The Ceiling Effect: The 6MWT or Glittreprotokollen in COPD Patients with High Initial Functional Capacity

Transcription

1 Fontys University of Applied Sciences The Ceiling Effect: The 6MWT or Glittreprotokollen in COPD Patients with High Initial Functional Capacity A retrospective observational study Peter Johnson* *Corresponding Author, Department of Physiotherapy, English Stream 4A, Fontys University of Applied Sciences, Eindhoven, The Netherlands. Tel: address: peter.johnson@student.fontys.nl Version 1.0 Supervisory teachers; Frank Vossen Ingrid Janssen

2 PREFACE I spent my last clinical affiliation period before completing my bachelor s degree at Glittreklinikken in Norway. Glittreklinikken is a hospital specializing in pulmonary rehabilitation. It was conversations and discussions with the health professionals at this hospital that inspired me with the idea and to further carry out the research. This paper presents one widely used test in pulmonary rehabilitation measuring functional capacity, the 6MWT, and compares the outcomes to another test used at Glittreklinikken called Glittreprotokollen. Glittreprotokollen has been used for many years at Glittreklinikken and the health care professionals using it have good experience with it. However, the test has not been published. This paper is primarily addressed to health care professionals interested in or working with pulmonary patients. It is the hope of the author that this research might spark further interest in Glittreprotokollen, and that it might be a small first step for future research on the test. 1

3 SUMMARY Objectives. To investigate whether Glittreprotokollen is more accurate in measuring the effect of pulmonary rehabilitation (PR) than the 6 Minute Walk Test (6MWT) in Chronic Obstructive Pulmonary Disease (COPD) patients with a high initial functional capacity, because of the ceiling effect related to the 6MWT. Design. A retrospective observational study reviewing and comparing the results of the 6MWT and Glittreprotokollen pre- and post-an in-patient PR with the duration of four weeks. Setting. Multidisciplinary PR mainly consisted of endurance and strength training, patient education, mucous evacuation, breathing therapy, nutrition counseling, relaxation therapy, psychosocial education and smoking cessation support. Data collection. Data was collected from an electronic database at Glittreklinikken A/S. The data was dated from a period between the 15 th of November 2010 and the 9 th of March Participants. Nineteen subjects, diagnosed with COPD according to the GOLD classification, were included. Thirteen of the included subjects were diagnosed with moderate and six with severe COPD. They had undertaken both a 6MWT and Glittreprotokollen pre- and post-pr. Subjects had undertaken spirometry testing. Subjects with missing data in the electronic data files were excluded. Results. Compared to the first week of PR, the average increase in 6 Minute Walk Distance (6MWD) was 7.4m (SD 35.8m), or 1%. The average increase in power output in Glittreprotokollen was 33.2W (SD 31.2W) or 39.8%. Conclusion. Decisive conclusions in relation to the research question cannot be made at this point. This study does however show a tendency in the direction of the 6MWT being unsuccessful in detecting the change in functional capacity of subjects walking 550 m on their initial 6MWT after a four week in-patient PR program. Glittreprotokollen on the other hand, did not show this limitation. Keywords. COPD, pulmonary rehabilitation, 6MWT, Glittreprotokollen, ceiling effect. 2

4 Table of contents INTRODUCTION... 4 METHODS... 6 Setting Study design Data collection Inclusion of subjects MWT Glittreprotokollen... 7 The modified Borg scale... 8 Procedures The statistical analysis of the data Ethics RESULTS DISCUSSION CONCLUSION ACKNOWLEDGEMENT RERERENCES APPENDICES.. 21 Appendix I: Project plan Appendix II: Approval project plan Appendix III: Agreement from Glittreklinikken regarding access to data Appendix IV: Approval of project plan from Glittreklinikken Appendix V: Mail from Regional Ethical Committee (REK) regarding ethical approval Appendix VI: Protocol 6MWT Appendix VII: Protocol Glittreprotokollen Appendix VIII: Protocol 1 RM leg strength Appendix IX: Protocol strength training Appendix X: The modified Borg scale 3

