The effects of refeeding on peripheral and respiratory muscle function in malnourished chronic obstructive pulmonary disease patients

We carried out a prospective randomized controlled trial to investigate the effects of short-term refeeding (16 days) in 10 malnourished inpatients with chronic obstructive pulmonary disease (COPD). Six patients were randomized to receive sufficient nasoenterically administered calories to provide a total caloric intake equal to 1,000 kcal above their usual intake. The other four patients were sham fed, receiving only 100 kcal more. Measurements of nutritional status, respiratory muscle strength and endurance, adductor pollicis function, and pulmonary function were performed initially and at study end. The refed group gained significantly more weight and showed significant increases in maximal expiratory pressure and mean sustained inspiratory pressure. There were no significant changes in the maximal inspiratory pressure or in adductor pollicis function. In malnourished inpatients with COPD, short-term refeeding leads to improvement in respiratory muscle endurance and in some parameters of respiratory muscle strength in the absence of demonstrable changes in peripheral muscle function.     

Training with inspiratory pressure support in patients with severe COPD.

This study evaluates the effects of training with noninvasive ventilatory support in patients with chronic obstructive pulmonary disease in a randomised, controlled, observer-blinded trial. Twenty-nine patients with chronic obstructive pulmonary disease and with a ventilatory limited exercise capacity (forced expiratory volume in one second < 60% predicted, breathing reserve at maximal exercise < 20% of maximally voluntary ventilation, resting arterial oxygen tension > or = 8 kPa (60 mmHg), end-exercise arterial oxygen saturation measured by pulse oximetry > or = 85%) completed an 8-week supervised outpatient cycle exercise programme. Fourteen patients were randomised to training with inspiratory pressure support of 10 cmH2O and 15 patients to training with control (sham) inspiratory pressure support of 5 cmH2O. Outcome measures were the incremental shuttle walking test and a constant-load cycle endurance test at 75% of peak work rate including the measurement of physiological responses, and health status measured using the St. George's Respiratory Questionnaire. Statistically significant between-group differences were found in favour of the inspiratory pressure support of 10 cmH2O group for improvement in shuttle walking distance (16+/-17 versus 3+/-13%), cycle endurance (164+/-124 versus 88+/-128%), and the reduction in minute ventilation during exercise (-11+/-10 versus -2+/-9%). It was concluded that exercise training with inspiratory pressure support of 10 cmH2O resulted in statistically significantly larger improvements in exercise performance than training with inspiratory pressure support of 5 cmH2O in patients with chronic obstructive pulmonary disease suffering from a ventilatory limited exercise capacity. Inspiratory pressure support of 10 cmH2O may be considered as adjunct during high-intensity exercise training.     

Targeted inspiratory muscle training improves respiratory muscle function and reduces dyspnea in patients with chronic obstructive pulmonary disease

STUDY OBJECTIVE: To examine the effects of targeted inspiratory muscle training on respiratory muscle function, clinical ratings of dyspnea, and perception of resistive loads in symptomatic patients with chronic obstructive pulmonary disease. DESIGN: Randomized, placebo-controlled trial with an 8-week treatment period. SETTING: Outpatient pulmonary clinic and pulmonary function laboratory. PARTICIPANTS: We studied 19 patients with moderate to severe chronic obstructive pulmonary disease, assigning 10 patients to an experimental group and 9 to a control group. INTERVENTIONS: Patients in both groups trained for 15 minutes twice each day using a device that provided breath-to-breath visual feedback of training intensity. Patients in the experimental group trained at six increasing levels of inspiratory resistance, whereas the patients in the control group trained at a constant, nominal level of resistance. MEASUREMENTS AND RESULTS: Although there was no statistically discernible difference in the effects of targeted muscle training on the mean difference in maximal inspiratory pressures between the two groups (9.83 cm H2O; 95% CI, -7.37 to 27.03), patients in the experimental group did show a significant increase in inspiratory muscle strength (15.03 cm H2O; P = 0.01). Experimental subjects also had decreased dyspnea after 8 weeks of training compared with control subjects (P = 0.003). Improvements in physiologic values and in dyspnea ratings were correlated. The perception of added resistive loads was not affected by inspiratory muscle training. CONCLUSIONS: Targeted inspiratory muscle training may enhance respiratory muscle function and reduce dyspnea in symptomatic patients with moderate to severe chronic obstructive pulmonary disease.     

