The Efficacy of Therapeutic Respiratory Muscle Training Interventions in People with Bronchiectasis: A Systematic Review and Meta-Analysis

Journal of Clinical Medicine Review The Efficacy of Therapeutic Respiratory Muscle Training Interventions in People with Bronchiectasis: A Systematic Review and Meta-Analysis Rocio Martín-Valero 1,* , Ana Maria Jimenez-Cebrian 2, Jose A Moral-Munoz 3,4 , Maria de-la-Casa-Almeida 5, Manuel Rodriguez-Huguet 3,6 and Maria Jesus Casuso-Holgado 5 1Department of Physiotherapy, Faculty of Health Sciences, University of Malaga, Arquitecto Francisco Peñalosa 3, Ampliación de Campus de Teatinos, 29071 Malaga, Spain 2Department Nursing and Podiatry, Faculty of Health Sciences, University of Malaga, Arquitecto Francisco Peñalosa 3, Ampliación de Campus de Teatinos, 29071 Malaga, Spain; [email protected] 3Department Nursing and Physiotherapy, Faculty of Nursing and Physiotherapy, University of Cadiz, Avenue Ana de Viya 52, 11009 Cadiz, Spain; [email protected] (J.A.M.-M.); [email protected] (M.R.-H.) 4 Institute of Research and Innovation in Biomedical Sciences of the Province of Cadiz (INiBICA), University of Cadiz, 11009 Cadiz, Spain 5Department Physiotherapy, Faculty of Nursing, Physiotherapy and Podiatry, University of Seville, C/Avicena s/n, 41009 Seville, Spain; [email protected] (M.d.-l.-C.-A.); [email protected] (M.J.C.-H.) 6La Línea de la Concepción Hospital, 11009 Cadiz, Spain *Correspondence: [email protected]; Tel.: +34-657-834-413 Received: 16 December 2019; Accepted: 10 January 2020; Published: 15 January 2020   Abstract: Background: Respiratory muscle dysfunction is an important health problem with high morbidity and mortality and associated costs in patients with bronchiectasis (BC). The aim of this study was to analyse the effects of therapeutic respiratory muscle training (RMT) interventions on improving sputum clearance, ventilator function, muscle strength and functional capacity in BC. Methods: Systematic review and meta-analysis wereconducted following PRISMA guidelines. Two independent investigators searched using several electronic databases. The methodological quality of nine studies was assessed using the PEDro scale. Study selection/eligibility criteria: The following were included: randomised controlled trials, randomised crossover trials and pilot studies of patients with BC that used the intervention as RMT (inspiratory/expiratory) and evaluations of respiratory muscle strength (maximal expiratory pressure/maximal inspiratory pressure). This systematic review was registered in PROSPERO (CRD42017075101). Nine studies were included, five of which obtained an A recommendation grade, three with B, and one with C. Study quality was poor to good (mean PEDro Score of 6.375 out of 10). Studies had small sample sizes (8–98). Results show improvements on PImax in favour of therapeutic respiratory muscle training intervention (MD =6.08; 95% CI =1.38, 10.77; p<0.01; I2=92%). However, high heterogeneity was identified on meta-analysis. Keywords: bronchiectasis; respiratory muscle training; respiratory muscle strength; maximum inspiratory pressure; maximum expiratory pressure; meta-analysis 1. Introduction Bronchiectasis (BC) is a chronic respiratory condition characterised by bronchial dilatation secondary to airway inflammation, infection and dysfunction of mucociliary clearance [ 1 – 4 ]. BC, permanent damage and widening of one or more of the large connecting bronchi (airways) may occur J. Clin. Med. 2020,9, 231; doi:10.3390/jcm9010231 www.mdpi.com/journal/jcm J. Clin. Med. 2020,9, 231 2 of 17 in nearly one third of individuals with chronic obstructive pulmonary disease (COPD) [ 1 ]. A variety of factors may affect the efficacy of inspiratory muscle training, including the degree of lung hyperinflation and severity of airway obstruction [ 5 ]. Both cause dyspnoea, which is a symptom of respiratory failure; inspiratory muscle weakness may lead to muscle load and capacity discordance. BC is heterogeneous in its clinical features, causes and outcomes [ 6 ]. Respiratory secretions in individuals with BC have poor transport properties, which manifest as reduced mucociliary transport, higher contact