564087
research-article2015
CRE0010.1177/0269215514564087Clinical RehabilitationReyes et al.
CLINICAL REHABILITATION
Original Article
Respiratory muscle training on pulmonary and swallowing function in patients with huntington’s disease: A pilot randomised controlled trial
Clinical Rehabilitation 1–13 © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0269215514564087 cre.sagepub.com
Alvaro Reyes1, Travis Cruickshank1, Kazunori Nosaka2 and Mel Ziman1,3
Abstract Objective: To examine the effects of 4-month of respiratory muscle training on pulmonary and swallowing function, exercise capacity and dyspnoea in manifest patients with Huntington’s disease. Design: A pilot randomised controlled trial. Setting: Home based training program. Participants: Eighteen manifest Huntington’s disease patients with a positive genetic test and clinically verified disease expression, were randomly assigned to control group (n=9) and training group (n=9). Intervention: Both groups received home-based inspiratory (5 sets of 5 repetitions) and expiratory (5 sets of 5 repetitions) muscle training 6 times a week for 4 months. The control group used a fixed resistance of 9 centimeters of water, and the training group used a progressively increased resistance from 30% to 75% of each patient’s maximum respiratory pressure. Main measures: Spirometric indices, maximum inspiratory pressure, maximum expiratory pressure, six minutes walk test, dyspnoea, water-swallowing test and swallow quality of life questionnaire were assessed before, at 2 and 4 months after training. Results: The magnitude of increases in maximum inspiratory (d=2.9) and expiratory pressures (d=1.5), forced vital capacity (d=0.8), forced expiratory volume in 1 second (d=0.9) and peak expiratory flow (d=0.8) was substantially greater for the training group in comparison to the control group. Changes in swallowing function, dyspnoea and exercise capacity were small (d≤0.5) for both groups without substantial differences between groups. Conclusions: A home-based respiratory muscle training program appeared to be beneficial to improve pulmonary function in manifest Huntington’s disease patients but provided small effects on swallowing function, dyspnoea and exercise capacity. 1School
of Medical Sciences, Edith Cowan University, Joondalup, WA, Australia 2School of Exercise and Health Sciences, Centre for Exercise and Sports Science Research, Edith Cowan University, Joondalup, WA, Australia 3School of Pathology and Laboratory Medicine, University of Western Australia, Crawley, WA, Australia
Corresponding author: Alvaro Reyes, School of Medical Sciences, Edith Cowan University, 270 Joondalup Drive, Joondalup, WA 6027, Australia. Email: [email protected]
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2
Clinical Rehabilitation
Keywords Respiratory function, swallowing, Huntington’s disease, dysphagia, pulmonary rehabilitation Received: 1 September 2014; accepted: 22 November 2014
Introduction Patients with Huntington’s disease experience pulmonary and swallowing abnormalities leading to difficulties in clearing airway secretions.1 Huntington’s disease patients generally have restricted mobility which may lead to poor exercise tolerance resulting in fatigue and dyspnoea on exertion.2,3 This limits their ability to perform activities of daily living, which further lead to muscle weakness.4,5 Our recent study has shown that manifest Huntington’s disease patients have lower respiratory pressure, forced vital capacity, peak expiratory flow and maximum voluntary ventilation in comparison to age and gender matched healthy individuals with similar anthropometric characteristics.6 Given that the main cause of death in Huntington’s disease is a complication arising from poor pulmonary function,7 interventions to maintain and improve pulmonary function are crucial for these patients. Respiratory muscle training has been utilized in neurodegenerative disorders such as Parkinson’s disease,8–11 amyotrophic lateral sclerosis,12 and multiple sclerosis4,13–16 to improve pulmonary and swallowing function as well as exercise capacity. The results of these studies have shown that a respiratory muscle training program for 4–10 weeks, 5–6 days a week (at least 25 inspiratory or expiratory manoeuvres each day) with progressively increased load, improves maximum respiratory pressures, cough function, dyspnoea sensation and spirometric indices in patients with Parkinson’s disease and multiple sclerosis.17 However, no previous studies have reported the effects of respiratory muscle training on pulmonary function in Huntington’s disease patients. Because of some similarities between Huntington’s disease and the aforementioned neurodegenerative disorders at least for the symptoms associated with pulmonary dysfunction,17 it was assumed that respiratory
muscle training would be also effective for Huntington’s disease patients. Therefore, the purpose of this study was to examine the effects of 4-month of respiratory muscle training on pulmonary and swallowing function, exercise capacity and dyspnoea in manifest patients with Huntington’s disease.
