ORIGINAL ARTICLE
The Clinical Respiratory Journal
Deep breathing exercises with positive expiratory pressure in patients with multiple sclerosis – a randomized controlled trial Elisabeth Westerdahl1, Anna Wittrin2, Margareta Kånåhols2, Martin Gunnarsson2 and Ylva Nilsagård3 1 Faculty of Medicine and Health, Surgery, Örebro University, Örebro, Sweden 2 Faculty of Medicine and Health, Department of Neurology and Neurophysiology, Örebro University, Örebro, Sweden 3 Faculty of Medicine and Health, Medicine, Örebro University, Örebro, Sweden
Abstract Introduction: Breathing exercises with positive expiratory pressure are often recommended to patients with advanced neurological deficits, but the potential benefit in multiple sclerosis (MS) patients with mild and moderate symptoms has not yet been investigated in randomized controlled trials. Objectives: To study the effects of 2 months of home-based breathing exercises for patients with mild to moderate MS on respiratory muscle strength, lung function, and subjective breathing and health status outcomes. Methods: Forty-eight patients with MS according to the revised McDonald criteria were enrolled in a randomized controlled trial. Patients performing breathing exercises (n = 23) were compared with a control group (n = 25) performing no breathing exercises. The breathing exercises were performed with a positive expiratory pressure device (10–15 cmH2O) and consisted of 30 slow deep breaths performed twice a day for 2 months. Respiratory muscle strength (maximal inspiratory and expiratory pressure at the mouth), spirometry, oxygenation, thoracic excursion, subjective perceptions of breathing and self-reported health status were evaluated before and after the intervention period. Results: Following the intervention, there was a significant difference between the breathing group and the control group regarding the relative change in lung function, favoring the breathing group (vital capacity: P < 0.043; forced vital capacity: P < 0.025). There were no other significant differences between the groups. Conclusion: Breathing exercises may be beneficial in patients with mild to moderate stages of MS. However, the clinical significance needs to be clarified, and it remains to be seen whether a sustainable effect in delaying the development of respiratory dysfunction in MS can be obtained. Please cite this paper as: Westerdahl E, Wittrin A, Kånåhols M, Gunnarsson M and Nilsagård Y. Deep breathing exercises with positive expiratory pressure in patients with multiple sclerosis – a randomized controlled trial. Clin Respir J 2015; ••: ••–••. DOI:10.1111/crj.12272.
Key words breathing exercises – multiple sclerosis – positive expiratory pressure – respiratory function tests Correspondence Elisabeth Westerdahl, RPT, PhD, Örebro University Hospital, Centre for Health Care Sciences, Box 1324, SE-701 85 Örebro, Sweden. Tel: +46 19 602 5847 Fax: +46 19 602 5778 email: [email protected] Received: 20 August 2014 Revision requested: 16 December 2014 Accepted: 20 January 2015 DOI:10.1111/crj.12272 Authorship and contributorship All of the authors contributed to the design of the study. AW and MK performed the data collection. EW performed the statistical analysis and wrote the manuscript. AW, MK, MG and YN contributed to the interpretation of results and helped draft the final manuscript. All authors read and approved the final manuscript. Ethics The Regional Ethical Review Board in Uppsala, Sweden, approved the study (2012/077). The trial was registered at ClinicalTrials.gov NCT01774201; URL: www.clinicaltrials.gov. Conflict of interest The authors have stated explicitly that there are no conflicts of interest in connection with this article.
Introduction Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease affecting widespread areas of
the central nervous system. Consequently, injuries in motor pathways are common in MS patients, resulting in muscle weakness and impaired mobility.
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 1 © 2015 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Deep breathing exercises for MS patients
Westerdahl et al.
Symptoms and disease progression vary among individuals, depending on the localization, size and the number of lesions. Disease severity is often rated with the Expanded Disability Status Scale (EDSS), which is influenced by ambulatory status (1, 2). Impaired respiratory function has been observed in the end stage of the disease, and pulmonary manifestations have long been recognized to cause morbidity and mortality in individuals with advanced MS (3). Respiratory muscle weakness, however, may also occur in early-stage disease (4), causing impaired ventilation and poor cough even in patients with more moderate disease (5, 6). The impairment in respiratory muscle function increases with MS severity. Expiratory muscle weakness is more prominent than inspiratory muscle weakness, and may impair coughing ability (7). Strategies to improve expiratory muscle function are important in preventing deterioration of pulmonary function (3). Possible mechanisms of breathing exercises with positive expiratory pressure (PEP) include improved respiratory muscle strength and a momentary increase in lung volumes that may facilitate secretion mobilization. Eight weeks of expiratory muscle strength training with a threshold trainer in patients with mild to moderate disability have been shown to increase maximal expiratory pressure (MEP) and peak expiratory flow (PEF) in a before-after trial (4). In a recently published before-after trial, 5 weeks of inspiratory and expiratory muscle training were shown to increase muscle strength and reduce fatigue in patients with mild to moderate MS (8). Only two randomized trials have been performed evaluating expiratory muscle strength training for severely disabled MS patients (3, 9). It is unknown whether breathing exercises with PEP device may improve respiratory function or delay the development of respiratory dysfunction in patients with MS. To our knowledge, no randomized controlled trials have been performed evaluating breathing exercises in patients with mild to moderate MS, and no studies have evaluated breathing exercises performed at home. Our aim was to evaluate the effects of 8 weeks of home-based deep breathing exercises with PEP for MS patients with mild to moderate neurological deficits and early stages of physical impairment, concerning respiratory muscle strength, lung function, oxygenation and subjective perceptions of breathing.
Materials and methods Patients and study design We performed a randomized, controlled, singleblinded, parallel-group trial. Eligible for inclusion were
2
all patients aged 18 years or older with mild to moderate MS according to the revised McDonald criteria (10), living in Örebro County, and registered in the Swedish MS Registry in September 2012. To quantify the disability of MS, the EDSS was used, based on an examination by a neurologist. The score range from 0 to 10: 0 represents no impairment, 4 represents onset of significant walking impairment, 6 represents onset of assistive device during ambulation, and 10 represents death due to MS (1, 2). A total of 149 patients were contacted by letter and then by phone, and were assessed for eligibility. Of these, 71 declined participation due to participation in other studies, long distance to the hospital, or personal or social reasons, and 26 did not meet the inclusion criteria (Fig. 1). The inclusion criteria were relapse-free for at least 3 months prior to study entry, able to understand verbal and written information, and preserved ability to walk with or without use of walking devices. The exclusion criteria for randomization in the study were the following: other diseases or conditions impacting functional ability (e.g. other neurological diseases, severe ischaemic heart disease, orthopedic conditions), or language or cognitive difficulties which could adversely influence the performance of lung function tests. Informed written consent was obtained from each patient, the Regional Ethical Review Board in Uppsala, Sweden, approved the study (2012/077), and the trial was registered at ClinicalTrials.gov (NCT01774201; URL: www.clinicaltrials.gov).
Sample size determination and randomization A difference in MEP of 12 cmH2O (35 vs 47 cmH2O) between the two groups was considered possible, and of clinical interest. Sample size calculation showed that 22 patients per group would be required for a power of 80% to detect a 10% difference between the groups, assuming a standard deviation of 14 cmH2O. To account for missing values, another five patients were included in each group, giving a total of 52 patients. After four dropouts, 48 patients were analyzed (Fig. 1). A computer-generated list was used to randomize eligible patients. This list had been administered by an independent secretary, who printed notes showing group assignment and put them in sequentially numbered, sealed, nontransparent envelopes. Patients were allocated to groups after their informed consent had been obtained for inclusion.
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2015 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd
Westerdahl et al.
Deep breathing exercises for MS patients
Assessed for eligibility (n = 149)
Enrollment
•
Declined to participate (n = 71) Did not meet inclusion criteria, or excluded after baseline assessment (n = 26):
• • • • •
Disease affecting walking ability (n = 11) No walking ability (n = 7) Language difficulties (n = 4) Unclear MS diagnosis (n = 3) Cognitive dysfunction (n = 1)
Randomized (n = 52)
Allocation Allocated to breathing group
Allocated to control group
(n = 26)
(n = 26)
Follow-Up Lost to follow-up (n = 3)
Lost to follow-up (n = 1)
Analysis Analyzed
Analyzed
(n = 23)
(n = 25)
Figure 1. Flowchart of the patients in the study. MS, multiple sclerosis.
