Physical therapy in lung transplantation.

[Downs AM. Physical therapy in lung transplantation. Phys Ther. 1996;76: 626-642.] Key Words: Cardiopulmonary physical therapy; Exercise; Lung; Pulmonary, thoracic surgery; Rehabilitation; Transplantation.

Lung transplantation is used throughout the world as a treatment for end-stage lung disease. Increasing numbers of physical therapists are being exposed to these patients, and they also are being challenged to maintain optimal function and level of activity for patients awaiting lung transplantation. Treatment of a lung transplant recipient requires knowledge of possible complications and their effects on activity and of the appropriate progression of activity postsurgically.

Although much of the physical therapy for lung transplant recipients is similar to that for patients with other organ transplants, the unique properties of the lung present the clinician with additional considerations. Physical therapy for lung transplant recipients requires a sound grasp of pulmonary anatomy and physiology as well as knowledge of pulmonary disease and normal and abnormal responses to exercise.

History of Lung Transplantation

Hardy,[1] in 1963, performed the first human lung transplant at the University of Mississippi after many years of laboratory study. The patient died of renal failure and malnutrition after surviving for 18 days. Successive attempts at different centers were made over the next 20 years, but there was no long-term success.[2-4] There was a need to improve bronchial healing because the portion of the main-stem bronchus where the transplanted lung is attached is predisposed to ischemia, having no systemic arterial blood supply.[5,6] The use of high dosages of steroids immediately after transplantation also resulted in delayed healing.[7] To remedy this problem, an omental wrap or omentopexy around the bronchial anastomosis was introduced.[8] The omentum, a fatty, vascular tissue attached to the intestines, was brought up from the abdomen and wrapped around the anagtomosis to provide an adequate blood supply to the bronchus.

In 1983, the omentopexy procedure was used by Cooper at the University of Toronto to perform the first successful single--lung transplant on a patient with end-stage pulmonary fibrosis.9 Three years later, Cooper and colleagues[10] performed the first successful double-lung transplant on a patient with end-stage emphysema.

Recent modifications of lung transplantation include foregoing the omentopexy technique and using a procedure for telescoping the bronchus to diminish the ischemic area.[11] Single-lung transplants are becoming increasingly frequent for patients with pulmonary vascular disease and for patients with chronic obstructive pulmonary disease. The development of living related lobar transplantation by Starnes at the University of Southern California has expanded the available donor pool.[12] The introduction of new forms of immunosuppressive medications continues to alter the protocols at different lung transplant centers.[13]

Indications

Lung transplantation is generally reserved for patients with irreversible, end-stage pulmonary disease.[14-19] Candidate selection criteria include limited life expectancy due to pulmonary disease, limited use of steroids (less than 10 mg per day), no major coronary artery disease, no other systemic disease, and an age of less than 50 years for double-lung transplantation and of less than 60 years for single-lung transplantation.[17] In addition, candidates should be nonsmokers and should be ambulatory, possess adequate social support and psychological stability, and demonstrate compliance with medical regimens. Criteria for patient selection have been modified at various centers.[18,19]

Indications for single-lung transplantation include chronic obstructive pulmonary disease (including alpha-1 antitrypsin deficiency), pulmonary fibrosis, and primary pulmonary hypertension. Through 1994, emphysema and alpha-1 antitrypsin deficiency accounted for almost 60% of all single-lung transplants performed.[20] The shortage of donors makes it prudent to use single-lung transplantation whenever possible, as only 1 out of every 10 to 15 potential donors has lungs suitable for transplantation.[21]

Double-lung transplantation is indicated for patients with an infective process (eg, cystic fibrosis, bronchiectasis) and also has been performed for chronic obstructive pulmonary disease, pulmonary fibrosis, and primary pulmonary hypertension. Patients with cystic fibrosis comprised more than 35% of patients with double-lung transplants performed through 1994, with more than 30% performed for emphysema and alpha-1 antitrypsin deficiency.[20]

Primary pulmonary hypertension had initially been treated with heart-lung transplantation, but more recently isolated single- or double-lung transplantation has been used with varying success.[17,21,22] Through 1994, patients with primary pulmonary hypertension comprised more than 9% of patients with single-lung transplants and 10% of patients with double-lung transplants.[20] Discussion continues on the most appropriate surgery for this challenging population.[12,23]

Pediatric lung transplantation statistics have been reported for patients who are less than 18 years of age. Cystic fibrosis is the primary indication for double-lung transplantation in children, whereas primary pulmonary hypertension is the primary indication for single-lung transplantation.[24] Pediatric lung transplantation also has been performed for congenital heart disease.

Donor/Recipient Matching

There is a shortage of suitable donors for transplantation; only 1 out of every 10 to 15 available donors has lungs suitable for transplantation.[21] Requirements for the donor lung(s) are strict. The donor must have a partial pressure of oxygen of 300 mm Hg on 100% oxygen with 5 cm of positive end-expiratory pressure, a normal chest roentgenogram, clear bronchoscopy, and no significant chest trauma or pulmonary contusion.[14]

In matching a donor with a prospective recipient, the guidelines include compatibility of ABO blood group, of thoracic dimensions (chest circumference measurements as well as chest roentgenogram evaluation), and of predicted lung volumes based on height, age, and gender.[14] Human leukocyte antigen matching is not currently used to match donor to recipient because of the increased time required to receive the test results.