Methods Participants Participants with manifest Huntington’s disease were screened for eligibility using the Huntington’s Enrichment Research Optimisation Scheme Database. This database includes a group of patients who had recently participated in a multidisciplinary rehabilitation program so generally met the inclusion criteria.18 Participants were also screened by the Western Australia Huntington’s Disease Association. Potential participants were first contacted by telephone and later visited at their home. Inclusion criteria were a positive genetic test, clinically verified disease expression (Unified Huntington’s Disease Rating Scale–Total Motor Score [UHDRS-TMS] ≥5),19 and the ability to understand and respond to the instructions given in the study. Exclusion criteria were other confounding neurological disorders, current smokers, participants with a history of cardiovascular pathology, lung disease or the presence of respiratory symptoms such as cough, phlegm, wheezing or dyspnoea at the time of assessment. Participants who had difficulties in maintaining a proper mouth seal, unable to avoid air leakage, or had excessive choreic movements of the tongue during pulmonary function testing were excluded. Informed written consent was obtained from the participants, and the study was approved by the Human Research Ethics Committee of Edith Cowan University.
Downloaded from cre.sagepub.com at UNIV NEBRASKA LIBRARIES on October 11, 2015
3
Reyes et al.
Recruitment
Assessed for eligibility (n= 26) Excluded (n= 8) Not meeting inclusion criteria (n= 3) Declined to participate (n= 5)
Randomized (n= 18)
Baseline Allocated to control group (n=9) Did not receive allocated intervention (n= 0)
Allocated to training group (n=9) Did not receive allocated intervention (n= 0) 2 months
Lost to follow-up (n= 0) Discontinued intervention (n= 0)
Lost to follow-up (n=0) Discontinued intervention (n=0)
4 months Analysed (n=9) Excluded from analysis (n=0)
Analysed (n=9) Excluded from analysis (n=0)
Figure 1. Progress of participants through the trial.
Study design All the participants of the study were interviewed regarding their general health status, cardio-vascular and smoking history as well as their respiratory condition. The body mass and height were recorded for each participant using an accurate and calibrated scale (HW200, A&D Mercury Pty, Ltd, Thebarton, SA) and a wall-mounted stadiometer (Model 220, SECA, Hamburg, Germany). After baseline measurements, participants were randomly divided into two groups using the randomisation block method. Given that 18 participants were recruited, randomisation was performed using six blocks and three cells per block (number of participants=number of blocks*number of cells per block). Nine participants were assigned to receive home-based respiratory muscle training (training group), and 9 participants were assigned to receive home-based respiratory muscle training at minimum and fixed load (control group). Allocation concealment was implemented
using sequential sealed envelopes prepared by an independent research assistant (Figure 1).
Training protocol Participants in the training group used a Threshold® Inspiratory Muscle Trainer (HS730-010. Phillips Respironics, USA) and an Expiratory Muscle Trainer (EMST150. Aspire Products, LLC). They performed a home-based inspiratory (5 sets of 5 repetitions) and expiratory muscle training (5 sets of 5 repetitions), 6 times a week for 4 months. These training parameters were chosen, because a previous study17 has shown significant improvements in pulmonary and swallowing function in patients with Parkinson’s disease and multiple sclerosis using a similar protocol. Participants in the training group started training at a resistance equal to 30% of their average maximum inspiratory pressure and maximum expiratory pressure, respectively which were calculated based on maximum inspiratory
Downloaded from cre.sagepub.com at UNIV NEBRASKA LIBRARIES on October 11, 2015
4
Clinical Rehabilitation
pressure and maximum expiratory pressure baseline measurements described below. This initial resistance training was based on the results of a study20 showing that a resistance lower than 30% of maximum inspiratory pressure was insufficient to produce improvements in pulmonary function. The training protocol was designed to reach a training intensity of 75% of maximum inspiratory pressure/ maximum expiratory pressure in the fourth month of training, therefore the resistance was increased progressively by 15% of each participant’s maximum inspiratory pressure and maximum expiratory pressure every month at the end of each month of training. Participants in the control group used a Threshold® PEP (HS-735-010. Phillips Respironics, USA) for both inspiratory muscle training and expiratory muscle training, because this device provides lower resistance for both inspiratory and expiratory flows than those devices used by the training group. They trained with the same protocol to the participants in the training group for the same number of repetitions, frequency and duration, but the intensity was fixed at the minimum load of the device, 9 centimetres of water throughout the training period. Before the commencement of the training, participants in both groups were instructed for the correct use of the training devices. For inspiratory muscle training, they were instructed to initiate their inspiration from near to residual volume, while for expiratory muscle training, they were asked to blow as forcefully as possible into the mouthpiece of the trainer device from total lung capacity. In both cases participants used a nose clip in order to ensure that airflow occurred entirely through the mouth. All participants were asked to mark on the provided training diary when they completed a training session. We visited the home or caregiver institution of each participant in both groups, every two weeks, and made daily phone contacts or sent daily text messages from Monday to Friday throughout the study period to ensure that they were training as instructed. Every two weeks, maximum inspiratory pressure and maximum expiratory pressure were reassessed at each participant’s home or caregiver institution as described
below. In this study we used the pressure threshold modality in which the load valve of the training device remains closed until enough inspiratory or expiratory pressure is generated against the valve to release it and allow airflow. Therefore maximum inspiratory and expiratory pressure measurements were used to adjust the resistance of the devices every two weeks for the training group.