Intervention Before baseline measurements, patients were randomly assigned to perform home-based deep breathing exercises for 2 months (breathing group, n = 23) or to perform no breathing exercises (control group, n = 25). The breathing group was instructed to perform 30 deep breaths in a sitting position twice a day: three series of 10 calm and deep breaths with a 30–60 s pause between each set. A PEP device (Rium breathing exerciser; Rium Medical AB, Åkersberga, Sweden) (Fig. 2) was used to create an expiratory pressure of 10–15 cmH2O. Patients were instructed to inspire as deep as possible, hold their breath for 2 s and then expire through the PEP device, ending the expiration before emptying their lungs to minimize the risk of airway closure. They were also taught how to clean the PEP device. Two weeks after the intervention start, patients in the breathing group were telephoned at
Figure 2. Breathing exerciser, Rium Medical AB, Åkersberga, Sweden.
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2015 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd
3
Deep breathing exercises for MS patients
Westerdahl et al.
home for coaching of the breathing exercises, and after 4 weeks a letter was sent to remind them about the exercises. These patients documented compliance with training in an exercise diary. Patients in the control group performed no breathing exercises. Otherwise, all patients received standard medical care during the study period.
Measurements Measurements were performed at baseline and immediately after the 2-month intervention period at Örebro University Hospital, Sweden. First, a medical doctor performed a neurological examination and recorded the patient’s EDSS score. Data on demographics and medical history, such as disease phenotype, were collected from medical charts or written down (self-reported) by the patient. Next, a physiotherapist experienced in neurology and blinded to group allocation assessed the lung function and respiratory muscle strength, and each patient answered self-reported questionnaires covering descriptive data, ability to breathe and cough, physical activity, and health-related quality of life. The primary outcome was expiratory respiratory muscle strength. Secondary outcomes were lung function assessed by spirometry, peripheral oxygen saturation (SpO2), subjective breathing and coughing ability, and self-reported health status.
Respiratory muscle strength Respiratory muscle strength was defined as the maximal static pressures measured at the mouth. Measurements were performed from total lung capacity for MEP and from residual volume for maximal inspiratory pressure (MIP) as described in the American Thoracic Society/European Respiratory Society (ATS/ERS) statement on respiratory muscle testing (11). Measurements were performed in a sitting position and with a nose-clip (Micro RPM; MicroMedical/ CareFusion, Kent, UK). Patients were instructed to press their lips tightly against the flanged mouthpiece and to support their cheeks manually during the maneuver to prevent air leak. The highest value from at least five technically acceptable attempts was recorded and expressed as an absolute value (cmH2O) and as a percentage of predicted value adjusted for age and sex (12).
try was performed with a MicroLab spirometer (MicroMedical/CareFusion), calibrated every morning prior to measurements. Patients were in a sitting position, a nose-clip was used, and measurements were performed as recommended by the ATS/ERS (13). The highest value of three technically satisfactory maneuvers was retained. An inspiratory maneuver was obtained for measurement of slow vital capacity (VC), followed by measurement of forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), PEF and FEV% (FEV1/VCmax). Predicted values for pulmonary function were related to age, sex and height (14). Peak cough flow was measured by a portable peak flow meter (Vitalograph, Ennis, Ireland) connected to a face mask. Patients were asked to take a deep breath without the mask, and then cough as much as possible with the mask tightly sealed against the face. The best value of three attempts was noted. The SpO2 was measured using a pulse oximeter device (Rad-5v; Masimo, Irvine, CA, USA).
Thoracic excursion Thoracic excursions were measured using a tape (marked in millimeters) around the circumference of the chest at the level of the xiphoid process to give a measurement of chest expansion or mobility. Patients were asked to stand with their hands on their head and given the instructions ‘Breathe in maximally and make yourself as big as possible’ and ‘Breathe out maximally and make yourself as small as possible’. Chest expansion was taken as the difference between full expiration and inspiration using the best of two attempts (15).
Subjective breathing and coughing ability All patients scored their perceived breathing and coughing ability on a numeric rating scale, from 0 (‘no difficulty’) to 10 (‘impossible’), and their level of dyspnea while walking indoors and while climbing stairs on a numeric rating scale from 0 (‘no dyspnea’) to 10 (‘worst imaginable dyspnea’). Patients in the breathing group were asked to score compliance with, subjective benefit from, and discomfort associated with the breathing exercises on a scale from 0 (‘not at all’) to 2 (‘very much’).
Lung function measurements
Self-reported health status
Lung function variables were measured by a physiotherapist blinded to treatment allocation. Spirome-
Patients rated their perception of overall health status on the EuroQoL EQ-5D visual analogue scale
4
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2015 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd
Westerdahl et al.
Deep breathing exercises for MS patients
(EQ-5D VAS) from 0 (‘worst imaginable’) to 100 (‘best imaginable’) (16).
Statistical analysis Continuous baseline data were compared with Student’s t-test and categorical data with Fisher’s exact test or a chi-squared test. Differences between groups were assessed with Student’s unpaired t-test, the Mann– Whitney U-test or a chi-squared test. All results refer to two-sided tests, with P values ≤ 0.05 considered significant. Version 15.0 of the SPSS software package (SPSS Inc., Chicago, IL, USA) was used for statistical analysis.
Results Of the 52 randomized patients, 48 were analyzed (Fig. 1). Reasons for withdrawal after randomization in the breathing group (n = 3) and the control group (n = 1) were other morbidities, failure to cooperate or unwillingness to perform the follow-up. Baseline demographic data did not differ significantly between the two groups (Table 1). Median EDSS score was 5.0 (3–7) in the breathing group and 4.5 (1.5–8) in the control group. Patients in the breathing group (n = 23) reported having performed the breathing exercises once or twice a day with 30 ± 8 breaths during each training occasion. Eleven patients (48%) reported subjective benefit from the breathing exercises, and four (17%) reported some discomfort.
Table 1. Demographic data
Male/female, n Age, years BMI, kg/m2 Never smoked/ ex-smoker/smoker, n Airway obstruction, n MS disease duration, years Relapsing-remitting MS Secondary progressive MS Primary progressive MS EDSS, median
Breathing group (n = 23)
Control group (n = 25)
6/17 55 ± 12 27 ± 5 12/8/3
7/18 56 ± 9 26 ± 4 9/9/7
1 24 ± 11 11 11 1 5.0
3 23 ± 11 9 15 1 4.5
Patients with preoperative FEV1/VCmax < 0.70 were defined as having airway obstruction. Data are presented as mean ± standard deviation or number (n) of patients. No significant differences between groups. BMI, body mass index; EDSS, Expanded Disability Status Scale; MS, multiple sclerosis; FEV1, forced expiratory volume in 1 s; VC, vital capacity.
dicted values ranged from 59% to 169% (mean 104% ± 29%), with two patients reaching below the lower limit of normal according to reference values by Evans and Whitelaw (12). After the 2-month intervention period, there was no significant difference between the breathing and control groups regarding change in MIP and MEP (Table 2).
Lung function Respiratory muscle strength In the total sample, baseline MIP values ranged from 26 to 143 (mean 80 ± 28) cmH2O, and the percentage predicted values ranged from 39% to 165% (mean 98% ± 31%). Baseline MEP values ranged from 43 to 166 (mean 97 ± 25) cmH2O, and percentage pre-
Baseline lung function was normal in relation to predicted values (VC: 103 ± 16% predicted; FEV1: 95 ± 15% predicted; FVC: 103 ± 15; FEV%: 98 ± 9), with no significant difference between the groups. Spirometry values at baseline and follow-up are presented in Table 3.
