Background: Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) are associated with severe dyspnea and exercise intolerance. Early Pulmonary Rehabilitation (EPR) may lead to improvements in dyspnea and exercise tolerance, as it does in stable COPD patients.
Objective: To investigate the potential benefits of EPR, following AECOPD, in terms of multidimensional aspects of dyspnea and exercise performance.
Methods: One hundred and six patients admitted in a university hospital with AECOPD were randomized after discharge to either EPR for 8 weeks (EPR group) or Usual Care (UC) (UC group). All patients carried out the following tests, initially and after 8 weeks: spirometry, 6 Minute Walk Test (6MWT), and a symptom-limited incremental cycle Cardiopulmonary Exercise Test (CPET), and different dyspnea dimensions evaluation as following: Dyspnea intensity during incremental exercise using Borg scale, dyspnea 12 questionnaire and COPD Assessment Test (CAT) to assess sensory perceptual, affective distress, and symptom impact domains respectively.
Results: Forty male patients in each group well matched for age, body mass index, smoking index and spirometry completed the study. Significant improvements were detected following EPR in different dyspnea domains (sensory-perceptual, affective, and impact domains), and exercise performance and endurance. A highly significant difference (P=0.0001) was found in the magnitude of improvement of 6MWT (32.75 meters), CAT score (0.37), dyspnea 12 questionnaire (0.68), Borg scale during incremental exercise (0.31), and CPET duration (15.86 seconds), in the EPR group compared to UC group.
Conclusion: EPR following AECOPD was associated with clinically significant improvements in different domains of dyspnea, and exercise performance and endurance.
Trial Registration: ClinicalTrials.gov NCT03611127.
Date of registration: August 2, 2018.
Retrospectively registered
Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) are associated with severe dyspnea, activity restriction, accelerated physiological impairment and increased mortality [1]. These events are usually associated with worsening expiratory flow limitation. These, in combination, give rise to acute Dynamic Hyperinflation (DH) and dyspnea [1]. Respiratory muscle function is negatively affected by DH, functional weakening of the diaphragm is also encountered, and development of respiratory acidosis occurs, requiring hospital admission [1].
Following hospital discharge for an acute exacerbation, patients are typically more breathless and less active, and they may remain so for many weeks [2].
Interventions designed to fasten the recovery and improve COPD patients’ symptoms after hospital admission have many benefits, it lead to significant improvement in functional performance, and hence the quality of life of those patients, and it may also lead to reduction in further hospital admissions and future health care utilization [3].
Pulmonary Rehabilitation (PR), an intervention based on individually tailored exercise training, has emerged as arguably the most effective non-pharmacological intervention in improving dyspnea, exercise capacity and health status in COPD patients [4,5].
An Early Pulmonary Rehabilitation (EPR) following hospital discharge after AECOPD may have several benefits, exercise training is expected to decrease the ventilatory requirements during physical effort, which will reduce DH that leads to exercise limitation [6-9]; this, in turn, would be expected to be associated with an improvement of the three major dimensions of dyspnea: the sensory-perceptual domain, the affective distress, and the symptom impact or burden.
Thus, we aimed to determine the potential physiological and clinical impact of EPR on the multidimensional aspects of dyspnea (sensory perceptual, affective distress, and symptom impact domains) and exercise performance in COPD patients following hospital discharge from AECOPD.
Study Subjects: Hospitalized COPD patients with a diagnosis of AECOPD with no clinically significant arterial hypoxemia at rest or on exercise (resting percutaneous oxygen saturation (SpO2)>90% or a sustained decrease of <4% during exercise) were recruited. Diagnosis of COPD, AECOPD and spirometric assessment of airflow limitation severity was based on Global Initiative for Chronic Obstructive Lung Disease (GOLD) [10]. Patients with a prior diagnosis of other cardiorespiratory conditions (i.e., bronchial asthma, interstitial lung diseases, primary pulmonary hypertension, chronic congestive heart failure), as well as other conditions such as orthopedic, muscular and peripheral vascular diseases that could cause or contribute to breathlessness and exercise intolerance and/or could interfere with carrying out of exercise testing, were excluded.
