Abstract
BACKGROUND: An increase in respiratory work load and resistance to respiration cause a decrease in respiratory muscle endurance (RME) in patients with obesity hypoventilation syndrome (OHS). We aimed to evaluate and compare RME in subjects with OHS and a control group using an incremental load test and compare the RME of subjects with OHS in whom noninvasive ventilation (NIV) was and was not used.
METHODS: Forty subjects with OHS (divided according to body mass index [BMI] as group I: 30–40 kg/m2; and group II: ≥ 40 kg/m2) and 20 subjects with obesity (control group: 30–40 kg/m2) were included in the study. RME was evaluated using the incremental load test, and respiratory muscle strength (RMS) was evaluated using mouth pressure measurements. The 6-min walk test, Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), Fatigue Severity Scale (FSS), EQ-5D Health-Related Quality of Life Questionnaire (EQ-5D), and the Obesity and Weight-Loss Quality of Life Instrument (OWLQOL) were performed.
RESULTS: RME and RMS (%) in group I were lower than the control group (P = .001, P = .005, and P = .001, respectively). No significant difference was found between the 3 groups in terms of 6-min walk distance (6MWD) percentage predicted values (P = .98). RME in the NIV user group was higher than the non-user group (P = .006). ESS, total PSQI, and FSS scores in the control group were less than group I (P = .01, P = .009, and P = .005, respectively) and group II (P = .01, P < .001, and P < .001, respectively). The EQ-5D scores of the control group were higher than group II only (P = .005 and P = .005, respectively). There were no differences in OWLQOL between the groups (P = .053).
CONCLUSIONS: RME was low in subjects with OHS but higher in those who used NIV. The incremental load test could be performed easily and safely in a clinic setting.
Introduction
Obesity hypoventilation syndrome (OHS) is defined as a combination of obesity (body mass index [BMI] ≥ 30 kg/m2), chronic daytime hypercapnia (arterial carbon dioxide tension ≥ 45 mm Hg), and sleep-disordered breathing after ruling out other disorders that may cause alveolar hypoventilation.1 Clinically, patients may present with symptoms such as excessive daytime sleepiness, fatigue, or morning headaches, which are similar to symptoms seen in obstructive sleep apnea-hypopnea syndrome.2 Respiratory mechanics, pulmonary gas exchange, respiratory control, respiratory muscle performance, lung function, and exercise capacity are adversely affected in OHS.3 Respiratory system compliance decreases and resistance increases in OHS. This causes an increase in the work of breathing and the oxygen cost of breathing, which may result in respiratory muscle fatigue.4 In turn, respiratory muscle fatigue is a potential mechanism that impairs exercise tolerance.5
Respiratory muscle performance measures respiratory muscle strength (RMS) and respiratory muscular endurance (RME).6 RME is the capacity of the respiratory muscles to maintain a specific task over a period of time and is associated with respiratory muscle fatigue.7 It more accurately reflects the normal function of respiratory muscles than muscle strength8 because respiratory muscles are required to perform submaximal contractions throughout life.9 Thus, RME measurements can be useful in some clinical and research settings for the evaluation of patient populations and responses to treatment and rehabilitation.7 No such generally accepted method exists for the measurement of global RME, although the maximum threshold pressure sustained during an incremental load test, the time to exhaustion while inspiring against a constant submaximal load test, and sustained maximal voluntary ventilation are commonly used for this purpose.6,7 Compared with the constant loading protocol, the incremental loading protocol is reported to be more reliable because it shows less variability and greater powers of prediction.10 Furthermore, the incremental load test seems to follow a better standardization and is better tolerated and reproducible.11
An increase in respiratory work load and resistance to respiration are expected to cause a decrease in RME in patients with OHS. However, noninvasive ventilation (NIV) is well established as an effective approach in the treatment of patients with OHS.12 In the literature, studies evaluating RME in subjects with OHS are limited. To our knowledge, no study has evaluated RME using the incremental load test in subjects with OHS. Furthermore, no study was found on the impact of the use of NIV on RME. Accordingly, we aimed to evaluate and compare RME in subjects with OHS and a control group. Another aim was to compare the RME of subjects with OHS who did and did not use NIV.
