Post-Lung Transplant - Exercise Guidelines : ACSM's Health & Fitness Journal

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Post-Lung Transplant - Exercise Guidelines

LaSala, Toni T. Ph.D., ACSM-EP, EIM-II

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ACSM's Health & Fitness Journal: 11/12 2022 - Volume 26 - Issue 6 - p 31-37
doi: 10.1249/FIT.0000000000000818
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Abstract

INTRODUCTION

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Chronic inflammatory lung conditions affect approximately 40 million people in the United States (1). Individuals with chronic, end-stage lung disease who are not getting relief from current therapies are typically recommended for a single- or double-lung transplant. Lung transplantation is the surgical replacement of either one or two diseased lungs with healthy lungs from a human donor. More than 50,000 lung transplants are performed worldwide; however, in the United States, the year 2019 had the highest number of transplants (2,174) compared with 33 transplants done in 1988 (2). Since 1988, 36,100 lung transplants have been performed in those aged 18 to 64 years (2). Lung transplantation is not that common (2,000 people) compared with kidney transplants (18,000 people) in the United States because of the limited number of donors. Compared with other solid-organ transplants, there is a median survival rate of approximately 5.6 years because of the fragility of the lung(s) (3); however, improvements of survival rate because of advances in how organs are preserved, immunosuppressant therapies, and surgical techniques have been demonstrated (4).

The most common diseases resulting in lung transplantation are chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), idiopathic pulmonary fibrosis (IPF), and pulmonary arterial hypertension (PAH) (5). Diseased lungs make it difficult to breathe (dyspnea), leading to exercise intolerance and respiratory failure impairing one's quality of life. Damage to the lungs from COPD cannot be reversed. The etiology of each of these diseases is different and result in blocked airflow, making it difficult to breathe (Table 1). Therefore, individuals waiting for a lung transplant are encouraged to exercise to either maintain or improve their respiratory muscles and functional capacity and minimize the effects posttransplantation (6).

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TABLE 1 - Common Diseases That Affect the Lungs and May Result in Transplantation
Cystic Fibrosis
Genetic disease lungs — mucus-producing cells become thick and plug up tubes and ducts making it difficult to cough. Leads to severe lung infections.
Symptoms: cough, wheezing, exercise intolerance, lung infections
(Mayo Clinic, CF)
Idiopathic Pulmonary Fibrosis
Causes scar tissue to grow in the lung. Leads to slow delivery of oxygen to the lungs.
Symptoms: a persistent dry, hacking cough, chest pain or tightness, swelling in the legs, shortness of breath (SOB) during activity.
(Mayo Clinic, IPF)
Pulmonary Hypertension (PH)
It is a type of high blood pressure where the blood vessels in the lungs are narrowed, blocked, or destroyed. Classified as idiopathic (cause unknown), and related to heredity, illegal drugs, congenital heart disease, connective tissue disorder (scleroderma, lupus), HIV, and cirrhosis.
(Mayo Clinic, PH)

The most common diseases resulting in lung transplantation are COPD, CF, IPF, and PAH. Diseased lungs make it difficult to breathe leading to exercise intolerance then respiratory failure.

Antirejection, Antibacterial, and Antifungal Drugs

Recipients may take all or some of the following medications listed in Table 2 to suppress the immune system and will begin the medication regimen immediately after surgery to prevent rejection and may affect physiologic responses to exercise.

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Photos courtesy of Toni T. LaSala, Ph.D., ACSM-EP, EIM-II.
TABLE 2 - Antirejection, Antibacterial, and Antifungal Drugs and Their Effects on the Body and Exercise
• Antirejection medications or immunosuppressants ( https://columbiasurgery.org/lung-transplant/antibiotic-medications-after-lung-transplantation)
Glucocorticoids (Prednisone)
   can induce a selective atrophy of type II fibers (loss of muscle tissue)
   joint discomfort
   increased blood sugar levels (steroid-induced diabetes)
   excessive weight gain and obesity
   suppresses ability to absorb calcium resulting in osteoporosis, increasing risk of hip and vertebral fractures
   increases in cholesterol and triglyceride levels
   results in hypertension — may cause leg swelling or hypotension
   viral infections resulting in severe hemoglobin concentration — affects exercise tolerance and lactate threshold
Calcineurin (cyclosporine or tacrolimus)
   inhibits skeletal muscle dysfunction-reducing aerobic capacity
   infections (bacterial, viral, and fungal)
   hypertension
   nephrotoxicity — most common
   neurotoxicity — severe headaches, tremors, visual abnormalities, seizures
   myopathy or neuropathy
   electrolyte abnormalities
   gastrointestinal (nausea, vomiting, diarrhea, abdominal discomfort)
Mycophenolate
• Antibacterial medications to prevent the risk of infections such as aspergillosis ( https://columbiasurgery.org/lung-transplant/antibiotic-medications-after-lung-transplantation )
• Antifungal and antiviral medications (adjusted based on culture results (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222063/)

