Inspiratory Muscle Training Compared with Other Rehabilitation Interventions in Adults with Chronic Obstructive Pulmonary Disease: A Systematic Literature Review and Meta-Analysis

Abstract

The purpose of this systematic review was to determine the effect of inspiratory muscle training (IMT) (alone or combined with exercise and/or pulmonary rehabilitation) compared to other rehabilitation interventions such as: exercise, education, other breathing techniques or exercise and/or pulmonary rehabilitation among adults with chronic obstructive pulmonary disease (COPD). A systematic review of the literature on IMT and COPD was conducted according to the Cochrane Collaboration protocol. Inclusion criteria for the review included randomized controlled trials, published in English, comparing IMT or combined IMT and exercise/pulmonary rehabilitation with other rehabilitation interventions such as general exercise, education, other breathing techniques or exercise/pulmonary rehabilitation among adults with COPD. 274 articles were retrieved, and 16 met the inclusion criteria. Seven meta-analyses were performed that compared targeted or threshold IMT to exercise (n = 3) or to education (n = 4). Results showed significant improvements in inspiratory muscle strength and endurance, and in the dyspnea scale on a quality of life measure, for participants in the IMT versus education group. In other instances where meta-analyses could not be performed, a qualitative review was performed. IMT results in improved inspiratory muscle strength and endurance compared to education. Further trials are required to investigate the effect of IMT (or combined IMT) compared to other rehabilitation inventions for outcomes such as dyspnea, exercise tolerance, and quality of life.

Key words: :

• Respiratory muscles
• Respiratory muscle training
• Breathing exercises
• Lung diseases
• Obstructive
• Chronic obstructive pulmonary disease

Introduction

Approximately 3% of the adult North American population has chronic obstructive pulmonary disease (COPD), primarily caused by smoking [1&2]. The major pathophysiology of COPD is airflow limitation, which is worse on expiration and leads to compression of small airways, and results in an increasing volume of air becoming trapped in the lungs and in hyperinflation [1]. Persons with severe COPD have markedly increased residual volumes, resulting in changed mechanical properties for the muscles of ventilation [3]. All inspiratory muscles become shortened, and the diaphragm loses its dome shape, decreasing its range of motion, area of opposition and pumping ability [4&5]. Inspiratory muscle dysfunction is exacerbated by malnutrition, hypercapnia, hypoxemia and frequently by corticosteroid usage [4&5]. Because of the natural progression of this disorder combined with individual clinical manifestations, it is likely that the inspiratory muscles of people with COPD might be over-trained in some and under-trained in others. Inspiratory muscle weakness and/or over-use injury has been reported by several investigators [4-9].

Pulmonary rehabilitation, comprising limb muscle exercise, patient education and psychosocial support, can decrease dyspnea and improve both exercise tolerance and the sense of mastery that an individual feels over his or her symptoms [10]. Training the inspiratory muscles for patients with COPD has been described in the literature [11] and included in position papers and evidence-based guidelines from several organizations. IMT was described as being of potential benefit in two papers [4][12] however two statements [4][13] concluded that additional research was required.

Three meta-analyses of the evidence for use of IMT in patients with COPD were published over a span of 11 years and differed in their results. Smith et al. [14] demonstrated little evidence that IMT improved ventilatory muscle strength when compared with controls. Lotters et al. [15] reported that both IMT alone, and IMT in combination with a general exercise program, significantly increased inspiratory muscle strength and endurance, as well as decreased dyspnea at rest and during exercise. Salman et al. [16] assessed the effectiveness of pulmonary rehabilitation, and concluded that the 2 included trials consisting of IMT alone showed no differences between IMT and controls, as measured by walk test or a dyspnea scale. In contrast, two recent studies comparing IMT with sham were not included in any of these meta-analyses, and provide support for the usage of IMT with this population [17&18].

This systematic review was conducted to determine the effect of IMT (alone or combined with exercise and/or pulmonary rehabilitation) compared to other rehabilitation interventions such as: exercise, education, other breathing techniques or exercise and/or pulmonary rehabilitation among adults with chronic obstructive pulmonary disease (COPD). We were interested in the outcomes of inspiratory muscle strength and endurance, exercise tolerance, dyspnea and quality of life.