Table 2. Respiratory muscle strength at baseline and after the intervention Two-month follow-up
Baseline
MIP (cmH2O) MIP (%predicted) MEP (cmH2O) MEP (%predicted)
Two-month values in percentage of baseline values
Difference between groups [95% CI] Change after 2 months
Breathing
Control
Breathing
Control
Breathing
Control
78 ± 33 96 ± 38 95 ± 31 101 ± 31
81 ± 23 101 ± 24 98 ± 18 106 ± 26
77 ± 32 95 ± 36 98 ± 28 104 ± 27
82 ± 24 102 ± 28 100 ± 23 107 ± 26
100 ± 13%
101 ± 15%
1% [−7–9]
P value 0.74
105 ± 15%
102 ± 17%
−3% [−12–6]
0.52
Data are presented as mean ± standard deviation [95% confidence interval of the difference]. P values refer to the difference between the breathing group and the control group after the 2-month intervention regarding the relative changes in lung function, with 2-month values as % of baseline values (P < 0.05 considered significant). CI, confidence interval; MEP, maximal expiratory pressure; MIP, maximal inspiratory pressure.
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2015 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd
5
Deep breathing exercises for MS patients
Westerdahl et al.
Table 3. Spirometry data at baseline and after the intervention Baseline
VC (L) FEV1 (L) FVC (L) FEV1/VC (%) PEF (L/min)
Two-month follow-up
Two-month values in percentage of baseline values
Difference between groups [95% CI]
Breathing
Control
Breathing
Control
Breathing
Control
Change after 2 months
P value
3.3 ± 0.8 2.6 ± 0.7 3.3 ± 0.8 78.4 ± 7.1 351 ± 86
3.7 ± 1.0 2.8 ± 0.7 3.7 ± 1.1 74.8 ± 6.6 385 ± 90
3.3 ± 0.9 2.6 ± 0.7 3.3 ± 0.8 77.5 ± 6.0 375 ± 87
3.5 ± 1.0 2.7 ± 0.7 3.6 ± 1.0 75.3 ± 6.6 382 ± 92
100.1 ± 8.1% 100.8 ± 5.7% 101.8 ± 6.6% 99.1 ± 5.2% 108.6 ± 14.9%
95.7 ± 6.4% 97.6 ± 6.9% 97.0 ± 7.6% 100.7 ± 4.4% 100.4 ± 17.1%
−4.4% [−8.6–−0.1] −3.2% [−6.9–0.5] −4.8% [−9.0–−0.6] 1.6% [−17.5–1.2] −8.2% [−1.1–4.4]
0.043 0.092 0.025 0.242 0.086
Data are presented as mean ± standard deviation [95% confidence interval of the difference]. P values refer to the difference between the breathing group and the control group after the 2-month intervention regarding the relative changes in lung function, with 2-month values as % of baseline values (P < 0.05 considered significant). CI, confidence interval; FEV1, forced expiratory volume in 1 s; VC, vital capacity; FVC, forced vital capacity; PEF, peak expiratory flow.
At follow-up, there was a significant between-group difference in relative change in lung function, favoring the breathing group (VC: P < 0.043; FVC: P < 0.025) (Table 3). Peak cough flow decreased significantly from 389 ± 70 at baseline to 374 ± 76 (P = 0.044) at followup, but with no significant difference between the groups regarding the change from baseline (P = 0.305).
In addition, 56% reported that the breathing exercises made it easier to take deep breaths, and 92% reported that the breathing technique was easy to perform. Discomfort related to the exercises was reported by 4% to a high degree and 13% to some extent. Adverse perceptions were related to dizziness, strenuousness and tediousness. Patients reported having performed 30 ± 9 (range 7–60) breaths at each training session.
Peripheral oxygen saturation SpO2 did not differ significantly between the groups, either at baseline (97.2 ± 1.6% vs 97.6 ± 1.8%, P = 0.491) or at follow-up (97.5 ± 1.5% vs 97.2 ± 1.5%, P = 0.470).
Self-reported health status Overall health status as measured by EQ-5D VAS was 64.6 ± 21.5 at baseline and 67.3 ± 21.6 at follow-up, with no significant differences between the groups (P < 0.136).
Thoracic excursion Baseline thoracic mobility, measured as difference in size of thoracic cage between inspiration and expiration, did not differ significantly between the groups (2.8 ± 2.0 cm vs 3.9 ± 2.0 cm, P = 0.055). Change in thoracic excursion after the study period did not differ between groups (P = 0.905).
Subjective breathing and coughing ability The groups did not differ in terms of perceived ability to take deep breaths (median 0; range 0–5; P = 0.440), coughing ability (0; 0–6; P = 0.484), dyspnea while walking indoors (0; 0–6; P = 0.889) or dyspnea while climbing stairs (0; 0–8; P = 0.777). In the breathing group, 48% perceived benefit from the exercises; positive effects were easier breathing, reduced dyspnea, stronger trunk, less snoring and fresher legs.
6
Discussion We found a significant difference in the relative change of VC and FVC in patients with mild to moderate MS after 2 months of home-based deep breathing exercises, compared with a control group performing no breathing exercises. There were no effects on respiratory muscle strength or subjective benefits. Earlier studies on MS patients have reported expiratory muscle weakness in those who are bedridden or full-time wheelchair users (17–19). Few studies have evaluated breathing exercises performed by MS patients, with only two randomized controlled trials evaluating the effect of expiratory muscle training (3, 9). In 15 patients with clinically definite MS (EDSS 6.5–9.5) and baseline MEP of 45%–60% predicted, 3 months of expiratory muscle training could increase the strength of expiratory muscles (9). In 28 MS patients (EDSS 6.5–9.5) who were bedridden or
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2015 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd
Westerdahl et al.
full-time wheelchair users and had baseline MEP of 18% predicted, 3 months of expiratory muscle training resulted in subjectively and objectively improved cough efficacy, but had no effect on expiratory muscle strength (3). Since impaired pulmonary function and respiratory muscle strength have been reported in severely affected but ambulatory MS patients as compared with healthy controls (20), we were interested in finding out whether less disabled patients could also benefit from breathing exercises. We consequently invited MS patients with suspected or documented mobility impairment with or without use of walking aids, but excluded those who were bedridden or who used a wheelchair full time. In our study, baseline respiratory muscle strength was normal (MIP 98%, MEP 104% of predicted value) according to reference values by Evans and Whitelaw (12), with only two patients reaching below the lower limit of normal, so we did not expect increased lung function after 2 months of breathing exercises. However, the significant difference regarding VC and FVC between the breathing and control groups suggests that breathing exercises might slow down or prevent deterioration in lung function. This hypothesis must be further evaluated and confirmed in larger trials with longer follow-up periods. Pulmonary manifestations of MS primarily comprise respiratory muscle weakness leading to impaired ventilation and cough (5, 7, 19). Expiratory muscle strength is more affected than inspiratory muscle strength, and impairment in expiratory muscle strength is related to decreased FVC, cough efficacy and functional status (3). Respiratory muscle force is indirectly measured through the pressure generated during inspiration and expiration, and the normal range in healthy subjects is very large (21). Test/retest reliability is adequate (intraclass correlation coefficient >0.80) in the sitting position in healthy volunteers (22). MIP and MEP are effort-dependent tests, and two practice sessions are preferred in MS patients to obtain consistent MIP and MEP values (23). Patients’ motivation and cooperation, number of attempts, learning effects, and degree of fatigue may affect measurements of pulmonary function and muscle strength. Discarding the first-session values could have increased the reliability of the measurement (22), but we were not able to do this; however, the patients had careful instructions at the first session to avoid a learning effect at follow-up. Expiratory muscle weakness may create problems with speech, swallowing and cough efficacy (4, 24, 25).
