Abstract
Background Little is known of the early changes in physical activity after lung transplantation.
Objectives The purposes of this study were: (1) to describe physical activity levels in patients up to 6 months following lung transplantation and (2) to explore predictors of the change in physical activity in that population.
Design This was a prospective cohort study.
Methods Physical activity (daily steps and time spent in moderate-intensity activity) was measured using an accelerometer before and after transplantation (at hospital discharge, 3 months, and 6 months). Additional functional measurements included submaximal exercise capacity (measured with the 6-Minute Walk Test), quadriceps muscle torque, and health-related quality of life (measured with the Medical Outcomes Study 36-Item Short-Form Health Survey 36 [SF-36] and the St George's Respiratory Questionnaire).
Results Thirty-six lung transplant recipients (18 men, 18 women; mean age=49 years, SD=14) completed posttransplant measurements. Before transplant, daily steps were less than a third of the general population. By 3 months posttransplant, the largest improvement in physical activity had occurred, and level of daily steps reached 55% of the general population. The change in daily steps (pretransplant to 3 months posttransplant) was inversely correlated with pretransplant 6-minute walk distance (r=−.48, P=.007), daily steps (r=−.36, P=.05), and SF-36 physical functioning (SF-36 PF) score (r=−.59, P=.0005). The SF-36 PF was a significant predictor of the change in physical activity, accounting for 35% of the variation in change in daily steps.
Limitations Only individuals who were ambulatory prior to transplant and discharged from the hospital in less than 3 months were included in the study.
Conclusions Physical activity levels improve following lung transplantation, particularly in individuals with low self-reported physical functioning. However, the majority of lung transplant recipients remain sedentary between 3 to 6 months following transplant. The role of exercise training, education, and counseling in further improving physical activity levels in lung transplant recipients should be further explored.
An important goal of lung transplantation is the improvement of physical function in individuals with end-stage lung disease.1 Physical functioning is an important component of health-related quality of life (HRQOL) that affects the ability to perform activities of daily living, the ability to return to work, and participation in leisure and social activities. Physical activity also has been identified as an important predictor of all-cause mortality in chronic obstructive pulmonary disease (COPD).2 However, it is not known what role physical activity has on survival or the long-term health of lung transplant recipients.
Lung transplant candidates have markedly reduced levels of physical activity before transplant, with increased time spent in sedentary pursuits.3–5 Although participation in pretransplant rehabilitation improves physical activity, levels remain low.5 Reduced levels of daily steps, walking time, and time spent engaged in moderate-intensity physical activity have been reported in lung transplant recipients more than 1 year following transplantation.3,6–8 Lung transplant recipients are at risk for chronic conditions, including hypertension, diabetes, and hyperlipidemia,9 and physical activity and exercise training may have a potential role in the long-term management of comorbidities that could improve posttransplant outcomes. Langer and colleagues3 showed that lung transplant recipients 1 year following hospital discharge who underwent exercise training immediately after transplant had higher levels of physical activity and lower average ambulatory blood pressure compared with a more sedentary control group who did not participate in early structured exercise training. The majority of studies reporting physical activity have been cross-sectional, with only one study examining physical activity before and after lung transplantation. This fairly homogeneous cohort included individuals between 40 and 65 years of age; 80% were patients diagnosed with COPD who experienced an uncomplicated postoperative period.3 These findings may not be generalizable to the entire adult lung transplant population because this population includes a wide range of ages (from 18 to over 75 years) and individuals with multiple respiratory diagnoses.9 Factors predicting the change in physical activity from pretransplant to posttransplant have not been previously explored and may highlight areas to target both pretransplant and posttransplant rehabilitation to further improve functional outcomes.
The primary aim of this study was to describe the change in physical activity from pretransplant to hospital discharge and 3 and 6 months post-lung transplantation in individuals with heterogeneous end-stage lung disease who participated in exercise training before and after transplant. The secondary aim was to explore predictors of change in daily steps from pretransplant to 3 and 6 months posttransplant.