QUICK LOOK
Current Knowledge
There is currently no widely accepted method for calculating global respiratory muscle endurance (RME). Limited studies evaluate RME in subjects with obesity hypoventilation syndrome (OHS), and evidence is scant on the impact of noninvasive ventilation use on RME.
What is this paper contributes to our knowledge
This paper provides objective data as a result of the evaluation of RME with the incremental load test in subjects with OHS. Evaluation of RME with the incremental load test was a simple, accessible, and easily tolerated. Noninvasive mechanical ventilation use can improve RME.
Methods
This study was approved by Istanbul University, Faculty of Istanbul Medicine Institutional Ethical Board (2017/1280). The study was conducted in accordance with the rules of the Declaration of Helsinki and registered at ClinicalTrials.gov (NCT04835558). All subjects gave written informed consent.
All patients from the sleep laboratory with a diagnosis of OHS (BMI ≥ 30 kg/m2 and daytime hypercapnia and sleep-disordered breathing) between February–November 2018 were screened. Patients with OHS with any additional severe respiratory disease and subjects with orthopedic, neurologic, or cardiovascular disease that could interfere with the exercise test were excluded. The remaining subjects with OHS were divided into 2 groups according to their BMI: group I: 30–40 kg/m2; and group II: > 40 kg/m2. The STOP-Bang questionnaire was used for the determination of the control group. Age and sex-matched subjects with obesity (BMI 30–40 kg/m2) with low risk of obstructive sleep apnea (OSA) (STOP-Bang score < 3) were included in the study as the control group.13
Age, sex, BMI, smoking habits, comorbidities, and the use of NIV (CPAP, bi-level positive airway pressure, and average volume-assured pressure support) were questioned. RMS, RME, functional exercise capacity, excessive daytime sleepiness, sleep quality, fatigue severity, and quality of life were assessed. First, RMS and RME were assessed. Rest periods were given between tests. The subjects were then evaluated using the questionnaires. Lastly, functional exercise capacity was evaluated after the subjects rested. All assessments took 45 min for each individual, excluding rest periods. All assessments were performed by the same physiotherapist.
Respiratory Muscle Strength
Maximal inspiratory pressure (PImax) and peak expiratory pressure (PEmax) were measured using mouth pressure measurements (MicroRPM, Vyaire, Chicago, Illinois). The measurements were performed while each subject was seated and wearing a nose clip. During the measurements, the mouthpiece was pressed tightly against the subjects’ lips to prevent air leakage. PImax was measured starting from close to the residual volume after a maximal expiration. PEmax measurements were based on the total lung capacity after a maximal inspiration. The measurements were repeated at least 3 times (until there was < 10% variance between the best 2 values).14 The highest value was taken for analysis. Values were calculated according to age and sex variables using Black and Hyatt reference thresholds and recorded as a percentage of predicted values (for PImax, male = 143 − [0.55 × age], female = 104 − [0.51 × age]; and for PEmax, male = 268 − [1.03 × age], female = 170 – [0.53 × age]).15
Respiratory Muscle Endurance
Subjects were allowed to rest 15 min before the RME test. The incremental load test was performed using an electronic inspiratory loading device (POWERbreathe KHP2; POWER breathe, Southam, Warwickshire, United Kingdom). The subjects were comfortably seated on a chair with their feet on the ground and trunk at a 90° angle in relation to the hips. All subjects were allowed to perform some breathing cycles in the equipment using different loads before starting the test.
