Impact of Pulmonary Rehabilitation On Activities of Daily Living in Patients With Chronic Obstructive Pulmonary Disease (2018)

1
3 The impact of pulmonary rehabilitation on activities of daily living in patients with
4 COPD
6 A.W. Vaes1, J.M.L. Delbressine1, R. Mesquita1, Y.M.J. Goertz1, D.J.A. Janssen1, N. Nakken1,
7 F.M.E. Franssen1,2,3, L.E.G.W. Vanfleteren1,2, E.F.M. Wouters1,3, M.A. Spruit1,2,3
1
9 Department of Research and Education, Ciro, Horn, the Netherlands
2
10 NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht
11 University Medical Centre (MUMC+), Maastricht, The Netherlands

3
12 Department of Respiratory Medicine, MUMC+, Maastricht, the Netherlands
13
14 Corresponding author:
15 Anouk W. Vaes, PhD
16 Ciro
17 Hornerheide 1
18 6085 NM Horn
19 0031-475587602
20 anoukvaes@ciro-horn.nl
21
22 Running head: Pulmonary rehabilitation and ADLs in COPD
23
24 Author contribution
Downloaded from www.physiology.org/journal/jappl by ${individualUser.givenNames} ${individualUser.surname} (130.241.016.016) on December 1, 2018.

Copyright © 2018, Journal of Applied Physiology. All rights reserved.
25 Study concept and design: AWV, NN, EFMW, and MAS; acquisition of data: AWV, JMLD,
26 RM, and YMJG, DJAJ, FMEF, and LEGWV; analysis and interpretation of data: AWV,
27 JMLD and MAS; drafting the article: AWV; revising it critically for important intellectual
28 content: all authors; final approval of the version to be published: all authors.
29

30 ABSTRACT
31 Introduction A high proportion of patients with COPD experience problems during the
32 performance of activities of daily living (ADLs). We aimed to determine the effects of a
33 comprehensive eight-week pulmonary rehabilitation program on the physiologic response to
34 and performance of ADLs in patients with COPD.
35 Methods Before and after pulmonary rehabilitation, 31 patients with COPD (71% men; mean
36 age: 64.2±8.4 years; mean FEV1: 54.6±19.9% predicted) performed physical function tests,
37 the Canadian Occupational Performance Measure (COPM) and an ADL-test consisting of
38 putting on socks, shoes and vest; stair climbing; washing up four dishes, cups and saucers;
39 doing groceries and putting away groceries in a cupboard; folding eight towels; and vacuum
40 cleaning for four minutes. Metabolic load, ventilation and dynamic hyperinflation were
41 assessed using an Oxycon mobile device. In addition, symptoms of dyspnea and fatigue and
42 time to complete ADLs were recorded.
43 Results After rehabilitation, patients with COPD used a significantly lower proportion of their
44 peak aerobic capacity and ventilation to perform ADLs, accompanied by lower Borg scores
45 for dyspnea and fatigue. Furthermore, patients needed significantly less time to complete
46 ADLs. Dynamic hyperinflation occurred during the performance of ADLs, which did not
47 change following pulmonary rehabilitation. Changes in physical function, including six-
48 minute walk distance, constant work rate test, quadriceps muscle strength and COPM were
49 significantly correlated with change in average total oxygen uptake during the performance of
50 the ADL test.
51 Conclusion A comprehensive pulmonary rehabilitation program can improve the physiologic
52 response to and actual performance of ADLs in patients with COPD.
53

54 New & Noteworthy: A high proportion of patients with COPD experience problems during
55 the performance of activities of daily living (ADLs). This study clearly demonstrated that a
56 comprehensive pulmonary rehabilitation program can improve the performance of ADLs in
57 patients with COPD, indicated by a significantly shorter time to perform ADLs and a lower
58 metabolic load and dyspnea sensation.
59
60 Key words: Chronic obstructive pulmonary disease, dyspnea, rehabilitation, activities of
61 daily living

62 INTRODUCTION
63 Patients with COPD frequently experience problems during the performance of activities of
64 daily living (ADLs), such as cleaning, climbing stairs or getting washed or dressed (3, 43). A
65 high proportion of patients with COPD consider themselves partially or fully dependent on
66 help from others in the performance of one or more ADLs (4), which may result in social
67 isolation and therefore a reduction in their quality of life (20, 34).
68
69 Dyspnea is often reported as limiting factor for performance of ADLs (3, 34). Indeed, patients
70 with COPD experience a higher degree of dyspnea during ADLs compared to healthy
71 subjects, even in the earliest stages of the disease, which may be attributed to the occurrence
72 of dynamic hyperinflation (23, 43, 45). It has been demonstrated that simple ADLs, such as
73 getting dressed, dish washing and walking, are sufficient to increase ventilatory demands and
74 induce dynamic hyperinflation in patients with COPD (15, 23, 43, 45). Moreover, patients are
75 often not satisfied with the performance of problematic ADLs (3). This emphasizes the
76 importance to focus on strategies aimed at improving ADL performance in patients with
77 COPD.
78
79 Exercise training can be considered to reduce the task-related dyspnea sensation in patients
80 with COPD, which may result in an improved performance of ADLs. Indeed, exercise
81 training can result in a lower ventilation and a reduction in dynamic hyperinflation during
82 submaximal exercise and, in turn, in a lower dyspnea sensation (32). Moreover,
83 desensitization to dyspnea enables patients to perform at higher levels of work with reduced
84 symptoms (9). Furthermore, strength training of the upper limbs has shown to alleviate
85 dyspnea and enables improvements in arm activities, whilst lower limb training may result in
86 an improved ability to perform ADLs, such as walking, stair climbing, and sit-to-stand (7, 30).

