Functional benefits of respiratory muscle training

Structural adaptations to RMT

The data pertaining to structural adaptations following RMT are derived from studies employing two forms of measurement: firstly, analysis of muscle biopsy samples taken from patients and secondly ultrasound measurements of muscle thickness derived from both patients and healthy people. This evidence is currently confined to inspiratory muscles following resistance training.

Functional adaptations to RMT

Principally, muscles respond to training by improving their strength, speed of contraction, power output and / or endurance. Because muscles respond to training stimuli in highly specific ways (see Ch. 5, ‘Methods of respiratory muscle training’), different training regimens tend to elicit slightly different changes in each property. For example, training that consists of maximal, static efforts with high force improves strength, but not contraction speed (Romer & McConnell, 2003). However, there is also a good deal of cross-over, such that training regimens that are ostensibly strength orientated can also give rise to improvements in endurance, but generally not vice versa (see Ch. 5, ‘Specificity’). The following section describes what is known about improvements in each functional property following resistance training.

A helpful method of characterizing the functional properties of muscles is to plot a graph of the relationship between strength and contraction speed; the so-called force–velocity relationship (see also Ch. 5, ‘Specificity’). It is also possible to add a third dimension to this in the form of muscle power output, which is the product of force and velocity. Figure 4.1 illustrates these interrelationships for the inspiratory muscles, and encapsulates the three key and interrelated functional properties of muscles (strength, speed and power), all of which can be modified by appropriate training.

Influence of RMT upon time trials and tests of endurance

Most of the studies of respiratory muscle training (RMT) in healthy people have examined endurance sports, and two types of exercise tests have been used: fixed-intensity exercise undertaken to the limit of tolerance (T_lim) and time trials. The majority have been randomized placebo-controlled trials; unfortunately, some weaker studies with either a simple no-training control or no control at all have found their way into the literature (Illi et al, 2012). However, only placebo-controlled and controlled trials are considered within this section.

There are no competitive events that require athletes to keep going at the same intensity for as long as they can (a T_lim test), but this type of test does provide an excellent laboratory model for studying the effects of ‘ergogenic aids’ such as RMT (i.e., interventions that purport to improve performance). This is because T_lim tests are extremely sensitive to small physiological improvements, they yield large changes (typically greater than 30%) and they allow physiological and perceptual responses to be studied under identical conditions before and after the intervention. In contrast, the obvious advantage of using a time trial to assess performance is that it simulates a race. However, for this very reason the magnitude of the changes that are typically observed after ergogenic interventions is extremely small, typically less than 5% (Currell & Jeukendrup, 2008). In addition, it is impossible to compare physiological responses in a meaningful way before and after the intervention using a time trial because the exercise conditions are not identical. For example, if performance is enhanced post-RMT, athletes will be working at a greater intensity, which cannot then be compared with the pre-intervention test. Both types of tests have provided useful insights into the effects of RMT.

Typically T_lim tests are conducted at intensities that are just above the lactate threshold. The ability to sustain exercise above the lactate threshold is limited, and the more the intensity of exercise exceeds the lactate threshold the sooner is the onset of exercise intolerance. Studies on RMT have used exercise intensities that can be tolerated for 20 to 40 minutes. In contrast, time trials have varied considerably depending on the sport being studied; for example, studies have used as little as 1 minute for swimming, and as much as 1 hour for cycling.

Studies that have used resistance training of the respiratory muscles (see Ch. 5) have done so using cycling, rowing, swimming and running modalities. In the case of cycling and running, this has been undertaken using both T_lim tests and time trials. For rowing and swimming, only time trials have been used. Table 4.1 summarizes the findings of placebo-controlled studies. Many more studies than those presented have been conducted, but their quality is variable (Illi et al, 2012) so the table is limited to those with robust designs.

Table 4.1 indicates clearly that inspiratory muscle training (IMT) produces statistically significant improvements in performance, but that expiratory muscle training (EMT) does not. As demonstrated statistically by Illi et al (2012), performance improvements occur whether tested using time trials (1.7% to 4.6% improvement for tests lasting 1 to 60 minutes), or T_lim tests (greater than 30% improvement for a 30-minute test). For higher-intensity, shorter-duration T_lim tests, the improvements are smaller (~ 4% for a test lasting less than 4 minutes). This difference in the size of the improvements occurs because of differences in the factors that lead to people stopping exercise and the rate at which these factors accumulate and lead to intolerance (Currell & Jeukendrup, 2008).

Endurance training of the respiratory muscles involves hyperventilation at high levels for prolonged periods (see Ch. 5). Table 4.2 summarizes the controlled and placebo-controlled trials using endurance RMT. Despite the profound difference in the training method, the results are strikingly similar to those for resistance IMT, a finding confirmed statistically by Illi and colleagues (Illi et al, 2012). Typically, T_lim increases by 20% to 50%, whereas a time trial shows ~ 4% improvement. This similarity is quite unlike the response to whole-body endurance and resistance training, which suggests that breathing muscle training taps into a unique and profoundly important mechanism. As was described in the Chapter 3, the most likely candidate mechanism for this effect is an increase in the threshold for activation of the inspiratory muscle metaboreflex.

It is impossible to separate the inspiratory and expiratory effects of hyperventilation training, but when this has been done for resistance training the independent roles of the two groups of muscles in performance changes become clear (Griffiths & McConnell, 2007): only IMT improves performance. Indeed, adding EMT to IMT during the same breath cycle seems to impair inspiratory muscle responses to IMT (Griffiths & McConnell, 2007) and to negate any performance benefits (Wells et al, 2005), which provides a strong argument against using this approach or, perhaps, undertaking EMT in healthy young people at all.

Tables 4.1 and 4.2 also summarize some of the physiological changes that accompany RMT, and these help to shed some light on the potential mechanisms that do, and do not, lead to the improvement in performance. Specifically, after IMT there are no changes in the ‘usual suspects’ underpinning improved exercise performance after training, viz., maximal oxygen uptake (O_2max) and lactate threshold (see Ch. 2). Since breathing does not limit oxygen diffusion (see Ch. 1), we would not expect O_2max to improve. However, the absence of a change in lactate threshold is slightly puzzling given that IMT reduces blood lactate concentrations [La]_b during exercise at equivalent intensities (see Tables 4.1 and 4.2). It seems that IMT reduces [La]_b, but not the intensity of exercise at which accumulation commences, or indeed the critical power, which is a functional correlate of the lactate threshold (Johnson et al, 2007). The mechanism by which steady state [La]_b is reduced without an accompanying change in the lactate threshold is an intriguing one. It is common for different people to have different steady-state lactate concentrations but very similar lactate thresholds, so it is clear that the [La]_b per se is not a determinant of the lactate threshold. There is good evidence that IMT increases the metabolic potential of the inspiratory muscles, and thus their ability to consume lactate during submaximal exercise (Brown et al, 2011). One might also hypothesize a lower production of lactate by locomotor muscles due to enhanced oxygen delivery, which could arise because of a reduction in sympathetic vasoconstriction. However, improving oxygen delivery in sub-elite athletes by inhaling an oxygen-rich inspirate does not enhance their lactate threshold (Sadowsky et al, 1995). Thus the most likely explanation for the lower steady state [La]_b without a change in the lactate threshold is enhanced consumption of lactate by the inspiratory muscles (Peter Brown & Graham Sharpe, personal communication). However, this does not imply that an improved muscle blood flow is redundant. Enhancing muscle blood flow by manipulating the work of breathing reduces exercise-induced locomotor muscle contractile fatigue (Romer et al, 2006). Furthermore, the removal of muscle metabolites may also influence the central contribution to fatigue (see Ch. 1, ‘Mechanisms of fatigue’).

So far as the factors that do change after IMT are concerned, these include reductions in [La]_b, heart rate, and perception of breathing and limb effort, as well as a speeding of oxygen uptake kinetics during heavy exercise. In addition, breathing becomes deeper and slower, as well as more metabolically efficient (Turner et al, 2012). Perhaps most importantly, IMT delays or abolishes the exercise-induced decrease in MIP observed post-exercise, i.e., IMT attenuates inspiratory muscle fatigue (Romer et al, 2002d). These changes are all consistent with the respiratory-related exercise-limiting factors described in Chapter 3. The attenuation of inspiratory muscle fatigue is indicative of an improvement in the functional capacity of the respiratory pump muscles. Since metabolite accumulation contributes to deficits in the ability to produce muscular force at both a peripheral and a central level (see Ch. 2, ‘Mechanisms of fatigue’), the attenuation of inspiratory muscle fatigue is consistent with a reduction and / or delay in both metabolite accumulation and activation of the inspiratory muscle metaboreflex. Activation of this reflex induces vasoconstriction in the locomotor muscles, but IMT has been shown to increase the intensity of inspiratory muscle work required to activate this reflex (McConnell & Lomax, 2006; Witt et al, 2007; Bailey et al, 2010), and to reduce La production by the inspiratory muscles (Brown et al, 2011). As a result, muscle blood flow may be preserved, and limb fatigue attenuated or delayed (McConnell & Lomax, 2006). This mechanism may also explain the reduction in [La]_b, and leg effort, as better-perfused locomotor muscles generate less lactate and have lower levels of metabolites to stimulate the group III and IV afferents that contribute to effort perception (Amann et al, 2010) and fatigue (Gandevia, 2001; Amann et al, 2009) (see Ch. 3). In addition, if inspiratory muscle fatigue is attenuated the perception of breathing effort will be reduced, making it possible to maintain a more efficient deep, slow breathing pattern (Turner et al, 2012). In short, the physiological changes point strongly to the ergogenic effect of IMT being underpinned by preservation of limb blood flow and reduction in breathing effort. These effects are arguably even more important in patients, since exercise tolerance is frequently limited by dyspnoea and / or muscle dysfunctions that are exacerbated by impaired blood flow.

In respect of the inspiratory muscle metaboreflex, there is one particular study of IMT that is worthy of detailed scrutiny because it has particular relevance to patients. The study in question not only demonstrated that IMT extends T_lim, but it also demonstrated that oxygen uptake kinetics were hastened during ‘severe’- and ‘maximal’-intensity cycling (Bailey et al, 2010), a finding that has since been confirmed (Brown et al, 2011). The authors’ interpretation was that their observations were due to ‘increased blood flow to the exercising limbs’, and that this arose because of the absence of inspiratory muscle metaboreflex activation post-IMT (Bailey et al, 2010). These findings are especially relevant to patients since the oxygen uptake kinetics of patients are slowed by disease and inactivity (Chiappa et al, 2008a). The speed of this ‘on transient’ of the oxygen uptake kinetics determines the size of the oxygen deficit during exercise, and thus the size of the anaerobic contribution at the onset of exercise (see Ch. 1). Enhancing the amount of energy liberated from aerobic sources minimizes the production of fatiguing metabolic by-products, and reduces the ventilatory requirement for exercise. In patients for whom walking constitutes ‘severe’-intensity exercise, and who are consequently teetering on the edge of the ‘anaerobic abyss’, this effect on oxygen uptake kinetics may be particularly important and make a disproportionate contribution to improving exercise tolerance. Interestingly, reducing the work of breathing using a low-density inspirate (heliox) speeds oxygen uptake kinetics and improves exercise tolerance in patients with COPD (Chiappa et al, 2009); this response is strikingly similar to that observed in healthy people following IMT (Bailey et al, 2010; Brown et al, 2011).