Method
Study Protocol
This prospective cohort study included lung transplant candidates on the waiting list at the Toronto General Hospital, Toronto, Canada. Individuals were excluded if they were listed for retransplantation or multi-organ transplantation, were awaiting transplantation as an inpatient or were experiencing a rapid clinical deterioration, had limited English proficiency, or exhibited significant difficulty following instructions during rehabilitation sessions. All participants gave written informed consent, and recruitment occurred between September 2010 and August 2011.
All participants were actively undergoing pretransplant rehabilitation for a minimum of 4 weeks prior to recruitment. This mandatory rehabilitation program took place in a hospital outpatient setting and was designed and supervised by physical therapists. Exercise sessions occurred 3 times per week during the entire waiting period prior to transplant. Individualized training included resistance and aerobic exercise, with treadmill walking and cycle ergometry targeted for 20 consecutive minutes each. Aerobic training intensity was prescribed and progressed as tolerated by ensuring an adequate oxygen saturation for exertion (typically above 88%), staying within symptom tolerance (modified Borg dyspnea score of 3 or 4),10 and not exceeding 85% of the age-predicted maximum heart rate.11 Resistance training was prescribed and progressed according to a 10-repetition maximum and included one set of 10 repetitions of all major muscle groups.
After transplant, early mobility was initiated in the intensive care unit, followed by progressive mobility and general strengthening on the ward until time of hospital discharge. Individuals resumed a mandatory outpatient rehabilitation program 3 times per week until 3 months posttransplant. Exercise training was similar to the pretransplant program in frequency, duration, and mode. However, upper extremity resistance training was limited to 10 lb (1 lb=0.45 kg), and aerobic training intensity was progressed weekly using a modified Borg leg fatigue score of 3 or 4 instead of a modified Borg dyspnea score due to the alleviation of ventilatory impairment and symptoms and the presence of peripheral muscle limitations observed after transplant.
Standard immunosuppression in the first 3 months posttransplant consisted of cyclosporine, azathioprine (mycophenolate for recipients with panel reactive antibodies), and prednisone. Target cyclosporine trough whole blood levels were 250 to 350 μg/mL in recipients under 55 years or over 55 years of age with panel reactive antibodies and were 200 to 250 μg/mL for older recipients without antibodies. Prednisone doses were tapered from 0.5 to 0.25 mg/kg/d over the first 3 months posttransplant.
Physical Activity Measures
Measures were conducted pretransplant, at hospital discharge, and 3 and 6 months posttransplant and were taken within a 2-week time frame at each of the 4 time points using a previously described protocol.5 Physical activity was measured with an activity monitor worn during the waking hours for 7 consecutive days. The Actigraph GT3X (Actigraph, Pensacola, Florida), a lightweight (0.95 oz [26.6 g]), compact (1.5 × 1.44 × 0.7 in) triaxial accelerometer, was worn at the hip attached to a waist belt and recorded the amount, type, and pattern of activity, including step count. The Actigraph GT3X has been previously validated against portable indirect calorimetry for measuring energy expenditure in physically active adults.12 Valid days for data collection were defined as days with recorded wear time greater than 8 hours, and activity counts were recorded in 30-second sampling epochs. All participants kept an activity diary during the week the accelerometer was worn and were asked to maintain their typical level of daily activity. Participants with at least 2 valid days during the week of the assessment were included in the analysis. The measurements derived were daily steps and time spent in moderate-intensity activity per day (3–6 metabolic equivalents [1 MET=3.5 mL O2·kg−1·min−1]).
Other Measures
Quadriceps muscle torque (QT) was measured on the dominant limb as isometric peak torque (in newton-meters) with the hip positioned at 90 degrees of flexion and the knee at 60 degrees of flexion using an isokinetic dynamometer (Biodex Medical Systems Inc, Shirley, New York). A maximum voluntary contraction of 5 seconds was performed with a 1-minute rest. Following a warm-up contraction, the highest peak torque from up to 5 reproducible trials (<10% coefficient of variation) was recorded. Standardized instructions, encouragement, and visual and verbal feedback were provided. Results were compared with predicted values.13 Functional exercise capacity was measured using the 6-Minute Walk Test (6MWT), which was performed according to published guidelines.14 The test was administered using the flow rate of supplemental oxygen prescribed for exertion using the gait aid typically used outdoors. The 6-minute walk distance (6MWD) was compared with Canadian reference values.15 Health-related quality of life was measured using both a generic questionnaire (the Medical Outcomes Study 36-Item Short-Form Health Survey [SF-36]) and a disease-specific questionnaire (St George's Respiratory Questionnaire [SGRQ]).16,17 Both questionnaires have been used previously in lung transplant candidates and recipients.18–20 Each questionnaire is scored from 0 to 100, with higher scores denoting better HRQOL on the SF-36 and worse HRQOL on the SGRQ.