Ethics, Consent and Permissions:
Study Design: The study was conducted in the Chest department of Ain Shams University hospital, Cairo, Egypt. After receiving ethical approval from Ain Shams University, Faculty of Medicine research ethics committee (FWA00017585), informed consent obtained from all participants. Each participant performed 2 visits. At visit 1 (within one week following hospital discharge), patients were familiarized with dyspnea and quality of life questionnaires/scales and carried out spirometric lung function test, 6MWT, and a symptom-limited incremental cycle Cardiopulmonary Exercise Test (CPET). Then, simple randomization method using coin flipping was done by the principal investigator, patients were randomized to either EPR or Usual Care (UC), both were receiving their standard maintenance therapy, the patients and investigators were not blinded to allocation due to the nature of the intervention and the participation of investigators in the pulmonary rehabilitation process. Eight weeks rehabilitation program offered to EPR group only, featuring two directly supervised sessions per week, each lasting 2 hours, in accordance with recommended and well described exercise-training programs [4,11]. At visit 2, conducted 8 weeks after visit 1, all patients completed spirometric lung function test followed by an incremental CPET, dyspnea and quality of life questionnaires/scales. Subjects continued their respiratory medications except for short-acting bronchodilators prior to exercise testing (short-acting B2-agonists=4 hours, short-acting anticholinergics=6 hours). Subjects were asked to avoid smoking for at least 60 minutes prior to each visit, caffeine-containing beverages and heavy meals at least 4-6 hours prior to testing, as well as strenuous physical exertion for at least 12 hours before each visit day. Visits were conducted at the same time of the day for each subject. The study adheres to CONSORT guidelines and include a completed CONSORT checklist as an additional file.
Methods:
Spirometric lung function test: Assessment of baseline spirometry according to recommended techniques [12,13].
Dyspnea evaluation: Dyspnea was assessed before and after (visit 1 and 2) EPR program by evaluating its multidimensional aspects which comprise three major dimensions: the sensory-perceptual domain, the affective distress domain, and the symptom impact/burden domain [12,13].
The sensory-perceptual dimension, which includes ratings of dyspnea intensity and its quality (that is, “how breathing feels like”), was evaluated by using the Borg scale during incremental cycle exercise [14]. The affective distress domain, which addresses the question of “how distressing breathing is” and focuses on the perception of immediate unpleasantness or the cognitive evaluative response about the potential consequence of what is perceived, was assessed by using the dyspnea-12 questionnaire [15]. The symptom impact/burden dimension, which evaluates how dyspnea impacts on functional ability/disability, health status, and quality of life, was evaluated by using the COPD Assessment Test (CAT) [16].
Exercise Testing: Cardiopulmonary Exercise Tests (CPETs) were conducted on an electronically braked cycle ergometer in accordance with recommended techniques and previously published studies. All incremental exercise tests consisted of a steady-state resting period of 6 minutes and a 3-min warm-up of unloaded pedaling followed by an incremental test in which the work rate (WR) increased at 1-minute intervals (ramp protocol) by increments of 5 watts until the point of symptom-limitation (peak exercise) [8,12,13,17,18]. Patients were instructed to maintain the pedaling rate between 50 and 70 revolutions per minute. Breath-by-breath data were collected at baseline and throughout exercise while subjects breathe through a mouthpiece with attached low-resistance flow transducer with nasal passages occluded by a nose-clip: Minute volume (VE), oxygen uptake (VO2), carbon dioxide production (VCO2), end-tidal carbon dioxide partial pressure (PETCO2), tidal volume (VT), respiratory frequency (Rf) were calculated. Electrocardiographic monitoring of heart rate (HR), rhythm, ST-segment changes, blood pressure by indirect sphygmomanometry, and percutaneous oxygen saturation (SpO2) by pulse oximetry were carried out continuously throughout exercise testing [8,12,13,17,18]. During incremental CPET, the Ventilatory Anaerobic Threshold (VAT), and VE/VCO2 slope were calculated in accordance with recommended techniques and previously published studies [12,17].