The United Network of Organ Sharing maintains a list of eligible recipients. Priority on the list is determined primarily by the date the candidate was placed on the list. The only distinction between diagnoses or clinical status of the patients placed on the lung transplant waiting list involved the crediting of 90 additional days to patients with idiopathic pulmonary fibrosis.[25]

Evaluative Studies

As the waiting period for a transplant has increased, it has become more difficult for referring physicians to estimate the appropriate timing for lung transplant evaluation. In this process, many factors must be considered in addition to declining pulmonary function, including the frequency of hospital admissions, sensitivity of infecting organisms to antibiotics, and the functional status of the patient.[16]

After an initial screening, a decision may be made to proceed with a formal evaluation, and the patient is admitted for a short hospital stay or studies may be scheduled on an outpatient basis. These studies provide information about the presence of an active systemic disease, renal or hepatic insufficiency, severe right ventricular dysfunction, or significant coronary artery disease, any of which could be contraindications to lung transplantation. 14 Pulmonary studies assist with quantifying the severity of impairment of diffusion capacity, ventilation, and gas exchange. The evaluation procedures are listed in Table 1. In addition, many members of the lung transplant team conduct interviews or evaluations of the lung transplant candidate (Tab. 2). The lung transplant coordinator schedules the evaluation, compiles the results, facilitates communication among team members, and communicates with the prospective transplant candidate and his or her family.

Table 1.
Tests and Procedures for Lung Transplant Evaluation(a)

Laboratory
  Arterial blood gases
  Complete blood count
  Electrolytes-BUN-creatinine-liver function tests
  Chest roentgenogrom
  Sputum culture
  Urinalysis

Pulmonary assessment
  Pulmonary function tests
  Ventilation/perfusion scan
  Computed tomography scan when indicated

Cardiac assessment
  12-lead electrocardiogram
  Echocardiogram
  MUGA scan
  Right heart catheterization when indicated
  Coronary angiography for patients >40 y of age

Other
  Bone density scan when indicated

(a) Adapted from Egan TM, Kaiser LR, Cooper JD. Lung
transplantation. Curr Probl Surg. 1989:26:673-752. BUN=blood, urea,
nitrogen; MUGA=multiple gated acquisition.
Table 2.
Evaluation by Lung Transplant Team Members(a)

Medical staff                 Medical history
                              Nature and progression of lung
                                disease
                              Smoking history
                              Prior surgery
                              Medications, including steroid
                                history
                              Physical examination
Physical therapist            Exercise tolerance test and
                                exercise prescription
                              Musculoskeletal assessment
                              Cough/mucociliary clearance
Dietician                     Ideal body weight
                              Caloric intake
Social worker                 Psychosocial assessment
Psychologist/psychiatrist     Psychological testing

(a) Adapted from Egan TM, Kaiser LR, Cooper JD. Lung transplantation.
Curr Probl Surg. 1989;26:673-752.

The results of the evaluative studies are discussed by the lung transplant team members, and the determination of candidacy is made. The varied perspectives of members of the lung transplant team are the key to forming a comprehensive view of the patient's current status and acceptability for transplantation. Physiological and psychosocial factors and fiscal resources all play important roles in the outcome of the transplantation process. The importance of receiving accurate information is paramount to the patient's decision to pursue transplantation. The members of the lung transplant team should provide a realistic picture of lung transplantation and its outcomes.

Physical Therapy Evaluation

The physical therapist identifies causes and effects of impaired ventilation and gas exchange, as reflected by the lung transplant candidate's cardiopulmonary status and functional capacity. The therapist should assess the patient's ventilatory effort, musculoskeletal function, mucociliary clearance, and exercise tolerance.[26]

Breathing or ventilation assessment is initiated by taking a history of the patient's symptoms (eg, shortness of breath, dyspnea on exertion) and their effect on functional ability. Observation of the patient includes the skin color, breathing pattern and depth, preferred body position, use of accessory muscles of respiration, and work of breathing. Palpation of the chest wall provides information about the movement of the diaphragm and other muscles of respiration and areas of decreased chest expansion.

Components of the musculoskeletal evaluation assess mobility, general or musculoskeletal strength, and posture and establish a baseline against which future comparisons may be made.[27] Range of motion of the thoracic and cervical spines and shoulder girdle should be assessed, as limitations in these areas may restrict thoracic expansion. Postural deviations and muscle group imbalances may result in decreased diaphragmatic excursion, and assessment of these factors also should be included.

Several assessments assist with evaluation of mucociliary clearance. The patient's report of symptoms (eg, audible wheezing, coughing, sputum production) and previous history of airway clearance techniques and their effectiveness should be obtained. The lungs are auscultated for the presence of crackles and wheezes, and the quality and productivity of coughing and the quantity and consistency of sputum are evaluated. The conventional treatment for secretion clearance remains postural drainage and percussion. The evaluation period provides an opportunity to introduce alternative methods for airway clearance that may be more effective[26-28]

The physical therapist also assesses the patient's exercise tolerance. Exercise tolerance is determined at the time of the initial evaluation for lung transplantation and at intervals during the waiting period in order to reassess the patient's status. An exercise tolerance evaluation should be omitted in patients with primary pulmonary hypertension in whom exercise testing is not appropriate; this is determined on an individual basis.[27]

The 6-minute walk test (6MW) is a widely used assessment of exercise tolerance in patients with pulmonary disease.[29,30] The 6MW was adapted from the original 12-minute field test.[31] In conducting a 6MW, the patient is encouraged to cover as much ground as possible over a flat, measured course in 6 minutes. Supplemental oxygen is administered as needed to maintain oxygen saturation above a prescribed level (usually 88%-90%). The patient is allowed to stop and rest as needed, but the clock is not stopped. The tester needs to carry all necessary equipment and needs to walk slightly behind the patient, allowing the patient to set the pace unencumbered. Due to the effects of learning and motivation, it is essential to repeat the 6MW and report the better effort.[32,33] Given the low functional status of patients with end-stage lung disease, it may be necessary to administer the test on different days to allow ample recovery time. Reports of 6MW evaluations for lung transplant candidates from various centers average from 100 to 400 M.[17,34-36]

The 6MW can be administered in a clinic or hospital corridor using only a stopwatch, a portable pulse oximeter, and portable oxygen, if needed. The 6MW is easily reproducible,[33] well-tolerated by most patients, and not time-consuming, making it inexpensive. Because the 6MW is self-paced, even patients with severe limitations are able to complete the test. A disadvantage of the 6MW is the inability to record the patient's ventilatory parameters or electrocardiographic activity during the exercise test; the pulse oximeter provides information about heart rate, but telemetry is necessary to obtain information about dysrhythmias. The 6MW also is difficult to administer postoperatively when patients attain a higher exercise capacity and are able to run.

