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Lung transplantation is the surgical replacement of severely diseased lungs(s) to reestablish adequate lung function. Pulmonary rehabilitation is a multidisciplinary and comprehensive intervention, including exercise and educational sessions, for patients with chronic respiratory system diseases to improve health-related quality of life and functional status, promote stabilization of symptoms, and prevention of complications.


Chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are the leading causes of lung transplantation. Although no data exist on the worldwide prevalence of respiratory failure requiring lung transplant, it is estimated at tens of thousands, one-third of whom have fibrotic lung diseases and another one-third of whom have severe COPD.1 Cystic fibrosis (CF), emphysema caused by alpha-1 antitrypsin deficiency, sarcoidosis, non-CF bronchiectasis, and lymphangioleiomyomatosis represent other less common indications.2,3

Epidemiology including risk factors and primary prevention

In 2011, 1830 lung transplants were performed; of these, 29.9% were single lung transplants, and 70.1% were bilateral. Bilateral transplants are associated with increased long term survival in COPD patients.4 The most common age range being 50 to 64 years old.2 The most common recipient were men (59.8%), with COPD being more common in men than women. Morbidity increased with age. The most common risk factor for COPD is tobacco smoke; more than 10 packs per year is identified as the threshold for increased risk.5 Among other risk factors included environmental exposures such as organic and inorganic occupational dusts associated with coal miners, hard rock miners, tunnel workers, industrial workers, and transportation industry workers. Additional factors included prior tuberculosis history, outdoor air pollution, respiratory infections, genetics, lower socioeconomic status, nutrition, and other medical comorbidities. Lung growth and development deficits and oxidative stress have also been linked to COPD. Influenza and pneumococcal vaccines are recommended for COPD patients to prevent respiratory tract infection.6


During a lung transplant, the host lung is surgically denervated. When this occurs the lung’s lymphatic drainage and circulation is altered.7 The lung receives blood supply from the pulmonary and bronchial arteries, but during lung transplantation, only the pulmonary artery circulation is reattached. The rationale behind this decision is that direct revascularization has been seen as too difficult and often unreliable to perform routinely; also, de novo regrowth of the bronchial arteries has been observed. There is some association of this alteration in lung vasculature to bronchiolitis obliterans, which is a common postoperative complication.8 There is increased airway hyperesponsiveness, altered cough reflex, and mucociliary clearance. Injury to the vagus, recurrent laryngeal nerve, and superior laryngeal nerve during surgical procedure can also lead to swallowing and gastroesophageal dysfunction.9

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) formulated a staging system as follows:

  1. Stage I: forced expiratory volume in one second (FEV1) more than 80% of expected; minimal shortness of breath with/without cough and/or sputum.
  2. Stage II: FEV1 50% to 80% of predicted; moderate to severe shortness of breath on exertion, with/without cough, and sputum or dyspnea.
  3. Stage III: FEV1 30% to 50% of predicted; severe shortness of breath, with/without cough, sputum or dyspnea, exacerbation, reduced exercise capacity, and fatigue.
  4. Stage IV: FEV1 less than 30% of predicted; serious impairment in quality of life caused by shortness of breath with frequent exacerbation, and life threatening at times.

Specific secondary or associated conditions and complications

Recurrence of primary disease in the allograft may appear as early as 2 weeks or as late as 2 years after transplantation, with sarcoidosis being the most commonly recurrent primary disease (approximately 35% recurrence).10 Lymphangioleiomyomatosis has also been found to recur. Rejection is possible of the hyperacute, acute, and chronic type (bronchiolitis obliterans syndrome occurs in 50% of the recipients at 5 y). Neurologic complications occur in approximately 25% of patients, including leukoencephalopathy, stroke (5%), hyperammonemia and neuropathies, among others. Pulmonary complications, including pulmonary embolism and infarction, account for 27%.11 Nephrotoxicity and kidney disease also can occur (25.5% at 1 y). Infections are possible, including cytomegalovirus, aspergillosis (5%), and bacterial infections. Other related conditions include diabetes mellitus (24.3% at 1 y), arterial hypertension (51.9%), hyperlipidemia (20.5%), and posttransplant lymphoproliferative disease (1.8-%7.9% incidence associated with Epstein-Barr virus). Malignancy (3.7% at 1 y), lung cancer (2%-4%), osteoporosis (6%-18% fracture rate posttransplant) and gastrointestinal complications are also possible.12

Essentials of Assessment


  1. Medical history: respiratory disease, cough, sputum production, oxygen supplementation needs, dyspnea, lung infections, malignancy, hospitalization as a result of pulmonary issues, and assessment for any associated conditions (e.g., heart disease, weight loss).
  2. Environmental history: high pollution environment and biomass disease fuel use in enclosed spaces.
  3. Occupational history: work type and exposure to inhaled gases and/or particulate matter inhalation.
  4. Social history: tobacco use or any inhaled illicit drugs, social support, and resources available.
  5. Functional history: premorbid functional status, current functional status, assistive device use, and dyspnea during activity.

