Gundeep Dhillon, MD, MPH

All Publications

• Multiple Listing in Lung Transplant Candidates: A Cohort Study. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons Mooney, J. J., Yang, L., Hedlin, H., Mohabir, P., Dhillon, G. S. 2018

  Abstract

  Lung transplant candidates can be waitlisted at more than one transplant center, a practice known as multiple listing. The factors associated with multiple listing and whether multiple listing modifies waitlist mortality or likelihood of lung transplant is unknown. US lung transplant waitlist candidates were identified as either single or multiple listed using data from the Scientific Registry of Transplant Recipients. Characteristics of single and multiple listed candidates were compared and multivariable logistic regression was used to estimate associations with multiple listing. Multiple listed candidates were matched to single listed candidates using a combination of exact and propensity score matching methods. Cox proportional hazard models were used to estimate the relationship of multiple listing on waitlist mortality and receiving a transplant. Multiple listing occurred in 2.3% of lung transplant waitlist candidates. Younger age, female gender, white race, short stature, high antibody sensitization, college or post-college education, lower lung allocation score, and a cystic fibrosis diagnosis were independently associated with multiple listing. Multiple listing was associated with an increased likelihood of lung transplant (adjusted hazard ratio [aHR] 2.74, 95% CI 2.37 to 3.16) but was not associated with waitlist mortality (aHR 0.99, 95% CI 0.68 to 1.44). This article is protected by copyright. All rights reserved.

  View details for PubMedID 30253057

• Effect of broader geographic sharing of donor lungs on lung transplant waitlist outcomes. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Mooney, J. J., Bhattacharya, J. n., Dhillon, G. S. 2018

  Abstract

  The United States lung allocation system prioritizes allocation based on medical urgency and benefit but does not address a federal mandate for broader geographic organ sharing. It is unknown whether broader geographic sharing of donor lungs would improve lung transplant waitlist outcomes.A discrete event microsimulation model simulated donor lung allocation according to different geographic lung-sharing policies, including the historic local donor service area (DSA)-based policy and hypothetical policies that prioritize candidates to donors within 500-mile or 1,000-mile geographic radii. Candidate waitlist mortality, number of transplants, and 1-year survival were compared across organ allocation policies. Waitlist mortality rates were further stratified by diagnosis, Lung Allocation Score (LAS) threshold, ABO blood type, and region.Under broader geographic lung sharing, the proportion of chronic obstructive pulmonary disease transplant recipients decreased, whereas the proportion of pulmonary fibrosis recipients increased. Waitlist mortality decreased with broader geographic lung sharing with a 21.3% decrease in waitlist mortality with 500-mile lung sharing and a 31.8% decrease in waitlist mortality with 1,000-mile lung sharing. The decrease in waitlist deaths occured across all U.S. geographic regions and was greatest in candidates with pulmonary fibrosis and/or high medical urgency.Broader geographic sharing of donor lungs could reduce waitlist mortality, particularly among pulmonary fibrosis and high-medical-urgency candidates.

  View details for PubMedID 30344025

• Racial and ethnic disparities in lung transplant listing and waitlist outcomes. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Mooney, J. J., Hedlin, H. n., Mohabir, P. n., Bhattacharya, J. n., Dhillon, G. S. 2017

  Abstract

  The United States lung transplant registry data demonstrate differences in adult waitlist mortality by race/ethnicity. It is unknown whether these differences persist after risk adjustment or occur secondary to disparities in disease severity at the time of listing.Adult lung transplant waitlist candidates between May 4, 2005 and March 5, 2015 were identified and compared by non-Hispanic white (NHW), non-Hispanic black (NHB), Hispanic and Asian race/ethnicity. A competing risk proportional hazards model was used to assess the association of race/ethnicity with the unadjusted and adjusted risk of waitlist death or removal for too sick, transplant, or removal for other reason. Disease illness severity at transplant listing was compared by race/ethnicity.There were 20,684 lung transplant candidates identified (82% NHW, 9% NHB, 6% Hispanic, 2% Asian and 1% other). Non-white candidates had higher unadjusted waitlist mortality, which was fully mitigated by adjusting for other risk factors (NHB: hazard ratio [HR] 1.05, 95% confidence interval [CI] 0.93 to 1.18; Hispanic: HR 1.02, 95% CI 0.99 to 1.18; Asian: HR 0.90, 95% CI 0.70 to 1.16). Adjusted waitlist access to transplant was lower in non-white candidates (NHB: HR 0.88, 95% CI 0.83 to 0.94; Hispanic: HR 0.87, 95% CI 0.81 to 0.94; Asian: HR 0.83, 95% CI 0.73 to 0.96). NHW candidates with obstructive lung disease and pulmonary fibrosis were older with less illness severity at listing than non-white candidates.Within the current lung allocation system, there is no difference in risk-adjusted waitlist mortality by race/ethnicity, but non-white waitlist candidates have lower risk-adjusted access to lung transplant. Non-white candidates are generally younger with greater disease-specific illness severity at the time of lung transplant listing.

  View details for PubMedID 29129372

• Effect of Transplant Center Volume on Cost and Readmissions in Medicare Lung Transplant Recipients. Annals of the American Thoracic Society Mooney, J. J., Weill, D., Boyd, J. H., Nicolls, M. R., Bhattacharya, J., Dhillon, G. S. 2016; 13 (7): 1034-1041

  Abstract

  While lung transplant recipient survival is better at higher volume centers, the effect of center volume on admission cost and early hospital readmission is unknown.To understand the association between transplant center volume and recipient risk-adjusted transplant admission cost, in-hospital mortality, and early hospital readmission in lung transplant recipients.Medicare lung transplant recipients from May 4, 2005 to December 31, 2011 were identified through linkage of transplant registry and Medicare administrative claims. Transplant admission cost was extracted, adjusted for regional price variation, and compared across low, intermediate, and high volume centers. A multivariable hierarchical generalized linear regression model was used to assess the effect of transplant center volume on recipient adjusted cost. Modified Poisson regression models were used to assess adjusted in-hospital mortality and early hospital readmission by transplant center volume.There were 3,128 Medicare lung transplant recipients identified. Unadjusted transplant cost was lower at high volume centers (mean $131,352, SD±$106,165; median $90,177, IQR $79,165-$137,915) than intermediate (mean $138,792, SD±$106,270; median $93,024, IQR $82,700-$154,857) or low volume (mean $143,609, SD±$123,316; median $95,234, IQR $83,052-$152,149) centers (p<0.0001). After adjusting for recipient health risk, low volume centers had an 11.66% greater transplant admission cost (p=0.040), a 41% greater risk for in-hospital mortality (p=0.015), and a 14% greater risk for early hospital readmission (p=0.033) compared to high volume centers. There was no significant difference in transplant cost, in-hospital mortality, or early hospital readmission between intermediate and high volume centers.Lung transplant admission cost, in-hospital mortality, and early hospital readmission rate are lower at high volume centers compared to low volume centers.

  View details for DOI 10.1513/AnnalsATS.201601-017OC

  View details for PubMedID 27064753

• Lung Quality and Utilization in Controlled Donation After Circulatory Determination of Death Within the United States AMERICAN JOURNAL OF TRANSPLANTATION Mooney, J. J., Hedlin, H., Mohabir, P. K., Vazquez, R., Nguyen, J., Ha, R., Chiu, P., Patel, K., Zamora, M. R., Weill, D., Nicolls, M. R., Dhillon, G. S. 2016; 16 (4): 1207-1215

  Abstract

  Although controlled donation after circulatory determination of death (cDCDD) could increase the supply of donor lungs within the United States, the yield of lungs from cDCDD donors remains low compared with donation after neurologic determination of death (DNDD). To explore the reason for low lung yield from cDCDD donors, Scientific Registry of Transplant Recipient data were used to assess the impact of donor lung quality on cDCDD lung utilization by fitting a logistic regression model. The relationship between center volume and cDCDD use was assessed, and the distance between center and donor hospital was calculated by cDCDD status. Recipient survival was compared using a multivariable Cox regression model. Lung utilization was 2.1% for cDCDD donors and 21.4% for DNDD donors. Being a cDCDD donor decreased lung donation (adjusted odds ratio 0.101, 95% confidence interval [CI] 0.085-0.120). A minority of centers have performed cDCDD transplant, with higher volume centers generally performing more cDCDD transplants. There was no difference in center-to-donor distance or recipient survival (adjusted hazard ratio 1.03, 95% CI 0.78-1.37) between cDCDD and DNDD transplants. cDCDD lungs are underutilized compared with DNDD lungs after adjusting for lung quality. Increasing transplant center expertise and commitment to cDCDD lung procurement is needed to improve utilization.

  View details for DOI 10.1111/ajt.13599

  View details for Web of Science ID 000373075400021

• Increased Resource Use in Lung Transplant Admissions in the Lung Allocation Score Era AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE Maxwelll, B. G., Mooney, J. J., Lee, P. H., Levitt, J. E., Chhatwani, L., Nicolls, M. R., Zamora, M. R., Valentine, V., Weill, D., Dhillon, G. S. 2015; 191 (3): 302-308

  Abstract

  Rationale: In 2005, the lung allocation score (LAS) was implemented to prioritize organ allocation to minimize waiting-list mortality and maximize one-year survival. It resulted in transplantation of older and sicker patients without changing one-year survival. Its effect on resource utilization is unknown. Objective: To determine changes in resource utilization over time in lung transplant admissions Methods: Solid organ transplant recipients were identified within the Nationwide Inpatient Sample (NIS) data from 2000 to 2011. Joinpoint regression methodology was performed to identify a time point of change in mean total hospital charges amongst lung transplant and other solid organ transplant recipients. Two temporal lung transplant recipient cohorts identified by joinpoint regression were compared for baseline characteristics and resource utilization, including total charges for index hospitalization, charges per day, length of stay, discharge disposition, tracheostomy, and need for extracorporeal membrane oxygenation (ECMO). Measurements and Main Results: A significant point of increased total hospital charges occurred for lung transplant recipients in 2005, corresponding to LAS implementation, that was not seen in other solid organ transplant recipients. Total transplant hospital charges increased by 40% in the post-LAS cohort [$569,942 ($53,229) vs. $407,489 ($28,360)] along with an increased median length of stay, daily charges, and discharge disposition other than to home. Post-LAS recipients also had higher post-transplant utilization of ECMO (OR 2.35, 95% CI 1.56, 3.55) and higher incidence of tracheostomy (OR 1.52, 95% CI 1.22, 1.89). Conclusions: LAS implementation is associated with a significant increase in resource utilization during index hospitalization for lung transplant.

  View details for DOI 10.1164/rccm.201408-1562OC

  View details for Web of Science ID 000348827000014

  View details for PubMedID 25517213

• Impact of the Lung Allocation Score on Survival Beyond 1 Year AMERICAN JOURNAL OF TRANSPLANTATION Maxwell, B. G., Levitt, J. E., Goldstein, B. A., Mooney, J. J., Nicolls, M. R., Zamora, M., Valentine, V., Weill, D., Dhillon, G. S. 2014; 14 (10): 2288-2294

  Abstract

  Implementation of the lung allocation score (LAS) in 2005 led to transplantation of older and sicker patients without altering 1-year survival. However, long-term survival has not been assessed and emphasizing the 1-year survival metric may actually sustain 1-year survival while not reflecting worsening longer-term survival. Therefore, we assessed overall and conditional 1-year survival; and the effect of crossing the 1-year threshold on hazard of death in three temporal cohorts: historical (1995-2000), pre-LAS (2001-2005) and post-LAS (2005-2010). One-year survival post-LAS remained similar to pre-LAS (83.1% vs. 82.1%) and better than historical controls (75%). Overall survival in the pre- and post-LAS cohorts was also similar. However, long-term survival among patients surviving beyond 1 year was worse than pre-LAS and similar to historical controls. Also, the hazard of death increased significantly in months 13 (1.44, 95% CI 1.10-1.87) and 14 (1.43, 95% CI 1.09-1.87) post-LAS but not in the other cohorts. While implementation of the LAS has not reduced overall survival, decreased survival among patients surviving beyond 1 year in the post-LAS cohort and the increased mortality occurring immediately after 1 year suggest a potential negative long-term effect of the LAS and an unintended consequence of increased emphasis on the 1-year survival metric.

  View details for DOI 10.1111/ajt.12903

  View details for Web of Science ID 000342663300014

• Lung Transplant Airway Hypoxia A Diathesis to Fibrosis? AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE Dhillon, G. S., Zamora, M. R., Roos, J. E., Sheahan, D., Sista, R. R., van der Starre, P., Weill, D., Nicolls, M. R. 2010; 182 (2): 230-236

  Abstract

  Chronic rejection, manifested pathologically as airway fibrosis, is the major problem limiting long-term survival in lung transplant recipients. Airway hypoxia and ischemia, resulting from a failure to restore the bronchial artery (BA) circulation at the time of transplantation, may predispose patients to chronic rejection. To address this possibility, clinical information is needed describing the status of lung perfusion and airway oxygenation after transplantation.To determine the relative pulmonary arterial blood flow, airway tissue oxygenation and BA anatomy in the transplanted lung was compared with the contralateral native lung in lung allograft recipients.Routine perfusion scans were evaluated at 3 and 12 months after transplantation in 15 single transplant recipients. Next, airway tissue oximetry was performed in 12 patients during surveillance bronchoscopies in the first year after transplant and in 4 control subjects. Finally, computed tomography (CT)-angiography studies on 11 recipients were reconstructed to evaluate the post-transplant anatomy of the BAs.By 3 months after transplantation, deoxygenated pulmonary arterial blood is shunted away from the native lung to the transplanted lung. In the first year, healthy lung transplant recipients exhibit significant airway hypoxia distal to the graft anastomosis. CT-angiography studies demonstrate that BAs are abbreviated, generally stopping at or before the anastomosis, in transplant airways.Despite pulmonary artery blood being shunted to transplanted lungs after transplantation, grafts are hypoxic compared with both native (diseased) and control airways. Airway hypoxia may be due to the lack of radiologically demonstrable BAs after lung transplantation.

