Inspiratory pressure support reduces slowing of inspiratory muscle relaxation rate during exhaustive treadmill walking in severe COPD.

When patients with COPD walk to a state of intolerable dyspnea, there is excessive inspiratory muscle loading, as evidenced by slowing of the maximum relaxation rate of the inspiratory muscles, measured from esophageal pressure during a sniff (Sn Pes MRR). In this setting, inspiratory pressure support (IPS) delivered via an orofacial mask increases walking distance and reduces dyspnea, but the mechanism by which this benefit is achieved remains unclear. In this study we compared Sn Pes MRR after equidistant treadmill walking in six men with severe COPD (mean FEV1: 0.6 L, 22% predicted). After the free walk there was a mean slowing of Sn Pes MRR of 41% (p < 0.03). After the IPS-assisted walks, the slowing of Sn Pes MRR was 20% of baseline; this was significantly less than after the free walk (p < 0.05). Four subjects performed shorter walks; after free walks of one third and two thirds of maximum distance, the mean slowing of Sn Pes MRR was 23% and 28%, respectively. We conclude that when patients with COPD walk to exhaustion, IPS reduces slowing of inspiratory muscle MRR, and that this represents a considerable unloading of the inspiratory muscles. The magnitude of the reduction is approximately the same as reducing the distance walked by two thirds.

Effect of L-arginine on renal blood flow in normal subjects and patients with hypoxic chronic obstructive pulmonary disease.

BACKGROUND: L-arginine is the precursor of endothelium derived nitric oxide (NO) and increasing the available substrate may increase the production of NO. This has been shown by local infusion in peripheral vascular beds but there are few studies of the effects during systemic infusion. Renal vasoconstriction is known to be important in the pathogenesis of cor pulmonale in patients with hypoxic chronic obstructive pulmonary disease (COPD). The effects of a systemic infusion of L-arginine on renal and aortic haemodynamics were therefore investigated in normal subjects and in patients with hypoxic COPD. METHODS: Ten normal volunteers were recruited from the research staff of King's College Hospital Six patients with COPD and hypoxia (arterial oxygen tension (PaO2) < 8.5 kPa) were recruited from the thoracic medicine outpatient clinic at King's College Hospital and five age and sex matched normal subjects were recruited from a group of normal subjects recruited from the database of the Department of Health Care for the Elderly as volunteers for medical research. There was no history of renal, cardiac, or hepatic disease. Baseline values of time averaged mean of the maximum instantaneous velocity (Tamx) and maximum velocity (Vmax) of blood flow in intrarenal arteries were obtained using colour flow Doppler ultrasound. Using the same technique, Vmax was obtained from the abdominal aorta just distal to the xiphisternum before and after infusion of L-arginine via a large peripheral vein (20 g in 100 ml sterile water over 30 minutes). RESULTS: In normal subjects L-arginine increased blood velocity in the intrarenal vessels from a mean of 0.22 m/s to 0.26 m/s, an increase of 19.8%. There was no effect on arterial blood pressure, heart rate, or aortic blood velocity. L-arginine had no effect on intrarenal or aortic blood velocity in patients with hypoxic COPD. In age matched controls L-arginine increased blood velocity in the intrarenal vessels from a mean of 0.20 m/s to 0.26 m/s, an increase of 36.8%. There was no effect on arterial blood pressure, heart rate, or aortic blood velocity. CONCLUSIONS: L-arginine, at the doses administered, increased renal blood flow, as assessed by renal arterial velocity. This effect was not seen in patients with hypoxic COPD but was present in age matched controls. This suggests that the abnormal renal vascular control seen in hypoxic patients with COPD may reflect a disturbance of the L-arginine/nitric oxide pathway.

Exhaustive exercise slows inspiratory muscle relaxation rate in chronic obstructive pulmonary disease.

The excessive load placed on inspiratory muscles when patients with COPD exercise could lead to fatigue and contribute to exercise limitation. Slowing of maximal relaxation rate (MRR) of skeletal muscle is an early index of the fatiguing process. We investigated whether inspiratory muscle MRR slows when patients with COPD walk to exhaustion. We studied nine well-trained and motivated patients with stable severe COPD (mean FEV1: 0.7 L, 28% predicted). Each subject performed sniff maneuvers before and after walking on a treadmill until they were forced to stop because of dyspnea. Esophageal (Pes), gastric, and transdiaphragmatic pressures were measured using balloon-tipped catheters. MRR was calculated as the percent Pes drop/10 ms. In the first minute after exercise there was a mean decrease of Pes MRR of 42% (range, 21 to 65%) (p < 0.01), which returned to baseline within 3 to 5 min. The fall in MRR indicates that the inspiratory muscles of patients with COPD walking to exhaustion are sufficiently heavily loaded to initiate the fatiguing process.

Exhaustive treadmill exercise does not reduce twitch transdiaphragmatic pressure in patients with COPD.