Physical examination

Patient assessment should focus on the following:

  1. Lung auscultation to evaluate for effusion, areas of atelectasis and bronchial constriction.
  2. Assessment of supplemental oxygen requirements
  3. Inspection to evaluation for accessory muscle use and to assess for any deformity.
  4. Heart auscultation to assess for cardiac/valvular disease.
  5. Examination of the muscle bulk for any signs of atrophy or cachexia.
  6. Manual muscle testing to assess strength focusing on muscles used for ambulation.

Both before and after transplant, examination should also focus on signs of comorbid and secondary diseases (eg, diabetes, renal disease, neurologic examination, gastrointestinal involvement).

Functional assessment

  1. Mobility: six-minute walk test, FIM, and cardiopulmonary exercise study.
  2. Self-care: index of independence in activities of daily living, instrumental activities of daily living, Barthel Index of activities of daily living, and FIM.
  3. Cognition/behavior/affective state evaluation tools: Minnesota Multiphasic Personality Inventory-2, clinical interview, Montreal Cognitive Assessment, among others.

Laboratory studies

During the posttransplant period, surveillance of immunosuppressant levels for dosage titration is indicated, and its frequency will be dictated based on the patient’s clinical status. Monitor for electrolyte disturbance, such as hypomagnesemia (34%) and hypophosphatemia (49%), among others. Further laboratory monitoring and workup should be tailored to what is indicated for each individual patient.


The needs for imaging will be dictated by the patient’s clinical status and time frame posttransplant. The following are some of the most used:

  1. Chest radiographs with a selection of views depending on the suspected diagnosis. Useful to assess for lung expansion, donor size mismatches, pulmonary infection, presence of effusions, and/or diaphragmatic paralysis. Routine follow-up radiographs are usually done monthly during the first 3 months posttransplant.
  2. Fluoroscopic examination to rule out diaphragmatic paralysis, if suspected, posttransplant.
  3. Chest computed tomography (CT), both non-contrast and contrast enhanced, is useful to assess the presence of common pulmonary pathology, such as effusions and consolidation, among others. CT is useful for confirming and quantifying infiltrates, selecting appropriate regions of the lung for bronchoscopy, and determining the response to specific antimicrobial treatment. It is also useful to evaluate for well-established complications of transplant such as vascular and bronchial anastomotic abnormality, lung torsion, pulmonary embolism, rejection, infection and bronchiolitis obliterans.13

Early predictions of outcomes

Decreased 1-year survival has been associated with the number of human leukocyte antigen mismatches, primary pulmonary hypertension and pulmonary fibrosis, pretransplant psychologic illness, clinical status, mechanical ventilator dependency, and age over 60 years. Transplant recipient selection criteria vary from center to center; nonetheless, because of lung allocation scoring system changes, increased transplant recipient age has been observed and associated with decreased survival.


Particulate aspiration and gases (biomass fuel, diesel exhaust, etc) have been identified as triggering agents for airflow limitation, therefore contributing to COPD and COPD-like illnesses. During the posttransplant stage, some patients will possibly require droplet precautions and/or contact precautions caused by the development of viral infections or resistant bacteria during their hospital stay. The proper hand-washing technique is the most advocated infection control measure per the Centers for Disease Control 2002 guidelines. Some immunocompromised patients with neutropenia benefit from positive air pressure and a high-efficiency particulate filter.14Some transplant centers will, after discharge, require the avoidance of enclosed spaces/densely populated spaces, favor face mask use until steroids are tapered to the lowest possible dose, and require the avoidance of handling pet feces and plants.15 When handling materials with a higher chance of contamination such as soil, moss and manure, gloves should be worn. Shoes, long sleeves and pants should be worn while participating in activities such as gardening, yard work and being in parks and heavily wooded areas. As for possible percutaneous infectious exposure, body piercing and tattoos should be obtained from reputable centers with strict adherence to sterile technique. As for all activities mentioned above, extra caution should be taken during periods of enhanced immunosuppression. The same can be said for times when community spread of viral illness is increased.16

Social role and social support system

Pretransplant, an evaluation is conducted to determine whether the patient has support from family/friends or access to care services for transition to the community posttransplant. A patient’s cognitive abilities will be crucial regarding medication management to yield a higher rate of success posttransplant and help prevent complications. Household contacts should be educated on good hygiene practices such as hand washing, coughing and sneezing etiquette. Additionally, all close contacts should remain up to date on standard immunizations and yearly influenza vaccine.