Finally, there has long been speculation that IMT may enhance the mechanical efficiency of breathing, as some studies have shown small (often non-significant) decreases in the oxygen cost of exercise (Romer et al, 2002a; Griffiths & McConnell, 2007; Turner et al, 2011). A recent study found that 6 weeks of IMT (30 repetitions against a load equivalent to 50% of MIP) reduced the oxygen cost of hyperpnoea by 5–12% (Turner et al, 2012). The greatest decrement in oxygen cost was seen at the highest intensity of respiratory muscle work. This finding has important implications for patients in whom disease-related impairments of breathing mechanics increase the oxygen cost of breathing. Since the latter may account for a considerable proportion of available oxygen uptake, reducing this burden may release oxygen for use by other muscle groups, thereby enhancing exercise tolerance.

In summary, the research using time trials and tests of endurance indicates that, for bouts of exercise involving a sustained effort against the clock of 1 to 60 minutes duration, IMT improves performance significantly by 1.7% to 4.6%. Although there is no direct research evidence that similar improvements will be seen during longer events (e.g., marathons or triathlons), the fact that a decline in MIP has been demonstrated after such events means that performance in these events may be limited by breathing-related factors. Accordingly, there is every reason to believe that IMT will improve performance in events lasting more than 1 hour. The mechanisms that underlie the changes in performance described above are applicable universally and have equal, if not greater, relevance to exercise-limited patients. Indeed, Illi and colleagues’ systematic review revealed that the ergogenic effect of RMT was greatest in the least fit participants (Illi et al, 2012).

Influence of RMT upon tests of anaerobic endurance and sprinting

Sprinting is such a brief activity that the benefits of IMT are not immediately obvious. However, the changes that IMT induces in underlying physiology appear to be so fundamental that it is now clear that performance in sprint tasks can also benefit from IMT. This is relevant to patients because the metabolic demands of activities of daily living can be akin to those of a sprint in a young healthy individual. In the previous section we have already discussed the fact that maximal cycling to the limit of tolerance is extended significantly following IMT, and that this was accompanied by a significant speeding up of oxygen uptake kinetics (Bailey et al, 2010; Brown et al, 2011). Repeated sprinting may not be something that many patients engage in during their everyday lives, but it is encountered in interval training, which is finding increasing favour within rehabilitation programmes (Mador et al, 2009). Thus, the results of studies on repeated sprinting suggest potential benefits of IMT for tolerance to repeated bouts of anaerobic exercise, such as interval training. Improving the tolerability of training interventions has the benefit of enhancing the potency of the training stimulus, and the resulting performance benefits. Indeed, it has been shown that athletes undertaking a period of IMT prior to a programme of interval training were able to train significantly harder, and showed significantly greater improvements in repeated sprint performance, compared with a group that did not receive prior IMT (Tong et al, 2010). Unfortunately, there was no placebo control within this trial.

In the context of team sports, a sense of increased breathing effort between sprints has a profound influence on a player's ability to sprint again, and in competition this has implications for the quality of the athlete's contribution to the match or game. For this reason, the first study to examine the effect of IMT on sprinting used perceived rate of recovery during continuous bouts of repeated sprinting (Romer et al, 2002b). The expectation was that IMT would reduce breathing effort between sprints and delay the onset of inspiratory muscle fatigue, thereby making the participants feel as if they had recovered more quickly. However, because the sprint was very brief (3.2 seconds) and punctuated with periods of recovery, there was no expectation that actual sprint performance would improve. These expectations were confirmed; after 6 weeks of IMT (30 repetitions against a load equivalent to 50% of MIP) the athletes showed a significantly faster rate of recovery compared with baseline and placebo, but no change in sprint performance. The potential relevance of these findings for a patient who is limited acutely by dyspnoea is that IMT may reduce the duration that they must spend ‘catching their breath’; this hypothesis awaits evaluation.

Using a slightly different approach, two controlled studies (one of which was placebo controlled) have explored the benefits of IMT to the ability to sustain repeated sprinting, with gradually escalating sprint speed, and short active recovery breaks between sprints (Yo-Yo test) (Bangsbo et al, 2008). Performance in a test of this kind is influenced by both effort perception and factors related to limb blood flow, such as oxygen delivery and metabolite removal. As has been explained previously, both of these factors are potentially influenced by IMT, via its hypothesized effects upon breathing effort and activation of the inspiratory muscle metaboreflex. After 5–6 weeks of IMT (30 repetitions against a load equivalent to 50% of MIP), both studies found that performance in the Yo-Yo test improved significantly by ~ 17% (Tong et al, 2008; Nicks et al, 2009). Accompanying the improvement in performance were significant reductions in perception of breathing and whole-body effort, as well as markers of metabolic stress. In a more recent study, the distribution of blood flow to the legs and respiratory muscles during repeated sprinting has been studied (Tong et al, 2012). As the sprint test progressed, minute ventilation showed a progressive increase and, at the point where respiratory compensation for the developing metabolic acidosis commenced, there was a clear reduction in the oxygenation of both the respiratory and leg muscles. The timing of the two events was correlated significantly. These data are consistent with activation of the inspiratory muscle metaboreflex by the escalating ventilatory demand, followed by vasoconstriction of both the respiratory and leg muscle vasculature. Thus, as suggested for endurance exercise, IMT may improve performance during repeated sprinting by increasing the intensity of respiratory muscle work required to activate the metaboreflex, thereby preserving limb blood flow (McConnell & Lomax, 2006; Witt et al, 2007; Bailey et al, 2010).

Most recently, the effects of combining IMT with a specific inspiratory muscle warm-up (see Ch. 6) have been tested in a placebo-controlled trial on semi-professional football players (Lomax et al, 2011). The same IMT protocol and repeated sprint test were used as in previous studies; after 4 weeks of IMT, sprint performance increased significantly by 12%. At baseline, the warm-up increased sprint performance significantly by 5–7% in both groups, which is consistent with previous findings (Tong & Fu, 2006). When an inspiratory muscle warm-up was added after IMT, performance increased significantly by a further 2.9%. Thus, the benefit of the inspiratory muscle warm-up and IMT were additive (14.9%).

In summary, IMT was once thought to be of benefit only for performance in activities dominated by aerobic metabolism. However, studies now suggest that IMT is more versatile, and that the fundamental nature of the underlying mechanisms makes it an effective tool for enhancing tolerance to both prolonged moderate-intensity exercise and brief intense exercise. The similarity between the physiological changes observed following IMT during sprint and endurance exercise in healthy people is to be expected, given that IMT is probably operating via the same underlying mechanisms in both situations, i.e., attenuation of breathing effort and enhancement of limb blood flow.

Influence of RMT under hypoxic conditions

The addition of an hypoxic drive to breathe during exercise places a large additional demand upon the respiratory muscles. Therefore, the potential benefits of RMT are arguably even greater to people exercising in an hypoxic environment, or those who have hypoxaemia due to the effects of disease. To date, only one placebo-controlled study has assessed the influence of IMT on exercise tolerance and physiological responses to exercise in hypoxia (Downey et al, 2007). The results of the randomized controlled study were both impressive and surprising. The IMT group trained for 40 breaths, 5 days per week at a load of ~ 50% of MIP, whilst the placebo group used the same regimen at a load of 15% of MIP. The hypoxic environment simulated an altitude of ~ 3500 metres (~ 12 000 feet), which was sufficient to reduce arterial saturation to ~ 93% at rest and ~ 77% at end of exercise. Following 4 weeks of IMT, minute ventilation, cardiac output and oxygen uptake of hypoxic treadmill exercise were reduced significantly in the IMT group by 25%, 14% and 8–12% respectively. Despite the lower minute ventilation, arterial oxygen saturation (S_aO₂) and lung-diffusing capacity were increased by 4% and 22%, respectively. Perceived exertion and dyspnoea were also reduced significantly. No such changes were observed in the placebo group. The changes in minute ventilation and S_aO₂ appear to be completely at odds with one another, as an increase in S_aO₂ normally requires an increase in minute ventilation. The clue to resolving this paradox resides in the improvement in the diffusing capacity of the lungs, which can increase only if the lung diffusion surface area increases. The pulmonary vasculature is responsive to muscle metaboreflex activation (Lykidis et al, 2008). Thus, if IMT were to delay or abolish activation of the inspiratory muscle metaboreflex, it is conceivable that blood flow would be preserved in the pulmonary circulation. Should this occur, an increase in diffusion surface area would result, thereby increasing S_aO₂. The effect of IMT upon S_aO₂ in hypoxic conditions has been confirmed under resting conditions in a randomized controlled study of military personnel during an expedition to the Nepali Himalayas (Lomax, 2010). At altitudes of 4880–5550 metres, the resting S_aO₂ was 6% higher in the IMT group compared with the control group. This protective effect upon S_aO₂ was not observed at 1400 metres.

High altitude is the only environment where the lungs limit oxygen transport in healthy people. However, there are many disease states that result in hypoxaemia and pulmonary vasoconstriction, both at rest and during exercise. Under these conditions, patients may be particularly sensitive to an additional vasoconstrictor input to the pulmonary vasculature from the inspiratory muscle metaboreflex. Accordingly, IMT may provide even greater benefits to these patients than those observed in normoxic, healthy people. In the following section, the evidence relating to the influence of RMT upon patients with a range of conditions will be reviewed.

Respiratory disease

Chronic heart failure

The literature relating to RMT in patients with chronic heart failure (CHF) has been growing steadily over the past decade. The first study to examine RMT in patients with CHF appeared in the literature in 1995 (Mancini et al, 1995). The 3-month intervention combined isocapnic hyperpnoea, maximum static inspiratory efforts and pressure threshold loading. Training produced improvements in the MIP (37%) and endurance of the respiratory muscles (57%), as well as alleviating dyspnoea during activities of daily living. Exercise performance during submaximal and maximal exercise tests was also enhanced. The authors suggest that RMT may provide ‘a simple and useful adjunct to medical therapy’ for patients with CHF. These early findings were replicated either fully or in part over the course of the following decade using pressure threshold IMT (Cahalin et al, 1997; Johnson et al, 1998; Weiner et al, 1999; Martinez et al, 2001). Typically, MIP improves 25–30% over an 8- to 12-week period, whereas the magnitude of changes in exercise tolerance and dyspnoea varies according to the tests used; typically 6-minute walk distance improves by around 20–30% (Mancini et al, 1995; Weiner et al, 1999).