87
88 In addition to exercise training, occupational therapy may be beneficial to reduce the burden
89 of ADLs by learning and applying energy conservation techniques (ECTs) (16). These
90 techniques aim to decrease energy expenditure during ADLs and may improve dyspnea
91 perception, functional performance and quality of life (46, 47). Although largely
92 recommended, only limited data are available on the effects of ECTs during the performance
93 of ADLs in patients with COPD. Velloso and Jardim demonstrated that patients with COPD
94 had a significant lower oxygen uptake and dyspnea perception when using ECTs (47). In
95 addition, Silva and colleagues demonstrated that simple ECTs can prevent the occurrence
96 dynamic hyperinflation during the performance of ADLs (37).
97
98 Pulmonary rehabilitation can reduce the level of care dependency during the performance of
99 basic and instrumental ADLs in patients with COPD (19). Whether pulmonary rehabilitation
100 also has beneficial effect on the actual performance of ADLs has only been studied once.
101 Skumlien and colleagues showed that patients with COPD significantly improved time to
102 perform the Glittre ADL test after a 4-week inpatient pulmonary rehabilitation program,
103 containing both exercise training and occupational therapy (38). Since an improved ability to
104 perform tasks is an important goal for patients attending pulmonary rehabilitation (36), more
105 insight is needed on the possible beneficial effects of pulmonary rehabilitation on time to
106 perform ADLs, but also on the psychological response during the performance of ADLs.
107
108 Therefore, this study aimed to determine the effects of a comprehensive pulmonary
109 rehabilitation program on the physiologic response to and performance of ADLs in patients
110 with COPD. In addition, we aimed to determine whether changes in physical function
111 following pulmonary rehabilitation correspond to changes in the performance of ADLs.

112
113 METHODS
114 Subjects
115 Clinically stable patients (no exacerbation within previous 4 weeks) with mild to very severe
116 COPD were recruited at the start of pulmonary rehabilitation at Ciro (Horn, the Netherlands)
117 (42). Patients with neuromuscular comorbidities, who were not able to perform the ADLS,
118 and patients using long term oxygen therapy, who could not use the Oxycon mobile, were
119 ineligible. The study was approved by the institutional review board of the Maastricht
120 University Medical Centre (METC 13-3-055) and registered on www.trialregister.nl
121 (NTR4452) before enrolment of the first participant. All participants gave written informed
122 consent to participate in this study.
123
124 Study design
125 All patients with COPD participated in a comprehensive eight-week inpatient pulmonary
126 rehabilitation program at Ciro, as defined by the latest international ATS/ERS statement on
127 pulmonary rehabilitation (40). In addition to agroup-based exercise training program,
128 including strength training (5x/week, alternating upper body (i.e. chest press, upper back
129 and/or vertical traction) and lower body exercises (i.e. leg press, leg extension and/or leg curl)
130 (Technogym SpA, Gambettola, Italy); 3 sets of 8 repetitions at 70% of one-repetition
131 maximum) and high-intensity interval training on a stationary cycle ergometer (1x/week 12x1
132 min exercise at 80% of maximal exercise capacity (Wmax) alternating with 1 min rest and 1-
133 2x/week 8x2 min exercise at 60% of Wmax, alternating with 1 min rest), and treadmill
134 (1x/week 12x1 min exercise at 100% of average speed on six minute walk test (6MWT)
135 alternating with 1 min rest and 1-2x/week 4x5 min exercise at 75% of average speed on
136 6MWT alternating with 1 min rest) supervised by a physiotherapist, patients received weekly

137 individually tailored sessions of occupational therapy for learning and applying ECTs (i.e.
138 planning and prioritizing ADLs, balancing between activity and rest, using alternative
139 working methods and breathing techniques, adjusting tempo and body positioning, and using
140 assistive devices (i.e. long-handed shoe horns, rollator, shower seat)) (46). In addition, the
141 program consisted of nutritional modulation, exacerbation management strategies, optimizing
142 medication use and adherence to medication, educational sessions and psychosocial
143 counselling.
144
145 All patients underwent a routine baseline and outcome assessment in which the following
146 variables were obtained: demographics, body composition (body mass index, fat free mass
147 using whole-body dual-energy x-ray absorptiometry), post-bronchodilator spirometry (forced
148 expiratory volume in the first second (FEV1), and forced vital capacity (FVC)) , single breath
149 carbon monoxide diffusing capacity (DLCO% predicted), arterial oxygen saturation (SaO2),
150 modified Medical Research Council (mMRC) dyspnea scale, history of exacerbations and
151 hospitalizations in the previous 12 months,
152 Peak aerobic capacity (peakV̇O2), ventilation (peakVE), heart rate (peakHR) and work rate
153 (W) were determined using a symptom-limited cardiopulmonary exercise test (1, 21). In
154 addition, functional exercise capacity was assessed using a six-minute walk test (17), cycle
155 endurance time during constant work rate test (CWRT) at 75% of the peak work rate (44)),
156 and quadriceps isokinetic strength was assessed using a Biodex (Biodex System 4 Pro, Biodex
157 Medical Systems, Inc., New York, USA) (5, 33).
158 Patient-reported problematic ADLs were obtained using the Canadian Occupational
159 Performance Measure (COPM). The COPM is a reliable and responsive measure of a client's
160 self-perception of occupational performance in the areas of self-care, productivity and leisure
161 (8, 24). Using a semi-structured interview, patients identified their most important daily