Measurements Spirometric indices, maximum inspiratory pressure, maximum expiratory pressure, six minute walk test, dyspnoea, water-swallowing test and the swallow quality of life questionnaire were taken during the three weeks before the commencement of the training to obtain baseline assessment. Measurements of maximum inspiratory pressure and maximum expiratory pressure were performed over 3 testing sessions with a week apart to assess the test-retest reliability. For those participants who had difficulties achieving acceptable and reproducible spirograms (standardization of spirometry) on a testing day, the measurement was repeated on a different day, to ensure an accurate spirometry (acceptability criteria).21 Spirometry, maximum inspiratory pressure, maximum expiratory pressure and water-swallowing test measurements were repeated at 2 and 4 months after training. Dyspnoea, six minute walk test and swallow quality of life questionnaire measurements were taken at baseline and at 4 months in the training period. All measurements were performed at the same place and same time of the day. To minimize possible acute effects of the training session on the measures, 1 or 2 days were inserted between the training session and the measurements. For maximum inspiratory pressure and maximum expiratory pressure measurements, each participant was asked to sit upright with a nose clip in place to prevent nasal air leakage. A flanged rubber mouthpiece was connected to a pressure manometer (Micro RPM, Micro Medical-Care Fusion, Kent, UK) and placed in the mouth. Participants were asked to hold the pressure manometer with both hands and to create a tight lip seal around the flanged mouthpiece. A flanged mouthpiece was
Downloaded from cre.sagepub.com at UNIV NEBRASKA LIBRARIES on October 11, 2015
5
Reyes et al. used as recommended by the American Thoracic Society and European Respiratory Society.21 This method was used, since the portability of the manometer was advantageous for clinical use and its reliability had been assessed.22 For maximum expiratory pressure assessment, participants were asked to breathe in to total lung capacity and then to blow hard into the mouthpiece. For maximum inspiratory pressure assessment, they were instructed to breath out to residual volume and then to breath in with maximum effort through the mouthpiece. Inspiratory and expiratory efforts were required to be maintained for more than one second. The order of procedures was the inspiratory followed by the expiratory effort. Both manoeuvres were repeated a minimum of 5 times with a 30-s rest until three trials showed values within 5% variation of each other. The best result from at least five respiratory manoeuvres was used for further analysis as described by Black and Hyatt (1969)21 and the professional society guidelines. Results of maximum inspiratory pressure and maximum expiratory pressure are expressed as absolute values, because no suitable predictive equations are available. Spirometric assessment was performed using a spirometer (Medgraphics, model CPFS/D, St. Paul MN, USA) connected to a laptop computer (Dell, Latitude E6510, USA). The spirometer met all the quality control requirements of the American Thoracic Society and was calibrated before each testing session with a Hans Rudolph 3.0 syringe, based on the manufacturer’s recommendations. In accordance with the professional society guidelines, each participant was asked to sit upright with a nose clip in place to prevent nasal air leakage. Participants were instructed to perform spirometric maneuvers in the following order: slow vital capacity, a forced vital capacity and maximal voluntary ventilation. Each manoeuvre was repeated at least 3 and a maximum of 8 times, with 1–2 min rest between attempts. The best result from the three technically acceptable manoeuvres was used for further analysis. From these measurements, forced expiratory volume in one second, peak expiratory flow and the ratio of forced expiratory volume in one second to forced vital capacity from the largest
forced expiratory volume in one second and forced vital capacity were calculated. Predicted values were calculated for all participants using Stanojevic (2008) prediction equations, which include age, height, weight and gender. These prediction equations include reference values for forced vital capacity and forced expiratory volume in one second, and have been validated for a Caucasian Australasian population.23 Peak expiratory flow predicted values were calculated using Nunn and Gregg (1989)21 regression equations. To assess functional exercise capacity, participants performed the six-minute walk test. The test was performed outdoors on a 20 m long walking course. The length of the walking course was marked every 5 m with plastic cones. The test was performed following the professional society guidelines.24 Perception of dyspnoea was recorded before and immediately after the test using a Borg scale. Predicted values for six-minute walk test were calculated using Enright25 regression equations. Swallowing function was evaluated by the water-swallowing test26 and the swallow quality of life questionnaire that is a specific autoadministered test for evaluating