angle, dyspnoea and decreased exercise tolerance [ 6 ]. BC is an important health problem with high morbidity, mortality and associated costs [ 7 ]. International guidelines for managing BC include referral to pulmonary rehabilitation (PR) that improves exercise tolerance and quality of life [ 8 , 9 ]. The current evidence stresses the importance of the future development of process and performance metrics to monitor PR programs, to be able to start international benchmarking, and to provide recommendations for international standards based on evidence and best practice [ 10 ]. Previous to therapeutic respiratory muscle training (RMT) intervention, airway clearance techniques (ACTs) have been an important component in the management of patients with bronchiectasis [ 11 ]. Previous studies indicated the importance of mobilising secretions and facilitating effective expectoration in order to get improving airway clearance [11–13]. There are two distinct types of specific therapeutic RMT interventions, namely respiratory muscle strength (resistive/threshold) training (RMST) and respiratory muscle endurance (hyperpnoea) training (RMET), which have been established to improve the endurance performance of healthy individuals [ 14 ]. Various methods of therapeutic RMT interventions have been described. Firstly, RMST performed by breathing against an external inspiratory and/or expiratory load. This load consists either of a flow-dependent resistance or of a pressure threshold that needs to be overcome and sustained to generate flow. When a patient breathes against an external expiratory load, these devices are known as positive expiratory pressure trainers (PEP). Secondly, patients perform concurrent inspiratory and expiratory muscle training (CRMT). Third, patients clean bronchial by oscillatory or temporary PEP training devices. Finally, target flow and target pressure respiratory muscle training is where patients are trained to generate a target respiratory flow rate through a fixed resistance. Previous studies have supported, with a B recommendation grade, offering the use of IMT (inspiratory muscle training) in conjunction with conventional PR to enhance the maintenance of the training effect [ 15 ]. IMT provides breathing training together with resistance loading produced by a valve and was regarded as a mixture of strength and endurance training [ 16 ]. Two smaller studies yielded consistent results supporting the use of either inspiratory or expiratory pressure threshold load breathing exercises to improve pulmonary muscle strength in people with BC [ 5 , 17 ]. However, there are several unanswered issues regarding intensity, frequency and duration of training, as well as the optimal strategy for maintenance of benefit for patients with BC [ 18 ]. There is still scarce literature regarding the benefits of physical training and long-term effects in BC [ 12 , 19 – 21 ]. Therefore, it is necessary to establish the most effective management strategies at the earliest stage possible. The major purpose of this research is to detect recommendation grades regarding therapeutic RMT interventions in BC. This systematic review and meta-analysis examined the available evidence of different modalities of therapeutic RMT interventions that improve sputum clearance and respiratory muscle weakness in BC. Hence, the most suitable protocol to improve the respiratory muscle weakness and the respiratory function must be established. 2. Methods 2.1. Search Strategy This systematic review was performed following the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) [ 22 ]. The PRISMA Checklist is detailed in Appendix A. The review protocol was registered with an international registration database (PROSPERO, Registration J. Clin. Med. 2020,9, 231 3 of 17 Number: CRD42017075101). All analyses were performed on data of previously published studies, and thus no ethical approval and patient consent were required. A literature search was performed to identify the clinical studies that addressed the effect of instrumental mechanical devices for RMT in BC. The following databases were searched for relevant studies: MEDLINE (PubMed), Physiotherapy Evidence Database (PEDro), Cochrane Database of Systematic Reviews and CINAHL. Two reviewers carried out several searches in the databases using combinations of key words: bronchiectasis, respiratory muscle training, respiratory muscle strength, maximum inspiratory pressure and maximum expiratory pressure. The search strategy is detailed in Appendix B. The research was limited to studies published between 2004 and November 2019. 