Our research team included physical therapists with clinical, academic, and research expertise, and a researcher with special expertise in the development of systematic reviews using the Cochrane Collaboration approach. The intended audience for this review is clinicians practicing in acute, rehabilitation and home care settings, who treat adults with COPD.

Subjects and Methods

We performed a systematic review of the literature using methods of the Cochrane Collaboration [19]. Electronic databases up to August 2003 were searched, as well as reference lists from appropriate texts and articles. We contacted authors for additional data, and hand-searched targeted journals to locate articles for inclusion.

Selection of Articles and Data Abstraction

Copies of the articles identified by the citations were reviewed individually by two reviewers to identify those trials which met the five inclusion criteria: 1) adult participants (18 years of age or older); 2) chronic obstructive pulmonary disease; 3) an inspiratory muscle training intervention; 4) a randomized comparison group which received an intervention other than sham, and 5) were published in English. Comparisons of IMT with sham IMT are outside the scope of this paper. When there was a lack of agreement between the reviewers, a third reviewer read the study and made the decision about inclusion of the trial in this review.

Inspiratory muscle training was defined as any intervention(s) aimed at training the inspiratory muscles. Modes of IMT varied and were classified as either targeted/threshold IMT, normocapneic hyperventilation IMT or “other” inspiratory resistance training IMT. Rehabilitation interventions included but were not limited to exercise and/or pulmonary rehabilitation, education or other breathing techniques. Exercise was defined as any upper or lower extremity strength or aerobic training that may or may not include components of a pulmonary rehabilitation program. Pulmonary rehabilitation was defined as exercise training for at least 4 weeks, with or without education, and with or without psychological support [3]. Education was defined as patient teaching that included the pathophysiology of COPD, along with strategies for its management. Other breathing techniques were defined as any type of breathing technique or exercise other than IMT.

Two team members extracted the relevant data from each included trial and entered it onto standardized data abstraction forms. Extracted data included the study citation, design and objectives, duration of the study, times at which outcomes were assessed, description of IMT training interventions (type of device used, frequency and intensity of training per session, strategies for exercise progression, and level of supervision), description of participants, and description of co-interventions and alternate interventions (education and general exercise). Outcomes measured in the trials included inspiratory muscle strength and endurance, exercise tolerance, dyspnea, pulmonary function and quality of life.

The methodological quality of the studies was assessed using Jadad et al. criteria [20]. We also assessed all trials for similarity of groups of participants on entry to the trial, and whether an intention-to-treat analysis was used. We did not generate an overall quality score, but have provided a table indicating methodological quality for all included studies. Consensus among reviewers was used to abstract all data. Authors were contacted if additional data were required.

Data Analysis/Meta-Analysis

Where studies were comparable, using similar participants, similar modes of IMT, similar training protocols and measurement of outcomes, we performed meta-analyses using RevMan 4.2.2 computer software (Review Manager (RevMan) [Computer program]. Version 4.2 for Windows. Oxford, England: The Cochrane Collaboration, 2002). Outcomes were analyzed as continuous outcomes using a random effects model to calculate a weighted mean difference and 95% confidence interval. We used a random effects model based on the assumption that differences among studies exist that might not be readily explained [19]. None of the outcomes were dichotomous. A p value of less than 0.05 was considered statistically significant for overall effect. A p value of less than 0.1 was considered as statistically significant for heterogeneity [21]. In instances where there was statistical significance for heterogeneity, sensitivity analyses were performed whereby studies were systematically removed from the analyses to determine robustness of findings. When sensitivity analyses were not possible because meta-analyses only included 2 studies, we attempted to explain potential reasons for heterogeneity and provide a rationale for combining or not combining the studies. In situations where meta-analyses were not possible, we report qualitative descriptions of the studies.

Results

The initial search revealed 274 articles, of which 16 met the inclusion criteria for this paper. The following subgroup comparisons were conducted: 1) IMT compared to exercise, 2) IMT compared to education, 3) IMT compared to other breathing techniques, and 4) IMT combined with exercise/pulmonary rehabilitation compared to exercise/pulmonary rehabilitation alone or with sham. Two studies included several comparison groups and are included in more than one comparison [22&23]. Characteristics of the included studies are included in Table 1.