Evaluation of an inspiratory muscle trainer in healthy humans.

The Powerbreathe is an inspiratory muscle trainer promoted as improving inspiratory muscle strength (and consequently exercise performance) in athletes and patients with respiratory disease. No published evidence supports its efficacy. We performed a prospective randomized controlled study in which 12 normal subjects received either Powerbreathe training or sham training for a 6-week period. The primary outcome measure was diaphragm strength evaluated as twitch transdiaphragmatic pressure (Tw Pdi) but secondary outcome measures were provided by full respiratory muscle assessment and cardiopulmonary exercise testing. An advantage to training was observed when outcome was assessed by maximal static inspiratory mouth pressure (mean advantage 14.5 cm H2O, 95% CI 2.2-26.9 cm H2O, P=0.025). However. no significant difference was observed between the groups in any other parameter. In particular the deltaTw Pdi was not different between groups (mean 'advantage' 0.7 cmH2O, 95% CI- 7.0+/-5.5 cmH2O, P=0.8). The continued sale and use of the Powerbreathe device is not justified by our data. A sample size calculation showed that 234 subjects would need to be randomized to definitively refute the hypothesis that Powerbreathe improves Tw Pdi and we argue that such a study is required.     

Effects of biphasic positive airway pressure in patients with chronic obstructive pulmonary disease.

Biphasic positive airway pressure (BiPAP) is a ventilatory mode in which two pressure levels (higher (Phigh) and lower (Plow)) acting as continuous positive airway pressure (CPAP) alternate at preset time intervals. BiPAP combines pressure-controlled ventilation with unrestricted spontaneous breathing. BiPAP has not yet been evaluated in patients with chronic obstructive pulmonary disease (COPD). Therefore, the effects of BiPAP (15 cmH2O Phigh and 5 cmH2O Plow) pressure support (PS; 15 cmH2O and positive end-expiratory pressure (PEEP) 5 cmH2O) and CPAP (5 cmH2O) on respiratory mechanics in COPD patients were compared. Twenty-one COPD patients were supported in randomized order with BiPAP, PS and CPAP. Pressure-time product (PTP), work of breathing (WOB), change in oesophageal pressure (deltaPoes), mouth occlusion pressure (P0.1), intrinsic PEEP (PEEPi), tension time index (TTI), respiratory frequency, and tidal volume (VT) were measured. During BiPAP, the COPD patients showed a significantly higher PTP, WOB, deltaPoes, P0.1, TTI and PEEPi than during PS. Comparing the Plow phases of BiPAP and CPAP, the breaths during the Plow phases of BiPAP had a lower VT and a greater WOB and PTP due to a higher PEEPi than on CPAP alone. In conclusion, biphasic positive airway pressure carries the risk of increased work of breathing in spontaneously breathing chronic obstructive pulmonary disease patients. Pressure support is superior for reducing their respiratory muscle effort.     

The voluntary drive to breathe is not decreased in hypercapnic patients with severe COPD.

How do the respiratory centres of patients with chronic obstructive pulmonary disease (COPD) and hypercapnia respond to acute increases in inspiratory load? A depressed respiratory motor output has long been postulated, but studies on this issue have yielded inconsistent results, partly due to limitations of investigative techniques. Many of these limitations can be overcome by the twitch interpolation technique, which is capable of accurately quantifying the degree of diaphragmatic activation, termed the voluntary drive to breathe. The hypothesis that patients with COPD and hypercapnia compensate for an acute increase in mechanical load on the inspiratory muscles with a lower voluntary drive to breathe than is the case with normocapnic patients was tested. Measurements were obtained in 15 patients with COPD, six of whom displayed hypercapnia and nine normocapnia. The maximum degree of diaphragmatic activation, expressed as a voluntary activation index (mean +/- SEM), was higher in hypercapnic than in normocapnic patients (98.7 +/- 0.7 versus 94.5 +/- 0.9% (p = 0.006)), as was the mean value (94.5 +/- 0.7 versus 88.5 +/- 1.9% (p = 0.01)). Within-patient values of the index were also less variable in the hypercapnic patients (coefficients of variation, 3.4 +/- 0.3 versus 6.1 +/- 0.9%, p = 0.01). Multiple regression analysis revealed the ratio of dynamic elastance to maximum transdiaphragmatic pressure, an index of inspiratory muscle loading, and pH as the only variables that correlated with maximum voluntary activation index (r2 = 0.69, p = 0.02 for each variable). Contrary to the hypothesis, it was concluded that voluntary activation of the diaphragm was greater and less variable in hypercapnic patients than normocapnic patients with severe chronic obstructive pulmonary disease during an acute increase in inspiratory mechanical load. Whether greater diaphragmatic recruitment during episodes of a severe exacerbation of chronic obstructive pulmonary disease provides a survival advantage for hypercapnic patients with chronic obstructive pulmonary disease remains to be determined.     

