Chronic obstructive pulmonary disease (COPD) is a condition that adversely affects the autonomic function of the heart, promoting reduced heart rate variability (HRV).1–9 Subsequently, it results in the onset of arrhythmias and increased risk of morbidity and mortality.10 Analysis of HRV is an important valuable noninvasive marker of autonomic nervous system modulation of the sinoatrial node and is regularly used to study the underlying physiological processes involved in cardiovascular control, both at rest and during exercise.11
In addition to autonomic dysfunction, COPD also produces significant systemic consequences such as nutritional depletion, physical deconditioning, systemic inflammation, and structural and functional changes in the respiratory and locomotor muscles,12 , 13 resulting in deterioration in the quality of life (QoL)14 and functional capacity (FC).15
Pulmonary rehabilitation is one effective intervention in patients with established COPD. Exercises usually consist of walking, cycling and gym work. Gym-based exercises may be difficult for some patients with COPD, who tend to be mainly elderly and may have other comorbidities that may impair their ability to exercise at higher intensities.16 Therefore water exercise training may be an option, since immersion produces an increased stroke volume and decreased heart rate (HR), improves cardiovascular fitness, and optimizes the work of the respiratory muscles, beyond reducing the residual FC and residual volume, consequently causing a decreased sensation of dyspnea and facilitating the performance of aerobic exercises.17–20
Land-based exercise programs have demonstrated positive effects on HRV, QoL, and exercise tolerance of the patients with COPD.21–25 However, the effect of water-based exercise program needs to be further investigated. Whereas immersion has profound biological effects, extending across essentially all homeostatic systems and water-based therapies are beneficial in the management of patients with cardiopulmonary pathology and other conditions17 the hypothesis is that the exercises performed in water could also promote beneficial adaptations in COPD patients. So, the aim of this study was to evaluate the effects of a water aerobic interval physical training program on the autonomic modulation of HR, QoL, and FC of COPD patients.
The sample size was based on a previous pilot study performed by the primary researcher to identify the presence of autonomic modulation of HR response to exercise of the men with a diagnosis of COPD. This study used the GraphPad StatMate version 2.0 (GraphPad) for sample size calculation in which the effect size of 0.75 (α = .05) and the statistical power of 80% were adopted, which resulted in a minimum number of 14 patients considering an analysis of variance for repeated measures.
Patients were allocated to 2 groups, by random drawing, one being the usual care group (UCG), which underwent conventional medical treatment and participated only in the evaluations, and the other the training group (TG) that underwent conventional medical treatment and participated in the assessments and water-based aerobic interval training. This study was approved by the research ethics committee of the university (#13.11). All patients signed the informed consent form and this randomized clinical trial study was registered with the Clinical Trials Registry (NCT02116114).
SETTING AND PARTICIPANTS
The study was conducted in the Laboratory of Evaluation and Intervention in Cardiorespiratory Physical Therapy of the Postgraduate Program in Physical Therapy at the Methodist University of Piracicaba. A total of 62 men were screened, of whom, 24 were selected and initially included in the experimental protocol. Inclusion criteria consisted of diagnosis of COPD according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classifications I/II/III/IV26; clinically stable with a sedentary lifestyle according to the IPAQ (International Physical Activity Questionnaire)27; no exacerbations in the previous 3 mo; absence of diabetes mellitus, endocrine disorders, chronic renal failure, liver disease, other lung diseases, associated inflammatory diseases, or heart diseases; not using medications that prevented physical exercise; no presenting musculoskeletal or neuromuscular issues that made it impossible to perform the experimental protocols; and not presenting with dermatological disorders, hypersensitivity to the products used for the treatment of swimming pool water, or hydrophobia. Patients were discontinued if they did not attend ≥80% of the training sessions.
The randomization was carried out by means of a numeric table generated by randomization software (StatMate 2.0 for Windows, GraphPad). The table was made with a list of 24 numbers to be distributed in 2 groups. Each list number with the group sequence was individually placed in an opaque envelope, which was numbered and closed. This step was performed by a researcher in charge of the randomization of the study who was blinded to other aspects of the study. The set of envelopes was given to the researcher responsible for the interventions and, later, the envelopes were opened to identify to which group the patients were assigned. The study was blinded, so data collection and analysis of results were performed by different teams of researchers.