Skeletal Muscle and Cardiorespiratory Changes and Effects on Exercise

Life expectancy may improve in specific patients after lung transplant; however, exercise intolerance is characteristic of lung transplant recipients. It has been documented that muscle weakness and low levels of cardiorespiratory fitness are persistent and common after transplant even though pulmonary function is normal (7). Furthermore, research has shown that post-lung transplant recipients' cardiopulmonary function at rest is normal, where exercise testing demonstrates a reduced work rate and a reduced peak oxygen uptake by 40% to 60% compared with predicted values and did not improve through time (8). In contrast, it was found that V˙O2 values during cardiopulmonary exercise testing were close to normal as well as exercise capacity in long-term (>10 years) bilateral lung transplant survivors with normal lung function tests. Lung transplant recipients have demonstrated normal cardiac and ventilatory responses to exercise; however, skeletal muscle dysfunction has been shown to contribute to increases in dyspnea during exertion and limited exercise capacity (9).

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After transplant, there is a decline in skeletal muscle force and mass because of factors such as hypoxemia; malnutrition; high doses and/or long-term use of corticosteroids and is associated with limb atrophy; calcineurin inhibitors (cyclosporin A), which negatively impact mitochondrial respiration and muscle remodeling; and tacrolimus (10). These all contribute to significant muscle dysfunction, which then impacts ventilatory limitations and therefore contributes to exercise intolerance (11). Other factors such as how long one is hospitalized may result in intensive care unit (ICU) critical illness myopathies (muscle weakness caused by a dysfunction of the muscle fibers) (12). In addition, lack of muscle strength because of inactivity before transplant may affect impairment of skeletal muscle oxidative capacity resulting in peripheral limitations to exercise posttransplant (13). Few studies looked at exercise tolerance and muscle strength after lung transplant; however, Maury, Langer, Verleden, et al. (2008) were the first to demonstrate a reduction in skeletal muscle force immediately after lung transplantation, especially those who were in the ICU longer. Preassessments to postassessments have shown a modest improvement for isometric peak quadriceps force (QF) and significant improvement in exercise capacity as determined by the 6-minute walk test (6-MWT). The training program included cycling, treadmill walking, stairclimbing, and leg extensions of a 60% one-repetition maximum (1RM) 3 times/week for 3 months. Interestingly, QF was slower to recover for women compared with men, and after 3 months of training was still lower than pretransplant values (14). Although the study was observational, Maury, Langer, Verleden, et al. (2008) considered testosterone was reduced posttransplantation, resulting in slower recovery in women compared with men. More recently, a systematic review confirmed impairments in exercise capacity (15). They also looked at evidence for the effect of exercise training on functional outcomes for lung transplant recipients and found that a small number of studies demonstrated beneficial effects on skeletal muscle strength as well as functional and maximal exercise capacity (15).

After transplant, there is a decline in skeletal muscle force and mass because of factors such as hypoxemia, malnutrition, high doses of corticosteroids, calcineurin inhibitors (cyclosporin A), and tacrolimus and may result in significant muscle dysfunction, which limits exercise for more than 1 year posttransplant.

