Effect of portable noninvasive ventilation on thoracoabdominal volumes in recovery from intermittent exercise in patients with COPD.

We previously showed that use of portable noninvasive ventilation (pNIV) during recovery periods within intermittent exercise improved breathlessness and exercise tolerance in patients with COPD compared with pursed-lip breathing (PLB). However, in a minority of patients recovery from dynamic hyperinflation (DH) was better with PLB, based on inspiratory capacity. We further explored this using Optoelectronic Plethysmography to assess total and compartmental thoracoabdominal volumes. Fourteen patients with COPD (means ± SD) (FEV1: 55% ± 22% predicted) underwent, in a balanced order sequence, two intermittent exercise protocols on the cycle ergometer consisting of five repeated 2-min exercise bouts at 80% peak capacity, separated by 2-min recovery periods, with application of pNIV or PLB in the 5 min of recovery. Our findings identified seven patients showing recovery in DH with pNIV (DH responders) whereas seven showed similar or better recovery in DH with PLB. When pNIV was applied, DH responders compared with DH nonresponders exhibited greater tidal volume (by 0.8 ± 0.3 L, P = 0.015), inspiratory flow rate (by 0.6 ± 0.5 L/s, P = 0.049), prolonged expiratory time (by 0.6 ± 0.5 s, P = 0.006), and duty cycle (by 0.7 ± 0.6 s, P = 0.007). DH responders showed a reduction in end-expiratory thoracoabdominal DH (by 265 ± 633 mL) predominantly driven by reduction in the abdominal compartment (by 210 ± 494 mL); this effectively offset end-inspiratory rib-cage DH. Compared with DH nonresponders, DH responders had significantly greater body mass index (BMI) by 8.4 ± 3.2 kg/m2, P = 0.022 and tended toward less severe resting hyperinflation by 0.3 ± 0.3 L. Patients with COPD who mitigate end-expiratory rib-cage DH by expiratory abdominal muscle recruitment benefit from pNIV application.NEW & NOTEWORTHY Compared with the pursed-lip breathing technique, acute application of portable noninvasive ventilation during recovery from intermittent exercise improved end-expiratory thoracoabdominal dynamic hyperinflation (DH) in 50% of patients with COPD (DH responders). DH responders, compared with DH nonresponders, exhibited a reduction in end-expiratory thoracoabdominal DH predominantly driven by the abdominal compartment that effectively offset end-expiratory rib cage DH. The essential difference between DH responders and DH nonresponders was, therefore, in the behavior of the abdomen.

Low oxygen tension enhances hepatitis C virus replication.

Low oxygen tension exerts a significant effect on the replication of several DNA and RNA viruses in cultured cells. In vitro propagation of hepatitis C virus (HCV) has thus far been studied under atmospheric oxygen levels despite the fact that the liver tissue microenvironment is hypoxic. In this study, we investigated the efficiency of HCV production in actively dividing or differentiating human hepatoma cells cultured under low or atmospheric oxygen tensions. By using both HCV replicons and infection-based assays, low oxygen was found to enhance HCV RNA replication whereas virus entry and RNA translation were not affected. Hypoxia signaling pathway-focused DNA microarray and real-time quantitative reverse transcription-PCR (qRT-PCR) analyses revealed an upregulation of genes related to hypoxic stress, glycolytic metabolism, cell growth, and proliferation when cells were kept under low (3% [vol/vol]) oxygen tension, likely reflecting cell adaptation to anaerobic conditions. Interestingly, hypoxia-mediated enhancement of HCV replication correlated directly with the increase in anaerobic glycolysis and creatine kinase B (CKB) activity that leads to elevated ATP production. Surprisingly, activation of hypoxia-inducible factor alpha (HIF-α) was not involved in the elevation of HCV replication. Instead, a number of oncogenes known to be associated with glycolysis were upregulated and evidence that these oncogenes contribute to hypoxia-mediated enhancement of HCV replication was obtained. Finally, in liver biopsy specimens of HCV-infected patients, the levels of hypoxia and anaerobic metabolism markers correlated with HCV RNA levels. These results provide new insights into the impact of oxygen tension on the intricate HCV-host cell interaction.