Emphysema, a common feature of Chronic Obstructive Pulmonary Disease (COPD), is strongly linked to disease severity and prognosis. Patients with emphysematous COPD often experience dyspnea, limited exercise capacity, cardiac issues, and poor outcomes due to lung hyperinflation.1,2 To address this, bronchoscopic lung volume reduction (BLVR) therapies like valve and coil treatments have gained prominence in COPD research. These procedures aim to alleviate hyperinflation, leading to improved lung function, exercise capacity, and quality of life. BLVR procedures were integrated into the GOLD guidelines in 2017.3

Hyperinflation can have significant repercussions on respiratory muscle function, particularly impacting the diaphragm. This crucial muscle experiences a mechanical decrease in activity, primarily due to compression.4 Moreover, structural alterations occur within the respiratory muscles under such circumstances. Biopsies of the diaphragm reveal a decline in Type II (fast) fibers, accompanied by an increase in Type I (slow, fatigue-resistant) fibers. Studies have demonstrated that during hyperinflation, the length of the diaphragm can decrease by up to 40% compared to normal levels at Functional Residual Capacity. This alteration in length profoundly affects the force–capacity relationship of the diaphragm.4,5 Furthermore, systemic factors prevalent in hyperinflation cases, such as weight loss, electrolyte imbalances, hypercapnia, hypoxia, and oxidative stress, also exert a considerable influence on respiratory muscle function.5

Inspiratory Muscle Training (IMT), one of the components of pulmonary rehabilitation (PR), has been used in chronic lung diseases for years. There is data showing that IMT reduces diaphragmatic activation by strengthening the respiratory muscles, and that reduced excessive diaphragmatic activation also reduces the perceived level of dyspnea.6–8 It improves patients’ ability to sustain high levels of ventilation. In the ATS/ERS guideline published in 2013, it is stated that IMT applied in addition to PR in patients with respiratory muscle weakness will provide additional benefit by increasing respiratory muscle strength.7 The benefits mentioned here are not detailed, and the patient group primarily includes respiratory diseases such as COPD.

Preoperative PR programs are recommended for BLVR procedures.9 Guidelines in this area emphasize the importance of implementing PR or a comprehensive exercise program prior to making decisions regarding procedures such as BLVR.10 The primary objective is to assess the potential benefits of PR on patients’ clinical outcomes, particularly in alleviating dyspnea and improving quality of life.11 PR has the potential to either eliminate the need for procedures or enhance the success rate of such interventions. Pulmonary functions and exercise capacity play pivotal roles in determining the necessity of procedures for individuals with COPD. Literature consistently reports the beneficial impact of PR on these parameters.12 Consequently, understanding the positive effects of PR on pulmonary functions and exercise capacity is paramount in guiding clinical decisions regarding appropriate interventions for COPD patients. However, there is a lack of information regarding the specific content of the program for this patient group, and standard PR programs are typically applied. In the literature, there is only one study that examines the effectiveness of home-based and hospital-based PR programs before the bronchoscopic procedure.13 No study investigating the effectiveness of IMT in this patient group has been found. In the study, the aim was to investigate whether IMT might increase the gains of the PR program or not. Our study holds the distinction of being the first to explore this aspect. The hypothesis of our study is that adding IMT to PR will reduce perceived dyspnea levels, improve exercise capacity, physical activity level and also quality of life.

A total of 68 emphysema patients were referred for PR before BLVR. Sixty-four were randomized into study groups, while eleven were excluded for various reasons (Fig. 1). The average age was 64 years, with 86.8% males. Baseline characteristics showed no significant differences between groups, except for fatigue scores (p=0.028). Refer to Table 1 for detailed demographic and baseline clinical data.

Fig. 1.

Study flow chart.

(0.37MB).

In the comparison between the PR group and the group with IMT added to PR, except for MIP, the groups were similar; there were no superiority of one group over the other (Tables 2 and 3).