Exercise tolerance in patients with pulmonary disease may be assessed using a treadmill or cycle ergometer.[37] Exercise levels should be advanced by small increments in work load (0.5 metabolic equivalents [METs] per stage) and may be continuous or discontinuous with short durations at each stage.[37] A standard Bruce protocol treadmill test is not well-suited for most patients with pulmonary disease.[37] This test, however, has been modified to include stages 0 and 1/2 in addition to the standard stages. This modification allows patients who are incapable of exercise at stage 1 to be assessed.[35] Some centers use their own submaximal treadmill test protocols for purposes of evaluation and subsequent reevaluation.[27]

Exercise testing on a treadmill allows closer physiologic monitoring of ventilatory and hemodynamic parameters than does the 6MW and, because it is externally paced, does not require repetition for increased reliability.[33] Reevaluation of high-functioning transplant recipients is more easily accomplished on a treadmill or cycle ergometer. These tests, however, are more expensive and more technically difficult to perform than the 6MW and depend on availability of equipment.

Complete cardiopulmonary exercise testing is not routinely performed as part of the evaluation for lung transplantation, but Howard et al[38] have reviewed a few cardiopulmonary exercise studies that have been reported. In cardiopulmonary exercise studies of patients with primary pulmonary hypertension or Eisenmenger's syndrome (cyanosis, particularly during exercise, resulting from right to left intracardiac shunt), transplant candidates exhibited severely reduced aerobic capacity, with abnormalities in the pulmonary circulation cited as the reason for the exercise limitation.[39] In another group of lung transplant candidates with varying diagnoses undergoing exercise testing, limitations in aerobic capacity were shown.[40] In this study, the reduction in aerobic capacity was attributed to a combination of abnormalities in ventilation and circulation.

The physical therapy evaluation is used to develop an individual exercise prescription for the patient and to provide input to the lung transplant team about the candidate's exercise limitations. Regardless of whether the candidate is scheduled for transplantation, the information gained from the evaluation should be provided to the patient, family, and referring physician. This information is useful in prescribing appropriate activity/ exercise guidelines for the patient. The physical therapist (in conjunction with the physician) may counsel the patient about supplemental oxygen needs during exercise. In addition to endurance exercise, instruction in breathing exercises, relaxation techniques, energy conservation measures, and mobilization/flexibility exercises may be prescribed, as indicated.

Education

After a candidate has been accepted onto the waiting list, the process of educating the patient and significant others continues. The physical therapist plays an important role in this process because the therapist may be asked to reassess the exercise tolerance of the patient during the waiting period. Because the time from evaluation to the time of transplant can be as long as 2 years, it may be beneficial to schedule an education session when the candidate nears the top of the list to review components of physical therapy intervention in the postoperative period.

Discussions about the postoperative period conducted prior to transplantation will provide the patient with realistic expectations. Topics to discuss include the typical preoperative and postoperative courses; the intensive care environment; mechanical ventilation of the lungs; airway clearance; and treatments such as breathing control and coughing maneuvers, body positioning, chest wall mobility exercises, and mobilization and activity progression.

These issues may be addressed in a classroom setting with a group small enough to encourage questions and discussion and in one-on-one discussions during exercise sessions. A lung transplant support group that meets regularly is valuable in combining education with social support.

Preoperative Rehabilitation

Candidates waiting for a donor are encouraged to stay as active as possible, and some candidates are able to enroll in a local pulmonary rehabilitation program for supervised exercise. When a candidate's name approaches the top of the waiting list, some lung transplant programs require the patient to relocate near to the center so that they can participate in a monitored exercise program.[41,42] This program enables them to be followed by the medical staff and to be readily available at the time of transplantation.

The need for rehabilitation in the preoperative period arises from limitations in exercise tolerance, decreased strength and thoracic mobility, and altered posture. Thus, preoperative rehabilitation should include training to improve ventilation and mucociliary clearance, and exercise with aerobic, strengthening, and stretching components, with supplemental oxygen, as indicated.[43] The goal in the preoperative phase of rehabilitation is to enhance the physical condition of the patient to withstand the stresses of lung transplantation. Education about all aspects of lung transplantation should continue during this period.

Each patient should have a specific exercise prescription that includes guidelines for mode, intensity, frequency, and duration of exercise. Progression of exercise should occur at an individual rate. Acute changes in the patient's status, sometimes requiring hospitalization, must be expected as a result of the progression of the disease. These changes require reevaluation of the exercise prescription and a possible cessation of exercise until the patient is clinically stable.[44]

Modes for aerobic exercise may include the cycle ergometer and the treadmill, or a combination of these modes. A stair climber may not be tolerated initially, but will be useful for patients with higher exercise capacity or for patients who have increased their exercise tolerance over time. Although the increased ventilatory demand of upper-extremity exercise versus lower-extremity exercise may contribute to dyspnea in patients with pulmonary disease, upper-extremity exercise training has been safely implemented in rehabilitation programs.[45,46] In patients with severe pulmonary disease, however, upper-extremity exercise has been shown to result in decreased exercise duration and may result in dyssynchronous thoracoabdominal breathing, demonstrating the need for caution when using this mode of exercise in patients awaiting lung transplantation.[47]