Acute effect of oral steroids on muscle function in chronic obstructive pulmonary disease.

Prospective data to support the hypothesis that corticosteroids are a significant cause of muscle weakness in patients with chronic obstructive pulmonary disease (COPD) are lacking. The authors studied respiratory and quadriceps muscle function, using both volitional techniques and magnetic nerve stimulation, as well as measuring metabolic parameters during incremental cycle ergometry, in 25 stable COPD patients. The forced expiratory volume in one second was 37.6 +/- 21.4% predicted, before and after a 2-week course of o.d. prednisolone 30 mg. Quadriceps strength was also assessed in 15 control patients on two occasions. Only two patients met the British Thoracic Society definition of steroid responsiveness. There was no change either in sniff transdiaphragmatic pressure (pre: 96.8 +/- 19.7 cmH2O; post: 98.6 +/- 22.4 cmH2O) or in twitch transdiaphragmatic pressure elicited by bilateral anterolateral magnetic phrenic-nerve stimulation (pre: 16.8 +/- 9.1 cmH2O; post: 17.9 +/- 10 cmH2O). Quadriceps twitch force did not change significantly either in the steroid group (pre: 9.5 +/- 3.1 kg; post: 8.9 +/- 3.7 kg) or in the control patients (pre: 8.1 +/- 2.7 kg; post: 7.9 +/- 2.2 kg). There were no changes in either peak or isotime ventilatory and metabolic parameters during exercise. In conclusion, in stable patients with chronic obstructive pulmonary disease, a 2-week course of 30 mg prednisolone daily does not cause significant skeletal muscle dysfunction or alter metabolic parameters during exercise.     

The effect of aging on respiratory muscle function

To elucidate the effect of aging on respiratory muscle function, the authors performed respiratory muscle function tests in 116 normal subjects. Respiratory muscle function was evaluated with maximal expiratory mouth pressure at the TLC level (PEmax) and maximal inspiratory mouth pressure at the RV level (PImax). PEmax and PImax in both sexes showed significant correlations with age. PEmax in males was significantly higher than that in females (123.6 +/- 29.7 cmH2O and 79.0 +/- 21.1 cmH2O, p less than 0.01, respectively). PImax in males was also significantly higher than that in females (98.4 +/- 26.0 cmH2O and 71.9 +/- 26.4 cmH2O, p less than 0.01, respectively). PEmax correlated significantly with TLC, and PImax showed a significant inverse correlation with RV/TLC. Furthermore, there was a significant inverse correlation between RV/TLC and age. Our data suggest that inspiratory muscle weakness in aging may be responsible for the increase in RV/TLC.     

Inspiratory muscle resistive training in respiratory failure

In this study, 4 patients who had failed weaning attempts using traditional methods underwent inspiratory muscle resistive training (IRT). Three patients showed improvements in inspiratory muscle strength (mean peak negative inspiratory pressure improved from 38 to 54 cm H2O) and in respiratory muscle endurance (mean PCO2 at the end of the same or a longer period of spontaneous breathing improved from 70 to 52 mmHg). These 3 patients were successfully weaned from mechanical ventilation after 10 to 24 days of IRT. A fourth patient showed no improvement and could not be weaned. This pilot study demonstrated that IRT can be useful in preparing patients with chronic respiratory failure for weaning from mechanical ventilation.     