  View details for DOI 10.1164/rccm.200910-1573OC

  View details for Web of Science ID 000280206700014

  View details for PubMedID 20339145

  View details for PubMedCentralID PMC3269232

• Increasing Lung Allocation Scores Predict Worsened Survival Among Lung Transplant Recipients AMERICAN JOURNAL OF TRANSPLANTATION Liu, V., Zamora, M. R., Dhillon, G. S., Weill, D. 2010; 10 (4): 915-920

  Abstract

  Implemented in 2005, the lung allocation score (LAS) aims to distribute donor organs based on overall survival benefits for all potential recipients, rather than on waiting list time accrued. While prior work has shown that patients with scores greater than 46 are at increased risk of death, it is not known whether that risk is equivalent among such patients when stratified by LAS score and diagnosis. We retrospectively evaluated 5331 adult lung transplant recipients from May 2005 to February 2009 to determine the association of LAS (groups based on scores of < or =46, 47-59, 60-79 and > or =80) and posttransplant survival. When compared with patients with LAS < or = 46, only those with LAS > or = 60 had an increased risk of death (LAS 60-79: hazard ratio [HR], 1.52; 95% confidence interval [CI], 1.21-1.90; LAS > or = 80: HR, 2.03; CI, 1.61-2.55; p < 0.001) despite shorter median waiting list times. This risk persisted after adjusting for age, diagnosis, transplant center volume and donor characteristics. By specific diagnosis, an increased hazard was observed in patients with COPD with LAS > or = 80, as well as those with IPF with LAS > or = 60.

  View details for DOI 10.1111/j.1600-6143.2009.03003.x

  View details for Web of Science ID 000275768300030

  View details for PubMedID 20121747

  View details for PubMedCentralID PMC2860663

• Development and validation of primary graft dysfunction predictive algorithm for lung transplant candidates. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Diamond, J. M., Anderson, M. R., Cantu, E., Clausen, E. S., Shashaty, M. G., Kalman, L., Oyster, M., Crespo, M. M., Bermudez, C. A., Benvenuto, L., Palmer, S. M., Snyder, L. D., Hartwig, M. G., Wille, K., Hage, C., McDyer, J. F., Merlo, C. A., Shah, P. D., Orens, J. B., Dhillon, G. S., Lama, V. N., Patel, M. G., Singer, J. P., Hachem, R. R., Michelson, A. P., Hsu, J., Russell Localio, A., Christie, J. D. 2024; 43 (4): 633-641

  Abstract

  Primary graft dysfunction (PGD) is the leading cause of early morbidity and mortality after lung transplantation. Accurate prediction of PGD risk could inform donor approaches and perioperative care planning. We sought to develop a clinically useful, generalizable PGD prediction model to aid in transplant decision-making.We derived a predictive model in a prospective cohort study of subjects from 2012 to 2018, followed by a single-center external validation. We used regularized (lasso) logistic regression to evaluate the predictive ability of clinically available PGD predictors and developed a user interface for clinical application. Using decision curve analysis, we quantified the net benefit of the model across a range of PGD risk thresholds and assessed model calibration and discrimination.The PGD predictive model included distance from donor hospital to recipient transplant center, recipient age, predicted total lung capacity, lung allocation score (LAS), body mass index, pulmonary artery mean pressure, sex, and indication for transplant; donor age, sex, mechanism of death, and donor smoking status; and interaction terms for LAS and donor distance. The interface allows for real-time assessment of PGD risk for any donor/recipient combination. The model offers decision-making net benefit in the PGD risk range of 10% to 75% in the derivation centers and 2% to 10% in the validation cohort, a range incorporating the incidence in that cohort.We developed a clinically useful PGD predictive algorithm across a range of PGD risk thresholds to support transplant decision-making, posttransplant care, and enrich samples for PGD treatment trials.

  View details for DOI 10.1016/j.healun.2023.11.019

  View details for PubMedID 38065239

  View details for PubMedCentralID PMC10947904

• The Impact of Donor Smoking on Primary Graft Dysfunction and Mortality after Lung Transplantation. American journal of respiratory and critical care medicine Diamond, J. M., Cantu, E., Calfee, C. S., Anderson, M. R., Clausen, E. S., Shashaty, M. G., Courtwright, A. M., Kalman, L., Oyster, M., Crespo, M. M., Bermudez, C. A., Benvenuto, L., Palmer, S. M., Snyder, L. D., Hartwig, M. G., Todd, J. L., Wille, K., Hage, C., McDyer, J. F., Merlo, C. A., Shah, P. D., Orens, J. B., Dhillon, G. S., Weinacker, A. B., Lama, V. N., Patel, M. G., Singer, J. P., Hsu, J., Localio, A. R., Christie, J. D. 2023

  Abstract

  Primary graft dysfunction (PGD) is the leading cause of early morbidity and mortality after lung transplantation. Prior studies implicated proxy defined donor smoking as a risk factor for PGD and mortality.We aimed to more accurately assess the impact of donor smoke exposure on PGD and mortality using quantitative smoke exposure biomarkers.We performed a multicenter prospective cohort study of lung transplant recipients enrolled in the Lung Transplant Outcomes Group cohort between 2012-2018. PGD was defined as grade 3 at 48 or 72 hours after lung reperfusion. Donor smoking was defined utilizing accepted thresholds of urinary biomarkers of nicotine exposure (cotinine) and tobacco-specific nitrosamine (NNAL) in addition to clinical history. The donor smoking-PGD association was assessed using logistic regression and survival analysis was performed using inverse probability of exposure weighting according to smoking category.Active donor smoking prevalence varied by definition, with 34-43% based on urinary cotinine, 28% by urinary NNAL, and 37% by clinical documentation. The standardized risk of PGD associated with active donor smoking was higher across all definitions, with an absolute risk increase of 11·5% (95%CI 3·8, 19·2) by urinary cotinine, 5·7% (95%CI -3·4, 14·9) by urinary NNAL, and 6·5% (95%CI -2·8, 15·8) defined clinically. Donor smoking was not associated with differential post-lung transplant survival using any definition.Donor smoking associates with a modest increase in PGD risk but not with increased recipient mortality. Use of lungs from smokers is likely safe and may increase lung donor availability.

  View details for DOI 10.1164/rccm.202303-0358OC

  View details for PubMedID 37734031

• A randomized controlled trial of presatovir for respiratory syncytial virus after lung transplant. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Gottlieb, J., Torres, F., Haddad, T., Dhillon, G., Dilling, D. F., Knoop, C., Rampolla, R., Walia, R., Ahya, V., Kessler, R., Budev, M., Neurohr, C., Glanville, A. R., Jordan, R., Porter, D., McKevitt, M., German, P., Guo, Y., Chien, J. W., Watkins, T. R., Zamora, M. R. 2023

  Abstract

  Respiratory syncytial virus (RSV) infection in lung transplant recipients is associated with high morbidity. This study evaluated the RSV fusion inhibitor presatovir in RSV-infected lung transplant recipients.In this international Phase 2b, randomized, double-blind, placebo-controlled trial (NCT02534350), adult lung transplant recipients with symptomatic confirmed RSV infection for ≤7 days received oral presatovir 200 mg on day 1 and 100 mg daily on days 2 to 14, or placebo (2:1), with follow-up through day 28. There were 2 coprimary endpoints: time-weighted average change in nasal RSV load from day 1 to 7, calculated from nasal swabs, in the full analysis set ([FAS]; all patients who received study drug and had quantifiable baseline nasal RSV load) and time-weighted average change in nasal RSV load from day 1 to 7 in the subset of patients with pretreatment symptom duration at the median or shorter of the FAS. Secondary endpoints were changes in respiratory infection symptoms assessed using the Influenza Patient-Reported Outcomes questionnaire and lung function measured by spirometry.Sixty-one patients were randomized, 40 received presatovir, 20 placebo, and 54 were included in efficacy analyses. Presatovir did not significantly improve the primary endpoint in the FAS (treatment difference [95% CI], 0.10 [-0.43, 0.63] log10 copies/ml; p = 0.72) or the shorter symptom-duration subgroup (-0.12 [-0.94, 0.69] log10 copies/ml; p = 0.76). Secondary endpoints were not different between presatovir and placebo groups. Presatovir was generally well tolerated.Presatovir treatment did not significantly improve change in nasal RSV load, symptoms, or lung function in lung transplant recipients.

  View details for DOI 10.1016/j.healun.2023.01.013

  View details for PubMedID 36964084

• Tumor Microenvironment Determinants of Immunotherapy Response Identified By Integrated Host & Viral Analysis of Post-Transplant Lymphoproliferative Disorders Schroers-Martin, J., Garofalo, A., Soo, J., Boegeholz, J., Alig, S. K., Sworder, B., Liu, C., Luikart, H., Gamino, G., Morales, D., Freystaetter, K., Hamilton, J., Kurtz, D. M., Hollander, S., Rosenthal, D., Dhillon, G., Raikhelkar, J., Verleden, S., Nijland, M., Agbor-Enoh, S., Andreas, M., Kfoury, A., Ross, H., Zaffiri, L., Natkunam, Y., Diehn, M., Khush, K., Alizadeh, A. A. AMER SOC HEMATOLOGY. 2022

  View details for DOI 10.1182/blood-2022-158647

  View details for Web of Science ID 000893223200073

• Contemporary trends in PGD incidence, outcomes, and therapies. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Cantu, E., Diamond, J. M., Cevasco, M., Suzuki, Y., Crespo, M., Clausen, E., Dallara, L., Ramon, C. V., Harmon, M. T., Bermudez, C., Benvenuto, L., Anderson, M., Wille, K. M., Weinacker, A., Dhillon, G. S., Orens, J., Shah, P., Merlo, C., Lama, V., McDyer, J., Snyder, L., Palmer, S., Hartwig, M., Hage, C. A., Singer, J., Calfee, C., Kukreja, J., Greenland, J. R., Ware, L. B., Localio, R., Hsu, J., Gallop, R., Christie, J. D. 2022

  Abstract

  BACKGROUND: We sought to describe trends in extracorporeal membrane oxygenation (ECMO) use, and define the impact on PGD incidence and early mortality in lung transplantation.METHODS: Patients were enrolled from August 2011 to June 2018 at 10 transplant centers in the multi-center Lung Transplant Outcomes Group prospective cohort study. PGD was defined as Grade 3 at 48 or 72 hours, based on the 2016 PGD ISHLT guidelines. Logistic regression and survival models were used to contrast between group effects for event (i.e., PGD and Death) and time-to-event (i.e., death, extubation, discharge) outcomes respectively. Both modeling frameworks accommodate the inclusion of potential confounders.RESULTS: A total of 1,528 subjects were enrolled with a 25.7% incidence of PGD. Annual PGD incidence (14.3%-38.2%, p=.0002), median LAS (38.0-47.7 p=.009) and the use of ECMO salvage for PGD (5.7%-20.9%, p=.007) increased over the course of the study. PGD was associated with increased 1 year mortality (OR 1.7 [95% C.I. 1.2, 2.3], p=.0001). Bridging strategies were not associated with increased mortality compared to non-bridged patients (p=.66); however, salvage ECMO for PGD was significantly associated with increased mortality (OR 1.9 [1.3, 2.7], p=.0007). Restricted mean survival time comparison at 1-year demonstrated 84.1 days lost in venoarterial salvaged recipients with PGD when compared to those without PGD (ratio 1.3 [1.1, 1.5]) and 27.2 days for venovenous with PGD (ratio 1.1 [1.0, 1.4]).CONCLUSIONS: PGD incidence continues to rise in modern transplant practice paralleled by significant increases in recipient severity of illness. Bridging strategies have increased but did not affect PGD incidence or mortality. PGD remains highly associated with mortality and is increasingly treated with salvage ECMO.

  View details for DOI 10.1016/j.healun.2022.08.013

  View details for PubMedID 36216694

• First lung and kidney multi-organ transplant following COVID-19 Infection. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Guenthart, B. A., Krishnan, A., Alassar, A., Madhok, J., Kakol, M., Miller, S., Cole, S. P., Rao, V. K., Acero, N. M., Hill, C. C., Cheung, C., Jackson, E. C., Feinstein, I., Tsai, A. H., Mooney, J. J., Pham, T., Elliott, I. A., Liou, D. Z., La Francesca, S., Shudo, Y., Hiesinger, W., MacArthur, J. W., Brar, N., Berry, G. J., McCarra, M. B., Desai, T. J., Dhillon, G. S., Woo, Y. J. 2021

  Abstract

  As the world responds to the global crisis of the COVID-19 pandemic an increasing number of patients are experiencing increased morbidity as a result of multi-organ involvement. Of these, a small proportion will progress to end-stage lung disease, become dialysis dependent, or both. Herein, we describe the first reported case of a successful combined lung and kidney transplantation in a patient with COVID-19. Lung transplantation, isolated or combined with other organs, is feasible and should be considered for select patients impacted by this deadly disease.