Exercise intensity must be determined for each individual, and it must be carefully monitored.[37] The appropriate exercise intensity for a patient with lung disease can be determined using a variety of methods individually or in combination. Target heart rates have been applied to patients with pulmonary disease.[48] An exercise program that uses 60% of peak heart rate (as determined by an exercise test) as a target has been shown to increase exercise tolerance.[37,48] In severe lung disease, predicted maximal heart rates are not reached with exercise testing because exercise is limited by pulmonary, not cardiac, function. This finding points to the need for a tool that can be used to prescribe and monitor exercise intensity by dyspnea.[37] The dyspnea index shown in Figure 1 is such a tool. This index involves noting the number of breaths a patient must take while counting from 1 to 15.49 Another measure is the dyspnea scale, a four-point scale (ie, 1-4) by which the patient rates the degree of dyspnea during exercise.[37] An alternative, the Borg Rating Scale of Perceived Exertion (RPE),[50] is a measure of the overall effort needed during an activity (or at rest) (Fig. 2). In using the RPE scale, the patient is asked to take into account all bodily sensations that contribute to the effort of exercise.[50] This scale has been used with patients who have pulmonary disease to complement the information gathered with other measures.[51]

The frequency and duration of the exercise prescribed depend on the patient's level of exercise capacity. Interval training may be more appropriate than continuous exercise for patients with end-stage lung disease because of its decreased ventilatory demand.[37] The rest periods can gradually be decreased and the exercise intervals can be increased to progress the patient to continuous exercise.[37] Because interval training incorporates rest or periods of relatively lower exercise intensity, the session may be spread over a prolonged period of time and tolerated well. Patients who are able to exercise at very low levels (less than 3 METs) benefit from shorter periods of exercise (5-10 minutes) performed more often during the day. For patients who are able to tolerate moderate levels of exercise (3-5 METs), daily exercise is recommended. Once a patient is able to exercise for 20 minutes continuously, he or she may exercise four or five times a week with the goal of completing 30 minutes of continuous exercise.

The exercise prescription should include an individual strengthening program, often using Thera-Band[R],(*) free weights, or items found at home. Chest mobility and postural correction should be addressed with a prescription of individual stretching and flexibility exercises to improve thoracic expansion. Proprioceptive neuromuscular facilitation diagonal patterns, for example, can be used to increase thoracic mobility.

Impaired mucociliary clearance may be augmented by techniques for improving coughing and airway clearance. Several techniques are available to supplement or replace conventional postural drainage, percussion, and coughing.[52] Some techniques use controlled breathing to mobilize secretions. The active-cycle-of-breathing technique uses alternate periods of breathing control, thoracic expansion exercises, and huffing with an open glottis in place of coughing.[53] Autogenic drainage is a method using three different levels of breathing in a controlled fashion to mobilize pulmonary secretions.[28,52] Additional equipment is required for other techniques. Positive expiratory pressure therapy uses collateral ventilation to mobilize secretions with a mask or mouthpiece apparatus.[28] The Flutter valve([dagger]) is a pipe-like device used to interrupt expiratory airflow. It promotes secretion mobilization with a combination of positive expiratory pressure and airway oscillation.[28,52] The ThAIRapy[R] system([double dagger]) consists of a vest worn by the patient and tubing that connects to an air-pulse generator. This device provides various frequencies of oscillation to provide increased expiratory flow for clearance of airways.[28] Use of these techniques requires an evaluation as to their effectiveness with each patient, and additional treatment sessions may be needed for the patient to become independent in the use of these methods.[28]

Some interventions are intended to improve function of the pulmonary system. Diaphragmatic and segmental breathing exercises increase lung volume and improve gas exchange.[54] Exercise training of inspiratory muscles may be indicated to improve their function.[55] Other interventions are meant to help the patient adjust to the low functional capacity caused by pulmonary disease. Energy conservation techniques can be useful in helping a patient accomplish daily activities with less effort expended and to spread the effort throughout the day. Relaxation techniques may be used to decrease the energy used in overactive muscles and to decrease the anxiety that may be present in patients with pulmonary disease.

The regular and extended contact that the physical therapist has with the patient during the waiting period for a transplant puts the therapist in a unique position. The physical therapist may be the first member of the transplant team alerted to an exacerbation of a medical problem or a marked decline in a patient's status requiring medical attention. Many patients and family members come to depend on the physical therapy staff for support and encouragement during the time many transplant recipients refer to as the most frustrating of the entire transplantation process.

Exercise Responses of Patients With End-Stage Lung Disease

Patients with end-stage lung disease demonstrate reduced exercise tolerance.[46] Close monitoring of a patient's response to exercise enables the physical therapist to titrate the exercise program to achieve the optimal rate of progression while limiting untoward consequences.

An initial or baseline measurement should be taken, and measurements should also be recorded during exercise and during recovery. The patient's respiratory rate, oxygen saturation, heart rate, blood pressure, RPE or dyspnea ratings, and amount of supplemental oxygen needed to maintain oxygen saturation at an appropriate level should be monitored. Auscultation of breath sounds, hand-held spirometry measures (forced vital capacity and forced expiratory volume in 1 second), and weight also are noted.[27]

The need for supplemental oxygen is determined by the exercise evaluation. A physician's order or a standing order should be obtained to allow titration of the oxygen to maintain an appropriate level of oxygen saturation during exercise and recovery. Continuous pulse oximetry is used throughout the exercise session.

Exercise should be terminated, at least temporarily, and the exercise prescription altered if any of the following adverse effects are observed: tachycardia greater than 85% of predicted maximum heart rate, bradycardia, blood pressures greater than 180/110, ap increase in diastolic pressure greater than 20 mm Hg or a drop in systolic pressure, chest pain, severe dyspnea, blurred vision, deterioration in neurological status, or an oxygen saturation of less than 85% despite maximum oxygen supplementation.[7]

The likelihood of exercise-induced hypoxemia during aerobic exercise and the increased demand on the cardiopulmonary system during resistive exercise necessitates stringent monitoring of all exercise program components.[56,57] After a safe and optimal level of exercise has been determined, the patient can be placed on a home program with education in recognizing unfavorable responses and guidance as to when to seek out medical attention.