Sniff nasal inspiratory pressure as a marker of respiratory function in motor neuron disease.

Vital capacity (VC) and maximum mouth pressures are often used to monitor respiratory function in motor neuron disease (MND), but require the use of a mouthpiece. Sniff nasal inspiratory pressure (SNIP) is a simple and reliable means of measuring inspiratory muscle strength; it does not involve the use of a mouthpiece and might therefore be better than VC or mouth pressures for assessing patients with bulbar disease. SNIP, maximum inspiratory (MIP) and expiratory mouth pressure (MEP), VC and arterial carbon dioxide tension (Pa,CO2) were measured in 59 consecutive patients attending a specialist MND clinic. Thirty-one had bulbar involvement on clinical grounds. Both SNIP and VC were inversely related to Pa,CO2 in nonbulbar patients only. Neither MIP nor MEP were related to Pa,CO2. The 10 patients with an elevated Pa,CO2 (>6 kPa) had significantly lower SNIP and VC than normocapnic patients. Sniff nasal inspiratory pressure can be used to monitor respiratory function in motor neuron disease. It is quick and easy for patients to perform, but otherwise appears to offer little advantage over vital capacity measurement. Patients with bulbar disease are often poor at performing sniff nasal inspiratory pressure manoeuvres, possibly because of upper airway collapse or inability to close the mouth completely during the manoeuvre.     

慢性阻塞性肺疾病患者呼吸肌肌力和耐力的测定

呼吸肌功能测定通常包括呼吸肌肌力（ＲＭＳ）和呼吸肌耐力（ＲＭＥ）。应用自行研制的ＲＭＳＥ－１型呼吸肌功能测定仪对健康正常人和缓解期慢性阻塞性肺疾病（ＣＯＰＤ）患者进行测定。如果表明，缓解期ＣＯＰＤ患者ＲＭＳ指标如最大吸气口腔压（ＭＩＰ）和最大呼气口腔压（ＭＥＰ）与正常人组差异无显著性；而ＲＭＥ指标如最大吸气负荷（Ｌｏａｄ＿ｍ）、最大负荷时的平均口腔压（Ｐ＿（ｍｅａｎ））以及最大负荷时的最大持续吸气压（ＳＩＰ＿ｍ）与ＭＩＰ之比（ＳＩＰ＿ｍ／ＭＩＰ）较正常人组明显减低，差异非常显著。提示ＲＭＥ测定较ＲＭＳ测定更为敏感。认为ＲＭＥ测定作为呼吸肌功能评定的客观方法，对观察ＣＯＰＤ患者呼吸肌锻炼效果和指导呼吸康复治疗有重要意义。     

Control of breathing in patients with chronic pulmonary obstructive disease: response to bamiphylline.

In two groups (A and B) of patients with severe chronic obstructive pulmonary disease (COPD), matched for age and routine pulmonary function testing, we evaluated inspiratory muscle strength (MIP), breathing pattern, mouth occlusion pressure (P0.1), inspiratory neural drive, assessed in terms of electromyographic activity of both diaphragm (EMGd) and intercostal (EMGint) muscles, and P0.1/EMGd ratio, an index of inspiratory neuromuscular coupling. Group A (8 patients) was studied before and after a 7-day period of a new oral xanthine derivative (bamiphylline, 1.2 g daily), and group B (7 patients) was given a placebo. Under control conditions, compared with an age-matched normal control group, groups A and B both exhibited a decrease in MIP, more rapid (increase in respiratory frequency RF) and shallower (decrease in tidal volume; VT) breathing (RSB), a marked increase in both EMGd and EMGint and a lower P0.1/EMGd ratio. With bamiphylline FEV1 and PaO2 significantly increased, while a substantial increase in MIP was found in 5 out of the 8 patients. VT and inspiratory time (Ti) also significantly increased, and RF decreased. Both EMGd and EMGint significantly decreased, whereas P0.1/EMGd exhibited a substantial increase in 5 out of the 8 patients. Conversely, no significant changes were observed in group B during the study period. From these data we conclude that in patients with COPD, clinical manifestations, probably associated with inspiratory muscle overloading (decrease in muscle strength, RSB, increase in respiratory neural drive, and derangement in neuromuscular coupling) may benefit from a short-term treatment with bamiphylline.     