162 activities and rated their current level of performance and how satisfied they were with this
163 performance using a scale from 1 to 10 (24). Higher ratings indicate greater performance and
164 satisfaction.
165 In addition, participants performed three ADL tests at the Department of Occupational
166 Therapy of Ciro: two times before pulmonary rehabilitation, in order to account for possible
167 learning effects, and once after pulmonary rehabilitation. ADL tests at the beginning of
168 pulmonary rehabilitation were performed on two consecutive days. Best baseline ADL test
169 (i.e. lowest oxygen uptake during performance of ADLs before the start of the pulmonary
170 rehabilitation program) was used for further analyses, or in case of comparability, mean
171 values of both ADL tests.
172
173 ADL test
174 The ADL test consisted of both basic and instrumental ADLs, which had to be performed
175 consecutively: 1) getting dressed (putting on 2 socks, 2 shoes and a vest); 2) stair climbing
176 (climb a three-steps staircase three times, including walking to the stairs and back (two times
177 25 m)); 3) washing up four dishes, four cups, and four saucers; 4) doing groceries (loading
178 two 400 grams cans of beans, two 1 liter cartons of milk, and two 0.5 liter bottles of water in a
179 basket, walking with groceries (35 m) and putting away groceries in a cupboard); 5) folding
180 eight towels; 6) vacuum cleaning for four minutes. These ADLs have been identified as
181 problematic valued ADLs in patients with COPD (3). Patients were instructed to perform the
182 ADLs as usual at a self-selected pace. Patients were allowed to use aids, such as walking aids
183 or a shoehorn. If necessary, patients were allowed to take rest between activities, but had to
184 resume the ADLs as soon as they could.
185

186 An Oxycon mobile device (Oxycon Mobile, CareFusion, San Diego, USA) was used to
187 continuously assess the metabolic load, ventilation and inspiratory capacity (IC) (43). Earlier
188 studies demonstrated that the Oxycon mobile device provides valid and reliable measures of
189 oxygen uptake, ventilation and IC at rest and during exercise (2, 14). Assuming constant total
190 lung capacity (TLC), a decrease in IC is used to reflect an increase in end-expiratory lung
191 volume (EELV), and, in turn, DH (48). IC was measured at rest, using the mean of three
192 acceptable maneuvers, and immediately after the performance of each ADL. All IC
193 maneuvers were performed in an upright position to avoid influence of body position on total
194 lung capacity and IC. Dynamic hyperinflation was defined as a decrease in IC of at least 10%
195 and/or 150 ml compared to resting IC (28). As time to perform ADL and peakVE might vary
196 before and after pulmonary rehabilitation, IC measurement at iso-time and iso-ventilation are
197 less useful, and therefore, IC was also expressed as a function of ventilation (change in IC per
198 L/min of ventilation) (10). Symptoms of dyspnea and fatigue were scored at the beginning
199 and end of the test using a modified Borg symptom scale ranging from 0 (no symptoms) to 10
200 points (worst symptoms). In addition, time to complete each ADL was recorded.
201
202 Outcomes
203 Change in oxygen uptake during the performance of ADLs before and after the pulmonary
204 rehabilitation program was chosen as primary outcome (expressed as proportion of the peak
205 aerobic capacity %peakV̇O2 at the corresponding time point (before or after pulmonary
206 rehabilitation)). In addition, several secondary outcomes were assessed: ventilation and heart
207 rate (expressed as %peakVE and %peakHR); dynamic hyperinflation; time to accomplish the
208 ADLs; Borg symptom scores for dyspnea and fatigue at the end of the ADL test; and relation
209 between changes in performance of ADLs and physical function measures of pulmonary
210 rehabilitation, including six-minute walk distance (6MWD), cycle endurance time during
10

