Nutrition and the respiratory muscles

Malnutrition may be an important complicating factor in acute and chronic lung disease. Animal studies have demonstrated significant atrophy of diaphragm muscle fibers following prolonged undernutrition resulting in a marked reduction in diaphragm muscle strength as well as alteration in other contractile and fatigue properties of the muscle. In severe chronic obstructive pulmonary disease (COPD), malnutrition is common and may, in conjunction with the influences of hyperinflation on diaphragm performance, predispose to respiratory muscle fatigue and failure. The course of progressive weight loss in patients with COPD is not known but may, in part, be related to a "hypermetabolic" state arising from an increased oxygen consumption of the respiratory muscles secondary to enhanced resistive loads and impaired mechanical efficiency of the respiratory muscles. Reports of the impact of nutritional repletion on respiratory muscle performance in critically ill patients, as well as in patients with COPD, are preliminary. Further studies are necessary to establish whether such measures impact meaningfully on both the morbidity and mortality of these patients.     

The application of muscle endurance training techniques to the respiratory muscles in COPD

Standard treatments for chronic obstructive pulmonary disease (COPD) that are directed at reducing the degree of obstruction may be insufficient to relieve symptoms and improve exercise tolerance in severe cases. Many severely affected patients have reduced respiratory muscle endurance, which makes them less able to tolerate their excessive respiratory workloads. Despite the absence of a naturally-occurring endurance-training effect, the respiratory muscles of patients with COPD can be trained for increased endurance when periodic respiratory exertion is deliberately induced by isocapnic hyperventilation or added inspiratory resistance. Such training has resulted either in improved sustainable ventilatory capacity or in improved exercise tolerance. These improvements due to respiratory muscle training were better than those observed with whole body exercise training programs in some cases but not in others. Respiratory muscle training is a promising new adjunct in the management of COPD, but further investigation is required to delineate its indications and contraindications.     

Respiratory muscle fatigue limiting physical exercise?

Inspiratory muscle fatigue has been documented during loaded breathing or acute respiratory failure, but its role in exercise limitation is still undetermined. Electromyographic (EMG) signs of diaphragmatic fatigue develop in normal subjects hyperventilating above 70% of maximal voluntary ventilation (MVV), a ventilatory level commonly attained at peak exercise. EMG signs of diaphragmatic fatigue also occur during high power cycling exercise in normal subjects and chronic obstructive pulmonary disease (COPD) patients. However, a loss of respiratory muscle strength has rarely been documented following strenuous physical exercise with techniques independent of the subjects' collaboration. Prior inspiratory muscle fatigue decreases exercise tolerance in normal subjects but its effect is largely unknown in COPD patients. Respiratory muscle rest by negative pressure ventilation was reported to improve exercise tolerance in COPD, but this beneficial effect was not confirmed by controlled studies. The effect of inspiratory muscle training on exercise tolerance is still undefined by existing data, in part because of differences in methods and selection criteria between studies. Although respiratory muscle fatigue may occur during exercise, it is not clearly established whether interventions directed at respiratory muscles may improve exercise tolerance in COPD.     

Effect of respiratory muscle endurance training in patients with COPD undergoing pulmonary rehabilitation

BACKGROUND: Respiratory muscle endurance training (hyperpnea training) has been shown to have beneficial effects in patients with COPD. STUDY OBJECTIVES: The purpose of this study was to determine whether hyperpnea training, when added to an endurance exercise training program, would lead to additional benefits compared with endurance training alone in patients with COPD. SETTING AND PARTICIPANTS: Patients with COPD entering an 8-week outpatient pulmonary rehabilitation program. Fifteen patients (mean [+/- SE] FEV1, 45 +/- 6% predicted) were randomized to combined therapy, and 14 patients (mean FEV1, 44 +/- 4% predicted) were randomized to endurance training. METHODS: Peak exercise capacity, exercise endurance time during constant workload cycle exercise, 6-min walk distance, quality of life as measured by the chronic respiratory questionnaire, respiratory muscle strength and endurance, and quadriceps fatigability were measured before and after endurance or combined training. RESULTS: After rehabilitation, peak exercise capacity, exercise endurance time, 6-min walk distance, and quality of life all increased in both groups, but there was no significant difference in the extent of improvement between groups. Mean respiratory muscle endurance increased to a significantly greater extent in the combined therapy group (17.5 +/- 2.7 vs 8.5 +/- 2.5 min, respectively; p = 0.02). Respiratory muscle strength was significantly increased, and quadriceps fatigability was significantly reduced after rehabilitation in the combined therapy group but not in the endurance training group, but the difference between groups did not reach statistical significance. CONCLUSION: The endurance of the respiratory muscles can be improved by specific training beyond that achieved by endurance training alone in patients with COPD. However, this improvement did not translate into additional improvement in quality of life or exercise performance.     

