Respiratory Medicine (2008) 102, 1715e1729

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Inspiratory muscle training in adults with chronicobstructive pulmonary disease: An update ofa systematic review

E. Lynne Geddes a,*, Kelly O’Brien b, W. Darlene Reid c,Dina Brooks b, Jean Crowe a

a School of Rehabilitation Science, Institute of Applied Health Science, Room 403, McMaster University,1400 Main Street West, Hamilton, ON, Canada L8S 1C7b Department of Physical Therapy, University of Toronto, 500 University Avenue, Room 160,Toronto, ON, Canada M5G 1V7c Department of Physical Therapy, University of British Columbia, 617 e 828 W. 10th Avenue,Research Pavilion, VCHRI Vancouver, BC, Canada V5Z 1L8

Received 17 March 2008; accepted 8 July 2008Available online 15 August 2008

KEYWORDSRespiratory muscles;Inspiratory muscletraining;Breathing exercises;Lung diseases,obstructive;Chronic obstructivepulmonary disease;Pulmonaryrehabilitation

* Corresponding author. Tel.: þ1 905E-mail address: geddesl@mcmaste

0954-6111/$ - see front matter ª 200doi:10.1016/j.rmed.2008.07.005

Summary

The purpose was to update an original systematic review to determine the effect of inspiratorymuscle training (IMT) on inspiratory muscle strength and endurance, exercise capacity, dys-pnea and quality of life for adults with chronic obstructive pulmonary disease (COPD).

The original MEDLINE and CINAHL search to August 2003 was updated to January 2007 andEMBASE was searched from inception to January 2007. Randomized controlled trials, publishedin English, with adults with stable COPD, comparing IMT to sham IMT or no intervention, lowversus high intensity IMT, and different modes of IMT were included.

Nineteen of 274 articles in the original search met the inclusion criteria. The updated searchrevealed 17 additional articles; 6 met the inclusion criteria, all of which compared targeted,threshold or normocapneic hyperventilation IMT to sham IMT. An update of the sub-group anal-ysis comparing IMT versus sham IMT was performed with 10 studies from original review and 6from the update.

Sixteen meta-analyses are reported. Results demonstrated significant improvements ininspiratory muscle strength (PImax, PImax % predicted, peak inspiratory flow rate), inspiratorymuscle endurance (RMET, inspiratory threshold loading, MVV), exercise capacity (Vemax, BorgScore for Respiratory Effort, 6MWT), Transitional Dyspnea Index (focal score, functionalimpairment, magnitude of task, magnitude of effort), and the Chronic Respiratory DiseaseQuestionnaire (quality of life).

525 9140x27813; fax: þ1 905 524 0069.r.ca (E.L. Geddes).

8 Elsevier Ltd. All rights reserved.

1716 E.L. Geddes et al.

Results suggest that targeted, threshold or normocapneic hyperventilation IMT significantlyincreases inspiratory muscle strength and endurance, improves outcomes of exercise capacityand one measure of quality of life, and decreases dyspnea for adults with stable COPD.ª 2008 Elsevier Ltd. All rights reserved.

Introduction

Chronic obstructive pulmonary disease (COPD) is a diseaseof the small airways and lung parenchyma characterized byairflow limitation that is not fully reversible.1 BecauseCOPD commonly is associated with long-term smoking, ittends to arise in middle age1 and progresses with aging.1,2

As a result, the prevalence, morbidity and mortality ofCOPD increase with age.2

Worldwide, the prevalence of moderate (FEV1< 80%predicted) to very severe (FEV1< 30% predicted) COPD is10%.3 COPD also is associated with substantial societalburden and mortality. Using disability-adjusted life years(DALYs) as a measure of burden of disease, COPD is pro-jected to increase from the 11th leading cause of DALYs in2002 to the seventh leading cause in 2030.4 Similarly, in2002 COPD was the fifth leading cause of death and isprojected to be the fourth leading cause of death in 2030.4

Pulmonary rehabilitation is an important component inthe management of COPD. It has been shown to improveexercise capacity and health related quality of life, and toreduce breathlessness, anxiety or depression, and thefrequency and length of hospitalizations related toCOPD.1,5 Exercise training, a key component of a pulmonaryrehabilitation program, may include aerobic exercise suchas cycling or walking as well as upper and lower extremitystrength training.1,6,7

The role of inspiratory muscle training (IMT) for indi-viduals with stable COPD is unclear. The first systematicreview on IMT found little evidence to support the use ofIMT. However, given limitations in the included studies,Smith and colleagues8 recommended further research bedone. A second systematic review, published in 2002,supported the inclusion of IMT as a part of pulmonaryrehabilitation.9 A third systematic review of randomizedcontrol studies compared IMT with sham IMT or no inter-vention, low versus high intensities of IMT, and differentmodes of IMT.10 Results showed improvements in somemeasures of inspiratory muscle strength and endurance,exercise capacity, and dyspnea with individuals with COPDusing targeted or threshold type IMT compared to sham IMTor no intervention.