5 INTRODUCTION Chronic Obstructive Pulmonary Disease (COPD) is a disease with widely spread clinical presentations, the shared abnormality being airflow limitations. It is defined as a preventable and treatable disease with some significant extra pulmonary effects that may contribute to the severity in individual patients. Its pulmonary component is characterized by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lung to noxious particles or gases [1]. According to the World Health Organization (WHO), COPD was by 2002 the fifth leading cause of mortality worldwide [2]. WHO-estimates predict COPD to rank as number three in leading cause of chronic mortality in 2030 [2]. According to the Global initiative for Chronic Obstructive Lung Disease (GOLD), effective management of COPD consists of four different components: (1) assess and monitor disease, (2) reduce risk factors, (3) manage stable COPD, and (4) manage exacerbations [1]. Pulmonary rehabilitation (PR) takes aim at these factors, and research leaves little doubt that PR can considerably limit the burden of this disease [3, 4, 5]. This is achieved by reducing symptoms related to COPD such as dyspnea and improving the functional capacity of these patients [4, 5]. As functional capacity is dependent on several systems afflicted by COPD, tests describing the functional capacity of patients with COPD are a cornerstone in determining the effect of PR [6, 7, 8, 9]. The 6 Minute Walk Test (6MWT) is one of the most widely used tests for this purpose in PR today [7, 8, 10, 11, 12, 13]. It is easy to administer and it demands little and inexpensive equipment. There are however certain limitations to the 6MWT. Two prominent limitations related to the 6MWT occur when the subject being tested either has a very low or a very high baseline functional capacity. These limitations are often referred to as floor or ceiling effects. Frost et al. (2005) describes the ceiling and floor effect as follows; All tests suffer from floors and ceilings, i.e., a point at which the performance is so good or so bad that further significant (clinically and statistically) deterioration or improvement becomes hard to detect [14]. The floor effect of the 6MWT has been extensively researched in COPD patients [7, 10]. Schünemann et al. (2005) defined the minimal important difference (MID) as the smallest difference in score in the outcome of interest that informed patients or informed proxies perceive as important, either beneficial or harmful, and which would lead the patient or clinician to consider a change in the management [15]. Put simply, the MID is used to interpret whether the observed change is important from the patient's or clinician's perspective [16]. The original MID of the 6 Minute Walk Distance (6MWD) was set by Redelmeier et al. to 54 m in More recently, Puhan et al. opted for a change of the MID from the original 54 m to 35 m and later to 24 m [7, 10, 17]. This was however in patients with respectively moderate to severe, and severe COPD. On the opposite side of the specter, there is a well-known ceiling effect related to the 6MWT [14, 18, 19]. In relation to the 6MWT, the ceiling effect is attributed to the combination of the 6MWT limiting the subject to walk and the physical limitation of how fast it is possible to walk [18, 19]. Using the 6MWT to determine the effect of PR in subjects with a high initial functional capacity might give the impression of the PR being without results. This is because in contrast to the MID being lowered for patients with moderate to severe and severe COPD, there are no such regulations for patients with an initial high functional capacity. Glittreklinikken is a hospital specialized for pulmonary rehabilitation located in Norway. At this hospital, Glittreprotokollen is used to measure the effects of PR as one of its applications. Glittreprotokollen is a modified version of the Bruce treadmill test [20], which has been adapted for use with pulmonary patients. The test is performed to the patient s symptoms limit maximum rather than a specified time. Additionally, it does not limit the patients to walk. 4

6 Therefore the purpose of this study is to investigate whether Glittreprotokollen is more accurate in measuring the effect of PR than the 6MWT in COPD patients with a high initial functional capacity, because of the ceiling effect related to the 6MWT. 5

7 METHODS Setting. Before patients were admitted to Glittreklinikken for the 4 week in-patient PR, an application had to be submitted by either their general practitioner (GP) or by a hospital doctor. When the application was approved, the patients and their respective GPs received a letter confirming the approval of the application and expected duration before admittance. Patients were contacted by phone to map smoking habits. At least 4 weeks before admittance, patients received a letter containing information stating date of admission, a brochure regarding the stay and information regarding communicable diseases. Patients were then placed in one of six multidisciplinary teams where rehabilitation was organized according to the guidelines of the ATS/ERS [4, 5]. Shortly after initiating their stay at Glittreklinikken, an anamnesis was carried out by a hospital doctor as well as a conversation with the nursing service regarding the patients goals for the coming four weeks. Patients were then tested for baseline strength and endurance by a physical therapist and received an individualized training program. Strength was assessed on a leg press machine by a 1 repetition maximum (1RM) test for leg strength (Appendix VIII: Protocol 1RM leg strength, Norwegian) and endurance was tested by utilizing Glittreprotokollen (Appendix VII: Protocol Glittreprotokollen, Norwegian). The individualized training program consisted of a strength program mainly focusing on big muscle groups (Appendix IX: Protocol Strength training, Norwegian) and an endurance program on a treadmill. The endurance program was based on the results of the initial Glittreprotokollen test and was in most cases based on the principles of interval training. Routine tests were carried out such as chest x-rays, spirometry testing, body-box and blood gasses as well as the 6MWT (Appendix VI: Protocol 6MWT, Norwegian). The first of in total three multidisciplinary team meetings were held within the first week of PR where the rehabilitation plan for the patient was discussed and set up. During the PR, patients received a weekly scheduled meeting with their team doctor. The hospital doctors also offered the patients group education regarding themes such as COPD, asthma, allergy and medicines. When relevant, patients received smoking cessation support as well as group education by the nursing service regarding the use of medicine, inhalation technique and use of supplementary oxygen. Furthermore, patients were offered conversation groups with topics such as how to cope with exacerbations, how to live with a chronic pulmonary disease as well as nutritional advice. Patients received individual follow up by a nurse during the full duration of the stay. In addition to their individualized training programs, patients were offered morning gymnastics, Nordic walking, training in a swimming pool and occasional spinning and climbing groups by the physical therapists. The physical therapists also offered patient education in form of breathing techniques, mucous evacuation, training theory and relaxation therapy. Progression of the patients individualized training program was provided during weekly meetings with the physical therapist. Patients also received advice on how to continue training post-pr and assistance in locating a physical therapist in their local environment if needed. In addition to this, occupational therapy was offered focusing on ADL-activities as well as psychosocial education by psychologists, nutritional advice by dietitians and social economic assistance by social workers. Study design. The study design was that of a retrospective observational study reviewing and comparing the results of the 6MWT and Glittreprotokollen pre- and post-an in-patient PR with the duration of four weeks. 6

