systemic inflammation is now known to be an important aspect of chronic obstructive pulmonary disease ( copd ) which is able to extend its effects to the skeletal muscular structure .
even if this muscular dysfunction does not similarly involve all the peripheral muscles , available evidence suggests that respiratory muscles are almost always involved ( gosselink et al 2000 ) .
the weakness of the respiratory musculature ( with reduced strength and muscular resistance )  has significant clinical consequences for copd  ( decramer 2001 ) and this reason may partially explain the appearance of common symptoms like the effort dyspnea , hypercapnia , and reduced tolerance to physical exercise .
so far , a clinical study has demonstrated that respiratory muscle weakness is likely to increase health care resources and is correlated to reduced survival in copd ( gray - donald et al 1996 ) .
respiratory muscle dysfunction is attributed to multiple factors related to the presence and severity of copd .
indeed , intrinsic ( muscular and metabolism mass ) as well as extrinsic factors ( changes in chest wall geometry and diaphragm position , and systemic metabolic factors ) may alter respiratory muscle function ( gosselink et al 2000 ) .
the mismatch between the demand for respiratory muscle work and the capacity to meet that demand is mainly caused by dynamic hyperinflation ( dh ) produced by the incomplete emptying of the lungs during expiration .
hence , one of the most critical factors able to impair respiratory muscle function is the pulmonary hyperinflation which induces the so - called intrinsic positive end expiratory pressure ( peepi ) generating an inspiratory threshold load which accounts for a higher ventilatory demand and a reduced tolerance during exercise .
while inspiratory muscle weakness is at least partially attributed to hyperinflation ( placing the inspiratory muscles at a mechanical disadvantage ) , expiratory muscle weakness is a feature of the generalized myopathy observed in patients with copd ( decramer 2001 ) including very low lactate threshold ( gallagher 1994 ) which in turn reduces muscle oxidative enzyme activities ( whittom et al 1998 ) .
the most common forms of respiratory muscle training ( rmt ) generally include both inspiratory muscle training ( imt ) and expiratory muscle training ( emt ) component to a various extent .
imt assumes a prominent role in this type of training and the definitive role of emt is still under debate .
the positive influence of inspiratory muscle strengthening upon dyspnea is supported by observations on healthy young individuals ( volianitis et al 2001 ; romer et al 2002 ) where pressure threshold imt has also been associated with improved athletic performance .
two exhaustive meta - analyses ( smith et al 1992 ; lotters et al 2002 ) have collected available data from randomized trials focused on the effectiveness of imt in patients with copd : results have shown a compelling body of evidence in favour of such training , so far included by the joint statement from the american college of chest physicians and american association of cardiovascular and pulmonary rehabilitation committee ( accp / aacvpr ) among the recommended activities in the pulmonary rehabilitation programs ( accp / aacvpr 1997 ) . in particular , it has also been demonstrated that placing a load on the respiratory muscle during contraction is sufficient in increasing strength , thus causing a meaningful reduction of breathlessness and an increase of physical exercise ability ( lotters et al 2002 ) . additionally , a more recent trial that evaluated the 1-year effects of imt ( beckerman et al 2005 ) provides evidence that imt also decreases the use of healthcare services , which may translate into economic benefits as well .
there is still debate in regards to which is the mechanism responsible for the enhanced inspiratory muscle force output ( strength ) following imt .
some authors argue that inspiratory muscles of copd patients are already well adapted to chronic loading and do not express any adaptation in response to training .
nonetheless , a substantial increase in the proportion of type i fibers ( by 38% ) and in the size of type ii fibers ( by 21% ) of the external intercostal muscles have been found after imt ( ramirez - sarmiento et al 2002 ) .
these structural changes presumably represent adaptive effects with the genuine remodeling of inspiratory muscle structure during imt .
in contrast with the plentitude of existing data inherent to imt , the literature is still lacking in showing clinical and physiological studies related to emt .