Patients remained on their usual medications during evaluations and training program. They used short-acting and long-acting bronchodilators but did not use medications such as oral steroids, antibiotics, antihypertensives, or β-blockers.
PULMONARY FUNCTION TESTING
Patients underwent pulmonary function testing using a spirometer (Easy One, ndd Medical Technologies), according to the criteria of the American Thoracic Society and the European Respiratory Society.28 The prediction equations were used considering the reference values for the Brazilian population, determined by Pereira et al.29
MEASUREMENT AND ANALYSIS OF HRV
A model RS800CX HR monitor (Polar Electro Company) was used to record the HR and R-R interval (RRi). Data acquisition was collected using the Polar system at rest in the supine position for 15 min. An elastic belt was attached to the chest of the patients at the level of the lower third of the sternum. The belt contained a stable case with HR electrodes, an electronic processing unit, and an electromagnetic field transmitter. The HR signals were continuously transmitted to the Polar Advantage receiver unit via an electromagnetic field.
The HRV was analyzed using Kubios HRV analysis software (Kubios) from linear and nonlinear models. Visual inspection of the distribution of RRi in milliseconds was also performed of the data from the total collection time in the supine position. Next, a section of 5 min of data was selected. We discarded the initial 60 sec of data and selected the most stable signal. Heart rate variability was analyzed by time (index of parasympathetic modulation of HR and the overall HRV) and frequency domain methods (expressing the components of low frequency [0.04-0.15 Hz] that was attributed to the modulation of the sympathetic and parasympathetic nervous system with sympathetic predominance and high frequency [0.15-0.4 Hz], which related to parasympathetic modulation).11
The analysis of the Poincaré plot was based on the nonlinear dynamic, a geometric method to analyze the RRi variations. For the quantitative analysis, the following indices were calculated: SD1 (standard deviation of the instantaneous beat-to-beat variability) and SD2 (long-term standard deviation of continuous RRi).30
EVALUATION OF QOL
The QoL was evaluated using the version of the St George's Respiratory Questionnaire validated for use in Brazil.31 This instrument includes 3 domains: Symptoms, Activities, and Impact. A total score is also calculated. The results were expressed in percentages ranging from 0% to 100%. Higher scores equate to worse QoL.32
EVALUATION OF FC
The FC evaluation was performed using the 6-min walk test (6MWT), using 30 m of a corridor that was ventilated, illuminated, and quiet, with a smooth, nonslippery surface, delimited by 2 cones and with markings every meter. Two tests were performed with a minimum interval of 30 min between them, which were administered by 2 evaluators.33 The repetition of the test was aimed to eliminate a possible learning effect and to ensure reproducibility of the procedure, with the better performance used for the data analysis. The patients were monitored during the test and, so as not to influence the walking speed, the therapist stayed behind them. They were instructed to walk at the maximum possible speed for 6 min. During the walk, they received incentives from the therapist, through verbal stimuli every minute. The test was performed according to the recommendations of the American Thoracic Society.34 Blood pressure (BP), HR, respiratory rate (RR), oxygen saturation as measured by pulse oximetry (SpO2), and dyspnea and fatigue in the lower limbs scores, as assessed by the Borg scale, were recorded at the beginning and end of the 6MWT. If desaturation (SpO2<90%) occurred, the test was stopped, supplemental oxygen was provided, and another test was started.35 , 36
WATER-BASED AEROBIC EXERCISE INTERVAL TRAINING PROTOCOL
The training was conducted according to the water aerobic interval exercise protocol for approximately 60 min every other day, 3 times per week for 8 wk for a total of 24 sessions.37 , 38 Before each session, BP, HR, respiratory rate, SpO2, subjective perceived exertion for dyspnea (Borg scale), and lower limb fatigue (Borg LL) were obtained and recorded. The sessions were individual and, at every 10 min of therapy, the HR, SpO2, and subjective perception of respiratory and lower limb effort were monitored using a model FT1 HR monitor (Polar Electro Company), a model 9500 ONYX pulse oximeter (Nonin), and the Borg CR-10 scale, respectively.39