Reduced diaphragm contractility has been described in normal subjects after whole body endurance exercise, and it indicates low frequency fatigue (LFF); it is unknown whether LFF is of clinical importance. We therefore studied the effect of treadmill exercise to exhaustion on diaphragm contractility in six patients with severe chronic obstructive pulmonary disease (COPD) (mean FEV1, 0.71, 27% predicted). The subjects first performed a short (control), treadmill walk and then, after resting, a second walk to a state of severe dyspnea. Cervical magnetic stimulation of the phrenic nerve roots was performed at the start of the study and 20 and 30 min after each walk. The twitch transdiaphragmatic pressure (Tw Pdi) was reproducible (mean coefficient of variation, 5.3%; range, 2 to 12.5%). Mean Twi Pdis were 18.4 cm H2O at baseline and 19.6 cm H2O and 19.2 cm H2O 20 and 30 min after the control walk. At the same times after the exhaustive walk, mean Tw Pdis were 19.6 and 20.4 cm H20. Tw Pdi was not reduced by exhaustive treadmill walking (p > 0.9), and a power calculation showed that the study had a 95% chance of detecting a 10% fall at the 5% significance level. We conclude that Tw Pdi is not reduced when patients with severe COPD walk to a state of extreme breathlessness and that therefore low frequency fatigue of the diaphragm does not occur.

Effect of inspiratory pressure support on exercise tolerance and breathlessness in patients with severe stable chronic obstructive pulmonary disease.

BACKGROUND: In patients with chronic obstructive pulmonary disease exercise tolerance is commonly limited by breathlessness. These patients have an increased ventilatory load at rest which is exacerbated during exercise. The purpose of this study was to investigate the effect of supporting ventilation by non-invasive inspiratory pressure support (IPS) during submaximal treadmill exercise in such patients to see if they would experience less breathlessness and improve their exercise capacity. METHODS: Eight men with disabling breathlessness due to chronic obstructive pulmonary disease (COPD) (mean (SD) FEV1 0.73 (0.2) 1) were studied. Patients walked on a treadmill until their sensation of breathlessness, scored at one minute intervals, reached level 5 ("severe") on the 10-point Borg scale. Studies were performed with IPS (mean airway pressure 12-15 cm H2O), continuous positive airway pressure (CPAP 6 cm H2O), and with oxygen (2 l/min via a mask) in random order on three separate days. Each of these walks was compared with a control walk using a sham circuit (breathing air via an oxygen mask at 2 l/min from an unlabelled cylinder), and with a baseline walk in which patients walked freely on the treadmill. On cessation of exercise, distance achieved and a leg fatigue score were recorded. RESULTS: No patients stopped due to leg fatigue, all stopping only when their sensation of breathlessness had reached level 5 on the Borg scale. IPS improved median walking distance by 62% compared with the control walk (sham circuit). There was no change in walking distance with either CPAP or oxygen at 2 l/min. There was no difference between the control and the baseline walks. CONCLUSIONS: Inspiratory pressure support can reduce breathlessness and increase exercise tolerance to submaximal treadmill exercise in patients with COPD. This could have implications for the rehabilitation of these severely disabled patients.

Randomised controlled trial of nasal ventilation in acute ventilatory failure due to chronic obstructive airways disease.

Acute exacerbations of chronic obstructive airways disease (COAD) are a common cause of admission to hospital, and have a high mortality. Nasal intermittent positive pressure ventilation (NIPPV) has been used successfully in patients with respiratory failure due to neuromuscular and skeletal disorders, but the outcome of treatment in patients with COAD is less well known. We carried out a prospective randomised controlled trial of conventional treatment versus conventional treatment plus NIPPV, in 60 patients with acute ventilatory failure due to exacerbations of COAD. For the NIPPV group there was a rise in pH, compared with a fall in the controls (mean difference of change between the groups 0.046 [95% CI 0.06-0.02, p < 0.001]), and a larger fall in PaCO2 (mean difference in change between the groups 1.2 kPa [95% CI 0.45 to 2.03, p < 0.01]). Median visual analogue scores over the first 3 days of admission showed less breathlessness in the NIPPV group (2.3 cm [range 0.1-5.5]) than in the control group (4.5 cm [range 0.9-8.8]) (p < 0.025). Survival rates at 30 days were compared for intention-to-treat and efficacy populations. In the efficacy mortality comparison, mortality in the NIPPV group was reduced: 1/26 vs 9/30 (relative risk = 0.13, CI = 0.02-0.95, p = 0.014). This effect was less in the intention-to-treat analysis: 3/30 vs 9/30 (relative risk = 0.33, CI = 0.10-1.11, p = 0.106). In patients with acute ventilatory failure due to COAD who received NIPPV there was a significant rise in pH, a reduction in PaCO2 and breathlessness, and reduced mortality.