Improvements in exercise capacity and functional status have been reported in patients with severe lung disease following exercise training, even though lung function did not improve.[58,59] Increased exercise capacity has been shown to reduce morbidity after thoracotomies.[60] Compared with education alone, pulmonary rehabilitation has been shown to increase exercise performance and to decrease muscle fatigue and shortness of breath.[61] Even though pulmonary function continues to decline in lung transplant candidates, exercise tolerance, independence with activities of daily living, and quality of life all improve during the preoperative waiting period. Improvements in the 6MW distance have been demonstrated during the preoperative phase of rehabilitation and are believed to improve postoperative recovery.[17,36,42]

Surgical Technique

The incision used for a single-lung transplant is a standard posterolateral thoracotomy.[14] If either side is equally suited to transplantation, the left side is preferred because the surgery is easier technically.[14]

Double-lung transplants were initially performed via a median sternotomy with a tracheal anastomosis.[62] Subsequently, transplantation with bilateral main-stem bronchial anastomoses was used.[62] Currently, the procedure is performed with sequential single-lung transplants, using separate bronchial anastomoses in which cardiopulmonary bypass is needed much less frequently.[35] The incision used for this procedure is a bilateral transverse thoracosternotomy, also known as the "clamshell incision."[63] This approach provides the surgeon with increased exposure of both pleural spaces and with better control of bleeding.

The technique of omentopexy was introduced to address the problem of poor bronchial healing at the anastomosis.[8] A small upper midline incision is made to mobilize the omentum from the colon. The omentum is brought upward into the chest and wrapped completely around the bronchial anastomosis and secured.[21] Omentopexy was utilized in the first successful lung transplant surgery and was used routinely for years at various lung transplant centers with the aim of improving bronchial healing. Currently, however, omentopexy is used far less frequently, as other surgical and perioperative strategies have been introduced.

Another technique for revascularizing the anastomosis involves use of the internal mammary artery. In this technique, the internal mammary artery and the surrounding tissue are mobilized from the anterior chest wall, and the pedicle is wrapped completely around the anastomosis and secured.[64] Yet another approach aimed at addressing the problem of poor bronchial healing is the telescoping technique.[11] This technique involves overlapping one ring of the bronchus and shortening the length of donor airway to minimize problems with blood supply.

Khaghani et al[64] conducted a randomized study to compare wrapping the anastomosis of a single-lung transplant with omentum, wrapping the anastomosis with an internal mammary artery pedicle, and not wrapping the bronchus. The results demonstrated that none of these techniques prevented complications with bronchial healing; patients from all three groups required bronchial dilatation, and one patient from each group required a stent.[64] The authors pointed to the shortened bronchus in the unwrapped anastomoses as a key to minimizing the amount of potentially ischemic tissue.

Egan and Cooper describe the surgical aspects of lung transplantation in this way:

Transplantation of the lung ... is a complex logistic undertaking

requiring a large team of professionals who attend to

... patient selection, preoperative rehabilitation, donor

selection, postoperative care, immunosuppression, rehabilitation,

and long-term follow-up. The operation itself represents

an integral, but small, component.[65(p204)]

Acute Postoperative Rehabilitation

The physical therapist should be cognizant of the many issues confronting the transplant recipient in the immediate postoperative period. Problems following lung transplantation include impaired gas exchange, shunt, impaired mucociliary clearance, and disrupted lung fluid balance.[14] In addition, these problems are confounded by intubation and mechanical ventilation, prolonged static positioning during surgery, immunosuppression, pain, recumbency, and restricted mobility.[26,27]

Denervation of the transplanted lung(s) and interruption of the pulmonary lymphatics play a part in the altered pulmonary physiology after lung transplantation. Lung denervation causes a ventilation-perfusion imbalance until recovery of autonomic function occurs and contributes to decreased mucociliary clearance.[66,67] The increase in extravascular water from disrupted pulmonary lymphatics is evident in decreased pulmonary compliance, radiologic evidence of congestion, and an increased arterial-alveolar gradient.[41,66,68]

Body positioning and mobilization by the physical therapist in the acute postoperative period is important. Bed rest has many negative effects on the cardiopulmonary system, including orthostatic intolerance, reduced ventilation, increased resting heart rate, and decreased oxygen uptake.[69-71] Body positioning and mobilization have been shown to benefit oxygen transport by promoting better ventilation-perfusion matching and enhancing arterial oxygenation.[69,72,73] Changing the patient's position from supine to side lying or upright has been noted to increase drainage from chest tubes, and positioning to augment the drainage of pulmonary secretions has been shown to be effective.[74-76]

Decreased mucociliary clearance has been demonstrated in denervated lungs.[67] Altered mucociliary clearance may contribute to an increased susceptiblilty to infection in the early postoperative period.[66] These factors underlie the importance of assisting the patient with airway clearance.

Clearance of pulmonary secretions should be initiated on the first postoperative day, provided the patient is stable, and may be needed three or four times each day initially.[27] Postural drainage with shaking or vibration may be better tolerated than percussion due to incisional and chest tube discomfort. Transplant recipients who are mechanically ventilated may benefit from a combination of shaking and hyperinflation with a manual ventilation bag.[53] After extubation, the patient may prefer using the active-cycle-of-breathing technique or a Flutter valve, if the patient is familiar with this technique or this device. Positive expiratory pressure therapy has been used in the posttransplantation period.[77] As the secretions become less copious and the patient becomes more independent in clearing the airways, the frequency of airway clearance treatments is decreased. Need for secretion clearance is assessed daily, but treatments usually become unnecessary by the time of discharge from the hospital.

An effective cough is crucial to secretion removal. In the lung transplant recipient, an ineffective cough results from incisional pain and decreased sensation in the transplanted airway due to lung denervation.[14] Adequate pain control, optimal positioning, and modifications in coughing technique can improve the effectiveness of coughing. The upright sitting position should be encouraged for coughing, as it has been shown to produce the greatest expiratory flow rates.[78] Huff coughing, performed without closure of the glottis, has been shown to produce a larger volume of expired air at a higher flow rate than conventional coughing.[79] Huff coughing also takes less effort and is less painful than regular coughing, making it ideal for use with patients postoperatively. In patients who are unable to generate substantial airflow, the technique of stacking breaths before the expulsion phase can increase the effectiveness of a cough. Splinted coughing, with a pillow against the incision, is helpful in decreasing pain.