8 Data collection. Data was collected from an electronic database at Glittreklinikken A/S. The data was dated from a period between the 15 th of November 2010 and the 9 th of March Subject characteristics, 6MWD of the 6MWT and maximum velocity and inclination of Glittreprotokollen were recorded. Data was printed, ID labeled and accumulated in a folder which was stored in a secure location at Glittreklinikken. Data was imported into an excel spread sheet and later in MedCalc statistical software. All data was fully anonymous. Inclusion of subjects. All subjects were diagnosed with COPD according to the GOLD classification. They had undertaken both a 6MWT and Glittreprotokollen pre- and post-pr. During the baseline 6MWT, subjects had to walk a distance of 550 m on minimum one of the two initial trials. During Glittreprotokollen, they had to walk on protocol 3 or 4 (table 1). Subjects had undertaken spirometry testing. Subjects with missing data in the electronic data files were excluded. Subjects had undergone a four week in-patient PR program in accordance to evidence based guidelines [4, 5]. 6MWT. The 6 Minute Walk Test followed standard procedure and recommendations from the American Thoracic Society [21]. The test was performed in a corridor with 30m markers. Standard instruction was given. Standard encouragement phrases were used every minute. The initial test was performed twice, with a pause of at least 30 min, to account for a learning effect [21, 22]. The test was performed again at the end of the PR period. 6MWD was noted as well as saturation (SpO2) and the patients subjective grading of dyspnea according to the modified Borg scale (also known as the Borg CR-10 scale, ranging from 0 10) before and after the completion of the test [23]. Glittreprotokollen. Glittreprotokollen is a modified version of the Bruce treadmill test which has been adapted to pulmonary patients [20]. It has a lower initial speed and earlier inclination than the original test. The test follows a stepwise progression, with increasing load every 2 nd minute based on the set protocol. The test is performed on a treadmill. Patients are instructed to perform the test until the patients symptoms limit maximum rated by the modified Borg scale. Pulse oximetry and heart rhythm is continuously monitored during the test. The subjects are asked to rate their perceived exertion of dyspnea and legs during the last half minute of each exercise step using the modified Borg scale [23]. There are four set protocols ranging from a low (protocol 1), to a high (protocol 4) work rate (WR). The four protocols increase similarly during each exercise step, but primarily differ in initial walking speed. Patients in this particular study walked on protocol 3 or 4 (table 1). As the test starts, the treadmill is set to a speed which the patient experiences as his or her habitual walking speed in accordance to one of the four preset protocols. The test is designed with the intention to run for about 8-12 minutes and never exceeds 30 minutes. When patient s symptoms limit maximum, rated by the modified Borg scale, the inclination was set to 0% and speed was returned to the initial setting, according to the chosen protocol. The last measurements were done at the first and the third minute at initial WR. Protocol 3 started with an initial speed of 3.6 km/h and protocol 4 on 4.8 km/h. The speed was then increased by 0.6 km/h every 2 nd minute. The speed was increased until 5.4 km/h was reached. For further increases in workload, the inclination was initially increased by 4%, and then by 2% every 2 nd minute. In protocol 3, maximum inclination was reached at 14%, in protocol 4 maximum inclination was reached at 8%. For further increases, the speed was increased by 0.6 km/h every 2 nd minute until a maximum of 8.4 km/h in protocol 3 and 11.4 km/h in protocol 4 (table 1). The same protocol was used at pre- and post-testing. Post-testing was preferably performed at the same time of day to minimize intraday variability in physical functioning of the subjects [21]. 7

9 Table 1: Work load during Glittreprotokollen Protocol 3 Protocol 4 Min Km/h Inclination % Km/h Inclination % The modified Borg scale. A parameter in addition to the primary outcomes typically measured in PR-candidates in functional tests such as the 6MWT and Glittreprotokollen is dyspnea [5, 24]. Dyspnea is often measured by utilizing the modified Borg scale (Appendix X: The modified Borg Scale, Norwegian) [4]. The Borg scale has been recommended to measure the effect of PR in relation to the patient s subjective grading of dyspnea and exertion of legs in addition to estimation of training intensity [5, 24]. The MID of the Borg scale has been investigated and set to a change in one unit for dyspnea [25]. Procedures. Of the two initial 6MWT, the one which gave the highest 6MWD was used as the baseline measurement. During Glittreprotokollen, subjects had to walk on a specific exercise step for at least 30 seconds in order for it to be registered as the peak exercise step. As Glittreprotokollen increases in WR by both increasing in velocity and inclination, the Jaeger formula was used to produce one primary outcome [26]. This was done to be able to compare the primary outcomes of the 6MWT and Glittreprotokollen. The primary outcome of Glittreprotokollen was calculated to Watts (W) based on weight, peak speed and inclination of the specific subject [26]. The Jaeger formula is divided in to two separate formulas reflecting the increase of WR related to running compared to that of walking. In this study, this limit was set to 8 km/h. Difference in weight of the subjects from baseline to the end of the PR period was taken into account when this was mentioned in the collected data. Outcomes of the tests were compared pre- and post-pr. For the 6MWT, outcomes were compared pre- and post-testing. For Glittreprotokollen, outcomes were compared pre- and post-testing at ISO time and at peak time. The statistical analysis of the data. Data was analyzed and compared using MedCalc statistical software (software version ). Descriptive statistics (age, weight, height, BMI, FEV1 % predicted and FEV1/FVC) were extracted from the spirometry datasheets and calculated as summary statistics including mean, standard deviation (SD), minimum and maximum values. The data was presented in tables and graphs made in Microsoft Excel (2010). 8