Statistical Analyses
The assumption of normality was assessed with the Shapiro-Wilk statistic. Data were expressed as mean, standard deviation, and 95% confidence interval (95% CI) for normally distributed variables or as median and interquartile range (IQR) for nonnormally distributed variables. A within-patient analysis was performed using a repeated-measures analysis of variance (ANOVA) or Friedman test for nonnormally distributed variables to examine changes in physical activity and other functional measures over time. A Mauchly test with a Huynh-Feldt correction factor was performed, and corrected degrees of freedom were reported for variables that did not meet the assumption of sphericity. Unpaired t tests were used to examine differences in the change in physical activity between sexes and to compare study participants included in the analysis with individuals excluded during the study. Bivariate analysis was used to examine the relationship between the change in daily steps (pretransplant to 3 months posttransplant and pretransplant to 6 months posttransplant) and the following pretransplant variables: age, body mass index (BMI), 6MWD, QT, daily steps, SF-36 physical functioning (PF) score, and SGRQ activity score. Posttransplant variables included the length of time in the intensive care unit after transplant and the number of rehabilitation days attended between hospital discharge and 3 months posttransplant. A P value tested whether the observed coefficients differed from zero. Variables that were significantly correlated to physical activity and demonstrated homoscedasticity were entered into a multiple regression model. For all analyses, a P value of ≤.05 was considered statistically significant. Statistical analysis was performed using SAS statistical package (version 9.3, SAS Institute Inc. Cary, North Carolina).
A sample of 35 participants was calculated to detect a change of 1,000 steps after transplant with a 99% confidence interval using a standard deviation of 2,300 daily steps previously reported in lung transplant recipients.8 Based on patient outcomes at our center over the previous 5 years relating to transplant rates and pretransplant and posttransplant morbidity and mortality, a 70% completion rate was anticipated, so the sample size was inflated to 50 lung transplant candidates.
Role of the Funding Source
Funding for this study was provided by the Ontario Lung Association through an Ontario Respiratory Care Society Research grant. Mrs Wickerson was supported in her graduate studies through research fellowships from the Ontario and Canadian Lung Associations. Dr Brooks is supported by a Canada Research Chair.
Results
The Figure shows the flow of participants throughout the study. Fifty lung transplant candidates who had been on the wait list for a median of 2 months (IQR=2.5) at the time of the study assessment were recruited. Before transplant, the 6MWT was performed every 3 months while lung transplant candidates participated in pretransplant rehabilitation. Twenty-two study participants were on the wait list for more than 3 months following the study assessment and, therefore, underwent a replicate 6MWT. The 6MWD was maintained (decline of 3.5 m) (IQR=5), which is consistent with previous findings at our center.21 Table 1 shows the baseline characteristics of the 36 participants who underwent posttransplant measures at all 3 time points. All participants were discharged home with the exception of 2 patients who were first transferred to an inpatient rehabilitation facility for 18 and 29 days. The median time between transplant and starting outpatient rehabilitation was 22 days (IQR=18). Participants underwent 22 (SD=6) supervised outpatient exercise sessions between hospital discharge and 3 months posttransplant. Forced expiratory volume (FEV1) increased at all time points after transplant and reached 2.4 L (SD=0.7) or 73% predicted (SD=20%) at 6 months posttransplant.
Flow of study participants. HLTx=heart-lung transplantation.