  View details for DOI 10.1016/j.healun.2021.02.015

  View details for PubMedID 34059432

• Gastric per-oral endoscopic myotomy for severe post-lung transplant gastroparesis: A single-center experience. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Podboy, A. J., Clarke, J. O., Nguyen, L. A., Mooney, J. J., Dhillon, G. S., Hwang, J. H. 2020

  View details for DOI 10.1016/j.healun.2020.06.019

  View details for PubMedID 32711933

• Multiple listing in lung transplant candidates: A cohort study AMERICAN JOURNAL OF TRANSPLANTATION Mooney, J. J., Yang, L., Hedlin, H., Mohabir, P., Dhillon, G. S. 2019; 19 (4): 1098–1108

  View details for DOI 10.1111/ajt.15124

  View details for Web of Science ID 000462258700016

• Effect of broader geographic sharing of donor lungs on lung transplant waitlist outcomes JOURNAL OF HEART AND LUNG TRANSPLANTATION Mooney, J. J., Bhattacharya, J., Dhillon, G. S. 2019; 38 (2): 136–44

  View details for DOI 10.1016/j.healun.2018.09.007

  View details for Web of Science ID 000456717200006

• Estimated Impact of Hepatitis C Positive Lung Donor Utilization on US Donor Lung Supply. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons Mooney, J. J., Purington, N. n., Mohabir, P. n., Dhillon, G. S. 2019

  Abstract

  The availability of highly effective direct-acting antiviral agent (DAA) medications for Hepatitis C virus (HCV) has led to reports of safely transplanting HCV+ donor lungs to HCV- candidates. However, it remains unclear how the ability to use HCV+ donor lungs for lung transplant could impact the number of donor lungs available for transplant. Using Scientific Registry of Transplant Recipient data we identified all deceased organ donors within the United States from March 1, 2015 to February 28, 2018 and stratified by HCV status. A donor prediction model for lung donation was derived and validated within HCV- donors and applied to HCV+ donors to estimate the number of acceptable HCV+ lung donors. Of 29,481 eligible donors, 2,054 (7.0%) were HCV+ donors with 82 HCV+ donors' lungs being utilized for transplant during the study period. The prediction model for donor lung donation (specificity 92.6%, sensitivity 65.6%) estimated 248 HCV+ donors (75 non-viremic, 173 viremic) were acceptable for lung transplant during the study period, suggesting that 166 acceptable HCV+ lung donors were discarded. The ability to transplant lungs from HCV+ organ donors would lead to an estimated nationwide increase of at least 55 donor lungs per year, including 44 from HCV viremic donors. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/ajt.15558

  View details for PubMedID 31394016

• Fortification of Preservation Solution With Nitroprusside Does Not Alter Lung Allograft Survival in Clinical Human Lung Transplantation. The Ochsner journal Boys, J. A., Bowdish, M. E., Subramanyan, R. K., Shemanski, K. A., Dhillon, G. S., Toda, K., Perrillo, J., Seoane, L., Bates, M. J., Parrino, P. E., Kooperkamp, H., Valentine, V. G., Emory, W. B., Ochsner, J. L., McFadden, P. M. 2019; 19 (3): 235–40

  Abstract

  Background: Nitric oxide improves gas exchange following primary lung allograft dysfunction. Nitroprusside, a potent nitric oxide donor, has reduced reperfusion injury and improved oxygenation in experimental lung transplantation. Methods: We sought to study the effect on lung allograft outcomes of fortifying the preservation solution with nitroprusside. We conducted a single-center clinical study of 46 consecutive lung recipients between 1998 and 2000: 24 patients received donor organs preserved in modified Euro-Collins solution with prostaglandin E1 (PGE1) (control group), and 22 patients received organs preserved in modified Euro-Collins with PGE1 and nitroprusside (NP group). The primary endpoint was overall survival. Results: Baseline characteristics were similar between the groups except for a significantly longer graft ischemic time in the NP group vs the control group (253.3 ± 52 vs 225.3 ± 41 minutes, respectively, P=0.04). No significant differences were found in partial pressure arterial oxygen to fraction inspired oxygen ratio at ≤48 hours, primary graft dysfunction, or bronchiolitis obliterans-free days. Overall survival at 1, 3, and 5 years was 89%, 73%, and 63% in the control group and 76%, 38%, and 23% in the NP group. Log-rank survival analysis showed that the NP group had a significantly increased risk of mortality (P=0.034) compared to the control group. Conclusion: The addition of nitroprusside to the lung transplant perfusate in this clinical trial did not improve survival; however, a large randomized trial would likely reduce confounding ischemia times and increase the power of the study.

  View details for DOI 10.31486/toj.19.0027

  View details for PubMedID 31528134

• Human leukocyte antigens antibodies after lung transplantation: Primary results of the HALT study AMERICAN JOURNAL OF TRANSPLANTATION Hachem, R. R., Kamoun, M., Budev, M. M., Askar, M., Ahya, V. N., Lee, J. C., Levine, D. J., Pollack, M. S., Dhillon, G. S., Weill, D., Schechtman, K. B., Leard, L. E., Golden, J. A., Baxter-Lowe, L., Mohanakumar, T., Tyan, D. B., Yusen, R. D. 2018; 18 (9): 2285–94

  Abstract

  Donor-specific antibodies (DSA) to mismatched human leukocyte antigens (HLA) are associated with worse outcomes after lung transplantation. To determine the incidence and characteristics of DSA early after lung transplantation, we conducted a prospective multicenter observational study that used standardized treatment and testing protocols. Among 119 transplant recipients, 43 (36%) developed DSA: 6 (14%) developed DSA only to class I HLA, 23 (53%) developed DSA only to class II HLA, and 14 (33%) developed DSA to both class I and class II HLA. The median DSA mean fluorescence intensity (MFI) was 3197. We identified a significant association between the Lung Allocation Score and the development of DSA (HR = 1.02, 95% CI: 1.001-1.03, P = .047) and a significant association between DSA with an MFI ≥ 3000 and acute cellular rejection (ACR) grade ≥ A2 (HR = 2.11, 95% CI: 1.04-4.27, P = .039). However, we did not detect an association between DSA and survival. We conclude that DSA occur frequently early after lung transplantation, and most target class II HLA. DSA with an MFI ≥ 3000 have a significant association with ACR. Extended follow-up is necessary to determine the impact of DSA on other important outcomes.

  View details for PubMedID 29687961

• Cell-free hemoglobin promotes primary graft dysfunction through oxidative lung endothelial injury JCI INSIGHT Shaver, C. M., Wickersham, N., McNeil, J., Nagata, H., Miller, A., Landstreet, S. R., Kuck, J. L., Diamond, J. M., Lederer, D. J., Kawut, S. M., Palmer, S. M., Wille, K. M., Weinacker, A., Lama, V. N., Crespo, M. M., Orens, J. B., Shah, P. D., Hage, C. A., Cantu, E., Porteous, M. K., Dhillon, G., McDyer, J., Bastarache, J. A., Christie, J. D., Ware, L. B., Lung Transplant Outcomes Grp LTOG 2018; 3 (2)

  Abstract

  Primary graft dysfunction (PGD) is acute lung injury within 72 hours of lung transplantation. We hypothesized that cell-free hemoglobin (CFH) contributes to PGD by increasing lung microvascular permeability and tested this in patients, ex vivo human lungs, and cultured human lung microvascular endothelial cells. In a nested case control study of 40 patients with severe PGD at 72 hours and 80 matched controls without PGD, elevated preoperative CFH was independently associated with increased PGD risk (odds ratio [OR] 2.75, 95%CI, 1.23-6.16, P = 0.014). The effect of CFH on PGD was magnified by reperfusion fraction of inspired oxygen (FiO2) ≥ 0.40 (OR 3.41, P = 0.031). Isolated perfused human lungs exposed to intravascular CFH (100 mg/dl) developed increased vascular permeability as measured by lung weight (CFH 14.4% vs. control 0.65%, P = 0.047) and extravasation of Evans blue-labeled albumin dye (EBD) into the airspace (P = 0.027). CFH (1 mg/dl) also increased paracellular permeability of human pulmonary microvascular endothelial cell monolayers (hPMVECs). Hyperoxia (FiO2 = 0.95) increased human lung and hPMVEC permeability compared with normoxia (FiO2 = 0.21). Treatment with acetaminophen (15 μg/ml), a specific hemoprotein reductant, prevented CFH-dependent permeability in human lungs (P = 0.046) and hPMVECs (P = 0.037). In summary, CFH may mediate PGD through oxidative effects on microvascular permeability, which are augmented by hyperoxia and abrogated by acetaminophen.

  View details for PubMedID 29367464

• Microhemorrhage-associated tissue iron enhances the risk forAspergillus fumigatusinvasion in a mouse model of airway transplantation. Science translational medicine Hsu, J. L., Manouvakhova, O. V., Clemons, K. V., Inayathullah, M. n., Tu, A. B., Sobel, R. A., Tian, A. n., Nazik, H. n., Pothineni, V. R., Pasupneti, S. n., Jiang, X. n., Dhillon, G. S., Bedi, H. n., Rajadas, J. n., Haas, H. n., Aurelian, L. n., Stevens, D. A., Nicolls, M. R. 2018; 10 (429)

  Abstract

  Invasive pulmonary disease due to the moldAspergillus fumigatuscan be life-threatening in lung transplant recipients, but the risk factors remain poorly understood. To study this process, we used a tracheal allograft mouse model that recapitulates large airway changes observed in patients undergoing lung transplantation. We report that microhemorrhage-related iron content may be a major determinant ofA. fumigatusinvasion and, consequently, its virulence. Invasive growth was increased during progressive alloimmune-mediated graft rejection associated with high concentrations of ferric iron in the graft. The role of iron inA. fumigatusinvasive growth was further confirmed by showing that this invasive phenotype was increased in tracheal transplants from donor mice lacking the hemochromatosis gene (Hfe -/- ). The invasive phenotype was also increased in mouse syngrafts treated with topical iron solution and in allograft recipients receiving deferoxamine, a chelator that increases iron bioavailability to the mold. The invasive growth of the iron-intolerantA. fumigatusdouble-knockout mutant (ΔsreA/ΔcccA) was lower than that of the wild-type mold. Alloimmune-mediated microvascular damage and iron overload did not appear to impair the host's immune response. In human lung transplant recipients, positive staining for iron in lung transplant tissue was more commonly seen in endobronchial biopsy sections from transplanted airways than in biopsies from the patients' own airways. Collectively, these data identify iron as a major determinant ofA. fumigatusinvasive growth and a potential target to treat or preventA. fumigatusinfections in lung transplant patients.

  View details for PubMedID 29467298

• Pulmonary Infections in Immunocompromised Hosts: Clinical. Journal of thoracic imaging Vazquez Guillamet, C. n., Hsu, J. L., Dhillon, G. n., Vazquez Guillamet, R. n. 2018

  Abstract

  Pulmonary infections in immunocompromised patients remain a significant contributor to mortality, morbidity, and health care-associated costs in such a vulnerable patient population. Their epidemiology is changing, set forth by new trends in immunosuppressive regimens and also prophylaxis. The host characteristics, presenting clinical symptomatology, along with radiographic patterns, have also evolved. The microbiology diagnostics are now enriched with nonculture methods for better identification of the causative pathogens. Chest imaging remains the cornerstone of the initial workup. Our article will examine the new trends in epidemiology, clinical findings, and diagnostics for immunocompromised patients with pulmonary infections (transplant recipients, neutropenic hosts, HIV-infected patients, and patients with autoimmune conditions). We will also review the differential diagnosis that most of the times includes malignancies and drug or radiation-related toxicities.

  View details for PubMedID 30048345

• Delirium after Lung Transplantation: Association with Recipient Characteristics, Hospital Resource Utilization, and Mortality Sher, Y., Maldonado, J., Mooney, J., Dhillon, G., Lee, R. PERGAMON-ELSEVIER SCIENCE LTD. 2017: 168

  View details for DOI 10.1016/j.jpsychores.2017.03.288

  View details for Web of Science ID 000403523800098

• Combined heart lung transplantation: an updated review of the current literature. Transplantation Pasupneti, S., Dhillon, G., Reitz, B., Khush, K. 2017

  Abstract

  Heart lung transplantation is a viable treatment option for patients with many end stage heart and lung pathologies. However, given the complex nature of the procedure, it is imperative that patients are selected appropriately and the clinician is aware of the many unique aspects in management of this population. This review seeks to describe updated organ selection policies, peri and postoperative management strategies, monitoring of graft function, and clinical outcomes for patients following combined heart-lung transplantation in the current era.

  View details for DOI 10.1097/TP.0000000000001820

  View details for PubMedID 28505026

• Leukotriene B-4 antagonism ameliorates experimental lymphedema SCIENCE TRANSLATIONAL MEDICINE Tian, W., Rockson, S. G., Jiang, X., Kim, J., Begaye, A., Shuffle, E. M., Tu, A. B., Cribb, M., Nepiyushchikh, Z., Feroze, A. H., Zamanian, R. T., Dhillon, G. S., Voelkel, N. F., Peters-Golden, M., Kitajewski, J., Dixon, J. B., Nicolls, M. R. 2017; 9 (389)

  View details for DOI 10.1126/scitranslmed.aal3920

  View details for Web of Science ID 000400897600004

• Delirium after lung transplantation: Association with recipient characteristics, hospital resource utilization, and mortality. Clinical transplantation Sher, Y., Mooney, J., Dhillon, G., Lee, R., Maldonado, J. R. 2017; 31 (5)

  Abstract

  Delirium is associated with increased morbidity and mortality. The factors associated with post-lung transplant delirium and its impact on outcomes are under characterized.The medical records of 163 consecutive adult lung transplant recipients were reviewed for delirium within 5 days (early-onset) and 30 hospital days (ever-onset) post-transplantation. A multivariable logistic regression model assessed factors associated with delirium. Multivariable negative binomial regression and Cox proportional hazards models assessed the association of delirium with ventilator duration, intensive care unit (ICU) length of stay (LOS), hospital LOS and one-year mortality.Thirty six % developed early-onset and 44% - ever-onset delirium. Obesity (OR 6.35, 95% CI 1.61-24.98) and bolused benzodiazepines within the first post-operative day (OR 2.28, 95% CI 1.07-4.89) were associated with early-onset delirium. Early-onset delirium was associated with longer adjusted mechanical ventilation duration (p=0.001), ICU LOS (p<0.001), and hospital LOS (p=0.005). Ever-onset delirium was associated with longer ICU (p<0.001) and hospital LOS (p<0.001). After adjusting for clinical variables, delirium was not significantly associated with one-year mortality (early-onset HR 1.65, 95% CI 0.67-4.03; ever-onset HR 1.70, 95% CI 0.63-4.55).Delirium is common after lung transplant surgery and associated with increased hospital resources. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/ctr.12966

  View details for PubMedID 28314081

• Post Lung Transplant Survival of Recipients with Sarcoidosis in LAS Era Mooney, J., Boyd, J., Chhatwani, L., Dhillon, G. S. ELSEVIER SCIENCE INC. 2017: S307

  View details for Web of Science ID 000398839801078

• Investigating the value of right heart echocardiographic metrics for detection of pulmonary hypertension in patients with advanced lung disease. The international journal of cardiovascular imaging Amsallem, M., Boulate, D., Kooreman, Z., Zamanian, R. T., Fadel, G., Schnittger, I., Fadel, E., McConnell, M. V., Dhillon, G., Mercier, O., Haddad, F. 2017

  Abstract

  This study determined whether novel right heart echocardiography metrics help to detect pulmonary hypertension (PH) in patients with advanced lung disease (ALD). We reviewed echocardiography and catheterization data of 192 patients from the Stanford ALD registry and echocardiograms of 50 healthy controls. Accuracy of echocardiographic right heart metrics to detect PH was assessed using logistic regression and area under the ROC curves (AUC) analysis. Patients were divided into a derivation (n = 92) and validation cohort (n = 100). Experimental validation was assessed in a piglet model of mild PH followed longitudinally. Tricuspid regurgitation (TR) was not interpretable in 52% of patients. In the derivation cohort, right atrial maximal volume index (RAVI), ventricular end-systolic area index (RVESAI), free-wall longitudinal strain and tricuspid annular plane systolic excursion (TAPSE) differentiated patients with and without PH; 20% of patients without PH had moderate to severe RV enlargement by RVESAI. On multivariate analysis, RAVI and TAPSE were independently associated with PH (AUC = 0.77, p < 0.001), which was confirmed in the validation cohort (0.78, p < 0.001). Presence of right heart metrics abnormalities did not improve detection of PH in patients with interpretable TR (p > 0.05) and provided moderate detection value in patients without TR. Only two patients with more severe PH (mean pulmonary pressure 35 and 36 mmHg) were missed. The animal model confirmed that right heart enlargement discriminated best pigs with PH from shams. This study highlights the frequency of right heart enlargement and dysfunction in ALD irrespectively from presence of PH, therefore limiting their use for detection of PH.