the impact of swallowing problems on quality of life.27 For the water-swallowing test, participants were asked to drink 50-mL water at ambient temperature (20–25°C) from a plastic cup as quickly and as comfortably as possible in a sitting position, while being timed. Using a stopwatch, the time taken from when the first drop of water touched the lips to when the larynx of the patient came to rest after the last swallow was measured. Participants were instructed to drink all water without stopping. The swallowing test was performed three times, with an interval of at least 30 seconds between times. The examiner counted the number of swallows determined by the number of upper movements of the larynx. Each measurement was performed in the presence of at least two examiners to ensure when to start and stop the measurement. In addition to the time and number of swallows needed to ingest 50 mL of water, the drinking speed (ml/s), the time for one swallow (s), and the amount of water in one swallow (ml) were calculated.26
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6
Clinical Rehabilitation
Statistical analysis Descriptive data are given as mean, standard deviation and range. To compare physical and physiological characteristics and baseline measurements between training and control groups, an independent t-test was performed. To assess the test-retest reliability of maximum inspiratory pressure and maximum expiratory pressure measurements, an interclass correlation coefficient (ICC) and the coefficient of variation (CV) were calculated for each group (training and control). Statistical significance was set at P≤0.05. Given that there are no previous studies regarding respiratory muscle training in Huntington’s disease patients, we were unable to estimate a sample size, thus under a null hypothesis significance approach, it was not possible to control the size of type II error. This, and our interest to estimate the magnitude of the effect of respiratory muscle training on pulmonary and swallowing function for clinical significance, led us to use the magnitude based inference analysis. Changes between training and control groups in spirometric indices, maximum inspiratory pressure, maximum expiratory pressure, six minute walk test, dyspnoea, water-swallowing test and swallow quality of life questionnaire at 2 and 4 months from baseline, were analyzed using standardized effect sizes (Hedges’g). The arithmetic difference between baseline and each time point (2 and 4 months) was calculated for training and control groups. The standardized effect size was then calculated from the mean differences between groups at each time point. Qualitative descriptors of standardized effects were assessed using these criteria: trivial, 0.8. Precision of estimated means and effect sizes was indicated with 95% confidence limits. Statistical analyses were performed using STATA version 9.1 and customwritten Excel spread sheets.
Results There were no significant differences between groups for gender balance, age, height, body mass and body mass index (Table 1). There were 5 ex-smokers in the training group and 4 in the control
group. No significant differences between groups were found for smoking history, time elapsed since smoking cessation, pulmonary and swallowing function variables, dyspnoea and 6 minute walk test scores at baseline. There was 100% adherence to the training program by all participants in both groups. None of the participants decided to withdraw from the study and all participants attended testing sessions at baseline, 2 and 4 months. All participants were able to increase their maximum inspiratory and expiratory pressure by 15% each month. None of the participants reported adverse events, such as respiratory infections, associated diseases or other unfavorable or unintended signs or symptoms during the experimental period.
Reliability of maximum respiratory pressure measurements The test-retest reliability of maximum inspiratory pressure (ICC: 0.94; 95% CI: 0.89 – 0.98) and maximum expiratory pressure (ICC: 0.92; 95% CI: 0.86 – 0.98) measurements were acceptable with no significant differences between three testing sessions. The variability across testing sessions was similar between maximum inspiratory pressure (CV: 10.8%) and maximum expiratory pressure (CV: 11.1%). The variability in maximum inspiratory pressure and maximum expiratory pressure was lower (maximum inspiratory pressure: CV 9.2%, maximum expiratory pressure: CV 9.0%) when the result from the first testing session was discarded.
Maximum respiratory pressure Between baseline and 2-months of training, respiratory muscle training had a small positive effect (improvement) for maximum inspiratory pressure in the training (d=0.47) and control (d=0.32) groups. After 4-months of training, respiratory muscle training had a moderate positive effect (d=0.7) for the training group, but a trivial effect (d=0.02) for the control group (Table 2). The effects of respiratory muscle training on maximum expiratory pressure for the training group was small at 2 (d=0.37) and 4 months (d=0.47), while the effects were trivial (
research-article2015
CRE0010.1177/0269215514564087Clinical RehabilitationReyes et al.