211 CWRT (performed at 75% of determined peak work rate), quadriceps isokinetic strength and
212 performance score and satisfaction score of problematic ADLs on the COPM (COPM-P and
213 COPM-S, respectively).
214
215 Data analyses
216 Data are presented as mean and standard deviation, unless noted otherwise. Normal
217 distribution was tested by the Shapiro-Wilk test. Comparability of ADL tests before
218 rehabilitation and differences between pre and post rehabilitation for ADL parameters (e.g.
219 V̇O2, VE, HR, IC, Borg scores, time to complete ADLs) and physical function outcomes of
220 pulmonary rehabilitation (e.g. CWRT, 6MWD, COPM-P, COPM-S) were assessed using
221 paired-sample t-test or Wilcoxon test. Pearson's correlation coefficient was used to assess the
222 association between changes in physical function following pulmonary rehabilitation and
223 changes in the performance of ADLs. The level of significance was set at ≤0.05. Data were
224 analysed with SPSS, version 25.0.
225
226 RESULTS
227 Patient characteristics
228 Three-hundred thirty-three patients with COPD subjects referred for a pulmonary
229 rehabilitation program including high-intensity interval training and occupational therapy
230 were screened between June 2014 and December 2016. Two-hundred thirty-six patients were
231 ineligible to participate due to various reasons (see Figure 1 for details). In addition, 53
232 eligible subjects declined participation because of disinterest, dyspnea and/or fatigue. Clinical
233 and functional characteristics of these patients were not significantly different from those
234 enrolled in this study. Thirteen patients were not included in the analyses: three patients were
235 not able to complete the first ADL test at the beginning of rehabilitation due to dyspnea, two
11

236 patients did not perform the second ADL test at the beginning of rehabilitation due to an
237 exacerbation, and 8 patients did not perform the end ADL test after rehabilitation because of
238 an exacerbation (n=2), hospitalisation (n=2) or drop out from pulmonary rehabilitation due to
239 orthopaedic problems or personal reasons (n=4). Finally, 31 patients with COPD completed
240 all ADL tests. There were no differences in baseline characteristics of patients who
241 completed the study and patients who dropped out, except for number of exacerbations and
242 hospitalisations in the previous 12 months.
243
244 Patient characteristics are listed in Table 1. In general, patients were mostly men (71%) with
245 an average age of 64.2 years. Patients had mild to very severe COPD (mean FEV1: 55±20 %
246 pred) and an impaired exercise capacity, as assessed by CPET (91±33 W; 55±19% pred),
247 6MWT (483±91 m; 76±15% pred) and CWRT (365±232 s). Furthermore, patients reported a
248 poor performance (COPM-P: 3.8±1.6 points) and low satisfaction with the performance
249 (COPM-S: 2.9±1.8 points) of identified problematic ADLs.
250
251 Outcomes of the two pre-rehabilitation ADL-tests were comparable for all ADL parameters
252 (p>0.05), and therefore, mean values of these test were used for further analyses.
253 On average, patients used 54% to 79% of their peak aerobic capacity during the performance
254 of the ADL. Ventilation and heart rate (expressed as %peakVE and %peakHR) ranged from
255 47 to 65% and 74 to 80%, respectively. Dynamic hyperinflation occurred during the
256 performance of all ADLs, with a change in IC ranging from -291 to -396 mL (-12 to -17%
257 compared to resting IC) compared to resting IC. On average, patients needed 942±166 s to
258 perform the ADLs. Borg symptom scores for dyspnea and fatigue at the end of the ADL test
259 were 4.1±1.7 and 3.3±2.1, respectively.
260
12

261 Changes following pulmonary rehabilitation
262 6MWD (mean difference (95% Confidence Interval (CI)): 39 (19-58) m), CWRT (mean
263 difference (95%CI): 308 (182-435) s), quadriceps isokinetic strength (mean difference
264 (95%CI): 5.6 (-1.5-9.6) Nm), COPM-P (mean difference (95%CI): 3.2 (1.9-4.4) points) and
265 COPM-S (mean difference (95%CI): 4.7 (3.5-5.9) points) improved significantly following
266 rehabilitation (all p<0.05), while no change was observed in peak workload (mean difference
267 (95%CI): 5.8 (-3.2-14.8) W) and peakV̇O2 (mean difference (95%CI): 64 (-30-159) mL).
268
269 Resting values before the start of the ADL test were comparable before and after
270 rehabilitation: mean oxygen uptake: 34.7±11.5 vs. 31.4±10.6 %peak V̇O2; mean ventilation:
271 35.6±14.5 vs. 34.0±13.3 %peak VE; mean heart rate: 66.9±11.7 vs. 65.9±12.8 %peak HR;
272 mean IC: 2.36±0.65 vs. 2.34±0.78 L; and Borg symptom scores for dyspnea and fatigue:
273 1.9±1.1 and 1.6±1.1 points vs. 1.4±1.2 and 1.3±1.3 points, respectively (all p>0.05).
274
275 Mean oxygen uptake during the performance of ADLs, expressed as proportion of peak
276 oxygen uptake, was significantly lower after pulmonary rehabilitation, except for washing
277 dishes: mean difference (95% CI) getting dressed: -7.7 (-13.3--2.1)%, p=0.018; stair climbing:
278 -8.6
279 (-17.6-0.4)%, p=0.021; washing dishes: -3.3 (-12.0-5.4)%, p=0.232; doing groceries: -7.5 (-
280 16.1-1.1)%, p=0.028; folding towels: -7.1 (-15.9-1.7)%, p=0.038; and vacuum cleaning: -5.6
281 (-14.1-2.9)%, p=0.041 (Figure 2a)).
282
283 In general, patients also performed the ADLs after rehabilitation at a lower proportion of their
284 peak ventilation (mean difference (95%CI) for getting dressed: -5.5 (-12.1-1.1)%, p=0.017;
285 stair climbing: -4.5 (-13.5-4.5)%, p=0.037; washing dishes: -1.3 (-9.9-7.3)%, p=0.704; doing
13

