Respiratory muscle training and resting in COPD

INTRODUCTION — The respiratory muscles constitute a vital component of the respiratory pump. Their contraction during part of the breathing cycle changes the anatomic configuration of the thorax and displaces its components, so that air moves into and out of the gas exchanging portion of the lungs [1-3]. The importance of the respiratory musculature in chronic obstructive pulmonary disease (COPD) is underscored by diaphragmatic structural changes which render patients more resistant to fatigue, including an increased quantity of slow twitch fibers and slow isomers of myosin light chains, tropomyosin, and troponins [4,5].

The effect of training and resting the respiratory muscles in patients with COPD will be presented here. An overview of the management of stable COPD, tests of respiratory muscle strength, and the roles of pulmonary rehabilitation and nocturnal ventilatory support are discussed separately. (See "Stable COPD: Overview of management" and "Pulmonary rehabilitation" and "Nocturnal ventilatory support in COPD" and "Tests of respiratory muscle strength".)

STRENGTH AND ENDURANCE TRAINING — A number of studies have demonstrated that respiratory muscle strength and endurance can be increased with specific training, similar to skeletal muscle training [6-10]. A sufficient stimulus, such as greater than 30 percent of maximal force, is needed for training to occur.

Since reduced inspiratory muscle strength is evident in patients with COPD, considerable efforts have been made to define the role of respiratory muscle training in this setting. Theoretically, an increase in inspiratory muscle strength (and perhaps endurance) could result in improved respiratory muscle function. However, this may only be relevant when patients must handle inspiratory loads that are greater than baseline, such as during an acute exacerbation or exercise.

Inspiratory muscle training (IMT) improved the six-minute walk distance and reduced dyspnea in a study that compared expiratory, inspiratory, and combined training [11]. Systematic reviews and meta-analyses that included data from 55 randomized controlled trials (RCTs) have assessed the impact of IMT alone as well as IMT in addition to pulmonary rehabilitation (PR). IMT alone compared with no IMT or use of a sham device improves inspiratory muscle strength, endurance time, 6- or 12-minute walk distance, quality of life, and some measures of dyspnea, but much of the evidence is of poor quality and at risk for bias [7,12]. When added to PR (22 trials with 1446 participants), IMT did not meaningfully improve dyspnea scores, six-minute walk distance, or St. George's respiratory questionnaire score compared with PR alone [12]. Pooled data indicated a statistical but not clinically meaningful improvement in maximum inspiratory pressures (11 cmH₂0, 95% CI 7.4-15.5). These analyses suggest that IMT may not improve dyspnea, functional exercise capacity, and quality of life when used with PR. However, IMT is likely to improve these outcomes when provided alone.

A separate systematic review indicated that expiratory muscle training improves expiratory muscle forces, but not the six minute walk distance or dyspnea in patients with COPD [13]. More data are needed to clarify the possible role of expiratory muscle training on clinical outcomes.

Strength training — Training for strength is achieved by a high intensity, short duration stimulus, such as performance of inspiratory maneuvers against a closed glottis or shutter. An increase in maximal inspiratory pressures has been demonstrated when the respiratory muscles have been specifically trained for strength [14,15]. Respiratory muscle strength has also been shown to increase as a by-product of endurance training. It is therefore possible that some of the observed benefits reported after endurance training may be related to the associated increase in strength.

Endurance training — Training for endurance is achieved by low intensity, high repetition training. Three types of programs have been used: flow resistive loading; threshold loading; and voluntary isocapnic hyperpnea.

Flow resistive loading — Data from numerous studies indicate that ventilatory muscle training with flow resistive breathing results in improved ventilatory muscle strength and endurance, but has marginal effects on overall exercise performance [7]. It is not clear whether improved strength and endurance will result in decreased morbidity or mortality or offers other clinical advantages.

In flow resistive load training, the load consists of using a device with an adjustable inspiratory breath hole size. The load will increase provided that frequency, tidal volume, and inspiratory time are held constant. Although most studies in patients with COPD have shown an improvement in the time that a given respiratory load can be maintained (ventilatory muscle endurance), the results have to be interpreted with caution, since endurance can be increased with changes in the pattern of breathing.