More recently, further studies have consolidated and extended the earlier findings (Laoutaris et al, 2004; Dall'Ago et al, 2006; Padula et al, 2009; Bosnak-Guclu et al, 2011; Mello et al, 2012). Typically, IMT improves MIP and inspiratory muscle endurance, reduces exertional dyspnoea, increases exercise tolerance and improves quality of life. Four systematic reviews have examined the influence of IMT, one focussing upon its effect upon quality of life (Sbruzzi et al, 2012) whereas the other three also examined exercise tolerance (Lin et al, 2012; Plentz et al, 2012; Smart et al, 2012). Sbruzzi and colleagues included four studies in their analysis, concluding that, on balance, these did not support a significant effect of IMT upon quality of life; however, they suggested that further research is required. In contrast, Smart and colleagues included 11 studies (148 IMT participants and 139 placebo or non-training participants). Significant effects were identified for MIP, peak oxygen uptake (1.8 ml·min^− 1.kg^− 1, 9.2%), 6-minute walk distance (34 metres), quality of life (12.2 units) and _E–CO₂ gradient (an index of ventilatory efficiency). Based upon comparison of effect sizes with previous meta-analyses of exercise training in patients with CHF, the authors concluded that: ‘IMT improves cardiorespiratory fitness and quality of life to a similar magnitude to conventional exercise training and may provide an initial alternative to the more severely deconditioned CHF patients who may then transition to conventional [exercise training]’. Similar findings for outcomes relating to MIP, exercise tolerance and dyspnoea were also reported in the systematic reviews by Lin et al (2012) and Plentz et al (2012).

Recent studies have also shed light on the potential mechanisms underlying improvements in exercise tolerance following IMT (Chiappa et al, 2008b; Stein et al, 2009). The first study is an elegant experiment that examined whether IMT influenced activation of the inspiratory muscle metaboreflex (Chiappa et al, 2008b). Before IMT, breathing against an inspiratory load activated the inspiratory muscle metaboreflex, inducing vasoconstriction in both resting and exercising limbs. In contrast, after 4 weeks of IMT the metaboreflex response to the same loaded breathing task was delayed, and the time to fatigue during subsequent forearm exercise task was extended. The study also documented a 54% increase in contracted diaphragm thickness, which explained 77% of the change in MIP. The finding of a change in the work threshold for activation of the inspiratory muscle metaboreflex after IMT is similar to that in healthy people described above (McConnell & Lomax, 2006; Witt et al, 2007; Bailey et al, 2010), and suggests that this mechanism plays an important role in mediating improvements in exercise tolerance.

The role of improved oxygen delivery in the improvements in exercise tolerance observed after IMT is supported by Stein and colleagues’ retrospective analysis (2009) of the data published by Dall'Ago et al (2006). Stein and colleagues used the oxygen uptake efficiency slope (OUES, or gradient of O₂ vs log_E) (Baba et al, 1996) during submaximal treadmill exercise as an index of the ‘cardiorespiratory functional reserve’ and demonstrated that this was not only improved post-IMT, but that the increase in MIP accounted for 69% of the increase in OUES. The OUES is essentially an index of the rate of increase of O₂ in response to a given _E ; thus it provides an index of the efficiency with which oxygen is being taken up at the lungs, which is in turn affected by the pulmonary diffusion area and alveolar ventilation (_A). The OUES also provides an index of systemic perfusion (Baba et al, 1996). Both diffusion area and _A are impaired in patients with CHF, and both have the potential to be improved by IMT. In the case of the diffusion area, the influence of IMT upon the threshold for activation of the inspiratory muscle metaboreflex may enhance pulmonary perfusion (see the section ‘Improvements in hypoxic conditions’, above). Furthermore, data from healthy people suggest that IMT increases V_T (Romer et al, 2002a), which theoretically improves _A, by reducing V_D/ V_T. Similar changes in patients with CHF after IMT might also contribute to the improved OUES observed by Stein and colleagues (2009). These mechanistic studies provide good evidence that IMT improves exercise tolerance in patients via credible and important physiological mechanisms.

The influence of IMT upon autonomic balance has also received attention both in patients with CHF and in those with hypertension. Mello et al (2012) found that 12 weeks of IMT not only yielded significant improvements in MIP (47%), peak oxygen uptake (31%) and quality of life, but also these changes were accompanied by an increase in cardiac vagal tone (increase in the ratio of low-frequency to high-frequency components of heart rate variability (LF / HF) and a decrease in muscle sympathetic nerve activity (27%; assessed using microneurography). The influence of IMT upon sympathetic activity and arterial blood pressure (ABP) has also been examined in hypertensive patients (Ferreira et al, 2011); this randomized, placebo-controlled trial lasted 8 weeks, at the end of which the IMT group exhibited a 46% increase in MIP, which was accompanied by a significant reduction in 24-hour systolic and diastolic blood pressures of 8 mmHg and 5 mmHg, respectively. These changes appeared to be underpinned by improvements in autonomic balance as sympathetic activity was reduced significantly (increase in LF / HF). The authors speculated that this might be due to a reduction in the sympathoexcitatory input from the inspiratory muscle metaboreflex. An alternative explanation is that IMT prompted a slower, deeper breathing pattern, which has also been shown to reduce ABP in hypertensive patients, especially when combined with a small inspiratory load (Jones et al, 2010). Breathing exercises have also been shown to increase cardiac vagal tone in healthy people (Hepburn et al, 2005), which is suggestive of an ability to influence autonomic balance. The magnitude of improvements in ABP after breathing training is comparable to, or better than, those observed following exercise training (2–3 mmHg) (NICE, 2011) and pharmacotherapy (~ 13–17 mmHg) (Wright & Musini, 2009).

A recent double-blind, randomized placebo-controlled study has examined the influence of IMT upon functional balance in patients with CHF, as well as the more traditional indices of function such as exercise tolerance and dyspnoea (Bosnak-Guclu et al, 2011). The beneficial effects upon exercise, dyspnoea and quality of life were confirmed, but the study also identified a significant improvement in the Berg Balance Scale score of 1.36 units. This is consistent with the role of the respiratory muscles in postural control (Hodges & Gandevia, 2000).

A recent consensus statement from the Heart Failure Association and the European Association for Cardiovascular Prevention and Rehabilitation concluded that IMT ‘can improve exercise capacity and quality of life, particularly in those who present with inspiratory muscle weakness (IMW). Hence, routine screening for IMW is advisable and specific inspiratory muscle training in addition to standard endurance training might be beneficial’ (Piepoli et al, 2011). This recommendation is echoed by Ribeiro and colleagues in a recent review of the contribution of inspiratory muscles to exercise limitation in patients with CHF (Ribeiro et al, 2012). Perhaps the only contention in respect of current advice regarding implementation of IMT is the restriction to patients with overt inspiratory muscle weakness. The reasons for this are: (1) inspiratory muscle strength needs to be considered in the broader context of the demand / capacity relationship of the respiratory pump (see Ch. 3), and (2) if one accepts that changes to the threshold for activation of the inspiratory muscle metaboreflex contribute to functional improvements after IMT, the similarity of the changes in metaboreflex activation in patients with CHF and in healthy people (McConnell & Lomax, 2006; Chiappa et al, 2008b) supports the notion that similar mechanisms underlie functional improvements. Accordingly, since healthy people have normal inspiratory muscle function and show functional improvements following IMT, it is reasonable to suggest that IMT should also be considered for patients without overt inspiratory muscle weakness.

In summary, the strength of evidence supporting the efficacy of RMT, and in particular IMT, in patients with CHF is growing, and has now achieved a level where it is possible to recommend IMT as a stand-alone treatment. Improvements in inspiratory muscle strength, exercise capacity and dyspnoea can be expected but improvements in quality of life are less consistent. Studies examining limb blood flow and the OUES response to exercise suggest that changes to the inspiratory muscle metaboreflex response may contribute to enhancement of exercise capacity after IMT. Some studies have included only patients with inspiratory muscle weakness, giving rise to the recommendation that this be a prerequisite for IMT. However, there is no direct evidence indicating that patients with normal MIP cannot also benefit. Further research is required to build critical mass within the evidence base, as well as to evaluate the combined benefits of IMT and exercise. The influence of IMT upon autonomic nervous system balance is also worthy of further exploration. For specific recommendations regarding implementation of IMT see Chapters 5 and 6.

Neurological and neuromuscular disease

Neurological and neuromuscular diseases include conditions that affect the brain, spinal cord, nerves and muscles. Impairment can be the result of intrinsic muscle dysfunction, or arise indirectly via neurological / nerve dysfunction. The functional consequences are broadly divided into spasticity and paralysis. For simplicity, these conditions are considered collectively in this section under the terminology of neuromuscular disease (NMD), beginning with spinal cord injury.

Obesity

To date, three studies have examined the influence of RMT in patients with obesity, two of which used hyperpnoea RMT (Frank et al, 2011; Villiot-Danger et al, 2011) and one IMT (Edwards et al, 2012). The premise for the study by Frank and colleagues (2011) was that the attenuating influence of hyperpnoea RMT upon exertional dyspnoea would make exercise ‘more enjoyable’, thereby increasing spontaneous physical activity. The study had a randomized controlled design in which one group undertook just exercise plus nutrition counselling (E + N) whilst the other undertook RMT (30 minutes hyperventilation five times per week) in addition to E + N. There was a 1-month run-in period during which the RMT group trained and the control group received no intervention. This was followed by a 3-month block of supervised RMT and / or E + N, and a second 3-month block of unsupervised RMT and / or E + N. Both groups improved their 12-minute treadmill walk / run distance, but the improvement was significantly greater in the group who also received RMT (8.7% vs 3.6%). Using a case–control design, Villiot-Danger and colleagues (2011) also implemented hyperpnoea RMT (30 minutes of hyperventilation, 3–4 times per week); 10 participants underwent 26 days of inpatient dietary control and exercise plus RMT, whilst the control group received only dietary control and exercise. There were significantly larger improvements in 6-minute walk distance (54 metres, ~ 10%), dyspnoea and quality of life in the group who also received RMT. Furthermore, improvements in 6-minute walk distance were correlated significantly with improvements in respiratory muscle endurance. Finally, Edwards and colleagues (2012) examined the influence of IMT in 15 obese and overweight individuals using a randomized placebo-controlled design. The 4-week training intervention consisted of 30 breaths, twice daily at 55% of MIP. There were no changes in lung function, but the 6-minute walk distance increased significantly (62 metres ~ 20%) in the IMT group, but not in the placebo group. Interestingly, the improvement in 6-minute walk distance correlated positively both with change in MIP and with baseline body mass index.

In summary, specific recommendations regarding the use of RMT and IMT to reduce dyspnoea and improve exercise tolerance in obese people await further research. However, there is preliminary evidence that both RMT and IMT enhance exercise tolerance and reduce dyspnoea in obese individuals, a finding that is supported by a strong theoretical rationale. Accordingly, this is an area worthy of future exploration, particularly in light of the potential of RMT and IMT to enhance the ability to tolerate exercise training for weight loss.

