UCLA Lung & Heart-Lung Transplant Program
During my professional and academic career, I have focused on clinical and collaborative studies in the fields of lung transplantation and pulmonary arterial hypertension [PAH]. Unifying these two fields has been rewarding since many patients with refractory PAH will ultimately require bilateral lung transplantation. The clinical successes of our UCLA Lung Transplant Program have been realized by our own center's studies which demonstrated, firstly, that a modified leukocyte-depleted and nutrient enriched allograft reperfusion strategy could ameliorate or prevent "reperfusion lung injury" [Ardehali A, et al. Modified reperfusion and ischemia-reperfusion injury in human lung transplantation. Thorac Cardiovasc Surg 2003].
Secondly, that utilizing this strategy, liberalization of the traditional arbitrarily strict "donor lung criteria" permitted maintenance of outstanding clinical outcomes with benefit of increased donor availability and shortened "waiting times" for transplantation [Whiting D, et al. Liberalization of donor criteria in lung transplantation. Am Surg 2003].
Our transplant program presently performs approximately 50-60 cases per annum and ranks UCLA Medical Center among the top programs in the nation. Since its inception in 1990 through July 1, 2006; our program has performed 313 lung and heart-lung transplant procedures on a spectrum of cardiopulmonary maladies such as interstitial pulmonary fibrosis, chronic obstructive pulmonary disease, cystic fibrosis, pulmonary arterial hypertension, sarcoidosis and collagen vascular diseases. Our program is among only just a few in the nation, who routinely evaluate and transplant the complex patients afflicted with scleroderma and other collagen vascular diseases [Saggar R, et al. American College of Rheumatology, 2006.].
Our median waiting time for transplantation is 4.6 months which compares quite favorably to 19.9 months for our UNOS Region 5 and 31 months for the national median waiting time. This foreshortened waiting time has resulted in a reduction in our mortality rate while awaiting transplantation - 5.4% at 18 months for our center as compared to a national mortality of 17.5% for "actively UNOS listed" transplant candidates [Scientific Registry of Transplant Recipients, SRTR, 2006].
Our center's lung transplant recipient survival statistics for the most recent analysis of the interval 7/1/02-12/31/04 (N=78 cases) for 1-month, 1-year, 3-year were 94%, 88%, 78% as contrasted to national rates of 95%, 84% and 64% while the 3-year survival rate was statistically higher for our center (p<.05). With the clinical availability of the pulmonary vasodilator, inhaled nitric oxide [iNO], our studies further demonstrated that the prophylactic use of iNO could not prevent acute lung injury but significantly increased the total cost of transplantation [Ardehali A, et al. A prospective trial of inhaled nitric oxide in clinical lung transplantation. Transplantation 2001]. This study resulted in an evidence-based modification of our clinical pathways such that iNO is currently only utilized for established reperfusion acute lung injury after transplantation. Collaborative studies with the basic sciences have also been promoted with our lung transplant program. As coordinated John Belperio, M.D, bronchoalveolar lavage fluid [BALF] obtained on protocol routinely after clinical lung transplantation has been interrogated for sundry mediators of airway inflammation and remodeling to thereby advance our understanding of the immunology of both acute and chronic allograft rejection.
To date these studies have focused on C-C chemokines (e.g. MCP-1/CCR2, RANTES), interleukin-1 receptor antagonist, interleukin-13 and the C-X-CR3 related chemokines as putatively contributing to allograft dysfunction. Further, collaboration with Tomas Ganz, M.D., Ph.D. and Alexander Cole, Ph.D. in the Will Rogers Institute for Pulmonary Research has highlighted a novel and potential role for the innate immune system (e.g. Beta-2-defensins) in pathogenesis of chronic lung allograft rejection [Ross DJ, et al. Increased BAL human Beta-Defensin Type 2 in Bronchiolitis Obliterans Syndrome after lung transplantation. Transplantation 2004].
We recently received grant support to pursue a novel and intriguing investigator-initiated pilot trial for recipients experiencing lung allograft rejection. This protocol, approved by our Human Subjects Protection Committee, will examine the potential immunologic and physiologic benefits of endobronchial surfactant augmentation therapy during allograft rejection. Our ultimate goals relate to the further characterization of the complicated immunologic milieu responsible for development of chronic lung allograft rejection. The prevalence of Bronchiolitis Obliterans Syndrome [BOS] or chronic rejection, has consistently been approximately two-thirds of patients by five years after lung transplantation and represents, either directly or indirectly, the leading cause of late mortality.
I have also concentrated on the subspecialty of pulmonary arterial hypertension [PAH] with emphasis on development of a "center of excellence" at UCLA Medical Center. The program integrates a consultation service, pulmonary vasodilator hemodynamic studies and participation in both collaborative basic science and clinical research. Our program has participated in multi-center Phase II/III investigations of novel therapies, including prostacyclin analogues, phosphodiesterase-5 inhibitors and endothelin-receptor antagonists (ERA) for the spectrum of diseases associated with PAH.
We are presently investigating the aberrant angiogenesis of PAH and a potential role of inflammation and angiogenic C-X-C chemokines. Our pulmonary arterial hypertension program is currently spear-heading the development of a "Southern California PAH Consortium" which will promote collaboration in pivot drug trials and translational research in this field.
Department of Medicine resident involvement with both Lung & Heart-Lung Transplant as well as the Pulmonary Arterial Hypertension Programs has also been realized. Residents glean experience both in the outpatient clinic and inpatient functions of these programs. Further, Pulmonary & Critical Care Fellows with special interest in these areas, have increasingly participated in these programs. Presently, a senior Fellow with expertise in transplantation, is concurrently pursuing a Masters degree in Clinical Research and will join our faculty upon its completion. He will achieve this additional subspecialty training as well as qualify for certification as a "transplant pulmonologist" with United Network for Organ Sharing [UNOS].
My goals for the future of these programs will be the further integration of the clinical with collaborative and investigator-initiated research. Due to a limited numbers of lung transplant procedures performed at any one center, coordination of multi-center investigations are required to further address numerous clinical questions relating to the optimal immunosuppression, prophylaxis against opportunistic infection and treatment of BOS. With increasing integration of these clinical programs into our Division of Pulmonary, Critical Care Medicine, I anticipate the opportunity to dedicate more time to development of these vital
Dr Y. Michael Shino, my bilateral lung transplant pulmonologist