A number of controlled studies of resistive breathing have shown an increase in the endurance time that the ventilatory muscles could tolerate a known load [15-23]. Some have also shown a significant increase in strength [15-17,19-22] and exercise tolerance [22], and a decrease in dyspnea during inspiratory loading [16,22]. The pressure required to achieve training must exceed 30 percent of maximal inspiratory pressure [15,22]. In the studies which evaluated systemic exercise performance, there was a minimal increase in walking distance [15,19,21-23].

Threshold loading — With threshold loading, the patient breathes through a device that requires the patient to generate a threshold or target level of work before inspiratory airflow can begin. The threshold pressure needed to initiate inspiratory flow is high enough to ensure training, independent of inspiratory flow rate. When threshold devices are used, the breathing pattern (inspiratory time and respiratory rate) is not as critically important because the pressure required to activate the threshold is independent of the flow.

The benefit of inspiratory threshold loading was demonstrated in a trial of 33 patients with severe COPD who were randomly assigned to receive high intensity training (highest tolerable inspiratory threshold load) or sham training (only 10 percent of the maximal inspiratory pressure) three times per week for eight weeks [8]. High intensity training resulted in a greater increase of the maximum inspiratory pressure (18 versus 5 cm H₂O), maximum threshold pressure (21 versus 2 cm H₂O), and six-minute walking distance (27 versus 5 meters), as well as improved dyspnea and fatigue, compared to sham training.

The utility of IMT in facilitating liberation from mechanical ventilation has been explored in several studies that included but were not limited to patients with COPD:

●In a randomized trial, 92 patients on mechanical ventilation were assigned to inspiratory muscle training (40 percent of maximal pressure 5 sets of 10 breaths twice a day, seven days a week) or usual care until extubation, tracheostomy, or death [24]. Muscle training improved inspiratory muscle strength and tidal volume compared with usual care but had no effect on weaning outcome.

●IMT with a threshold inspiratory device, starting at the highest tolerated pressure and titrating upwards, has been tested in patients unable to wean from prolonged mechanical ventilation. A single-center randomized trial enrolled 69 patients unable to wean from MV; 35 to the IMT and 34 to the sham group [25]. IMT was performed with a threshold inspiratory device, set at the highest pressure tolerated and progressed daily. Subjects completed four sets of 6 to 10 training breaths, five days per week. The weaning criterion was 72 consecutive hours without MV support. The IMT and sham groups respectively received 42 ± 26 versus 47 ± 33.0 days of mechanical ventilatory support prior to starting intervention. The sham group's pre- to post-training maximal inspiratory pressure (MIP) change was not significant, while the IMT group's MIP increased (-44 ± 18 versus -54 ± 18 cm H₂O). Twenty-five of 35 IMT subjects weaned (71 percent, 95% CI 55 to 84 percent), while 16 of 34 (47 percent, 95% CI 31-63 percent) sham subjects weaned. The number of patients needed to be treated for effect was 4 (95% CI 2 to 80).

An IMT program can lead to increased MIP and improved weaning outcome in failure-to-wean patients compared with sham treatment. These results are further supported by a randomized trial of 101 patients of whom 48 were assigned to the IMT group and 53 to the control group [26]. IMT was associated with a substantially higher gain in muscle strength as assessed by the maximal inspiratory pressure (-71 cm H₂O [-51 to -83 cm H₂O] versus -48 cm H₂O [-36 to -72 cm H₂O]). Outcomes at the 60th day of ICU were significantly better in the intervention group regarding both survival (71 versus 49 percent) and weaning success (75 versus 45 percent). These studies support a potential use of IMT in patients with weak respiratory muscles unable to wean after prolonged MV.

For patients who have already weaned from mechanical ventilation, a course of IMT may improve exercise capacity. In a small study, 29 patients with COPD who remained hypercapnic after successful weaning from mechanical ventilation to noninvasive ventilation were randomized to IMT or sham training for four weeks during a pulmonary rehabilitation program [9]. Patients in the IMT group significantly improved their walking distance (3 to 186 m) and their maximal inspiratory pressure (-6 to -33 cm H₂O), suggesting that IMT significantly enhances functional exercise capacity and increases respiratory muscle strength and power. However, no major changes were seen in arterial blood gases and no evidence was presented for effect on health status.