CLINICAL REHABILITATION
Original Article
Respiratory muscle training on pulmonary and swallowing function in patients with huntington’s disease: A pilot randomised controlled trial
Clinical Rehabilitation 1–13 © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0269215514564087 cre.sagepub.com
Alvaro Reyes1, Travis Cruickshank1, Kazunori Nosaka2 and Mel Ziman1,3
Abstract Objective: To examine the effects of 4-month of respiratory muscle training on pulmonary and swallowing function, exercise capacity and dyspnoea in manifest patients with Huntington’s disease. Design: A pilot randomised controlled trial. Setting: Home based training program. Participants: Eighteen manifest Huntington’s disease patients with a positive genetic test and clinically verified disease expression, were randomly assigned to control group (n=9) and training group (n=9). Intervention: Both groups received home-based inspiratory (5 sets of 5 repetitions) and expiratory (5 sets of 5 repetitions) muscle training 6 times a week for 4 months. The control group used a fixed resistance of 9 centimeters of water, and the training group used a progressively increased resistance from 30% to 75% of each patient’s maximum respiratory pressure. Main measures: Spirometric indices, maximum inspiratory pressure, maximum expiratory pressure, six minutes walk test, dyspnoea, water-swallowing test and swallow quality of life questionnaire were assessed before, at 2 and 4 months after training. Results: The magnitude of increases in maximum inspiratory (d=2.9) and expiratory pressures (d=1.5), forced vital capacity (d=0.8), forced expiratory volume in 1 second (d=0.9) and peak expiratory flow (d=0.8) was substantially greater for the training group in comparison to the control group. Changes in swallowing function, dyspnoea and exercise capacity were small (d≤0.5) for both groups without substantial differences between groups. Conclusions: A home-based respiratory muscle training program appeared to be beneficial to improve pulmonary function in manifest Huntington’s disease patients but provided small effects on swallowing function, dyspnoea and exercise capacity. 1School
of Medical Sciences, Edith Cowan University, Joondalup, WA, Australia 2School of Exercise and Health Sciences, Centre for Exercise and Sports Science Research, Edith Cowan University, Joondalup, WA, Australia 3School of Pathology and Laboratory Medicine, University of Western Australia, Crawley, WA, Australia
Corresponding author: Alvaro Reyes, School of Medical Sciences, Edith Cowan University, 270 Joondalup Drive, Joondalup, WA 6027, Australia. Email: [email protected]
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2
Clinical Rehabilitation
Keywords Respiratory function, swallowing, Huntington’s disease, dysphagia, pulmonary rehabilitation Received: 1 September 2014; accepted: 22 November 2014
Introduction Patients with Huntington’s disease experience pulmonary and swallowing abnormalities leading to difficulties in clearing airway secretions.1 Huntington’s disease patients generally have restricted mobility which may lead to poor exercise tolerance resulting in fatigue and dyspnoea on exertion.2,3 This limits their ability to perform activities of daily living, which further lead to muscle weakness.4,5 Our recent study has shown that manifest Huntington’s disease patients have lower respiratory pressure, forced vital capacity, peak expiratory flow and maximum voluntary ventilation in comparison to age and gender matched healthy individuals with similar anthropometric characteristics.6 Given that the main cause of death in Huntington’s disease is a complication arising from poor pulmonary function,7 interventions to maintain and improve pulmonary function are crucial for these patients. Respiratory muscle training has been utilized in neurodegenerative disorders such as Parkinson’s disease,8–11 amyotrophic lateral sclerosis,12 and multiple sclerosis4,13–16 to improve pulmonary and swallowing function as well as exercise capacity. The results of these studies have shown that a respiratory muscle training program for 4–10 weeks, 5–6 days a week (at least 25 inspiratory or expiratory manoeuvres each day) with progressively increased load, improves maximum respiratory pressures, cough function, dyspnoea sensation and spirometric indices in patients with Parkinson’s disease and multiple sclerosis.17 However, no previous studies have reported the effects of respiratory muscle training on pulmonary function in Huntington’s disease patients. Because of some similarities between Huntington’s disease and the aforementioned neurodegenerative disorders at least for the symptoms associated with pulmonary dysfunction,17 it was assumed that respiratory
muscle training would be also effective for Huntington’s disease patients. Therefore, the purpose of this study was to examine the effects of 4-month of respiratory muscle training on pulmonary and swallowing function, exercise capacity and dyspnoea in manifest patients with Huntington’s disease.