Table 1.  Characteristics of included studies

Characteristics	Interventions compared by group	Sample size at baseline	Type of IMT device	Monitoring of breathing rate and rhythm	Time and intensity of IMT exercise	Frequency and duration of IMT exercise	Progression of IMT/supervision of IMT	Outcomes measured
Berry 1996	1) IMT + general exs	27	Threshold	NR	15% PImax, increased to 80% PImax.	2 × day	Yes/Diary	Insp muscle strength, exs capacity, dyspnea, PFT
	2) Sham IMT + exs				15 min/session	7 days/week
	3) Sham IMT + breathing and flexibility/stretch exs					12 weeks
Chen 1985	1) IMT + PR	13	Inspiratory resistance training—no target	Not monitored	Unable to calculate intensity	2 × day	No/Diary	Insp muscle strength and endurance, exs capacity
	2) Sham IMT + PR				15 min/session	7 days/week
						4 weeks
Covey 2001	1) IMT2) Education	37	Threshold	NR	30% PImax, increased to 60% PImax	1 × day	Yes/Diary and weekly visits by nurse who supervised training	Insp muscle strength and endurance, quality of life—dyspnea PFT
					30 min/session	5 days/week
						16 weeks
Dekhuijzen 1991	1) IMT + PR	40	Inspiratory resistance training—with target	Yes—metronome	70% PImax	2 × day	Yes/Supervised by PT	Insp muscle strength and endurance, exs capacity, quality of life
	2) PR				15 min/session	5 days/week
						10 weeks
Goldstein 1989	1) IMT + PR	12	Threshold	Yes—nose-clips	Unable to calculate intensity	2 × day	Yes/Supervised by respiratory therapist	Insp muscle strength exs capacity, PFT
	2) Sham IMT + PR				10 to 20 min/session	5 days/week
						4 weeks
Jones 1985	1) IMT	30	Inspiratory resistance training—no target	NR	Unable to calculate intensity	2 × day	Yes/Supervised every 2 weeks at laboratory	Exs capacity, dyspnea, PFT
	2) General exs and walking				15 min/session	7 days/week
	3) Sham IMT					10 weeks
Larson 1999	1) IMT	130	Threshold	NR	30% PImax increased to 60% PImax	1 × day	Yes/Diary and weekly visits by nurse	Insp muscle strength and endurance, exs capacity, quality of life—dyspnea and fatigue
	2) Cycle				30 min/session	5 days/week
	3) IMT + cycle					16 weeks
	4) Education
Levine 1986	1) IMT + IPPB	48	Normocapnic hyper-ventilation	Yes	Target flow rate @ 56 L/min (which is maximum sustained ventilatory capacity at baseline)	1 × day	Yes/Supervised in laboratory	Insp muscle strength and endurance, exs capacity, quality of life, PFT
	2) IPPB				15 min/session	5 days/week
						6 weeks
Minoguchi 2002	1) IMT	16	Threshold	NR	30% PImax	2 × day	No/Not supervised	Insp muscle strength, exs capacity, PFT
	2) Respiratory muscle stretch and breathing exs				10 min/session	7 days/week
						4 weeks
Noseda 1987	1) IMT	25	Inspiratory resistance training—no target	Not monitored or controlled	Unable to calculate intensity (highest intensity able to tolerate)	2 × day	Yes/Supervised by PT for first 2 weeks	Insp muscle endurance, exs capacity
	2) Respiratory muscle stretch and breathing exs				15 min/session	7 days/week
						8 weeks
Nosworthy 1992	1) IMT + ACBT	46	Threshold	NR	70% PImax or less, until able to sustain for 15 min	2 × day	Yes/Supervised by PT 3 × week, encouraged to do daily	Insp muscle strength and endurance, exs capacity
	2) Treadmill + ACBT				15 min/session	3 days/week
	3) PD + ACBT					6 weeks
Reid 1984	1) IMT	12	Inspiratory resistance training with target	Yes—metronome for rate control (16/min)	At maximum intensity tolerable	1 × day	Yes/Supervised by PT	Insp muscle strength, exs capacity, PFT
	2) Treadmill				30 min/session	5 days/week
	3) No intervention					6 weeks
Ries 1986	1) IMT + PR	18	Normocapnic hyper-ventilation	NR	15 min/session based on maximum sustainable ventilation for 15 min	3 × day	Yes/Diary	Insp muscle strength, exs capacity
	2) Walking + PR					7 days/week
						6 weeks
Sherer 2002	1) IMT	34	Normocapnic hyper-ventilation	Yes—metronome	50–60% of participant's vital capacity	2 × day	Yes/Diary	Insp muscle strength and endurance, exs capacity, dyspnea, quality of life, PFT
	2) IS with minimal resistance				15 min/session	5 days/week
						8 weeks
Wanke 1994	1) IMT + cycle	60	Threshold	Yes—metronome	80% PImax (strength) and 70% PImax (endurance)	1 × day	Yes/Supervised by PT	Insp muscle strength and endurance, exs capacity
	2) Cycle				16 min/session	7 days/week
						8 weeks
Weiner 1992	1) IMT + general exs	36	Threshold	NR	15% PImax, increased to 80% PImax	1 × day	Yes/Supervised by PT	Insp muscle strength and endurance, exs capacity, PFT
	2) Sham IMT + exs				30 min/session during cycling and rowing	3 days/week
	3) No intervention					24 weeks
	*co-intervention IMT during cycle and rowing