Deep breathing exercises for MS patients
The diagnosis of a weak cough is often based on anamnestic data and is arbitrarily given. In our study, peak cough flow was evaluated and shown to be normal according to standard values (26). Respiratory muscle weakness produces a restrictive pattern on spirometry, but VC and its subdivisions are relatively insensitive indicators of respiratory muscle weakness. Indeed, respiratory muscle strength has to fall below half normal before VC is significantly impacted (18, 27). An increase in residual volume may be attributed to expiratory muscle weakness, while poor inspiration may result from diaphragmatic fatigue (27). Unfortunately, we did not measure static lung volumes. Neuromuscular disorders involving the thoracic cage may lead to a reduction in chest wall muscle contraction (28). Thoracic mobility, measured as difference in circumference of the thoracic cage between inspiration and expiration, was normal and did not differ significantly between the breathing and control groups. Exercise training programs have long been considered an integral component in the rehabilitation of patients with MS. In our study, patients were instructed to perform deep breathing exercises with PEP twice a day. The frequency of 30 deep breaths per session was chosen according to clinical practice. An increased frequency is likely to be more efficacious, but we considered a total of 60 breaths a day as reasonable. A limitation in this study is that sample size was rather small, but only four of the randomized patients were excluded. In the study by Smeltzer et al., home visits were conducted to assure compliance with the training protocols and to obtain measurements (9). In the present study, the patients were only contacted once by telephone in order to emphasize the importance of executing the exercises, but without any further supervision after discharge, which might be one explanation for failure of treatment effects in variables other than spirometry. The patients completed training diaries, but as with all home exercising it was not possible to observe how well each person performed the breathing exercises. We unfortunately did not repeat measurement of pulmonary function or strength after the final measurement immediately after the training period. The effects of treatment have been reported up to 4 weeks after detraining, with MEP and PEF significantly higher at this point compared with pretraining (4). There is little scientific evidence to support one technique over another. The expiratory resistance method (PEP) used in the present study is thought to slow
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2015 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd
7
Deep breathing exercises for MS patients
Westerdahl et al.
down expiration and increase lung volume, and may prevent or reduce airway collapse. The initial deep inspiration in combination with expiratory resistance possibly extends time at a higher lung volume, leading to better ventilation. Patients with advanced MS have a high risk of pulmonary complications, including decreased lung function, and hence early detection of respiratory impairments is important. The possibility to delay progression of respiratory dysfunction in MS patients with mild to moderate symptoms needs to be further studied in future trials. Deterioration in respiratory muscle function occurs slowly in progressive diseases, but there may also be acute declines that can benefit from breathing exercises, for example impaired airway clearance during an upper respiratory tract infection or an episode of aspiration. Few studies have focused on expiratory muscle strength, and to our knowledge this study is the first to evaluate breathing interventions in patients with moderate disability. If the results can be confirmed in larger studies, breathing exercises for MS patients can be recommended to be performed at home. The exercises are easy to perform, at a low cost. Delaying the onset of respiratory problems would be a valuable contribution to maintaining good health. Further studies are warranted to determine optimal training prescriptions for frequency and duration, and to determine the optimal onset of breathing exercises in a progressive disease such as MS.
Conclusions After 2 months of deep breathing exercises, MS patients showed a significantly different relative change in lung function, as compared with a control group. Even if lung function does not increase, breathing exercises might help these patients preserve lung function. The exercises are easy to perform and feasible as home training. However, the clinical importance of breathing interventions in order to prevent pulmonary complications or prolong survival needs to be further investigated.
Acknowledgments Financial support was provided by grants from BiogenIdec Sweden AB, Sweden, NorrbackaEugeniastiftelsen, Stockholm, Sweden, the Research Committee of Örebro County Council, Örebro, Sweden, and the Swedish Research Council (Reg. No. 2009-1385).
8
References 1. Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983;33(11): 1444–52. 2. Kurtzke JF. Historical and clinical perspectives of the Expanded Disability Status Scale. Neuroepidemiology. 2008;31(1): 1–9. 3. Gosselink R, Kovacs L, Ketelaer P, Carton H, Decramer M. Respiratory muscle weakness and respiratory muscle training in severely disabled multiple sclerosis patients. Arch Phys Med Rehabil. 2000;81(6): 747–51. 4. Chiara T, Martin AD, Davenport PW, Bolser DC. Expiratory muscle strength training in persons with multiple sclerosis having mild to moderate disability: effect on maximal expiratory pressure, pulmonary function, and maximal voluntary cough. Arch Phys Med Rehabil. 2006;87(4): 468–73. 5. Tantucci C, Massucci M, Piperno R, Betti L, Grassi V, Sorbini CA. Control of breathing and respiratory muscle strength in patients with multiple sclerosis. Chest. 1994;105(4): 1163–70. 6. Buyse B, Demedts M, Meekers J, Vandegaer L, Rochette F, Kerkhofs L. Respiratory dysfunction in multiple sclerosis: a prospective analysis of 60 patients. Eur Respir J. 1997;10(1): 139–45. 7. Mutluay FK, Gurses HN, Saip S. Effects of multiple sclerosis on respiratory functions. Clin Rehabil. 2005;19(4): 426–32. 8. Ray AD, Udhoji S, Mashtare TL, Fisher NM. A combined inspiratory and expiratory muscle training program improves respiratory muscle strength and fatigue in multiple sclerosis. Arch Phys Med Rehabil. 2013;94(10): 1964–70. 9. Smeltzer SC, Lavietes MH, Cook SD. Expiratory training in multiple sclerosis. Arch Phys Med Rehabil. 1996;77(9): 909–12. 10. Polman CH, Reingold SC, Banwell B, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011;69(2): 292–302. 11. American Thoracic Society/European Respiratory S. ATS/ERS statement on respiratory muscle testing. Am J Respir Crit Care Med. 2002;166(4): 518–624. 12. Evans JA, Whitelaw WA. The assessment of maximal respiratory mouth pressures in adults. Respir Care. 2009;54(10): 1348–59. 13. Miller MR, Hankinson J, Brusasco V, et al. Standardisation of spirometry. Eur Respir J. 2005;26(2): 319–38. 14. Quanjer PH, Tammeling GJ, Cotes JE, Pedersen OF, Peslin R, Yernault JC. Lung volumes and forced ventilatory flows. Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society. Eur Respir J Suppl. 1993;16: 5–40. 15. Fagevik Olsén M, Lindstrand H, Lind Broberg J, Westerdahl E. Measuring chest expansion; A study
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2015 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd
Westerdahl et al.
16.
17.
18.
19.
20.
21.
comparing two different instructions. Adv Physiother. 2011;13: 128–32. EuroQol Group. EuroQol: a new facility for the measurement of health-related quality of life. Health Policy (New York). 1990;16(3): 199–208. Smeltzer SC, Utell MJ, Rudick RA, Herndon RM. Pulmonary function and dysfunction in multiple sclerosis. Arch Neurol. 1988;45(11): 1245–9. Smeltzer SC, Skurnick JH, Troiano R, Cook SD, Duran W, Lavietes MH. Respiratory function in multiple sclerosis. Utility of clinical assessment of respiratory muscle function. Chest. 1992;101(2): 479–84. Gosselink R, Kovacs L, Decramer M. Respiratory muscle involvement in multiple sclerosis. Eur Respir J. 1999;13(2): 449–54. Savci S, Inal-Ince D, Arikan H, et al. Six-minute walk distance as a measure of functional exercise capacity in multiple sclerosis. Disabil Rehabil. 2005;27(22): 1365–71. Enright PL, Kronmal RA, Manolio TA, Schenker MB, Hyatt RE. Respiratory muscle strength in the elderly. Correlates and reference values. Cardiovascular Health Study Research Group. Am J Respir Crit Care Med. 1994;149(2 Pt 1): 430–8.
Deep breathing exercises for MS patients
22. Dimitriadis Z, Kapreli E, Konstantinidou I, Oldham J, Strimpakos N. Test/retest reliability of maximum mouth pressure measurements with the MicroRPM in healthy volunteers. Respir Care. 2011;56(6): 776–82. 23. Smeltzer SC, Lavietes MH. Reliability of maximal respiratory pressures in multiple sclerosis. Chest. 1999;115(6): 1546–52. 24. Chiara T, Martin D, Sapienza C. Expiratory muscle strength training: speech production outcomes in patients with multiple sclerosis. Neurorehabil Neural Repair. 2007;21(3): 239–49. 25. Aiello M, Rampello A, Granella F, et al. Cough efficacy is related to the disability status in patients with multiple sclerosis. Respiration. 2008;76(3): 311–6. 26. Bianchi C, Baiardi P. Cough peak flows: standard values for children and adolescents. Am J Phys Med Rehabil. 2008;87(6): 461–7. 27. Rochester DF, Esau SA. Assessment of ventilatory function in patients with neuromuscular disease. Clin Chest Med. 1994;15(4): 751–63. 28. Estenne M, Heilporn A, Delhez L, Yernault JC, De Troyer A. Chest wall stiffness in patients with chronic respiratory muscle weakness. Am Rev Respir Dis. 1983;128(6): 1002–7.