Ageing

Normal ageing is associated with a number of changes that affect breathing, and the senescent changes to the pulmonary system have been dubbed ‘senile emphysema’ (Janssens et al, 1999). These changes impact upon the demand / capacity relationship of the respiratory muscles, which may contribute to exercise limitation via dyspnoea. Indeed, respiratory muscle strength is independently related to decline in mobility in older people (Buchman et al, 2008). Whether mobility is the chicken or the egg is unclear, but a randomized double-blind placebo-controlled trial has shown that improving inspiratory muscle function through IMT significantly increases participation in moderate-to-vigorous physical activity (Aznar-Lain et al, 2007). The latter may arise because exertional dyspnoea is lower, rendering exercise less uncomfortable.

To date, there have been only a handful of studies of resistance RMT in healthy elderly people (Copestake & McConnell, 1995; Aznar-Lain et al, 2007; Watsford & Murphy, 2008). Collectively, these studies indicate that 6–8 weeks of IMT induce consistent increases in MIP (~ 20–46%), treadmill exercise capacity (peak performance and T_lim duration) and spontaneous physical activity (measured by accelerometry), as well as reducing exertional dyspnoea. One randomized controlled trial implemented IMT + EMT (within the same breath cycle) and demonstrated significant increases in both MIP (20%) and MEP (30%) (Watsford & Murphy, 2008). In addition, the same study demonstrated that, when walking at 5.5 km·h^− 1, the heart rate, breathing effort and oxygen uptake were significantly lower in the training group. Similar reductions have also been observed in healthy young people (see the section ‘Responses to RMT in healthy people’). Finally, one randomized controlled trial has examined the effect of 8 weeks of hyperpnoea RMT (Belman & Gaesser, 1988); it observed a significant increase in maximum sustained ventilatory capacity (17%), but no significant improvement in incremental or single-stage treadmill performance, or in breathing effort during exercise.

In summary, specific recommendations regarding the use of RMT to reduce dyspnoea and improve exercise tolerance in older people await further research. However, the small number of studies to date suggest that both IMT and IMT + EMT improve a range of exercise-related outcomes in healthy elderly people, although hyperpnoea RMT does not appear to generate any benefits. The strong theoretical rationale for [strength] RMT in older people, combined with the finding of an apparent relationship between improvement in MIP and participation in moderate-to-vigorous physical activity, also supports its use as a potential means of enhancing physical functioning. The demographic shift towards an increasingly older population makes this a potentially impactful area for future research. For specific recommendations regarding implementation of IMT see Chapters 5 and 6.

Miscellaneous conditions

General conclusions

The range of conditions in which RMT has been implemented to date spans the obvious (e.g., COPD) to the unexpected (e.g., diabetes). In conditions where RMT has been implemented, the strength of evidence also varies widely, from conditions where IMT is supported by systematic reviews and meta-analyses (e.g., COPD) to those where there is currently only a theoretical rationale for assessing potential benefits (e.g., OSA). A better understanding of the load / capacity relationship of the respiratory muscles is emerging, and this is providing impetus for research to characterize and address imbalance. Furthermore, the development of a greater understanding of RMT and its potential benefits, combined with greater knowledge regarding implementation, as well as advances in training equipment, should amalgamate to stimulate further advances in RMT research and applications.

Aboussouan, L.S. Mechanisms of exercise limitation and pulmonary rehabilitation for patients with neuromuscular disease. Chron. Respir. Dis. 2009;6:231–249.

Aldrich, T.K., Uhrlass, R.M. Weaning from mechanical ventilation: successful use of modified inspiratory resistive training in muscular dystrophy. Crit. Care Med. 1987;15:247–249.

Aldrich, T.K., Karpel, J.P., Uhrlass, R.M., et al. Weaning from mechanical ventilation: adjunctive use of inspiratory muscle resistive training. Crit. Care Med. 1989;17:143–147.

Amann, M., Proctor, L.T., Sebranek, J.J., et al. Opioid-mediated muscle afferents inhibit central motor drive and limit peripheral muscle fatigue development in humans. J. Physiol. 2009;587:271–283.

Amann, M., Blain, G.M., Proctor, L.T., et al. Group III and IV muscle afferents contribute to ventilatory and cardiovascular response to rhythmic exercise in humans. J. Appl. Physiol. 2010;109:966–976.

Asher, M.I., Pardy, R.L., Coates, A.L., et al. The effects of inspiratory muscle training in patients with cystic fibrosis. Am. Rev. Respir. Dis. 1982;126:855–859.

Aznar-Lain, S., Webster, A.L., Canete, S., et al. Effects of inspiratory muscle training on exercise capacity and spontaneous physical activity in elderly subjects: a randomized controlled pilot trial. Int. J. Sports Med. 2007;28:1025–1029.

Baba, R., Nagashima, M., Goto, M., et al. Oxygen uptake efficiency slope: a new index of cardiorespiratory functional reserve derived from the relation between oxygen uptake and minute ventilation during incremental exercise. J. Am. Coll. Cardiol. 1996;28:1567–1572.

Bailey, S.J., Romer, L.M., Kelly, J., et al. Inspiratory muscle training enhances pulmonary O(2) uptake kinetics and high-intensity exercise tolerance in humans. J. Appl. Physiol. 2010;109:457–468.

Baker, S.E., Sapienza, C.M., Collins, S. Inspiratory pressure threshold training in a case of congenital bilateral abductor vocal fold paralysis. Int. J. Pediatr. Otorhinolaryngol. 2003;67:413–416.

Baker, S.E., Sapienza, C.M., Martin, D., et al. Inspiratory pressure threshold training for upper airway limitation: a case of bilateral abductor vocal fold paralysis. J. Voice. 2003;17:384–394.

Baker, S., Davenport, P., Sapienza, C. Examination of strength training and detraining effects in expiratory muscles. J. Speech Lang. Hear. Res. 2005;48:1325–1333.

Bangsbo, J., Iaia, F.M., Krustrup, P. The Yo-Yo intermittent recovery test : a useful tool for evaluation of physical performance in intermittent sports. Sports Med. 2008;38:37–51.

Barbalho-Moulim, M.C., Miguel, G.P., Forti, E.M., et al. Effects of preoperative inspiratory muscle training in obese women undergoing open bariatric surgery: respiratory muscle strength, lung volumes, and diaphragmatic excursion. Clinics. 2011;66:1721–1727.

Beckerman, M., Magadle, R., Weiner, M., et al. The effects of 1 year of specific inspiratory muscle training in patients with COPD. Chest. 2005;128:3177–3182.

Belman, M.J., Gaesser, G.A. Ventilatory muscle training in the elderly. J. Appl. Physiol. 1988;64:899–905.

Bhandari, A., Xia, Y., Cortright, R., et al. Effect of respiratory muscle training on GLUT-4 in the sheep diaphragm. Med. Sci. Sports Exerc. 2000;32:1406–1411.

Bissett, B., Leditschke, I.A. Inspiratory muscle training to enhance weaning from mechanical ventilation. Anaesth. Intensive Care. 2007;35:776–779.

Bissett, B., Leditschke, I.A., Green, M. Specific inspiratory muscle training is safe in selected patients who are ventilator-dependent: a case series. Intensive Crit. Care Nurs. 2012;28:98–104.

Bissett, B., Leditschke, I.A., Paratz, J.D., et al. Respiratory dysfunction in ventilated patients: can inspiratory muscle training help? Anaesth. Intensive Care. 2012;40:236–246.

Bosnak-Guclu, M., Arikan, H., Savci, S., et al. Effects of inspiratory muscle training in patients with heart failure. Respir. Med. 2011;105:1671–1681.

Bott, J., Blumenthal, S., Buxton, M., et al. Guidelines for the physiotherapy management of the adult, medical, spontaneously breathing patient. Thorax. 2009;64(Suppl. 1):i1–i51.

Britto, R.R., Rezende, N.R., Marinho, K.C., et al. Inspiratory muscular training in chronic stroke survivors: a randomized controlled trial. Arch. Phys. Med. Rehabil. 2011;92:184–190.

Brooks, D., O'Brien, K., Geddes, E.L., et al. Is inspiratory muscle training effective for individuals with cervical spinal cord injury? A qualitative systematic review. Clin. Rehabil. 2005;19:237–246.

Brown, P.I., Sharpe, G.R., Johnson, M.A. Inspiratory muscle training abolishes the blood lactate increase associated with volitional hyperpnoea superimposed on exercise and accelerates lactate and oxygen uptake kinetics at the onset of exercise. Eur. J. Appl. Physiol. 2011;12(6):2117–2129.

Brunherotti, M.A., Bezerra, P.P., Bachur, C.K., et al. Inspiratory muscle training in a newborn with anoxia who was chronically ventilated. Phys. Ther. 2012;92:865–871.

Buchman, A.S., Boyle, P.A., Wilson, R.S., et al. Respiratory muscle strength predicts decline in mobility in older persons. Neuroepidemiology. 2008;31:174–180.

Budweiser, S., Moertl, M., Jorres, R.A., et al. Respiratory muscle training in restrictive thoracic disease: a randomized controlled trial. Arch. Phys. Med. Rehabil. 2006;87:1559–1565.

Cader, S.A., Vale, R.G., Castro, J.C., et al. Inspiratory muscle training improves maximal inspiratory pressure and may assist weaning in older intubated patients: a randomised trial. Journal of Physiotherapy. 2010;56:171–177.

Cader, S.A., de Souza Vale, R.G., Zamora, V.E., et al. Extubation process in bed-ridden elderly intensive care patients receiving inspiratory muscle training: a randomized clinical trial. Clinical Interventions in Aging. 2012;7:437–443.

Cahalin, L.P., Semigran, M.J., Dec, G.W. Inspiratory muscle training in patients with chronic heart failure awaiting cardiac transplantation: results of a pilot clinical trial. Phys. Ther. 1997;77:830–838.

Caine, M.P., McConnell, A.K. The inspiratory muscles can be trained differentially to increase strength or endurance using a pressure threshold, inspiratory muscle training device. Eur. Respir. J. 1998;12:58–59.

Caine, M.P., McConnell, A.K. Pressure threshold inspiratory muscle training improves submaximal cycling performance. In: Sargeant A.J., Siddons H., eds. Third Annual Conference of the European College of Sport Science. Manchester: Centre for Health Care Development; 1998:101.

Callahan, L.A. Invited editorial on ‘acquired respiratory muscle weakness in critically ill patients: what is the role of mechanical ventilation-induced diaphragm dysfunction?’. J. Appl. Physiol. 2009;106:360–361.

Carlucci, A., Ceriana, P., Prinianakis, G., et al. Determinants of weaning success in patients with prolonged mechanical ventilation. Crit. Care. 2009;13:R97.

Caruso, P., Denari, S.D., Ruiz, S.A., et al. Inspiratory muscle training is ineffective in mechanically ventilated critically ill patients. Clinics. 2005;60:479–484.