  View details for DOI 10.1007/s10554-017-1069-3

  View details for PubMedID 28120156

• Report of the International Society for Heart and Lung Transplantation Working Group on Primary Lung Graft Dysfunction, part II: Epidemiology, risk factors, and outcomes-A 2016 Consensus Group statement of the International Society for Heart and Lung Transplantation. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Diamond, J. M., Arcasoy, S. n., Kennedy, C. C., Eberlein, M. n., Singer, J. P., Patterson, G. M., Edelman, J. D., Dhillon, G. n., Pena, T. n., Kawut, S. M., Lee, J. C., Girgis, R. n., Dark, J. n., Thabut, G. n. 2017; 36 (10): 1104–13

  View details for PubMedID 28802530

• Long-Term Impact Of Non Invasive Open Ventilation (niovtm) On Dyspnea In Patients With Chronic Obstructive Pulmonary Disease And Idiopathic Pulmonary Fibrosis Lam, K., Breiburg, A., Kuschner, W., Zone, C., Dhillon, G. AMER THORACIC SOC. 2017

  View details for Web of Science ID 000400372505516

• Lung transplantation following death by drowning: a review of the current literature CLINICAL TRANSPLANTATION Pasupneti, S., Patel, K., Mooney, J. J., Chhatwani, L., Dhillon, G., Weill, D. 2016; 39 (10): 1195-1197

  Abstract

  While multiple donor characteristics have been cited as ideal for lung transplantation, there are minimal widely accepted exclusion criteria. One criterion that many centers view with hesitation is death by drowning. However, recent literature suggests such donors may result in acceptable outcomes following transplation. This review highlights a case of a patient who underwent successful bilateral lung transplant from a donor following a drowning event. A review of the current literature is presented, concluding with a new proposed set of favorable donor criteria following death by drowning. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/ctr.12822

  View details for Web of Science ID 000385758800002

• Analysis of pulmonary non-tuberculous mycobacterial infections after lung transplantation. Transplant infectious disease Shah, S. K., McAnally, K. J., Seoane, L., Lombard, G. A., LaPlace, S. G., Lick, S., Dhillon, G. S., Valentine, V. G. 2016; 18 (4): 585-591

  Abstract

  Non-tuberculous mycobacteria (NTM) are important pathogens in lung transplant recipients. This study describes the spectrum of NTM respiratory tract infections and examines the association of NTM infections with lung transplant complications.Data from 208 recipients transplanted from November 1990 to November 2005 were analyzed. Follow-up data were available to November 2010. Lung infection was defined by bronchoalveolar lavage, sputum, or blood cultures in the appropriate clinical setting. All identified NTM respiratory tract infections were tabulated. The cohort of patients with NTM lung infections (NTM+) were compared to the cohort without infection (NTM-). Univariate and multivariate analysis was performed to determine characteristics associated with NTM infection. Survival analyses for overall survival and development of bronchiolitis obliterans syndrome (BOS) were also performed.In total, 52 isolates of NTM lung infection were identified in 30 patients. The isolates included Mycobacterium abscessus (46%), Mycobacterium avium complex (MAC) (36%), Mycobacterium gordonae (9%), Mycobacterium chelonae (7%), and Mycobacterium fortuitum (2%), with multiple NTM isolates seen on 3 different occasions. The overall incidence was 14%, whereas cumulative incidences at 1, 3, and 5 years after lung transplantation were 11%, 15%, and 20%, respectively. Comparisons between the NTM+ and NTM- cohorts revealed that NTM+ patients were more likely to be African-American and have cytomegalovirus mismatch. Although no difference was seen in survival, the NTM+ cohort was more likely to develop BOS (80% vs. 58%, P = 0.02). NTM+ infection, however, was not independently associated with development of BOS by multivariate analysis.With nearly 20 years of follow-up, 14% of lung recipients develop NTM respiratory tract infections, with M. abscessus and MAC more commonly identified. M. gordonae was considered responsible for nearly 10% of NTM infections. Although survival of patients with NTM infections is similar, a striking difference in BOS rates is present in the NTM+ and NTM- groups.

  View details for DOI 10.1111/tid.12546

  View details for PubMedID 27368989

• Critical assessment of right heart echocardiography for detection of pulmonary hypertension in advanced lung disease Amsallem, M., Boulate, D., Kooreman, Z. E., Zamanian, R., Fadel, G., Schnittger, I., Fadel, E., Dhillon, G., McConnell, M. V., Haddad, F. OXFORD UNIV PRESS. 2016: 1363

  View details for Web of Science ID 000383869506551

• Complement-Fixing Donor Specific Antibody and Pathologic Findings in Lung Atlografts Chhatwani, L., Mooney, J., Patel, K., Emtiazjoo, A., Lawrence, A., Berry, G., Tyan, D., Dhillon, G. ELSEVIER SCIENCE INC. 2016: S108

  View details for DOI 10.1016/j.healun.2016.01.297

  View details for Web of Science ID 000374718100272

• Combined Lung-Liver Transplantation: The United States Experience Pasupneti, S., Lawrence, A., Chhatwani, L., Patel, K., Ha, R., Boyd, J., Dhillon, G., Mooney, J. ELSEVIER SCIENCE INC. 2016: S311

  View details for DOI 10.1016/j.healun.2016.01.887

  View details for Web of Science ID 000374718101214

• A Critical Role for Airway Microvessels in Lung Transplantation. American journal of respiratory and critical care medicine Nicolls, M. R., Dhillon, G. S., Daddi, N. 2016; 193 (5): 479-481

  View details for DOI 10.1164/rccm.201511-2117ED

  View details for PubMedID 26930430

• Addressing the Controversy of Estimating Pulmonary Arterial Pressure by Echocardiography JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY Amsallem, M., Sternbach, J. M., Adigopula, S., Kobayashi, Y., Vu, T. A., Zamanian, R., Liang, D., Dhillon, G., Schnittger, I., McConnell, M. V., Haddad, F. 2016; 29 (2): 93-102

  Abstract

  There is currently controversy over whether echocardiography provides reliable estimations of pulmonary pressures. The objective of this study was to determine the factors influencing the accuracy and reliability of estimating right ventricular systolic pressure (RVSP) using echocardiography in patients with advanced lung disease or pulmonary arterial hypertension.Between January 2001 and December 2012, 667 patients with advanced lung disease or pulmonary arterial hypertension underwent right heart catheterization and transthoracic echocardiography. Of those, 307 had both studies within 5 days of each other. The correlation and bias in estimating RVSP according to tricuspid regurgitation (TR) signal quality and reader expertise were retrospectively determined. Reasons for under- and overestimation were analyzed. The diagnostic performance of estimated RVSP, relative right ventricular size, eccentricity index, and tricuspid annular plane systolic excursion was compared for classifying patients with pulmonary hypertension (mean pulmonary artery pressure ≥ 25 mm Hg).Invasive mean and systolic pulmonary artery pressures were strongly correlated (R(2) = 0.95, P < .001), with mean pulmonary artery pressure = 0.60 × systolic pulmonary artery pressure + 2.1 mm Hg. Among patients undergoing right heart catheterization and transthoracic echocardiography within 5 days, level 3 readers considered only 61% of TR signals interpretable, compared with 72% in clinical reports. Overestimation in the clinical report was related mainly to not assigning peak TR velocity at the modal frequency and underestimation to overreading of uninterpretable signals. When the TR signal was interpretable, the areas under the curve for classifying pulmonary hypertension were 0.97 for RVSP and 0.98 for RVSP and eccentricity index (P > .05). When TR signals were uninterpretable, eccentricity index and right ventricular size were independently associated with pulmonary hypertension (area under the curve, 0.77).Echocardiography reliably estimates RVSP when attention is given to simple quality metrics.

  View details for DOI 10.1016/j.echo.2015.11.001

  View details for Web of Science ID 000369168700003

• Recipient Management Pre-transplant Lung Transplantation: Principles and Practice. Dhillon, G., Weill, D. edited by Vigneswaran, W., Garrity, E., Odell, J. 2016: 55–64
• Impact Of Non Invasive Open Ventilation (niov) On Dyspnea And Quality Of Life In Patients With Chronic Obstructive Pulmonary Disease (COPD) And Idiopathic Pulmonary Fibrosis (ipf) Breiburg, A., Lam, K., Dhillon, G., Zone, C., Nicolls, M., Kuschner, W. AMER THORACIC SOC. 2016

  View details for Web of Science ID 000390749606652

• Recipient management before transplantation LUNG TRANSPLANTATION: PRINCIPLES AND PRACTICE Dhillon, G. S., Weill, D., Vigneswaran, W. T., Garrity, E. R., Odell, J. A. 2016: 55–63

  View details for Web of Science ID 000384447300006

• Multiple Listing In Lung Transplant Candidates: A Cohort Study Mooney, J. J., Hedlin, H., McKenzie, R., Mohabir, P., Chhatwani, L., Ha, R., Boyd, J., Patel, K., Bhattacharya, J., Dhillon, G. AMER THORACIC SOC. 2016

  View details for Web of Science ID 000390749604175

• Effect Of Broader Geographic Sharing Of Donor Lungs On Lung Transplant Candidate Outcomes Mooney, J. J., Chhatwani, L., Patel, K., Chiu, P., Ha, R., Boyd, J., Dhillon, G. AMER THORACIC SOC. 2016

  View details for Web of Science ID 000390749604176

• Circulating Elastase Confers A High Risk For The Development Of Bronchiolitis Obliterans Syndrome Milla, C. E., Zirbes, J. M., Yacob, A., Tian, L., Zamanian, R. T., Bental-Roof, M., Bland, R., Rabinovitch, M., Dhillon, G., Nicolls, M. AMER THORACIC SOC. 2016

  View details for Web of Science ID 000390749604185

• Addressing the Controversy of Estimating Pulmonary Arterial Pressure by Echocardiography. Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography Amsallem, M., Sternbach, J. M., Adigopula, S., Kobayashi, Y., Vu, T. A., Zamanian, R., Liang, D., Dhillon, G., Schnittger, I., McConnell, M. V., Haddad, F. 2015

  Abstract

  There is currently controversy over whether echocardiography provides reliable estimations of pulmonary pressures. The objective of this study was to determine the factors influencing the accuracy and reliability of estimating right ventricular systolic pressure (RVSP) using echocardiography in patients with advanced lung disease or pulmonary arterial hypertension.Between January 2001 and December 2012, 667 patients with advanced lung disease or pulmonary arterial hypertension underwent right heart catheterization and transthoracic echocardiography. Of those, 307 had both studies within 5 days of each other. The correlation and bias in estimating RVSP according to tricuspid regurgitation (TR) signal quality and reader expertise were retrospectively determined. Reasons for under- and overestimation were analyzed. The diagnostic performance of estimated RVSP, relative right ventricular size, eccentricity index, and tricuspid annular plane systolic excursion was compared for classifying patients with pulmonary hypertension (mean pulmonary artery pressure ≥ 25 mm Hg).Invasive mean and systolic pulmonary artery pressures were strongly correlated (R(2) = 0.95, P < .001), with mean pulmonary artery pressure = 0.60 × systolic pulmonary artery pressure + 2.1 mm Hg. Among patients undergoing right heart catheterization and transthoracic echocardiography within 5 days, level 3 readers considered only 61% of TR signals interpretable, compared with 72% in clinical reports. Overestimation in the clinical report was related mainly to not assigning peak TR velocity at the modal frequency and underestimation to overreading of uninterpretable signals. When the TR signal was interpretable, the areas under the curve for classifying pulmonary hypertension were 0.97 for RVSP and 0.98 for RVSP and eccentricity index (P > .05). When TR signals were uninterpretable, eccentricity index and right ventricular size were independently associated with pulmonary hypertension (area under the curve, 0.77).Echocardiography reliably estimates RVSP when attention is given to simple quality metrics.