286 groceries: -4.9 (-13.7-3.9)%, 0.028; folding towels: -4.3 (13.5-4.9)%, p=0.038; and vacuum
287 cleaning: -2.1 (-10.4-6.1)%, p=0.600 (Figure 2b)), and peak heart rate (mean difference
288 (95%CI) getting dressed: -3.8 (-8.6-1.0)%, p=0.020; stair climbing: -0.1 (-4.5-4.3)%, p=0.954;
289 washing dishes: -3.9 (-9.6-1.8)%, p=0.028; doing groceries: -5.0 (-8.6-1.4)%, p=0.014;
290 folding towels 5: -5.0 (-8.9-1.1)%, p=0.015; and vacuum cleaning: -4.2 (-7.7-0.7)%, p=0.021
291 (Figure 2c)).
292 Overall, dynamic hyperinflation occurred at the end of all ADLs, without significant
293 differences before and after rehabilitation (Figure 2d). In addition, changes in dynamic
294 hyperinflation as a function of ventilation demonstrated no significant difference before and
295 after rehabilitation for all ADLs. Furthermore, proportion of patients developing dynamic
296 hyperinflation was comparable, ranging from 52% during washing up to 71% during vacuum
297 cleaning before rehabilitation versus 45% to 68% after rehabilitation (Table 2).
298
299 After rehabilitation, COPD patients needed significantly less time to complete stair climbing,
300 washing dishes, doing groceries and folding towels compared to baseline (90±27 vs. 103±44
301 s; 125±42 vs. 139±51 s; 126±21 vs. 141±28 s; and 142±45 vs. 158±51 s; all p<0.05; Figure
302 2e). Consequently, total time to complete all ADLs was significantly shorter after
303 rehabilitation: 874±129 vs. 942±166s; p<0.001. Moreover, after rehabilitation, patients
304 reported significantly lower Borg symptom scores for dyspnea and fatigue at the end of the
305 ADL test (3.2±1.7 vs 4.1±1.7 points and 2.5±1.6 vs 3.3±2.1 points, respectively; p<0.01).
306
307 Correlations
308 There was a significant correlation between the changes in functional outcomes and changes
309 in average total oxygen uptake during the performance of the ADL test: peakV̇O2: r=-0.748,
14

310 6MWD: r=-0.578, CWRT: r=-0.552, quadriceps isokinetic strength: -0.791, COPM-P: r=-
311 0.657, and COPM-S: r=-0.592 (all p<0.01) (Figure 3).
312
313 DISCUSSION
314 This study provides new insights into the beneficial effects of a comprehensive pulmonary
315 rehabilitation program, including exercise training and occupational therapy, on the actual
316 performance of ADLs in patients with COPD. We demonstrated that patients significantly
317 improved their performance of ADLs, indicated by a lower metabolic load, less symptoms
318 and a shorter time to perform the ADLs. Changes in functional outcomes of pulmonary
319 rehabilitation are significantly correlated with improved performance of the ADLs.
320 In recent years, it has been frequently demonstrated that patients with COPD are seriously
321 limited in their performance of ADLs (23, 37, 43). Although more than half of the included
322 patients in this study had only a mild to moderate airflow limitation, they experienced serious
323 problems in daily functioning. Indeed, these patients reported a low level of performance and
324 low satisfaction of performance of multiple problematic ADLs (Table 1), and performed
325 ADLs at a considerable high proportion of their maximum aerobic capacity, ranging from
326 50% while putting on socks, shoes and a vest to 75% while climbing stairs. Difficulties in
327 performing ADLs may be an important reason that these patients with less severe airflow
328 limitation were referred for pulmonary rehabilitation.
329
330 This study clearly demonstrated that a comprehensive pulmonary rehabilitation program
331 significantly improved functional outcomes in patients with COPD, including 6MWD, CWRT
332 and quadriceps isokinetic strength, which may have resulted in the improved performance of
333 ADLs. Indeed, earlier has been suggested that improvements in functional capacity are
334 necessary to allow changes in daily physical activities (27). This is confirmed by our results,
15

335 which show moderate to strong correlations between functional outcomes and changes in
336 ADL performance (r=-0.578; -0.552; -0.791; -0.657 and -0.592, Figure 3).
337 It has been recognized that high-intensity interval training and moderate intensity continuous
338 training are both effective in improving exercise capacity and quality of life in patients with
339 COPD, though, high-intensity interval training may be more appropriate for symptom-limited
340 patients who are unable to tolerate continuous training (22, 40, 41). In addition, high-
341 intensity interval training has been suggested as a useful exercise strategy for patients with
342 COPD to improve their ability to perform ADLs (6). Indeed, physiological requirements
343 during the performance of ADLs are high in patients with COPD, which can be over 90% of
344 peak aerobic capacity while sweeping the floor (43). It is known that high-intensity interval
345 training is tolerable to patients with COPD and that it may reduce the degree of dyspnea and
346 dynamic hyperinflation through a reduced ventilatory demand (6). Moreover, it can induce
347 clinically meaningful improvements in daily physical activity level (25).
348 In addition, strength training has been shown to significantly improve peripheral muscle
349 strength in patients with COPD, which may result in an improved performance of ADLs,
350 such as walking, standing up from a chair and household tasks (30). This is confirmed by our
351 findings, showing a strong significant association between improvements in quadriceps
352 muscle strength and improved ADL performance (figure 3c). Though, a systematic review on
353 the effects of upper limb exercises was not able to determine whether upper limb training
354 may lead to improvements in arm activities, then again, authors concluded that it is reasonable
355 to assume that the improvements shown in dyspnea and upper limb endurance capacity may
356 lead to improved performance of arm activities (26).
357
358 ECTs have been widely recommended to decrease both the perception of dyspnea and energy
359 expenditure during the performance of ADL in patients with COPD (46, 47). Furthermore, it
16