Casali, C.C., Pereira, A.P., Martinez, J.A., et al. Effects of inspiratory muscle training on muscular and pulmonary function after bariatric surgery in obese patients. Obes. Surg. 2011;21:1389–1394.

Cejudo, P., Lopez-Marquez, I., Lopez-Campos, J.L., et al. Factors associated with quality of life in patients with chronic respiratory failure due to kyphoscoliosis. Disabil. Rehabil. 2009;31:928–934.

Chatham, K., Ionescu, A.A., Nixon, L.S., et al. A short-term comparison of two methods of sputum expectoration in cystic fibrosis. Eur. Respir. J. 2004;23:435–439.

Cheah, B.C., Boland, R.A., Brodaty, N.E., et al. INSPIRATIonAL – INSPIRAtory muscle training in amyotrophic lateral sclerosis. Amyotroph. Lateral Scler. 2009;10:1–9.

Cheng, S., Butler, J.E., Gandevia, S.C., et al. Movement of the human upper airway during inspiration with and without inspiratory resistive loading. J. Appl. Physiol. 2011;110:69–75.

Chiappa, G.R., Borghi-Silva, A., Ferreira, L.F., et al. Kinetics of muscle deoxygenation are accelerated at the onset of heavy-intensity exercise in patients with COPD: relationship to central cardiovascular dynamics. J. Appl. Physiol. 2008;104:1341–1350.

Chiappa, G.R., Roseguini, B.T., Vieira, P.J., et al. Inspiratory muscle training improves blood flow to resting and exercising limbs in patients with chronic heart failure. J. Am. Coll. Cardiol. 2008;51:1663–1671.

Chiappa, G.R., Queiroga, F., Jr., Meda, E., et al. Heliox improves oxygen delivery and utilization during dynamic exercise in patients with chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 2009;179:1004–1010.

Chiara, T., Martin, D., Sapienza, C. Expiratory muscle strength training: speech production outcomes in patients with multiple sclerosis. Neurorehabil. Neural Repair. 2007;21:239–249.

Conti, G., Montini, L., Pennisi, M.A., et al. A prospective, blinded evaluation of indexes proposed to predict weaning from mechanical ventilation. Intensive Care Med. 2004;30:830–836.

Copestake, A.J., McConnell, A.K. Inspiratory muscle training reduces exertional breathlessness in healthy elderly men and women. In: International Conference on Physical Activity and Health in the Elderly. Scotland: University of Sterling; 1995:150.

Correa, A.P., Ribeiro, J.P., Balzan, F.M., et al. Inspiratory muscle training in type 2 diabetes with inspiratory muscle weakness. Med. Sci. Sports Exerc. 2011;43:1135–1141.

Currell, K., Jeukendrup, A.E. Validity, reliability and sensitivity of measures of sporting performance. Sports Med. 2008;38:297–316.

Dall'Ago, P., Chiappa, G.R., Guths, H., et al. Inspiratory muscle training in patients with heart failure and inspiratory muscle weakness: a randomized trial. J. Am. Coll. Cardiol. 2006;47:757–763.

de Jong, W., van Aalderen, W.M., Kraan, J., et al. Inspiratory muscle training in patients with cystic fibrosis. Respir. Med. 2001;95:31–36.

De Jonghe, B., Bastuji-Garin, S., Durand, M.C., et al. Respiratory weakness is associated with limb weakness and delayed weaning in critical illness. Crit. Care Med. 2007;35:2007–2015.

Demoule, A., Verin, E., Montcel, S.T., et al. Short-term training-dependent plasticity of the corticospinal diaphragm control in normal humans. Respir. Physiol. Neurobiol. 2008;160:172–180.

DePalo, V.A., Parker, A.L., Al-Bilbeisi, F., et al. Respiratory muscle strength training with nonrespiratory maneuvers. J. Appl. Physiol. 2004;96:731–734.

Derrickson, J., Ciesla, N., Simpson, N., et al. A comparison of two breathing exercise programs for patients with quadriplegia. Phys. Ther. 1992;72:763–769.

Dettling, D.S., van der Schaaf, M., Blom, R.L., et al, Feasibility and effectiveness of pre-operative inspiratory muscle training in patients undergoing oesophagectomy: a pilot study. Physiother. Res. Int. 2012; doi:10.1002/pri.1524. [Apr 10. [Epub ahead of print]. Available at:].

Dickinson, J., Whyte, G., McConnell, A. Inspiratory muscle training: a simple cost-effective treatment for inspiratory stridor. Br. J. Sports Med. 2007;41:694–695. [discussion 695].

DiMarco, A.F., Kelling, J.S., DiMarco, M.S., et al. The effects of inspiratory resistive training on respiratory muscle function in patients with muscular dystrophy. Muscle Nerve. 1985;8:284–290.

Donath, J., Miller, A. Restrictive chest wall disorders. Semin. Respir. Crit. Care Med. 2009;30:275–292.

Downey, A.E., Chenoweth, L.M., Townsend, D.K., et al. Effects of inspiratory muscle training on exercise responses in normoxia and hypoxia. Respir. Physiol. Neurobiol. 2007;156:137–146.

Dronkers, J., Veldman, A., Hoberg, E., et al. Prevention of pulmonary complications after upper abdominal surgery by preoperative intensive inspiratory muscle training: a randomized controlled pilot study. Clin. Rehabil. 2008;22:134–142.

Dronkers, J.J., Lamberts, H., Reutelingsperger, I.M., et al. Preoperative therapeutic programme for elderly patients scheduled for elective abdominal oncological surgery: a randomized controlled pilot study. Clin. Rehabil. 2010;24:614–622.

Edwards, A.M., Cooke, C.B. Oxygen uptake kinetics and maximal aerobic power are unaffected by inspiratory muscle training in healthy subjects where time to exhaustion is extended. Eur. J. Appl. Physiol. 2004;93:139–144.

Edwards, A.M., Wells, C., Butterly, R. Concurrent inspiratory muscle and cardiovascular training differentially improves both perceptions of effort and 5000 m running performance compared with cardiovascular training alone. Br. J. Sports Med. 2008;42:523–527.

Edwards, A.M., Maguire, G.P., Graham, D., et al. Four weeks of inspiratory muscle training improves self-paced walking performance in overweight and obese adults: a randomised controlled trial. Journal of Obesity. 2012;2012:918202.

Enright, S., Chatham, K., Ionescu, A.A., et al. Inspiratory muscle training improves lung function and exercise capacity in adults with cystic fibrosis. Chest. 2004;126:405–411.

Enright, S.J., Unnithan, V.B., Heward, C., et al. Effect of high-intensity inspiratory muscle training on lung volumes, diaphragm thickness, and exercise capacity in subjects who are healthy. Phys. Ther. 2006;86:345–354.

Epstein, C.D., El-Mokadem, N., Peerless, J.R. Weaning older patients from long-term mechanical ventilation: a pilot study. Am. J. Respir. Crit. Care Med. 2002;11:369–377.

Ferreira, J.B., Plentz, R.D., Stein, C., et al. Inspiratory muscle training reduces blood pressure and sympathetic activity in hypertensive patients: A randomized controlled trial. Int. J. Cardiol. 2011. [Oct 8. [Epub ahead of print]].

Fitting, J.W. Respiratory muscles during ventilatory support. Eur. Respir. J. 1994;7:2223–2225.

Frank, I., Briggs, R., Spengler, C.M. Respiratory muscles, exercise performance, and health in overweight and obese subjects. Med. Sci. Sports Exerc. 2011;43:714–727.

Fregonezi, G.A., Resqueti, V.R., Guell, R., et al. Effects of 8-week, interval-based inspiratory muscle training and breathing retraining in patients with generalized myasthenia gravis. Chest. 2005;128:1524–1530.

Fry, D.K., Pfalzer, L.A., Chokshi, A.R., et al. Randomized control trial of effects of a 10-week inspiratory muscle training program on measures of pulmonary function in persons with multiple sclerosis. J. Neurol. Phys. Ther. 2007;31:162–172.

Furrer, E., Baur, S., Boutellier, U. Treatment of snoring by training of the upper airway muscles. Am. J. Respir. Crit. Care Med. 1998;157:A284.

Gandevia, S.C. Spinal and supraspinal factors in human muscle fatigue. Physiol. Rev. 2001;81:1725–1789.

Geddes, E.L., O'Brien, K., Reid, W.D., et al. Inspiratory muscle training in adults with chronic obstructive pulmonary disease: An update of a systematic review. Respir. Med. 2008;102:1715–1729.

Gething, A.D., Williams, M., Davies, B. Inspiratory resistive loading improves cycling capacity: a placebo controlled trial. Br. J. Sports Med. 2004;38:730–736.

Gomez-Fernandez, P., Sanchez Agudo, L., Calatrava, J.M., et al. Respiratory muscle weakness in uremic patients under continuous ambulatory peritoneal dialysis. Nephron. 1984;36:219–223.

Goosey-Tolfrey, V., Foden, E., Perret, C., et al. Effects of inspiratory muscle training on respiratory function and repetitive sprint performance in wheelchair basketball players. Br. J. Sports Med. 2010;44:665–668.

Gosselink, R., Kovacs, L., Ketelaer, P., et al. Respiratory muscle weakness and respiratory muscle training in severely disabled multiple sclerosis patients. Arch. Phys. Med. Rehabil. 2000;81:747–751.

Gosselink, R., De Vos, J., van den Heuvel, S.P., et al. Impact of inspiratory muscle training in patients with COPD: what is the evidence? Eur. Respir. J. 2011;37:416–425.

Gozal, D., Thiriet, P. Respiratory muscle training in neuromuscular disease: long-term effects on strength and load perception. Med. Sci. Sports Exerc. 1999;31:1522–1527.

Griffiths, L.A., McConnell, A.K. The influence of inspiratory and expiratory muscle training upon rowing performance. Eur. J. Appl. Physiol. 2007;99:457–466.

Hajghanbari, B., Yamabayashi, C., Buna, T., et al, Effects of respiratory muscle training on performance in athletes: a systematic review with meta-analyses. J. Strength Cond. Res. 2012; doi:10.1519/JSC.0b013e318269f73f. [[Epub ahead of print]. Available at:].

Heijdra, Y.F., Dekhuijzen, P.N., van Herwaarden, C.L., et al. Nocturnal saturation improves by target-flow inspiratory muscle training in patients with COPD. Am. J. Respir. Crit. Care Med. 1996;153:260–265.

Heimer, D., Brami, J., Lieberman, D., et al. Respiratory muscle performance in patients with type 1 diabetes. Diabet. Med. 1990;7:434–437.

Hennis, P.J., Meale, P.M., Grocott, M.P. Cardiopulmonary exercise testing for the evaluation of perioperative risk in non-cardiopulmonary surgery. Postgrad. Med. J. 2011;87:550–557.