10 The change in 6MWD was calculated as percentual change. The percentual change in WR of Glittreprotokollen and the percentual change in 6MWD were compared and presented in graphs. This was in order to see whether or not these tests would give different impressions of the physical function after the four week in-patient PR. Ethics. An application for ethical approval was sent to Regional Ethical Committee (REK sør-øst), on which it was made clear that Fontys University of Applied Sciences and eventual other relevant institutions (Glittreklinikken) should be responsible for ensuring the ethical standard of the project (Appendix V: Mail from REK regarding ethical approval, Norwegian). The ethical standard was approved together with the signed consent of the project plan by both parties (Appendix II: Approval project plan, Appendix IV Approval project plan form Glittreklinikken, Norwegian). 9

11 RESULTS All eligible subjects meeting the inclusion criteria were included in the study. Of 372 patient files, 34 subjects completed both tests according to the inclusion criteria and had no missing data in the electronic database. Of these 34 subjects, 14 were excluded due to not being diagnosed with COPD according to the GOLD classification and an additional one subject did not complete post-pr 6MWT. This resulted in 19 participants. Thirteen of the subjects were diagnosed with moderate and six with severe COPD (table 2). Table 2: Baseline characteristics of participants (n = 19) Mean SD Min Max Age Height (m) Weight (Kg) BMI FEV1 (% predicted) FEV1/FVC MWD (m) Power output (W) Protocol walked during Glittreprotokollen, No COPD severity according to GOLD standards, No. II 13 III 6 Male/female ratio Male Female 7 12 Compared to the first week of PR, the average increase in 6MWD was 7.4m (SD 35.8m), or 1% (table 3). As subjects are asked to walk as far as possible during the test, it was expected that the Borg score would not change notably during pre- and post-pr testing. This fact is reflected in the results, which showed a mean change of -0.1 (SD 0.7) points before the test was performed and 0 (SD 2.4) points after the test was performed (table 3). Table 3: Changes in perceived rating of exertion of dyspnea and legs and 6MWD pre- and post-pr (n = 19) 6MWT Mean SD Min Max Changes in primary outcome 6MWD pre (m) MWD post (m) MWD change (m) MWD change (%) Changes in Borg CR-10 scale (dyspnea) Pre-PR results Borg pre (week 1) Borg pre (week 4) Borg change Post-PR results Borg post (week 1) Borg post (week 4) Borg change

12 Table 4 shows a sub-analysis of the 6MWT. The results presented are divided into subjects who showed an increase in 6MWD and subjects who did not show an increase in 6MWD. The Mean change in the 6MWT for subjects increasing 6MWD was 26.2m (SD 19.9m), or 4% (SD 2.5), and the mean change for subjects who did not increase 6MWD was -33.3m (SD 30.8), or 5.9% (SD 5.3). Table 4: Sub-analysis of the 6MWD pre- and post-pr Mean SD Minimum Maximum 6MWD showing increase post-pr (n = 13) 6MWD pre MWD post MWD change MWD change(%) MWD not showing increase post-pr (n = 6) 6MWD pre MWD post MWD change MWD change(%) The average increase in power output in Glittreprotokollen was 33.2W (SD 31.2W) or 39.8% (table 5). The increase of peak power output in Glittreprotokollen was paralleled by decreased scores on the modified Borg scale for perceived rating of exertion of dyspnea and legs at ISO time (table 5). Table 5: Changes in perceived rating of exertion of dyspnea and legs at ISO time measured by the modified Borg scale and work rate (W) pre- and post-pr (n = 19) Glittreprotokollen Mean SD Min Max Changes in primary outcome Watt pre (W) Watt post (W) Watt change (W) Watt change (%) Changes in Borg CR-10 scale Dyspnea (ISO) Borg pre Borg post Borg change Legs (ISO) Borg pre Borg post Borg change The changes in the 6MWD pre- and post-pr are graphically presented in figure 1. Results show small variations in pre- and post-6mwd. Out of the 19 subjects, only one surpassed the MID (54m) with a change in 6MWD of 60 m (figure 1). Further, it can be seen that five subjects decreased their 6MWD on post-testing (figure 1). 11

13 Figure 1: The change in 6MWD pre- (blue bars) and post- (red bars) PR. The changes in power output in Glittreprotokollen pre- and post-pr is graphically presented in figure 2. Results here show bigger variations in change pre- and post-pr than the results of the 6MWT. One subject shows a decrease in WR post-pr (figure 2). The subject who showed a decrease in WR (figure 2), also showed an increase in 6MWD (figure 1). Figure 2: The change in WR pre- (blue bars) and post- (red bars) PR Comparing the change of the primary outcomes of 6MWT and Glittreprotokollen shows large variation in results (figure 3). While Glittreprotokollen demonstrates several peaks in percentual change in WR, percentual change of 6MWD has a more even distribution. 12