the first and complete study that explored the efficacy of emt has shown that the change in expiratory muscle strength and endurance and the six - minute walk distance were significantly greater after emt compared with controls ; however , this advantage did not translate into any significant change in the sensation of dyspnea during daily activities ( weiner et al 2003a ) . in another study emt
has been compared with both imt and combined imt+emt , showing that there is no additional benefit in including emt to the training of the respiratory muscles ( weiner et al 2003b ) .
overall , the inclusion of a specific rmt in a typical program focused on rehabilitation of symptomatic copd is recommended .
so far , the general guideline consensus ( accp / aacvpr 1997 ) indicated that rmt should be considered in  selected patients with inspiratory muscle weakness or with ventilatory limitation during physical activity , who remain symptomatic despite optimal therapy  .
it appears obvious that providing imt in a patient with maximal inspiratory pressure ( mip ) below 60 cmh2o , can allow optimal benefits for that patient .
however , adding imt might also benefit those patients with preserved and higher inspiratory muscular abilities .
similarly , highly trained athletes with mip values above 120 cmh2o have also shown improvements in dyspnea and exercise performance ( volianitis et al 2001 ; romer et al 2002 ) .
these data support the notion that since there are no known side - effects of imt , this modality of training attenuates respiratory effort sensation irrespectively of the functional status of the inspiratory muscle .
thus it is likely that all the patients with symptomatic copd ( well - motivated patients with low response to other treatments ) can benefit from rmt . to confirm this assumption ,
the most recent consensus on pulmonary rehabilitation considers imt as an  adjunctive therapy in pulmonary rehabilitation , primarily in patients with suspected or proven respiratory muscle weakness
although , rmt is associated with intra - thoracic decompression , there are almost no side - effects associated with the training itself ( pardy et al 1988 ) .
furthermore , patients with heart failure experience no deterioration of their cardiac output during training . hence , with the exception of patients with unstable asthma and low perception of dyspnea , a history of spontaneous pneumothorax or emphysema bubbles near pleura
rmt can be delivered as an in - patient , out - patient , or domiciliary program setting , and it is typically administered and supervised by suitably trained physiotherapists . it may be implemented as a stand - alone intervention or as part of a comprehensive program of pulmonary rehabilitation .
the domiciliary setting is generally the most convenient for the patient and it usually follows a period during which patients rmt is closely supervised in an in - patient or out - patient clinic .
involvement of family members may also be beneficial as they can provide encouragement and sustain patient s motivation .
the three most common used modalities of rmt in patients with copd are based on breathing against resistive loading ( rl ) , breathing against pressure threshold loading ( ptl ) and voluntary normocapnic hyperpnea ( nh ) .
this method requires individuals to inspire or expire via a variable - diameter orifice , whereby , for a given airflow , the smaller the orifice the greater the load achieved .
although rl may improve respiratory muscle function ( aldrich and karpel 1985 ; clanton et al 1985 ) conclusions from these studies should be interpreted with caution .
a reasonable limitation of inspiratory rl is that inspiratory pressure , and consequently the training load , varies with flow rate according to a power function and not just to the orifice size ( pardy et al 1988 ) .
therefore , it is crucial that the individual s breathing pattern is monitored during training , thus allowing for the provision of a quantifiable training stimulus . in their meta - analysis on imt delivered on patients with copd , smith and coworkers ( 1992 ) concluded that the use of inspiratory rl without controlling the inspiratory flow rate fails to elicit significant improvement in inspiratory muscle function . on the other hand ,
several studies which provided feedback control of flow rate during rl resulted in effective benefits , with particular regard to strength , dyspnea and physical exercise tolerance ( harver et al 1989 ; belman and mittman 1991 ; sanchez riera et al 2001 ) .
nonetheless , such modifications require additional hardware , because of the increasing cost and complexity of this type of imt .
this technique requires individuals to produce a negative pressure sufficient to overcome the load of the device and thereby initiate inspiration .
threshold loading allows variable loading at a detectable intensity by providing near flow independent resistance to inspiration .
it has been achieved in several ways , by way of a weighted plunger ( nickerson and keens 1982 ) , a solenoid valve ( bardsley et al 1993 ) , a constant negative pressure system ( chen et al 1998 ) , or a spring - loaded poppet valve ( larson et al 1988 ; gosselink et al 1996 ; caine and mcconnell 2000 ) .