Methods Participants Participants with manifest Huntington’s disease were screened for eligibility using the Huntington’s Enrichment Research Optimisation Scheme Database. This database includes a group of patients who had recently participated in a multidisciplinary rehabilitation program so generally met the inclusion criteria.18 Participants were also screened by the Western Australia Huntington’s Disease Association. Potential participants were first contacted by telephone and later visited at their home. Inclusion criteria were a positive genetic test, clinically verified disease expression (Unified Huntington’s Disease Rating Scale–Total Motor Score [UHDRS-TMS] ≥5),19 and the ability to understand and respond to the instructions given in the study. Exclusion criteria were other confounding neurological disorders, current smokers, participants with a history of cardiovascular pathology, lung disease or the presence of respiratory symptoms such as cough, phlegm, wheezing or dyspnoea at the time of assessment. Participants who had difficulties in maintaining a proper mouth seal, unable to avoid air leakage, or had excessive choreic movements of the tongue during pulmonary function testing were excluded. Informed written consent was obtained from the participants, and the study was approved by the Human Research Ethics Committee of Edith Cowan University.
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3
Reyes et al.
Recruitment
Assessed for eligibility (n= 26) Excluded (n= 8) Not meeting inclusion criteria (n= 3) Declined to participate (n= 5)
Randomized (n= 18)
Baseline Allocated to control group (n=9) Did not receive allocated intervention (n= 0)
Allocated to training group (n=9) Did not receive allocated intervention (n= 0) 2 months
Lost to follow-up (n= 0) Discontinued intervention (n= 0)
Lost to follow-up (n=0) Discontinued intervention (n=0)
4 months Analysed (n=9) Excluded from analysis (n=0)
Analysed (n=9) Excluded from analysis (n=0)
Figure 1. Progress of participants through the trial.
Study design All the participants of the study were interviewed regarding their general health status, cardio-vascular and smoking history as well as their respiratory condition. The body mass and height were recorded for each participant using an accurate and calibrated scale (HW200, A&D Mercury Pty, Ltd, Thebarton, SA) and a wall-mounted stadiometer (Model 220, SECA, Hamburg, Germany). After baseline measurements, participants were randomly divided into two groups using the randomisation block method. Given that 18 participants were recruited, randomisation was performed using six blocks and three cells per block (number of participants=number of blocks*number of cells per block). Nine participants were assigned to receive home-based respiratory muscle training (training group), and 9 participants were assigned to receive home-based respiratory muscle training at minimum and fixed load (control group). Allocation concealment was implemented
using sequential sealed envelopes prepared by an independent research assistant (Figure 1).
Training protocol Participants in the training group used a Threshold® Inspiratory Muscle Trainer (HS730-010. Phillips Respironics, USA) and an Expiratory Muscle Trainer (EMST150. Aspire Products, LLC). They performed a home-based inspiratory (5 sets of 5 repetitions) and expiratory muscle training (5 sets of 5 repetitions), 6 times a week for 4 months. These training parameters were chosen, because a previous study17 has shown significant improvements in pulmonary and swallowing function in patients with Parkinson’s disease and multiple sclerosis using a similar protocol. Participants in the training group started training at a resistance equal to 30% of their average maximum inspiratory pressure and maximum expiratory pressure, respectively which were calculated based on maximum inspiratory
Downloaded from cre.sagepub.com at UNIV NEBRASKA LIBRARIES on October 11, 2015
4
Clinical Rehabilitation
pressure and maximum expiratory pressure baseline measurements described below. This initial resistance training was based on the results of a study20 showing that a resistance lower than 30% of maximum inspiratory pressure was insufficient to produce improvements in pulmonary function. The training protocol was designed to reach a training intensity of 75% of maximum inspiratory pressure/ maximum expiratory pressure in the fourth month of training, therefore the resistance was increased progressively by 15% of each participant’s maximum inspiratory pressure and maximum expiratory pressure every month at the end of each month of training. Participants in the control group used a Threshold® PEP (HS-735-010. Phillips Respironics, USA) for both inspiratory muscle training and expiratory muscle training, because this device provides lower resistance for both inspiratory and expiratory flows than those devices used by the training group. They trained with the same protocol to the participants in the training group for the same number of repetitions, frequency and duration, but the intensity was fixed at the minimum load of the device, 9 centimetres of water throughout the training period. Before the commencement of the training, participants in both groups were instructed for the correct use of the training devices. For inspiratory muscle training, they were instructed to initiate their inspiration from near to residual volume, while for expiratory muscle training, they were asked to blow as forcefully as possible into the mouthpiece of the trainer device from total lung capacity. In both cases participants used a nose clip in order to ensure that airflow occurred entirely through the mouth. All participants were asked to mark on the provided training diary when they completed a training session. We visited the home or caregiver institution of each participant in both groups, every two weeks, and made daily phone contacts or sent daily text messages from Monday to Friday throughout the study period to ensure that they were training as instructed. Every two weeks, maximum inspiratory pressure and maximum expiratory pressure were reassessed at each participant’s home or caregiver institution as described
below. In this study we used the pressure threshold modality in which the load valve of the training device remains closed until enough inspiratory or expiratory pressure is generated against the valve to release it and allow airflow. Therefore maximum inspiratory and expiratory pressure measurements were used to adjust the resistance of the devices every two weeks for the training group.