14 Figure 3: Change in percent of 6MWT (blue line) and Glittreprotokollen (red line) pre- and post-pr. 13

15 DISCUSSION The purpose of this study was to determine whether Glittreprotokollen is more accurate in measuring the effect of PR than the 6MWT in COPD patients with a high initial functional capacity, because of the ceiling effect related to the 6MWT. Before presenting a final conclusion, there are several points of discussion worth mentioning. There exists, to the author s knowledge, no exact limit from where the ceiling effect will be demonstrable in COPD patients. This is because such a limit depends on several factors such as habitual walking velocity and leg length. However 550 m was chosen as a compromise between including enough subjects and that it was believed that this level was close to where a subject would have to change gait pattern from walking to running. It would have been beneficial to have a higher number of subjects participating in the study. This was limited by several factors. Perhaps the greatest limitation in this respect was the high demands of the functional capacity of the subjects. However this requirement was necessary to demonstrate the ceiling effect related to the 6MWT. Furthermore, only subjects being tested on protocol 3 or 4 during Glittreprotokollen were included. This was chosen due to the time limitation of the study. Including subjects who were tested on protocol 1 and 2 might have resulted in a larger study population, however it is the opinion of the author that most subjects being tested on protocol 1 and 2 do not have the functional capacity of being able to achieve a 6MWD 550 m. The reason for this is that Glittreprotokollen is designed with the intention to last about 8-12 minutes on the initial test. Protocol 2 reaches a speed of 5.4 km/h at 12 minutes and protocol 1 at 16 minutes (at that point, both protocols are at 0% inclination). The velocity of this exercise step would be equivalent to walking 540 m during the 6MWT. It can also be said that the criteria for men and women for initial 6MWD should differ. This is because in general, men have a greater 6MWD than do women [22, 27, 28]. If the criteria for the 6MWD would have been lowered for women, this probably would have resulted in a larger study population. It is at this point unclear how this would have influenced the results. If, on the other hand, the criteria for the 6MWD would have been increased for men, this would have resulted in a lower study population which would have been unbeneficial. It might also be a point of interest that all subjects received an endurance program on a treadmill. This endurance program was based on the results of the initial test of Glittreprotokollen. Subjects were thus trained at performing on a treadmill. This might have worked in favor of Glittreprotokollen, as the 6MWT does not take place on a treadmill whereas Glittreprotokollen does. Subjects were however encouraged to train endurance exercises according to their own preferences. This might have included using a stationary bike, utilizing the stairs or performing outdoor Nordic walking. The 6MWT is an internally paced test, which always takes place on a level surface. Glittreprotokollen on the other hand is externally paced and increases in WR are achieved by a stepwise shift in both velocity and in inclination. Furthermore, the 6MWT follows a continuous protocol, while Glittreprotokollen follows a step wise protocol. A direct comparison of the two tests is for these reasons not completely accurate. As Glittreprotokollen increases in two separate parameters, using the distance change in Glittreprotokollen as the primary outcome would not be appropriate. Use of the Jaeger formula was therefore necessary to merge the two parameters to one. There exist formulas to calculate WR on a level surface which might have been appropriate to use in conjunction with the 6MWT. This was however not done, as it might raise additional questions to the accurateness of the formulas used. Furthermore, WR depends on many aspects, among other if the subject is walking or running. As the study was retrospective, the patients were not observed by the author during testing. A set limit for walking/running was therefore used (8 km/h). 14