The physical training program was developed in a heated swimming pool with water temperature of approximately 32°C and included (1) warm-up (10 min) including stretching, calisthenics, and low-intensity exercises; and (2) aerobic exercises (20-40 min) including exercises for the trunk, upper limbs, and lower limbs that involved the hips, feet, ankles, hands/wrists, and shoulders. The specific water exercises used in the study were performed according to a previously described protocol,40 adapted to the conditions of patients with COPD. The prescribed intensity was based on a Borg CR-10 scale rating of 4 to 6.41–43 Training was divided into 6 steps with a break of 1 min between them. The 6 steps were as follows: Step 1: moderate intensity with the aim of reaching 4 on the Borg scale; steps 2 and 4: moderate-high intensity with the aim of reaching 5 on the Borg scale; steps 3 and 5: moderate-high intensity with the aim of reaching 6 on the Borg scale; and step 6: moderate intensity with the aim of reaching 4 on the Borg scale. The initial duration was eight 20-min sessions, progressing to 8 sessions of 30 min, and finishing with eight 40-min sessions.37 , 38 During all sessions, the patients were instructed to breathe with pursed lips. If during the execution of the exercises the SpO2 values fell below 90%, supplemental oxygen was made available.35 , 36 The third part of each exercise session was a cooldown (10 min), which consisted of stretching and respiratory exercises to allow the BP and HR to return to near-basal values.
Data were expressed as mean ± standard deviation. Statistical analysis was done using the SPSS 13.0 program (IBM). The Shapiro-Wilk test was used to check the distribution of the data that were normality distributed for all variables. The χ2 test was used to compare the physical activity level, GOLD classification, and medications used between the groups. The paired Student t test was used for the analyses of intragroup significance, and the unpaired Student t test for the intergroup analyses. To analyze the relationship between the variables, the Pearson product-moment correlation coefficient was used. A P value of <.05 was used to determine statistical significance.
The influence of the training was tested using a measure of effect size to compare the results of the TG with those of the UCG. For this, the pooled Cohen d method was used. This analysis was performed using the Effect Size Generator, version 2.3 (Swinburne University of Technology, Australia) program. Results were interpreted according to the proposal of Cohen,44 with 0.2 being considered a small effect, 0.5 an average effect, and >0.8 a large effect.
A total of 19 patients with COPD were included in the final analysis and their baseline characteristics are presented in Table 1. There were no significant between-group differences in baseline characteristics. The inclusion, allocation, monitoring, and analysis of the patients are shown in Figure 1. Over the course of the study, 5 patients dropped out because of exacerbations and, therefore, the study was completed with 9 and 10 patients in the UCG and the TG, respectively.
The HRV, QoL, and FC results are presented in Tables 2 to 4, respectively. In the TG following the training intervention, there were significant improvements in all the HRV indices, whereas the UCG did not present with any significant changes. In between-group comparisons, significant differences were observed for all post-training variables in the TG (Table 2).
Regarding QoL, it was observed that between the pre- and post-training conditions, there was a significant worsening in the Symptoms, Impact, and Total domains in the UCG, whereas in the TG, there was improvement in all domains. In comparing between the groups, there were significant differences in all domains in the post-training condition in the TG (Table 3).
In the 6-min walk test distance (6MWD), there was no significant difference when comparing pre- and post-training conditions in the CG; however, there was a significant increase of 15.8% in the TG. In the intergroup comparison, the TG showed higher values than the CG in the post-training condition (Table 4).
The calculation of the effect size between the UCG and TG showed that for all variables, the water-based exercise training protocol provided a large training effect, with values above 0.8.
