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


Chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are the leading causes of lung transplantation, with COPD encompassing 22% of lung transplants and IPF encompassing 37% of lung transplants in North America in 2012. Cystic fibrosis (CF) (16%), emphysema caused by alpha-1 antitrypsin deficiency (3%-5%), sarcoidosis (3%), non-CF bronchiectasis (3%), and lymphangioleiomyomatosis (1%) represent other less common indications.1,2

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. The most common age range being 50 to 64 years old.1The 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.3 Among other risk factors are organic and inorganic occupational dusts with coal miners, hard rock miners, tunnel workers, industrial workers, and transportation industry workers. Prior tuberculosis history, outdoor air pollution, respiratory infections, genetics, lower socioeconomic status, nutrition, and comorbidities are also factors. 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.4


When the transplanted lung is denervated, its lymphatic drainage and circulation is altered.5The lung receives blood supply from the pulmonary and bronchial arteries, but usually, 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 unreliable to perform routinely; also, de novo regrowth of the bronchial arteries has been observed. There has been some association of this alteration in lung vasculature to bronchiolitis obliterans, which is a common postoperative complication.6There 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.7

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).8Lymphangioleiomyomatosis 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 occurs in approximately 25% of patients, including leukoencephalopathy, stroke (5%), hyperammonemia and neuropathies, among others. Pulmonary complications, including pulmonary embolism and infarction, account for 27%.9 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.10



  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 (eg, 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 avaliable.
  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. Any signs of hypoxemia, lung auscultation to evaluate for any effusion, and areas of atelectasis or bronchial constriction.
  2. Inspection to evaluation for accessory muscle use and to assess for any deformity.
  3. Heart auscultation to assess for cardiac/valvular disease.
  4. Examination of the muscle bulk for any signs of atrophy.
  5. Manual muscle testing to assess strength focusing on muscles used for ambulation.

In the transplanted patient, examination should also focus on identifying signs of 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%) causing arrhythmias and neuromuscular manifestations (eg, weakness, tetany) and hypophosphatemia (49%) causing encephalopathy, myopathy, hematologic dysfunction, among others.


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

  1. Fluoroscopic examination to rule out diaphragmatic paralysis, if suspected, posttransplant.
  2. Follow-up chest radiograph 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 once a month during the first 3 months posttransplant.
  3. Chest computed tomography (CT) to assess the presence of effusions, 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.

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.11Some 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.12

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 in regard to medication management to guarantee a higher rate of success posttransplant and prevent complications.

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. Anxiety and dyspnea management during the rehabilitation process will be key to the completion of a successful rehabilitation process. Accurate documentation and coding will safeguard proper reimbursement and accounting for the patient’s complexity during evaluation and management.


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.13The GOLD4has also published guidelines on the diagnosis, management, and prevention of COPD. Prior to transplantation, the recommendation is for patients to be actively participating in a pulmonary rehabilitation program to assist with quality of life, symptoms, and prevent further loss of function while waiting for an available organ. Continuation of pulmonary rehabilitation program posttransplant is recommended.

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.

Posttransplant: during the inpatient stay, the rehabilitation process should be started early posttransplant, 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 be started, if recommended, but taking into account sternal precautions. Breath retraining, control, and pulmonary hygiene techniques are also part of this phase.

Chronic: aerobic exercises are to be continued and complemented by resistance exercises, which are emphasized during this phase to regain muscle mass and strength lost as a consequence of prolonged disease, with limited activity over time.

Coordination of care

Arrangements for surveillance bronchoscopies and biopsies during acute inpatient rehabilitation will require close work with the transplant team. The transplant and infectious disease teams are responsible for titering of immunosuppressant drugs and surveillance for any infectious processes. The rehabilitation team will take a key role in the identification of functional progress, symptomatology, and clinical changes in the patient during the rehabilitation process. Good communication among team members is essential.

Patient & family education

Education of patient and family members must take place during the pretransplant phase for better understanding of the disease and how to self-monitor. In the patient exploring transplantation, strong education must take place in order to better understand procedure candidacy, risk versus benefits, and what to expect during the postoperative course.