Baseline Characteristics (N=36)a
Excluded Study Participants
The 7 participants excluded due to pretransplant and posttransplant mortality or hospitalization greater than 3 months posttransplant (3 men, 4 women; interstitial lung disease [ILD] [n=6], pulmonary hypertension [PH] [n=1]) (Figure) were older (mean age=63 years [SD=6] versus 49 years [SD=14], respectively; P=.005), had a higher pretransplant BMI (26.8 kg/m2 versus 23.3 kg/m2, respectively; P=.02), and were less physically active before transplant (daily steps=1,919 [SD=1,294] versus 2,857 [SD=1,291], respectively; P=.04; and time spent in moderate-intensity activity=1.6 minutes [IQR=2.1] versus 4.3 minutes [IQR=8.3], respectively; P=.04) compared with the participants included in the analysis.
Longitudinal Changes in Physical Activity and Function Measures
Daily steps changed over time (F3,57=8.16, P=.0001) (Tab. 2). Before transplant, physical activity levels were less than a third of the general Canadian population.22 There were no immediate changes in daily steps or time spent in moderate-intensity physical activity at hospital discharge from pretransplant levels (Tab. 2). By 3 months posttransplant, daily steps increased by 2,024 steps (95% CI=1,371, 2,676; P≤.001) and reached 55% of the daily steps compared by age and sex with the Canadian general population,22 with no further increase at 6 months (Tab. 2). By 6 months posttransplant, a minimum of 1,172 daily steps and a maximum of 13,402 daily steps were recorded. In classifying activity level using step count, 62% of participants were sedentary, 24% were low active, 7% were somewhat active, 3.5% were active, and 3.5% were highly active.23 Time spent in moderate-intensity physical activity also showed an increase over time (χ23=25.99, P<.0001), with a significant increase in time spent in moderate-intensity physical activity from hospital discharge to 3 months posttransplant. There were no further increases by 6 months posttransplant (Tab. 2).
Daily Steps and Time Spent in Moderate-Intensity Physical Activity: Before and After Transplant (N=36)a
Quadriceps muscle torque showed a significant change over time (F3,30=15.34, P<.0001). Peripheral muscle weakness was evident before transplant (X̅=116 N·m [SD=40] or 74% predicted [SD=23%])12 and decreased 20 N·m or 17% (95% CI=−35, −4.4; P≤.001) at hospital discharge. At 3 months posttransplant, QT recovered 23 N·m (95% CI=8.6, 36.8; P ≤.001) to pretransplant levels (X̅=119 N·m [SD=40] or 74% predicted [SD=15%]) and by 6 months posttransplant reached 129 N·m (SD=42) or 78% predicted (SD=18%). The 6MWD showed a change over time (F2.6,77.5=43.79, P<.0001) using a Huynh-Feldt correction factor (Tab 3). The 6MWD was reduced before transplant14 and showed no significant change at hospital discharge. By 3 months posttransplant, the 6MWD increased by 113 m (95% CI=84, 142; P≤.001), with no additional improvements at 6 months posttransplant. Health-related quality of life showed significant improvement over time in both the SF-36 PF (χ23=79.58, P<.0001) and the activity domain of the SGRQ (χ23=69.70, P<.0001) (Tab. 4). Before transplant, all subscales of the SF-36 were decreased, with the greatest impairment in the physical domains, and all domains of the SGRQ were impaired, with the greatest impairment in the activity domain (Tab. 4). At hospital discharge, only physical functioning, general health, and vitality subscales improved, and bodily pain was worse on the SF-36 questionnaire, whereas all domains in the SGRQ improved (Tab. 4). By 3 months posttransplant, physical functioning and vitality continued to improve; bodily pain returned to pretransplant levels; general health did not change; and role–physical, social function, role–emotional, and mental health increased from pretransplant levels. All domains of the SGRQ continued to improve at 3 months posttransplant. There were no additional improvements at 6 months posttransplant. By 6 months posttransplant, the SF-36 PF approached Canadian population norms (Tab. 4).24
6-Minute Walk Test: Before and After Transplant (N=36)a
Health-Related Quality of Life: Before and After Transplant (N=36)a
Predictors of Change in Physical Activity
There was no difference in the change in physical activity between sexes. There was a negative correlation between the change in daily steps from pretransplant to 3 months posttransplant and the following variables: pretransplant 6MWD (r=−.48, 95% CI=−0.71, −0.14; P=.007), daily steps (r=−.36, 95% CI=−0.63, −0.008; P=.05), and SF-36 PF score (r=−.59, 95% CI=−0.78, −0.29; P=.0005). Baseline 6MWD did not meet the assumption of homoscedasticity and was not entered into the multiple regression analysis. Multiple linear regression analysis was performed using baseline SF-36 PF scores and daily steps. Self-reported physical functioning on the SF-36 was identified as a predictor of change (β=−0.526, P=.03), whereas baseline steps was not significant (β=−0.172, P=.29). Self-reported physical functioning accounted for 35% of the variation in the change in daily steps. There were no significant relationships between the change in daily steps from pretransplant to 6 months posttransplant and any of the predefined variables.