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2015 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd
9
The Clinical Respiratory Journal
Deep breathing exercises with positive expiratory pressure in patients with multiple sclerosis – a randomized controlled trial Elisabeth Westerdahl1, Anna Wittrin2, Margareta Kånåhols2, Martin Gunnarsson2 and Ylva Nilsagård3 1 Faculty of Medicine and Health, Surgery, Örebro University, Örebro, Sweden 2 Faculty of Medicine and Health, Department of Neurology and Neurophysiology, Örebro University, Örebro, Sweden 3 Faculty of Medicine and Health, Medicine, Örebro University, Örebro, Sweden
Abstract Introduction: Breathing exercises with positive expiratory pressure are often recommended to patients with advanced neurological deficits, but the potential benefit in multiple sclerosis (MS) patients with mild and moderate symptoms has not yet been investigated in randomized controlled trials. Objectives: To study the effects of 2 months of home-based breathing exercises for patients with mild to moderate MS on respiratory muscle strength, lung function, and subjective breathing and health status outcomes. Methods: Forty-eight patients with MS according to the revised McDonald criteria were enrolled in a randomized controlled trial. Patients performing breathing exercises (n = 23) were compared with a control group (n = 25) performing no breathing exercises. The breathing exercises were performed with a positive expiratory pressure device (10–15 cmH2O) and consisted of 30 slow deep breaths performed twice a day for 2 months. Respiratory muscle strength (maximal inspiratory and expiratory pressure at the mouth), spirometry, oxygenation, thoracic excursion, subjective perceptions of breathing and self-reported health status were evaluated before and after the intervention period. Results: Following the intervention, there was a significant difference between the breathing group and the control group regarding the relative change in lung function, favoring the breathing group (vital capacity: P < 0.043; forced vital capacity: P < 0.025). There were no other significant differences between the groups. Conclusion: Breathing exercises may be beneficial in patients with mild to moderate stages of MS. However, the clinical significance needs to be clarified, and it remains to be seen whether a sustainable effect in delaying the development of respiratory dysfunction in MS can be obtained. Please cite this paper as: Westerdahl E, Wittrin A, Kånåhols M, Gunnarsson M and Nilsagård Y. Deep breathing exercises with positive expiratory pressure in patients with multiple sclerosis – a randomized controlled trial. Clin Respir J 2015; ••: ••–••. DOI:10.1111/crj.12272.
Key words breathing exercises – multiple sclerosis – positive expiratory pressure – respiratory function tests Correspondence Elisabeth Westerdahl, RPT, PhD, Örebro University Hospital, Centre for Health Care Sciences, Box 1324, SE-701 85 Örebro, Sweden. Tel: +46 19 602 5847 Fax: +46 19 602 5778 email: [email protected] Received: 20 August 2014 Revision requested: 16 December 2014 Accepted: 20 January 2015 DOI:10.1111/crj.12272 Authorship and contributorship All of the authors contributed to the design of the study. AW and MK performed the data collection. EW performed the statistical analysis and wrote the manuscript. AW, MK, MG and YN contributed to the interpretation of results and helped draft the final manuscript. All authors read and approved the final manuscript. Ethics The Regional Ethical Review Board in Uppsala, Sweden, approved the study (2012/077). The trial was registered at ClinicalTrials.gov NCT01774201; URL: www.clinicaltrials.gov. Conflict of interest The authors have stated explicitly that there are no conflicts of interest in connection with this article.
Introduction Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease affecting widespread areas of
the central nervous system. Consequently, injuries in motor pathways are common in MS patients, resulting in muscle weakness and impaired mobility.
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 1 © 2015 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Deep breathing exercises for MS patients
Westerdahl et al.
Symptoms and disease progression vary among individuals, depending on the localization, size and the number of lesions. Disease severity is often rated with the Expanded Disability Status Scale (EDSS), which is influenced by ambulatory status (1, 2). Impaired respiratory function has been observed in the end stage of the disease, and pulmonary manifestations have long been recognized to cause morbidity and mortality in individuals with advanced MS (3). Respiratory muscle weakness, however, may also occur in early-stage disease (4), causing impaired ventilation and poor cough even in patients with more moderate disease (5, 6). The impairment in respiratory muscle function increases with MS severity. Expiratory muscle weakness is more prominent than inspiratory muscle weakness, and may impair coughing ability (7). Strategies to improve expiratory muscle function are important in preventing deterioration of pulmonary function (3). Possible mechanisms of breathing exercises with positive expiratory pressure (PEP) include improved respiratory muscle strength and a momentary increase in lung volumes that may facilitate secretion mobilization. Eight weeks of expiratory muscle strength training with a threshold trainer in patients with mild to moderate disability have been shown to increase maximal expiratory pressure (MEP) and peak expiratory flow (PEF) in a before-after trial (4). In a recently published before-after trial, 5 weeks of inspiratory and expiratory muscle training were shown to increase muscle strength and reduce fatigue in patients with mild to moderate MS (8). Only two randomized trials have been performed evaluating expiratory muscle strength training for severely disabled MS patients (3, 9). It is unknown whether breathing exercises with PEP device may improve respiratory function or delay the development of respiratory dysfunction in patients with MS. To our knowledge, no randomized controlled trials have been performed evaluating breathing exercises in patients with mild to moderate MS, and no studies have evaluated breathing exercises performed at home. Our aim was to evaluate the effects of 8 weeks of home-based deep breathing exercises with PEP for MS patients with mild to moderate neurological deficits and early stages of physical impairment, concerning respiratory muscle strength, lung function, oxygenation and subjective perceptions of breathing.
Materials and methods Patients and study design We performed a randomized, controlled, singleblinded, parallel-group trial. Eligible for inclusion were
2
all patients aged 18 years or older with mild to moderate MS according to the revised McDonald criteria (10), living in Örebro County, and registered in the Swedish MS Registry in September 2012. To quantify the disability of MS, the EDSS was used, based on an examination by a neurologist. The score range from 0 to 10: 0 represents no impairment, 4 represents onset of significant walking impairment, 6 represents onset of assistive device during ambulation, and 10 represents death due to MS (1, 2). A total of 149 patients were contacted by letter and then by phone, and were assessed for eligibility. Of these, 71 declined participation due to participation in other studies, long distance to the hospital, or personal or social reasons, and 26 did not meet the inclusion criteria (Fig. 1). The inclusion criteria were relapse-free for at least 3 months prior to study entry, able to understand verbal and written information, and preserved ability to walk with or without use of walking devices. The exclusion criteria for randomization in the study were the following: other diseases or conditions impacting functional ability (e.g. other neurological diseases, severe ischaemic heart disease, orthopedic conditions), or language or cognitive difficulties which could adversely influence the performance of lung function tests. Informed written consent was obtained from each patient, the Regional Ethical Review Board in Uppsala, Sweden, approved the study (2012/077), and the trial was registered at ClinicalTrials.gov (NCT01774201; URL: www.clinicaltrials.gov).
Sample size determination and randomization A difference in MEP of 12 cmH2O (35 vs 47 cmH2O) between the two groups was considered possible, and of clinical interest. Sample size calculation showed that 22 patients per group would be required for a power of 80% to detect a 10% difference between the groups, assuming a standard deviation of 14 cmH2O. To account for missing values, another five patients were included in each group, giving a total of 52 patients. After four dropouts, 48 patients were analyzed (Fig. 1). A computer-generated list was used to randomize eligible patients. This list had been administered by an independent secretary, who printed notes showing group assignment and put them in sequentially numbered, sealed, nontransparent envelopes. Patients were allocated to groups after their informed consent had been obtained for inclusion.
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2015 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd
Westerdahl et al.
Deep breathing exercises for MS patients
Assessed for eligibility (n = 149)
Enrollment
•
Declined to participate (n = 71) Did not meet inclusion criteria, or excluded after baseline assessment (n = 26):
• • • • •
Disease affecting walking ability (n = 11) No walking ability (n = 7) Language difficulties (n = 4) Unclear MS diagnosis (n = 3) Cognitive dysfunction (n = 1)
Randomized (n = 52)
Allocation Allocated to breathing group
Allocated to control group
(n = 26)
(n = 26)
Follow-Up Lost to follow-up (n = 3)
Lost to follow-up (n = 1)
Analysis Analyzed
Analyzed
(n = 23)
(n = 25)
Figure 1. Flowchart of the patients in the study. MS, multiple sclerosis.