ACBT = active cycle of breathing training, IMT = inspiratory muscle training, insp = inspiratory, exs = exercises, IPPB = intermittent positive pressure breathing, IS = incentive spirometry, L/min = liters per minute, NR = not reported, PD = postural drainage, PI_max = maximal inspiratory pressure, PFT = pulmonary function testing, PT = physical therapist, PR = pulmonary rehabilitation.

Methodological Quality of Included Studies

A summary of the methodological quality of included studies is included in Table 2. We assumed that in 11 studies an intention-to-treat analysis was used in which subjects were analyzed in the groups to which they were assigned [23-33]. The remaining five studies [22][34-37] reported a per-protocol analysis, in which subjects who were not compliant with the intervention were excluded from the analysis (Table 2). There were no withdrawals in 4 studies [25][29][31&32]. Withdrawal rates in the other studies ranged up to 59% [22] (Table 2). The 2 most common reasons for withdrawals were health reasons (acute exacerbations of COPD and other conditions) and lack of interest or other social reasons.

Table 2.  Methodological quality of included studies

Methodological quality criteria	Study described as randomized	Method of randomization described	Were the groups similar at baseline?	Study described as double-blinded	Description of blinding	Was there description of withdrawals and dropouts?	Reasons given for withdrawals	% of withdrawals/dropouts (lost to follow-up)	Was there an intention-to-treat analysis?
Berry 1996	Yes	No	Yes	No (single-blind)	Participants—sham	Yes	Yes	7% (2/27)	Assumed
Chen 1985	Yes	NR	No. control group weighed more and had more males compared with IMT group	No (single-blind)	Participants—sham	Yes	Yes	0%	Assumed
Covey 2001	Yes	NR	Yes	No (single-blind)	Assessors of outcomes	Yes	Yes	27% (10/37)	Assumed
Dekhuijzen 1991	Yes	NR	Yes	No	NR	Yes	N/A	0%	Assumed
Goldstein 1989	Yes	NR	Yes—groups similar for 6 min walk test and sub-maximal exs test	No (single-blind)	Participants—sham	Yes	Yes	8% (1/12)	Assumed
			No—not similar for FEV1, weight
Jones 1985	Yes	Drew names from box, and allocated to group	No—Sham group had more females compared with IMT group	No (single-blind)	Participants—sham	Yes	Yes	30% (9/30)	Assumed
Larson 1999	Yes	NR	Yes	No (single-blind)	NR	Yes	Yes	59% (77/130)	No—data excluded from non-compliant subjects (per-protocol analysis)
Levine 1986	Yes	NR	Yes	No (single-blind)	Participants—sham	Yes—partly	Yes	33% (16/48)	Assumed
						No reasons given for withdrawals but subjects who completed protocol similar to those who withdrew
Minoguchi 2002	Yes	Crossover with 4 week washout	Yes	No	NR	Yes	Yes	25% (4/16)	No—data excluded from non-compliant subjects (per-protocol analysis)
Noseda 1987	Yes	NR	Yes	No	NR	Yes	Yes	20% (5/25)	Assumed
Nosworthy 1992	Yes	NR	Yes	No	NR	No	Yes	15% (7/46)	No—data excluded from non-compliant subjects (per-protocol analysis)
Reid 1984	Yes	NR	NR	No	NR	No	NR	0%	Assumed
Ries 1986	Yes	NR	No—IMT group had higher walking endurance time	No	NR	Yes	Yes	33% (6/18)	No—data excluded from non-compliant subjects (per-protocol analysis)
Sherer 2002	Yes	Yes—computer generated random table	Yes	No—single blind	Participants—sham	Yes	Yes	12% (4/34)	Assumed
Wanke 1994	Yes	NR	Yes	No	NR	Yes	Yes	30% (18/60)	No, data excluded from non-compliant subjects (per-protocol analysis)
Weiner 1992	Yes	NR	Yes	No—single blind	Participants—sham	Yes	N/A	0%	Assumed