the spring characteristics are linear such that a given change in spring length results in the same change in valve opening pressure at each spring length .
the valve only opens when the inspiratory pressure generated by the patient exceeds the spring tension .
threshold loading has been shown to induce improvements in strength ( larson et al 1988 ; lotters et al 2002 ) , maximum rate of muscle shortening ( romer et al 2002 ; villafranca et al 1998 ; romer and mcconnell 2003 ) , maximum power output ( lisboa et al 1994 ; villafranca et al 1998 ; romer and mcconnell 2003 ) , and muscle endurance ( lisboa et al 1994 ; weiner et al 2004 ) . due to its flow independence
in addition , ptl using a device with a mechanical poppet valve is both portable and easy to use , with evidence of efficacy when implemented in a domiciliary setting , as well as in long - term use ( see also figure 1 ) . to cut short ,
although it appears to be as effective as rl , ptl ( probably due to its simplicity , reliability and  user - friendliness  ) has been implemented most widely , especially using the poppet valve method . to the best of our knowledge , the nh technique has been applied in very few studies ( belman and mittman 1980 ; levine et al 1986 ) .
this method requires individuals to maintain high target levels of ventilation up to 30 minutes . to prevent hypocapnia
training sessions are typically conducted 3 to 5 times per week at about 70%90% of maximal sustainable voluntary ventilation and the training effect is evaluated by monitoring the change in the time to exhaustion during either sustained or incremental isocapnic ventilation . because the complicated equipment needed to prevent hypocapnia this technique has usually been carried on in hospital facilities or research laboratory , and it has not been available for domiciliary purposes .
this method requires individuals to inspire or expire via a variable - diameter orifice , whereby , for a given airflow , the smaller the orifice the greater the load achieved .
although rl may improve respiratory muscle function ( aldrich and karpel 1985 ; clanton et al 1985 ) conclusions from these studies should be interpreted with caution .
a reasonable limitation of inspiratory rl is that inspiratory pressure , and consequently the training load , varies with flow rate according to a power function and not just to the orifice size ( pardy et al 1988 ) .
therefore , it is crucial that the individual s breathing pattern is monitored during training , thus allowing for the provision of a quantifiable training stimulus . in their meta - analysis on imt delivered on patients with copd , smith and coworkers ( 1992 ) concluded that the use of inspiratory rl without controlling the inspiratory flow rate fails to elicit significant improvement in inspiratory muscle function . on the other hand ,
several studies which provided feedback control of flow rate during rl resulted in effective benefits , with particular regard to strength , dyspnea and physical exercise tolerance ( harver et al 1989 ; belman and mittman 1991 ; sanchez riera et al 2001 ) .
nonetheless , such modifications require additional hardware , because of the increasing cost and complexity of this type of imt .
this technique requires individuals to produce a negative pressure sufficient to overcome the load of the device and thereby initiate inspiration .
threshold loading allows variable loading at a detectable intensity by providing near flow independent resistance to inspiration .
it has been achieved in several ways , by way of a weighted plunger ( nickerson and keens 1982 ) , a solenoid valve ( bardsley et al 1993 ) , a constant negative pressure system ( chen et al 1998 ) , or a spring - loaded poppet valve ( larson et al 1988 ; gosselink et al 1996 ; caine and mcconnell 2000 ) .
the spring characteristics are linear such that a given change in spring length results in the same change in valve opening pressure at each spring length .
the valve only opens when the inspiratory pressure generated by the patient exceeds the spring tension .
threshold loading has been shown to induce improvements in strength ( larson et al 1988 ; lotters et al 2002 ) , maximum rate of muscle shortening ( romer et al 2002 ; villafranca et al 1998 ; romer and mcconnell 2003 ) , maximum power output ( lisboa et al 1994 ; villafranca et al 1998 ; romer and mcconnell 2003 ) , and muscle endurance ( lisboa et al 1994 ; weiner et al 2004 ) . due to its flow independence , ptl training can be undertaken without monitoring the individual s breathing pattern .
