Chronic obstructive pulmonary disease
BODE index of at least 7 or at least 1 of the following:
• FEV1 < 20 % predicted and either DLCO < 20 % predicted or homogenous distribution of emphysema
• History of recurrent exacerbations with associated hypercapnia (pCO2 > 50 mmHg) despite aggressive medical management
• Pulmonary hypertension or cor pulmonale, or both, despite oxygen therapy
Idiopathic pulmonary fibrosis
Histologic or radiographic evidence of UIP and any of the following:
• A 10 % or greater decrement in FVC during 6 months of follow-up
• A decrease in pulse oximetry <88 % during a 6-minute walk test
• Honeycombing on high-resolution CT of the chest
• A DLCO <39 % predicted
• FEV1 < 30 % predicted or rapidly declining lung function
• Pulmonary hypertension
• Increasing oxygen requirements
• Baseline hypercapnia (pCO2 > 50 mmHg)
• Persistent NYHA class III or IV symptoms on maximal medical therapy
• Low or declining 6-min walk
• Failing therapy with intravenous epoprostenol or equivalent
• Cardiac index <2 L/min/m2
• Right atrial pressure >15 mmHg
To determine the appropriateness for listing for lung transplantation, several studies should be performed during the evaluation process. Complete pulmonary function testing, including measurement of FEV1, FVC, lung volumes, and bronchodilator challenge when appropriate, allows the medical team to gauge the severity and trajectory of lung function. A 6-min walk test assesses exertional hypoxia and functional status of a potential candidate. Radiographic imaging of the chest with chest x-ray and CT scan is necessary to measure the size of the chest cavity and to exclude any underlying malignancy or invasive pulmonary disease. A ventilation and perfusion scan provides information about segmental pulmonary blood flow and helps determine which lung to transplant in the case of single lung transplantation. As preoperative assessment, an electrocardiogram and left heart catheterization is performed in individuals over 45 years of age. An echocardiogram and right heart catheterization can be performed to assess for cardiac contractility and underlying pulmonary hypertension respectively, which can affect the priority on the transplant waiting list. A barium swallow, pH probe, and esophageal manometry help gauge the presence and severity of gastroesophageal reflux and risk of microaspiration, which may be clinically significant in patients with known esophageal dysfunction such as scleroderma. Age-appropriate health maintenance exams for malignancy screening such as a colonoscopy, PAP smear, and mammogram along with bone densitometry to assess for osteoporosis and fracture risk are also required to exclude these comorbidities.
Hematologic and biochemical laboratory assessment through blood sampling is essential to assess for end-organ disease. A sputum culture is necessary to assess for fungal or bacterial colonization of the tracheobronchial tree and to assess for indolent invasive pulmonary disease. Serologies to assess for cytomegalovirus, Epstein-Barr virus, hepatitis B and C virus, toxoplasmosis, varicella, and herpes simplex virus exposure are utilized to determine antimicrobial prophylaxis and risk stratify recipients after lung transplant. Additional immunologic testing includes HLA typing, blood group typing, and HLA antibody assessment to ensure an adequate donor and to avoid immediate complications such as hyperacute rejection.
Multidisciplinary Approach to Evaluation
Due to the inherent complexity of evaluating a chronically ill patient for an extraordinary intervention—transplantation—transplant programs almost uniformly consist of a number of health care providers who have complementary areas of expertise. Involvement of the many team members begins with the detailed evaluation process that typically extends over several days. In the initial years of lung transplantation, evaluations were uniformly conducted in the inpatient setting; however, for well over a decade now, the testing and consultations are accomplished in the outpatient arena. In addition to the testing outlined above, patients and a family member undergo individual evaluations by the team members listed in Table 7.2. These consultations provide an opportunity for the team members to assess the medical, surgical, psychosocial, and financial issues that impact a patient’s suitability for lung transplant listing. In addition, they provide an opportunity for the team members to educate the patient and family, particularly with respect to the risks and benefits of transplant for the specific patient, and the rigors of post transplant care. Lastly, the multiple meetings and consultations provide opportunities to make an informed decision regarding whether transplant is consistent with life goals and whether the patient wishes to endure the complex surgery, commit to the demanding medical regimen and attend routine follow-up appointments essential for long term survival after lung transplantation.
Transplant team members
Transplant infectious disease physician
Transplant nurse coordinator
Behavioral health specialist/psychiatrist
Pulmonary rehabilitation specialist/physical therapist
Primary care physician
At the conclusion of the evaluation process, most transplant programs have a candidate selection committee meeting to make team recommendations and decisions on transplant candidacy. At the meeting, each team member who interacted with the patient is provided an opportunity for input, specifically expressing concerns that impact the patient’s candidacy. After discussion, one or more recommendations are made to the patient and referring provider, including a decision to list for transplant, decline for transplant, or defer listing for one more reasons. When patients are referred prior to becoming critically ill on high flow oxygen, there are often remediable issues that can be addressed to alleviate concerns and convert an unacceptable candidate for transplant into an eligible patient. Prime examples of such issues are obesity or malnutrition, deconditioning, and completion of vaccinations. More complex and nebulous are issues related to significant comorbidities, including coronary artery or other vascular disease, psychiatric issues related to depression and/or anxiety, and degree of psychosocial and financial support to ensure medication compliance and optimal post transplant care.