360 has been suggested that these techniques might be useful in the prevention of dynamic
361 hyperinflation (29), which frequently occurs during the performance of ADLs and is
362 considered one of the main factors responsible for the increased perception of dyspnea in
363 patients with COPD (15, 23, 37). Velloso et al. were the first to demonstrate that the use of
364 ECTs in patients with COPD can significantly improve their ability to perform ADLs, by
365 reduced oxygen uptake and dyspnea perception (47). In addition, ECTs, including pursed lips
366 breathing and not bending the thorax over the abdomen, have been shown to prevent the
367 development of dynamic hyperinflation in tasks like taking a shower and changing shoes (37).
368 Interestingly, this did not result in a reduced sensation of dyspnea perception (37).
369 Our findings did not indicate any effect on the occurrence of dynamic hyperinflation during
370 ADLs. Indeed, both the level of dynamic hyperinflation as the proportion of patients
371 experiencing dynamic hyperinflation did not change. It has been recognized that high-
372 intensity exercise training programs can lower ventilatory demand, resulting in less dynamic
373 hyperinflation and, therefore, in lower levels of dyspnea (9), though, these training-induced
374 changes in dynamic hyperinflation are highly variable in patients with COPD (32). Moreover,
375 proportion of patients with very severe disease severity is small and patients had a relatively
376 well preserved exercise tolerance. It is possible that patients develop relatively mild dynamic
377 hyperinflation at baseline, which might not improve after pulmonary rehabilitation.
378 Then again, we demonstrated that patients were able to complete the ADLs in a significantly
379 shorter time, with a lower metabolic load and lower levels of dyspnea and fatigue. More
380 important, this was also reflected in the perception of the patients, represented by the higher
381 scores for performance and satisfaction of problematic ADLs on the COPM. This improved
382 performance of ADLs may result in lower levels of care dependency and, in turn, improve
383 patients´ health status and prognosis (18, 36).
384
17

385 Earlier studies already suggested that pulmonary rehabilitation has a positive impact on
386 ADLs, using self-reported measures of ADLs, such as the London Chest Activity of Daily
387 Living, Manchester Respiratory Activities of Daily Living Questionnaire, and COPM (13, 36,
388 49). These self-reported functional outcome measures can provide important information,
389 such as self-perceived symptoms and ability to perform ADLs. Though, it has been
390 recognized that psychological factors and cognitive impairments might influence patients’
391 answers. Moreover, an objective assessment of ADLs can provide important complementary
392 information regarding oxygen uptake, ventilation and symptoms. Despite the growing interest
393 in the objective assessment of ADLs through performance-based protocols, little is known
394 about the impact of pulmonary rehabilitation on actual performance of ADLs (38). This study,
395 therefore, contributes to a better understanding of problematic ADL performance in patients
396 with COPD.
397
398 Several methodological limitations need to be addressed. Proportion of patients in GOLD
399 stage I and IV, and modified Medical Research Council (mMRC) dyspnea grade 4 is limited
400 and, therefore, caution is required when generalizing results to the whole COPD population.
401 Moreover, due to the portable metabolic system we were not able to measure patients with
402 long-term oxygen therapy, who may experience more problematic ADLs compared to those
403 without long-term oxygen therapy (35). Then again, it has been shown that these patients have
404 a good response to a comprehensive pulmonary rehabilitation program, represented by
405 improved exercise performance, dyspnea perception, and health status (39), and it is expected
406 that this is also reflected in improvements in actual performance of ADLs. Though, further
407 studies will be needed to understand the effects of pulmonary rehabilitation on the
408 performance of ADLs in more severe patients with COPD.
18

