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Lung Transplant Clinical Year in Review at the ATS 2015


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Tereza Martinu, MD
Toronto General Hospital
Toronto, ON, Canada
tereza.martinu@uhn.ca



I had the pleasure to present the Clinical Year in Review session on lung transplantation at this year's American Thoracic Society (ATS) annual meeting in Denver, in May. It really was a "clinical 3 years in review," since our topic was last presented in 2012. That made the choosing of the top articles that much more impossible.

My task was to select and discuss the 6 most important articles in lung transplantation published since 2012. I was allowed to further highlight another 15 articles. I have to admit that this was an incredibly difficult task, over which I agonized for many weeks. During my talk at the ATS I acknowledged all the hard work and dedication of so many members of our lung transplant community who have advanced the research in our field. There are so many other relevant articles that deserved discussion but that I couldn't cover in my 30-minute session.

The somewhat vague criteria that I used for my article selection were: novelty of the findings, multi-center collaboration, and clinical significance for lung transplant patients and providers. I chose articles that covered a wide range of important topics: candidate selection, expansion of the donor pool, anti-HLA antibodies, chronic lung allograft dysfunction and the emergence of new phenotypes, as well as a qualitative aspect of lung transplantation such as exercise and physical functioning. This allowed me to describe these important concepts to the general audience at the ATS.

These are the 6 main articles presented and discussed:

  1. Weill D, Benden C, Corris PA, Dark JH, Davis RD, Keshavjee S, Lederer DJ, Mulligan MJ, Patterson GA, Singer LG, Snell GI, Verleden GM, Zamora MR, Glanville AR. A consensus document for the selection of lung transplant candidates: 2014-An update from the Pulmonary Transplantation Council of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant 2015;34:1-15.
    This is an international expert consensus that outlines recommendation for lung transplant candidate selection. In this iteration, the authors discuss the role of extra-corporeal life support and retransplantation in transplant candidacy. During the discussion, I emphasized the importance of early referral, especially in the case of interstitial lung diseases and pediatric candidates. I also explained that the decision to list a patient for transplant depends significantly on the overall clinical and psycho-social picture of the patient, centre-specific experience and comfort with issues at hand, as well as the local allocation system and expected waiting times.

  2. Krutsinger D, Reed RM, Blevins A, Puri V, De Oliveira NC, Zych B, Bolukbas S, Raemdonck DV, Snell GI, Eberlein M. Lung transplantation from donation after cardiocirculatory death: a systematic review and meta-analysis. J Heart Lung Transplant 2014; 34:675-684.
    The use of donors after cardiocirculatory death is increasing but brain death donors are still favoured. This is a key article showing that using DCD donors is a safe and effective method to increase the donor pool. However, additional long-term data is needed.

  3. Tinckam KJ, Keshavjee S, Chaparro C, Barth D, Azad S, Binnie M, Chow CW, de Perrot M, Pierre AF, Waddell TK, Yasufuku K, Cypel M, Singer LG. Survival in sensitized lung transplant recipients with perioperative desensitization. Am J Transplant 2015;15:417-26.
    This article builds upon many other high-quality manuscripts on anti-HLA antibodies and desensitization. The authors show that patients can be safely transplanted against donor-specific antibodies. The advantage of the described desensitization protocol is that it is administered in the operating room at a time when the donor HLA typing is known. The use of this protocol will increase the donor pool for highly sensitized patients.

  4. Meyer KC, Raghu G, Verleden GM, Corris PA, Aurora P, Wilson KC, Brozek J, Glanville AR; ISHLT/ATS/ERS BOS Task Force Committee; ISHLT/ATS/ERS BOS Task Force Committee. An international ISHLT/ATS/ERS clinical practice guideline: diagnosis and management of bronchiolitis obliterans syndrome. Eur Respir J. 2014;44:1479-503.
    I introduced this topic by describing the current concept of chronic lung allograft dysfunction and the potential phenotypes, including BOS, that fall under the CLAD umbrella. This manuscript by Meyer et al. is a result of a multi-year multi-societal endeavour to develop comprehensive guidelines in the diagnosis and treatment of bronchiolitis obliterans syndrome. The authors describe the known risk factors for BOS and outline potential therapies, although the level of evidence for these therapies is low and the recommendations remain conditional. One important recommendation is that against the use of augmented immunosuppression for BOS (in the absence of concurrent acute rejection). The article devotes a large section to discuss many unanswered questions with regards to BOS and outlines important research needs for the future.