IMT is not routinely used or recommended.7,11,12 Neitherthe American Thoracic Society/European RespiratorySociety standards12 nor the Canadian Thoracic SocietyRecommendations for the Management of COPD7 recom-mend the incorporation of IMT into management plan. TheGlobal Initiative for Chronic Obstructive Lung Disease1

states that ‘‘respiratory muscle training is beneficial,especially when combined with general exercise training’’(p. 56) based on Level C evidence from non-randomizedtrials and observational studies.

The purpose of this article is to update the results of theoriginal systematic review conducted by Geddes et al.10

The objective was to determine the effect of IMT oninspiratory muscle strength and endurance, exercisecapacity, dyspnea and quality of life in adults with COPD.

Methods

Search strategy

A systematic review was conducted using the methods ofthe Cochrane Collaboration.13 In the original review, MED-LINE and CINAHL databases, and reference lists fromappropriate articles were searched up to August 2003.Authors were contacted for additional data and targetedjournals were hand-searched to locate articles for inclu-sion. In this update, an additional search of the literaturewas conducted from September 2003 to January 2007 usingsimilar methods to the original review. In addition, EMBASEwas searched from inception to January 2007.

Study inclusion

All articles retrieved from the updated search werereviewed independently by two reviewers (KO and DB) toidentify the studies that met the inclusion criteria of (i)randomized controlled trial or randomized cross-over trial;(ii) published in English; (iii) with adult participants 18years of age or older with a diagnosis of stable COPD; and(iv) compared IMT to sham IMT or no intervention, lowversus high intensities of IMT, and different modes of IMT. Ifthere was lack of agreement between the reviewers oninclusion, a third reviewer independently read the articleand determined study inclusion.

Types of inspiratory muscle training

IMT was defined as any intervention with the goal oftraining the inspiratory muscles. Types of IMT were classi-fied as non-targeted, targeted, threshold or normocapneichyperventilation. Sham IMT was defined as using the sametype of IMT device at an intensity of �8.3 cm H2O for nor-mocapneic individuals or �11.5 cm H2O for individuals withmoderate hypercapnia.10 These definitions are furtherexplained in the original review.10

Data abstraction

Two reviewers (LG and WDR) independently abstracted therelevant data from each included article onto standardizeddata abstraction forms. Outcomes assessed for thissystematic review included measures of inspiratory musclestrength and endurance, exercise capacity, dyspnea andquality of life. Data abstraction was confirmed between thetwo reviewers. If needed, a third reviewer confirmed any

IMT in adults with COPD: A systematic review update 1717

discrepancies or uncertainties related to the dataabstraction process (KO). Authors were contacted foradditional data or information, as necessary.

Methodological quality of the included studies wasassessed by two reviewers (LG and WDR) using the Jadadcriteria, including randomization, blinding and with-drawals.14 All studies also were assessed for similarity ofgroups of participants at baseline and whether an inten-tion-to-treat analysis was conducted. Given the absence ofa validated scoring system for assessing the true validity ofa trial, a descriptive summary of the methodological qualityfor all included studies is provided rather than generatingan overall quality score.13

Data analysis

Where studies were comparable, using similar participants,similar interventions, similar training protocols, and similaroutcome measures, meta-analyses were performed usingRevMan 4.2.2 computer software.15 Given that targeted,threshold and normocapneic hyperventilation modes of IMTall include a baseline maximum inspiratory pressure andinvolve working toward a targeted percentage of the maximalworkload, they were considered comparable for this update.

Outcomes were analyzed as continuous variables usinga random effects model to determine the weighted meandifference and 95% confidence interval (CI). There were nodichotomous outcomes in this review. A p value less than0.05 indicated statistical significance for an overall effectand a p value less than 0.1 indicated statistical significancefor heterogeneity between studies.16 In instances ofsignificant heterogeneity, sensitivity analyses were per-formed whereby studies were systematically removed fromthe analyses to determine the robustness of the results.Potential reasons for significant heterogeneity were dis-cussed and a rationale determined for whether combiningstudies made practical sense, as suggested by Lau et al.16

Results

Included studies

The search from the initial review revealed 274 articles, ofwhich 19 articles17e35 met the inclusion criteria. Ten ofthese studies compared targeted or threshold IMT to shamIMT,26e35 two studies compared IMT to no intervention,17,18

one study compared low to high intensity IMT19 and sixstudies compared non-targeted IMT to sham IMT.20e25 Thesearch for this update resulted in an additional 17 articlesof which six36e41 met the inclusion criteria. The tworeviewers (KO and DB) achieved total agreement pertainingto study inclusion for this review update. All six of thesestudies compared targeted, threshold or normocapneichyperventilation IMT to sham IMT.36e41 Hence, it waspossible to perform an update of those types of IMT versussham IMT sub-group analysis. This update focuses on theresults of the sub-group analysis comparing targeted,threshold or normocapneic hyperventilation IMT versussham IMT with 16 studies (10 from original review and 6from the update). None of these 16 studies reported a co-intervention in conjunction with IMT or sham IMT.