16 Keeping in mind that a change of 1 unit in the modified Borg Scale is considered to be the MID, there are some points worth mentioning. The positive results of the primary outcome in Glittreprotokollen were further underscored by the outcomes of the Borg scale at ISO-time, which improved by the mean of 1.5 units for both perceived rating of exertion of dyspnea (SD 2.1 units) and legs (SD 2.4 units). This means that, not only were the patients able to achieve a higher peak exercise step, but they also found the WR at ISO-time less strenuous than on pre-testing. In other words, their exercise tolerance had increased. Had the 6MWT showed similar results, one might say that the test was successful in presenting clinical important differences post-pr even though there were no significant changes in the 6MWD. However the mean change of Borg score during the 6MWT post-pr testing was that of 0 units (SD 2.4 units). Of the 19 subjects included in the study, five subjects decreased their 6MWD on post-testing. In the case of Glittreprotokollen, only one subject had a decrease (of 18 W) in WR. There are two likely reasons for this gap. The reason for patients generally not decreasing in Glittreprotokollen might be related to a training effect, i.e. subjects getting used to training on a treadmill. This would further aid in explaining how subjects were able to increase as much as is seen in this study (up to 178 %). The second probable reason for more patients showing a decrease in functional capacity in the 6MWT after PR compared to Glittreprotokollen, is related to the ceiling effect of the 6MWT. This claim is further supported by the sub-analysis of the 6MWT. The no-increase group showed an average decrease of 33.3m (SD 30.8) and the increase group showed an average increase of 26.2 m (SD 17.9). Even when separating the subjects into an increase and a no-increase group, the MID is still not reached. Interestingly enough, the subject who showed a decrease in WR in Glittreprotokollen, showed an increase in 6MWD of 20 m. Comparing the Borg scores during Glittreprotokollen of the same subject, revealed that the perceived rating of dyspnea at ISO time was 2 units higher during post-testing (7 units during the initial test, and 9 units during the post-test). This might be attributable to a number of factors. Perhaps the test was not performed at the same time of day affecting the intraday variability in physical functioning, or maybe the patient had forgotten to take his/her medication related to improving ventilation. This was however not noted in the test sheets and at this point it can only be speculated in the actual cause of this abnormality. Another possible explanation might be related to the psychometric properties of Glittreprotokollen. Irregardless of these discussion points, it seems clear from the results that the 6MWT and Glittreprotokollen gave different impressions of the gain in functional capacity pre- and post-pr. Whereas the 6MWT showed a mean change in 6MWD of merely 1% (7.4m) (SD 35.8m), Glittreprotokollen gave a mean change of 39.8% (33.2W) (SD 31.2W). These results clearly demonstrate that the ceiling effect was reached during the 6MWT whereas this was not the case with Glittreprotokollen. Looking at the strengths of this study and the relevance in clinical practice, there are some points worth mentioning. If the results in relation to the ceiling effect of the 6MWT presented in this study are further investigated and confirmed in future studies with larger populations, this might change the application of the 6MWT. In that respect, one possible outcome proposed, is to investigate whether the 6MWT should be performed in a population who one can expect will not reach the current MID for the 6MWT at all. In other words, it should be investigated if there should be a certain limit on the initial 6MWD where one would not carry out post-testing. Another possible outcome might be to further develop the MID taking the ceiling effect into account in specific populations such as COPD patients with an initial high functional capacity. What makes this particular study interesting is that it compares a well-known test for physical capacity, to a test which previously has not been investigated. From the results obtained in this study, it seems like the weaknesses of the 6MWT are not present in Glittreprotokollen, and thus that Glittreprotokollen might be a more accurate measurement tool in the specified patient group. 15

17 However, if Glittreprotokollen is to be used as a new measurement tool in PR, it is proposed that the accurateness of the test is further investigated. To further investigate the accurateness of Glittreprotokollen and its psychometric properties, it is proposed to compare the results of Glittreprotokollen to that of a Cardiopulmonary Exercise Test (CPET). This would further help determining the validity and reliability of the outcomes, as the CPET has been shown to hold a high level of validity and reliability. Future research describing a new MID in relation to the ceiling effect of the 6MWT in the same manner as the MID has been changed for moderate to severe and severe COPD patients is also proposed. 16

18 CONCLUSION Decisive conclusions in relation to the research question cannot be made at this point. This is due to the design of the study being a direct comparison of a continuous (6MWT) and a stepwise ( Glittreprotokollen ) protocol. This study does however show a tendency in the direction of the 6MWT being unsuccessful in detecting the change in functional capacity of subjects walking 550 m on their initial 6MWT after a four week in-patient PR program. Glittreprotokollen on the other hand, did not show this limitation as subjects were able to increase their primary outcome (work rate) with up to 178% (with a mean increase of 39.8%) on post-pr testing. Further research is proposed to study the psychometric properties of Glittreprotokollen in order to determine the validity and reliability of Glittreprotokollen. 17

19 ACKNOWLEDGEMENT My sincere thanks go to Frank Vossen and Ingrid Janssen, acting supervisors for the project, for their comments on the manuscript. I thank the people representing FOU at Glittreklinkken A/S for allowing access to the much needed data of which the project would not be possible to complete without. I thank Anne Edvardsen, Anita Grongstad, Ulla Dagrunn Pedersen and Siri Skumlien at Glittreklinikken for valuable input during several discussions regarding the project. This research would not have reached its present form without their invaluable help. I thank Tjarco Koppenaal for his support; I thank Marte Nystad Glad, Kari Saksenvik, Vasileios Polatoglou and Ole Jonas Liereng for comments during peer reviewing. I thank Thomas John Johnson for his kind contribution in linguistically checking this manuscript. 18