  5. Todd JL, Jain R, Pavlisko EN, Finlen Copeland CA, Reynolds JM, Snyder LD, Palmer SM. Impact of forced vital capacity loss on survival after the onset of chronic lung allograft dysfunction. Am J Respir Crit Care Med 2014;189:159-66.
    This article focuses on the restrictive phenotype of CLAD, first described as restrictive allograft syndrome (RAS). The authors redefine this restrictive phenotype by using spirometric data alone. The advantage of this approach is that it is applicable to all centers around the world that do not measure post-transplant lung volumes on a routine basis. This study confirms that restrictive CLAD, defined by a 20% FVC drop at CLAD diagnosis, is associated with worse outcomes, interstitial infiltrates on radiologic studies, and parenchymal fibrosis and organizing pneumonia on pathology.

  6. Langer D, Burtin C, Schepers L, Ivanova A, Verleden G, Decramer M, Troosters T, Gosselink R. Exercise training after lung transplantation improves participation in daily activity: a randomized controlled trial. Am J Transplant 2012;12:1584-92.
    I cited the study by Langer et al. to emphasize the focus on functional and quality of life outcomes post lung transplantation. It is not all just about survival. This study randomized post-transplant patients to 3 months of supervised exercise training vs. no intervention. The authors demonstrated that exercise training was associated with improved strength, increased daily walking and 6 minute walk distance, better self-reported physical functioning, as well as lower blood pressure, compared to the control group. This study stresses the importance of post-transplant exercise and physical conditioning in improving post-transplant health and quality of life.

Finally, I highlighted 15 additional studies:

ISHLT REGISTRY REPORT:
Yusen et al. The registry of the International Society for Heart and Lung Transplantation: thirty-first adult lungand heart-lung transplant report--2014; focus theme: retransplantation. J Heart Lung Transplant 2014;33:1009-24.

EXTRA-CORPOREAL LIFE SUPPORT AS BRIDGE TO TRANSPLANT:
Fuehner et al. Extracorporeal membrane oxygenation in awake patients as bridge to lung transplantation. Am J Respir Crit Care Med 2012;185:763-8.

LUNG ALLOCATION SCORE:

EX-VIVO LUNG PERFUSION
Tikkanen et al. Functional outcomes and quality of life after normothermic ex vivo lung perfusion lung transplantation. J Heart Lung Transplant 2014. In Press.

PRIMARY GRAFT DYFUNCTION
Diamond et al. Clinical risk factors for primary graft dysfunction after lung transplantation. Am J Respir Crit Care Med 2013;187:527-34.

POST-TRANSPLANT FUNCTIONAL / COGNITIVE STATUS
Smith et al. Neurobehavioral functioning and survival following lung transplantation. Chest 2014;145:604-11.

PATHOLOGY OF REJECTION
Berry et al. Pathology of pulmonary antibody-mediated rejection: 2012 update from the Pathology Council of the ISHLT. J Heart Lung Transplant. 2013;32:14-21.

ADVANCES IN IMMUNOLOGICAL PHENOTYPING
Greenland et al. Bronchoalveolar lavage cell immunophenotyping facilitates diagnosis of lung allograft rejection. AJT 2014;14:831-40.

BIOMARKERS OF LUNG ALLOGRAFT INJURY
Neujahr et al. Bile acid aspiration associated with lung chemical profile linked to other biomarkers of injury after lung transplantation. Am J Transplant 2014;14:841-8.

MICROBIOME
Willner et al. Reestablishment of recipient-associated microbiota in the lung allograft is linked to reduced risk of bronchiolitis obliterans syndrome. Am J Respir Crit Care Med 2013;187:640-7.

ANTIBODIES
Snyder et al. Implications for human leukocyte antigen antibodies after lung transplantation: a 10-year experience in 441 patients. Chest 2013;144:226-33.

RANDOMIZED CONTROLLED TRIALS

EFFECT OF AIR POLLUTION
Bhinder et al. Air pollution and the development of posttransplant chronic lung allograft dysfunction. Am J Transplant 2014;14:2749-57. ■

Disclosure Statement: The author has no conflicts of interest to disclose.




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