Targeted, threshold, or normocapneichyperventilation IMT versus sham IMT

Characteristics of the 16 included studies are provided inTable 1.26e41 Two authors were contacted for additionaldata.

Participant characteristics

Participants in the included studies were adults withmoderate to very severe COPD1,12 as shown by a mean FEV1

ranging from 24 to 54% predicted27e33,35e41 or FEV1/FVCratio of 0.33e0.39.26,34 The mean age of participants for allthe studies was between 56 and 68 years.26e41 Participantswere predominantly males26e37,39e41 with the exception ofone study that included more females.38 The mean inspi-ratory muscle strength of participants at baseline rangedfrom 42 to 72 cm H2O for the studies that reportedmeasuring PImax from residual volume28,30,36,38e41 or from35.8 to 68.5 H2O for the studies that reported measuringPImax from functional residual capacity.26,27,31e34,37

Methodological quality of included studies

All 16 included studies26e41 were described as randomizedbut only three described the randomization process: eithera random number table36,40 or a computer generatedrandom number sequence stratified for sex and severity ofairflow obstruction.37

Ten of the 16 studies were described as double-blinded in which both the participants and outcomeassessors were blind to the intervention and allocation ofparticipants within groups.29e31,33,34,36,37,39e41 One studywas assumed to be double-blinded since the assessorswere blinded to the intervention and the allocation ofparticipants within groups, and the participants wereunaware of the intervention they received due to the useof sham IMT.38 Single-blinding occurred in the remainingfive studies in which participants were unaware of theintervention they received due to the use of shamIMT.26e28,32,35

Fourteen of the 16 included studies reported on partic-ipants who withdrew from the study. Five of these 14studies reported no withdrawals.28,33,35,39,41 Withdrawalrates in the remaining nine studies ranged from 5.7 to51.1%.26,27,29e31,36e38,40 Reasons for withdrawal included:respiratory problems or exacerbations,27,29,30,38 intercur-rent illness,26,29,37 family or transportation issues,29,37

death,36,40 or other reasons, including lack of interest in theprogram.29,36,40

Thirteen of the 16 included studies reported thatcomparison groups were similar at baseline.26e29,32,33,35e41

Two studies did not report on group similarity at base-line31,34 and one study had older participants with lowerarterial oxygen in the sham group.30

Intention-to-treat analysis was performed in the threestudies that reported no withdrawals28,39,41 and was infer-red in nine studies because group participants appeared tobe analyzed based on the groups to which they were orig-inally randomized.26,31e34,36e38,40 In the remaining fourstudies, a per protocol analysis was conducted whereby

Table 1 Characteristics of studies included in the systematic review: targeted inspiratory resistive IMT or threshold IMT versus sham IMT

Study Method Sample size(N Z at baseline;W Z %withdrawal)

Patientcharacteristics(mean age inyears; % maleupon completionof study)

Severity of COPD(FEV1 % predictedor FEV1/FVC;mean pCO2 atbaseline)

Mode of IMT andsupervision

Monitoring ofbreathingpattern

Time,intensity andprogression ofIMT

Frequencyand durationof IMT

Intensity ofsham IMT(cmH2O)

Outcomes ofinterest assessed

Beckermanet al.36,a

RT; high versuslow IMT(redefined asIMT versus shamfor this review)

N Z 42;W Z 26.1%

67 Years;76% male

FEV1 42%predicted;pCO2 NR

Threshold loadtrainer e

POWERbreathe;supervised by RThduring 1st month,daily phone callsand weekly visitby RTh forremaining 11months of study

NR 15 min persession @ 15%PImax week 1;increased 5e

10% eachsession toachieve 60%PImax by endof week 4,intensity thenadjustedmonthly tomaintain 60%PImax

2� per day, 6times perweek for 12months

7 Inspiratory musclestrength, exercisecapacity, quality oflife, pulmonaryfunction tests/spirometry

Belman et al.26 RT; high versuslow IMT(redefined asIMT versus shamfor this review)

N Z 20;W Z 15.0%

64 Years; 59%male

FEV1/FVC Z 0.33;39 mmHg

Targetedinspiratoryresistancetrainer; daily logand supervisiononce per week inlab

Controlled at12.5 breathsper minute

15 min persession @ themaximumpressuretolerated

2� per day, 7days per weekfor 6 weeks

7.5e10 Inspiratory musclestrength,inspiratory muscleendurance,exercise capacity,pulmonary functiontests/spirometry

Harver et al.27 RT; IMT versussham

N Z 23;W Z 17.4%

63 Years; 84%male

FEV1 38%predicted; pCO2

NR

PFlex adapted togive targetedvisual feedback;not supervised.Biweekly phonecalls to home.