in addition , ptl using a device with a mechanical poppet valve is both portable and easy to use , with evidence of efficacy when implemented in a domiciliary setting , as well as in long - term use ( see also figure 1 ) . to cut short , although it appears to be as effective as rl , ptl ( probably due to its simplicity , reliability and  user - friendliness  ) has been implemented most widely , especially using the poppet valve method .
to the best of our knowledge , the nh technique has been applied in very few studies ( belman and mittman 1980 ; levine et al 1986 ) .
this method requires individuals to maintain high target levels of ventilation up to 30 minutes . to prevent hypocapnia
training sessions are typically conducted 3 to 5 times per week at about 70%90% of maximal sustainable voluntary ventilation and the training effect is evaluated by monitoring the change in the time to exhaustion during either sustained or incremental isocapnic ventilation . because the complicated equipment needed to prevent hypocapnia this technique has usually been carried on in hospital facilities or research laboratory , and it has not been available for domiciliary purposes .
interpretation of the data relating to rmt in patients with copd has been hampered by some studies with inadequate experimental designs ; flaws have often included a failure to apply basic training theories .
the negative outcomes of most studies contributed to early scepticism about the value of rmt .
however , in the overall assessment of the respiratory muscle training it is also important to consider both physiological ( eg , respiratory muscle strength and lung function ) and clinical responses ( eg , individual s dyspnea , exercise tolerance , and even quality of life ) . from the individual s functional ability , the efficacy of rmt needs to be assessed in terms of inspiratory and expiratory muscle function .
the most straight - forward non - invasive assessment of respiratory muscle function are mip and maximal expiratory pressure ( mep ) .
these measures are indicative for weakness of the respiratory muscles and are indirectly assessed through the maximal and voluntary pressure generated during inspiration or expiration . to confirm the importance of the appraisal of the respiratory muscle function measurements there are updated documents in recent literature clarifying these aspects ( ats / ers 2002 ; troosters et al 2005 ) .
an argument favoring the use of mip is that this functional improvement is linked to changes in dyspnea ; additionally , it has been clearly defined that changes in dyspnea only occur when training results in improved muscle strength .
this has been so far recognized in clinical trials ( harver et al 1989 ; lisboa et al 1994 ) .
regular monitoring of mip also provides both reassurance that patients are adhering to the prescribed training regimen , and the basis for resetting training loads : ideally , monitoring should be undertaken once per week .
it is notable that a significant positive relationship exists between the percentage increase in mip and the relative magnitude of the imt load ( pardy and rochester 1992 ) , thus suggesting that the higher the load relative to the subject s inspiratory muscle strength , the greater is the increase in strength achieved .
the existing data suggest that to achieve a 20% increase in mip , a load of 30% mip is then required ( lotters et al 2002 ) . the lack of effectiveness of training at a load < 30% of mip is supported by previous observation ( presseur et al 1994 ) showing that mip failed to improve significantly after 12 weeks of imt at a load equal to 22% of mip .
reid has recommended the following parameters for imt in copd : an initial training interval as short as 35 min , progressing to two 15 min or one 30 min session per day , 46 days per week at a training intensity of 40%70% mip indefinitely ( reid et al 2004 ) . finally , more recent studies ( sturdy et al 2003 ; hill et al 2006 ) have examined the feasibility of using high - intensity , interval - based threshold loading imt ( a total of about 20 minutes alternating cycles of 2-minutes of breathing at the maximum load tolerable , followed by 1 minute of rest ) .
the results regarding duration of mip s improvements have been studied in only one randomized trial of imt ( weiner et al 2004 ) : in this study the largest improvement of mip has been recorded during the first 3 months of their study ( 32% ) , then followed by a smaller increase ( ~6% ) in the four subsequent 3-month blocks of imt .
the early plateau effect of imt has been observed so far in pathology ( larson et al 1988 ; lisboa et al 1997 ) as well as in healthy individuals .
the development of a plateau can not be ascribed to a lack of load progression ( increasing the training load to accommodate increases in mip ) , since it occurs regardless of this measure .