Intervention Before baseline measurements, patients were randomly assigned to perform home-based deep breathing exercises for 2 months (breathing group, n = 23) or to perform no breathing exercises (control group, n = 25). The breathing group was instructed to perform 30 deep breaths in a sitting position twice a day: three series of 10 calm and deep breaths with a 30–60 s pause between each set. A PEP device (Rium breathing exerciser; Rium Medical AB, Åkersberga, Sweden) (Fig. 2) was used to create an expiratory pressure of 10–15 cmH2O. Patients were instructed to inspire as deep as possible, hold their breath for 2 s and then expire through the PEP device, ending the expiration before emptying their lungs to minimize the risk of airway closure. They were also taught how to clean the PEP device. Two weeks after the intervention start, patients in the breathing group were telephoned at
Figure 2. Breathing exerciser, Rium Medical AB, Åkersberga, Sweden.
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2015 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd
3
Deep breathing exercises for MS patients
Westerdahl et al.
home for coaching of the breathing exercises, and after 4 weeks a letter was sent to remind them about the exercises. These patients documented compliance with training in an exercise diary. Patients in the control group performed no breathing exercises. Otherwise, all patients received standard medical care during the study period.
Measurements Measurements were performed at baseline and immediately after the 2-month intervention period at Örebro University Hospital, Sweden. First, a medical doctor performed a neurological examination and recorded the patient’s EDSS score. Data on demographics and medical history, such as disease phenotype, were collected from medical charts or written down (self-reported) by the patient. Next, a physiotherapist experienced in neurology and blinded to group allocation assessed the lung function and respiratory muscle strength, and each patient answered self-reported questionnaires covering descriptive data, ability to breathe and cough, physical activity, and health-related quality of life. The primary outcome was expiratory respiratory muscle strength. Secondary outcomes were lung function assessed by spirometry, peripheral oxygen saturation (SpO2), subjective breathing and coughing ability, and self-reported health status.
Respiratory muscle strength Respiratory muscle strength was defined as the maximal static pressures measured at the mouth. Measurements were performed from total lung capacity for MEP and from residual volume for maximal inspiratory pressure (MIP) as described in the American Thoracic Society/European Respiratory Society (ATS/ERS) statement on respiratory muscle testing (11). Measurements were performed in a sitting position and with a nose-clip (Micro RPM; MicroMedical/ CareFusion, Kent, UK). Patients were instructed to press their lips tightly against the flanged mouthpiece and to support their cheeks manually during the maneuver to prevent air leak. The highest value from at least five technically acceptable attempts was recorded and expressed as an absolute value (cmH2O) and as a percentage of predicted value adjusted for age and sex (12).
try was performed with a MicroLab spirometer (MicroMedical/CareFusion), calibrated every morning prior to measurements. Patients were in a sitting position, a nose-clip was used, and measurements were performed as recommended by the ATS/ERS (13). The highest value of three technically satisfactory maneuvers was retained. An inspiratory maneuver was obtained for measurement of slow vital capacity (VC), followed by measurement of forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), PEF and FEV% (FEV1/VCmax). Predicted values for pulmonary function were related to age, sex and height (14). Peak cough flow was measured by a portable peak flow meter (Vitalograph, Ennis, Ireland) connected to a face mask. Patients were asked to take a deep breath without the mask, and then cough as much as possible with the mask tightly sealed against the face. The best value of three attempts was noted. The SpO2 was measured using a pulse oximeter device (Rad-5v; Masimo, Irvine, CA, USA).
Thoracic excursion Thoracic excursions were measured using a tape (marked in millimeters) around the circumference of the chest at the level of the xiphoid process to give a measurement of chest expansion or mobility. Patients were asked to stand with their hands on their head and given the instructions ‘Breathe in maximally and make yourself as big as possible’ and ‘Breathe out maximally and make yourself as small as possible’. Chest expansion was taken as the difference between full expiration and inspiration using the best of two attempts (15).
Subjective breathing and coughing ability All patients scored their perceived breathing and coughing ability on a numeric rating scale, from 0 (‘no difficulty’) to 10 (‘impossible’), and their level of dyspnea while walking indoors and while climbing stairs on a numeric rating scale from 0 (‘no dyspnea’) to 10 (‘worst imaginable dyspnea’). Patients in the breathing group were asked to score compliance with, subjective benefit from, and discomfort associated with the breathing exercises on a scale from 0 (‘not at all’) to 2 (‘very much’).
Lung function measurements
Self-reported health status
Lung function variables were measured by a physiotherapist blinded to treatment allocation. Spirome-
Patients rated their perception of overall health status on the EuroQoL EQ-5D visual analogue scale
4
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2015 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd
Westerdahl et al.
Deep breathing exercises for MS patients
(EQ-5D VAS) from 0 (‘worst imaginable’) to 100 (‘best imaginable’) (16).
Statistical analysis Continuous baseline data were compared with Student’s t-test and categorical data with Fisher’s exact test or a chi-squared test. Differences between groups were assessed with Student’s unpaired t-test, the Mann– Whitney U-test or a chi-squared test. All results refer to two-sided tests, with P values ≤ 0.05 considered significant. Version 15.0 of the SPSS software package (SPSS Inc., Chicago, IL, USA) was used for statistical analysis.
Results Of the 52 randomized patients, 48 were analyzed (Fig. 1). Reasons for withdrawal after randomization in the breathing group (n = 3) and the control group (n = 1) were other morbidities, failure to cooperate or unwillingness to perform the follow-up. Baseline demographic data did not differ significantly between the two groups (Table 1). Median EDSS score was 5.0 (3–7) in the breathing group and 4.5 (1.5–8) in the control group. Patients in the breathing group (n = 23) reported having performed the breathing exercises once or twice a day with 30 ± 8 breaths during each training occasion. Eleven patients (48%) reported subjective benefit from the breathing exercises, and four (17%) reported some discomfort.
Table 1. Demographic data
Male/female, n Age, years BMI, kg/m2 Never smoked/ ex-smoker/smoker, n Airway obstruction, n MS disease duration, years Relapsing-remitting MS Secondary progressive MS Primary progressive MS EDSS, median
Breathing group (n = 23)
Control group (n = 25)
6/17 55 ± 12 27 ± 5 12/8/3
7/18 56 ± 9 26 ± 4 9/9/7
1 24 ± 11 11 11 1 5.0
3 23 ± 11 9 15 1 4.5
Patients with preoperative FEV1/VCmax < 0.70 were defined as having airway obstruction. Data are presented as mean ± standard deviation or number (n) of patients. No significant differences between groups. BMI, body mass index; EDSS, Expanded Disability Status Scale; MS, multiple sclerosis; FEV1, forced expiratory volume in 1 s; VC, vital capacity.
dicted values ranged from 59% to 169% (mean 104% ± 29%), with two patients reaching below the lower limit of normal according to reference values by Evans and Whitelaw (12). After the 2-month intervention period, there was no significant difference between the breathing and control groups regarding change in MIP and MEP (Table 2).
Lung function Respiratory muscle strength In the total sample, baseline MIP values ranged from 26 to 143 (mean 80 ± 28) cmH2O, and the percentage predicted values ranged from 39% to 165% (mean 98% ± 31%). Baseline MEP values ranged from 43 to 166 (mean 97 ± 25) cmH2O, and percentage pre-
Baseline lung function was normal in relation to predicted values (VC: 103 ± 16% predicted; FEV1: 95 ± 15% predicted; FVC: 103 ± 15; FEV%: 98 ± 9), with no significant difference between the groups. Spirometry values at baseline and follow-up are presented in Table 3.