Discussion
This study describes the early recovery of physical activity in a heterogeneous population of lung transplant candidates. To our knowledge, this is the first study to examine predictors of change in physical activity following lung transplantation. Lung transplant candidates have very low levels of physical activity and show their greatest improvement between hospital discharge and 3 months posttransplant. However, physical activity levels for this population remain considerably lower than those of the general population, with no further improvements at 6 months. Low pretransplant 6MWD, daily step count, and SF-36 PF score were associated with a greater change in daily steps 3 months following transplant, suggesting that individuals who have lower levels of functioning and physical activity before transplant may have a greater potential to improve physical activity levels following successful lung transplantation. Low pretransplant self-reported physical functioning was the only predictor of change in physical activity, accounting for 35% of the variability of change in daily steps.
Change in Physical Activity
Many factors may affect physical activity in the first 3 months such as regular medical tests and clinic visits, required supervised exercise training at our center, posttransplant restrictions, hospitalizations, and episodes of infection and rejection. Despite improvement in physical activity levels after transplant, lung transplant recipients reached only half of the physical activity levels in the general population by 3 and 6 months posttransplant, although a large range of physical activity levels were observed. After 3 months, transplant recipients are no longer required to attend supervised exercise training at our center. Despite this procedure, there was no difference between physical activity at 3 and 6 months, indicating that either individuals were performing exercises at home or in the community or had resumed household or work-related activities.
Although the average daily steps for the study cohort were similar at 3 and 6 months, there was variability within the group, with some individuals engaging in significantly higher or lower levels of physical activity at 6 months compared with the 3-month time point. Regular and structured maintenance exercise programs may lead to further increases in physical activity after the first 3 months following transplantation. Moderate- to vigorous-intensity physical activity (MVPA) is associated with health benefits, and the accumulation of 150 minutes of MVPA per week is recommended in the general population.25
Although daily step count was comparable, the time spent in moderate-intensity physical activity was lower in our cohort than what was observed by Langer and colleagues,3 which may be due to the fact that different activity monitors were used to measure physical activity. In addition, culture and environmental infrastructure may account for some of the disparities in time spent in moderate-intensity physical activity. Walking, biking, and the use of public transit are more common in Europe than in North America, where there is an increased reliance on cars for transportation, and this difference may lead to differences in the amount of physical activity during activities such as shopping or attending medical appointments.26 Langer and colleagues3 found a further increase in physical activity levels at 12 months following hospital discharge in their exercise intervention group (7,400 steps). It is possible that it may take longer than 6 months for lung transplant recipients to comfortably increase their physical activity levels. Bossenbroek et al7 found that levels of physical activity varied in long-term lung transplant recipients and appeared to be associated with body weight (daily steps were 7,524 in individuals with normal weight, 5,919 in those who were overweight, and 3,146 in those who were obese). Determinants of a higher BMI included a low mean daily step count, a lower percentage of fat-free mass, and lower resting energy expenditure,7 and involvement in regular physical activity may decrease the risk of obesity in lung transplant recipients.