2.2. Inclusion and Exclusion Criteria Our research question was established following from the PICO (population, intervention, control/comparison and outcomes) model. First, this review describes non-cystic fibrosis BC confirmed in adults by clinical history, such as coughing, shortness of breath and exertional dyspnoea, pulmonary function tests and high-resolution computed tomography (HRCT) [ 5 , 17 ]. It was necessary to have a clinically stable disease with no requirements of antibiotics in the four weeks prior to starting the study [ 12 , 20 , 23 ]. Clinical trials, randomised controlled trials and pilot studies that used therapeutic RMT interventions were included. The articles that did not use threshold trainers or did a postural drainage were excluded [ 24 – 26 ]. Studies were excluded if steroids (inhalation or oral) such as Salbutamol were used [ 27 ]. Studies were excluded if patients were experiencing an acute exacerbation [ 25 ]. An acute exacerbation was defined as the presence of four out of 12 symptoms of a respiratory exacerbation, and requiring a course of oral antibiotics [28]. 2.3. Quality Assessment and Data Extraction Two independent reviewers (MJCH and RMV) completed the assessment list based on the PEDro score. This scale (0–10) is based on the list developed by Verhagen et al. [ 29 ], and assesses the internal validity of randomised controlled trials. A study with a PEDro score of 6 or more is considered level-1 evidence (6–8: good; 9–10: excellent) and a score of 5 or less is considered level-2 evidence (4–5: fair; <4: poor) [ 30 ]. The methodological quality of the eight studies was evaluated using the PEDro scale [ 30 – 32 ]. Disagreements between authors were initially resolved via discussion, and then by consultation with a third reviewer (JAMM). The following characteristics were extracted: different therapeutic RMT interventions, namely inspiratory or expiratory exercises. Firstly, therapeutic inspiratory muscle intervention could be performed with different intensities and duration exercises through resistance offered by a valve threshold, adapting to the needs and changes of the individual as it progressed through the study. Secondly, therapeutic expiratory muscles intervention included four different types of instrumental mechanical devices: flutter, Acapella, UNIKO-TPEP®and Origen-Dual Valve®. The outcome measures included were maximum inspiratory pressure (PImax) [ 5 , 17 ], maximum expiratory pressure (PEmax) [ 5 , 12 , 20 , 23 ], respiratory muscle strength, forced vital capacity (FVC) [5,12,20,27] , and maximum oxygen consumption or VO 2 peak [ 17 ]. Other used measures included the sputum volume (SV) [ 11 ] or measurement of respiratory mechanics associated with peripheral airway resistance (such as the first derivative of resistance as a function of frequency) [ 33 ], transport velocity (TV) [ 34 ], exercise capacity (Six Minute Walk test (6MWT)) [ 5 , 20 ] and hand dynamometry (using a Jamar hydraulic) [ 21 ]. Regarding anthropometric outcomes related with body composition, Body Mass Index (BMI) and Fat Free Mass Index (FFMI) with Dual-energy X-Ray Absorpiometry (DEXA), mid-arm muscle circumference (MAMC), and phase angle by Bio-impedance were found [ 21 ]. Self-Reported outcomes measures included The Borg Scale, St George’s Respiratory Questionnaire [ 5 , 12 , 20 ], Quality of Life Questionnaire for Bronchiectasis (QOL-B-Spain-v3.0) and a seven-day prospective dietary questionnaire [21]. J. Clin. Med. 2020,9, 231 4 of 17 The results for the primary and secondary outcome measures were described and where possible study results were pooled and meta-analysis was conducted. Effect size (ES) was calculated using the difference between the mean (MD) and the standard deviation of the difference (SMD) with 