Voluntary isocapnic hyperpnea — Voluntary isocapnic hyperpnea is a training method in which patients maintain high levels of ventilation over time (for 15 minutes, two or three times daily). Sufficient carbon dioxide is added to inspired gas to maintain a constant arterial tension of carbon dioxide (PaCO₂), which is measured indirectly by the end-tidal partial pressure of CO₂ (EtCO₂). (See "Carbon dioxide monitoring (capnography)".)

Studies evaluating the efficacy of respiratory muscle endurance training using voluntary isocapnic hyperpnea have had different results. Two controlled studies reported increases of maximal sustained ventilatory capacity (MSVC) in patients with COPD who were trained for six weeks, but the improvement in exercise endurance was no better than that observed in the control group [27,28]. In contrast, a subsequent study demonstrated improvement of endurance exercise capacity, respiratory muscle endurance capacity, perception of dyspnea, and quality of life compared to control subjects [29].

In a variation of hyperpnea training, 313 patients who underwent open cardiac surgery were randomly assigned to daily home training with deep breathing exercises for two months or to usual care. No differences were observed in health status measured with the short form 36 questionnaire or in lung function [30].

Novel training methods — The use of non-conventional methods of training to improve ventilator muscle synchronization and function has gained some attention. Amongst them, the implementation of Tai-Chi techniques for patients with COPD was the topic of a Cochrane Database Systematic review of 12 randomized trials with 984 patients, lasting from six weeks up to one year. In total, the review documented a small but significant improvement in the six-minute walk distance (mean difference [MD] 29.6 meters, 95% CI 10.5-48.8 meters) and in the FEV₁ (0.11 L, 95% CI 0.02-0.20 L). However, the effect on dyspnea and health status remained inconclusive. More studies are needed to establish the value of these training methods on health resource utilization and outcomes.

Potential deleterious effects — There is also the potential for ventilatory muscle training to be deleterious. Breathing at a high proportion of the functional reserve or with a prolonged inspiratory time may induce muscle fatigue [31]. Both factors are an intrinsic part of training; it is therefore possible that a sufficiently intense training program may precipitate fatigue. This may explain why compliance with such training programs is low, with up to 50 percent of patients failing to complete the studies.

RESPIRATORY MUSCLE RESTING — Respiratory muscles may fatigue when working against a sufficiently large load. This has been shown to occur experimentally in normal volunteers and patients with chronic obstructive pulmonary disease (COPD) [1-3]. Clinically, respiratory muscle fatigue appears to play an important role in the acute respiratory failure of patients with COPD. In comparison, patients with chronic stable COPD are not suffering from chronic respiratory muscle fatigue.

Acute on chronic respiratory failure — For patients with acute on chronic respiratory failure due to an exacerbation of COPD, the use of noninvasive ventilation (NIV), which enables respiratory muscle unloading and resting, has been shown to be beneficial [32-35]. The implementation of NIV for acute on chronic respiratory failure in COPD is discussed separately. (See "Noninvasive ventilation in adults with acute respiratory failure: Benefits and contraindications".)

Patients best suited for this method were those with elevated arterial PCO₂ who were able to cooperate with the care givers and had no other important co-morbid problems, such as sepsis or severe pneumonia. Because NIV is potentially dangerous, patients considered for this therapy should be closely monitored and treated by individuals familiar with this ventilatory technique [36].

The various trials evaluated different outcomes, including rate of intubation, length of stay in the intensive care unit or in the hospital, dyspnea, and mortality. Although not all studies found the same results in the most important outcomes (such as mortality, intubation, length of hospital stay, and complications such as pneumonia), there was uniform agreement that respiratory muscle resting using NIV was effective in reversing acute respiratory failure and preventing complications. Approximately, five patients need to be treated with acute NIV to prevent one intubation and only eight patients need to be treated to prevent one death [37].

Chronic stable COPD — The possibility that the respiratory muscles of patients with severe COPD are functioning close to the threshold for fatigue, as suggested by chronic hypoventilation and consequent hypercapnia, has led numerous investigators to explore a potential role of resting the respiratory muscles with noninvasive negative or positive pressure ventilation. While older trials showed no benefit to NIV for most of the outcomes studied [31,38-43], subsequent trials that employed higher inspiratory pressures (so-called high-intensity NIV) with an aim to reduce arterial tension of carbon dioxide (PaCO₂) to normal or near-normal levels have offered more favorable results [44-46].