409 Dynamic hyperinflation was assessed at the end of each ADL. Though, for evaluating the
410 effect of an intervention, quantification of dynamic hyperinflation at iso-time or iso-
411 ventilation has been recommended. However, since time to perform ADLs and peak
412 ventilation varied before and after pulmonary rehabilitation, this measurement may be less
413 useful and precise (10). It has been demonstrated that quantification of dynamic
414 hyperinflation as a function of ventilation can be a valid, alternative method, which has the
415 advantage to assess the effect of an intervention without requiring the same exercise time or
416 ventilation (10).
417 Although we demonstrated a significant improvement in ADL performance, it is unclear
418 whether this can be attributed to the full comprehensive pulmonary rehabilitation program or
419 just a specific component of the program (e.g. exercise training, occupational therapy,
420 nutritional intervention).
421 The used ADL test has not been validated. To date, a handful performance-based protocols
422 are available, of which only three have been validated in patients with COPD (Glittre ADL
423 Test, Londrina ADL Protocol and Monitored Functional Task Evaluation) (12, 31, 38). In
424 contrast to these validated tests, we preferred to use a longer, continuous protocol, in which
425 patients have to perform the ADLs at their usual pace, since we believe this corresponds
426 better to patients’ real-life situation (12, 31, 38). Moreover, the test provides information
427 regarding ADLs involving both the upper and lower limbs, which have been identified as
428 problematic in patients with COPD (3). However, a performance-based test that would allow
429 patients to perform self-nominated activities in their home setting would be preferable.
430 Thirteen patients (30%) were excluded from the analyses, since they were not able to
431 complete all ADL tests. It is possible that the continuous character of the test was too stressful
432 for patients with COPD. Then again, only three patients had to terminate the ADL test due to
433 intolerable dyspnea. Furthermore, six patients dropped out because of an exacerbation or
19

434 hospitalization, which are recognized as important contributors to non-completion of
435 pulmonary rehabilitation (11).
436 We did not include a control group. Though, given the widely recognized benefits of
437 pulmonary rehabilitation (40), it would be considered unethical to deny rehabilitation to a
438 control group.
439 Finally, we did not measure physical activity. Therefore, it is not known if the demonstrated
440 improvements in functional outcomes and ADL performance actually result in a more active
441 lifestyle.
442
443 To conclude, our findings clearly show that a comprehensive pulmonary rehabilitation is not
444 only able to improve important functional outcomes, but also the actual performance of ADLs
445 in patients with COPD. Indeed, patients needed significantly shorter time to perform the
446 ADLs, with a lower metabolic load and lower dyspnea sensation.
447
448 Disclosures
449 No conflicts of interest, financial or otherwise, are declared by the authors.
450
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586
23

587 FIGURE LEGENDS
588
589 Figure 1 Flowchart
590 Figure 2 The effect of pulmonary rehabilitation on performance of ADLs
591 a. Mean oxygen uptake during the performance of ADLs (%peakV̇O2)
592 b. Mean ventilation during the performance of ADLs (%peakVE)
593 c. Heart rate during the performance of ADLs (%peakHR)
594 d. Dynamic hyperinflation at the end of ADLs (a decrease of ≥ 150 ml in IC
595 compared to resting IC)
596 e. Time to complete ADLs
597 Figure 3 Association between changes in average total oxygen uptake during the
598 performance of the ADL test and functional outcomes of pulmonary
599 rehabilitation
600 a. Association between change in %peakV̇O2 and change in peakV̇O2
601 b. Association between change in %peakV̇O2 and change in 6MWD
602 c. Association between change in %peakV̇O2 and change in CWRT
603 d. Association between change in %peakV̇O2 and change in quadriceps
604 isokinetic strength
605 e. Association between change in %peakV̇O2 and change in COPM-P
606 f. Association between change in %peakV̇O2 and change in COPM-S
607
24

608 Table 1 Patient characteristics (n=31)
Men (%) 71
Age (years) 64.2 (8.4)
FEV1 (L) 1.52 (0.58)
FEV1 (% predicted) 54.6 (19.9)
FEV1/FVC (%) 41.1 (12.1)
DLCO (% predicted) 60.3 (15.5)
SaO2 (%) 93.6 (3.0)
GOLD grade I/II/III/IV (%) 10/42/39/10
GOLD grade A/B/C/D (%) 0/19/0/81
Exacerbations in previous 12 months ≥2 (%) 67.7
Hospitalizations in previous 12 months ≥1 (%) 32.3
mMRC grade 0-1/2/3/4 (%) 20/58/19/3
Body weight (kg) 84.0 (20.1)
Body mass index (kg/m2) 28.4 (6.2)
FFMI (kg/m2) 18.0 (2.5)
Peak workload (W) 91.4 (33.1)
Peak workload (%predicted) 55.2 (19.1)
Peak V̇O2 (mL/min) 1300 (347)
Peak V̇O2 (%pred) 61.6 (16.3)
Peak VE (L) 51.7 (16.1)
Peak VE (% MVV) 89.3 (18.9)
Peak HR (bpm) 126 (20)
Peak HR (% max HR) 79.8 (11.9)
6MWD (m) 483 (91)
6MWD (%predicted) 75.5 (14.8)
CWRT (s) 365 (232)
COPM – P (points) 3.8 (1.6)
COPM – S (points) 2.9 (1.8)
Isokinetic peak torque (Nm) 116.0 (39.8)
Isokinetic peak torque (%predicted) 78.2 (23.9)
Values are means ± SD
FEV1=forced expiratory volume in the first second; L=liter; IVC=inspiratory vital capacity; DLCO= diffusing
capacity of carbon monoxide; SaO2= oxygen saturation; mMRC= modified Medical Research Council; kg=kilogram;
kg/m2=kilogram per squared meters; FFMI=fat free mass index; W: Watt; V̇O2=oxygen uptake; mL=milliliter;
min=minute; VE =ventilation; MVV=maximum voluntary ventilation; HR=heart rate; bpm=beats per minute;
6MWD=six-minute walk distance; CWRT=constant work rate test; s=seconds; COPM-P=performance score on
Canadian Occupational Performance Measure; COPM-S=satisfaction score on Canadian Occupational Performance
Measure; Nm=newton meter
609
610
25