Exs = exercises, FEV₁ = forced expired volume in 1 second, IMT = inspiratory muscle training, min = minutes, N/A = not applicable, NR = not reported.

Characteristics of Participants

All studies enrolled patients with stable COPD. Thirteen of the 16 included studies enrolled more males than females. One included only males [26] and 1 included predominantly females [36]. The mean age for subjects in most studies was between 56 and 72, however 3 included some subjects under the age of 50 years [22][31&32]. Subjects in all studies were described as moderately to severely affected by their COPD, with 1 exception that included some subjects who were mildly affected [37]. The forced expired volume in one second (FEV₁) was described as being less than 65% of predicted [22&23][27-35][37] or less than 1.3 liters [24-26][36]. Some studies included data on the FEV₁/FVC (forced vital capacity) ratio indicating mean values below 0.7 [22&23][26][28][30&31][33][35-37].

IMT Compared to Exercise

Five of the 16 included studies compared IMT with a general exercise program. The exercise in all five studies comprised lower extremity aerobic exercise, however Jones et al. [24] also included some upper extremity training.

Meta-analysis was possible for 2 studies for which there was sufficient data available and which used a similar mode of IMT (targeted/threshold) [22][25]. Reid and Warren, and Larson and colleagues compared a group of participants who trained with IMT with a group who underwent lower extremity training. Both studies included older participants with moderate to severe COPD. Reid and Warren exercised participants on a treadmill, while Larson et al. used a cycle ergometer; both used interval training. Meta-analysis of these results showed a significant improvement in exercise capacity (minute ventilation and maximal oxygen uptake) for subjects undergoing lower extremity training compared with those undergoing IMT (Table 3). There was a non-significant difference in improvement in inspiratory muscle strength (maximal inspiratory pressure [PI_max]) of 6.53 cm H₂O ( − 1.06, 14.11) favoring participants undergoing IMT versus exercise. Despite the lack of significance, the 95% confidence interval demonstrates a trend towards a favorable influence of IMT compared to exercise for inspiratory muscle strength.

Table 3.  Results of meta-analysis

Outcomes: (measures used)	Effect in favor of	Weighted main difference (natural units)	95% Confidence intervals	Number of subjects in meta-analysis
Target/Threshold IMT versus education (Larson 1999 and Covey 2001)
Inspiratory muscle strength	IMT	12.39 cm H2O	(6.16, 18.22)	N = 52
Maximal inspiratory pressure (PImax)
Inspiratory muscle endurance	IMT	14.00 cm H2O	(0.20, 17.80)	N = 52
Mouth pressure (Pm)	IMT	8.53%	(5.19, 11.86)	N = 52
Threshold loading (Pm%)
Quality of Life: CRQ dyspnea scale	IMT	4.06	(1.31, 6.80)	N = 52
Target/Threshold IMT versus exercise (Reid 1984 and Larson 1999)
Inspiratory muscle strength	IMT	6.53 cm H2O	(− 1.06, 14.11)	N = 35
Maximal inspiratory pressure (PImax)
Exercise tolerance	Exercise	6.00 L/min	(1.09, 10.9)	N = 35
(max. min ventilation) (VO2 max)	Exercise	0.19 L/min	(0.08, 0.29)	N = 35

cm H₂O = centimeters of water, CRQ = Chronic Respiratory Questionnaire, L/min = liters per minute, max = maximal, min = minute, PI_max = maximal inspiratory pressure, Pm = peak pressure, VO_{2 max} = maximal oxygen uptake.