  View details for DOI 10.1016/j.echo.2015.11.001

  View details for PubMedID 26691401

• Heart-lung vs. double-lung transplantation for idiopathic pulmonary arterial hypertension. Clinical transplantation Hill, C., Maxwell, B., Boulate, D., Haddad, F., Ha, R., Afshar, K., Weill, D., Dhillon, G. S. 2015; 29 (12): 1067-1075

  Abstract

  Patients with idiopathic pulmonary arterial hypertension (IPAH) have improved survival after heart-lung transplantation (HLT) and double-lung transplantation (DLT). However, the optimal procedure for patients with IPAH undergoing transplantation remains unclear. We hypothesized that critically-ill IPAH patients, defined by admission to the intensive care units (ICU), would demonstrate improved survival with HLT versus DLT. All adult IPAH patients (>18 years) in the Scientific Registry of Transplant Recipients (SRTR) database, who underwent either HLT or DLT between 1987 and 2012, were included. Baseline characteristics, survival, and adjusted survival were compared between the HLT and DLT groups. Similar analyses were performed for the sub-groups as defined by the recipients' hospitalization status. 928 IPAH patients (667 DLT, 261 HLT) were included in this analysis. The HLT recipients were younger, more likely to be admitted to the ICU, and have had their transplant in previous eras. Overall the adjusted survivals after HLT or DLT were similar. The recipients who were hospitalized in the ICU, DLT was associated with worse outcomes (HR 1.827; 95% CI 1.018-3.279). In IPAH patients, the overall survival after HLT or DLT is comparable. HLT may provide improved outcomes in critically-ill IPAH patients admitted to the ICU at time of transplantation. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/ctr.12628

  View details for PubMedID 26358537

• Invasive mold infections in lung and heart-lung transplant recipients: Stanford University experience TRANSPLANT INFECTIOUS DISEASE Vazquez, R., Vazquez-Guillamet, M. C., Suarez, J., Mooney, J., Montoya, J. G., Dhillon, G. S. 2015; 17 (2): 259-266

  Abstract

  Recipients of lung transplantation (LT) and heart-lung transplantation (HLT) are at increased risk of infection, including invasive mold infections (IMIs). The clinical presentation, radiographic correlates, and outcomes of Aspergillus and non-Aspergillus IMIs in this population have not been well documented.LT and HLT recipients diagnosed with IMIs between 1990 and 2012 were identified using the Stanford Translational Research Integrated Database Environment and Stanford LT and HLT clinical database. Recipient clinical and radiographic characteristics were obtained via retrospective review of medical records and compared between Aspergillus and non-Aspergillus mold recipients. Risk factors for mortality were identified using multivariate logistic regression analysis.During the study period, 87 (14%) transplant recipients were diagnosed with IMIs. Aspergillus species were isolated in 63 (72%) and non-Aspergillus molds in 24 (28%) recipients. No significant difference was seen in presenting symptoms or radiographic findings between Aspergillus and non-Aspergillus mold recipients. Median time to diagnosis was 363 days in the Aspergillus group and 419 days in the non-Aspergillus group, with dissemination occurring only within the non-Aspergillus group (12.5%). Overall 90-day and 1-year mortality following IMI was 24% and 44%. One-year mortality was increased in the non-Aspergillus group (39.5% vs. 60.5%, P = 0.03).There is significant overlap in risk factors, presentation, and radiographic patterns in IMI in LT or HLT recipients. Non-Aspergillus molds were more likely to present late, with disseminated disease, and portend increased 1-year mortality. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/tid.12362

  View details for Web of Science ID 000352219400011

  View details for PubMedID 25648194

• Lung Retransplantation in the Lung Allocation Score Era Schaffer, J. M., Chiu, P., Reitz, B. A., Dhillon, G., Woo, J., Ha, R. ELSEVIER SCIENCE INC. 2015: S171–S172

  View details for DOI 10.1016/j.healun.2015.01.466

  View details for Web of Science ID 000353251500443

• Recipient Outcomes in Donation After Circulatory Determination of Death Lung Donors Within the United States Mooney, J. J., Hedlin, H., Mohabir, P. K., Guillamet, R. V., Ha, R., Chiu, P., Patel, K., Weill, D., Nicolls, M. R., Dhillon, G. S. ELSEVIER SCIENCE INC. 2015: S279

  View details for DOI 10.1016/j.healun.2015.01.782

  View details for Web of Science ID 000353251500748

• Delirium After Lung Transplantation: Occurrence and Its Relationship to Morbidity and Mortality Sher, Y., Dhillon, G., Maldonado, J. R. ELSEVIER SCIENCE INC. 2015: S173

  View details for DOI 10.1016/j.healun.2015.01.469

  View details for Web of Science ID 000353251500446

• Donation After Circulatory Determination of Death Donor Characteristics and Lung Donor Utilization Within the United States Mooney, J. J., Hedlin, H., Mohabir, P. K., Guillamet, R. V., Ha, R., Chiu, P., Patel, K., Weill, D., Nicolls, M. R., Dhillon, G. S. ELSEVIER SCIENCE INC. 2015: S280–S281

  View details for DOI 10.1016/j.healun.2015.01.785

  View details for Web of Science ID 000353251500751

• Donor-Specific HLA Antibodies After Lung Transplantation: Extended Follow-Up From the HALT Study Hachem, R. R., Budev, M., Askar, M., Farver, C., Lee, J., Kamoun, M., Dhillon, G., Tyan, D., Levine, D. J., Pollack, M., Leard, L. E., Raja, R., Mohanakumar, T., Yusen, R. D. ELSEVIER SCIENCE INC. 2015: S121

  View details for DOI 10.1016/j.healun.2015.01.320

  View details for Web of Science ID 000353251500301

• Finding an early warning signal for acute respiratory distress syndrome: are we getting closer? Critical care medicine Rogers, A. J., Dhillon, G. S. 2015; 43 (3): 721-722

  View details for DOI 10.1097/CCM.0000000000000800

  View details for PubMedID 25700066

• Pulmonary Hypertension and Lung Transplant in Connective Tissue Disease-Interstitial Lung Disease CURRENT RESPIRATORY MEDICINE REVIEWS Melendres-Groves, L., Vazquez-Guillamet, R., Dhillon, G. 2015; 11 (2): 156–62

  View details for DOI 10.2174/1573398X11666150619183225

  View details for Web of Science ID 000212728100012

• Long Term Survival of Lung Transplant Recipients After Implementation of Lung Allocation Score Mooney, J., Maxwell, B., Levitt, J., Goldstein, B., Nicolls, M., Weill, D., Dhillon, G. LIPPINCOTT WILLIAMS & WILKINS. 2014: 802

  View details for Web of Science ID 000339104605175

• Long Term Survival of Lung Transplant Recipients After Implementation of Lung Allocation Score. Mooney, J., Maxwell, B., Levitt, J., Goldstein, B., Nicolls, M., Weill, D., Dhillon, G. WILEY-BLACKWELL. 2014: 802

  View details for Web of Science ID 000338033303506

• Donor-derived west nile virus infection in solid organ transplant recipients: report of four additional cases and review of clinical, diagnostic, and therapeutic features. Transplantation Winston, D. J., Vikram, H. R., Rabe, I. B., Dhillon, G., Mulligan, D., Hong, J. C., Busuttil, R. W., Nowicki, M. J., Mone, T., Civen, R., Tecle, S. A., Trivedi, K. K., Hocevar, S. N. 2014; 97 (9): 881-889

  Abstract

  : We describe four solid-organ transplant recipients with donor-derived West Nile virus (WNV) infection (encephalitis 3, asymptomatic 1) from a common donor residing in a region of increased WNV activity. All four transplant recipients had molecular evidence of WNV infection in their serum and/or cerebrospinal fluid (CSF) by reverse transcription polymerase chain reaction (RT-PCR) testing. Serum from the organ donor was positive for WNV IgM but negative for WNV RNA, whereas his lymph node and spleen tissues tested positive for WNV by RT-PCR. Combination therapy included intravenous immunoglobulin (4 cases), interferon (3 cases), fresh frozen plasma with WNV IgG (2 cases), and ribavirin (1 case). Two of the four transplant recipients survived.Review of the 20 published cases of organ-derived WNV infection found that this infection is associated with a high incidence of neuroinvasive disease (70%) and severe morbidity and mortality (30%). Median time to onset of symptomatic WNV infection was 13 days after transplantation (range 5-37 days). Initial unexplained fever unresponsive to antibiotic therapy followed by rapid onset of neurologic deficits was the most common clinical presentation. Confirmation of infection was made by testing serum and CSF for both WNV RNA by RT-PCR and WNV IgM by serological assays. Treatment usually included supportive care, reduction of immunosuppression, and frequent intravenous immunoglobulin. The often negative results for WNV by current RT-PCR and serological assays and the absence of clinical signs of acute infection in donors contribute to the sporadic occurrence of donor-derived WNV infection. Potential organ donors should be assessed for unexplained fever and neurological symptoms, particularly if they reside in areas of increased WNV activity.

  View details for DOI 10.1097/TP.0000000000000024

  View details for PubMedID 24827763

• Complement-Fixing Donor-Specific Antibody and Lung Transplant Outcomes Chhatwani, L., Mooney, J., Balestra, R., Lee, R., Lou, C., Weill, D., Tyan, D., Dhillon, G. ELSEVIER SCIENCE INC. 2014: S160

  View details for DOI 10.1016/j.healun.2014.01.430

  View details for Web of Science ID 000333866700424

• Impact Of The Lung Allocation Score On Survival Beyond One Year Post Lung Transplantation Levitt, J. E., Maxwell, B. G., Goldstein, B. A., Nicolls, M. R., Zamora, M. R., Valentine, V. G., Weill, D., Mooney, J. J., Dhillon, G. S. AMER THORACIC SOC. 2014

  View details for Web of Science ID 000209838204648

• West Nile Virus RNA in Tissues from Donor Associated with Transmission to Organ Transplant Recipients EMERGING INFECTIOUS DISEASES Blau, D. M., Rabe, I. B., Bhatnagar, J., Civen, R., Trivedi, K. K., Rollin, D., Hocevar, S. N., Kuehnert, M., Staples, J. E., Zaki, S. R., Fischer, M. 2013; 19 (9): 1518-1520

  Abstract

  We identified West Nile virus (WNV) RNA in skin, fat, muscle, tendon, and bone marrow from a deceased donor associated with WNV transmission through solid organ transplantation. WNV could not be cultured from the RNA-positive tissues. Further studies are needed to determine if WNV can be transmitted from postmortem tissues.

  View details for DOI 10.3201/eid1909.130365

  View details for Web of Science ID 000328173800026

  View details for PubMedID 23965573

  View details for PubMedCentralID PMC3810926

• Blocking macrophage leukotriene b4 prevents endothelial injury and reverses pulmonary hypertension. Science translational medicine Tian, W., Jiang, X., Tamosiuniene, R., Sung, Y. K., Qian, J., Dhillon, G., Gera, L., Farkas, L., Rabinovitch, M., Zamanian, R. T., Inayathullah, M., Fridlib, M., Rajadas, J., Peters-Golden, M., Voelkel, N. F., Nicolls, M. R. 2013; 5 (200): 200ra117-?

  Abstract

  Pulmonary hypertension (PH) is a serious condition that affects mainly young and middle-aged women, and its etiology is poorly understood. A prominent pathological feature of PH is accumulation of macrophages near the arterioles of the lung. In both clinical tissue and the SU5416 (SU)/athymic rat model of severe PH, we found that the accumulated macrophages expressed high levels of leukotriene A4 hydrolase (LTA4H), the biosynthetic enzyme for leukotriene B4 (LTB4). Moreover, macrophage-derived LTB4 directly induced apoptosis in pulmonary artery endothelial cells (PAECs). Further, LTB4 induced proliferation and hypertrophy of human pulmonary artery smooth muscle cells. We found that LTB4 acted through its receptor, BLT1, to induce PAEC apoptosis by inhibiting the protective endothelial sphingosine kinase 1 (Sphk1)-endothelial nitric oxide synthase (eNOS) pathway. Blocking LTA4H decreased in vivo LTB4 levels, prevented PAEC apoptosis, restored Sphk1-eNOS signaling, and reversed fulminant PH in the SU/athymic rat model of PH. Antagonizing BLT1 similarly reversed established PH. Inhibition of LTB4 biosynthesis or signal transduction in SU-treated athymic rats with established disease also improved cardiac function and reopened obstructed arterioles; this approach was also effective in the monocrotaline model of severe PH. Human plexiform lesions, one hallmark of PH, showed increased numbers of macrophages, which expressed LTA4H, and patients with connective tissue disease-associated pulmonary arterial hypertension exhibited significantly higher LTB4 concentrations in the systemic circulation than did healthy subjects. These results uncover a possible role for macrophage-derived LTB4 in PH pathogenesis and identify a pathway that may be amenable to therapeutic targeting.

  View details for DOI 10.1126/scitranslmed.3006674

  View details for PubMedID 23986401

• HLA Antibodies after Lung Transplantation: Early Results of the HALT Study Hachem, R. R., Kamoun, M., Budev, M., Askar, M., Vivek, A., Levine, D. J., Pollack, M. S., Dhillon, G., Schechtman, K., Lorriana, L. E., Baxter-Lowe, L. A., Mohanakumar, T., Tyan, D., Yusen, R. D. ELSEVIER SCIENCE INC. 2013: S76–S77

  View details for DOI 10.1016/j.healun.2013.01.191

  View details for Web of Science ID 000316712100189

• New methods for monitoring dynamic airway tissue oxygenation and perfusion in experimental and clinical transplantation AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY Khan, M. A., Dhillon, G., Jiang, X., Lin, Y., Nicolls, M. R. 2012; 303 (10): L861-L869

  Abstract

  A dual circulation, supplied by bronchial and pulmonary artery-derived vessels, normally perfuses the airways from the trachea to the terminal bronchioles. This vascular system has been highly conserved through mammalian evolution and is disrupted at the time of lung transplantation. In most transplant centers, this circulation is not restored. The Papworth Hospital Autopsy study has revealed that an additional attrition of periairway vessels is associated with the development of chronic rejection, otherwise known as the bronchiolitis obliterans syndrome (BOS). Experimental studies subsequently demonstrated that airway vessels are subject to alloimmune injury and that the loss of a functional microvascular system identifies allografts that cannot be rescued with immunosuppressive therapy. Therefore, surgical and medical strategies, which preserve the functionality of the existent vasculature in lung transplant patients, may conceivably limit the incidence of BOS. Given these unique anatomic and physiological considerations, there is an emerging rationale to better understand the perfusion and oxygenation status of airways in transplanted lungs. This article describes novel methodologies, some newly developed by our group, for assessing airway tissue oxygenation and perfusion in experimental and clinical transplantation.