The correlation between QoL and the HRV index, as well as the relationship between QoL and FC for all 19 patients, showed a negative correlation. Delta for the QoL Total domain, and delta for the root mean square of successive differences index, was r =−0.55 (P = .01) and delta for the QoL Total domain, and delta for the 6MWD, was r =−0.49 (P = .02). These data are presented in Figure 2.
The main results of this study showed significant improvement in the autonomic modulation of HR, QoL, and FC after the water-based aerobic interval exercise program for the rehabilitation of patients with COPD, as well as a large training effect for all the variables studied.
The significant changes in the HRV indices, observed through an increase in parasympathetic modulation after the water-based training, are consistent with results from studies with physical training conducted on land.21–25 The reasons for this improvement are possibly related to decreased anxiety and circulating catecholamine levels6 , 45 and the adaptations of the peripheral muscles, promoted by the physical training, since individuals with COPD have a higher sympathetic modulation due to the release of ischemic metabolites generated during muscle contraction, which stimulate receptor sites and cause increased HR, BP, and sympathetic activity.46 Another factor is that physical training promotes the release of nitric oxide, which has been shown to play a significant role in increasing the cardiac vagal modulation and to indirectly inhibit the sympathetic influence.47 , 48
In addition to the benefits inherent to the physical training itself, the physical characteristics of water and the physiological effects of immersion should also be considered as possible improvement mechanisms, since hydrostatic pressure increases peripheral blood flow, reduces venous pressure, and stimulates parasympathetic activity, promoting an increase in venous return as a result of baroreflex control.17 , 49
The improvement in QoL is one of the most important outcomes after pulmonary rehabilitation programs, with a ≥4% reduction in the St George's Respiratory Questionnaire scores, regarded as the minimum clinically important difference.50 The results from this study demonstrated that in the TG, there were significant reductions in all St George's Respiratory Questionnaire domains, demonstrating the beneficial effects of the proposed training on QoL, which is consistent with studies related to physical training on land.18 , 23 , 51 , 52 Together, the results of these studies and the present investigation suggest that the effect of physical training contributes to the improvement of QoL in patients with COPD.
In addition to the improvement in QoL, a correlation between QoL and the root mean square of successive differences temporal index was also observed, demonstrating its influence on cardiac autonomic modulation. Because autonomic dysfunction is related to stress, anxiety, and depression,53 the results suggest that a decrease in the QoL scores can contribute to an improvement in HRV.9 , 23 , 25
The water-based training also generated significant increases in FC in the TG, which was assessed by 6MWD. In the interpretation of the changes in the distance walked, the minimum clinically important difference of 26 ± 2 m and/or >10% was adopted.54 In the TG, it was verified that between the pre- and post-training there was an increase of 74.9 m, representing 16%. These results support the findings of studies conducted with land-based exercise programs.21 , 23 , 24
Aerobic exercise training promotes physiological adaptations, which may be enhanced when performed in the water, due to the added benefits of hydrostatic pressure and buoyancy, which offer constant resistance to motion.17 , 55 The improved FC obtained after the training program possibly relates to the beneficial effects of physical exercise itself, associated with the action of hydrostatic pressure, increasing stimulation of the production of mitochondrial oxidative enzymes, increasing capillarization of the trained muscles,56 and enlarging the muscle cross-sectional area.57
The results of this study are promising, since they suggest that water-based aerobic interval training resulted in beneficial adaptations of patients with COPD; however, study limitations must be mentioned. The small number of participants studied is a limitation. The sampling selection criteria and difficult access to this population made the recruitment of more participants impossible. Two additional limitations were the fact that all of the participants were males and so the results cannot be extrapolated to females, and this was a single center study with all patients recruited from 1 program, making the results less generalizable.
Considering the present results, we can conclude that the study demonstrated that 24 sessions of water-based aerobic interval exercise training promoted beneficial adaptations in the autonomic modulation of the HR at rest, improvements in QoL, and significant increases in FC, suggesting that it may be an important therapeutic strategy in the rehabilitation of patients with COPD.
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Keywords:Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
autonomic nervous system; COPD; functional capacity; hydrotherapy; quality of life