*Indicates statistical significance p < 0.05.

Outcomes examined from the two studies that were not included in the meta-analysis are: inspiratory muscle endurance [22], quality of life [22], and pulmonary function [25]. Larson et al. [22] reported a significant increase in inspiratory muscle endurance (measured by discontinuous incremental threshold loading) in subjects in the IMT group, decreased exercise-related dyspnea among those in the exercise group, and no differences between groups in the dyspnea or fatigue scales of the Chronic Respiratory Questionnaire. Reid and Warren [25] showed significant changes in pulmonary function in both groups over time but not between groups.

Three studies were retrieved which could not be included in the meta-analysis either because insufficient data were available despite attempts to contact the author [35] or because of the use of alternative modes of IMT [24][36]. Jones and colleagues (who used a non-targeted, inspiratory resistance training mode of IMT) reported that after training, all 3 groups (IMT, sham and exercise) showed an increased maximal work capacity on a progressive exercise test [24].

Nosworthy and colleagues (who used targeted/threshold IMT combined with active cycle breathing retraining) similarly found that patients in both groups (IMT and exercise) improved on the 12-minute walk test, but those in the treadmill (exercise) group improved significantly more (p < 0.05) [35]. No differences between groups were found on other measures of exercise performance (workload, maximal oxygen uptake, maximal ventilation), inspiratory muscle endurance (maximum sustained breathing capacity) or strength (PI_max). Reis and Moser (who used normocapnic hyperventilation mode of IMT) reported that those who trained their inspiratory muscles significantly increased their inspiratory muscle strength (maximal minute ventilation) and exercise tolerance (maximum oxygen uptake) on cycle ergometer testing, while those in the walking (exercise) group improved their treadmill endurance time [36].

IMT Compared to Education

Larson et al. [22] and Covey et al. [23] compared home-based IMT with education for cohorts of patients with moderately to severely limited airflow limitation. The patients in the Covey study were more severely affected, but there were no significant differences between the 2 groups in each study [23]. Patients were excluded who had experienced a recent exacerbation, or were oxygen dependent. The IMT and educational interventions were similar in both studies that used targeted/threshold mode of IMT.

Meta-analysis of these data showed significant improvement in inspiratory muscle strength (PI_max) and endurance (peak mouth pressure and ratio of peak mouth pressure to PI_max) for patients receiving IMT compared with those receiving education (Table 3). In addition, quality of life as measured by the dyspnea scale of the Chronic Respiratory Questionnaire, was significantly improved for patients in the IMT group compared with patients in the education group (Table 3). In the meta-analysis for the dyspnea scale of the Chronic Respiratory Questionnaire, there was a positive test for heterogeneity (p = 0.02). Because 3 of the 4 meta-analyses that included these 2 studies were not significant for heterogeneity, and because a review of the 2 studies confirmed that the administration of the questionnaire was similar in both, we decided that the comparison of these 2 groups was justifiable. Meta-analysis was not possible for outcomes of exercise performance or pulmonary function.

IMT Compared to Other Breathing Techniques

Five of the sixteen studies compared IMT with another breathing technique [26-28][34][35]. Levine compared IMT combined with intermittent positive pressure breathing (IPPB) with IPPB alone [26], whereas the other 4 studies compared IMT to incentive spirometry [27], postural drainage and active cycles of breathing techniques (ACBT) [35], conventional breathing retraining [28], or respiratory muscle stretch gymnastics [34]. No meta-analyses were possible due to differences in interventions and outcomes. Four out of five of these individual studies reported improvements in inspiratory muscle strength [34], endurance [26-28], exercise capacity [27], or quality of life [27] for participants in IMT groups. Two studies [26&27] used a normocapnic hyperpnea device which was custom-designed, limiting its clinical availability. Nosworthy et al. [35], in a small study that may have been underpowered, reported no differences between groups.