Hepburn, H., Fletcher, J., Rosengarten, T.H., et al. Cardiac vagal tone, exercise performance and the effect of respiratory training. Eur. J. Appl. Physiol. 2005;94:681–689.

Hodges, P.W., Gandevia, S.C. Activation of the human diaphragm during a repetitive postural task. J. Physiol. 2000;522(pt 1):165–175.

Holm, P., Sattler, A., Fregosi, R.F. Endurance training of respiratory muscles improves cycling performance in fit young cyclists. BMC Physiol. 2004;4:9.

How, S.C., McConnell, A.K., Taylor, B.J., et al. Acute and chronic responses of the upper airway to inspiratory loading in healthy awake humans: an MRI study. Respir. Physiol. Neurobiol. 2007;157:270–280.

Hull, J., Aniapravan, R., Chan, E., et al. British Thoracic Society guideline for respiratory management of children with neuromuscular weakness. Thorax. 2012;67(Suppl. 1):i1–40.

Hulzebos, E.H., Helders, P.J., Favie, N.J., et al. Preoperative intensive inspiratory muscle training to prevent postoperative pulmonary complications in high-risk patients undergoing CABG surgery: a randomized clinical trial. J. Am. Med. Assoc. 2006;296:1851–1857.

Hulzebos, E.H., van Meeteren, N.L., van den Buijs, B.J., et al. Feasibility of preoperative inspiratory muscle training in patients undergoing coronary artery bypass surgery with a high risk of postoperative pulmonary complications: a randomized controlled pilot study. Clin. Rehabil. 2006;20:949–959.

Hulzebos, E.H., Smit, Y., Helders, P.P., van Meeteren, N.L. Preoperative physical therapy for elective cardiac surgery patients. Cochrane Database Syst, Rev 11. 2012.

Illi, S.K., Held, U., Frank, I., et al. Effect of respiratory muscle training on exercise performance in healthy individuals: a systematic review and meta-analysis. Sports Med. 2012;42:707–724.

Innocenti, F., Fabbri, A., Anichini, R., et al. Indications of reduced pulmonary function in type 1 (insulin-dependent) diabetes mellitus. Diabetes Res. Clin. Pract. 1994;25:161–168.

Inzelberg, R., Peleg, N., Nisipeanu, P., et al. Inspiratory muscle training and the perception of dyspnea in Parkinson's disease. Can. J. Neurol. Sci. 2005;32:213–217.

Jack, S., West, M., Grocott, M.P. Perioperative exercise training in elderly subjects. Best Pract. Res. Clin. Anaesthesiol. 2011;25:461–472.

Janssens, J.P., Pache, J.C., Nicod, L.P. Physiological changes in respiratory function associated with ageing. Eur. Respir. J. 1999;13:197–205.

Johnson, P.H., Cowley, A.J., Kinnear, W.J. A randomized controlled trial of inspiratory muscle training in stable chronic heart failure. Eur. Heart. J. 1998;19:1249–1253.

Johnson, M.A., Sharpe, G.R., Brown, P.I. Inspiratory muscle training improves cycling time-trial performance and anaerobic work capacity but not critical power. Eur. J. Appl. Physiol. 2007;101:761–770.

Jones, C.U., Sangthong, B., Pachirat, O. An inspiratory load enhances the antihypertensive effects of home-based training with slow deep breathing: a randomised trial. Journal of Physiotherapy. 2010;56:179–186.

Just, N., Bautin, N., Danel-Brunaud, V., et al. The Borg dyspnoea score: a relevant clinical marker of inspiratory muscle weakness in amyotrophic lateral sclerosis. Eur. Respir. J. 2010;35:353–360.

Kaminski, D.M., Schaan, B.D., da Silva, A.M., et al. Inspiratory muscle weakness is associated with autonomic cardiovascular dysfunction in patients with type 2 diabetes mellitus. Clin. Auton. Res. 2011;21:29–35.

Kang, S.W., Shin, J.C., Park, C.I., et al. Relationship between inspiratory muscle strength and cough capacity in cervical spinal cord injured patients. Spinal Cord. 2006;44:242–248.

Keens, T.G., Krastins, I.R., Wannamaker, E.M., et al. Ventilatory muscle endurance training in normal subjects and patients with cystic fibrosis. Am. Rev. Respir. Dis. 1977;116:853–860.

Kikuchi, Y., Okabe, S., Tamura, G., et al. Chemosensitivity and perception of dyspnea in patients with a history of near-fatal asthma. N. Engl. J. Med. 1994;330:1329–1334.

Kilding, A.E., Brown, S., McConnell, A.K. Inspiratory muscle training improves 100 and 200 m swimming performance. Eur. J. Appl. Physiol. 2010;108:505–511.

Kim, J., Davenport, P., Sapienza, C. Effect of expiratory muscle strength training on elderly cough function. Arch. Gerontol. Geriatr. 2008;48(3):361–366.

Klefbeck, B., Lagerstrand, L., Mattsson, E. Inspiratory muscle training in patients with prior polio who use part- time assisted ventilation. Arch. Phys. Med. Rehabil. 2000;81:1065–1071.

Klefbeck, B., Hamrah Nedjad, J. Effect of inspiratory muscle training in patients with multiple sclerosis. Arch. Phys. Med. Rehabil. 2003;84:994–999.

Kodric, M., Trevisan, R., Torregiani, C. Inspiratory muscle training for diaphragm dysfunction after cardiac surgery. J. Thorac. Cardiovasc. Surg. 2012. [(in press).].

Koessler, W., Wanke, T., Winkler, G., et al. 2 years’ experience with inspiratory muscle training in patients with neuromuscular disorders. Chest. 2001;120:765–769.

Kulkarni, S.R., Fletcher, E., McConnell, A.K., et al. Pre-operative inspiratory muscle training preserves postoperative inspiratory muscle strength following major abdominal surgery – a randomised pilot study. Ann. R. Coll. Surg. Engl. 2010;92:700–707.

Lanini, B., Gigliotti, F., Coli, C., et al. Dissociation between respiratory effort and dyspnoea in a subset of patients with stroke. Clin. Sci. (Lond.). 2002;103:467–473.

Laoutaris, I., Dritsas, A., Brown, M.D., et al. Inspiratory muscle training using an incremental endurance test alleviates dyspnea and improves functional status in patients with chronic heart failure. Eur. J. Cardiovasc. Prev. Rehabil. 2004;11:489–496.

Leddy, J.J., Limprasertkul, A., Patel, S., et al. Isocapnic hyperpnea training improves performance in competitive male runners. Eur. J. Appl. Physiol. 2007;99:665–676.

Lerman, R.M., Weiss, M.S. Progressive resistive exercise in weaning high quadriplegics from the ventilator. Paraplegia. 1987;25:130–135.

Liaw, M.Y., Lin, M.C., Cheng, P.T., et al. Resistive inspiratory muscle training: its effectiveness in patients with acute complete cervical cord injury. Arch. Phys. Med. Rehabil. 2000;81:752–756.

Liaw, M.Y., Wang, Y.H., Tsai, Y.C., et al. Inspiratory muscle training in bronchiectasis patients: a prospective randomized controlled study. Clin. Rehabil. 2011;25:524–536.

Lin, S.J., McElfresh, J., Hall, B., et al. Inspiratory muscle training in patients with heart failure: a systematic review. Cardiopulm. Phys. Ther. J. 2012;23:29–36.

Lindstedt, S.L., Reich, T.E., Keim, P., et al. Do muscles function as adaptable locomotor springs? J. Exp. Biol. 2002;205:2211–2216.

Lisboa, C., Moreno, R., Fava, M., et al. Inspiratory muscle function in patients with severe kyphoscoliosis. Am. Rev. Respir. Dis. 1985;132:48–52.

Litchke, L.G., Russian, C.J., Lloyd, L.K., et al. Effects of respiratory resistance training with a concurrent flow device on wheelchair athletes. J. Spinal Cord Med. 2008;31:65–71.

Lomax, M. Inspiratory muscle training, altitude, and arterial oxygen desaturation: a preliminary investigation. Aviat. Space Environ. Med. 2010;81:498–501.

Lomax, M., Grant, I., Corbett, J. Inspiratory muscle warm-up and inspiratory muscle training: separate and combined effects on intermittent running to exhaustion. J. Sports Sci. Med. 2011;29:563–569.

Lötters, F., van Tol, B., Kwakkel, G., et al. Effects of controlled inspiratory muscle training in patients with COPD: a meta-analysis. Eur. Respir. J. 2002;20(3):570–576.

Lougheed, M.D., Lam, M., Forkert, L., et al. Breathlessness during acute bronchoconstriction in asthma. Pathophysiologic mechanisms. Am. Rev. Respir. Dis. 1993;148:1452–1459.

Loveridge, B., Badour, M., Dubo, H. Ventilatory muscle endurance training in quadriplegia: effects on breathing pattern. Paraplegia. 1989;27:329–339.

Lykidis, C.K., White, M.J., Balanos, G.M. The pulmonary vascular response to the sustained activation of the muscle metaboreflex in man. Exp. Physiol. 2008;93:247–253.

Maat, R.C., Roksund, O.D., Olofsson, J., et al. Surgical treatment of exercise-induced laryngeal dysfunction. Eur. Arch. Otorhinolaryngol. 2007;264:401–407.

Mador, M.J., Krawza, M., Alhajhusian, A., et al. Interval training versus continuous training in patients with chronic obstructive pulmonary disease. Journal of Cardiopulmonary Rehabilitation and Prevention. 2009;29:126–132.

Magadle, R., Berar-Yanay, N., Weiner, P. The risk of hospitalization and near-fatal and fatal asthma in relation to the perception of dyspnea. Chest. 2002;121:329–333.

Mancini, D.M., Henson, D., La Manca, J., et al. Benefit of selective respiratory muscle training on exercise capacity in patients with chronic congestive heart failure. Circulation. 1995;91:320–329.

Markov, G., Spengler, C.M., Knopfli-Lenzin, C., et al. Respiratory muscle training increases cycling endurance without affecting cardiovascular responses to exercise. Eur. J. Appl. Physiol. 2001;85:233–239.

Martin, A.J., Stern, L., Yeates, J., et al. Respiratory muscle training in Duchenne muscular dystrophy. Dev. Med. Child Neurol. 1986;28:314–318.

Martin, A.D., Davenport, P.D., Franceschi, A.C., et al. Use of inspiratory muscle strength training to facilitate ventilator weaning: a series of 10 consecutive patients. Chest. 2002;122:192–196.

Martin, A.D., Smith, B.K., Davenport, P.D., et al. Inspiratory muscle strength training improves weaning outcome in failure to wean patients: a randomized trial. Crit. Care. 2011;15:R84.

Martinez, A., Lisboa, C., Jalil, J., et al. Selective training of respiratory muscles in patients with chronic heart failure. Rev. Med. Chil. 2001;129:133–139.

McConnell, A.K. Breathe strong, perform better. Champaign, IL: Human Kinetics Publishers; 2011.