In the assessment conducted at the end of the rehabilitation program, intragroup changes in the IMTGr showed an increase in 6MWT distance, FVC, FEV1, all peak mouth pressure measurements, peripheral muscle strength, and physical activity level scores, except for the IPAQ-SF vigorous subcategory. Furthermore, there was a decrease in mMRC dyspnea, FSS fatigue, anxiety, and depression levels. Fatigue level was higher in baseline scoring in PRGr. At the end of the program, it dropped from 45 to 29 in IMTGr and from 54 to 40 in PRGr. Although baseline levels were different, the groups were similar at end-of-program evaluation (Tables 2 and 3).

In contrast, intragroup changes in PRGr showed improvements in 6MWT distance, peripheral muscle strength, and only MEP among maximal mouth pressure measurements. PRGr also demonstrated increased scores in all IPAQ-SF subparameters and a decrease in mMRC, FSS, and depression levels. However, no significant changes were observed in spirometric parameters (Tables 2 and 3).

The IMT group exhibited a median increase in walking distance of 66 meters, whereas the PRGr group showed a median increase of 33 meters (Table 2). Both groups achieved an increase in walking distance above the MCID (25m) value; however, the increase in walking distance in the IMT group is significantly greater.30 Despite this, the effect size, as measured by Cohen's d, was d=0.151, indicating a small effect size.

In current literature, respiratory muscle weakness was defined with a cutoff value of 62cmH2O for female and 83cmH2O for male.31 The number of cases with identified respiratory muscle weakness at baseline were 21 in IMTGr and 24 in PRGr. At the end of the program, these numbers were 18 in IMTGr and 21 in PRGr. There was no statistically significant difference between the groups at baseline (p=.140) or at the end of the program (p=.244).

In the intergroup analysis, statistically significant differences were observed in the maximal mouth pressure measurement parameter MIP (p=0.003) in favor of IMTGr. However, no statistically significant differences were observed in other parameter changes (p>0.05) (Tables 2 and 3).

No complications were encountered related to the practices conducted during the assessment and exercise program. But during the 2-month follow-up period, a total of 5 subjects were excluded from the IMTGr, and 6 from the PRGr. Four patients in both groups could not continue the exercise program due to COPD attacks. One participant from IMTGr and two from PRGr expressed their intention to come to the hospital for their final evaluations. The dropout rates in both groups were comparable, with a dropout rate of 16% in IMTGr and 19% in PRGr.

The study investigated whether the addition of IMT to the PR program had any additional impact on program outcomes. The main findings show that IMT does not provide any additional benefit other than increased respiratory muscle strength. The study results revealed that PR prior to BLVR leads to an increase in exercise capacity, peripheral muscle strength, quality of life, and physical activity level, while reducing perceived dyspnea and fatigue. Furthermore, the patients’ psychological well-being experiences a positive impact. Adding inspiratory muscle training to the standard PR program may have a positive effect on respiratory muscle strength and lung volumes. Although the addition of IMT to the PR exercise program did not reach statistical significance overall, an increase in percentages of measured and expected values for parameters such as FVC and FEV1 was observed. Importantly, a statistically significant increase in the measured liter quantity of FEV1 was achieved. Although the increase in FEV1 is modest, given that spirometric values typically do not increase with PR gains and tend to worsen in these patients, it can be concluded that this gain represents a small yet valuable improvement. This study marks the first investigation of the effects of adding IMT to the PR program in emphysema patients eligible for BLVR.