95% confidence intervals (95% CI). An alpha value <0.05 was considered as statistically significant. We decided to pool studies based on comparing the RMT and control group. The ES values were used to compare the different modalities of therapeutic RMT intervention with control group. Analysis of the effect size values was based on Cohen’s work, which determined that values below 0.2 were considered to have no effect, those between 0.2 and 0.5 as small effect, those between 0.5 and 0.8 a medium effect, and those above 0.8 a major effect [ 35 ]. The recommendation grades were studied according to the Duodecim (Finnish Medical Society Duodecim), a clinical practice guide developed in Finland to improve the quality of health care [ 36 ]. Grade A means that the recommendation is based on strong evidence. Grade B is based on sufficient evidence to make a clear recommendation. Grade C recommendations are based on limited evidence. Grade D refers to recommendations for which there is no evidence based on clinical studies [37]. 2.4. Statistical Analysis A meta-analysis was applied to compare changes in the effect size (post-intervention and pre-intervention) between the intervention group and the control group. For the meta-analysis, the standardised mean difference was calculated along with the 95% confidence interval, with a significance level set to p<0.05. Heterogeneity was determined by the chi-square test and the I 2 statistic. The results of all the subgroups included in this meta-analysis were represented in Forest plots. The statistical analyses were carried out with the statistical software REVIEW MANAGER 5.3 (The Cochrane Collaboration) (The Nordic Cochrane Centre 2014). 3. Results 3.1. Study Selection and Methodological Quality Assessment The initial database searches returned sixty-three potential studies. Sixteen relevant papers were found in the search strategy, and nine studies fulfilled the inclusion criteria (Figure 1). After reviewing titles and abstracts, fifteen papers were selected for full-text evaluation. Of these, nine papers were included in the systematic review and meta-analysis. Table 1shows the assessment of methodological quality according to PEDro scale (mean PEDro score of 6.375 out of 10). We found seven studies [ 5 , 17 , 21 , 23 , 33 , 38 , 39 ] with level 1 evidence (good; 75% [7/9]); one study [ 20 ] had score of 5, which is considered level 2 evidence (acceptable; 12.5% [1/9]); and another study [ 12 ] had scores of 4 or less, which is considered (poor; 12.5% [1/9]). Trials were considered of enough methodological quality if they had a score of at least 5 out of 10 points. This was based on the fact that the tests with a score close to 4 do not employ a triple blind methodology (i.e., patient, evaluator and providing treatment). J. Clin. Med. 2020,9, 231 5 of 17 J. Clin. Med. 2020, 9, x FOR PEER REVIEW 5 of 17 Figure 1. PRISMA flow chart of the study screening and selection process. Table 1. PEDro score for Methodological Quality assessment of nine studies. Section/ Theme Ozalp [39] Venture Lli [23] Liaw [5] Newall [17] Olveira [21] Tambascio [40] Figueiredo [33] Mandal [20] Murray [12] Eligibility criteria Yes Yes Yes Yes Yes Yes Yes Yes Yes Randomly allocated Yes Yes Yes Yes Yes Yes Yes Yes Yes Concealed allocation No Yes Yes Yes Yes Yes Yes No No Comparability of base Yes Yes Yes Yes Yes Yes No Yes No Blinding of subjects Yes Yes No No No No No No No Blinding of therapist No No Yes No No No Yes No No Blinding of assessor Yes No Yes No No No No No No Proper Yes Yes No Yes Yes No No Yes Yes Figure 1. PRISMA flow chart of the study screening and selection process. Table 1. PEDro score for Methodological Quality assessment of nine studies. Section/Theme Ozalp [39] Venture Lli [23] Liaw [5] Newall [17] Olveira [21] Tambascio [40] Figueiredo [33] Mandal [20] Murray [12] Eligibility criteria Yes Yes Yes Yes Yes Yes Yes Yes Yes Randomly allocated Yes Yes Yes Yes Yes Yes Yes Yes Yes Concealed allocation No Yes Yes Yes Yes Yes Yes No No Comparability of base Yes Yes Yes Yes Yes Yes No Yes No Blinding of subjects Yes Yes No No No No No No No Blinding of therapist No No Yes No No No Yes No No Blinding of assessor