McConnell, A.K., Lomax, M. The influence of inspiratory muscle work history and specific inspiratory muscle training upon human limb muscle fatigue. J. Physiol. 2006;577:445–457.

McConnell, A.K., Caine, M.P., Donovan, K.J., et al. Inspiratory muscle training improves lung function and reduces exertional dyspnoea in mild / moderate asthmatics. Clin. Sci. 1998;95:4P.

McMahon, M.E., Boutellier, U., Smith, R.M., et al. Hyperpnea training attenuates peripheral chemosensitivity and improves cycling endurance. J. Exp. Biol. 2002;205:3937–3943.

Meade, M., Guyatt, G., Cook, D., et al. Predicting success in weaning from mechanical ventilation. Chest. 2001;120:400S–424S.

Mello, P.R., Guerra, G.M., Borile, S., et al. Inspiratory muscle training reduces sympathetic nervous activity and improves inspiratory muscle weakness and quality of life in patients with chronic heart failure: a clinical trial. Journal of Cardiopulmonary Rehabilitation and Prevention. 2012;32(5):255–261.

Moodie, L., Reeve, J., Elkins, M. Inspiratory muscle training increases inspiratory muscle strength in patients weaning from mechanical ventilation: a systematic review. Journal of Physiotherapy. 2011;57:213–221.

Moran, F., Piper, A., Elborn, J.S., et al. Respiratory muscle pressures in non-CF bronchiectasis: repeatability and reliability. Chron. Respir. Dis. 2010;7:165–171.

Mota, S., Guell, R., Barreiro, E., et al. Clinical outcomes of expiratory muscle training in severe COPD patients. Respir. Med. 2007;101:516–524.

Neves, P.C., Guerra, M., Ponce, P., et al. Non-cystic fibrosis bronchiectasis. Interactive Cardiovascular and Thoracic Surgery. 2011;13(6):619–625.

Newall, C., Stockley, R.A., Hill, S.L. Exercise training and inspiratory muscle training in patients with bronchiectasis. Thorax. 2005;60:943–948.

NICE: National Clinical Guideline Centre, Hypertension: The clinical management of primary hypertension in adults. Royal College of Physicians: London, 2011. www.nice.org.uk/nicemedia/live/13561/56007/56007.pdf.

Nicks, C.R., Morgan, D.W., Fuller, D.K., et al. The influence of respiratory muscle training upon intermittent exercise performance. Int. J. Sports Med. 2009;30(1):16–21.

O'Brien, K., Geddes, E.L., Reid, W.D., et al. Inspiratory muscle training compared with other rehabilitation interventions in chronic obstructive pulmonary disease: a systematic review update. Journal of Cardiopulmonary Rehabilitation and Prevention. 2008;28:128–141.

Olgiati, R., Girr, A., Hugi, L., et al. Respiratory muscle training in multiple sclerosis: a pilot study. Schweiz. Arch. Neurol. Psychiatr. 1989;140:46–50.

Ortancil, O., Sarikaya, S., Sapmaz, P., et al. The effect(s) of a six-week home-based exercise program on the respiratory muscle and functional status in ankylosing spondylitis. J. Clin. Rheumatol. 2009;15:68–70.

Padula, C.A., Yeaw, E., Mistry, S. A home-based nurse-coached inspiratory muscle training intervention in heart failure. Appl. Nurs. Res. 2009;22:18–25.

Pellizzaro, C.O., Thome, F.S., Veronese, F.V. Effect of peripheral and respiratory muscle training on the functional capacity of hemodialysis patients. Ren. Fail. 2013;35:189–197.

Perkoff, G.T., Silber, R., Tyler, F.H., et al. Studies in disorders of muscle. XII. Myopathy due to the administration of therapeutic amounts of 17-hydroxycorticosteroids. Am. J. Med. 1959;26:891–898.

Piepoli, M.F., Conraads, V., Corra, U., et al. Exercise training in heart failure: from theory to practice. A consensus document of the Heart Failure Association and the European Association for Cardiovascular Prevention and Rehabilitation. Eur. J. Heart Fail. 2011;13:347–357.

Pinto, S., Turkman, A., Pinto, A., et al. Predicting respiratory insufficiency in amyotrophic lateral sclerosis: the role of phrenic nerve studies. Clin. Neurophysiol. 2009;120:941–946.

Pinto, S., Swash, M., de Carvalho, M. Respiratory exercise in amyotrophic lateral sclerosis. Amyotroph. Lateral Scler. 2012;13:33–43.

Plentz, R.D., Sbruzzi, G., Ribeiro, R.A., et al. Inspiratory muscle training in patients with heart failure: meta-analysis of randomized trials. Arq. Bras. Cardiol. 2012;99:762–771.

Prezant, D.J. Effect of uremia and its treatment on pulmonary function. Lung. 1990;168:1–14.

Puhan, M.A., Suarez, A., Lo Cascio, C., et al. Didgeridoo playing as alternative treatment for obstructive sleep apnoea syndrome: randomised controlled trial. BMJ. 2006;332:266–270.

Ram, F.S., Wellington, S.R., Barnes, N.C. Inspiratory muscle training for asthma. Cochrane Database Syst. Rev. 2003. [CD003792].

Ramirez-Sarmiento, A., Orozco-Levi, M., Guell, R., et al. Inspiratory muscle training in patients with chronic obstructive pulmonary disease: structural adaptation and physiologic outcomes. Am. J. Respir. Crit. Care Med. 2002;166:1491–1497.

Rassler, B., Hallebach, G., Kalischewski, P., et al. The effect of respiratory muscle endurance training in patients with myasthenia gravis. Neuromuscul. Disord. 2007;17:385–391.

Rassler, B., Marx, G., Hallebach, S., et al. Long-term respiratory muscle endurance training in patients with myasthenia gravis: first results after four months of training. Autoimmune Diseases. 2011;2011:808607.

Reid, W.D., Geddes, E.L., O'Brien, K., et al. Effects of inspiratory muscle training in cystic fibrosis: a systematic review. Clin. Rehabil. 2008;22:1003–1013.

Ribeiro, J.P., Chiappa, G.R., Callegaro, C.C. The contribution of inspiratory muscles function to exercise limitation in heart failure: pathophysiological mechanisms. Revista Brasileira de Fisioterapia. 2012;16(4):261–267.

Romer, L.M., McConnell, A.K. Specificity and reversibility of inspiratory muscle training. Med. Sci. Sports Exerc. 2003;35:237–244.

Romer, L.M., McConnell, A.K., Jones, D.A. Effects of inspiratory muscle training on time-trial performance in trained cyclists. J. Sports Sci. Med. 2002;20:547–562.

Romer, L.M., McConnell, A.K., Jones, D.A. Effects of inspiratory muscle training upon recovery time during high intensity, repetitive sprint activity. Int. J. Sports Med. 2002;23:353–360.

Romer, L.M., McConnell, A.K., Jones, D.A. Effects of inspiratory muscle training upon time trial performance in trained cyclists. J. Sports Sci. Med. 2002;20:547–562.

Romer, L.M., McConnell, A.K., Jones, D.A. Inspiratory muscle fatigue in trained cyclists: effects of inspiratory muscle training. Med. Sci. Sports Exerc. 2002;34:785–792.

Romer, L.M., Lovering, A.T., Haverkamp, H.C., et al. Effect of inspiratory muscle work on peripheral fatigue of locomotor muscles in healthy humans. J. Physiol. 2006;571:425–439.

Roth, E.J., Noll, S.F. Stroke rehabilitation. 2. Comorbidities and complications. Arch. Phys. Med. Rehabil. 1994;75:S42–S46.

Roth, E.J., Stenson, K.W., Powley, S., et al. Expiratory muscle training in spinal cord injury: a randomized controlled trial. Arch. Phys. Med. Rehabil. 2010;91:857–861.

Ruddy, B.H., Davenport, P., Baylor, J., et al. Inspiratory muscle strength training with behavioral therapy in a case of a rower with presumed exercise-induced paradoxical vocal-fold dysfunction. Int. J. Pediatr. Otorhinolaryngol. 2004;68:1327–1332.

Rutchik, A., Weissman, A.R., Almenoff, P.L., et al. Resistive inspiratory muscle training in subjects with chronic cervical spinal cord injury. Arch. Phys. Med. Rehabil. 1998;79:293–297.

Sabate, M., Rodriguez, M., Mendez, E., et al. Obstructive and restrictive pulmonary dysfunction increases disability in Parkinson disease. Arch. Phys. Med. Rehabil. 1996;77:29–34.

Sadowsky, S., Dwyer, J., Fischer, A. Failure of hyperoxic gas to alter the arterial lactate anaerobic threshold. J. Cardiopulm. Rehabil. 1995;15:114–121.

Sapienza, C.M., Davenport, P.W., Martin, A.D. Expiratory muscle training increases pressure support in high school band students. J. Voice. 2002;16:495–501.

Savci, S., Degirmenci, B., Saglam, M., et al. Short-term effects of inspiratory muscle training in coronary artery bypass graft surgery: A randomized controlled trial. Scand. Cardiovasc. J. 2011;45:286–293.

Sawyer, E.H., Clanton, T.L. Improved pulmonary function and exercise tolerance with inspiratory muscle conditioning in children with cystic fibrosis. Chest. 1993;104:1490–1497.

Sbruzzi, G., Dal Lago, P., Ribeiro, R.A., et al. Inspiratory muscle training and quality of life in patients with heart failure: systematic review of randomized trials. Int. J. Cardiol. 2012;156:120–121.

Scherer, T.A., Spengler, C.M., Owassapian, D., et al. Respiratory muscle endurance training in chronic obstructive pulmonary disease: impact on exercise capacity, dyspnea, and quality of life. Am. J. Respir. Crit. Care Med. 2000;162:1709–1714.

Schilero, G.J., Spungen, A.M., Bauman, W.A., et al. Pulmonary function and spinal cord injury. Respir. Physiol. Neurobiol. 2009;166:129–141.

Sheel, A.W., Reid, W.D., Townson, A.F., et al. Effects of exercise training and inspiratory muscle training in spinal cord injury: a systematic review. J. Spinal Cord Med. 2008;31:500–508.

Shoemaker, M.J., Donker, S., Lapoe, A. Inspiratory muscle training in patients with chronic obstructive pulmonary disease: the state of the evidence. Cardiopulmonary Physical Therapy Journal. 2009;20:5–15.

Silva, V.G., Amaral, C., Monteiro, M.B., et al. Effects of inspiratory muscle training in hemodialysis patients. Jornal Brasileiro de Nefrologia. 2011;33:62–68.

Silva Mdos, S., Martins, A.C., Cipriano, G., Jr., et al. Inspiratory training increases insulin sensitivity in elderly patients. Geriatrics and Gerontology International. 2012;12:345–351.