Lung Allocation Score
Prior to May 2005, lungs were allocated to recipients based upon waiting time on the transplant list. This practice resulted in early listing for noncritical lung dysfunction, large wait lists, frequent deactivation and activation of lung transplant candidates, and extremely long wait times for transplantation. Patients often waited well over 2 years for lung transplantation, which led to high mortality rates for patients with more rapidly progressive pulmonary disease such as idiopathic pulmonary fibrosis. In May 2005, the policy for lung allocation was changed by the Organ Procurement and Transplantation Network (OPTN) to a system that allocates lungs based upon a lung allocation score (LAS) , which reflects medical urgency rather than waiting time . The LAS reflects an adjusted scale from 0 to 100 that represents a weighted combination of a potential recipient’s predicted survival during the following year on the wait list and predicted survival during the first year following a transplant. The LAS considers the net benefit of the transplant to the candidate as well as clinical urgency; it is calculated using pre-transplant clinical diagnostic data that is predictive of both pre- and post transplant outcomes (Table 7.3). In the years following implementation of the LAS, the wait times for lung transplantation decreased and the LAS for recipients increased, reflective of the clinical urgency for lung transplantation in recipients with advanced respiratory failure .
Factors involved in the lung allocation score calculation
Factors predicting wait list survival
Factors predicting transplant survival
Forced vital capacity
Forced vital capacity (B, D)
Pulmonary arterial diastolic pressure (A, C, D)
Pulmonary capillary wedge pressure (D)
Oxygen requirement at rest (A, C, D)
Body mass index
Diabetes mellitus, insulin-dependent
6-min walk distance
Diagnosis (A, C, D)
Type of Lung Transplant
Until 1989, the most common type of lung transplantation in the United States was combined heart lung transplantation; currently double lung transplantation has become the most common type of transplant. Single lung transplantation may extend the limited supply of donor organs to more patients, but provides less lung function as a buffer for complications and is also associated with worse long-term survival . Elderly patients may benefit more from single lung transplantation due to the lower perioperative risk . However, the lower survival associated with single lung transplantation may be more associated with age-related morbidity and mortality rather than type of transplant procedure. The underlying lung disease is also an important factor in determining which type of transplant procedure to perform. Bilateral lung transplantation is the procedure of choice in patients with suppurative lung diseases such as cystic fibrosis, due to the risk of crossover infection from the native lung to the transplanted allograft. Bilateral lung transplantation is more common in patients with COPD, which may be due to the increased risk of hyperinflation of the native lung resulting in compression of the transplanted allograft in single lung recipients and improved survival after the onset of chronic allograft failure in double lung recipients [28, 29]. Currently the majority of single lung transplant procedures are performed in patients with IPF. Single lung transplantation appears to have a short term survival benefit whereas double lung transplantation confers a long term survival benefit in recipients with IPF . Combined heart lung transplantation was originally the procedure of choice in patients with pulmonary hypertension. Now patients with pulmonary hypertension generally receive double lung transplantation due to the plasticity of the right ventricle, which recovers shortly after lung transplantation. Heart lung transplantation is generally reserved for patients with concomitant lung and heart disease, which cannot be treated by lung transplantation alone, such as congenital heart disease with Eisenmenger syndrome.
Patients who have circulating antibodies that recognize human leukocyte antigens (HLA) on the donor organ are at increased risk of developing hyperacute rejection and graft failure shortly after lung transplantation. Even low levels of antibodies reactive to donor lung antigens may lead to upregulation of immune cell pathways resulting in rejection; thus more sensitive antibody tests are critical to reduce the risk of antibody-mediated damage after lung transplantation. HLA antibody testing provides an accurate assessment of a potential transplant recipient’s sensitization status and identification of the HLA antigens targeted by those antibodies. The tests to identify HLA antibodies are based upon reactions of antibodies to panels of lymphocytes (complement-dependent lymphocytotoxicity) and to purified HLA antigens couples to microspheres (Luminex, flow cytometry). Historically, prospective serologic crossmatches using serum from the recipient and lymphocytes from the donor were utilized to predict alloimmune reactivity; these were often time-consuming and limited lung donors from geographically distant locations. Crossmatch results can now be predicted prior to lung transplantation when the patient’s antibody specificities are identified using recombinant single HLA antigen bead testing and potential donor HLA type is known. The Luminex single HLA antigen bead assays report antibodies in terms of titer (dilutional positivity) and strength (mean fluorescent intensity), which may not correlate with a positive prospective crossmatch or have clinical relevance. More sensitive assays, such as C1q reactivity that is associated with complement fixation of the antibody, are more sensitive at predicting a positive prospective crossmatch and risk of antibody-associated allograft dysfunction .
Induction Strategies at the Time of Lung Transplantation
One main strategy of induction agents is to suppress the potentially robust T cell immune response to the allograft in the immediate postoperative period after lung transplantation. Virtually all lung transplant programs use high dose methylprednisolone for immunosuppression prior to implantation of the donor organ. Currently available induction agents are adjuncts to steroids and deplete existing T cells and/or interrupt T cell activation and proliferation. These induction strategies can be classified into two groups: Monoclonal and polyclonal agents. Despite these theoretical benefits, the use of induction agents in lung transplantation remains controversial, with only 53 % of lung transplant programs using induction therapies . The decision for using induction therapy and which type must be made on a patient-centered approach based upon comorbidities to balance the effects of immunosuppression on both risk of infection and rejection.