  View details for DOI 10.1152/ajplung.00162.2012

  View details for PubMedID 23002078

• Investigation of Donor-Derived West Nile Virus (WNV) Infection in Four Recipients. Vikram, H. R., Weber, I. B., Winston, D. J., Honng, J. C., Mulligan, D. C., Dhillon, G. S., Nowicki, M. J., Mone, T. D., Civen, R. H., Tecle, S. A., Trivedi, K. K., Hocevar, S. N. WILEY-BLACKWELL. 2012: 360

  View details for Web of Science ID 000303235503029

• Clarithromycin for prevention of bronchiolitis obliterans syndrome in lung allograft recipients CLINICAL TRANSPLANTATION Dhillon, G. S., Valentine, V. G., Levitt, J., Patel, P., Gupta, M. R., Duncan, S. R., Seoane, L., Weill, D. 2012; 26 (1): 105-110

  Abstract

  Bronchiolitis obliterans syndrome (BOS) is the major limitation to long-term survival following lung transplantation and strategies to reduce its incidence have remained elusive. Macrolides may stabilize lung function in patients with established BOS. Their role, however, in prevention of BOS remains unexamined.Survival and BOS-free survival of 102 lung allograft recipients (LARs), transplanted at a single center between July 1995 and December 2001 who routinely received clarithromycin, were compared with two different control groups. The first control group consisted of 44 LARs from the same center who were transplanted from January 2002 onwards and did not receive clarithromycin. The second control group consisted of a contemporaneous cohort of 5089 recipients, transplanted between 1995 and 2001, reported to the United Network for Organ Sharing database.When compared with the first control group, BOS-free survival was reduced in LARs receiving clarithromycin. Univariate (hazard ratio [HR] 3.13, p-value = 0.004) and multivariate (HR 3.49, p-value = 0.04) analyses showed that routine use of clarithromycin was associated with an increased risk of developing BOS. When compared with the second control group, the five-yr survival of clarithromycin group was similar (p-value = 0.24).Routine use of clarithromycin does not delay development of BOS or improve survival.

  View details for DOI 10.1111/j.1399-0012.2011.01420.x

  View details for PubMedID 21352378

• CD4(+) T Cells and Complement Independently Mediate Graft Ischemia in the Rejection of Mouse Orthotopic Tracheal Transplants CIRCULATION RESEARCH Khan, M. A., Jiang, X., Dhillon, G., Beilke, J., Holers, V. M., Atkinson, C., Tomlinson, S., Nicolls, M. R. 2011; 109 (11): 1290-U256

  Abstract

  While microvascular injury is associated with chronic rejection, the cause of tissue ischemia during alloimmune injury is not yet elucidated.We investigated the contribution of T lymphocytes and complement to microvascular injury-associated ischemia during acute rejection of mouse tracheal transplants.Using novel techniques to assess microvascular integrity and function, we evaluated how lymphocyte subsets and complement specifically affect microvascular perfusion and tissue oxygenation in MHC-mismatched transplants. To characterize T cell effects on microvessel loss and recovery, we transplanted functional airway grafts in the presence and absence of CD4(+) and CD8(+) T cells. To establish the contribution of complement-mediated injury to the allograft microcirculation, we transplanted C3-deficient and C3-inhibited recipients. We demonstrated that CD4(+) T cells and complement are independently sufficient to cause graft ischemia. CD8(+) T cells were required for airway neovascularization to occur following CD4-mediated rejection. Activation of antibody-dependent complement pathways mediated tissue ischemia even in the absence of cellular rejection. Complement inhibition by CR2-Crry attenuated graft hypoxia, complement/antibody deposition on vascular endothelium and promoted vascular perfusion by enhanced angiogenesis. Finally, there was a clear relationship between the burden of tissue hypoxia (ischemia×time duration) and the development of subsequent airway remodeling.These studies demonstrated that CD4(+) T cells and complement operate independently to cause transplant ischemia during acute rejection and that sustained ischemia is a precursor to chronic rejection.

  View details for DOI 10.1161/CIRCRESAHA.111.250167

  View details for PubMedID 21998328

• Regulatory T Cells Limit Vascular Endothelial Injury and Prevent Pulmonary Hypertension CIRCULATION RESEARCH Tamosiuniene, R., Tian, W., Dhillon, G., Wang, L., Sung, Y. K., Gera, L., Patterson, A. J., Agrawal, R., Rabinovitch, M., Ambler, K., Long, C. S., Voelkel, N. F., Nicolls, M. R. 2011; 109 (8): 867-U120

  Abstract

  Pulmonary arterial hypertension (PAH) is an incurable disease associated with viral infections and connective tissue diseases. The relationship between inflammation and disease pathogenesis in these disorders remains poorly understood.To determine whether immune dysregulation due to absent T-cell populations directly contributes to the development of PAH.Vascular endothelial growth factor receptor 2 (VEGFR2) blockade induced significant pulmonary endothelial apoptosis in T-cell-deficient rats but not in immune-reconstituted (IR) rats. T cell-lymphopenia in association with VEGFR2 blockade resulted in periarteriolar inflammation with macrophages, and B cells even prior to vascular remodeling and elevated pulmonary pressures. IR prevented early inflammation and attenuated PAH development. IR with either CD8 T cells alone or with CD4-depleted spleen cells was ineffective in preventing PAH, whereas CD4-depleting immunocompetent euthymic animals increased PAH susceptibility. IR with either CD4(+)CD25(hi) or CD4(+)CD25(-) T cell subsets prior to vascular injury attenuated the development of PAH. IR limited perivascular inflammation and endothelial apoptosis in rat lungs in association with increased FoxP3(+), IL-10- and TGF-β-expressing CD4 cells, and upregulation of pulmonary bone morphogenetic protein receptor type 2 (BMPR2)-expressing cells, a receptor that activates endothelial cell survival pathways.PAH may arise when regulatory T-cell (Treg) activity fails to control endothelial injury. These studies suggest that regulatory T cells normally function to limit vascular injury and may protect against the development of PAH.

  View details for DOI 10.1161/CIRCRESAHA.110.236927

  View details for PubMedID 21868697

• Lung function, radiological changes and exposure: analysis of ATSDR data from Libby, MT, USA EUROPEAN RESPIRATORY JOURNAL Weill, D., Dhillon, G., Freyder, L., Lefante, J., Glindmeyer, H. 2011; 38 (2): 376-383

  Abstract

  In 2000, the Agency for Toxic Substances and Disease Registry (ATSDR; Atlanta, GA, USA) investigated lung disease in those exposed to the tremolite-contaminated vermiculite mine in Libby, MT, USA. Previously unreported spirometric results are presented here in relation to exposure and radiographic findings. 4,524 study participants were assigned to one of seven mutually exclusive exposure categories. Associations among radiographic findings, spirometric results and exposure were investigated, along with the effect of a reduction in exposure potential when production was moved to a wet process mill in the mid 1970s. Spirometry data for the total population by smoking status and age were within the normal range. Prevalence of pleural plaque increased with age, but was lowest in the environmentally exposed group (0.42-12.74%) and greatest in the W.R. Grace & Co. mineworkers (20-45.68%). For males, there was a significant (4.5%) effect of pleural plaques on forced vital capacity. For W.R. Grace & Co. workers and household contacts, a reduction in plaque (0.11 versus 1.64%) and in diffuse pleural thickening or costophrenic angle obliteration (1.94 and 0.13%) was noted for those exposed after 1976. These analyses do not support a clinically important reduction in spirometry of this cohort. The 1976 reductions in exposure have led to decrease in radiographic changes.

  View details for DOI 10.1183/09031936.00050210

  View details for Web of Science ID 000293280400021

  View details for PubMedID 21177846

• Analysis of Non-Cutaneous Cancer after Lung Transplantation Broussard, B. A., Valentine, V. G., Nishi, S. P., Lick, S. D., Lombard, G. A., LaPlace, S. G., Seoane, L., Dhillon, G. S., Rampolla, R. ELSEVIER SCIENCE INC. 2011: S149

  View details for DOI 10.1016/j.healun.2011.01.447

  View details for Web of Science ID 000288924300435

• Review of Heart-Lung Transplantation at Stanford ANNALS OF THORACIC SURGERY Deuse, T., Sista, R., Weill, D., Tyan, D., Haddad, F., Dhillon, G., Robbins, R. C., Reitz, B. A. 2010; 90 (1): 329-337

  Abstract

  Long-term survival after heart-lung transplantation was first achieved in 1981 at Stanford and a total of 217 heart-lung transplantations had been performed by June 2008. This review summarizes Stanford's cumulative experience with heart-lung transplantation, demonstrates the progress that has been made, and discusses past and persistent problems. Diagnostic tools and treatment options for infectious diseases and rejection have changed and patient survival markedly improved over the almost three decades. Eight patients lived longer than 20 years. Further options to treat infections and strategies to control bronchiolitis obliterans syndrome, the main causes of early and long-term mortality, respectively, are required to achieve routine long-term survival.

  View details for DOI 10.1016/j.athoracsur.2010.01.023

  View details for PubMedID 20609821

• A multi-drug regimen for respiratory syncytial virus and parainfluenza virus infections in adult lung and heart-lung transplant recipients TRANSPLANT INFECTIOUS DISEASE Liu, V., Dhillon, G. S., Weill, D. 2010; 12 (1): 38-44

  Abstract

  Respiratory syncytial virus (RSV) and parainfluenza virus (PIV) can cause significant morbidity and mortality in lung and heart-lung transplant recipients. We evaluated the utility of a multi-drug protocol for the treatment of RSV- and PIV-related infections.RSV or PIV was identified in 25 patients with a total of 29 infectious episodes between January 2006 and December 2007. The study included 20 women and 5 men, mean age 42 +/- 13 years. Fifteen patients had received bilateral lung transplant and the remainder either received single lung or heart-lung transplant. Mean time from transplant to infection was 1192 days. RSV was identified in 23 cases, PIV in 7 cases. Patients underwent treatment with inhaled ribavirin, methylprednisolone, and intravenous immunoglobulin (IVIG). RSV-positive patients were also treated with palivizumab. We retrospectively evaluated their clinical status and pulmonary function for a 1-year interval before and after the date of infection.Average baseline forced expiratory volume in 1 s (FEV(1)) before infection was 2.14 +/- 0.68 L/min. Average decline in FEV(1) was 5.7% at the time of infection. Average FEV(1) during post-treatment follow-up was not significantly different than baseline (2.16 +/- 0.80 L/min). Among patients with bronchiolitis obliterans syndrome (BOS) stages 1, 2, or 3 at the time of infection, average FEV(1) declined by 14.8% and remained lower at 9.1% during follow-up when compared with patients with BOS stages 0 or 0p. No complications resulted from treatment. One patient died during follow-up as a result of pre-existing liver failure.This study of lung and heart-lung transplant recipients infected with RSV and PIV shows that a multi-drug regimen including inhaled ribavirin, corticosteroids, and IVIG (with or without palivizumab) is safe and effective. Prompt diagnosis and therapy for patients with RSV or PIV infections are critical for maintaining lung function.

  View details for DOI 10.1111/j.1399-3062.2009.00453.x

  View details for Web of Science ID 000273823500006

  View details for PubMedID 19761558

• The Contribution Of C3 To Allograft Hypoxia And Perfusion In Murine Model Of Orthotopic Tracheal Transplantation Khan, M. A., Tomlinson, S., Dhillon, G., Jiang, X., Nicolls, M. R. AMER THORACIC SOC. 2010

  View details for Web of Science ID 000208771000093

• Lung Transplant Airway Hypoxia: A Diathesis To Fibrosis? Dhillon, G. S., Zamora, M. R., Roos, J. E., Sheahan, D. E., Sista, R. R., van der Starre, P. R., Weill, D., Nicolls, M. R. AMER THORACIC SOC. 2010

  View details for Web of Science ID 000208771000010

• Clinical spectrum of gram-positive infections in lung transplantation TRANSPLANT INFECTIOUS DISEASE Gupta, M. R., Valentine, V. G., Walker, J. E., Lombard, G. A., LaPlace, S. G., Seoane, L., Taylor, D. E., Dhillon, G. S. 2009; 11 (5): 424-431

  Abstract

  Gram-positive (GP) organisms are among the most common cause of infections in early postsurgical and immunocompromised populations. Patients recovering from lung transplantation (LT) are particularly susceptible owing to the physiologic stress imposed by surgery and induction with intense immunosuppression. Sites, types, and timing of GP infections following LT are not well documented. This report describes the clinical spectrum of GP infections and their effects on surgical airway complications (SAC) and bronchiolitis obliterans syndrome (BOS) following LT.Data were collected from 202 patients undergoing 208 LT procedures at a single institution between November 1990 and November 2005. Data were retrospectively analyzed according to timing, location, and causative pathogen.In the median follow-up period of 2.7 years (range, 0-13.6 years), 137 GP infections were confirmed in 72 patients. Sites of infection included respiratory tract (42%), blood (27%), skin, wound and catheter (21%), and other (10%). GP pathogens identified were Staphylococcus species (77%), Enterococcus species (12%), Streptococcus species (6%), Pneumococcus (4%), and Eubacterium lentum (1%). The likelihood of SAC and BOS was increased in lung allograft recipients with GP pneumonia as compared with those without (hazard ratio 2.1; 95% confidence interval=1.5-3.1).GP organisms were responsible for infections in 40% of lung allograft recipients and most commonly isolated from the respiratory tract and blood stream. Staphylococcal species were most frequently identified, 42% of which were methicillin-resistant Staphylococcus aureus (MRSA). Given the strong association of respiratory tract infections with the development of SAC and BOS, empiric antimicrobial strategies after LT should include agents directed against GP organisms, especially MRSA.

  View details for DOI 10.1111/j.1399-3062.2009.00422.x

  View details for Web of Science ID 000270429700006

  View details for PubMedID 19659672

• Impact of Hepatitis B Core Antibody Positive Donors in Lung and Heart-Lung Transplantation: An Analysis of the United Network for Organ Sharing Database TRANSPLANTATION Dhillon, G. S., Levitt, J., Mallidi, H., Valentine, V. G., Gupta, M. R., Sista, R., Weill, D. 2009; 88 (6): 842-846

  Abstract

  The availability of suitable lung and heart-lung allografts for transplantation remains poor. Accepting organs from donors with positive serological studies for hepatitis B could potentially expand the donor pool. The aim of this study was to assess the impact of donor hepatitis B core antibody (HBcAb) status on outcomes of lung and heart-lung transplant recipients.Using United Network for Organ Sharing/Organ Procurement and Transplantation Network data, we compared outcomes of 13,233 recipients of HBcAb negative organs with 333 recipients of HBcAb positive donor organs.We found that the unadjusted 1-year survival of recipients of HBcAb positive donor was worse, but there was no difference in survival after adjusting for baseline donor and recipient differences. On multivariate analysis, recipient and donor age, procedure type, era of transplant, baseline medical condition, diagnosis, and donor hepatitis C antibody status impacted 1- and 5-year survival. However, donor HBcAb status did not impact 1- or 5-year survival posttransplant.Lung and heart-lung allografts from HBcAb positive donors may be safely used, which would increase the number of transplants performed without compromising recipient outcomes.