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

Management of the transplant patient inthe rehabilitation unit includes, but is not limited to, the following:

  1. Oxygen weaning as tolerated.
  2. Decannulation process if indicated.
  3. Immunosuppressant monitoring and management.
  4. Surveillance bronchoscopy coordination and follow-up: anticoagulation management if indicated.
  5. Monitoring for infectious process in the immunosuppressed patient.
  6. Incision site care.
  7. Management and monitoring of drains if present.
  8. Surveillance for any symptoms that could signify the presence of well-known transplant complications (eg, neuropathies, diabetes, hypertension).
  9. Arrangements for spirometer and nebulizer treatments and equipment required postdischarge.


Cutting edge concepts and practice

Current research has been oriented toward gene therapy targeting genetic factors predisposing patients to COPD, such as alpha-1 antitrypsin gene therapy, poor treatment response, and symptomatology (eg, targeting of matrix metalloproteinase-12, gene transfer of interleukin 2 and interferon gamma to decrease airway hyperresponsiveness, beta-2-adrenergic receptor gene, single nucleotide polymorphisms, insertion-deletion polymorphism of the hemopoietic cell kinase gene). Animal studies have shown promise; nonetheless, finding the appropriate vector and obtaining lasting effects have been the main barrier. Research in alpha-1 antitrypsin deficiency showed persistent expression of alpha-1 antitrypsin in mice, but still no firm evidence has been shown.


Gaps in the evidence-based knowledge

Most of the research has focused on patients with COPD. Further research in the form of double-blind multicenter randomized controlled trials, in other types of chronic pulmonary diseases and their response to pulmonary rehabilitation, pre- and postlung transplantation, is recommended.


1. International Society for Heart and Lung Transplantation. ISHLT transplant registry quarterly reports for lung in North America. Available at: http://www.ishlt.org/registries/quarterlyDataReportResults.asp?organ=LU&rptType=tx_demo&continent=4. Accessed February 1, 2014.

2. Health Resources and Services Administration, Scientific Registry of Transplant Recipients. 2011 annual data report. Available at: http://srtr.transplant.hrsa.gov/annual_reports/2011/. Accessed February 1, 2014.

3. United States Department of Veterans Affairs. Management of chronic obstructive pulmonary disease (2007). Available at: http://www.healthquality.va.gov/Chronic_Obstructive_Pulmonary_Disease_COPD.asp. Accessed February 5, 2014.

4. Global Initiative for Chronic Obstructive Lung Disease. Global strategies for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Available at: http://www.goldcopd.org. Accessed February 5, 2014.

5. Nador RG, Singer LG. Physiologic changes following lung transplantation. Available at: http://www.uptodate.com/contents/physiologic-changes-following-lung-transplantation?source=search_result&search=lung+transplant+physiological+changes&selectedTitle=5%7E150. Accessed February 1, 2014.

6. Nicolls M, Zamora M. Bronchial blood supply after lung transplantation without bronchial artery revascularization.Curr Opin Organ Transplant.2010;15:563-567.

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8. Collins J, Hartman MJ, Warner TF, et al. Frequency and CT findings of recurrent disease after lung transplantation.Radiology. 2001;219:503-509.

9. Ward S, Muller N. Pulmonary complications following lung transplantation.Clin Radiol. 2000;55:332-339.

10. Lyu D, Zamora M. Medical complications of lung transplantation.Proc Am Thorac Soc.2009;6:101-107.

11. Pizzo PA. Considerations for the prevention of infectious complications in patients with cancer.Rev Infect Dis.1989;11 Suppl 7:S1551-S1563.

12. Miller R, Assi M; AST Infectious Diseases Community of Practice. Endemic fungal infections in solid organ transplantation.Am J Transplant. 2013;13 Suppl 4:250-261.

13. Pulmonary rehabilitation: joint ACCP/AACVPR evidence-based guidelines. ACCP/AACVPR Pulmonary Rehabilitation Guidelines Panel. American College of Chest Physicians. American Association of Cardiovascular and Pulmonary Rehabilitation.Chest. 1997;112:1363-1396.


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Author Disclosure

Melissa M. Alvarez Perez, MD
Nothing to Disclose