Table 2. Respiratory muscle strength at baseline and after the intervention Two-month follow-up
Baseline
MIP (cmH2O) MIP (%predicted) MEP (cmH2O) MEP (%predicted)
Two-month values in percentage of baseline values
Difference between groups [95% CI] Change after 2 months
Breathing
Control
Breathing
Control
Breathing
Control
78 ± 33 96 ± 38 95 ± 31 101 ± 31
81 ± 23 101 ± 24 98 ± 18 106 ± 26
77 ± 32 95 ± 36 98 ± 28 104 ± 27
82 ± 24 102 ± 28 100 ± 23 107 ± 26
100 ± 13%
101 ± 15%
1% [−7–9]
P value 0.74
105 ± 15%
102 ± 17%
−3% [−12–6]
0.52
Data are presented as mean ± standard deviation [95% confidence interval of the difference]. P values refer to the difference between the breathing group and the control group after the 2-month intervention regarding the relative changes in lung function, with 2-month values as % of baseline values (P < 0.05 considered significant). CI, confidence interval; MEP, maximal expiratory pressure; MIP, maximal inspiratory pressure.
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2015 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd
5
Deep breathing exercises for MS patients
Westerdahl et al.
Table 3. Spirometry data at baseline and after the intervention Baseline
VC (L) FEV1 (L) FVC (L) FEV1/VC (%) PEF (L/min)
Two-month follow-up
Two-month values in percentage of baseline values
Difference between groups [95% CI]
Breathing
Control
Breathing
Control
Breathing
Control
Change after 2 months
P value
3.3 ± 0.8 2.6 ± 0.7 3.3 ± 0.8 78.4 ± 7.1 351 ± 86
3.7 ± 1.0 2.8 ± 0.7 3.7 ± 1.1 74.8 ± 6.6 385 ± 90
3.3 ± 0.9 2.6 ± 0.7 3.3 ± 0.8 77.5 ± 6.0 375 ± 87
3.5 ± 1.0 2.7 ± 0.7 3.6 ± 1.0 75.3 ± 6.6 382 ± 92
100.1 ± 8.1% 100.8 ± 5.7% 101.8 ± 6.6% 99.1 ± 5.2% 108.6 ± 14.9%
95.7 ± 6.4% 97.6 ± 6.9% 97.0 ± 7.6% 100.7 ± 4.4% 100.4 ± 17.1%
−4.4% [−8.6–−0.1] −3.2% [−6.9–0.5] −4.8% [−9.0–−0.6] 1.6% [−17.5–1.2] −8.2% [−1.1–4.4]
0.043 0.092 0.025 0.242 0.086
Data are presented as mean ± standard deviation [95% confidence interval of the difference]. P values refer to the difference between the breathing group and the control group after the 2-month intervention regarding the relative changes in lung function, with 2-month values as % of baseline values (P < 0.05 considered significant). CI, confidence interval; FEV1, forced expiratory volume in 1 s; VC, vital capacity; FVC, forced vital capacity; PEF, peak expiratory flow.
At follow-up, there was a significant between-group difference in relative change in lung function, favoring the breathing group (VC: P < 0.043; FVC: P < 0.025) (Table 3). Peak cough flow decreased significantly from 389 ± 70 at baseline to 374 ± 76 (P = 0.044) at followup, but with no significant difference between the groups regarding the change from baseline (P = 0.305).
In addition, 56% reported that the breathing exercises made it easier to take deep breaths, and 92% reported that the breathing technique was easy to perform. Discomfort related to the exercises was reported by 4% to a high degree and 13% to some extent. Adverse perceptions were related to dizziness, strenuousness and tediousness. Patients reported having performed 30 ± 9 (range 7–60) breaths at each training session.
Peripheral oxygen saturation SpO2 did not differ significantly between the groups, either at baseline (97.2 ± 1.6% vs 97.6 ± 1.8%, P = 0.491) or at follow-up (97.5 ± 1.5% vs 97.2 ± 1.5%, P = 0.470).
Self-reported health status Overall health status as measured by EQ-5D VAS was 64.6 ± 21.5 at baseline and 67.3 ± 21.6 at follow-up, with no significant differences between the groups (P < 0.136).
Thoracic excursion Baseline thoracic mobility, measured as difference in size of thoracic cage between inspiration and expiration, did not differ significantly between the groups (2.8 ± 2.0 cm vs 3.9 ± 2.0 cm, P = 0.055). Change in thoracic excursion after the study period did not differ between groups (P = 0.905).
Subjective breathing and coughing ability The groups did not differ in terms of perceived ability to take deep breaths (median 0; range 0–5; P = 0.440), coughing ability (0; 0–6; P = 0.484), dyspnea while walking indoors (0; 0–6; P = 0.889) or dyspnea while climbing stairs (0; 0–8; P = 0.777). In the breathing group, 48% perceived benefit from the exercises; positive effects were easier breathing, reduced dyspnea, stronger trunk, less snoring and fresher legs.
6
Discussion We found a significant difference in the relative change of VC and FVC in patients with mild to moderate MS after 2 months of home-based deep breathing exercises, compared with a control group performing no breathing exercises. There were no effects on respiratory muscle strength or subjective benefits. Earlier studies on MS patients have reported expiratory muscle weakness in those who are bedridden or full-time wheelchair users (17–19). Few studies have evaluated breathing exercises performed by MS patients, with only two randomized controlled trials evaluating the effect of expiratory muscle training (3, 9). In 15 patients with clinically definite MS (EDSS 6.5–9.5) and baseline MEP of 45%–60% predicted, 3 months of expiratory muscle training could increase the strength of expiratory muscles (9). In 28 MS patients (EDSS 6.5–9.5) who were bedridden or
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2015 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd
Westerdahl et al.
full-time wheelchair users and had baseline MEP of 18% predicted, 3 months of expiratory muscle training resulted in subjectively and objectively improved cough efficacy, but had no effect on expiratory muscle strength (3). Since impaired pulmonary function and respiratory muscle strength have been reported in severely affected but ambulatory MS patients as compared with healthy controls (20), we were interested in finding out whether less disabled patients could also benefit from breathing exercises. We consequently invited MS patients with suspected or documented mobility impairment with or without use of walking aids, but excluded those who were bedridden or who used a wheelchair full time. In our study, baseline respiratory muscle strength was normal (MIP 98%, MEP 104% of predicted value) according to reference values by Evans and Whitelaw (12), with only two patients reaching below the lower limit of normal, so we did not expect increased lung function after 2 months of breathing exercises. However, the significant difference regarding VC and FVC between the breathing and control groups suggests that breathing exercises might slow down or prevent deterioration in lung function. This hypothesis must be further evaluated and confirmed in larger trials with longer follow-up periods. Pulmonary manifestations of MS primarily comprise respiratory muscle weakness leading to impaired ventilation and cough (5, 7, 19). Expiratory muscle strength is more affected than inspiratory muscle strength, and impairment in expiratory muscle strength is related to decreased FVC, cough efficacy and functional status (3). Respiratory muscle force is indirectly measured through the pressure generated during inspiration and expiration, and the normal range in healthy subjects is very large (21). Test/retest reliability is adequate (intraclass correlation coefficient >0.80) in the sitting position in healthy volunteers (22). MIP and MEP are effort-dependent tests, and two practice sessions are preferred in MS patients to obtain consistent MIP and MEP values (23). Patients’ motivation and cooperation, number of attempts, learning effects, and degree of fatigue may affect measurements of pulmonary function and muscle strength. Discarding the first-session values could have increased the reliability of the measurement (22), but we were not able to do this; however, the patients had careful instructions at the first session to avoid a learning effect at follow-up. Expiratory muscle weakness may create problems with speech, swallowing and cough efficacy (4, 24, 25).