  View details for DOI 10.1097/TP.0b013e3181b4e1fd

  View details for PubMedID 19920785

• Effect of Etiology and Timing of Respiratory Tract Infections on Development of Bronchiolitis Obliterans Syndrome JOURNAL OF HEART AND LUNG TRANSPLANTATION Valentine, V. G., Gupta, M. R., Walker, J. E., Seoane, L., Bonvillain, R. W., Lombard, G. A., Weill, D., Dhillon, G. S. 2009; 28 (2): 163-169

  Abstract

  Among the many potential risk factors influencing the development of bronchiolitis obliterans syndrome (BOS), acute cellular rejection is the most frequently identified. Despite the unique susceptibility of the lung allograft to pathogens, the association with respiratory tract infections remains unclear. In this study we analyze the role respiratory tract infections have on the development of BOS after lung transplantation.Data from a single center were analyzed from 161 lung recipients transplanted from November 1990 to November 2005, and who survived >180 days. Univariate and multivariate Cox regression analyses were performed using BOS development and the time-scale was reported with hazard ratios (HRs) and confidence intervals (CIs).Significant findings by univariate analysis per 100 patient-days prior to BOS onset included acute rejection, cytomegalovirus (CMV) pneumonitis, Gram-negative respiratory tract infections, Gram-positive respiratory tract infections and fungal pneumonias. Multivariate analysis indicated acute rejection, Gram-negative, Gram-positive and fungal pneumonias with HRs (CI) of 84 (23 to 309), 6.6 (1.2 to 37), 6,371 (84 to 485,000) and 314 (53 to 1,856) to be associated with BOS, respectively. Acute rejection, CMV pneumonitis, Gram-positive pneumonia and fungal pneumonitis in the first 100 days had HRs (CI) of 1.8 (1.1 to 3.2), 3.1 (1.3 to 6.9), 3.8 (1.5 to 9.4) and 2.1 (1.1 to 4.0), respectively, and acute rejection and fungal pneumonitis in the late post-operative period with HRs (CI) of 2.3 (1.2 to 4.4) and 1.5 (1.1 to 1.9), respectively.In addition to acute rejection, pneumonias with GP, GN and fungal pathogens occurring prior to BOS are independent determinants of chronic allograft dysfunction. Early recognition and treatment of these pathogens in lung transplant recipients may improve long-term outcomes after transplantation.

  View details for DOI 10.1016/j.healun.2008.11.907

  View details for Web of Science ID 000263539900008

  View details for PubMedID 19201342

• Comparison of Double-Lung and Heart-Lung Transplantation for Pulmonary Hypertension: Analysis of the UNOS Database Afshar, K., Weill, D., Valentine, V. G., Dhillon, G. S. ELSEVIER SCIENCE INC. 2009: S310–S311

  View details for DOI 10.1016/j.healun.2008.11.712

  View details for Web of Science ID 000263539800701

• 27-Year Experience with Combined Heart-Lung Transplantation at Stanford University Deuse, T., Sista, R., Haddad, F., Weill, D., Dhillon, G., Tang, D., Mallidi, H., Hunt, S., Oyer, P., Robbins, R. C., Reitz, B. A. ELSEVIER SCIENCE INC. 2009: S134–S135

  View details for DOI 10.1016/j.healun.2008.11.204

  View details for Web of Science ID 000263539800197

• ABO Minor Mismatch In Lung Transplantation - An Analysis of die UNOS Database Tang, D. G., Mallidi, H. R., Weill, D., Reitz, B. A., Robbins, R. C., Dhillon, G. S. ELSEVIER SCIENCE INC. 2009: S69

  View details for DOI 10.1016/j.healun.2008.11.018

  View details for Web of Science ID 000263539800013

• Determinants of Time To Peak FEV1 after Lung Transplantation 29th Annual Meeting and Scientific Session of the International-Society-for-Heart-and-Lung-Transplantation Valentine, V. G., Raza, A., Nishi, S. P., Gupta, M. R., Seoane, L., Lombard, G. A., Dhillon, G. S. ELSEVIER SCIENCE INC. 2009: S107–S107

  View details for Web of Science ID 000263539800120

• Single-institution Study Evaluating the Utility of Surveillance Bronchoscopy After Lung Transplantation JOURNAL OF HEART AND LUNG TRANSPLANTATION Valentine, V. G., Gupta, M. R., Weill, D., Lombard, G. A., LaPlace, S. G., Seoane, L., Taylor, D. E., Dhillon, G. S. 2009; 28 (1): 14-20

  Abstract

  Many lung transplant physicians advocate surveillance bronchoscopy with transbronchial lung biopsy and bronchoalveolar lavage (TBB/BAL) to monitor lung recipients despite limited evidence this strategy improves outcomes. This report compares rates of infection (INF), acute rejection (AR), bronchiolitis obliterans syndrome (BOS) and survival in lung allograft recipients managed with surveillance TBB/BAL (SB) versus those with clinically indicated TBB/BAL (CIB).We reviewed 47 consecutive recipients transplanted between March 2002 and August 2005. Of these recipients, 24 consented to a multi-center trial requiring SB and 23 were managed by our usual practice of CIB. Rates of freedom from INF, AR, BOS and survival were compared. BOS and AR were diagnosed according to published guidelines from the International Society for Heart and Lung Transplantation.A total of 240 TBB/BALs were performed. CIB and SB groups underwent 84 (3.7 +/- 3.4/patient) and 156 (6.5 +/- 2.0/patient) TBB/BALs, respectively. In the SB group, 54 (2.2 +/- 1.6/patient) TBB/BALs were true surveillance procedures, whereas 102 (4.2 +/- 2.3/patient) were clinically indicated. No AR episode requiring treatment was detected by true surveillance. Freedom from respiratory INF, AR, BOS and survival in the SB and CIB groups showed no significant differences. Five patients in the CIB group remained stable without requiring TBB/BAL. In the SB group, 4 previously asymptomatic patients developed pneumonia within 2 weeks of surveillance TBB/BAL.With no obvious advantage identified, surveillance bronchoscopy may pose a risk to stable lung transplant recipients. A multi-center, controlled trial is required to validate the utility and safety of surveillance bronchoscopy in lung transplantation.

  View details for DOI 10.1016/j.healun.2008.10.010

  View details for Web of Science ID 000262554400003

  View details for PubMedID 19134525

• Impact of a Triage Protocol on Resource Utilization in Critically Ill BMT Recipients. Mahtosh, P., Jenkins, P., Rizk, N., Dhillon, G. AMER THORACIC SOC. 2009

  View details for Web of Science ID 000208733105427

• Determinants of Best FEV1 after Lung Transplantation Raza, A., Nishi, S. P., Gupta, M. R., Lombard, G. A., LaPlace, S. G., Dhillon, G. S., Seoane, L., Valentine, V. G. AMER THORACIC SOC. 2009

  View details for Web of Science ID 000208733104073

• Bone Mineral Density in Lung Transplantation Nishi, S. P., Gupta, M. R., Lombard, G. A., LaPlace, S. G., Seaone, L., Dhillon, G. S., Valentine, V. G. AMER THORACIC SOC. 2009

  View details for Web of Science ID 000208733104066

• Effect of Fluoroquinolones on Development of Stenotrophomonas maltophilia Infections in Lung Recipients. Broussard, B. A., Nguyen, A. N., Nishi, S. P., Gupta, M. R., Lombard, G. A., LaPlace, S. G., Raper, B., Seoane, L., Dhillon, G. S., Valentine, V. G. AMER THORACIC SOC. 2009

  View details for Web of Science ID 000208733100740

• Tissue Hypoxia in Lung Transplantation Dhillon, G., Jiang, X., Natarajan, R., Sista, R., Weill, D., van der Starre, P., Nicolls, M. AMER THORACIC SOC. 2009

  View details for Web of Science ID 000208733101659

• CMV-Specific T-Cell Responses in Lung Transplant Patients Using a Monocyte-Derived Dendritic Cell (MDDC) Assay. Chen, S. F., Liu, L. X., Dhillon, G., de Leon, V., Weill, D., Lewis, D. B. WILEY-BLACKWELL PUBLISHING, INC. 2009: 551

  View details for Web of Science ID 000265068801297

• Critical Care and Hematopoietic Stem Cell Recipients Thomas’ Hematopoietic Cell Transplantation 4th ed. Dhillon, G., Rizk, N. 2009: 1539–50
• Clostridium difficile colitis in lung transplantation TRANSPLANT INFECTIOUS DISEASE Gunderson, C. C., Gupta, M. R., LOPEZ, F., Lombard, G. A., LaPlace, S. G., Taylor, D. E., Dhillon, G. S., Valentine, V. G. 2008; 10 (4): 245-251

  Abstract

  Clostridium difficile colitis (CDC) is the most common nosocomial infection of the gastrointestinal tract in patients with recent antibiotic use or hospitalization. Lung transplant recipients receive aggressive antimicrobial therapy postoperatively for treatment and prophylaxis of respiratory infections. This report describes the epidemiology of CDC in lung recipients from a single center and explores possible associations with bronchiolitis obliterans syndrome (BOS), a surrogate marker of chronic rejection.Patients were divided into those with confirmed disease (CDC+) and those without disease (CDC-) based on positive C. difficile toxin assay. Because of a bimodal distribution in the time to develop CDC, the early postoperative CDC+ group was analyzed separately from the late postoperative CDC+ cohort with respect to BOS development.Between 1990 and 2005, 202 consecutive patients underwent 208 lung transplantation procedures. Of these, 15 lung recipients developed 23 episodes of CDC with a median follow-up period of 2.7 years (range, 0-13.6). All patients with confirmed disease had at least 1 of the following 3 risk factors: recent antibiotic use, recent hospitalization, or augmentation of steroid dosage. Of the early CDC+ patients, 100% developed BOS, but only 52% of the late CDC+ patients developed BOS, either preceding or following infection.CDC developed in 7.4% of lung transplant patients with identified risk factors, yielding a cumulative incidence of 14.7%. The statistical association of BOS development in early CDC+ patients suggests a relationship between early infections and future chronic lung rejection.

  View details for DOI 10.1111/j.1399-3062.2008.00305.x

  View details for Web of Science ID 000258399900005

  View details for PubMedID 18312477

• Ganciclovir for cytomegalovirus: a call for indefinite prophylaxis in lung transplantation JOURNAL OF HEART AND LUNG TRANSPLANTATION Valentine, V. G., Weill, D., Gupta, M. R., Raper, B., LaPlace, S. G., Lombard, G. A., Bonvillain, R. W., Taylor, D. E., Dhillon, G. S. 2008; 27 (8): 875-881

  Abstract

  Universal ganciclovir (GCV) prophylaxis is a strategy aimed at reducing cytomegalovirus (CMV) infection and delaying the development of bronchiolitis obliterans syndrome (BOS). However, the optimal duration of GCV prophylaxis remains unclear. We report our experience with GCV prophylaxis administered indefinitely and its effect on CMV pneumonitis, BOS and survival after lung transplantation (LT).One hundred fifty-one patients surviving >100 days after LT were analyzed. GCV was given to 130 CMV donor- or recipient-seropositive patients. Data from 90 patients who received indefinite GCV prophylaxis (IND) and 40 patients who discontinued their GCV prophylaxis (STOP) were compared.CMV pneumonitis occurred in 16%, 8%, 17% and 19% of patients in the D+R+, D-R+, D+R- and D-R- groups, respectively. In the STOP cohort, 15 of 40 patients developed CMV pneumonitis (median time 79 days) after GCV was stopped. Ten of these 15 patients developed BOS (median time 116 days) after discontinuing GCV. The risk of CMV pneumonitis in the STOP cohort was significantly higher when GCV prophylaxis was discontinued within the first year. Cumulative incidence of CMV pneumonitis in the IND and STOP groups at 5 years was 2% and 57%, respectively (p < 0.001). BOS-free survival and survival were similar across both groups.Indefinite GCV prophylaxis prevents CMV pneumonitis in 98% of LT recipients. Thirty-eight percent of patients discontinuing prophylaxis developed CMV pneumonitis, 50% of whom progressed to BOS within 1 year. Continuing ganciclovir prophylaxis indefinitely after lung transplantation should be considered.

  View details for DOI 10.1016/j.healun.2008.05.009

  View details for Web of Science ID 000258241200010

  View details for PubMedID 18656801

• Infections in lung allograft recipients: Ganciclovir era JOURNAL OF HEART AND LUNG TRANSPLANTATION Valentine, V. G., Bonvillain, R. W., Gupta, M. R., Lombard, G. A., LaPlace, S. G., Dhillon, G. S., Wang, G. 2008; 27 (5): 528-535

  Abstract

  Infections are common after lung transplantation. This report analyzes infections and associated pathogens identified in 202 lung transplant recipients.Infections were tallied according to sites of infection and associated pathogen(s). Infection events were also categorized by post-operative Days 0 to 100, 101 to 365, and after 365, and normalized to 100 patient-days before and after bronchiolitis obliterans syndrome (BOS).From November 1990 to November 2005, 202 patients received 208 lung transplants. The follow-up was 702.4 patient-years. A total of 178 lung transplant patients developed 859 infections, with 944 pathogens identified. Infections were in the lung in 559 (65.1%), mucocutaneous (skin, wound, catheter-related, and oral) in 88 (10.2%), in the blood in 85 (9.8%), and in other sites (urine, bowel, eye, and peritoneum) in 127 (14.8%). Most lung pathogens were bacterial (83.6%), and 57.9% were Pseudomonas aeruginosa. Fungi comprised 10.6%, with Aspergillus spp the most common (67.1%) isolate. Cytomegalovirus pneumonitis was seen in 4.3% of respiratory infections. BOS was diagnosed in 87 patients (43.1% of the total). Of all infections seen in the BOS population, there were 0.42 episodes/100 patient-days and 0.70 episodes/100 patient-days before and after BOS, respectively (p = 0.5).These data provide an updated infection profile in the ganciclovir era after lung transplantation. When compared with pre-ganciclovir times, post-transplant cytomegalovirus infection incidence has notably declined, with filamentous fungi emerging as prevalent pathogens in its place. Such findings are important for refining management of infections in order to offer more stringent treatment against aggressive pathogens.