The observed differences between the groups, while expected, are statistically significant within-group changes. Although the increase in 6MWD observed in the PRIMT group compared to the PRGr did not reach statistical significance, the mean increase in the IMT group was 66m compared to 33m in the PRGr group. This indicates a clinically relevant difference exceeding the 25-m minimal clinically important difference. However, this clinically relevant difference has a small effect size, as measured by Cohen's d=0.151. The greater improvement in walking distance observed in the IMTGr could be attributed to enhanced respiratory muscle strength, leading to a reduction in perceived dyspnea levels and potentially resulting in better performance during the tests. This finding aligns with a previous randomized controlled trial involving lung transplant candidates, which also reported a similar pattern of greater improvement in exercise capacity with the addition of IMT to the standard PR exercise program.15 This reference suggests that improved respiratory muscle strength could potentially enhance exercise capacity. However, beyond this article, no other studies have been found demonstrating a direct correlation between IMT and increased exercise capacity specifically in individuals with COPD. Nevertheless, there are indications that IMT may have a positive impact on exercise capacity in other patient populations.32,33 In our study, the increase in inspiratory muscle strength was noted to be 11cmH2O in the group receiving IMT, whereas the median change in this parameter was negative in the group not undergoing IMT. Comparing our findings with previous studies employing similar methodologies, the IMT groups demonstrated increases ranging from approximately 15cmH2O to 19cmH2O,34 while the non-IMT groups showed increases ranging from 9cmH2O to 10cmH2O.35 In the first study, the exercise program was conducted as a supervised inpatient regimen using ergometers. The supervision and the use of ergometers for aerobic training likely contributed to a greater effect on respiratory muscle strength. In contrast, the second study did not include home-based or supervised aerobic training, although IMT was performed under supervision. Consequently, the increase in respiratory muscle strength observed in the second study was less than that seen in our study. Notably, despite the considerably lower median change in respiratory muscle strength observed in the non-IMT group in our study, it is intriguing that no significant difference was observed between the two groups. The positive effect of increased MIP on walking distance may involve mechanisms such as reduced accessory respiratory muscle activity due to strengthened major respiratory muscles, thereby alleviating shortness of breath and fatigue. Our findings are consistent with moderate-certainty evidence presented in the Cochrane systematic review,36 particularly regarding the significant increase observed in MIP in the IMTGr. The Cochrane review suggests a similar trend of improvement in 6MWD following IMT, although not statistically significant. This consistency lends support to the potential benefits of IMT in enhancing respiratory muscle strength and functional exercise capacity in COPD patients. Furthermore, our study contributes to existing evidence by demonstrating the magnitude of change in MIP, thereby enhancing our understanding of the efficacy of IMT interventions in COPD management.

One of the key benefits of PR programs is the reduction in perceived dyspnea and fatigue levels.37 The PR exercise program achieves symptomatic improvement through gains in aerobic capacity, peripheral muscle strength, and a change in the perception of dyspnea.38 In our study, individuals with severe dyspnea perception were included. Similar to the literature, a decrease in dyspnea perception was observed in both groups. The lack of significant differences between the groups in terms of dyspnea perception may be due to the fact that respiratory muscle weakness, one of the causes of dyspnea, is not present in every case. It is observed that the expected MIP values of both groups are above 60%. Additionally, literature reports suggest that the response to IMT tends to be more pronounced in individuals with MIPmax below 60cmH2O.34,35 This information further corroborates our findings and provides additional support for our results.

In PR programs, not all patients may achieve spirometric improvements.39 In cases of advanced respiratory failure and parenchymal damage, obtaining improvements in spirometric values through PR can be challenging. The primary expectation from PR is often symptomatic improvement.40 In our study, there was a statistically significant increase in spirometric values in the IMTGr. However, in the PRGr, no improvement in lung volumes was observed. While there was a slight increase in spirometric values in the IMTGr group, the observed change in FEV1 (delta: 0.03L) was relatively small and below the Minimal Clinically Important Difference (MCID) for FEV1, which is typically considered to be 100ml. Therefore, the improvement in spirometric values is not clinically relevant. The literature presents varying results regarding the effects of PR13,41 and IMT15,42 on lung volumes, with some studies reporting significant changes while others do not. This inconsistency highlights the need for further research to better understand the impact of these interventions on lung function.

In a randomized controlled study investigating the benefits of adding IMT to PR in COPD, it was found that IMT provided no additional benefits, except for an increased MIP.34 Another study, implementing PR with additional IMT for three weeks in COPD cases without inspiratory muscle weakness, reported an improvement trend in dyspnea sensory intensity, particularly in cases with FEV1 values below 50% of predicted. However, IMT showed no impact on dyspnea and functional parameters in COPD cases with a maximum MIP exceeding 60cmH2O.43 In current studies, cut-off points for respiratory muscle weakness based on T-scores≥2.5 SD below the peak mean value were determined to be 62cmH2O for females and 83cmH2O for males for MIPmax.31 In our study, it appears that the majority of cases have respiratory muscle weakness. Moreover, the increase in MIP obtained was somewhat lower compared to existing literature examples.36,44 According to our results, the fact that adding IMT to the program did not make a difference may be due to insufficient training time or the fact that the exercises were performed unsupervised throughout the week, although weekly follow-ups were made.