Initially, mechanical ventilation and oxygen requirements may be quite high, but patients are weaned from these supports as early as possible. In the initial postoperative period, patients with obstructive lung disease often have inadequate inspiratory force to ventilate their relatively noncompliant lungs.[66] In addition, many patients after single-lung transplantation continue to exhibit a rapid respiratory rate and increased reliance on accessory respiratory muscles.[80] These sequela are presumably due to the continued input from a native diseased lung as well as anxiety. These patients benefit from training in breathing strategies to decrease the sensation of dyspnea and to improve ventilation efficiency.[54] It may be helpful to display the pulse oximetry readings to assure the patient that oxygenation is adequate, even though the patient may complain of dyspnea. Continuous pulse oximetry allows the patient to be weaned from supplemental oxygen more quickly. After extubation, use of an incentive spirometer throughout the day is encouraged.

Incisional pain may limit activity progression, deep breathing exercises, and coughing. Considerable pain may originate from the chest tube sites and the abdomen if an omental wrap is used. Epidural analgesia has been effective in managing pain, allowing the patient to engage more willingly in the process of rehabilitation.

Decreased mobility is evident in the transplant recipient, due not only to incisional discomfort but also to various equipment in the intensive care unit that limits movement in bed. A temporary decrease in exercise tolerance occurs postoperatively despite the patient's best efforts at preoperative rehabilitation. The demands of transplant surgery, including prolonged static Positioning, prolonged anesthesia, and postoperative recumbency for a minimum of 24 hours, limit the capacity for exercise in the period immediately after transplantation.

Progressive activity is initiated on the first postoperative day, beginning with range-of-motion exercises and progressing to transfers out of bed to a chair and then to ambulation. In the intensive care unit, ambulation is very labor intensive, especially if the patient continues to require mechanical ventilation. For patients who require mechanical ventilation, an additional health care provider uses a manual ventilation bag during ambulation. All the necessary equipment, including portable oxygen, pulse oximeter, chest tube drainage containers with portable suction, and bladder catheter drainage bag, are placed into a wheelchair. With assistance from the physical therapist, the patient pushes the wheelchair filled with equipment while a nurse follows with the intravenous pole(s). The wheelchair provides support for the patient much like a rolling walker.

Protective or reverse isolation precautions are observed after transplantation in order to protect these patients, who have suppressed immune systems as a result of transplant medications. For visitors and health care workers entering the patient's room, thorough hand washing is imperative. A mask is worn by those who enter the room and by the patient when leaving the room. Avoiding contact with persons with infections is another precaution.[26]

After the patient leaves the intensive care unit, rehabilitation continues to focus on alveolar ventilation, mucociliary transport, and ventilation-perfusion matching to maximize the efficiency of oxygen transport. The most important components include mobilization, breathing control and coughing maneuvers, and, if necessary, air-way clearance techniques.

Close monitoring allows the patient to proceed with rehabilitation at an optimal rate throughout the acute postoperative period. The extensive amount of treatment time required in this stage allows the physical therapist to become aware of changes in the patient's status and to alert the transplant team to possible complications of transplantation.

General mobility improves as the patient's ambulation distance increases and participation in activities of daily living progresses. Thoracic mobility may be improved by instructing the patient in chest and upper-extremity mobilization exercises.[26] Breathing exercises should be incorporated into thoracic mobility and cardiovascular exercise regimens, coughing and airway clearance, and general activities.

When the patient's ambulation distance allows, the patient may ambulate to an isolation exercise room (if available) to begin a progressive exercise program using a treadmill and cycle ergometer. This setting allows the patient to progress further with cardiovascular endurance and strengthening without coming into contact with other patients. Prior to discharge from the hospital, the patient begins stair climbing. For many patients, this is a hallmark of recovery, as most patients have been restricted from this activity by their pulmonary disease.

The therapist should set physical therapy goals to be achieved prior to discharge from the hospital, including improved ventilation, effective and independent secretion clearance, improved thoracic mobility, increased endurance and strength, independence in activities of daily living, and ability to continue with an exercise/activity program at home. Most patients do not require the use of supplemental oxygen at the time of discharge, although a few patients will continue to require it for exercise sessions.

At the time of discharge, the patient (or family of a pediatric patient) should be able to proceed independently with a daily regimen of recording (1) measurements obtained with a hand-held spirometer, (2) vital signs, (3) self-medication, and (4) self-monitoring of exercise intensity.[26] The patient should know the normal limits of these values and when to contact the transplant team. By the time a patient leaves the hospital, he or she is well on the way to improved function and improved quality of life.

Outpatient Pulmonary Rehabilitation

After discharge from the hospital, patients are often expected to continue pulmonary rehabilitation.[41,42,77] Because patients come to lung transplant centers from many different geographical areas, many programs require recipients to live nearby, permitting supervised, monitored outpatient exercise at the center. This requirement allows the patient to be closely followed medically by the transplant team while he or she continues to work on increased function, strength, and endurance.

The physical therapist who treated the patient during the acute period after the transplant should communicate with the therapist who supervises the outpatient exercise sessions, especially when these two programs take place in different facilities. The method(s) used to prescribe and measure exercise intensity and areas where reinforcement of teaching is needed should be shared. Knowledge of the patient's hospital course and response to increased activity in the acute setting will assist the outpatient therapist in individualizing the exercise program.