Predictors of weaning outcome in chronic obstructive pulmonary disease patients.

Several threshold values for predicting weaning outcome from mechanical ventilation have been proposed. These values, however, have been obtained in nonhomogeneous patient populations. The aim of the present study was to determine the threshold values in chronic obstructive pulmonary disease (COPD) patients and compare them to those reported for nonhomogeneous patient populations. The initial weaning trial included 81 COPD patients. Fifty-three of them underwent a successful weaning trial, whereas 28 failed it. The latter were enrolled into the present investigation, and were restudied during a subsequent successful trial. The weaning indices used were those reported in the literature. The threshold values obtained were within 10% of those reported for a nonhomogeneous patients population only for tidal volume and effective compliance. The classification error was <20% for maximal inspiratory pressure (MIP), occluded inspiratory pressure swing (deltaPI)/MIP, rapid and shallow breathing (respiratory frequency/tidal volume), and compliance, rate, oxygenation, pressure index (CROP), whereas the area under the receiver operating characteristic curves was >0.9 only for deltaPI/MIP and CROP. In conclusion, the threshold values obtained in chronic obstructive pulmonary disease patients who failed the first weaning attempt differed from those previously reported. Although a gold standard weaning index is not available for chronic obstructive pulmonary disease patients, the occluded inspiratory pressure swing/ maximal inspiratory pressure and compliance, rate, oxygenation, pressure index may be candidates for such a role.     

High-intensity inspiratory muscle training in patients with chronic obstructive pulmonary disease and severely reduced function

PURPOSE: This study examined the effects of inspiratory muscle training (IMT) with high-intensity inspiratory pressure loads on respiratory muscle performance and exertional dyspnea. METHODS: This was a randomized single-blind clinical trial. Twenty-seven patients with chronic obstructive pulmonary disease (18 men, 9 women) with severe to very severe airflow obstruction and severely limited functional performance were assigned randomly to an IMT group (n = 12) or an educational control group (n = 15). The IMT group trained with a threshold loaded device for 30 minutes a day for 16 weeks using interval training techniques. Training was initiated with inspiratory pressure loads equal to 30% of maximal inspiratory pressure (Plmax) and increased as tolerated to 60% of Plmax. Dependent variables were measured before and after 4 months of IMT: inspiratory muscle strength (Plmax), respiratory muscle endurance (discontinuous incremental threshold loading test [DC-ITL]), dyspnea (Chronic Respiratory Disease Questionnaire [CRQ]), and the Borg Category-Ratio Scale ratings of perceived breathing difficulty (RPBD) at equal loads during the DC-ITL. RESULTS: In the IMT group, Plmax increased from 64 +/- 15 to 75 +/- 17 cm H2O (P < .05), performance on the DC-ITL test increased from a maximal load of 37 +/- 12 to 53 +/- 13 cm H2O (P < .05), RPBD decreased from 5.5 +/- 2.5 to 3.8 +/- 2.6 for equal loads on the DC-ITL (P < .05) and the CRQ Dyspnea Scale improved from 18.1 +/- 5.1 to 22.4 +/- 5.2 (P < .05). CONCLUSIONS: Inspiratory muscle training at high-intensity loads significantly improved inspiratory muscle strength, respiratory muscle endurance, and respiratory symptoms during daily activities and respiratory exertion.     

Cross-over comparison between respiratory muscle stretch gymnastics and inspiratory muscle training

OBJECTIVES: To compare the effect of respiratory muscle stretch gymnastics (RMSG), proposed as a possible additional form of rehabilitation for patients with chronic obstructive pulmonary disease (COPD), with that of inspiratory muscle training (IMT). PATIENTS: Twelve naive outpatients with COPD at a university hospital. METHOD: The patients performed IMT (2 sessions of 10 minutes of training at 30% of PImax, daily) for 4 weeks and RMSG (3 sessions of 5 RMSG patterns 4 times each, daily) for 4 weeks, in randomized order, with a 4-week washout period between the two interventions. MEASUREMENTS AND RESULTS: PImax increased with IMT (mean 66.1 to 79.1 cmH2O), but not with RMSG (mean 66.0 to 69.4 cmH2O). RMSG and IMT similarly increased maximum chest wall expansion. FRC was significantly decreased by 158 ml with RMSG, but not with IMT. There were no significant changes in VC, FEV1, or PEF nor in arterial blood gases with either form of rehabilitation. Six-minute walking distance was more significantly increased with RMSG (mean 383 to 430 m), than with IMT (mean 386 to 412 m). CONCLUSIONS: RMSG may have clinically significant benefits, which may be somewhat different from the benefits of IMT, in patients with COPD.     