Professional Issues

A close evaluation of the patient’s medical needs, tolerance to activity, and need for supplemental oxygen is vital to establish goals for the rehabilitation process, inpatient or outpatient. Accurate documentation and coding will safeguard proper reimbursement and accounting for the patient’s complexity during evaluation and management.

As for patient professional considerations, lung transplant recipients have a lower pretransplant incidence of employment as compared to other solid organ transplant (SOT) recipients such as kidney, heart and liver. Additionally, compared to other SOT recipients, lung recipients are less likely to return to work posttransplant.17 Some factors shown to positively affect return to work include pretransplant employment, self-reporting being physically able to work, greater posttransplant improvement in percent predicted forced vital capacity, and posttransplant 6-minute walk > 550 meters.18 Return to work becomes much less likely greater than one year posttransplant. For individuals desiring returning to work in fields such as construction, outdoors and healthcare, individualized occupational counseling is important. For transplant recipients working with animals, work should be avoided during times of maximal immunosuppression. If returning to work, it is important to properly use personal protective equipment to limit any possible dangerous exposure. Additionally, while some patients may be willing to pursue work in other areas, some are tied to previous lines of work for various reasons such as psychological, social, financial and maintenance of health insurance or other benefits. Coworkers may also be encouraged to stay up to date on regularly scheduled and seasonal vaccinations such as influenza. Professional rehabilitation, including the help of a social worker, may be started prior to transplant.17

Rehabilitation Management and Treatments

Available or current treatment guidelines

Current treatment guidelines have been published by the American College of Chest Physicians and American Association of Cardiovascular and Pulmonary Rehabilitation.19 The GOLD has also published guidelines on the diagnosis, management, and prevention of COPD. Pulmonary rehabilitation is recommended both before and after transplantation to improve the quality of life, symptoms and to prevent further loss of function.  There is also a growing body of evidence of pulmonary rehab’s survival benefits.

At different disease stages

Pretransplant: participating in a pulmonary program is recommended to assist with prevention of further deconditioning and improvement in symptomatology, quality of life, and education. The goal is to improve endurance and activity tolerance to promote a better functional recovery posttransplant. There is also growing evidence of pre-transplantation rehab’s contribution to preventing complications and lowering the overall risk associated with transplantation, such as duration of intubation.

Posttransplant: during the inpatient stay, the rehabilitation process should be started early, once the patients is stabilized. Activities should start with functional mobility (eg, bed mobility, transfers, gait) and include treadmill training, with a progressive increase in distance, resistance, and inclination as tolerated. Resistance exercises involving large muscle groups should also be started, taking into account limitations due to sternal precautions. Breath retraining, control, and pulmonary hygiene techniques are also part of this phase.

Chronic: aerobic exercises should be continued but this phase places increased importance on resistance exercises.  This is to facilitate regaining the muscle mass and strength lost during prolonged illness and the disuse associated with prolonged illness.

Coordination of care

Arrangements for surveillance bronchoscopies and biopsies during acute inpatient rehabilitation requires close work with the transplant team. The transplant and infectious disease teams are typically responsible for titrating immunosuppressant drugs and surveillance for infectious processes. The rehabilitation team’s key role is in the identification and facilitation of functional progress, as well as monitoring symptoms, and clinical changes in the patient during the rehabilitation process. Good communication among team members is essential.

Patient & family education

Typically, well before a patient arrives for pulmonary rehabilitation, their primary care doctor, pulmonologist and transplant evaluation teams have worked to educate them and their family regarding their disease process, candidacy, risks and benefits of transplantation, and what to expect from the transplantation process and recovery, However, the rehabilitation team is essential in not-only reinforcing this knowledge, but in bridging the difference between verbal, pamphlet or book knowledge, and the patient and family’s lived experience, This critical piece is possible because we work alongside the patient during therapies while their physiology is pushed and they encounter the limits of their body, symptoms, and complications.  We also provide hands on caregiver training, helping families to recognize their own limitations and how their family member’s recovery will change their own daily life. Rehabilitation teams also add the experiential education of when a patient encounters a symptom or limitations, how to safely and effectively navigate them.