Yes No Yes No No No No No No Proper Continuation Yes Yes No Yes Yes No No Yes Yes Intention to treat Yes Yes Yes Yes Yes Yes Yes No No Between-group statistical comparison Yes Yes Yes Yes Yes Yes Yes Yes Yes Point measure and measures of variability Yes Yes Yes Yes Yes Yes Yes Yes Yes Total 8 8 8 7 7 6 6 5 4 J. Clin. Med. 2020,9, 231 6 of 17 3.2. Study Design and Population Characteristics Nine studies with a total of 262 participants clinically diagnosed with BC were included in this systematic review. Protocol characteristics, intensity of training, recommendation grades, effect size of clinical and self-reported outcomes are described in Table 2. Regarding therapeutic RMT interventions, namely inspiratory or expiratory exercises, we first found three studies: two randomised controlled trials [ 5 , 17 ] about therapeutic inspiratory muscle intervention. Besides, two different types of interventions were carried out [ 5 , 17 ]. Two groups were made: maximum controlled inspiratory training and non-intervention [ 5 ], in front of three groups were made: PR plus sham IMT (PR-SHAM), PR plus targeted IMT (PR-IMT), or control [17]. It was found that two of the studies reviewed used the Threshold trainer [ 5 , 17 ]. Regarding airway clearance, one study used Flutter VRP1 [ 40 ], one used Flutter valve TM [ 33 ], one used the UNIKO-TPEP ® [ 23 ], and two studies used oscillatory positive expiratory pressure (OPEP) device Acapella [ 12 , 20 ]. Furthermore, there is the Origen-Dual Valve [ 21 ], which allows both simultaneous and sequential dual training work (expiratory and inspiratory muscles). J. Clin. Med. 2020,9, 231 7 of 17 Table 2. Key findings of primary studies. Study, DR PEDro, Type of Study, Sample Size Training Protocol Intra-Group Outcomes Effect Size (%) Clinical OC Measures Effect Size (%) Self-Reported OC Measures Venturelli, 2013 [23] A PEDro: 8/10 Randomised controlled trial n=98 10 days twice a day 20-min cycles of manually assisted breathing techniques plus 15 min of temporary PEP PImax p=0.541 PEmax p=0.233 FVC p=0.495 PImax +6% pred PEmax +2.3% pred FVC +4.3% pred Liaw, 2011 [5] A PEDro: 8/10 Randomised controlled trial n=26 8 week 5 days/week 30 min/day I: 30% MIP increasing 2 cm H2O/week ↑PImax p=0.004 ↑PEmax p=0.004 ↑6MWD p=0.021 FVC p=0.309 PImax +23.85 cm H2O PEmax +31.92 cm H2O 6MWD +61.31 m FVC +2.51% pred TBS 1.46 SGRQ 32.46 Ozalp, 2019 [39] A PEDro: 8/10 Randomised controlled trial n=45 8 week 3 days/week Only 1 ss/week was performed under the supervision I: target workload was selected from 30% (first session) to 70% (third session) of MIP ↑PImax p=0.001 ↑PEmax p=0.233 SIP p<0.05 ISWT distance PImax +2.62 cm H2O PEmax +1.039 cm H2O ↓FSS −0.197 p=0.05 ↑LCQ 0.52 p=0.05 Newall, 2005 [17] A PEDro: 7/10 Randomised controlled trial n=32 8 week 3 days/week 2 sets/day 15 min/set I: 30% MIP and increased 5% each week until a training I of 60% MIP ↑PImax p=0.003 Vo2peak p=0.192 PImax (cm H2O): PR-sham 12, PR-IMT 21.4; PR-control −1.6 Vo2peak(ml/min/kg): PR-sham 1.96; PR-IMT 0.35; PR-control −1.91 ISWT (m): PR-sham 96.7; PR-IMT 124.5 PR-control 11 EE (m): PR-sham 392.8 PR-IMT 607.3; PR-control −112.6 Murray, 2009 [12] A PEDro: 4/10 Randomised crossover trial n=20 3 months of twice daily, each ss 20–30 min, 3 sets, 10 breath/set PImax p=0.2 PEmax p=0.3 FVC p=0.6 PImax +4.5 cm H2O PEmax −1.5 cm H2O FVC +0.18 L ↓SGRQ 0.7 p=0.004 J. Clin. Med. 2020,9, 231 8 of 17 Table 2. Cont. Study, DR PEDro, Type of Study, Sample Size Training Protocol Intra-Group Outcomes Effect Size (%) Clinical OC Measures Effect Size (%) Self-Reported OC Measures Mandal, 2012 [20] C PEDro: 5/10 RCT n=30 8 weeks, 3sets/ss, 20–30 min/ss Twice a day CG: chest physiotherapy IG: chest physiotherapy plus PR CG: PImax +5.9 cm H2O PEmax +5.3 cm H2O ISWT −4.6 m IG: PImax +6.6 cm H2O PEmax +14.7 cm H2O ISWT +56.7 m CG: SGRQ 1.4 IG: ↓SGRQ 4 p<0.001 Tambascio, 2011 [40] B PEDro: 6/10 RCT crossover n=18 4 weeks with Flutter VRP1®30 min daily and 1 weeek of a “wash-out” period vs. Flutter therapy Flutter Therapy ↓CAM: 6.11 ±0.5◦ p>0.05 Figueiredo, 2012 [33] B PEDro: 6/10 RCT crossover n=8 Flutter Valve TM vs Sham Flutter (placebo) 8.4 mL more secretions Olveira, 2015 [21] B