20 RERERENCES [1]: Rabe KF, Hurd S, Anzueto A, Barnes PJ, Buist SA, Calverley P et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J. Respir Crit Care Med. 2007;176: [2]: Chronic obstructive pulmonary disease (COPD) [Internet]. The World Health Organization; Accessed: 29/04/2012. Available at [3]: Lacasse Y, Goldstein R, Lasserson TJ, Martin S. Pulmonary rehabilitation for chronic obstructive pulmonary disease. The Cochrane Library. 2009; 3. [4]: Nici L, Donner C, Wouters E, Zuwallack R, Ambrosino N, Bourbeau J et al. American Thoracic Society/European Respiratory Society Statement on Pulmonary Rehabilitation [5]: Nici L, Donner C, Wouters E, Zuwallack R, Ambrosino N, Bourbeau J et al. American Thoracic Society/European Respiratory Society Statement on Pulmonary Rehabilitation. Am J Respir Crit Care Med. 2006; 173: [6]: Whipp BJ, Ward SA. Quantifying interventionrelated improvements in exercise tolerance. Eur Respir J. 2009; 33: [7]: Puhan MA, Mador MJ, Held U, Goldstein R, Guyatt GH, Schünemann HJ. Interpretation of treatment changes in 6-minute walk distance in-patients with COPD. WUR Respir J. 2008; 32: [8]: Sutherland ER, Make BJ. Maximum Exercise as an Outcome in COPD: Minimal Clinically Important Difference. COPD: Journal of Chronic Obstructive Pulmonary Disease. 2005, 2: [9]: Kocks JWH, Asijee GM, Tsiligianni IG, Kerstjens HAM, Molen T: Functional status measurement in COPD: a review of available methods and their feasibility in primary care. Prim Care Respir J. 2011; 20(3): [10]: Puhan MA, Chandra D, Mosenifar Z, Ries A, Make B, Hansel NN, Wise RA, Scuriba F. The minimal important difference of exercise tests in severe COPD. Eur Respir J. 2011; 37: [11]: Li AM, Yin J, Yu CCW, Tsang T, So HK, Wong E et al. The six-minute walk test in healthy children: reliability and validity. Eur Respir J. 2005; 25: [12]: Jenkins SC. 6-Minute walk test in-patients with COPD: clinical applications in pulmonary rehabilitation. Physiotherapy. 2007; 93: [13]: Wise RA, Brown CD. Minimal clinically important differences in the six-minute walk test and incremental shuttle walking test. COPD. 2005; 2: [14]: Frost AE, Langleben D, Oudiz R, Hill N, Horn E, McLaughlin V. The 6-min walk test (6MWT) as an efficacy endpoint in pulmonary arterial hypertension clinical trials: Demonstration of a ceiling effect. Vascular Pharmacology : [15]: Schünemann HJ, Guyatt GH. Commentary Goodbye M(C)ID! Hello MID, where do you come from? HSR 40:2: [16]: Revicki DA, Cella D, Hays RD, Sloan JA, Lenderking WR, Aaronson NK. Responsiveness and minimal important difference for patient reported outcomes. Health Qual Life Outcomes. 2006; 4:

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22 APPENDICES Appendix I: Project plan Appendix 4a. THE PROJECT PLAN 0. Project 0.1 Name of project The ceiling effect: The 6MWT or «Glittreprotokollen» in COPD patients with high initial functional capacity? - A retrospective observational study 0.2 Participating student Name: Peter Johnson peter.piiit@gmail.com Telephone: (+47) Address: Birkeland, 5392 Storebø, Norway 0.3 Date 12 th April, version number: Project leader/commissioner 1.1 Who is responsible LHL Helse A/S, avdeling; Glittreklinikken Contact person: Elisabeth Gerhardsen elisabeth.gerhardsen@glittreklinikken.no Telephone: (+47) Address: Glittreveien 31 (Pb. 104), Åneby Supervisory teachers Frank Vossen (General supervisor): f.vossen@fontys.nl Telephone: (+31) Address: Toledolaan 2, 5629 CC, Eindhoven Ingrid Janssen (Methodical supervisor) janssen.ingrid@hotmail.com Telephone: (+31) Address: Toledolaan 2, 5629 CC, Eindhoven

23 2. Definition of the problem 2.1. Background Chronic Obstructive Pulmonary Disease (COPD) is a disease with widely spread clinical presentations, the shared abnormality being airflow limitations. It is defined as a preventable and treatable disease with some significant extra pulmonary effects that may contribute to the severity in individual patients. Its pulmonary component is characterized by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lung to noxious particles or gases [1]. According to the World Health Organization (WHO), COPD ranks as number four in leading cause of chronic morbidity and mortality in the US, and further the WHO estimates that the burden of disease will be rated as fifth worldwide in Tests describing the functional capacity of patients with COPD are a cornerstone in determining the effect of pulmonary rehabilitation [2, 3, 4]. The 6 Minute Walk Test (6MWT) is one of the most widely used tests in pulmonary rehabilitation (PR) today [3, 4, 5, 6]. It is easy to administer and it demands little and inexpensive equipment. Parameters typically measured in PR-candidates besides the 6 minute walking distance (6MWD) are such as dyspnea measured by the Borg CR10 scale [8] and saturation (SpO2). The Borg scale has been recommended to measure the effect of PR in relation to the patients subjective grading of dyspnea and exertion of legs in addition to estimation of training intensity [9]. The minimal important difference (MID) has become the standard approach for the interpretation of the clinical relevance of changes in these outcomes induced by respiratory rehabilitation or other treatments [10, 11]. The MID of the 6MWD was set by Redelmeier et al. [12] to 54m in More recently, Puhan et al. opted for a change of the MID from the original 54 m to 35 m [3] and later to 24 m [5]. This was however in patients with respectively moderate to severe, and severe COPD. On the opposite side of the specter there is a well-known ceiling effect related to the 6MWT [13, 14]. This effect is attributed to the combination of the 6MWT limiting the subject to walk and the physical limitation of how fast it is possible to walk [13, 14]. Using the 6MWT to determine the effect of PR in subjects with a high initial functional capacity might give the impression of the PR being without results. At Glittreklinikken in Hakadal Norway, another test, «Glittreprotokollen», is used to measure the effects of PR. «Glittreprotokollen» is a modified version of the Bruce treadmill test [15], which has been adapted to pulmonary patients. The test is performed to the patients symptoms limit maximum rather than a specified time and further it does not limit the patients to walk. Therefore the purpose of this study is to find out if the «Glittreprotokollen» is more accurate to measure the effect of PR than the 6MWT in COPD patients with a high initial functional capacity, because of the ceiling effect that is related to the 6MWT Problem definition The 6MWT is widely used in clinical practice and research to measure the effect of PR [3, 4, 5, 6]. However there exists a ceiling effect of the 6MWT due to the physical limitation of how fast it is possible to walk [13, 14]. «Glittreprotokollen» is performed to the patients symptoms limit maximum rather than a specified time and further it does not limit the patients to walk. The goal of this study is to determine whether the 6MWT or «Glittreprotokollen» is a more accurate tool to measure the effect of a 4 week in-patient PR program on the functional capacity in COPD patients with an initial 6MWD 550 m.