Effects of the menstrual cycle on respiratory muscle function

To investigate the effect of the menstrual cycle on respiratory muscle function, respiratory muscle and pulmonary functions were measured and compared in the midfollicular phase and in the midluteal phase of the menstrual cycle in 30 healthy adult women. Respiratory muscle strength was indicated by maximal static inspiratory and expiratory pressures. Inspiratory muscle endurance was determined by the product of pressure load and the sustained time, i.e., pressure-time index, while the subject breathed against an inspiratory pressure load on a modified Nickerson-Keens device. The results showed that the inspiratory muscle endurance was greater in the midluteal phase than in the follicular phase (815 +/- 43 versus 649 +/- 62 cmH2O.min, respectively), whereas the respiratory muscle strength and pulmonary function were unchanged. We conclude that inspiratory muscle endurance is affected by the menstrual cycle, i.e., higher in the midluteal phase and lower in the midfollicular phase.     

Detection of expiratory flow limitation in COPD using the forced oscillation technique.

Expiratory flow limitation (EFL) during tidal breathing is a major determinant of dynamic hyperinflation and exercise limitation in chronic obstructive pulmonary disease (COPD). Current methods of detecting this are either invasive or unsuited to following changes breath-by-breath. It was hypothesised that tidal flow limitation would substantially reduce the total respiratory system reactance (Xrs) during expiration, and that this reduction could be used to reliably detect if EFL was present. To test this, 5-Hz forced oscillations were applied at the mouth in seven healthy subjects and 15 COPD patients (mean +/- sD forced expiratory volume in one second was 36.8 +/- 11.5% predicted) during quiet breathing. COPD breaths were analysed (n=206) and classified as flow-limited if flow decreased as alveolar pressure increased, indeterminate if flow decreased at constant alveolar pressure, or nonflow-limited. Of these, 85 breaths were flow-limited, 80 were not and 41 were indeterminate. Among other indices, mean inspiratory minus mean expiratory Xrs (deltaXrs) and minimum expiratory Xrs (Xexp,min) identified flow-limited breaths with 100% specificity and sensitivity using a threshold between 2.53-3.12 cmH2O x s x L(-1) (deltaXrs) and -7.38- -6.76 cmH2O x s x L(-1) (Xexp,min) representing 6.0% and 3.9% of the total range of values respectively. No flow-limited breaths were seen in the normal subjects by either method. Within-breath respiratory system reactance provides an accurate, reliable and noninvasive technique to detect expiratory flow limitation in patients with chronic obstructive pulmonary disease.     

Respiratory muscle endurance training in chronic obstructive pulmonary disease: impact on exercise capacity, dyspnea, and quality of life

Inspiratory muscle training may have beneficial effects in certain patients with chronic obstructive pulmonary disease (COPD). Because of the lack of a home training device, normocapnic hyperpnea has rarely been used as a training mode for patients with COPD, and is generally considered unsuitable to large-scale application. To study the effects of hyperpnea training, we randomized 30 patients with COPD and ventilatory limitation to respiratory muscle training (RMT; n = 15) with a new portable device or to breathing exercises with an incentive spirometer (controls; n = 15). Both groups trained twice daily for 15 min for 5 d per week for 8 wk. Training-induced changes were significantly greater in the RMT than in the control group for the following variables: respiratory muscle endurance measured through sustained ventilation (+825 +/- 170 s [mean +/- SEM] versus -27 +/- 61 s, p < 0.001), inspiratory muscle endurance measured through incremental inspiratory threshold loading (+58 +/- 10 g versus +21.7 +/- 9.5 g, p = 0.016), maximal expiratory pressure (+20 +/- 7 cm H(2)O versus -6 +/- 6 cm H(2)O, p = 0.009), 6-min walking distance (+58 +/- 11 m versus +11 +/- 11 m, p = 0.002), V O(2peak) (+2.5 +/- 0.6 ml/kg/min versus -0.3 +/- 0.9 ml/kg/min, p = 0.015), and the SF-12 physical component score (+9.9 +/- 2.7 versus +1.8 +/- 2.4, p = 0.03). Changes in dyspnea, maximal inspiratory pressure, treadmill endurance, and the SF-12 mental component score did not differ significantly between the RMT and control groups. In conclusion, home-based respiratory muscle endurance training with the new device used in this study is feasible and has beneficial effects in subjects with COPD and ventilatory limitation.     