The European Respiratory Society (ERS) and the American Thoracic Society (ATS) independently reviewed the role of NIV in stable hypercapnic COPD using evidence-based systematic review methodology [47,48]. The ERS concluded that high-intensity NIV may decrease exacerbations, reduce dyspnea (as measured by improvements in the Medical Research Council Dyspnea score), and improve health-related quality of life, although they noted a low certainty of evidence [47]. Similarly, the ATS systematic review found that potential benefits of NIV included reductions in hospital admissions and dyspnea and also improved functional capacity and six-minute walk distance [48]. It seems possible that high-intensity NIV achieves these results through more successful rest of the diaphragm than was achieved in the earlier studies of lower intensity NIV [47].  

Based on these evidence-supported documents, an expert panel from several societies (ATS, American College of Chest Physicians, American Association of Respiratory Care, and the American Academy of Sleep Medicine) published practical recommendations aimed at improving the application of NIV for patients with hypercapnic stable COPD (PaCO₂ ≥52 mmHg on the patient’s usual oxygen supplementation regimen) [49]. For such patients, the panel advises the following:

●Obstructive sleep apnea (OSA) should be considered and excluded on clinical grounds (no formal study needed).

●Bi-level positive airway pressure (BPAP) ventilation with a backup rate is preferred for initial therapy in most patients.

●The patient should be seen between 31 to 90 days after initiation of NIV to monitor adherence and response to therapy. If the ventilation goals are achieved (patient is adherent with four hours or more of NIV per night and clinical improvement noted), NIV should be continued with frequent monitoring. If the patient fails to achieve these goals, transition to a home mechanical ventilator should be considered.

In spite of the great advances in the appropriate selection of COPD patients who may benefit from long term NIV, more studies are needed to better identify patients who are likely to benefit and to clarify the optimal NIV settings.

The use of nocturnal NIV in patients with severe COPD and hypercapnia is discussed in greater detail separately. (See "Nocturnal ventilatory support in COPD".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Chronic obstructive pulmonary disease".)

SUMMARY

●In patients with COPD, respiratory muscle training increases the strength and capacity of the muscles to endure a respiratory load. Inspiratory muscle training (IMT) is likely to improve dyspnea, functional exercise capacity, and quality of life when provided alone. However, IMT may not improve these outcomes when used as a component of a pulmonary rehabilitation program. (See 'Strength and endurance training' above.)

●It seems logical to predict that increases in strength and endurance would help respiratory muscle function. However, this may only be relevant when patients must handle inspiratory loads that are greater than baseline, such as during an acute exacerbation or exercise. (See 'Strength and endurance training' above.)

●The exact criteria for patient selection remain unclear. Stable patients with dyspnea and respiratory muscle weakness are likely to benefit from respiratory muscle training. IMT may be beneficial in patients with respiratory muscle weakness who have been unable to wean after long-term mechanical ventilation, but further study is needed. (See 'Strength and endurance training' above.)

●Respiratory muscle training can induce deleterious effects, such as an uncomfortable degree of fatigue, when breathing at a high proportion of the functional reserve or with a prolonged inspiratory time. (See 'Potential deleterious effects' above.)

●For patients with an exacerbation of COPD complicated by hypercapnic acidosis (arterial tension of carbon dioxide [PaCO₂] >45 mmHg or pH <7.30) who do not require emergent intubation and lack contraindications to NIV, a trial of bilevel noninvasive ventilation (NIV) is advised, as described in detail separately. (See 'Respiratory muscle resting' above and "Noninvasive ventilation in adults with acute respiratory failure: Benefits and contraindications".)

●Intermittent respiratory muscle rest during nocturnal NIV using sufficient inspiratory pressures to reduce PaCO₂ to normal or near-normal levels (so-called high-intensity NIV) may be of benefit in stable patients with severe hypercapnic COPD. NIV appears more effective in patients discharged after hospitalization for an exacerbation who remain hypercapnic (PaCO₂ >55 mmHg) with a stable pH (>7.30), although more study is needed to clarify the risks and benefits. (See 'Chronic stable COPD' above.)