Psychological issues, such as anxiety and depression, are common in patients with chronic respiratory conditions. A review on the relationship between COPD exacerbations and depression-anxiety identified them as significant risk factors. In a randomized controlled trial exploring controlled breathing techniques in hospitalized COPD patients, respiratory control positively impacted anxiety and depression during exacerbations.45 Preoperative PR, administered for at least 3 weeks to lung transplant candidates, reduced depression levels.39 In another randomized controlled study investigating PR and IMT for terminally ill respiratory patients preoperatively, IMT was found not to provide additional benefits to psychological status, although the overall program improved depression levels.15 In our study, the IMT group showed a statistically significant improvement in anxiety and depression levels, while anxiety levels in the standard PR group remained unchanged. However, not detecting a difference between the groups provides insufficient evidence to reveal the effect of IMT on psychological state.

Our study has several limitations that should be acknowledged. Firstly, ethical considerations regarding the necessity of PR before BLVR precluded the inclusion of a placebo group without an exercise program, which could have provided valuable comparative data. Secondly, the lack of long-term follow-up after BLVR limits our understanding of the sustained effects of the interventions. Due to the problems experienced in health expenses, BLVR procedure could not be performed in our country for a while, and this caused deficiencies in the follow-up of our cases after BLVR. Additionally, the use of the mMRC scale to assess dyspnea levels may be limited in its sensitivity. Employing additional, more sensitive dyspnea scales could have offered a more comprehensive evaluation of outcomes. Another limitation of our study is the underpowering to detect such clinically relevant between-group differences in 6MWD. Although an increase in walking distance above the MCID value was achieved in both groups, no significant difference was observed in the IMTGr group. Additionally a statistically significant difference favoring the IMTGr was observed in the MIP parameter in the intergroup analysis, no statistically significant differences were noted in other parameter changes. The fact that IMT was not performed under supervision may have caused this and is a limitation.

In conclusion, our study sheds light on the potential benefits of integrating IMT into standard PR programs, particularly for enhancing respiratory muscle strength. However, it's noteworthy that our findings did not reveal a significant difference between the IMT and PR-alone groups in terms of exercise capacity or other patient-reported outcomes. This suggests that while IMT integration holds promise, its additional benefits over standard PR alone may not be statistically significant based on our study results. Nonetheless, our study underscores the positive effects of PR on the clinical status of BLVR-eligible patients, consistent with existing literature. This reaffirms the value of PR as a standalone intervention in optimizing patient outcomes in this population. Furthermore, our results emphasize the importance of PR as a precursor to BLVR procedures, indicating its role in optimizing patient outcomes. Nevertheless, it's important to acknowledge the limitations of our study, particularly its ability to detect significant differences between groups. Therefore, further research with larger sample sizes is warranted to fully elucidate the potential benefits of IMT integration and PR preceding BLVR. Such research could provide valuable insights into optimizing patient care and treatment strategies.

Registration number: NCT05540054.

The study was carried out at Yedikule Chest Diseases and Thoracic Surgery Training and Research Hospital.

This study protocol was reviewed and approved by the Ethics Committee of the Yedikule Chest Diseases and Chest Surgery Education and Research Hospital, approval number 2022-238 (05/12/2022).

None.

Esra Pehlivan conceived and designed the study, supervised patient training, interpreted the data, and drafted the manuscript. Zeynep Betül Özcan and Fulya Senem Karaahmetoğlu conducted the patient evaluations and exercises. Erdoğan Çetinkaya, Mustafa Çörtük, and Halit Çınarka contributed to the study's design, coordination, and manuscript review.

The authors declare that there is no conflict of interest.