Physical activity as well as respiratory exercises to improve breathing should be an integral part of rehabilitation before and after transplant to address deconditioning and the adverse effects of medications and should begin as soon as one gets out of bed (15). Exercises should be prescribed to improve activities of daily living and improve breathing in an effort to reduce the sense of dyspnea, which will increase the quality of life and long-term outcomes (Table 3). In addition, exercises to increase upper body (UB) and lower body (LB) strength and endurance help to prevent osteoporosis and low back pain as well as reduce anxiety and body weight (16). Aerobic conditioning may improve cardiorespiratory endurance such as walking, stair climbing, arm ergometry, or cycling. Intensity is based on the modified Borg or Dyspnea Scale (Table 4). A good starting point is 85% of the walking distance for the 6-MWT and a percentage of the peak work rate from the cardiopulmonary exercise test (CPET) (17) (Table 5). Stretching also is recommended by the American College of Sports Medicine (ACSM) (18), the American Thoracic Society (ATS) (19), and the American Association of Cardiovascular and Pulmonary Rehabilitation (AACPR) (20) with inclusion of balance exercises (Table 6) because most are on multiple medications and may have other underlying conditions. Finally, water exercises also are recommended for those with physical limitations and those who are in pain (Table 6) (21). Detailed recommendations by ACSM (18), ATS (19), and the European Respiratory Society (ERS) (22) are listed in Table 6. Although all types of exercises are recommended, some that are considered high risk and not recommended are scuba and sky diving because they can increase pressure in the lungs and contact sports because of the risk of broken bones (23).

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TABLE 3:
Breathing Exercises to Improve Respiratory Muscles and Function
TABLE 4 - Borg Modified Dyspnea Scale
0 Not breathless
0.5 Very, very, slight (just noticeable)
1 Very slight
2 Slight
3 Moderate
4 Somewhat severe
5 Severe
6
7 Very severe
8
9 Very, very, very severe
10 Maximal
Rate the difficulty of your breathing. 0 is no difficulty at all, where 10 is when you are having extreme difficulty breathing.

TABLE 5 - Exercise Testing Guidelines for Posttransplant
Functional Assessments
• The 6-minute walk test (6-MWT) — is used to measure function in those undergoing transplantation and has demonstrated that it is useful to assess those who need a transplant sooner rather than later. The American Thoracic Society recommends the 6-MWT be done in addition to cardiopulmonary testing (Brooks, et al. 2007).
• One-minute sit-to-stand (STS) test — use when the 6-MWT cannot be performed. STS was found to be a valid functional exercise test (Kohlbrenner, et al., 2020).
• Stair climbing — obtain baseline either number of stairs or time in minutes or seconds.
Maximal Aerobic Capacity
• Cardiopulmonary exercise test (CPET) – to determine the physiological competence of performance under stress. Performed on either a cycle ergometer or a treadmill with a 12-lead electrocardiogram and measure heart rate, blood pressure, blood lactate, oxygen saturation, and rating of perceived exertion (RPE).
Muscle Strength
Muscle strength is used to determine muscle weakness in major muscle groups. Measures should include 1RM or maximal number of reps.
Flexibility
Depending on client's limitations; sit and reach, seated hamstring stretch, back extension, shoulder extension
Neuromuscular
To determine fall risk, balance, gait, and walking speed. Measures include Berg Balance Scale (Berg, et al. 1989), timed up-and-go (TUG) (Podsiadlo, 1991), short performance battery (SPPB) (Welch, et al. 2020).
Terminate exercise testing when SpO2 is ≤80% but may start again >85% and monitor symptoms (SOB, dizziness, chest pain, and/or tightness [Holland, et al., 2014]).

TABLE 6 - Exercise Recommendations
Aerobic Resistance Balance/Fall Prevention Flexibility Aqua Therapy
Frequency/time: 3–5 days/week
5-minute increments if unable to do continuously.
Increase to 60 minutes.
Include rest periods.
Circuit training 4–6 min
Monitor SaO2
2–3 days/week 3–5 days/week 3–5 days/week.
Hold each stretch for 30–60 seconds
2–4 reps.
1–2 days/week
30–60 minutes/session
Type: Walking, cycling, upper body ergometer. Free weights, weight machines, body weight exercises. Static activities: e.g., reach while standing, single-leg stand.
Dynamic: Tai Chi, yoga, heel toe and tandem walks.
Static, dynamic and/or proprioceptive neuromuscular facilitation. Any type of activity with the head above water.
Must have no contraindications.
Intensity: Moderate/vigorous
intensity: 50%–80% of peak work rate 4–6 on the modified Borg scale
30%–40% 1RM (UB)
50%–60% 1RM (LB) or 8–15 comfortable reps.
Consistency, structured progression.
Meet the need for the individual.
Progress to add balance challenges.
To point of tension or slight discomfort. RPE: 3–4 modified BORG or 12–14 BORG dyspnea: 3–4 modified BORG
ACSM, ATS, ERS, AACPR, TSANZ, BTS, CTS.