IMT Combined with Exercise/Pulmonary Rehabilitation (PR) Compared to Exercise/Pulmonary Rehabilitation (PR) Alone or with Sham

Seven of the 16 included studies compared IMT combined with exercise and/or pulmonary rehabilitation with exercise and/or pulmonary rehabilitation alone [22][29][37] or with exercise and/or pulmonary rehabilitation combined with sham [30-33].

There were two potential studies to include in a meta-analysis that compared IMT combined with exercise to exercise alone [22][37]. We were unable to perform a meta-analysis on these 2 trials because the test for heterogeneity was significant (p values ranged from 0.0003 to 0.03 in 3 out of 4 meta-analysis comparisons) indicating that they could not be combined. Heterogeneity may be due to the differences in training time at each session and the duration of the interventions.

Six of these studies showed improvements either in inspiratory muscle strength [22][29][31&32][37] or endurance [22][29][31-33][37] among patients receiving IMT combined with exercise and/or pulmonary rehabilitation compared to exercise and/or pulmonary rehabilitation alone or with sham. In contrast, Berry et al. [30] reported neither increased inspiratory muscle strength nor endurance. The Threshold trainer used by Berry may have been modified to achieve higher training loads, because normally the Threshold trainer is only calibrated to 42 cm H₂O.

Discussion

Results of meta-analyses reveal potential improvements in inspiratory muscle strength and endurance for patients with COPD who engage in IMT compared to education. Results of individual studies also suggest potential benefits associated with IMT compared to other rehabilitation interventions for persons with COPD. Five trials which compared the addition of IMT to a general exercise and/or pulmonary rehabilitation program with exercise and/or pulmonary rehabilitation alone reported improved inspiratory muscle strength among subjects training with IMT [22][29][31&32][37] and 6 showed improved inspiratory endurance [22][29][31-33][37]. This indicates that for individuals with COPD, supplementing a general exercise or pulmonary rehabilitation program with IMT may improve inspiratory muscle function. Studies comparing IMT with other breathing techniques also showed improved inspiratory muscle strength [34] and endurance [26-28]. Trials comparing IMT with education showed improved inspiratory muscle strength and endurance, and dyspnea as assessed by the dyspnea scale of the Chronic Respiratory Questionnaire, among participants in the IMT group.

Of the 5 studies comparing IMT with exercise (lower extremity training), the 2 studies that were able to be included in meta-analysis showed a trend towards an improvement in inspiratory muscle strength [22][25] and endurance [22], while lower extremity training resulted in improved general exercise capacity [22][25][35&36]. Increases in maximal inspiratory pressures are the most commonly used estimates of inspiratory muscle strength whereas inspiratory muscle endurance can be estimated by using an incremental threshold loading [38-40]. There is a large normal variability of PI_max (± 40 cm H₂O) [41]. High values can preclude a diagnosis of weakness or difficulty in performing the test [42]. Learning can contribute to improved performance of PI_max. In the cited clinical trials, it is not possible to separate the contribution of improved neuromuscular recruitment, inspiratory muscle hypertrophy or learning to higher PI_max after inspiratory muscle training.

A meta-analysis of 2 trials of IMT versus education showed a significant improvement in quality of life measured by the dyspnea scale of the Chronic Respiratory Questionnaire favoring IMT [22&23]. No other studies included in this review reported improvement in dyspnea. Scherer was the only trial reporting improved quality of life (measured by the Medical Outcomes Scale—SF-36 physical scale) [27]. With these exceptions, we are unable to definitively assess whether improvements in inspiratory muscle strength and endurance result in improved quality of life or dyspnea. However, because the Chronic Respiratory Questionnaire is reliable [43], these data support the postulate that improved respiratory muscle function accompanied by decreased dyspnea as measured by the questionnaire, constitute a benefit to the patient. With one exception in which there was a change over time, but not between groups [25], there were no reported changes in measures of pulmonary function in any trials and these inspiratory training methods would not be expected to change the underlying pathology.