Smart, N.A., Giallauria, F., Dieberg, G. Efficacy of inspiratory muscle training in chronic heart failure patients: A systematic review and meta-analysis. Int. J. Cardiol. 2012. [May 3. [Epub ahead of print]].

Smeltzer, S.C., Lavietes, M.H., Cook, S.D. Expiratory training in multiple sclerosis. Arch. Phys. Med. Rehabil. 1996;77:909–912.

Smith, P.E., Coakley, J.H., Edwards, R.H. Respiratory muscle training in Duchenne muscular dystrophy. Muscle Nerve. 1988;11:784–785.

Smith, B.K., Bleiweis, M.S., Neel, C.R., et al. Inspiratory muscle strength training in infants with congenital heart disease and prolonged mechanical ventilation: a case report. Phys. Ther. 2012. [Mar 30. [Epub ahead of print]].

Sprague, S.S., Hopkins, P.D. Use of inspiratory strength training to wean six patients who were ventilator-dependent. Phys. Ther. 2003;83:171–181.

Spungen, A.M., Grimm, D.R., Lesser, M., et al. Self-reported prevalence of pulmonary symptoms in subjects with spinal cord injury. Spinal Cord. 1997;35:652–657.

Stambler, N., Charatan, M., Cedarbaum, J.M. Prognostic indicators of survival in ALS. ALS CNTF Treatment Study Group. Neurology. 1998;50:66–72.

Stein, R., Chiappa, G.R., Guths, H., et al. Inspiratory muscle training improves oxygen uptake efficiency slope in patients with chronic heart failure. Journal of Cardiopulmonary Rehabilitation and Prevention. 2009;29:392–395.

Stern, L.M., Martin, A.J., Jones, N., et al. Training inspiratory resistance in Duchenne dystrophy using adapted computer games. Dev. Med. Child Neurol. 1989;31:494–500.

Stuessi, C., Spengler, C.M., Knopfli-Lenzin, C., et al. Respiratory muscle endurance training in humans increases cycling endurance without affecting blood gas concentrations. Eur. J. Appl. Physiol. 2001;84:582–586.

Summerhill, E.M., Angov, N., Garber, C., et al. Respiratory muscle strength in the physically active elderly. Lung. 2007;185:315–320.

Sutbeyaz, S.T., Koseoglu, F., Inan, L., et al. Respiratory muscle training improves cardiopulmonary function and exercise tolerance in subjects with subacute stroke: a randomized controlled trial. Clin. Rehabil. 2010;24:240–250.

Takaso, M., Nakazawa, T., Imura, T., et al. Surgical correction of spinal deformity in patients with congenital muscular dystrophy. J. Orthop. Sci. 2010;15:493–501.

Taylor, B.J., Romer, L.M. Effect of expiratory resistive loading on inspiratory and expiratory muscle fatigue. Respir. Physiol. Neurobiol. 2009;16:164–174.

Thomas, M.J., Simpson, J., Riley, R., et al. The impact of home-based physiotherapy interventions on breathlessness during activities of daily living in severe COPD: a systematic review. Physiotherapy. 2010;96:108–119.

Tong, T.K., Fu, F.H. Effect of specific inspiratory muscle warm-up on intense intermittent run to exhaustion. Eur. J. Appl. Physiol. 2006;97:673–680.

Tong, T.K., Fu, F.H., Eston, R., et al. Chronic and acute inspiratory muscle loading augment the effect of a 6-week interval program on tolerance of high-intensity intermittent bouts of running. J. Strength Cond. Res. 2010;24(11):3041–3048.

Tong, T.K., Lin, H., McConnell, A., et al. Respiratory and locomotor muscle blood-volume and oxygenation kinetics during intense intermittent exercise. Eur. J. Sport Sci. 2012;12:321–330.

Topin, N., Matecki, S., Le Bris, S., et al. Dose-dependent effect of individualized respiratory muscle training in children with Duchenne muscular dystrophy. Neuromuscul. Disord. 2002;12:576–583.

Turner, L.A., Mickleborough, T.D., McConnell, A.K., et al. Effect of inspiratory muscle training on exercise tolerance in asthmatic individuals. Med. Sci. Sports Exerc. 2011;43:2031–2038.

Turner, L.A., Tecklenburg-Lund, S.L., Chapman, R.F., et al. Inspiratory muscle training lowers the oxygen cost of voluntary hyperpnea. J. Appl. Physiol. 2012;112:127–134.

Tzelepis, G.E., McCool, F.D., Friedman, J.H., et al. Respiratory muscle dysfunction in Parkinson's disease. Am. Rev. Respir. Dis. 1988;138:266–271.

Tzelepis, G.E., Vega, D.L., Cohen, M.E., et al. Pressure–flow specificity of inspiratory muscle training. J. Appl. Physiol. 1994;77:795–801.

Tzelepis, G.E., Kasas, V., McCool, F.D. Inspiratory muscle adaptations following pressure or flow training in humans. Eur. J. Appl. Physiol. Occup. Physiol. 1999;79:467–471.

Van Houtte, S., Vanlandewijck, Y., Gosselink, R. Respiratory muscle training in persons with spinal cord injury: a systematic review. Respir. Med. 2006;100:1886–1895.

Van Houtte, S., Vanlandewijck, Y., Kiekens, C., et al. Patients with acute spinal cord injury benefit from normocapnic hyperpnoea training. J. Rehabil. Med. 2008;40:119–125.

Verges, S., Boutellier, U., Spengler, C.M. Effect of respiratory muscle endurance training on respiratory sensations, respiratory control and exercise performance: a 15-year experience. Respir. Physiol. Neurobiol. 2008;161:16–22.

Villiot-Danger, J.C., Villiot-Danger, E., Borel, J.C., et al. Respiratory muscle endurance training in obese patients. Int. J. Obes. (Lond). 2011;35:692–699.

Vilozni, D., Bar-Yishay, E., Gur, I., et al. Computerized respiratory muscle training in children with Duchenne muscular dystrophy. Neuromuscul. Disord. 1994;4:249–255.

Vincent, K.R., Braith, R.W., Feldman, R.A., et al. Improved cardiorespiratory endurance following 6 months of resistance exercise in elderly men and women. Arch. Intern. Med. 2002;162:673–678.

Volianitis, S., McConnell, A.K., Koutedakis, Y., et al. Inspiratory muscle training improves rowing performance. Med. Sci. Sports Exerc. 2001;33:803–809.

Wanke, T., Toifl, K., Merkle, M., et al. Inspiratory muscle training in patients with Duchenne muscular dystrophy. Chest. 1994;105:475–482.

Ward, C.P., York, K.M., McCoy, J.G. Risk of obstructive sleep apnea lower in double reed wind musicians. Journal of Clinical Sleep Medicine. 2012;8:251–255.

Watsford, M., Murphy, A. The effects of respiratory-muscle training on exercise in older women. J. Aging Phys. Act. 2008;16:245–260.

Weinberg, J., Borg, J., Bevegard, S., et al. Respiratory response to exercise in postpolio patients with severe inspiratory muscle dysfunction. Arch. Phys. Med. Rehabil. 1999;80:1095–1100.

Weiner, P., Weiner, M. Inspiratory muscle training may increase peak inspiratory flow in chronic obstructive pulmonary disease. Respiration. 2006;73:151–156.

Weiner, P., Azgad, Y., Ganam, R., et al. Inspiratory muscle training in patients with bronchial asthma. Chest. 1992;102:1357–1361.

Weiner, P., Azgad, Y., Weiner, M., et al. Inspiratory muscle training during treatment with corticosteroids in humans. Chest. 1995;107:1041–1044.

Weiner, P., Ganem, R., Zamir, D., et al. Specific inspiratory muscle training in chronic hemodialysis. Harefuah. 1996;130(73–76):144.

Weiner, P., Man, A., Weiner, M., et al. The effect of incentive spirometry and inspiratory muscle training on pulmonary function after lung resection. J. Thorac. Cardiovasc. Surg. 1997;113:552–557.

Weiner, P., Gross, D., Meiner, Z., et al. Respiratory muscle training in patients with moderate to severe myasthenia gravis. Can. J. Neurol. Sci. 1998;25:236–241.

Weiner, P., Zeidan, F., Zamir, D., et al. Prophylactic inspiratory muscle training in patients undergoing coronary artery bypass graft. World J. Surg. 1998;22:427–431.

Weiner, P., Waizman, J., Magadle, R., et al. The effect of specific inspiratory muscle training on the sensation of dyspnea and exercise tolerance in patients with congestive heart failure. Clin. Cardiol. 1999;22:727–732.

Weiner, P., Berar-Yanay, N., Davidovich, A., et al. Specific inspiratory muscle training in patients with mild asthma with high consumption of inhaled beta(2)-agonists. Chest. 2000;117:722–727.

Weiner, P., Inzelberg, R., Davidovich, A., et al. Respiratory muscle performance and the Perception of dyspnea in Parkinson's disease. Can. J. Neurol. Sci. 2002;29:68–72.

Weiner, P., Magadle, R., Beckerman, M., et al. The relationship among inspiratory muscle strength, the perception of dyspnea and inhaled beta2-agonist use in patients with asthma. Can. Respir. J. 2002;9:307–312.

Weiner, P., Magadle, R., Massarwa, F., et al. Influence of gender and inspiratory muscle training on the perception of dyspnea in patients with asthma. Chest. 2002;122:197–201.

Weiner, P., Magadle, R., Beckerman, M., et al. Comparison of specific expiratory, inspiratory, and combined muscle training programs in COPD. Chest. 2003;124:1357–1364.

Weiner, P., Magadle, R., Beckerman, M., et al. Specific expiratory muscle training in COPD. Chest. 2003;124:468–473.

Wells, G.D., Plyley, M., Thomas, S., et al. Effects of concurrent inspiratory and expiratory muscle training on respiratory and exercise performance in competitive swimmers. Eur. J. Appl. Physiol. 2005;94:527–540.

West, C.R., Taylor, B.J., Campbell, I.G., et al. Effects of inspiratory muscle training in Paralympic athletes with cervical spinal cord injury. Med. Sci. Sports Exerc. 2009;41:S31–S32.

Wijnhoven, H.A., Kriegsman, D.M., Snoek, F.J., et al. Gender differences in health-related quality of life among asthma patients. J. Asthma. 2003;40:189–199.

Winkler, G., Zifko, U., Nader, A., et al. Dose-dependent effects of inspiratory muscle training in neuromuscular disorders. Muscle Nerve. 2000;23:1257–1260.

Witt, J.D., Guenette, J.A., Rupert, J.L., et al. Inspiratory muscle training attenuates the human respiratory muscle metaboreflex. J. Physiol. 2007;584:1019–1028.

Wright, J.M., Musini, V.M. First-line drugs for hypertension. Cochrane Database Sys. Rev. 2009. [CD001841].

Xiao, Y., Luo, M., Wang, J., et al. Inspiratory muscle training for the recovery of function after stroke. Cochrane Database Sys. Rev. 5, 2012. [CD009360].