PEDro: 7/10 RCT parallel groups n=30 12 weeks PR 45 min +15 min with Orygen-Dual Valve® 3 days/week (one unsupervised ss) BMD: 0.013 ±0.002 FFM: 1.1 ±0.1 p>0.01 ↑FFMI:0.4 p>0.01 Maximal Handgrip: 2.2 p>0.01 QOL-B: 8.1 ±4.6 p>0.05 J. Clin. Med. 2020,9, 231 9 of 17 3.3. Meta-Analysis The meta-analysis of the data of the RCTs was performed using the fixed effects model, as presented in Figures 2and 3. Because of the high heterogeneity, the sensitivity analysis was performed in relation to the type of training and intensity, analysing those RCT papers that used outcomes of PImax and PEmax. Therefore, the present review strengthens the evidence regarding the efficacy of respiratory muscle training for increasing respiratory muscle strength, because this review was based on meta-analyses of randomised trials with reasonable quality (mean PEDro Score of 6.375 out of 10). J. Clin. Med. 2020, 9, x FOR PEER REVIEW 9 of 17 3.3. Meta-Analysis The meta-analysis of the data of the RCTs was performed using the fixed effects model, as presented in Figures 2 and 3. Because of the high heterogeneity, the sensitivity analysis was performed in relation to the type of training and intensity, analysing those RCT papers that used outcomes of PImax and PEmax. Therefore, the present review strengthens the evidence regarding the efficacy of respiratory muscle training for increasing respiratory muscle strength, because this review was based on meta-analyses of randomised trials with reasonable quality (mean PEDro Score of 6.375 out of 10). Heterogeneity: Tau 2 = 430.9924; Chi 2 = 37.99, df = 3 (p < 0.01); I 2 = 92% Figure 2. Forest plot for overall studies about PImax. Heterogeneity: Tau 2 = 233.0066; Chi 2 = 19.76, df = 2 (p < 0.01); I 2 = 90% Figure 3. Forest plot for overall studies about PEmax. Pooled analysis of the four studies measuring PImax showed a significant overall effect in favour of intervention (MD = 6.08; 95% CI = 1.38, 10.77; p < 0.01; I 2 = 92%) (Figure 2). However, pooled analysis of the three studies measuring PEmax did not show a significant overall effect (MD = 2.04; 95% CI = −3.33, 7.31; p < 0.01; I 2 = 90%) (Figure 3). 4. Discussion This systematic review summarises recommendation grades of various therapeutic RMT interventions in BC. It was observed that RMT may improve PImax and PEmax strength of respiratory muscles in this population [5,17,23]. These benefits in respiratory muscles have also been found in patients with multiple sclerosis (MS) [41] and chronic obstructive pulmonary disease (COPD) [42]. There are scarce studies about RMT in BC. After performing this systematic review, eight studies about therapeutic RMT intervention in BC were carried out [5,12,17,20,21,23,33,40]. Three studies reviewed used the Threshold trainer [5,17]. Three studies were conducted about bronchial clearance with PEP with Flutter VRP1 [33,40], three studies used Acapella [12,20], one used Origen-Dual Valve ® [21], and one used the UNIKO-TPEP ® [23]. RMT could be performed using either inspiratory or expiratory muscle devices. Only one study compared the value of inspiratory versus expiratory training in patients with BC [11]. Three primary documents with an “A” recommendation grade for IMT were included in this review [5,17,39]. According to the treatment with positive expiratory pressure (PEP), two studies Figure 2. Forest plot for overall studies about PImax. J. Clin. Med. 2020, 9, x FOR PEER REVIEW 9 of 17 3.3. Meta-Analysis The meta-analysis of the data of the RCTs was performed using the fixed effects model, as presented in Figures 2 and 3. Because of the high heterogeneity, the sensitivity analysis was performed in relation to the type of training and intensity, analysing those RCT papers that used outcomes of PImax and PEmax. Therefore, the present review strengthens the evidence regarding the efficacy of respiratory muscle training for increasing respiratory muscle strength, because this review was based on meta-analyses of randomised trials with reasonable quality (mean PEDro Score of 6.375 out of 10). Heterogeneity: Tau 2 = 430.9924; Chi 2 = 37.99, df = 3 (p < 0.01); I 2 = 92% Figure 2. Forest plot for overall studies about PImax. Heterogeneity: Tau 2 = 233.0066; Chi 2 = 19.76, df = 2 (p < 0.01); I 2 = 90% Figure 3. Forest plot for overall studies about PEmax. Pooled analysis of the four studies measuring PImax showed a significant overall effect in favour of intervention (MD = 6.08; 95% CI = 1.38, 10.77; p < 0.01; I 2 = 92%) (Figure 2). However, pooled analysis of the three studies measuring PEmax did not show a significant overall effect (MD = 2.04; 95% CI = −3.33, 7.31; p < 0.01; I 2 = 90%) (Figure 3). 