instead , it is a reflection of a basic property of muscle adaptation to strength training stimuli , which necessitates periodic changes in the training stimulus in order to maintain the adaptation process . despite the now overwhelming evidence that rmt , and particularly imt using threshold loading , produces improvements in inspiratory muscle function , which in turn result in functional benefits to copd patients
, some researchers still ascribe these improvements to mechanisms other than an adaptation to a training stimulus .
ramirez - sarmiento and coworkers ( 2002 ) observed a significant increase in the size of type 2 muscle fibres taking biopsies from the external intercostals muscles following 5-week imt ; this is very strong evidence that imt induces genuine remodeling of inspiratory muscles .
assessments of individual s functional capacity ( in terms of 6-minute or 12-minute walked distance ) and dyspnea ( bdi , tdi ) are measures often associated with respiratory muscle strength recording .
the effect of rmt by isocapnic hyperpnea in copd patients has been translated into benefits of both respiratory muscle endurance and exercise tolerance , concluding that  respiratory muscle endurance training  improves health - related quality of life 
similar findings have been obtained using a target - flow incentive spirometry system to train the inspiratory muscles , thus showing a significant increase of the distance walked at 6 months with respect to controls ( sanchez riera et al 2001 ) .
the benefits of rmt to respiratory breathlessness , exercise tolerance and quality of life were confirmed in a recent published study of rmt by threshold loading method in severely impaired copd patients ( covey et al 2001 ) .
the improvements in inspiratory muscle strength and endurance , paralleled the reduction in the sense of respiratory effort experienced during a loaded breathing task and in the respiratory symptoms associated with activities of daily living .
these respiratory muscle function benefits have also been recently confirmed in terms of 6-minute walked distance and quality of life by using a high - intensity , interval - based threshold loading imt ( hill et al 2006 ) .
like other skeletal muscles , respiratory muscles undergo adaptation in response to stimuli overload during exercise training in stable copd patients , thus resulting in significant increases of strength and endurance and in a clinically significant change of dyspnea sensation at rest and during exercise .
three types of rmt have been reported , ( resistive training , pressure threshold loading , and normocapnic hyperpnea ) with no data , at present , to support one method over the other . for a training effect , the frequency , duration , and intensity of exercise must be considered .
a number of factors are associated with successful outcomes after rmt ; a training frequency of 12 times per day for a total amount of 30 minutes , with a frequency of 35 days per week for a duration of 6 weeks has been suggested and may induce desired changes . with concern to the inspiratory load ,
the evidence supports the use of training loads that exceed 30% of mip with a repetition duration dependent upon the load , as higher loads can not be sustained as long as lower loads . while it seems that imt is slightly superior to emt in providing additional benefit other than respiratory muscle function such as a reduction in dyspnea , the effects and the safety of emt in patients with copd is yet to be elucidated .
therefore , actual evidence for rmt , in addition to regular exercise training in stable copd patients with or without respiratory muscle weakness , needs to be further implemented .
 it is known that respiratory muscles undergo adaptation in response to overload stimuli during exercise training in stable copd patients , thus resulting in significant increase of respiratory muscle function as well as the individual s improvements . 
 the present article reviews the most updated evidence with regard to the use of respiratory muscle training ( rmt ) methods in copd patients . 
 basically , three types of rmt ( resistive training , pressure threshold loading , and normocapnic hyperpnea ) have been reported . 
 frequency , duration , and intensity of exercise must be carefully considered for a training effect . 
 in contrast with the plentitude of existing data inherent to inspiratory muscle training ( imt ) , literature is still lacking in showing clinical and physiological studies related to expiratory muscle training ( emt ) . 
 in particular , while it seems that imt is slightly superior to emt in providing additional benefits other than respiratory muscle function such as a reduction in dyspnea , both the effects and the safety of emt is still to be definitively elucidated in patients with copd . 
Rationale
Patient selection
Techniques
Resistive loading
Pressure threshold loading
Voluntary normocapnic hyperpnea
Outcomes
Conclusions and clinical implications