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Dublin, Ireland
Dr. Egan is affiliated with the Advanced Lung Disease and Lung Transplant Program, The Mater Misericordiae Hospital and St Vincents University Hospital, University College Dublin.
Correspondence to: Jim J. Egan MD, Consultant Respiratory Physician, Advanced Lung Disease and Lung Transplant Program, The Mater Misericordiae Hospital, University College Dublin, Eccles St, Dublin 7, Ireland; e-mail: jegan{at}mater.ie
Evidence-based medicine is most effectively applied in clinical scenarios, which are complex, expensive, and high-risk. In lung transplantation, applying evidence-based medicine is problematic because it involves diverse phenotypes (emphysema vs cystic fibrosis) and different surgical options (single vs double lung transplantation). Furthermore, irrespective of the frequency of advanced lung disease, lung transplantation is offered only to a select few. Therefore, to obtain evidence in the field of lung transplantation solely based on randomized controlled studies is pragmatically difficult. Alternative data sets may be equally effective in providing insight into clinical practice.1
In 1998, selection criteria for lung transplantation were published in an international consensus statement.2 This publication included all major international stakeholders and forged a discipline of common practice. Other groups followed this principle, including the Munch-Vienna collaboration and the European Australian investigators group.3 The study by Levine et al in this issue of CHEST (see page 1225), on behalf of the transplant network of the American College of Chest Physicians, is another example of the merits of collaborative data sharing. A Web-based questionnaire that was focused on common clinical problems was applied to transplant programs across North America. Its simplicity is its strength. The results are validated by closely replicating registry data pertaining to questions on the utilization of immunosuppression.
Interesting patterns of practice and uncertainty emerge. In general, prior to transplantation there appears to be a broad consensus. However, the data provided by Levine et al suggest that these criteria are being challenged. Following transplantation, a contrasting divergent approach to problems highlights the absence of published management guidelines.
The selection of patients for lung transplantation is central to the management of advanced lung disease. Age is perhaps the simplest but potentially the most controversial issue with respect to candidate selection. Published international guidelines recommend 60 years of age for single lung transplantation, and 55 years of age for double sequential lung transplantation. In contrast, 20% of programs offer single lung transplantation to patients > 65 years of age, and 25% offer double lung transplantation to patients > 60 years of age. This emerging practice is probably most pertinent to idiopathic pulmonary fibrosis patients, for whom there is no pharmacologic treatment that prevents disease progression and death. However, older recipients may demand tailored immunosuppression in light of immunosenescence and the infectious complications seen in other elderly organ transplant groups.4
The selection of patients colonized or infected with antibiotic-resistant organisms is another controversial area. A body of evidence has highlighted the importance of genomovar classification of Burkholderia cepacia, with poor outcome following transplantation being associated with B cenocepacia (genomovar III).5 However, a third of programs consider B cepacia globally to be an absolute contraindication to lung transplantation, and only 12% of programs embrace genomovar testing. In contrast, 60% of programs base their decisions regarding panresistant Pseudomonas aeruginosa on in vitro testing and synergy.
Seventy-five percent of programs consider noncompliance with medical therapy to be an absolute contraindication for lung transplantation. In practice, precluding a patient based on noncompliance may be very difficult to implement. First, the critical threshold of noncompliance is unclear. Second, a positive change in behavior to secure a place on the list does not necessarily guarantee appropriate behavior posttransplantation. These issues are especially important in the cystic fibrosis population where nonadherence to instructions is not uncommon.6
A small majority of programs have a minimum exercise requirement of 600 feet during a 6-min walk test. This appears to indicate a preference to select patients who are functionally relatively well.7 This may be a pragmatic approach to emphasize the importance of pulmonary rehabilitation. Alternatively, it may be a surrogate for initiating early listing, in order to compensate for the expected time accrued on the waiting list. However, many international programs would transplant patients who can only transfer from bed to chair.
Following transplantation, divergent patterns of treatment emerge. For instance, 50% of programs utilize induction therapy and 50% do not, while four different maintenance immunosuppression regimes are utilized equally across all programs. This heterogeneous theme is most obvious following the diagnosis of bronchiolitis obliterans syndrome (BOS), at which time 11 different treatment options may be employed. However, the most common therapy is a trial of corticosteroids combined with a change from cyclosporin to tacrolimus. The management of progressive BOS is notably consistent. The emerging pattern, based on the irreversible characteristics of the histopathology and the acknowledgment of the importance of clinical infection, is that the majority of programs utilize antibiotic therapy in the treatment of progressive BOS.8
The role of infection in the dynamic of graft survival is emphasized by the observation that 50% of programs utilize cytomegalovirus (CMV) Ig as part of their CMV prophylaxis regimen. Data have identified9 hypogammaglobulinemia as a potential risk factor for bacterial infection. Interestingly, this latter observation could indicate that the perceived survival advantage observed with the application of CMV Ig may result from broad nonspecific protection against infection.
The data provided by Levine et al emphasize that the published international selection criteria have forged some degree of standardized practice but highlight the diversity in approach to management following lung transplantation. The transplant network of the ACCP demonstrates interesting patterns of practice and uncertainty that can be used as a catalyst for further study and progress.
References
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