The incremental load test started at 20% of PImax. Subjects breathed for 2 min at this load without removing the equipment, using a nose clip, from their mouth during inspiration and expiration. They were instructed to inspire maximally and maintain a constant respiratory pattern during loaded breathing. Every 2 min, the load was increased by 20% of PImax. The final result was defined as the highest load, as a percentage of PImax, achieved and maintained for at least 1 min. The criteria used to terminate the protocol were intolerable fatigue, dyspnea, failure to open the valve at least 3 times consecutively, and the absence of auditory feedback. Audible feedback from devices with the correct respiratory pattern was absent when the respiratory pattern was disrupted. During the test, heart rate and oxygen saturation were monitored.14,16
Functional Exercise Capacity
The 6-min walk test was used to evaluate the functional capacity of the subjects, which was performed in accordance with the European Respiratory Society/American Thoracic Society technical standard.17 The subjects were rested for at least 15 min before commencing the test. They were instructed to walk as far as possible in 6 min in an enclosed 30-m-long corridor. They were encouraged every 60 s using standard phrases. The maximum distance covered at the end of the test was recorded. The test-predicted values were computed using the Enright and Sherrill formulas (for men, 6-min walk distance [6MWD] = [7.57 × heightcm] − [5.02 × age] − [1.76 × weightkg] − 309 m; and for women, 6MWD = [2.11 × heightcm] − [2.29 × weightkg] − [5.78 × age] + 667 m).18
The Turkish version of the Epworth Sleepiness Scale (ESS) was used for the assessment of excessive daytime sleepiness.19 A score of > 10 is accepted as daytime sleepiness.20 The Turkish version of the Pittsburgh Sleep Quality Index (PSQI) was used for sleep quality assessment.21 The total score was interpreted as follows: 0–5 indicated good sleep quality, > 5 indicated poor sleep quality, and > 10 indicated the presence of a sleep disorder.22 The Turkish version of the Fatigue Severity Scale (FSS) was used for fatigue severity assessment during the past week.23 This 7-point Likert scale was used for each item, and the final score was accepted as the mean value of the 9 items. Higher scores indicated greater fatigue severity.24 The Turkish version of the EuroQOL Five Dimensions Questionnaire was used for general quality of life assessment.25 This questionnaire includes 5 questions on mobility, self-care, pain, usual activities, and psychological status, with 3 possible answers for each item scored from 1–3. A summary index with a maximum score of 1 can be derived from these 5 dimensions by conversion with a table of scores. A maximum score of 1 indicates the best health state, and higher scores indicate more severe or frequent problems. In addition, a visual analog scale (VAS) was used to indicate the general health status, in which 100 indicated the best health status.26 The Turkish version of the Obesity and Weight Loss Quality of Life Instrument (OWLQOL) was used to determine the quality of life specific to obesity.27 The questions were answered using a 7-point Likert-type scale for all 17 items. As the total score from the scale approaches 0, the quality of life decreases; and as it approaches 100, the quality of life increases.28
The sample size was calculated according to a pilot study based on the absolute value of RME variables, which revealed that to achieve 90% power with a significance level of 5% the sample for each group should be 15 subjects. However, considering the possibility of subject dropout, 5 additional subjects were added to each group, making 60 subjects in total. The program used was MedCalc statistical software version 12.7.7 (MedCalc, Ostend, Belgium).
Data analysis and calculations were performed using the IBM SPSS Statistics 21.0 software package (IBM SPSS Statistics for Windows, Version 21.0; IBM, Armonk, New York). The variables were investigated using visual (histograms, probability plots) and analytical methods (Kolmogorov-Smirnov test) to determine whether they were normally distributed. Data are presented as mean ± SD, and ordinal variables are indicated as frequency (n) and percentage (%). Pearson chi-square test was used to compare the sex, smoking status, and comorbidities between the groups. The Kruskal-Wallis test was used to compare measurements among the 3 groups. Among the binary groups, variables were compared using Bonferroni corrections using the Mann-Whitney U test. Statistical significance was defined as a P value of < .017 (.05/3 = .017). In 2-group comparisons, P values of < .05 were considered significant. Correlations between RME and functional exercise capacity, sleep, fatigue, and quality of life were evaluated using Spearman correlation analysis. Correlation values are rated as follows: r ≥ 0.81–1.00 = excellent; 0.61–0.80 = very good; 0.41–0.60 = good; 0.21–0.40 = fair; and 0–0.20 = poor.29 The level of statistical significance was set as < 0.05.
Results
A total of 88 patients were screened. Forty subjects with OHS and 20 subjects with obesity were included in the study (Fig. 1). The subjects tolerated the pulmonary function assessments well. The demographic and clinical characteristics of each group are presented in Table 1. There was a significant difference in the BMI, kg/m2, waist/hip (cm), body fat (%), and muscle mass (kg) between the 3 groups. This difference was due to the difference between the group II and the other groups. RME, RMS, and functional exercise capacity are shown in Table 2. There was a significant difference between the 3 groups in terms of RME (P < .001). This difference was due to the difference between the control group and the other OHS groups. However, there was no difference between group I and group II (P = .91). RME, PImax (%), and PEmax (%) in group I were lower in the control group (P = .001, P = .005, and P = .001, respectively). RME and the 6MWD in group II were lower in the control group (P = .001 and P = .01, respectively). No significant difference was found between the 3 groups in terms of 6MWD percentage predicted values (P = .98).