Change in HRQOL
Health-related quality of life improved posttransplant; however, there was variability in the timing of change in different dimensions. At hospital discharge, all measures of the SGRQ improved. This questionnaire measures disease symptoms and impact, and improvements may be directly related to the relief of ventilatory limitation, decreased respiratory symptoms, and liberation from supplemental oxygen after transplant. The generic SF-36 questionnaire only showed immediate improvements in some subscales and a worsening of bodily pain. Bodily pain is likely related to postoperative incisional pain that was not experienced before transplant and subsequently underwent natural healing by 3 months posttransplant. Pain may limit levels of physical activity. However at our center, rehabilitation is resumed at the time of hospital discharge and individuals are educated on the importance of increasing activity levels, flexibility exercises, and lifting restrictions and encouraged to use pain medications appropriately in order to fully participate in physical therapy. Subscales that did not improve immediately (such as social function and role–physical) would be anticipated to be lower during hospitalization when individuals are not in their home environment and are dependent on health care professionals for basic and instrumental activities of daily living. The largest change in physical activity levels occurred at 3 months posttransplant, which was the time point that showed improvements in the majority of the SF-36 scores and continued improvement in all SGRQ domains. A low pretransplant physical functioning score on the generic SF-36 HRQOL questionnaire was related to the change in daily steps, whereas the pretransplant activity score on the disease-specific SGRQ activity did not show a significant relationship. A disease-specific questionnaire for chronic lung disease may not be applicable to lung transplant recipients whose ventilatory impairment is largely alleviated following surgery. Individuals with low pretransplant self-reported physical functioning have more potential to improve their score after transplant, and a perception of a significant improvement in physical functioning and HRQOL may have led to a further increase in physical activity levels.
Change in Peripheral Muscle Strength
Participants in this study also had peripheral muscle weakness before and after transplant, which is consistent with previous studies.3,27,28 Daily steps were associated with lower body strength in 2 cross-sectional studies of transplant recipients more than 1 year posttransplant.6,8 However, in this study, pretransplant QT was not associated with the change in daily steps at 3 months. Peripheral muscle dysfunction is thought to be the main contributor to exercise limitation in lung transplant recipients,29 and aspects of muscle function such as muscle endurance and fatigue may have a stronger association with changes in physical activity than muscle strength.
This cohort was representative of the lung transplant population with heterogeneous disease and a wide age range.9 However, there were a few limitations of our study that need to be considered when interpreting the study results. Only lung transplant candidates who were ambulatory outpatients were recruited. There are missing data due to pretransplant and posttransplant mortality, prolonged hospitalization greater than 3 months, and readmission to hospital. These issues may have created a selection bias of participants who experienced a less complicated posttransplant course and potentially achieved better functional outcomes and higher levels of physical activity. This study was underpowered due to multiple regression; therefore, the results should be interpreted with caution.
Future Directions
The efficacy of alternative strategies to traditional exercise training before and after transplant in further increasing physical activity should be investigated, including the role of home rehabilitation and maintenance programs.30 Further investigation into the role of physical activity on long-term cardiovascular outcomes also is warranted. In conclusion, lung transplantation improves physical activity; however, lung transplant recipients do not reach predicted levels by 3 and 6 months posttransplant. Low pretransplant self-reported physical functioning is a predictor of greater change in daily steps after transplant. Rehabilitation efforts should focus on optimizing physical activity both before and after lung transplantation through exercise training, education, and counseling.
Footnotes
All authors provided concept/idea/research design and institutional liaisons. Mrs Wickerson, Dr Mathur, and Dr Brooks provided writing, data analysis, and facilities/equipment. Mrs Wickerson provided data collection and participants. Mrs Wickerson and Dr Brooks provided project management and fund procurement. Dr Mathur, Dr Singer, and Dr Brooks provided consultation (including review of manuscript before submission). The authors acknowledge Polyana Mendes, who assisted with data collection, and Denise Helm and Chaya Gottesman, who assisted with recruitment.
Ethics approval was obtained from the University Health Network.
Funding for this study was provided by the Ontario Lung Association through an Ontario Respiratory Care Society Research grant. Mrs Wickerson was supported in her graduate studies through research fellowships from the Ontario and Canadian Lung Associations. Dr Brooks is supported by a Canada Research Chair.
- Received April 18, 2014.
- Accepted November 25, 2014.
- © 2015 American Physical Therapy Association
References