  View details for DOI 10.1016/j.healun.2007.12.013

  View details for Web of Science ID 000255556900010

  View details for PubMedID 18442719

• Effect of etiology and timing of respiratory tract infections on the development of bronchiolitis obliterans syndrome after lung transplantation 28th Annual Meeting of the International-Society-for-Heart-and-Lung-Transplantation Valentine, V. G., Gupta, M. R., Walker, J. E., Lombard, G. A., Weill, D., Dhillon, G. S. ELSEVIER SCIENCE INC. 2008: S99–S99

  View details for Web of Science ID 000253342300111

• Post-operative infections in cystic fibrosis and non-cystic fibrosis patients after lung transplantation JOURNAL OF HEART AND LUNG TRANSPLANTATION Bonvillain, R. W., Valentine, V. G., Lombard, G., LaPlace, S., Dhillon, G., Wang, G. 2007; 26 (9): 890-897

  Abstract

  Cystic fibrosis (CF) lung disease is the major cause of mortality in CF patients. Lung transplantation remains a valid therapeutic option. It is unknown whether CF patients receiving healthy lungs have an equal susceptibility to infections when compared with non-CF lung transplant patients. Herein we present the largest analyses to date of the post-operative infection profiles of 60 CF and 60 non-CF lung transplant patients.Bilateral allogeneic lung transplantations and post-transplant management were performed according to standard clinical procedures. Post-operative infections were diagnosed by conventional methods based on clinical symptoms and laboratory cultures.Sixty CF lung-transplant patients developed 278 post-operative respiratory infections, from which 307 pathogens were isolated. Pseudomonas aeruginosa predominantly occupied 60.3%, followed by Mycobacteria spp (7.2%), Aspergillus spp (5.9%) and Staphylococcus spp (5.5%). However, 60 non-CF transplant patients had 154 respiratory infections with 165 pathogens isolated. Pseudomonas aeruginosa was noted in 38.2%, followed by Aspergillus spp (9.7%), Staphylococcus spp (9.7%) and Mycobacteria spp (9.1%). The CF group demonstrated a significantly higher frequency of Pseudomonas respiratory infections than the non-CF group. Interestingly, no significant differences were detected in any infections from other systems including blood, sinuses, skin, wounds, oral cavity, bowel, eyes, peritoneal cavity and urinary tract. Moreover, the CF lung transplant patients had significantly less time free from Pseudomonas infections.The normal lungs implanted into CF patients had significantly higher susceptibility to Pseudomonas infections than those into non-CF patients, suggesting that defective innate immunity outside the lungs contributes to CF lung pathogenesis.

  View details for DOI 10.1016/j.healun.2007.07.002

  View details for Web of Science ID 000249751400004

  View details for PubMedID 17845927

• Ganciclovir for cytomegalovirus: A call for indefinite prophylaxis. Valentine, V. G., Weill, D., Lombard, G. A., LaPlace, S. G., Bonvillain, R. N., Taylor, D. E., Seoane, L., Dhillon, G. S. BLACKWELL PUBLISHING. 2007: 505

  View details for Web of Science ID 000246370202260

• Effect of gram-negative bacterial respiratory infections on development of bronchiolitis obliterans syndrome Dhillon, G. S., Valentine, V. G., Taylor, D. E., LaPlace, S. G., Lombard, G. A., Bonvillian, R., Weill, D. ELSEVIER SCIENCE INC. 2007: S165

  View details for DOI 10.1016/j.healun.2006.11.313

  View details for Web of Science ID 000244342200295

• A single-institution study evaluating the utility of surveillance bronchoscopy following lung transplantation Valentine, V. G., Weill, D., Lombard, G. A., LaPlace, S. G., Seoane, L., Taylor, D. E., Dhillon, G. S. ELSEVIER SCIENCE INC. 2007: S174

  View details for DOI 10.1016/j.healun.2006.11.337

  View details for Web of Science ID 000244342200318

• Effect of airway pressure display on interobserver agreement in the assessment of vascular pressures in patients with acute lung injury and acute respiratory distress syndrome CRITICAL CARE MEDICINE Rizvi, K., deBoisblanc, B. P., Truwit, J. D., Dhillon, G., Arroliga, A., Fuchs, B. D., Guntupalli, K. K., Hite, D., Hayden, D. 2005; 33 (1): 98-103

  Abstract

  Previous investigations have identified significant interobserver variability in the measurements of central venous pressure and pulmonary artery occlusion pressure in critically ill patients. Large interobserver variability in the measurement of vascular pressures could potentially lead to inappropriate treatment decisions.We postulated that adding an airway pressure signal (Paw) to pressure tracings of central venous pressure and pulmonary artery occlusion pressure would improve interobserver agreement by facilitating identification of end-expiration.To test this hypothesis, six independent experts used a standard protocol to interpret strip-chart recordings of central venous pressure and pulmonary artery occlusion pressure with or without Paw. Two observers were said to agree if their measurements were within 2 mm Hg of each other. SETTING/SUBJECTS/INTERVENTIONS: A total of 459 strip-chart recordings (303 without Paw and 156 with Paw) were obtained from 121 patients enrolled in the ARDSnet Fluids and Catheters Treatment Trial (FACTT) in 16 different hospitals.Agreement within 2 mm Hg between two measurements was 79% for central venous pressure strips without Paw vs. 86% with Paw. For pulmonary artery occlusion pressure, agreement increased from 71% without Paw to 83% with Paw. The increase in agreement with the addition of Paw was greater for strips demonstrating >8 mm Hg phasic respiratory variation compared with strips demonstrating less phasic respiratory variation.Paw display is a simple, inexpensive method to facilitate the identification of end-expiration that can significantly improve interobserver agreement.

  View details for DOI 10.1097/01.CCM.0000150350.70142.E9

  View details for Web of Science ID 000226336300013

  View details for PubMedID 15644654

• The New UNOS Lung Transplantation Allocation System Advances in Pulmonary Hypertension Dhillon G, Doyle R 2005; 4 (2): 12-13
• Estimation of pulmonary artery occlusion pressure by an artificial neural network CRITICAL CARE MEDICINE deBoisblanc, B. P., Pellett, A., Johnson, R., Champagne, M., McClarty, E., Dhillon, G., Levitzky, M. 2003; 31 (1): 261-266

  Abstract

  We hypothesized that an artificial neural network, interconnected computer elements capable of adaptation and learning, could accurately estimate pulmonary artery occlusion pressure from the pulsatile pulmonary artery waveform.University medical center.Nineteen closed-chest dogs.Pulmonary artery waveforms were digitally sampled before conventional measurements of pulmonary artery occlusion pressure under control conditions, during infusions of serotonin or histamine, or during volume loading. Individual beats were parsed or separated out. Pulmonary artery pressure, its first time derivative, and the beat duration were used as neural inputs. The neural network was trained by using 80% of all samples and tested on the remaining 20%. For comparison, the regression between pulmonary artery diastolic pressure and pulmonary artery occlusion pressure was developed and tested using the same data sets. As a final test of generalizability, the neural network was trained on data obtained from 18 dogs and tested on data from the remaining dog in a round-robin fashion.The correlation coefficient between the pulmonary artery diastolic pressure estimate of pulmonary artery occlusion pressure and measured pulmonary artery occlusion pressure was.75, whereas that for the neural network estimate of pulmonary artery occlusion pressure was.97 (p <.01 for difference between pulmonary artery diastolic pressure and pulmonary artery occlusion pressure estimates). The pulmonary artery diastolic pressure estimate of pulmonary artery occlusion pressure showed a bias of 0.097 mm Hg (limits of agreement -7.57 to 7.767 mm Hg), whereas the neural network estimate of pulmonary artery occlusion pressure showed a bias of -0.002 mm Hg (-2.592 to 2.588 mm Hg). There was no significant change in the bias of the neural network estimate over the range of values tested. In contrast, the bias for the pulmonary artery diastolic pressure estimate significantly increased with the increasing magnitude of the pulmonary artery occlusion pressure. During round-robin testing, the neural network estimate of pulmonary artery occlusion pressure showed suboptimal performance (correlation coefficient between estimated and measured pulmonary artery occlusion pressure.59).A neural network can accurately estimate pulmonary artery occlusion pressure over a wide range of pulmonary artery occlusion pressure under conditions that alter pulmonary hemodynamics. We speculate that artificial neural networks could provide accurate, real-time estimates of pulmonary artery occlusion pressure in critically ill patients.

  View details for DOI 10.1097/01.CCM.0000045022.14444.DB

  View details for Web of Science ID 000180714800041

  View details for PubMedID 12545026

• Success of lung transplantation without surveillance bronchoscopy JOURNAL OF HEART AND LUNG TRANSPLANTATION Valentine, V. G., Taylor, D. E., Dhillon, G. S., Knower, M. T., McFadden, P. M., Fuchs, D. M., Kantrow, S. P. 2002; 21 (3): 319-326

  Abstract

  No current evidence demonstrates improved survival or decreased rate of bronchiolitis obliterans syndrome (BOS) despite regularly scheduled fiberoptic bronchoscopy (FOB) with transbronchial biopsy and bronchoalveolar lavage (TBB/BAL) after lung transplantation. Reduced lung function detected with spirometry or oximetry in symptomatic and asymptomatic lung allograft recipients (LARs) may be a more appropriate indication for bronchoscopic sampling.Clinically indicated TBB/BAL without routine invasive surveillance sampling of the transplanted lung does not decrease survival or increase the rate of BOS in LARs.We reviewed 91 consecutive LARs transplanted at Ochsner Clinic between January 1995 and December 1999. Clinical indications for FOB with TBB/BAL include 10% decline in forced expiratory volume in 1 second below baseline; 20% decrease in forced expiratory flow rate between 25% and 75% of the forced vital capacity; or unexplained respiratory symptoms, signs, or fever. Along with demographic and clinical data, 1-year and 3-year survival rates for these 91 LARs were compared with 5,430 LARs from the International Society for Heart and Lung Transplantation (ISHLT) Registry transplanted during the same 60-month period. Ten of the 91 patients did not survive to hospital discharge after transplantation. We divided the remaining 81 LARs into 2 subsets: Group A patients (n = 43) underwent zero to 1 TBB/BAL and Group B patients (n = 38) required more than 1 procedure. Demographic data, rejection, infection, and incidence of BOS were compared between groups.The 1-year and 3-year survival rates in the Ochsner LAR cohort were 85% and 73%, respectively, vs 72% and 57% in the ISHLT cohort p < 0.01. The relative risks of death in the Ochsner group at 1- and 3-years were 0.56 (0.35-0.91) and 0.66 (0.48-0.92), respectively, p < 0.05. The median (range) follow-up was 910 days (60-1,886) for Group A and 961 days (105-1,883) for Group B, p = not significant. We observed twice as many patients with cystic fibrosis and twice as many pneumonia episodes in Group B. The rate of acute rejection in each group was not statistically different. The cumulative incidence of BOS was increased in Group B at 1 year and at 3 years (5% and 56%) when compared with Group A (3% and 13%), p < 0.01.Based on the findings from this observational, single-institution study, clinically indicated TBB/BAL without routine surveillance sampling of the lung allograft is unlikely to pose greater risk than does regularly scheduled bronchoscopy after lung transplantation.

  View details for Web of Science ID 000174396600003

  View details for PubMedID 11897519

• Inhibition of hematopoietic progenitor cell proliferation by ethanol in human immunodeficiency virus type 1 Tat-expressing transgenic mice ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH Prakash, O., Rodriguez, V. E., Tang, Z. Y., Zhou, P., Coleman, R., Dhillon, G., Shellito, J. E., Nelson, S. 2001; 25 (3): 450-456

  Abstract

  A number of hematological abnormalities are associated with both human immunodeficiency virus type 1 (HIV-1) infection and alcohol abuse. There is little information on how alcohol abuse might further influence the survival and growth of hematopoietic progenitors in HIV-infected individuals in the presence of immune system abnormalities and anti-HIV drugs. Because there is evidence that viral transactivator Tat itself can induce hematopoietic suppression, in this study we examined the role of ethanol as a cofactor in transgenic mice that expressed HIV-1 Tat protein.Tat transgenic mice and nontransgenic littermates were given ethanol (20% v/v) and the anti-HIV drug 3'-azido-3'-deoxythymidine (AZT; 1 mg/ml) in drinking water. Immunosuppression in mice was induced by weekly intraperitoneal injections of anti-CD4 antibody. Hematopoiesis was examined by erythroid colony forming unit (CFU-E) and granulocyte/macrophage colony-forming unit (CFU-GM) assays of the bone marrow progenitor cells.Administration of ethanol for 7 weeks resulted in a 50% decrease in the proliferative capacity of CFU-E- and CFU-GM-derived progenitors from transgenic mice compared with that of ethanol-treated nontransgenic controls. Similar decreases also were observed in transgenic mice treated with AZT or a combination of AZT and ethanol. Furthermore, ethanol and AZT were significantly more toxic to the granulopoietic progenitors (40-50% inhibition) than to the erythropoietic progenitors (10-20% inhibition) in Tat transgenic mice. Although a 10 day exposure of Tat transgenic and nontransgenic mice to a combination of ethanol and AZT had no suppressive effect on the erythropoietic and granulopoietic progenitor cells, there was a marked decrease (40-60%) in CFU-GM in mice made immunodeficient by CD4+ T-lymphocyte depletion. The ethanol-treated Tat transgenic mice but not the nontransgenic litter-mates also showed a significant decrease (25%) in CFU-GM.Our in vivo study strongly suggests that ethanol ingestion in HIV-1-infected individuals, particularly those on antiretroviral drugs, might increase bone marrow toxicity and contribute to HIV-1-associated hematopoietic impairment.

  View details for Web of Science ID 000167594300018

  View details for PubMedID 11290858

• Lung Under Stress Pulmonary Pathophysiology Dhillon, G., Kantrow, S. McGraw Hill. 1999: 313–331