tolerability study of nasal delivery of humidified & warmed air).
Introduction. Endobronchial ultrasound (EBUS) is a procedure that provides access to the mediastinal staging; however, EBUS cannot be used to stage all of the nodes in the mediastinum. In these cases, endoscopic ultrasound (EUS) is used for complete staging. Objective. To provide a synthesis of the evidence on the diagnostic performance of EBUS + EUS in patients undergoing mediastinal staging. Methods. Systematic review and meta-analysis to evaluate the diagnostic yield of EBUS + EUS compared with surgical staging. Two researchers performed the literature search, quality assessments, data extractions, and analyses. We produced a meta-analysis including sensitivity, specificity, and likelihood ratio analysis. Results. Twelve primary studies (1515 patients) were included; two were randomized controlled trials (RCTs) and ten were prospective trials. The pooled sensitivity for combined EBUS + EUS was 87% (CI 84-89%) and the specificity was 99% (CI 98-100%). For EBUS + EUS performed with a single bronchoscope group, the sensitivity improved to 88% (CI 83.1-91.4%) and specificity improved to 100% (CI 99-100%). Conclusion. EBUS + EUS is a highly accurate and safe procedure. The combined procedure should be considered in selected patients with lymphadenopathy noted at stations that are not traditionally accessible with conventional EBUS.