Spontaneousbreathingpattern

15 min persession @ 5e

35 cmH2O/L s.Participantsencouragedto increase toa new traininglevel (PFlexsetting) every7e10 days

2� per day,7 days perweek for 8weeks

5 cmH2O/L s Inspiratory musclestrength, dyspnea,pulmonary functiontests/spirometry

Heijdra et al.28 RT; high versuslow IMT(redefined asIMT versus shamfor this review)

N Z 20;W Z 0%

62 Years;75% male

FEV1 36%predicted;45 mmHg

Targetedinspiratoryresistancetrainer; PTchecked in onceper week withparticipants

3 sinspiration,4 s expirationmonitored bytarget ofincentivespirometry

15 min persession @ 60%PImax;intensityadjustedweekly tomaintainPImax of 60%

2� per day, 7days per weekfor 10 weeks

5.7 (10% PImax

at baseline)Inspiratory musclestrength,inspiratory muscleendurance,pulmonary functiontests/spirometry

Hill et al.37,a RT; IMT versussham

N Z 35;W Z 5.7%

68 Years;67% male

FEV1 37%predicted;pCO2 NR

Threshold loadtrainer;supervised

Spontaneousbreathingpattern

21 min persession with 7cycles of2 min at maxload tolerablefollowed by1 min rest;

1� per day, 3days per weekfor 8 weeks

6.7 (10% PImax

at baseline)Inspiratory musclestrength,inspiratory muscleendurance,exercise capacity,quality of lifepulmonary functiontests/spirometry

Kim et al.29 RT; IMT versussham

N Z 112;W Z 40.2%

65 Years;76% male

FEV1 40%predicted;42 mmHg

Threshold loadtrainer; diary andnurse calledparticipants athome to monitorprogress, providecoaching,encourageadherence

Noseclips 15e30 minper session @30% PImax;Intensityincreasedmonthly tosustain 30%PImax

1� per day, 7days per weekfor 24 weeks

‘‘Barelyperceptibleand too lightto influencestrength’’(p. 358)

Inspiratory musclestrength,inspiratory muscleendurance,exercise capacity,dyspnea

Koppers et al.38,a RT; IMT versussham

N Z 39;W Z 7.7%

56 Years;47% male

FEV1 54%predicted; pCO2

NR

Normocapnichyperpnea tubebreathingb;supervised

Noseclips andinstructed totake deepbreaths withmetronome tomax of 20breaths permin

15 min persession @ 60%MVV

2� per day, 7days per weekfor 5 weeks

3.6 (�5% PImax

at baseline)Inspiratory musclestrength,inspiratory muscleendurance,exercise capacity,quality of life,pulmonary functiontests/spirometry

Larson et al.30 RT; high versuslow IMT(redefined asIMT versus shamfor this review)

N Z 45;W Z 51.1%

63 Years;91% male

FEV1 32%predicted;41 mmHg

Threshold loadtrainer; daily logand telephonecall once perweek

NR 15 min (week1), 30 min(week 2e8) @30% PImax,progression ofintensity: NR

1� per day, 7days per weekfor 8 weeks

8 (15% PImax atbaseline)

Inspiratory musclestrength,inspiratory muscleendurance,exercise capacity,quality of life

Lisboa et al.31 RT; high versuslow IMT(redefined asIMT versus shamfor this review)

N Z 20;W Z NR

62 Years;65% male

FEV1 38%predicted;41 mmHg

Threshold loadtrainer; notsupervised

NR 30 min persession @ 30%PImax;intensityadjustedevery week toensure PImax

remained attarget level

1� per day, 6days per weekfor 10 weeks

5 (10% PImax atbaseline)

Inspiratory musclestrength, exercisecapacity, dyspnea,pulmonary functiontests/spirometry

Patessio et al.32 RT; IMT versussham

N Z 16;W Z NR

63 Years;100% male

FEV1 52%predicted;42 mmHg

Targetedinspiratoryresistance trainer(resistancetrainer withvisual feedback);not supervised

Spontaneousbreathingpattern

15 min persession @ 50%PImax,progression ofintensity NR

4� per day, 7days per weekfor 8 weeks

No inspiratoryresistance

Inspiratory musclestrength,inspiratory muscleendurance,pulmonary functiontests/spirometry

(continued on next page)

Table 1 (continued)

Study Method

Sample size(N Z at baseline;W Z %withdrawal)

Patientcharacteristics(mean age inyears; % maleupon completionof study)

Severity of COPD(FEV1 % predictedor FEV1/FVC;mean pCO2 atbaseline)