Normativa SEPAR sobre disfunción muscular de los pacientes con enfermedad pulmonar obstructiva crónica

In patients with chronic obstructive pulmonary disease (COPD), skeletal muscle dysfunction is a major comorbidity that negatively impacts their exercise capacity and quality of life. In the current guidelines, the most recent literature on the various aspects of COPD muscle dysfunction has been included. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) scale has been used to make evidence-based recommendations on the different features. Compared to a control population, one third of COPD patients exhibited a 25% decline in quadriceps muscle strength, even at early stages of their disease. Although both respiratory and limb muscles are altered, the latter are usually more severely affected. Numerous factors and biological mechanisms are involved in the etiology of COPD muscle dysfunction. Several tests are proposed in order to diagnose and evaluate the degree of muscle dysfunction of both respiratory and limb muscles (peripheral), as well as to identify the patients’ exercise capacity (six-minute walking test and cycloergometry). Currently available therapeutic strategies including the different training modalities and pharmacological and nutritional support are also described.     

Exercise dyspnea in patients with COPD

Dyspnea, a symptom limiting exercise capacity in patients with COPD, is associated with central perception of an overall increase in central respiratory motor output directed preferentially to the rib cage muscles. On the other hand, disparity between respiratory motor output, mechanical and ventilatory response of the system is also thought to play an important role on the increased perception of exercise in these patients. Both inspiratory and expiratory muscles and operational lung volumes are important contributors to exercise dyspnea. However, the potential link between dyspnea, abnormal mechanics of breathing and impaired exercise performance via the circulation rather than a malfunctioning ventilatory pump per se should not be disregarded. Change in arterial blood gas content may affect dyspnea via direct or indirect effects. An increase in carbon dioxide arterial tension seems to be the most important stimulus overriding all other inputs from dyspnea in hypercapnic COPD patients. Hypoxia may act indirectly by increasing ventilation and indirectly independent of changes in ventilation. A greater treatment effect is often achieved after the addition of pulmonary rehabilitation with pharmacological treatment.     

Muscle dysfunction in chronic obstructive pulmonary disease: update on causes and biological findings

Respiratory and/or limb muscle dysfunction, which are frequently observed in chronic obstructive pulmonary disease (COPD) patients, contribute to their disease prognosis irrespective of the lung function. Muscle dysfunction is caused by the interaction of local and systemic factors. The key deleterious etiologic factors are pulmonary hyperinflation for the respiratory muscles and deconditioning secondary to reduced physical activity for limb muscles. Nonetheless, cigarette smoke, systemic inflammation, nutritional abnormalities, exercise, exacerbations, anabolic insufficiency, drugs and comorbidities also seem to play a relevant role. All these factors modify the phenotype of the muscles, through the induction of several biological phenomena in patients with COPD. While respiratory muscles improve their aerobic phenotype (percentage of oxidative fibers, capillarization, mitochondrial density, enzyme activity in the aerobic pathways, etc.), limb muscles exhibit the opposite phenotype. In addition, both muscle groups show oxidative stress, signs of damage and epigenetic changes. However, fiber atrophy, increased number of inflammatory cells, altered regenerative capacity; signs of apoptosis and autophagy, and an imbalance between protein synthesis and breakdown are rather characteristic features of the limb muscles, mostly in patients with reduced body weight. Despite that significant progress has been achieved in the last decades, full elucidation of the specific roles of the target biological mechanisms involved in COPD muscle dysfunction is still required. Such an achievement will be crucial to adequately tackle with this relevant clinical problem of COPD patients in the near-future.     