Early pulmonary rehabilitation: The pulmonary rehabilitation program consisted of two supervised sessions per week for eight weeks. Each session lasted two hours: One hour of exercise training, conducted in 4 sets of aerobic walking and cycling, the initial exercise level was set at a work rate corresponding 70% of peak VO2 from the baseline CPET, and progressively increased by 5 Watt, until 80% of the baseline peak VO2 is reached, each set is 10 minutes. Strength training for the upper and lower limb was also applied. The second hour was dedicated to education concerning the disease (COPD) and its management, smoking cessation, nutrition and other lifestyle issues. Patients were also encouraged to perform daily home exercise of at least 20 minutes of ground walking. Any encountered side effects or complications related to EPR were recorded.
Blinding: The patients and investigators were not blinded to allocation due to the nature of the intervention and the participation of investigators in the pulmonary rehabilitation process.
Sample size calculation: The primary outcome measure of the study was to determine the effect of early pulmonary rehabilitation on the different aspects of dyspnea, as well as exercise performance in COPD patients following exacerbation. Sample size was calculated using STATA program, setting the type-1 error (α) at 0.05 and the power (1-β) at 0.8. On the basis of results from a previous study [3], calculation of sample size estimated that33 cases per group is needed, and with taking in consideration 20% drop out rate, the needed sample is 40 cases per group.
Statistical analysis: The collected data was revised, coded, tabulated and introduced to a PC using Statistical package for Social Science (IBM Corp. Released 2011. IBM SPSS Statistics for Windows, Version 20.0. Armonk, NY: IBM Corp). Quantitative non-parametric variables are expressed as mean and SD, Median and Interquartile Range (IQR). Qualitative variables are expressed as frequencies and percent. Student t test and Mann Whitney Test were used to compare a continuous variable between two study groups. Chi square test and Fisher’s exact test were used to examine the relationship between Categorical variables. Paired t test was used to assess the statistical significance of the difference between two means measured twice for the same study group. A P-value< 0.05 was considered statistically significant.
Socio-demographic data |
Group |
|||
EPR |
UC |
|||
Mean |
±SD |
Mean |
±SD |
|
Age |
57.4 |
7.93 |
58.43 |
7.72 |
Weight (kg) |
74.33 |
13.36 |
72.58 |
8.8 |
Height (cm) |
170.98 |
7.24 |
172.73 |
7.96 |
25.36 |
4.25 |
24.33 |
3.08 |
|
28.2 |
9.96 |
30.32 |
9.99 |
|
Sex : Male (n %) |
40 |
100.00% |
40 |
100.00% |
COPD spirometric GOLD classification |
|
|
|
|
GOLD 3 [30%≤FEV1<50%predicted]# (n %) |
11 |
27.50% |
15 |
37.50% |
GOLD 4 [FEV1<30% predicted]# (n %) |
29 |
72.50% |
25 |
62.50% |
Clinical assessment parameter |
|
|
|
|
CAT Score |
12.55 |
3.09 |
11.35 |
2.76 |
6-minute walk test (METERS) |
336.25 |
69.97 |
360 |
84.79 |
Dyspnea 12 questionnaire |