Mode of IMT andsupervision

Monitoring ofbreathingpattern

Time,intensity andprogression ofIMT

Frequencyand durationof IMT

Intensity ofsham IMT(cmH2O)

Outcomes ofinterest assessed

Sanchez-Rieraet al.33

RT; IMT versussham

N Z 20;W Z 0%

67 Years;90% male

FEV1 40%predicted; pCO2

NR

Targetedinspiratoryresistancetrainer; notsupervised

Controlled at8 breaths permin withmetronome

15 min persession @ 30%PImax;modifiedevery 6 weeksto maintain30% PImax

(target loadbegan at 6cmH20 andincreasedevery 2 minby 2 cmH20)

2� per day, 6days per weekfor 24 weeks

No inspiratoryresistance

Inspiratory musclestrength;inspiratory muscleendurance;exercise capacity;quality of life;dyspnea

Villafrancaet al.34

RT; high versuslow IMT(redefined asIMT versus shamfor this review)

N Z 20;W Z NR

62 Years;65% male

FEV1/FVC Z 0.39; pCO2

NR

Threshold loadtrainer; notsupervised

NR 15 min persession @ 30%PImax;intensityadjusted eachweek toensure PImax

remained attarget level

2� per day, 6days per weekfor 10 weeks

6.8 (10% PImax

at baseline)Inspiratory musclestrength;inspiratory muscleendurance

Ramırez-Sarmientoet al.35

RT; IMT versussham

N Z 14;W Z 0%

66 Years;100% male

FEV1 24%predicted;45 mmHg

Threshold loadtrainer;supervised bypersonnel

NR 30 min persession @ 60%maximumsustainedinspiratorypressure(SIP).Intensityadjusteddependent onparticipanttolerance

1� per day, 5days per weekfor 5 weeks

No inspiratoryresistance

Inspiratory musclestrength;inspiratory muscleendurance;exercise capacity;pulmonary functiontests/spirometry

Weiner andWeiner39,a

RT; high versuslow IMT(redefined asIMT versus shamfor this review)

N Z 28;W Z 0%

63 Years;57% male

FEV1 37%predicted; pCO2

NR

Threshold loadtrainer e

POWERbreathe;not supervised

NR 1 hses @ 15%PIm eek 1;inc ed 5e

10% chses toach e 60%PIm y endof k 4,int ty thenad edwe toma in 60%PIm

1� per day, 6days per weekfor 8 weeks

7 Inspiratory musclestrength

Weiner et al.40,a,c RT; high versuslow IMT(redefined asIMT versus shamfor this review)

N Z 32 (at 3months: time ofrandomization);W Z 34%

65 Years;82% male (atbaseline 0months)

FEV1 46%predicted; pCO2

NR

Threshold loadtrainer; dailyphone calls andonce weeklyvisits by RTh

NR 30 perses @ 60%PImad edmo ly tothe w PImax

ach ed.

1� per day, 3days per weekfor 12 months

7 Inspiratory musclestrength,inspiratory muscleendurance,dyspnea,pulmonary functiontests/spirometry

Weiner et al.41,a,d RT; high versuslow IMT(redefined asIMT versus shamfor this review).Note: this studyalso includedEMT andEMTþ IMTgroups notreported here

N Z 16;W Z 0%

62 Years; 81%males

FEV1 44%predicted; pCO2

NR

Threshold loadtrainer; notsupervised

NR 30 perses @ 15%PIm eek 1;inc ed 5e

10% chses toach e 60%PIm y endof k 4,int ty thenad edwe toma in 60%PIm

1� per day, 6days per weekfor 3 months

7 Inspiratory musclestrength,inspiratory muscleendurance,exercise capacity,dyspnea,pulmonary functiontests/spirometry

IMT e inspiratory muscle training; EMT e expiratory muscle training; N e number; % e percent; W e % withdrawal; FEV1 e forced piratory volume in 1 s; FVC e forced vital capacity; pCO2 e

arterial partial pressure of carbon dioxide; mmHg e millimeters of mercury; cmH2O e centimeters of water; RT e randomized l; @ - at; X e times; NR - not reported; PImax - maximuminspiratory pressure; MVV e maximum voluntary ventilation; min e minutes; s e second; PT e physical therapist; and RTh e res tory therapist.

a New studies included in this systematic review update.b Given targeted, threshold and normocapneic hyperventilation modes of IMT include a baseline maximum inspiratory pressu and

involve working toward a targeted workload, they were considered comparable for this update.c Based on 3e15 month data which was the duration of the IMT versus sham intervention in this study.d Only data from Specific IMT (SIMT) and sham groups are reported as they were the groups applicable to this review.