611 Table 2 Dynamic hyperinflation during the performance of ADLs pre and post rehabilitation
Pre Post
Rest IC, L 2.36 (0.65) 2.34 (0.78)
ΔIC (mL) -355 (320) -314 (305)
ΔIC (%IC rest) -15.4 (14.0) -14.0 (12.9)
Getting
dressed
% of patients developing dynamic hyperinflation 55 58

ΔIC/ΔVE (mL/L min-1) -65.1 (60.5) -62.1 (56.4)
ΔIC (mL) -336 (273) -280 (274)
Stair climbing
ΔIC (%IC rest) -14.9 (12.6) -11.5 (11.2)

ΔIC/ΔVE (mL/L min-1) -25.5 (23.5) -21.7 (24.0)
ΔIC (mL) -291 (273) -255 (293)
Washing
ΔIC (%IC rest) -12.3 (10.7) -10.9 (12.4)

dishes

ΔIC/ΔVE (mL/L min-1) -31.9 (31.0) -28.9 (33.5)
ΔIC (mL) -367 (283) -346 (326)
groceries
ΔIC (%IC rest) -16.1 (12.1) -14.2 (15.7)

Doing

ΔIC/ΔVE (mL/L min-1) -32.1 (31.4) -29.3 (27.9)
ΔIC (mL) -396 (260) -343 (330)
ΔIC (%IC rest) -17.1 (10.7) -13.8 (16.2)
Folding
towels

ΔIC/ΔVE (mL/L min-1) -46.9 (62.6) -41.1 (56.1)
ΔIC (mL) -365 (317) -367 (447)
ΔIC (%IC rest) -15.5 (13.0) -14.6 (14.3)
cleaning
Vacuum

ΔIC/ΔVE (mL/L min-1) -28.9 (28.9) -33.4 (39.7)
Values are means ± SD; *p<0.05 vs. pre rehabilitation
IC=inspiratory capacity; mL=litre; ΔIC=change in inspiratory capacity; ΔIC/ΔVE =change in IC per L min-1
of ventilation
612
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1

3 The impact of pulmonary rehabilitation on activities of daily living in patients with

7 F.M.E. Franssen1,2,3, L.E.G.W. Vanfleteren1,2, E.F.M. Wouters1,3, M.A. Spruit1,2,3

11 University Medical Centre (MUMC+), Maastricht, The Netherlands

15 Anouk W. Vaes, PhD

22 Running head: Pulmonary rehabilitation and ADLs in COPD

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32 performance of activities of daily living (ADLs). We aimed to determine the effects of a

33 comprehensive eight-week pulmonary rehabilitation program on the physiologic response to

34 and performance of ADLs in patients with COPD.

37 the Canadian Occupational Performance Measure (COPM) and an ADL-test consisting of

42 time to complete ADLs were recorded.

47 change following pulmonary rehabilitation. Changes in physical function, including six-

50 the ADL test.

51 Conclusion A comprehensive pulmonary rehabilitation program can improve the physiologic

52 response to and actual performance of ADLs in patients with COPD.

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56 comprehensive pulmonary rehabilitation program can improve the performance of ADLs in

58 metabolic load and dyspnea sensation.

60 Key words: Chronic obstructive pulmonary disease, dyspnea, rehabilitation, activities of

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67 isolation and therefore a reduction in their quality of life (20, 34).

76 importance to focus on strategies aimed at improving ADL performance in patients with

82 submaximal exercise and, in turn, in a lower dyspnea sensation (32). Moreover,

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96 dynamic hyperinflation during the performance of ADLs (37).

111 following pulmonary rehabilitation correspond to changes in the performance of ADLs.

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120 University Medical Centre (METC 13-3-055) and registered on www.trialregister.nl

122 consent to participate in this study.

124 Study design

127 pulmonary rehabilitation (40). In addition to agroup-based exercise training program,

130 (Technogym SpA, Gambettola, Italy); 3 sets of 8 repetitions at 70% of one-repetition

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141 program consisted of nutritional modulation, exacerbation management strategies, optimizing

147 using whole-body dual-energy x-ray absorptiometry), post-bronchodilator spirometry (forced

151 hospitalizations in the previous 12 months,

157 Medical Systems, Inc., New York, USA) (5, 33).

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171 values of both ADL tests.

173 ADL test

184 resume the ADLs as soon as they could.

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213 COPM-S, respectively).

215 Data analyses

224 analysed with SPSS, version 25.0.

227 Patient characteristics

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242 hospitalisations in the previous 12 months.

249 (COPM-S: 2.9±1.8 points) of identified problematic ADLs.

259 were 4.1±1.7 and 3.3±2.1, respectively.

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281 (-14.1-2.9)%, p=0.041 (Figure 2a)).

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291 (Figure 2c)).

294 hyperinflation as a function of ventilation demonstrated no significant difference before and

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311 0.657, and COPM-S: r=-0.592 (all p<0.01) (Figure 3).

328 limitation were referred for pulmonary rehabilitation.

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347 clinically meaningful improvements in daily physical activity level (25).