Measurements Spirometric indices, maximum inspiratory pressure, maximum expiratory pressure, six minute walk test, dyspnoea, water-swallowing test and the swallow quality of life questionnaire were taken during the three weeks before the commencement of the training to obtain baseline assessment. Measurements of maximum inspiratory pressure and maximum expiratory pressure were performed over 3 testing sessions with a week apart to assess the test-retest reliability. For those participants who had difficulties achieving acceptable and reproducible spirograms (standardization of spirometry) on a testing day, the measurement was repeated on a different day, to ensure an accurate spirometry (acceptability criteria).21 Spirometry, maximum inspiratory pressure, maximum expiratory pressure and water-swallowing test measurements were repeated at 2 and 4 months after training. Dyspnoea, six minute walk test and swallow quality of life questionnaire measurements were taken at baseline and at 4 months in the training period. All measurements were performed at the same place and same time of the day. To minimize possible acute effects of the training session on the measures, 1 or 2 days were inserted between the training session and the measurements. For maximum inspiratory pressure and maximum expiratory pressure measurements, each participant was asked to sit upright with a nose clip in place to prevent nasal air leakage. A flanged rubber mouthpiece was connected to a pressure manometer (Micro RPM, Micro Medical-Care Fusion, Kent, UK) and placed in the mouth. Participants were asked to hold the pressure manometer with both hands and to create a tight lip seal around the flanged mouthpiece. A flanged mouthpiece was
Downloaded from cre.sagepub.com at UNIV NEBRASKA LIBRARIES on October 11, 2015
5
Reyes et al. used as recommended by the American Thoracic Society and European Respiratory Society.21 This method was used, since the portability of the manometer was advantageous for clinical use and its reliability had been assessed.22 For maximum expiratory pressure assessment, participants were asked to breathe in to total lung capacity and then to blow hard into the mouthpiece. For maximum inspiratory pressure assessment, they were instructed to breath out to residual volume and then to breath in with maximum effort through the mouthpiece. Inspiratory and expiratory efforts were required to be maintained for more than one second. The order of procedures was the inspiratory followed by the expiratory effort. Both manoeuvres were repeated a minimum of 5 times with a 30-s rest until three trials showed values within 5% variation of each other. The best result from at least five respiratory manoeuvres was used for further analysis as described by Black and Hyatt (1969)21 and the professional society guidelines. Results of maximum inspiratory pressure and maximum expiratory pressure are expressed as absolute values, because no suitable predictive equations are available. Spirometric assessment was performed using a spirometer (Medgraphics, model CPFS/D, St. Paul MN, USA) connected to a laptop computer (Dell, Latitude E6510, USA). The spirometer met all the quality control requirements of the American Thoracic Society and was calibrated before each testing session with a Hans Rudolph 3.0 syringe, based on the manufacturer’s recommendations. In accordance with the professional society guidelines, each participant was asked to sit upright with a nose clip in place to prevent nasal air leakage. Participants were instructed to perform spirometric maneuvers in the following order: slow vital capacity, a forced vital capacity and maximal voluntary ventilation. Each manoeuvre was repeated at least 3 and a maximum of 8 times, with 1–2 min rest between attempts. The best result from the three technically acceptable manoeuvres was used for further analysis. From these measurements, forced expiratory volume in one second, peak expiratory flow and the ratio of forced expiratory volume in one second to forced vital capacity from the largest
forced expiratory volume in one second and forced vital capacity were calculated. Predicted values were calculated for all participants using Stanojevic (2008) prediction equations, which include age, height, weight and gender. These prediction equations include reference values for forced vital capacity and forced expiratory volume in one second, and have been validated for a Caucasian Australasian population.23 Peak expiratory flow predicted values were calculated using Nunn and Gregg (1989)21 regression equations. To assess functional exercise capacity, participants performed the six-minute walk test. The test was performed outdoors on a 20 m long walking course. The length of the walking course was marked every 5 m with plastic cones. The test was performed following the professional society guidelines.24 Perception of dyspnoea was recorded before and immediately after the test using a Borg scale. Predicted values for six-minute walk test were calculated using Enright25 regression equations. Swallowing function was evaluated by the water-swallowing test26 and the swallow quality of life questionnaire that is