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1722 E.L. Geddes et al.

participants who were non-adherent to the interventionwere excluded from the analysis.27,29,30,35

Meta-analyses

The addition of six new studies enabled an update of thesub-group analysis that compared targeted/threshold/nor-mocapneic hyperventilation IMT to sham IMT. This resultedin 16 meta-analyses, of which nine were updated with newstudies from this update incorporated in the meta-analyses,five were entirely new (i.e. there were previously insuffi-cient studies to perform the meta-analyses with onlystudies from the original review) and two were meta-analyses that only included studies from the original review(Table 2). The results and discussion focus on theseanalyses.

Of the 16 meta-analyses performed, statistical hetero-geneity was present in 11 of the meta-analyses. Hetero-geneity may be attributed to variation between studiesrelated to the type of participants, frequency, intensity,mode and duration of the intervention and sham IMT,whether or not the intervention was supervised, anddifferences in the way outcomes were measured. Ininstances where there was statistical heterogeneity,a random effects model was used and sensitivity analysesperformed. Sensitivity analyses for each of the 11 outcomesresulted in the same conclusions for overall effectcompared with the meta-analyses that included all possiblestudies (with heterogeneity). Further, meta-analyses thatincluded all possible studies often yielded a more conser-vative estimate. Hence, meta-analyses are reported withall possible included studies in this review.

Inspiratory muscle strengthThree meta-analyses using measures of inspiratory musclestrength (maximum inspiratory pressure [PImax], PImax %predicted, peak inspiratory flow rate) were conducted(Table 2.1). This sub-group analysis was not stratified basedon level of preservation of inspiratory muscle strength. Twoof these were updates of meta-analyses included in theoriginal review and showed a significant improvement inPImax of 11.6 cm H2O (95% CI: 8.7, 14.4; p< 0.0001;n Z 330) and in PImax % predicted of 23.2% (95% CI: 11.3,35.1; p Z 0.0001; n Z 67) favouring participants in the IMTgroup compared with the sham IMT group. A new meta-analysis was conducted for peak inspiratory flow rate, andsimilarly demonstrated a significant effect favouring IMTwith an increase of 12.6 L/min (95% CI: 9.7, 15.6;p< 0.0001: n Z 45) in the IMT group compared with thesham IMT group.

Inspiratory muscle enduranceThree meta-analyses using measures of inspiratory muscleendurance (respiratory muscle endurance time [RMET],inspiratory threshold loading, maximum voluntary ventila-tion [MVV]), were conducted (Table 2.2). Two of the meta-analyses (RMET, maximal inspiratory threshold load) wereupdates of those in the original review. Results showeda significant improvement in RMET of 4.4 min (95% CI 0.7,8.2; p Z 0.02; n Z 147) and in maximal inspiratorythreshold load of 1.4 kPa (95% CI: 0.8, 1.9; p< 0.0001;n Z 143) favouring participants in the IMT group compared

with the sham IMT group. The meta-analysis conducted forMVV also demonstrated a significant effect favouring IMTwith an increase of 6.6 L/min (95% CI: 1.8, 11.3; p Z 0.007;n Z 36) in the IMT group compared with the sham IMTgroup.

Exercise capacityFive meta-analyses using measures of exercise tolerancewere performed, three of which demonstrated a significanteffect favouring IMT compared to sham (Table 2.3). Resultsshowed a significant improvement in maximum exerciseminute ventilation (Vemax) of 4.9 L/min in the IMT groupcompared with the sham IMT group (95% CI: �8.2, �1.7;p Z 0.003; n Z 40). Updated meta-analyses’ resultsdemonstrated a significant improvement in the Borg Scorefor Respiratory Effort by 1.8 points (95% CI: �2.4, �1.2;p< 0.0001; n Z 109) and significant improvement in 6-minute walk test (6MWT) distance of 32.1 m (95% CI: 11.6,52.7; p Z 0.002; n Z 103) in the IMT group compared withthe sham IMT group. Results for maximal oxygenconsumption (VO2max) and work rate maximum were bothupdated in this review but remained not significant for anoverall effect (Table 2.3).

DyspneaFour meta-analyses of the Transitional Dyspnea Index (TDI)and its subscales were performed (Table 2.4). Meta-analysisof the TDI e Focal Score was updated in this review andremained significant demonstrating an improvement of 2.6points (95% CI: 0.9, 4.2; p Z 0.002; n Z 96) with IMTcompared with sham. Three new meta-analyses were per-formed for the other TDI subscales and demonstrateda significant improvement in the Functional Impairmentscore: 0.7 points (95% CI: 0.1, 1.3; p Z 0.02; n Z 56);Magnitude of Task score: 0.7 points (95% CI: 0.5, 1.0;p< 0.0001; n Z 56;) and Magnitude of Effort score: 0.5points (95% CI: 0.2, 0.7; p< 0.0001; n Z 56) in the IMTgroup compared with the sham IMT group.