Exercise Programming — Posttransplant

Although exercise is beneficial in the general population, a variety of factors need to be considered for those who have had organ transplants, such as medications, the disease process, and altered body composition (23). There is convincing evidence to support that exercise is an essential component that will improve functional exercise capacity and muscle strength, decrease fatigue, and improve health-related quality of life (6). However, specific recommendations for exercise programming are not possible because of the variety of protocols and outcomes. Recommendations may be extracted from the studies and from heart transplant as well as chronic pulmonary disease populations (15). A recent randomized control trial (7) investigated the effect of a 12-week high-intensity interval training on V˙O2peak and muscle strength. Although there were no significant differences in V˙O2peak, there seems to be some benefit in those who followed the program, with significant improvements in muscular strength. Another interesting finding was the participants who began an exercise program within 2 years after transplant showed greater increases in their V˙O2peak. These results are consistent with those of Langer et al. (2012), who found an increase in muscular strength after a 12-week endurance training and resistance training program with no effect on V˙O2peak. In addition, specific guidelines for exercise programming are difficult because of the variety of protocols and outcomes. Finally, all components of exercise also should be addressed (aerobic, muscle strength and endurance, balance, flexibility) as well as breathing exercises (24,25), and it is recommended to follow the frequency, intensity, time, and type (FIIT) principle. Programming should be based on the type of lung disease, patient's level of fitness, and pulmonary function tests. Table 6 is a summary of exercise recommendations from randomized control trials and guidance from ACSM (18), ATS (19) ERS (22), AACPR (20), Lung Foundation/Thoracic Society of Australia and New Zealand (TSANZ) (16), British Thoracic Society (BTS) (26), and the Canadian Thoracic Society (CTS) (27), which were developed for Exercise and Sports Science Australia (28).

Although exercise is beneficial in the general population, a variety of factors need to be considered such as medications, the disease process, and altered body composition for those who have had organ transplants. Therefore, exercise programing should be prescribed to the type of lung disease, patient's level of fitness, and pulmonary function tests.

Although exercise is beneficial in the general population, a variety of factors need to be considered such as medications, the disease process, and altered body composition for those who have had organ transplants. Therefore, exercise programing should be prescribed to the type of lung disease, patient's level of fitness, and pulmonary function tests.

Other guidelines to consider using during the exercise session are shown in Table 7.

TABLE 7 - Important Guidelines to Consider During Exercise
1 2 3 4 5
Monitor oxygen saturation or desaturation during exercise.
Use a dyspnea scale or the use of a pulse oximeter SpO2 should be no less than 88% during exercise, resume at 90%.
Monitor rate of perceived exertion.
RPE scales — for those who are on medications that suppress the heart rate (modified Borg).
Listen to musculoskeletal complaints.
Might be indicative of postsurgical pain or complications related to medications such as calcineurin inhibitors or statins.
Be aware of the time of day to exercise.
Response may be different for each person because of adverse effects of medications.
Do not exercise in extreme temperatures (higher than 90°F or lower than 32°F) and humidity (more than 50% or less than 30%).
Use of hypertensives and diuretics may increase complications.

In conclusion, pretransplant and posttransplant skeletal muscle issues, surgical factors, and medications result in reduced oxygen consumption and skeletal muscle fatigue, which is the most common reason for exercise termination. Exercise is an important component in pretransplant and posttransplant recovery, and many will achieve near-normal lung function, but it may take longer for the muscles of the lower extremity to recover. Research has demonstrated that with consistent exercise, there is improvement in leg strength and lung function resulting in better long-term outcomes. Finally, more randomly controlled trials need to be done to determine optimal exercise programming guidelines.

BRIDGING THE GAP

Medications to suppress the immune system begin immediately after lung transplant surgery to prevent rejection and may affect physiologic responses to exercise. Muscle weakness and low levels of cardiorespiratory fitness are persistent and common after transplant even though pulmonary function is normal. Exercise testing should be done to evaluate exercise tolerance and which system is limiting exercise and will determine how much exercise is appropriate and safe for the client. The type of exercise test and modality as well as exercise programming should be based on the individual and the stage of disease.

References

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Keywords:

Lung Transplant; Exercise Tolerance; Transplant Medications; Skeletal Muscle; Exercise Prescription

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