Emerging/unique Interventions

COPD Assessment Test: measures health status impairment, with good test-retest reliability, intraclass correlation, and internal consistency. Good validity with a high correlation with St George’s Respiratory Questionnaire (SGRQ) in European countries and the United States.

Clinical COPD Questionnaire: validated, disease specific, and correlated with FEV1, Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), and SGRQ. Good internal consistency and good retest reliability.

SGRQ: disease specific, validated. Good internal reliability, test-retest intraclass correlations, correlated with the Medical Research Council Dyspnea scale, six-minute walk test, all SF-36 concept scores, and 80% of Chronic Respiratory (Disease) Questionnaire domains.

Translation into practice: practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills

Managing a transplant patient in the rehabilitation unit includes, but is not limited to, the following:

  1. Airway normalization (Oxygen weaning and decannulation)
  2. Surveillance bronchoscopy coordination and follow-up
  3. Immunosuppressant monitoring and management coordination.
  4. Protection from, assessment for and coordinating management of infectious processes in the immunosuppressed patient.
  5. Post-operative wound care (including drain management).
  6. Prevention of, surveillance for and management coordination of complications (eg, venous thromboembolisms, arrythmia’s, neuropathies, dysphagia, rejection and hemorrhage).
  7. Minimize disability and facilitate functional recovery through therapies, training and strength-building
  8. Nutritional optimization
  9. Comorbidity management (such as anticoagulation, diabetes, arthritis, and hypertension)
  10. Symptom management (pain, anxiety, dyspnea)
  11. Home care and outpatient therapies coordination
  12. Arrangements for medical equipment and therapies needed post discharge (DME, spirometer, nebulizer etc.)

Cutting Edge/ Emerging and Unique Concepts and Practice

With the emergence of FDA approved gene therapies, such as for SMA or LCA, in addition to the introduction of CRISPR-based gene editing techniques, medicine is closer than ever to preventing and treating genetic factors predisposing patients to causes of respiratory disease and transplantation, such as cystic fibrosis and alpha-1 antitrypsin deficiency. Next generation DNA sequencing has also greatly reduced the cost and accelerated the timeline for better understanding which medical therapies work best for which patients, and possibly providing targets for rational drug design or gene therapy to improve symptoms and response to medications, such as matrix metalloproteinase-12, gene transfer of interleukin 2 and interferon gamma to decrease airway hyperresponsiveness, or beta-2-adrenergic receptor gene, single nucleotide polymorphisms and insertion-deletion polymorphism of the hemopoietic cell kinase gene.

We are also encountering new causes for respiratory failure and lung transplantation, such as e-cigarette, or vaping product use-associated lung injury (EVALI), and the Sars-Cov-2 virus (COVID-19). Both of these pathologies present with unique physiologies and comorbidities complicating both pre and post transplantation rehabilitation. Efforts are ongoing to adjust and optimize practices for these new diseases. Such adjustments have included the necessary growth of telemedicine, allowing access and refinement of home pulmonary rehabilitation programs for the outpatient and maintenance phases.  Wearable devices, such as smart watches, permit O2 and heart rate monitoring and documentation inexpensively and passively, providing rehabilitation teams with a wealth of data to further improve interventions and systems of care.

Gaps in The Evidence- Based Knowledge

Most research regarding pulmonary rehabilitation has focused on patients with COPD, however in the past decade, trials evaluating other diseases, such as pulmonary fibrosis, have expanded and improved upon our knowledge base. Unfortunately, though the benefits to function and short-term quality of life metrics are clear, much of the pulmonary rehab literature is focused on establishing efficacy in improving immediate physiologic and satisfaction based outcomes, and suffers from a number of design flaws, from inadequate power, to inadequate control groups, to establish evidence based guidelines for best practices or length of stay. Only in the last decade have studies even begun to assess the value added to medical systems and society through reducing pre and post-operative complications, reducing disability, and facilitating return to employment, but the potential in these fields is profound. Lastly, though a current and intense focus of research, the very novelty of COVID-19 and EVALI preclude rigorous evaluation of longitudinal outcomes. Further research in the form of double-blind multicenter randomized controlled trials, in these and other types of chronic pulmonary diseases and their outcomes-based response to pulmonary rehabilitation, pre- and post lung transplantation, is recommended.


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Original Version of the Topic

Melissa M. Alvarez Perez, MD. Pulmonary Rehabilitation Before and After Pulmonary Transplantation. Published 9/20/2014

Author Disclosures

Matthew Adamkin, MD
Nothing to Disclose

Blake Fechtel, MD
Nothing to Disclose

Dylan Lewis, DO
Nothing to Disclose

Katrina Slater, DO
Nothing to Disclose