Quality of lifeNo meta-analysis for quality of life was possible in theoriginal review. In this update, both Hill et al.37 and Kop-pers et al.38 showed data for the Chronic RespiratoryDisease Questionnaire (CRQ) as an outcome measure. Meta-analysis demonstrated a significant improvement in theCRQ total score of 0.3 points (95% CI: 0.2, 0.5; p< 0.0001;n Z 69) in the IMT group compared with the sham IMT group(Table 2.5).

Discussion

For this update, six additional studies were incorporated inthe review, all of which compared targeted, threshold, ornormocapneic hyperventilation IMT to sham IMT.36e41

Hence, the update of this systematic review focused on thesub-group analysis comparing those types of IMT versussham IMT. Five of the six new studies were incorporatedinto meta-analyses. Of the 16 meta-analyses performed, 14demonstrated significant effect favouring the IMT inter-vention compared with sham. Results demonstratedsignificant improvements in three measures of inspiratorymuscle strength (PImax, PImax % predicted, peak inspiratory

Table 2 Meta-analyses results comparing targeted inspiratory resistive IMT or threshold IMT versus sham IMT

(1) Inspiratory muscle strengthPImax (cmH20)a,c

PImax (% predicted)a,c

Peak inspiratory flow rate (L/min)b

(2) Inspiratory muscle enduranceRespiratory muscle endurance time (minutes)a,c

IMT in adults with COPD: A systematic review update 1723

Inspiratory threshold loading (kPa)a,c

Maximum voluntary ventilation (MVV) (L/min)

(3) Exercise capacityMaximal oxygen consumption e VO2max (L/min)a,c

Maximum minute ventilation (Vemax) (L/min)

1724 E.L. Geddes et al.

Borg scale for respiratory effort (modified Borg scale)a,c

6-minute walk test (metres)a

Work rate maximum (Watts)a,c

(4) DyspneaTransitional dyspnea index e focal scorea,c

IMT in adults with COPD: A systematic review update 1725

Transitional dyspnea index e functional impairmentb,c

Transitional dyspnea index e magnitude of taskb,c

Transitional dyspnea index e magnitude of effortb,c

(5) Quality of lifeChronic respiratory questionnaire e total scoreb

a Updated meta-analysis from the original review performed for this update.b New meta-analysis performed for this update.c Statistically significant for heterogeneity.

1726 E.L. Geddes et al.

IMT in adults with COPD: A systematic review update 1727

flow rate), three measures of inspiratory muscle endurance(RMET, inspiratory threshold loading, MVV), three measuresof exercise capacity (Vemax, Borg Score for RespiratoryEffort, 6MWT), four TDI subscales’ scores (focal score,functional impairment, magnitude of task and magnitude ofeffort), and the CRQ. No significant difference in effect wasfound for meta-analyses of VO2max or exercise work ratemaximum.

Nine of the 16 meta-analyses were updates of thoseperformed in the original review, six of which confirmedfindings from the original review, and three that demon-strated changes in the overall effect on outcomes. The twometa-analyses for inspiratory muscle strength (PImax, PImax

%) in this update reported similar significant improvementsfavouring IMT as seen in the original review. Four otherupdated findings for outcomes of inspiratory muscleendurance (inspiratory threshold loading), exercisecapacity (VO2max, Borg Score for Respiratory Effort) anddypnea (TDI-Focal Score) also were similar to those in theoriginal review, with all but VO2max showing significantimprovements favouring IMT.

The three updated meta-analyses that changed inoverall effect on outcomes included RMET, work ratemaximum and 6MWT. Meta-analyses results for RMET in thisupdate changed from no overall effect of IMT in the originalreview (WMD: 4.11 min; 95% CI: �0.6, 8.8) to demonstratinga significant improvement with IMT compared to sham inthis updated review (WMD: 4.4 min; 95% CI: 0.7, 8.2).Updated meta-analysis results for work rate maximumchanged from a significant effect of IMT in the originalreview (WMD: 13.8 W; 95% CI: 4.2, 23.3) to demonstratingno significant overall effect with IMT compared to sham inthis updated review (WMD: 5.8 W; 95% CI: �3.8, 15.4).Finally, most notably, when studies by Hill37 and Koppers38

were added, updated meta-analysis for the 6MWT distancechanged from no significant overall effect in the originalreview to demonstrating a significant increase of 32 m (95%CI: 11.6, 52.7) in 6MWT distance among those in the IMTgroup compared with the sham IMT group.

These results provide evidence supporting the use of IMTin persons with COPD. As with the original review, the typeof IMT used is important. This update focused on targeted,threshold and normocapneic hyperventilation types of IMTas they ensure or facilitate the attainment of a trainingintensity during the training session. This is in contrast tonon-targeted inspiratory resistive trainers that do notprovide a target or means of controlling the breathingpattern to ensure a sufficient, consistent training intensity.