A human model of the pathophysiology of chronic obstructive pulmonary disease

This short review summarizes a series of studies on the effects of expiratory flow limitation (EFL) at approximately 1 L/s during incremental exercise to maximal workload (Wmax) in normal subjects on exercise performance, respiratory muscle dynamics and control, and CO(2) elimination. Each subject served as his or her own control by performing the same protocol without EFL. Additionally, an index of cardiac output was measured before and after imposing EFL while the subjects exercised at Wmax, Wmax was reduced to 65% of control by severe dyspnoea. EFL forced a decrease in the shortening velocity of expiratory muscles, resulting in increased expiratory pressures which accounted for 66% of the variance in Borg scale ratings of dyspnoea. In spite of an increase in the shortening velocity of inspiratory muscles, inspiratory pressures and power increased, because EFL exercise induced hypercapnia, which increased the chemical drive to breathe. This was in part due to an increased alveolar dead space presumably resulting from a reduction in pulmonary capillary blood volume secondary to the high expiratory pressures. A vicious circle was established in which expiratory muscle pressures induced hypercapnia, which resulted in an even stronger expiratory muscle contraction. The imposition of EFL reduced cardiac output by 10% and decreased arterial O(2) saturation, reducing energy supplies to working locomotor and respiratory muscles. This model reproduces the most important clinical features of COPD, and these arise from ventilatory pump dysfunction rather than from the lung. It also leads to hypotheses that can be tested in patients with COPD.     

Target-flow inspiratory muscle training during pulmonary rehabilitation in patients with COPD

The effects of additional target-flow inspiratory muscle training (TF-IMT) on the performance of the inspiratory muscles, on general exercise capacity, and on psychologic parameters during a pulmonary rehabilitation program (PR) were studied in 40 patients with COPD selected for ventilatory limitation during exercise. The mean age of the patients was 59 years, and the mean FEV1 was approximately 50 percent of predicted. All patients participated in a ten-week PR program. They were randomized to receive either additional TF-IMT (PR + IMT) or not (PR). The TF-IMT was performed by means of a target-flow resistive device; the generated mouth pressure and the duration of inspiration and of the respiratory cycle were imposed. After the training period, maximal inspiratory mouth pressure and EMG-fatigability of the diaphragm were significantly better in the PR + IMT group than in the PR group. Maximal work load and psychologic symptoms increased to the same extent in both groups. The 12-minute walking distance also increased in both groups, but it increased significantly more in the PR + IMT group than in the PR group. We believe that additional TF-IMT during PR in a selected group of patients with COPD who have ventilatory limitation has an extra beneficial effect on the performance of the inspiratory muscles and on exercise performance.     

Nutrition and chronic obstructive pulmonary disease]

The malnutrition may exert deleterious effects on every constituent of the respiratory system: respiratory drive, respiratory muscles and pulmonary parenchyma. The occurrence of malnutrition in patients with chronic obstructive pulmonary disease (COPD) is associated with a poor prognosis. However the relationships between nutritional status and ventilatory function remain poorly defined. The malnutrition of COPD patients results mainly from a hypermetabolic state. In undernourished COPD patients, nutritional repletion has been reported to improve the performance of respiratory muscles. In COPD patients with acute respiratory failure, a hypercaloric nutrition may induce ventilatory complications that result mainly from an excessive CO2 production. The use of a lipid-enriched diet has been recently proposed in these patients to facilitate weaning from ventilatory support.     

Mechanisms of non-pharmacologic adjunct therapies used during exercise in COPD

Individuals with chronic obstructive pulmonary disease (COPD) are often limited in their ability to perform exercise due to a heightened sense of dyspnea and/or the occurrence of leg fatigue associated with a reduced ventilatory capacity and peripheral skeletal muscle dysfunction, respectively. Pulmonary rehabilitation programs have been shown to improve exercise tolerance and health related quality of life. Additional therapeutic approaches such as non-invasive ventilatory support (NIVS), heliox (He-O(2)) and supplemental oxygen have been used as non-pharmacologic adjuncts to exercise to enhance the ability of patients with COPD to exercise at a higher exercise-intensity and thus improve the physiological benefits of exercise. The purpose of the current review is to examine the pathophysiology of exercise limitation in COPD and to explore the physiological mechanisms underlying the effect of the adjunct therapies on exercise in patients with COPD. This review indicates that strategies that aim to unload the respiratory muscles and enhance oxygen saturation during exercise alleviate exercise limiting factors and improve exercise performance in patients with COPD. However, available data shows significant variability in the effectiveness across patients. Further research is needed to identify the most appropriate candidates for these forms of therapies.     