Flow chart. BMI = body mass index. OSA = obstructive sleep apnea
Demographic and Clinical Characteristics of the Subjects
Comparison of Respiratory Muscle Endurance, Respiratory Muscle Strength, and Functional Exercise Capacity
The RME and RMS of subjects with OHS who did and did not use NIV are shown in Table 3. RME in the NIV user group was higher in the non-user group (P = .006). Daytime sleepiness, sleep quality, fatigue severity, and quality of life are given in Table 4. ESS, total PSQI, and FSS scores in the control group were lower in group I (P = .01, P = .009, and P = .005, respectively) and group II (P = .01, P < .001, and P < .001, respectively). The EQ-5D Health-Related Quality of Life Questionnaire (EQ-5D) scores of the control group were higher in group II only (P = .005 and P = .005, respectively). There were no differences in OWLQOL between the groups (P = .053).
Comparison of Respiratory Muscle Endurance and Respiratory Muscle Strength of Subjects With Obesity Hypoventilation Syndrome According to NIV Use
Comparison of Daytime Sleepiness, Sleep Quality, Fatigue, and Quality of Life
There was a statistically significant fair and good correlation between RME and 6MWD (r = 0.319, P = .01), EQ-5D index (r = 0.527, P < .001), and EQ-5D VAS (r = 0.506, P < .001) scores in subjects with OHS and controls. No correlation was observed between RME and 6MWD percentage (r = 0.217, P = .10). In addition, there was a good negative correlation between RME and ESS (r = −0.408, P < .001), total PSQI (r = −0.526, P < .001), and FSS (r = −0.480, P < .001) scores in subjects with OHS and controls.
Discussion
Our study showed that the RME values of the OHS group were lower in the control group. It was also found that the RME values of the subjects with OHS who used NIV were higher in non-users. The incremental load test was easily applied and tolerated by our participants. RME was correlated with functional exercise capacity, quality of life, excessive daytime sleepiness, sleep quality, and fatigue severity in subjects with OHS and controls.
Respiratory muscle function in patients with obesity may be compromised by increased muscle load.30 As a result, respiratory muscle fatigue may develop, which is associated with RME.31 Therefore, RME measurements could be useful in clinical practice for evaluating patients and responses to treatment and rehabilitation.7 There is no generally accepted test in the literature for evaluating RME.7,9 Maximal voluntary ventilation, the incremental load test, and the constant load test are used for measuring RME.6,7 Maximal voluntary ventilation measurements are highly sensitive to relatively small changes in flow resistance, which has the disadvantage that its effects increase exponentially as ventilation increases.7
The incremental loading protocol is reported to be more reliable because it shows less variability and greater powers of prediction when compared with the constant loading protocol.10 Additionally, it seems to follow better standardization and is better tolerated and reproducible.11 Studies showed that maximal voluntary ventilation, which is an indicator of RME, was decreased in obese subjects and those with OHS.32,33 We found no studies that evaluated RME with the incremental load test in subjects with OHS. Therefore, in our study, we preferred to evaluate RME using the incremental load test, which can be easily applied in the clinic and is cost effective. We found that the incremental load test was well tolerated by our participants and could be performed safely.
Nocturnal-NIV can rest chronically fatigued muscles, and periods of rest may lead to recovery of the inspiratory muscle function, thereby leading to increased muscle strength and endurance capacity of respiratory muscles during the daytime.34 We found no studies about the effect of using NIV on RME in OHS. In patients with Duchenne muscular dystrophy, the load on respiratory muscles increases and endurance capacity decreases due to increased breathlessness during the day. Nocturnal NIV treatment improves this situation.35 Similarly, NIV is associated with an increase in inspiratory muscle endurance in restrictive ventilatory disease.36 RME was higher in NIV-using subjects than in those not using NIV in this study. This result may be interpreted that NIV improves RME in OHS.