While these results demonstrate statistical significancefor some outcomes of inspiratory muscle strength andendurance, exercise capacity, dyspnea and quality of life,the clinical importance of these findings for persons withCOPD is less clear. For example, a change score in the CRQof 0.5 is considered to be a clinically significant smallchange, while a change of 1.0 is medium importance and of1.5 is great importance.42 The difference between the IMTand sham groups in this meta-analysis was 0.3 pointsfavouring IMT, which is less than the clinically importantchange.

The clinically important difference for 6MWT is reportedto be 54 m.43 The updated meta-analysis found an effectsize of 32 m which is below the clinically important

difference. However, the Redeilmeier study43 founda difference of 54 m for those who walked an average of350 m. In this systematic review, the average 6MWTdistance was higher for participants in both of the includedstudies. In Hill et al.,37 the baseline mean distance on the6MWT was 446 m increasing to 473 post-training in the IMTgroup. Koppers38 reported a baseline 6MWT mean distanceof 512 m improving to 535 m post-training in the IMT group.Given participants in this review walked further at base-line, further research is needed to determine whether thechange in outcome was clinically important for the 6MWT.

The clinically important difference in the TDI e FocalScore is considered to be 1.0.44 The updated meta-analysisfound an effect size of 2.6 which is 2.6 times more than theclinically important difference, suggesting a clinicallyimportant improvement in dyspnea for those in the IMTgroup compared with the sham IMT group.

Some patients with severe COPD may not be able togenerate a sufficient flow rate to ensure optimal depositionof particles using certain inhalation devices.39 Following 8weeks of training with IMT, Weiner and Weiner39 reportedthat all patients exceeded the optimal flow rate of 60 L/min required to use one particular device. A positivecorrelation was found between peak inspiratory flow rateand PImax.

39 The significant effect in the updated meta-analyses for PImax and peak inspiratory flow rate impliesthat IMT might facilitate the use of certain inhalationdevices for some patients with COPD.

Results of the review should be interpreted cautiouslyfor a variety of reasons. The sub-group analysis of thisupdate is based on a small number of trials (n Z 16) thatincluded a small number of participants (range: 14e112participants). Further, individual studies were fraught withwithdrawal rates ranging from 0 to 51%. Thus, the overallfindings among those who continued to use IMT might notreflect the general use of IMT among adults with COPD.

The ability to perform meta-analyses remained limiteddue to the breadth of outcome measures used in the trials.While incorporation of five of the six new studies into themeta-analyses strengthened the review, most meta-anal-yses included only 2e6 studies with the exception of themeta-analysis for PImax that included 13 studies. The meta-analysis for PImax did not separate studies into those whoseparticipants presented with poorer inspiratory musclestrength at baseline and those whose participants pre-sented with relatively preserved inspiratory musclestrength at baseline. Doing so may be a consideration forfuture research, where a standardized protocol is used andreported for measuring PImax and an appropriate or validcategorization of inspiratory muscle strength is identified.

Two studies included in this update followed partici-pants for 12 months36,40 compared with the 24 weekmaximum duration of studies included in original review.This enabled the ability to explore the longer-termoutcomes associated with IMT for persons with COPD.Similar to the original review, individual studies in theupdate continued to include mostly men, as such, findingsshould be interpreted cautiously with respect to womenliving with COPD. Finally, this review specifically focused onthe effect of targeted, threshold, or normocapneic hyper-ventilation IMT versus sham IMT. Results exploringthe effect of IMT (either alone or combined with exercise

1728 E.L. Geddes et al.

and/or pulmonary rehabilitation) compared with otherrehabilitation interventions is published elsewhere.45

Conclusions

Results of this systematic review update suggest that tar-geted inspiratory resistive, threshold or normocapneichyperventilation IMT significantly increases inspiratorymuscle strength and endurance, improves outcomes ofexercise capacity, one measure of quality of life anddecreases dyspnea for adults with stable COPD. However,the clinical importance of these findings remains unclear.Further research is needed to explore the impact thatdifferent training protocols (frequency, intensity andduration of IMT, supervision) may have on outcomes and todetermine the extent to which changes in outcomes asso-ciated with IMT translate into clinically importantimprovements for adults with COPD.

Conflict of interest statement

There were no known perceived or real conflict of interestsfor any of the co-authors.

Acknowledgements

This study was supported by the Ontario Respiratory CareSociety (Ontario Lung Association) and the CanadianRespiratory Health Professionals (Canadian Lung Associa-tion). Kelly O’Brien is supported by a Fellowship from theCanadian Institutes for Health Research. Dr. Dina Brookswas supported by a New Investigator Award during thisproject. None of the study sponsors had any involvement inthe study design, collection, analysis and interpretation ofdata; in the writing of the manuscript; or in the decision tosubmit the manuscript for publication.

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