Malnutrition in chronic obstructive pulmonary disease

Malnutrition in patients with COPD is associated with an impaired pulmonary status, reduced diaphragmatic mass, lower exercise capacity, and higher mortality rate when compared with adequately nourished individuals with COPD. Deterioration in patients with COPD may be the result of malnutrition. In addition, malnutrition could be a sign of other factors directly altered by the disease.     

Effect of sustained release of theophylline on pulmonary physiologic function in elderly patients with chronic obstructive pulmonary disease

We tested the effects of the sustained release of theophylline on the physiologic function of the respiratory system in elderly patients with chronic obstructive pulmonary disease (COPD). We measured the pulmonary function, static respiratory pressures, and ventilation during exercise, before and after the administration of sustained release of theophylline. Unifil, in 12 male COPD patients (mean age 82.1 +/- 0.6 years old). Forced expiratory volume in one second was increased by the administration of 400 mg of Unifil, but not by 200 mg of Unifil, whereas the ratio of residual volume to total lung capacity was decreased by the administration of 400 mg Unifil. Maximum inspiratory pressure was significantly increased after the administration of 400 mg of Unifil. Dyspnea sensation during exercise assessed by the Borg scale was reduced by the administration of 400 mg of Unifil. These results indicate that the treatment with the greater dosage administration of Unifil is effective to improve the physiological function of the respiratory system in elderly patients with COPD, and it may be the treatment of choice for elderly COPD patients.     

死腔负荷对慢性阻塞性肺疾病患者肺功能及呼吸肌功能和运动耐力的影响

目的评价死腔负荷对肺通气功能和呼吸肌的影响,测试呼吸肌氧耗的检测方法,探讨呼吸肌氧耗在慢性阻塞性肺疾病(COPD)运动耐力下降中的作用.方法 26例中度COPD患者和29名年龄相近健康对照者在300 ml呼吸管路死腔(长46 cm)负荷下,完成30 W或55 W功率恒定运动试验,并在死腔负荷下检测运动前、后肺功能和运动中分钟通气量((V·)E)和摄氧量((V·)O2).结果无论COPD或健康对照组,在静息状态或运动后,增加死腔对用力肺活量(FVC)、一秒钟用力呼气容积(FEV1)和FEV1/FVC无显著影响.COPD组静息死腔负荷下FVC、FEV1和FEV1/FVC分别为(3.03±0.15)L、(1.95±0.09)L和(64.9±2.5)%;55 W运动后上述指标分别为(3.03±0.18)L、(2.00±0.13)L和(66.3±3.2)%(P均＞0.05).每例受试个体,无论静息或运动中,附加死腔均导致(V·)E和(V·)O2在原有基础上显著增加,卸除死腔后(V·)E和(V·)O2回落.死腔负荷下(V·)O2的增加量(Δ(V·)O2)在静息和30 W运动时,COPD组和健康对照组之间差异无显著性.在55 W运动时,COPD组Δ(V·)O2显著高于健康对照组[(272±24)ml/min与(194±19)ml/min,P<0.05].结论本组患者呼吸管路加长46 cm(300 ml死腔),伴随中等强度运动未导致COPD患者气流阻塞的进一步加重,也未出现明显呼吸肌疲劳征象.COPD患者呼吸肌具有氧耗优势,呼吸肌与肢体运动肌摄氧比例不平衡,可能是导致COPD患者运动耐力下降的因素之一.     

Respiratory muscles training in COPD patients

It is known that respiratory muscles undergo adaptation in response to overload stimuli during exercise training in stable COPD patients, thus resulting in significant increase of respiratory muscle function as well as the individual’s improvements. The present article reviews the most updated evidence with regard to the use of respiratory muscle training (RMT) methods in COPD patients. Basically, three types of RMT (resistive training, pressure threshold loading, and normocapnic hyperpnea) have been reported. Frequency, duration, and intensity of exercise must be carefully considered for a training effect. In contrast with the plentitude of existing data inherent to inspiratory muscle training (IMT), literature is still lacking in showing clinical and physiological studies related to expiratory muscle training (EMT). In particular, while it seems that IMT is slightly superior to EMT in providing additional benefits other than respiratory muscle function such as a reduction in dyspnea, both the effects and the safety of EMT is still to be definitively elucidated in patients with COPD.     