Deep breathing exercises for MS patients
The diagnosis of a weak cough is often based on anamnestic data and is arbitrarily given. In our study, peak cough flow was evaluated and shown to be normal according to standard values (26). Respiratory muscle weakness produces a restrictive pattern on spirometry, but VC and its subdivisions are relatively insensitive indicators of respiratory muscle weakness. Indeed, respiratory muscle strength has to fall below half normal before VC is significantly impacted (18, 27). An increase in residual volume may be attributed to expiratory muscle weakness, while poor inspiration may result from diaphragmatic fatigue (27). Unfortunately, we did not measure static lung volumes. Neuromuscular disorders involving the thoracic cage may lead to a reduction in chest wall muscle contraction (28). Thoracic mobility, measured as difference in circumference of the thoracic cage between inspiration and expiration, was normal and did not differ significantly between the breathing and control groups. Exercise training programs have long been considered an integral component in the rehabilitation of patients with MS. In our study, patients were instructed to perform deep breathing exercises with PEP twice a day. The frequency of 30 deep breaths per session was chosen according to clinical practice. An increased frequency is likely to be more efficacious, but we considered a total of 60 breaths a day as reasonable. A limitation in this study is that sample size was rather small, but only four of the randomized patients were excluded. In the study by Smeltzer et al., home visits were conducted to assure compliance with the training protocols and to obtain measurements (9). In the present study, the patients were only contacted once by telephone in order to emphasize the importance of executing the exercises, but without any further supervision after discharge, which might be one explanation for failure of treatment effects in variables other than spirometry. The patients completed training diaries, but as with all home exercising it was not possible to observe how well each person performed the breathing exercises. We unfortunately did not repeat measurement of pulmonary function or strength after the final measurement immediately after the training period. The effects of treatment have been reported up to 4 weeks after detraining, with MEP and PEF significantly higher at this point compared with pretraining (4). There is little scientific evidence to support one technique over another. The expiratory resistance method (PEP) used in the present study is thought to slow
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2015 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd
7
Deep breathing exercises for MS patients
Westerdahl et al.
down expiration and increase lung volume, and may prevent or reduce airway collapse. The initial deep inspiration in combination with expiratory resistance possibly extends time at a higher lung volume, leading to better ventilation. Patients with advanced MS have a high risk of pulmonary complications, including decreased lung function, and hence early detection of respiratory impairments is important. The possibility to delay progression of respiratory dysfunction in MS patients with mild to moderate symptoms needs to be further studied in future trials. Deterioration in respiratory muscle function occurs slowly in progressive diseases, but there may also be acute declines that can benefit from breathing exercises, for example impaired airway clearance during an upper respiratory tract infection or an episode of aspiration. Few studies have focused on expiratory muscle strength, and to our knowledge this study is the first to evaluate breathing interventions in patients with moderate disability. If the results can be confirmed in larger studies, breathing exercises for MS patients can be recommended to be performed at home. The exercises are easy to perform, at a low cost. Delaying the onset of respiratory problems would be a valuable contribution to maintaining good health. Further studies are warranted to determine optimal training prescriptions for frequency and duration, and to determine the optimal onset of breathing exercises in a progressive disease such as MS.
Conclusions After 2 months of deep breathing exercises, MS patients showed a significantly different relative change in lung function, as compared with a control group. Even if lung function does not increase, breathing exercises might help these patients preserve lung function. The exercises are easy to perform and feasible as home training. However, the clinical importance of breathing interventions in order to prevent pulmonary complications or prolong survival needs to be further investigated.
Acknowledgments Financial support was provided by grants from BiogenIdec Sweden AB, Sweden, NorrbackaEugeniastiftelsen, Stockholm, Sweden, the Research Committee of Örebro County Council, Örebro, Sweden, and the Swedish Research Council (Reg. No. 2009-1385).
8
References 1. Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983;33(11): 1444–52. 2. Kurtzke JF. Historical and clinical perspectives of the Expanded Disability Status Scale. Neuroepidemiology. 2008;31(1): 1–9. 3. Gosselink R, Kovacs L, Ketelaer P, Carton H, Decramer M. Respiratory muscle weakness and respiratory muscle training in severely disabled multiple sclerosis patients. Arch Phys Med Rehabil. 2000;81(6): 747–51. 4. Chiara T, Martin AD, Davenport PW, Bolser DC. Expiratory muscle strength training in persons with multiple sclerosis having mild to moderate disability: effect on maximal expiratory pressure, pulmonary function, and maximal voluntary cough. Arch Phys Med Rehabil. 2006;87(4): 468–73. 5. Tantucci C, Massucci M, Piperno R, Betti L, Grassi V, Sorbini CA. Control of breathing and respiratory muscle strength in patients with multiple sclerosis. Chest. 1994;105(4): 1163–70. 6. Buyse B, Demedts M, Meekers J, Vandegaer L, Rochette F, Kerkhofs L. Respiratory dysfunction in multiple sclerosis: a prospective analysis of 60 patients. Eur Respir J. 1997;10(1): 139–45. 7. Mutluay FK, Gurses HN, Saip S. Effects of multiple sclerosis on respiratory functions. Clin Rehabil. 2005;19(4): 426–32. 8. Ray AD, Udhoji S, Mashtare TL, Fisher NM. A combined inspiratory and expiratory muscle training program improves respiratory muscle strength and fatigue in multiple sclerosis. Arch Phys Med Rehabil. 2013;94(10): 1964–70. 9. Smeltzer SC, Lavietes MH, Cook SD. Expiratory training in multiple sclerosis. Arch Phys Med Rehabil. 1996;77(9): 909–12. 10. Polman CH, Reingold SC, Banwell B, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011;69(2): 292–302. 11. American Thoracic Society/European Respiratory S. ATS/ERS statement on respiratory muscle testing. Am J Respir Crit Care Med. 2002;166(4): 518–624. 12. Evans JA, Whitelaw WA. The assessment of maximal respiratory mouth pressures in adults. Respir Care. 2009;54(10): 1348–59. 13. Miller MR, Hankinson J, Brusasco V, et al. Standardisation of spirometry. Eur Respir J. 2005;26(2): 319–38. 14. Quanjer PH, Tammeling GJ, Cotes JE, Pedersen OF, Peslin R, Yernault JC. Lung volumes and forced ventilatory flows. Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society. Eur Respir J Suppl. 1993;16: 5–40. 15. Fagevik Olsén M, Lindstrand H, Lind Broberg J, Westerdahl E. Measuring chest expansion; A study
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2015 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd
Westerdahl et al.
16.
17.
18.
19.
20.
21.
comparing two different instructions. Adv Physiother. 2011;13: 128–32. EuroQol Group. EuroQol: a new facility for the measurement of health-related quality of life. Health Policy (New York). 1990;16(3): 199–208. Smeltzer SC, Utell MJ, Rudick RA, Herndon RM. Pulmonary function and dysfunction in multiple sclerosis. Arch Neurol. 1988;45(11): 1245–9. Smeltzer SC, Skurnick JH, Troiano R, Cook SD, Duran W, Lavietes MH. Respiratory function in multiple sclerosis. Utility of clinical assessment of respiratory muscle function. Chest. 1992;101(2): 479–84. Gosselink R, Kovacs L, Decramer M. Respiratory muscle involvement in multiple sclerosis. Eur Respir J. 1999;13(2): 449–54. Savci S, Inal-Ince D, Arikan H, et al. Six-minute walk distance as a measure of functional exercise capacity in multiple sclerosis. Disabil Rehabil. 2005;27(22): 1365–71. Enright PL, Kronmal RA, Manolio TA, Schenker MB, Hyatt RE. Respiratory muscle strength in the elderly. Correlates and reference values. Cardiovascular Health Study Research Group. Am J Respir Crit Care Med. 1994;149(2 Pt 1): 430–8.
Deep breathing exercises for MS patients
22. Dimitriadis Z, Kapreli E, Konstantinidou I, Oldham J, Strimpakos N. Test/retest reliability of maximum mouth pressure measurements with the MicroRPM in healthy volunteers. Respir Care. 2011;56(6): 776–82. 23. Smeltzer SC, Lavietes MH. Reliability of maximal respiratory pressures in multiple sclerosis. Chest. 1999;115(6): 1546–52. 24. Chiara T, Martin D, Sapienza C. Expiratory muscle strength training: speech production outcomes in patients with multiple sclerosis. Neurorehabil Neural Repair. 2007;21(3): 239–49. 25. Aiello M, Rampello A, Granella F, et al. Cough efficacy is related to the disability status in patients with multiple sclerosis. Respiration. 2008;76(3): 311–6. 26. Bianchi C, Baiardi P. Cough peak flows: standard values for children and adolescents. Am J Phys Med Rehabil. 2008;87(6): 461–7. 27. Rochester DF, Esau SA. Assessment of ventilatory function in patients with neuromuscular disease. Clin Chest Med. 1994;15(4): 751–63. 28. Estenne M, Heilporn A, Delhez L, Yernault JC, De Troyer A. Chest wall stiffness in patients with chronic respiratory muscle weakness. Am Rev Respir Dis. 1983;128(6): 1002–7.
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2015 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd
9