17.05 |
5.49 |
16.15 |
6.6 |
Pulmonary function test |
|
|
|
|
FEV1 (L) |
1.88 |
0.5 |
1.83 |
0.59 |
FEV1 % PREDICTED |
57.45 |
15.5 |
53.49 |
15.43 |
FVC (L) |
3.35 |
0.61 |
3.27 |
0.62 |
FVC % PREDICTED |
74.2 |
13.81 |
73.26 |
12.07 |
FEV1/FVC % |
55.95 |
8.03 |
54.68 |
9.34 |
MEF 50 (%) |
34.03 |
13.5 |
32.23 |
12.88 |
VE max (L/min) |
43.1 |
12.31 |
46.72 |
13.59 |
BMI: Body mass index |
Cardiopulmonary exercise test parameter |
Group |
P* |
Sig |
|||
EPR |
UC |
|||||
Mean |
±SD |
Mean |
±SD |
|||
Borg scale during incremental exercise |
7.58 |
0.9 |
7.85 |
0.95 |
0.188 |
NS |
VO2 (ml/min/Kg) |
18.68 |
8.72 |
18.58 |
9.17 |
0.962 |
NS |
VAT or VO2 at VT (ml/min/Kg) |
16.7 |
8.33 |
16.69 |
8.52 |
0.997 |
NS |
Resting PETCO2 (mmHg) |
36.53 |
1.34 |
36 |
1.15 |
0.064 |
NS |
Peak RER |
1.05 |
0.09 |
1.03 |
0.1 |
0.434 |
NS |
Resting SpO2 (%) |
98.07 |
0.92 |
98.37 |
0.7 |
0.105 |
NS |
Minimum SpO2 (%) |
95.48 |
1.04 |
95.3 |
1.11 |
0.469 |
NS |
Resting RR (breath/minute) |
16.93 |
1.7 |
16.3 |
1.54 |
0.089 |
NS |
Maximum RR (breath/minute) |
40.13 |
5.73 |
39.8 |
5.72 |
0.8 |
NS |
Resting HR (beat/minute) |
79.58 |
5.59 |
77.82 |
3.13 |
0.089 |
NS |
Peak HR (beat/minute) |
142.68 |
9.67 |
141.25 |
7.96 |
0.474 |
NS |
% of age predicted maximal HR |
87.6 |
4.7 |
87.25 |
3.71 |
0.713 |
NS |
Maximal work load (Watts) |
120.3 |
14.89 |
115.65 |
11.47 |
0.122 |
NS |
Test duration (sec) |
569.73 |
122.53 |
590.75 |
125.44 |
0.451 |
NS |
VO2: Oxygen uptake |
Variables |
Mean |
±SD |
P* |
Pre CAT Score |
12.55 |
3.08 |
0.002 |
Post CAT Score |
11.8 |
2.85 |
|
Pre 6 minute walk test (METERS) |
336.25 |
69.97 |
0.0001 |
Post 6 minute walk test (METERS) |
368 |
73.2 |
|
Pre Dyspnea 12 questionnaire |
17.05 |
5.49 |
0.0001 |
Post Dyspnea 12 questionnaire |
15.6 |
4.81 |
|
Pre Borg scale during incremental exercise |
7.58 |
0.9 |
0.0001 |
Post Borg scale during incremental exercise |
6.55 |
0.9 |
|
Pre Peak VO2 (ml/min/Kg) |
18.675 |
8.725 |
0.001 |
Post Peak VO2 (ml/min/Kg) |
19.365 |
8.4518 |
|
Pre Test duration (sec) |
569.73 |
122.533 |
0.0001 |
Post Test duration (sec) |
604.25 |
126.752 |
|
CAT : COPD assessment test |
Variables |
Mean |
±SD |
P* |
Initial CAT Score |
11.35 |
2.76 |
0.006 |
CAT Score (after 8 weeks) |
11.52 |
2.87 |
|
Initial 6 minute walk test (METERS) |
360 |
84.79 |
0.378 |
6 minute walk test (METERS) (after 8 weeks) |
359 |
83.13 |
|
Initial Dyspnea 12 questionnaire |
16.15 |
6.6 |
0.006 |
Post Dyspnea 12 questionnaire |
16.5 |
6.57 |
|
Initial Borg scale during incremental exercise |
7.85 |
0.949 |
0.281 |
Borg scale during incremental exercise (after 8 weeks) |
7.73 |
1.012 |
|
Initial Peak VO2 (ml/min/Kg) |
18.58 |
9.1653 |
0.038 |
Peak VO2 (ml/min/Kg) (after 8 weeks) |
18.173 |
8.6483 |
|
Initial Test duration (sec) |
590.75 |
125.441 |
0.098 |
Test duration (sec) (after 8 weeks) |
585.75 |
119.462 |
|
CAT: COPD assessment test |
Variables |
Group |
P* |
|||||||||
EPR |
UC |
||||||||||
Mean |
±SD |
Median |
IQR** |
Mean |
±SD |
Median |
IQR** |
||||
6MWT change |
31.75 |
24.74 |
26 |
0 |
40 |
-1 |
7.09 |
0 |
0 |