Respiratory muscle activity in patients with COPD walking to exhaustion with and without pressure support.

The function of the diaphragm and other respiratory muscles during exercise in chronic obstructive pulmonary disease (COPD) remains controversial and few data exist regarding respiratory muscle pressure generation in this situation. The inspiratory pressure/time products of the oesophageal and transdiaphragmatic pressure, and the expiratory gastric pressure/time product during exhaustive treadmill walking in 12 patients with severe COPD are reported. The effect of noninvasive positive pressure ventilation during treadmill exercise was also examined in a subgroup of patients (n=6). During free walking, the inspiratory pressure/time products rose early in the walk and then remained level until the patients were forced to stop because of intolerable dyspnoea. In contrast, the expiratory gastric pressure/time product increased progressively throughout the walk. When patients walked the same distance assisted by noninvasive positive pressure ventilation, a substantial reduction was observed in the inspiratory and expiratory pressure/time products throughout the walk. When patients walked with positive pressure ventilation for as long as they could, the pressure/time products observed at exercise cessation were lower than those observed during exercise cessation after free walking. It is concluded that, in severe chronic obstructive pulmonary disease, inspiratory muscle pressure generation does not increase to meet the demands imposed by exhaustive exercise, whereas expiratory muscle pressure generation rises progressively. Inspiratory pressure support was shown to substantially unload all components of the respiratory muscle pump.     

Respiratory muscle training in chronic obstructive pulmonary disease: inspiratory, expiratory, or both?

PURPOSE OF REVIEW: Most patients with significant chronic obstructive pulmonary disease (COPD) have inspiratory and expiratory muscle weakness. In addition, hyperinflation induces functional weakening of the inspiratory muscles, increased elastic load to breathing, and intrinsic positive end expiratory pressure (PEEPi). Therefore, it was rational to expect that patients with COPD would benefit from specific inspiratory or expiratory muscle training (SIMT, SEMT respectively). However, the functional benefits of SIMT have remained equivocal. In recent years, a number of studies have demonstrated that, when training loads are controlled, SIMT results in important functional benefits. The role of SEMT is still unclear. RECENT FINDINGS: Well-controlled SIMT in patients with COPD leads to relief of dyspnea, during both daily activities and during physical activity. This yields increased exercise tolerance, and thus the capacity to walk, improving health related quality of life. We argue that there is now evidence that SIMT is an important addition to pulmonary rehabilitation programs for patients with COPD. Although two recent studies have shown that SEMT also provides a beneficial effect in patients with COPD, this does not appear to be supplementary to the effect to SIMT. SUMMARY: Inspiratory and expiratory muscles can be specifically trained yielding improvements in both strength and endurance. The improvement in inspiratory muscle performance is associated with an improvement in the sensation of dyspnea, exercise tolerance, and quality of life. When the expiratory muscles are specifically trained, a significant increase in exercise performance has also been shown. However, there is probably no additional benefit in combining SEMT with SIMT.     

Effect of an inhaled beta 2-adrenergic agent on pulmonary function and quality of life in elderly patients with chronic obstructive pulmonary disease

We tested the effects of inhaled beta 2-adrenergic drug on the physiologic function of the respiratory system and quality of life (QOL) in elderly patients with chronic obstructive pulmonary disease (COPD). We measured the pulmonary function, static respiratory pressures, and ventilation during exercise, before and after inhalation of the beta 2-adrenergic drug, fenoterol bromide (FB) in 12 male COPD patients (mean age 82.1 +/- 0.6 years old), QOL was measured with a St George's Respiratory Questionnaire (SGRQ) in the patients. Forced expiratory volume in one second was increased by the inhalation of FB in the patients, whereas the ratio of residual volume to total lung capacity was decreased by the inhalation. Maximum inspiratory pressure was significantly increased after the inhalation of FB. Dyspnea sensation during exercise assessed by the Borg scale was reduced by the inhalation of FB. The scores on SGRQ were improved by one-month treatment with FB. These results indicate that treatment with FB is effective for both physiological function of the respiratory system and several aspects of QOL in elderly patients with COPD.