An exercise program consisting of four to five 30-minute sessions of continuous exercise weekly should be well tolerated in this phase of rehabilitation. The work load on both the treadmill and the cycle erometer is increased during the aerobic component of the exercise program, and stair climbing and an arm ergometer may be added to the exercise session. Strength and postural assessments should be continued in addition to an individual program of strengthening and stretching exercises. The target heart rate method of prescribing exercise intensity is more valid after transplantation, when pulmonary limitations to exercise are lessened.

During outpatient therapy, exercise tolerance should be reevaluated periodically and the exercise prescription modified. A 6-minute walk may be performed just after discharge from the hospital. Maximal cardiopulmonary exercise testing on a treadmill or cycle ergometer is generally performed 3 months after surgery when the patient may be more stable and free of medical complications.[38,81]

Following lung transplantation, pulmonary function is no longer the limiting factor to exercise. Patients, therefore, often develop musculoskeletal limitations to increased activity. Patients are now able to perform exercise and other activities at a higher level of intensity. This increased exercise intensity emphasizes problems of muscle group imbalances, postural deviations, and incorrect exercise technique. Shinsplints, back pain, and the need for shoe orthotic devices are some of the complaints that have been identified. Physical therapy for these complaints allows the patient to continue rehabilitation more comfortably and effectively, which will increase adherence to an exercise program in the long term.

At the time of discharge to their hometown, patients are followed by their local physicians for laboratory work and routine medical care. Patients return to the lung transplant clinic for regular visits, which include bronchoscopy/biopsy to screen for rejection or infection and follow-up with members of the lung transplant team. Exercise testing is conducted at regular intervals for months to years after lung transplantation. Figure 3 depicts a model of an exercise program from evaluation through follow-up after transplantation.

Exercise Responses in Lung Transplant Recipients

After lung transplantation, there is considerable restoration of functional ability in patients who were previously debilitated. Improvement in exercise tolerance has been demonstrated by an increase in 6-minute walk distances after transplantation.[17,27,34,36,82] A report from one center indicated that no lung transplant recipients stopped a maximal symptom-limited exercise test because of dyspnea; the chief complaint was lower-extremity pain.[38]

Cardiopulmonary exercise testing, including analysis of maximal oxygen uptake, has demonstrated areas of limitation in exercise capacity after lung transplantation. Aerobic capacity, as judged by maximal oxygen uptake, remains reduced (32%-60% of the predicted value).[40,83] Ross et also report a low ventilation-perfusion ratio with exercise in transplanted lungs, suggesting this mismatch is one possible cause for the decreased aerobic capacity. Nonetheless, veritilatory factors do not appear to limit exercise. Respiratory rate increases appropriately with exercise, hypoxemia occurs only infrequently during exercise in single-lung transplant recipients and is not a limiting factor, and breathing reser-ve at peak exercise remains in the normal to high range.[38,40,81,84] limitations in exercise performance of lung transplant recipients have been attributed to various peripheral factors."[38,83,84] These factors may include abnormalities in the peripheral circulation and peripheral neuromuscular structure and function.[38] It has been suggested that the muscle deconditioning and atrophy that occur before surgery play an important role in the decreased exercise performance exhibited after lung transplantation.[38,40,81,83]

Exercise capacity continues to improve during the first year following lung transplantation, with the largest improvement occurring within the first 3 months.[38,42,84] Even with a reduced capacity for maximal exercise, moderate levels of work and exercise are achieved, an the majority of recipients report overall satisfaction their state of physical health.[38,40,82]

Medications

Lung transplant recipients require multiple medications. These medications may be divided into three categories. The largest and most important category is medications prescribed for immunosuppression. Another group of medications is used for prophylaxis or treatment of infection. Additional medications are required to combat the side effects of medications required for transplantation, which vary from patient to patient.

Immunosuppressive medications prevent the body from rejecting an organ from another source. The protocol for long-term maintenance of immunosuppression may include cyclosporine (Cya) or FK 506, azathioprine (Imuran), and corticosteroids (prednisone).[12,15,26,62] Initially, prednisone was not used during the acute postoperative period because it impaired bronchial healing. Currently, however, low-dose steroids are started immediately postoperatively.[15,85] Episodes of projection are treated with pulse doses of methylprednisolone to boost immmunosuppression. Recently, a new oral form of cyclosporine (Neoral) has become available. This medication was developed to increase absorption, thereby decreasing the amount of medicine required. Long-term studies have not been conducted on this medication.

Patients with cystic fibrosis require additional medications because of their underlying disease. These medications include gastric motility agents to prevent ileus, ketoconazole to slow the metabolism of cyclosporine, and pancreatic enzymes.[86]

Medications are given routinely to treat or prevent bacterial, viral, and fungal infection.[15,86] Many additional medications are used in the treatment of transplant recipients. A full discussion of these medications is beyond the scope of this article.

Complications

The most common problems in the acute postoperative period are infection and acute cellular rejection. Of these complications, infection has been identified as the greater cause of early death (within 6 months of transplantation).[86,87] The treatment of infection is targeted at the identified organism. Based on histological examination, acute rejection is graded on a scale of 0 to 4, with 0 showing no abnormality and 4 being severe. Acute rejection is treated with a high-dose burst of steroids to augment immunosuppression, Both infection and rejection are manifested by low-grade fever, leukocytosis, and an increased arterial-alveolar oxygen gradient.[87] A decrease in pulmonary function tests and decreases in both arterial oxygen saturation and exercise tolerance often result. The physical therapist is often the first person to report hypoxemia with exercise or a decrease in exercise tolerance and can alert the lung transplant team to a change in the patient that may indicate rejection or infection.