4. Discussion This systematic review summarises recommendation grades of various therapeutic RMT interventions in BC. It was observed that RMT may improve PImax and PEmax strength of respiratory muscles in this population [5,17,23]. These benefits in respiratory muscles have also been found in patients with multiple sclerosis (MS) [41] and chronic obstructive pulmonary disease (COPD) [42]. There are scarce studies about RMT in BC. After performing this systematic review, eight studies about therapeutic RMT intervention in BC were carried out [5,12,17,20,21,23,33,40]. Three studies reviewed used the Threshold trainer [5,17]. Three studies were conducted about bronchial clearance with PEP with Flutter VRP1 [33,40], three studies used Acapella [12,20], one used Origen-Dual Valve ® [21], and one used the UNIKO-TPEP ® [23]. RMT could be performed using either inspiratory or expiratory muscle devices. Only one study compared the value of inspiratory versus expiratory training in patients with BC [11]. Three primary documents with an “A” recommendation grade for IMT were included in this review [5,17,39]. According to the treatment with positive expiratory pressure (PEP), two studies Figure 3. Forest plot for overall studies about PEmax. Pooled analysis of the four studies measuring PImax showed a significant overall effect in favour of intervention (MD =6.08; 95% CI =1.38, 10.77; p<0.01; I 2 =92%) (Figure 2). However, pooled analysis of the three studies measuring PEmax did not show a significant overall effect (MD =2.04; 95% CI =−3.33, 7.31; p<0.01; I2=90%) (Figure 3). 4. Discussion This systematic review summarises recommendation grades of various therapeutic RMT interventions in BC. It was observed that RMT may improve PImax and PEmax strength of respiratory muscles in this population [ 5 , 17 , 23 ]. These benefits in respiratory muscles have also been found in patients with multiple sclerosis (MS) [ 41 ] and chronic obstructive pulmonary disease (COPD) [ 42 ]. There are scarce studies about RMT in BC. After performing this systematic review, eight studies about therapeutic RMT intervention in BC were carried out [ 5 , 12 , 17 , 20 , 21 , 23 , 33 , 40 ]. Three studies reviewed used the Threshold trainer [ 5 , 17 ]. Three studies were conducted about bronchial clearance with PEP with Flutter VRP1 [ 33 , 40 ], three studies used Acapella [ 12 , 20 ], one used Origen-Dual Valve ® [ 21 ], and one used the UNIKO-TPEP ® [ 23 ]. RMT could be performed using either inspiratory or expiratory muscle devices. Only one study compared the value of inspiratory versus expiratory training in patients with BC [11]. Three primary documents with an “A” recommendation grade for IMT were included in this review [ 5 , 17 , 39 ]. According to the treatment with positive expiratory pressure (PEP), two studies were found with an “A” recommendation grade where there were improvements on lung function and symptoms in patients with chronic lung disease and mucus hyper-secretion [12,23]. Firstly, Newall et al. carried out an IMT protocol of eight weeks, three days per week, two sets per day and 15 min per set, with an intensity of 30% MIP with Threshold Trainer, which was increased by 5% each week until a training intensity of 60% PImax was reached [ 17 ]. Three groups were made: a PR J. Clin. Med. 2020,9, 231 16 of 17 5. Liaw, M.Y.; Wang, Y.H.; Tsai, Y.C.; Huang, K.T.; Chang, P.W.; Chen, Y.C.; Lin, M.C. Inspiratory muscle training in bronchiectasis patients: A prospective randomized controlled study. Clin. Rehabil. 2011 ,25, 524–536. [CrossRef] [PubMed] 6. Lima Afonso, J.; Tambascio, J.; Dutra de Souza, H.C.; Jardim, J.R.; Baddini Martinez, J.A.; Gastaldi, A.C. 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