Obesity has been reported to have various effects on RMS. It is thought that the stress caused by excessive fat accumulation in the thoracic and abdominal areas in individuals with obesity causes a mechanical disadvantage for the respiratory muscles.37 However, some studies have shown that subjects with obesity have normal RMS and even better strength than normal-weight subjects.38 This situation is explained by the adaptation of the muscle fibers against the increased load on the respiratory muscles of obese patients.39 In our study, when the groups with OHS were compared against each other, the PImax and PEmax values in group I were similar to those in group II. This result supports the adaptation of respiratory muscle fibers as BMI increases. On the other hand, PImax and PEmax values were found to be significantly lower in group I compared with the control group. This result can be interpreted as that the presence of hypoventilation may affect RMS in a person with a similar BMI.
Villiot-Danger et al40 found a positive relationship between the change in RME and 6MWD changes in their study, in which they gave RME training to subjects with obesity. Our study supports their results because longer 6MWD was associated with better RME when all participants were included in the analysis. However, better RME was not associated with a higher 6MWD percentage when analyzed as predicted values due to the effect of weight. When the groups were compared, only the 6MWD of the control group was longer than in group II. This result may be related to the fact that the subjects in group II were morbidly obese in addition to having low RME. The influence of weight, on the other hand, resulted in similar percentage predicted values between the groups.
In our study, higher RME was associated with better sleep quality, excessive daytime sleepiness, and fatigue severity in all subjects. Furthermore, when the groups were compared in terms of ESS, total PSQI, and FSS scale scores, the values of the control group were higher in group I and group II. This result supports that the presence of hypoventilation reduces sleep quality and increases excessive daytime sleepiness and fatigue severity. However, the better RME of the control group compared with the OHS groups may have been effective. The lack of difference between the OHS groups suggests that the increase in BMI in OHS does not affect sleep quality, excessive daytime sleepiness, and fatigue severity. The similar RME of OHS groups may have affected this situation.
We found that higher RME was associated with better quality of life in all subjects. When the groups were compared, only the control group's EQ-5D scale values were significantly higher in group II. In addition to the low RME of group II, morbid obesity may have affected this result. Although the RME of the control group was significantly higher in group I, there was no difference in terms of quality of life.
When the OWLQOL score was examined, there was no statistically significant difference between the groups. The OWLQOL score of the control group, whose RME was significantly higher compared with the OHS groups, was similar to these groups. Also, no relationship was found between RME and OWLQOL scores. The reason for this may be that, regardless of the RME, considering the content of the scale, the questions were mostly social (eg, not being able to wear what they want due to being overweight, not taking pictures, envying thin people); and the 3 groups were obese, resulting in a similar effect. A few studies have evaluated RME in subjects with OHS in the literature; however, our study is the first to evaluate RME in subjects with OHS using the incremental load test and to compare it with a control group. It was observed that the incremental load test, an easily applied, cost-effective clinic test, was well tolerated by the subjects and could be performed safely.
Subjects with obesity in the control group were not evaluated using polysomnography in the present study due to its high cost. They were only screened using the STOP-Bang questionnaire to exclude OSA. However, STOP-Bang is a highly sensitive screening tool for sleep apnea.13 In addition, those with a BMI over 40 kg/m2 were not included in the control group because they were at high risk for comorbidities and sleep apnea. Thus, no data could be given for this group. These may be limitations of this study.
Conclusions
The main points of our study are that the RME in the OHS groups was found lower than in the control group. The incremental load test was well tolerated by our participants and could be performed easily and safely in a clinic setting. In addition, RME in the NIV-using group was higher in non-users. Excessive daytime sleepiness, sleep quality, fatigue severity, and quality of life were significantly correlated with RME in all participants. In the control group, with better RME, daytime sleepiness and fatigue scores were lower and sleep quality was better than in the OHS groups. Further studies should investigate the effects of RME training on outcome measures such as functional exercise capacity, sleep, fatigue severity, and quality of life in OHS.
Acknowledgments
The authors would like to thank all the participants and all staff of Istanbul Medical Faculty, Department of Chest Diseases, Istanbul University.
Footnotes
- Correspondence: Goksen Kuran Aslan PT PhD, Istanbul University-Cerrahpasa, Faculty of Health Sciences, Division of Physiotherapy and Rehabilitation, Buyukcekmece, Istanbul, Turkey. E-mail: goksenkuran{at}yahoo.com
The study was registered at ClinicalTrials.gov, number NCT04835558.
The authors have disclosed no conflicts of interests.
This study was supported by Istanbul University-Cerrahpasa Research Foundation, project number 29713.
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