Other complications are directly related to lung transplant surgery. Adult respiratory distress syndrome/diffuse alveolar damage is an ischemic-reperfusion injury related to poor graft preservation.86 Airway complications include anastomotic dehiscence, necrosis, and bronchial stenosis requiring stenting or dilatation.[35,87] Trauma to the phrenic nerve may occur during surgery, resulting in a prolonged wean from mechanical ventilation, dyspnea, and a paradoxical breathing pattern, all of which contribute to a decrease in exercise tolerance.[88]

Immunosuppressive medications also can lead to complications. The nephrotoxic effect of cyclosporine is well documented and can cause both acute and chronic renal insufficiency.[89] Hypertension is a recognized side effect of cyclosporine, with a reported incidence of 66% in one study of transplant recipients.[90-92] Exercise-associated hypertension has been noted, even when the resting blood pressure is within normal sporine contributes to neurologic complications, commonly causing involuntary tremors and, less often, seizures.[16,89] Posttransplant lymphoproliferative disorder is related to the use of immunosuppressive medications, particularly azathioprine. As a result of long-term steroid use, lung transplant recipients may develop steroid myopathy, osteoporosis, and glucose intoleranie, necessitating the use of insulin.

Infection remains the leading cause of mortality even 6 months after lung transplantation.[15] The second leading cause of late mortality in lung transplant recipients is bronchiolitis obliterans, an inflammatory obstructive lung disease that appears to result from chronic rejection.[87,93,94] The term "bronchiolitis obliterans syndrome" is used to connote graft deterioration secondary to progressive airways disease, whereas the term "bronchiolitis obliterans" is reserved for histologically proven diagnoses.[95] The prevalence and mortality rates of bronchiolitis obliterans syndrome exceed 50% and 40%, respectively.[94]

Outcomes

Figures from the Registry of the International Society for Heart and Lung Transplantation demonstrate a steady, continued increase in lung transplantations performed worldwide since their introduction, although current figures suggest that the growth appears to have plateaued.[20] Through February 15, 1995, 2,465 single-lung transplantations and 1,344 double-lung transplantations, performed at a total of 111 centers, have been reported. For single-lung transplantation, patients with emphysema and alpha-1 antitrypsin deficiency had improved survival over patients with pulmonary fibrosis and primary pulmonary hypertension. The overall survival rates for single-lung transplantation are 67% at 1 year, 57% at 2 years, 49% at 3 years, and 42% at 4 years. The 1-year survival rate for bilateral/double-lung transplantation is 67%, and the 3 1/2-year survival rate is 47%.[20]

One measure of the success of lung transplantation is the recipient's ability to return to work and participate in sports and leisure activities. Most transplant recipients have been able to return to work or household duties.[83,96] Still others participate in classes at a local YMCA or health club without limitations, and some recipients have been able to return to strenuous activities such as waterskiing or surfing. Transplant recipients demonstrate their return to very active, athletic lives" at the biannual US Transplant Games.[97] High satisfaction with physical and emotional well-being has been reported by more than 50% of surviving recipients. Those recipients with suboptimal medical outcomes who reported lower satisfaction stated they were more satisfied with their lives than they were prior to transplantation.[96]

Recent Advances in Lung Transplantation

Complications following lung transplantation may be so severe that retransplantation is the only possibility for continued survival. Retransplantation has been performed for bronchiolitis obliterans, graft failure, intractable airway problems, severe acute lung rejection, and miscellaneous complications. A multicenter survey of 63 lung retransplantation operations demonstrated survival rates of 35% at 1 year and 32% at 2 years, significantly worse than the survival rates for first-time transplant recipients.[98,99] Controversy exists as to the ethics of offering retransplantation to lung transplant recipients in the face of a donor shortage for all candidates. Among patients with bronchiolitis obliterans, pulmonary function deteriorates again shortly after retransplantation, placing doubt on this indication for lung retransplantation.[98]

Another recent advance in the donor/recipient process has been the introduction of living related lobar transplantation.[12] In this surgery, a lobe is taken from each of two family members and reimplanted in a small adult or child. This technique is well suited to pediatric patients or patients with cystic fibrosis, who tend to be of small stature. Starnes[100] pioneered the technique and has reported a 1-year survival rate of 86%.

The major limitation to lung transplantation is the lack of available donors as the number of candidates listed for lung transplantation continues to rise. The United Network of Organ Sharing reports the number of candidates listed for lung transplantation in the United States at more than 1,700 people as of April 1995.[101] One proposal for increasing the number of organ donors is a system of mandated choice. in which all adults would be required to prospectively record whether they wish to become organ donors when they die; the decision could not be revoked by family members.[102]

Conclusion

The process of lung transplantation from initial evaluation through postoperative rehabilitation and beyond is a complex endeavor, requiring the skillful attention of a health care team to direct its course. The physical therapist plays a key role in the management of patients with lung transplants, providing expertise in exercise testing and prescription of exercise preoperatively and postoperatively. The physical therapist also should educate the patient and his or her family in order to promote independence and a lifetime habit of exercise. In addition, knowledge of musculoskeletar assessment and treatment, airway clearance and breathing techniques, and monitoring for complications of lung transplantation during activity are necessary to improve the outcome. The physical therapist providing care for this challenging patient population needs to stay abreast of new developments in the evolving field of transplantation.

As the interval from patient evaluation to transplantation lengthens, and many physical therapy departments are attempting to reduce staffing, research should be undertaken to determine the most effective utilization of rehabilitation resources. Issues warranting investigation include the most appropriate exercise testing for the preoperative and postoperative periods, timing and duration of treatment, use of strength versus endurance modalities, and the most effective exercise intensity assessment.

Lung transplantation is not a cure for end-stage lung disease; it should only be used for those patients for whom no other therapeutic option has been successful. The morbidity and mortality associated with the long-term use of immunosuppressive medications, the surgical risks, and the acute and long-term complications of transplantation are substantial. Fortunately, for many patients, the benefits outweigh the risks, providing increased survival, improved level of function, and satisfaction with quality of life.

Acknowledgments

I thank Dr Thomas Egan for my introduction to the exciting and challenging realm of lung transplantation and my colleague, Constance Arnold, for her pioneering work in lung transplantation rehabilitation at the University of North Carolina Hospitals.

[Figures 1 to 3 ILLUSTRATION OMITTED]

References

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