0 |
0.0001 |
CAT change |
0.75 |
1.43 |
0 |
0 |
1 |
-0.18 |
0.38 |
0 |
0 |
0 |
0.0001 |
Dyspnea 12 change |
1.45 |
1.97 |
0 |
0 |
2 |
-0.35 |
0.77 |
0 |
0 |
0 |
0.0001 |
Borg scale change |
1.03 |
1 |
1 |
0 |
2 |
0.13 |
0.72 |
0 |
0 |
1 |
0.0001 |
VO2 change |
0.69 |
1.25 |
0.4 |
-0.1 |
1.65 |
-0.41 |
1.2 |
0 |
-0.3 |
0 |
0.0001 |
VAT change |
-0.02 |
1.15 |
0.05 |
-0.6 |
0.45 |
-0.45 |
1.12 |
-0.15 |
-0.95 |
0.05 |
0.126 |
Peak RER change |
0 |
0.08 |
0 |
-0.06 |
0.08 |
0.01 |
0.05 |
0 |
-0.01 |
0 |
0.791 |
Work load change |
0.4 |
4.09 |
1 |
-2.5 |
3 |
0 |
0 |
0 |
0 |
0 |
0.301 |
Test duration change |
34.53 |
41.06 |
30 |
0 |
70 |
-5 |
18.67 |
0 |
-10 |
0 |
0.0001 |
**inter quartile range |
Since it was impossible to blind the patients to the intervention, we cannot exclude a placebo effect as a possible mechanism participating in the observed improvements. However, we documented significant improvement in exercise performance, exercise duration, oxygen consumption, and dyspnea perception.
The study investigators were not also blinded to PR allocation because they were directly involved in the delivery of PR, and this cannot exclude an element of bias in the results of some questionnaires, but the cardiopulmonary test completed by each patient is highly standardized and was not subject to any possible bias.
EPR, after hospital discharge of COPD exacerbations, was associated with clinically significant improvement in the sensory perceptual, affective, and impact domains of dyspnea, and improvement in exercise performance and endurance. These findings support and recommend the implementation of EPR after an acute exacerbation of COPD.
Availability of Data and Materials: The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
Ethics Approval and Consent to Participate: Ethics approval from Ain Shams University, Faculty of Medicine research ethics committee (FWA00017585).Written informed consent signed by each patient to participate in the study. Consent obtained from each participant to publish his data collected in the study.
Competing Interests: None.
Acknowledgments: The investigators would like to thank AstraZeneca Company for their help and support to perform this research.
Funding: This study was funded by AstraZeneca.
Consent to Publish: Not applicable
Author Contribution: Amr Mounir Shoukri participated in the study design, collected the patient data, participated in the data analysis, and performed the clinical cardiopulmonary exercise tests. Ashraf Mokhtar Madkour participated in the study design, and reviewed the collected data. Tarek Mohamed Safwat participated in the study design and reviewed the collected data.
All authors read and approved the final manuscript.
Citation: Shoukri AM, Madkour AM, Safwat TM (2019) The Impact of Early Pulmonary Rehabilitation on the Multidimensional Aspects of Dyspnea and Exercise Performance Following Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Randomized Trial. J Pulm Med Respir Res 5: 031.
Copyright: © 2019 Amr Mounir Shoukri, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.