24 2.3. Presentation of the question(s) Is «Glittreprotokollen» more accurate in measuring the effect of PR than the 6MWT in COPD patients with a high initial functional capacity, due to the ceiling effect related to the 6MWT? 2.4. Working definitions Pulmonary rehabilitation (PR): As defined by ATS/ERS (2006); Pulmonary rehabilitation is an evidence-based, multi-disciplinary, and comprehensive intervention for patients with chronic respiratory diseases who are symptomatic and often have decreased daily life activities. Integrated into the individualized treatment of the patient, pulmonary rehabilitation is designed to reduce symptoms, optimize functional status, increase participation, and reduce health care costs through stabilizing or reversing systemic manifestations of the disease [9]. Ceiling effect: The subject reaches near the maximum target of the outcome measure due to the design of the test, and is therefore unable to show much improvement on a following test [13, 16]. Functional capacity: Functional capacity is defined by Kocks WH et al. as one s maximum potential to perform activities and further he states that it can be tested, for example, using cycle ergometry [17]. I have chosen to test the functional capacity by looking at changes in outcomes of the 6MWT and «Glittreprotokollen» pre/post PR. In this study, high functional capacity was defined as a 6MWD 550m. 3. Objectives The objective of this study is to determine if either the 6MWT or «Glittreprotokollen» is more accurate measuring changes in functional capacity of a 4 week in-patient PR program in COPD patients with an initial 6MWD of 550m. 4. Project Products A report dealing with the proposed study An oral presentation of the findings 5. Method 5.1. Study design Approach to the research question: Quantitative research. Research method: Retrospective observational study Participants N = Inclusion/exclusion criteria All patients were diagnosed with COPD according to the GOLD classification. All participants were admitted to Glittreklinikken and completed a 4 week in-patient PR program. All patients had undertaken both a 6MWT and «Glittreprotokollen» pre- and post PR and spirometry testing. All participants had an initial 6MWD 550 m on the better of the two initial trails. All patients had walked at either protocol 3 or 4 during «Glittreprotokollen». Subjects with electronic data files with relevant missing data were excluded 5.4. Data collection Data is collected retrospectively from the electronic database at Glittreklinikken A/S. All allegeable subjects meeting the inclusion criteria in the period between the 15 th of November 2010 and the 9 th of March 2012 will be included. Data will be printed, ID labeled and stored in a folder which will be

25 located at Glittreklinikken at all times. Data will then be imported to an excel spreadsheet. All data will be fully anonymous. The following data will be collected from a database at Glittreklinikken; Subject characteristics: Age Sex Height Weight FEV1%pred FEV1/FVC GOLD classification BMI 6 Minute Walk Test: 6MWD «Glittreprotokollen»: Maximum velocity Maximum inclination 5.5. Measurement tools The 6 Minute Walk Test follows standard procedure and recommendations from the American Thoracic Society [18]. The test is performed in a corridor with 30m markers. Standard instruction is given. Standard encouragement phrases are used every minute. The initial test is performed twice, with a pause of at least 30 min, to account for a learning effect. The test leader is not allowed to walk together with the patient during the test. 6MWD is noted as well as SpO2 and the patients subjective grading of dyspnea and exertion of legs according to the modified Borg scale before and after the completion of the test. «Glittreprotokollen» is a modified version of the Bruce treadmill test [15], which is adapted to pulmonary patients. It has a lower initial speed and earlier inclination than the original test. The test is however not published. The test is performed to the patients symptoms limit maximum. Pulseoximetry and heart rhythm is continuously monitored during the test. The test is performed on a treadmill with increasing load every two minutes based on a set protocol. The subjects are asked to rate their perceived exertion for dyspnea and legs during the last half minute of each exercise step using the Borg CR-10 scale (ranging from 0 10) [19]. The test is designed with the intention to last about 8-12 minutes and never exceeds 30 minutes. When patients symptom limit maximum, the inclination is set to 0% and speed to the initial speed according to the chosen protocol. The last measurements are done at one and three minutes at initial work rate. There are four set protocols which primarily differ on initial walking speed. Patients in this particular study walked on protocol three or four. Which protocol was chosen, was based upon the physical therapists evaluation of the functional capacity of the patient. Protocol three started with an initial walking speed of 3.6 km/h and protocol four on 4.8 km/h. The speed was then increased by 0.6 km/h every 2 nd minute. The speed was increased until 5.4 km/h was reached. For further increases in workload, the inclination was initially increased by 4%, and then by 2% every 2 nd minute. In protocol three, maximum inclination was reached at 14%, in protocol four