a specific autoadministered test for evaluating the impact of swallowing problems on quality of life.27 For the water-swallowing test, participants were asked to drink 50-mL water at ambient temperature (20–25°C) from a plastic cup as quickly and as comfortably as possible in a sitting position, while being timed. Using a stopwatch, the time taken from when the first drop of water touched the lips to when the larynx of the patient came to rest after the last swallow was measured. Participants were instructed to drink all water without stopping. The swallowing test was performed three times, with an interval of at least 30 seconds between times. The examiner counted the number of swallows determined by the number of upper movements of the larynx. Each measurement was performed in the presence of at least two examiners to ensure when to start and stop the measurement. In addition to the time and number of swallows needed to ingest 50 mL of water, the drinking speed (ml/s), the time for one swallow (s), and the amount of water in one swallow (ml) were calculated.26
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Clinical Rehabilitation
Statistical analysis Descriptive data are given as mean, standard deviation and range. To compare physical and physiological characteristics and baseline measurements between training and control groups, an independent t-test was performed. To assess the test-retest reliability of maximum inspiratory pressure and maximum expiratory pressure measurements, an interclass correlation coefficient (ICC) and the coefficient of variation (CV) were calculated for each group (training and control). Statistical significance was set at P≤0.05. Given that there are no previous studies regarding respiratory muscle training in Huntington’s disease patients, we were unable to estimate a sample size, thus under a null hypothesis significance approach, it was not possible to control the size of type II error. This, and our interest to estimate the magnitude of the effect of respiratory muscle training on pulmonary and swallowing function for clinical significance, led us to use the magnitude based inference analysis. Changes between training and control groups in spirometric indices, maximum inspiratory pressure, maximum expiratory pressure, six minute walk test, dyspnoea, water-swallowing test and swallow quality of life questionnaire at 2 and 4 months from baseline, were analyzed using standardized effect sizes (Hedges’g). The arithmetic difference between baseline and each time point (2 and 4 months) was calculated for training and control groups. The standardized effect size was then calculated from the mean differences between groups at each time point. Qualitative descriptors of standardized effects were assessed using these criteria: trivial, 0.8. Precision of estimated means and effect sizes was indicated with 95% confidence limits. Statistical analyses were performed using STATA version 9.1 and customwritten Excel spread sheets.
Results There were no significant differences between groups for gender balance, age, height, body mass and body mass index (Table 1). There were 5 ex-smokers in the training group and 4 in the control
group. No significant differences between groups were found for smoking history, time elapsed since smoking cessation, pulmonary and swallowing function variables, dyspnoea and 6 minute walk test scores at baseline. There was 100% adherence to the training program by all participants in both groups. None of the participants decided to withdraw from the study and all participants attended testing sessions at baseline, 2 and 4 months. All participants were able to increase their maximum inspiratory and expiratory pressure by 15% each month. None of the participants reported adverse events, such as respiratory infections, associated diseases or other unfavorable or unintended signs or symptoms during the experimental period.
Reliability of maximum respiratory pressure measurements The test-retest reliability of maximum inspiratory pressure (ICC: 0.94; 95% CI: 0.89 – 0.98) and maximum expiratory pressure (ICC: 0.92; 95% CI: 0.86 – 0.98) measurements were acceptable with no significant differences between three testing sessions. The variability across testing sessions was similar between maximum inspiratory pressure (CV: 10.8%) and maximum expiratory pressure (CV: 11.1%). The variability in maximum inspiratory pressure and maximum expiratory pressure was lower (maximum inspiratory pressure: CV 9.2%, maximum expiratory pressure: CV 9.0%) when the result from the first testing session was discarded.
Maximum respiratory pressure Between baseline and 2-months of training, respiratory muscle training had a small positive effect (improvement) for maximum inspiratory pressure in the training (d=0.47) and control (d=0.32) groups. After 4-months of training, respiratory muscle training had a moderate positive effect (d=0.7) for the training group, but a trivial effect (d=0.02) for the control group (Table 2). The effects of respiratory muscle training on maximum expiratory pressure for the training group was small at 2 (d=0.37) and 4 months (d=0.47), while the effects were trivial (