All 16 studies in the review trained subjects at least 5 days each week, with one exception [35]. The duration of training in all studies was between 20 to 30 minutes of continuous training, or multiple shorter sessions for debilitated individuals. Thirteen of the trials used one of the training devices (either threshold style or targeted) that allow for close monitoring of the patient's breathing rate and pattern and for progression of exercise intensity. The remaining three trials [24][28][32] used non-targeted inspiratory resistance trainers with which monitoring of the breathing is not possible and progression is unreliable. For more details on these training devices the reader is referred to the paper by Reid et al. [11]. Initial IMT intensity used in 2 studies began at 15% PI_max and progressed to 80% PI_max[30&31]. Three studies began training at an initial 70–80% PI_max [29][35][37]. In accordance with the overload principle for training, it has been suggested that an intensity of at least 30% PI_max is required to achieve a training effect [1]. A range of methods and frequency of exercise supervision was employed in these trials. Of the 16 included studies, 7 indicated that IMT was regularly supervised [25&26][29][31][33][35][37], 6 studies indicated a diary was kept by participants recording their intervention [22&23][27][30][32][36], one indicated some supervision [28] and 2 studies indicated that IMT was not supervised [24][34]. We are unable to draw conclusions from these trials about the level of supervision required because of the different modes and intensities of training employed, however the 2 studies of home-based exercise with weekly nursing visits and diaries were effective [22&23].

This study is in agreement with the meta-analysis of Lotters et al. [15], which reported that IMT alone, and IMT in conjunction with a general exercise program, significantly improves inspiratory muscle strength and endurance. In contrast to Lotters et al., we were unable to document an improvement in dyspnea. We agree with the position papers [1],[4],[12] that state that IMT is of potential benefit although, at this time, these benefits appear to be impairment-based, and that more rigorous studies are required to specifically examine the effect on quality of life and functional capacity.

The purpose of a systematic review is to assist clinicians in using the best available evidence in their decision making and provision of care. We used the criteria by Cook et al. [44] to ensure a rigorous review, including research as far back as possible. The inclusion criteria were clear and we only included studies with stable COPD. No trials were located with participants during or immediately following acute exacerbations of COPD, and none measured the effect on acute exacerbations of IMT.

Meta-analyses were limited for a number of reasons. This review is based on a small number of trials (n = 16), only 4 of which were able to be included in meta-analyses. The ability to perform meta-analyses was limited due to differences in modes of IMT, types of interventions among the comparison groups and types of outcomes assessed in the included studies. Seven meta-analyses were performed, each of which included only 2 studies totaling a sample size of either 35 or 52 participants. While meta-analyses were fraught with limited studies and small sample sizes, there is the potential to incorporate additional studies that may be identified in future updates of this review. This may strengthen the meta-analyses already performed and potentially enable new meta-analyses to be performed for other outcomes of exercise tolerance, dyspnea and quality of life.

The intent of this study was to measure the effect of IMT (alone or combined with exercise and/or pulmonary rehabilitation) on outcomes of inspiratory muscle strength and endurance, exercise tolerance, dyspnea, and quality of life. However, 5 of the included studies conducted a per-protocol analysis by excluding participants from the analysis who were non-compliant with the intervention. Hence, results must be interpreted cautiously because these studies assessed efficacy, not effectiveness of IMT. Included studies were on the average small (inception cohorts were between 12 and 130), limiting generalizability of findings and increasing the possibility of being underpowered to detect a difference when in fact one exists [24][35]. Six studies did not report statistical analyses comparing the outcomes between groups [24&25][28][31&32][35]. Lastly, individual studies were fraught with a wide range of withdrawal rates from 0–59%, suggesting that the validity of some of the included studies with high withdrawal rates may be questioned.

In summary, this systematic review of the evidence of IMT for adults with COPD demonstrated that IMT is effective in improving inspiratory muscle strength and endurance compared to education alone. Individual studies suggest the potential for benefits with IMT compared to other rehabilitation interventions such as general exercise, education or other breathing techniques. We were unable to demonstrate concomitant improvement in exercise capacity, dyspnea, or quality of life.

Acknowledgment

The authors would like to thank Joanna Gorny, research assistant, for her assistance during the early stages of this study.

Supported by the Ontario Respiratory Care Society (Ontario Lung Association). D. B. was supported by a Canadian Institutes Health Research New Investigator Award.