Effect of a beta 2-agonist (broxaterol) on respiratory muscle strength and endurance in patients with COPD with irreversible airway obstruction.

The effect of broxaterol, a new beta 2-agonist, on respiratory muscle endurance and strength was studied in a double-blind, placebo-controlled, randomized crossover clinical trial in 16 patients with chronic obstructive pulmonary disease (COPD) with irreversible airway obstruction (FEV1 = 57.1 percent of predicted). One patient withdrew from the study because of acute respiratory exacerbation. Inspiratory muscle strength was assessed by maximal inspiratory pressure (MIP) and endurance time was determined as the length of time a subject could breathe against inspiratory resistance (target mouth pressure = 70 percent of MIP, Ti/Ttot = 0.4). Broxaterol (B) or placebo (P) was given orally for seven days at the dose of 0.5 mg three times a day with a washout period of 72 h between study treatments. Measurements were performed before administration of B or P and 2 h (six patients) or 8 h (nine patients) after the end of each treatment. No significant changes in FEV1 or FRC were observed after B or P suggesting that diaphragmatic length was maintained constant with each treatment. The MIP did not significantly change, while endurance time increased after B in the patients tested at 2 h (from 234.8 +/- 48.1 s to 284.0 +/- 48.0 s, p less than 0.05) and at 8 h (from 187.2 +/- 31.1 s to 258.2 +/- 40.4 s, p less than 0.005). No changes were observed after P. Minute ventilation, airway occlusion pressure (P0.1), integrated electromyographic activities of the diaphragm (Edi), and intercostal parasternals (Eic) (normalized to the value obtained during MIP) showed no change during the endurance run with different treatments. We conclude that in a group of COPD patients with irreversible airway obstruction, B significantly improves respiratory muscle endurance, and that this does not arise as a result of an effect on neuromuscular drive or pulmonary mechanics, but may be mediated by peripheral factors.     

Central respiratory drive in acute respiratory failure of patients with chronic obstructive pulmonary disease

Control of breathing was studied in patients with chronic obstructive pulmonary disease, both in the chronic state and during acute respiratory failure. The results were compared to those in a group of age-matched normal subjects. In patients breathing air, minute ventilation was not different during acute and chronic states, and was similar to that in normal subjects. The pattern of breathing, however, was different: acutely ill patients took shorter and smaller breaths, with a breathing frequency higher than that of normal subjects. The pattern of the chronic group was intermediate between that of acutely ill patients and that of normal subjects. Mouth occlusion pressure, an index of neuromuscular respiratory drive, was 5 times greater in acutely ill patients than in normal subjects. Administration of O2 at a flow of 5 L/min caused a small (14%), bus significant, decrease in minute ventilation due to decreased respiratory frequency. The tidal volume did not change, so the decrease in minute ventilation was the result of decreased inspiratory flow. This was associated with a decreased mouth occlusion pressure that was still 3 times greater than that of normal subjects. The increase in arterial PCO2, observed after administration of O2 was not correlated with the decrease in ventilation, indicating that other factors must be responsible for the increase in arterial PCO2. We concluded that (1) despite the poor mechanical advantage of the respiratory muscles in acute respiratory failure, the increased drive to breathe results in high mouth occlusion pressure and inspiratory flow, and (2) the increase in arterial PCO2, observed during administration of O2 is not related solely to changes in respiratory drive.