Lorriana Leard

University of California, San Francisco, San Francisco, California, United States

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Publications (44)233.41 Total impact

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    ABSTRACT: Frailty is associated with morbidity and mortality in abdominal organ transplantation but has not been examined in lung transplantation. To examine the construct and predictive validity of frailty phenotypes in lung transplant candidates. In a multicenter prospective cohort we measured frailty with the Fried Frailty Phenotype (FFP) and Short Physical Performance Battery (SPPB). We evaluated construct validity through comparisons to conceptually related factors. In a nested case-control study of frail and non-frail subjects, we measured serum IL-6, tumor necrosis factor-receptor 1 (TNFR1), insulin-like growth factor I (IGF-1), and leptin. We estimated the association between frailty and disability and risk of delisting/death before transplant using multivariate logistic and cox models, respectively. In 395 subjects, 28% were frail by FFP (95%CI 24-33%) and 10% by SPPB (95%CI 7-14%). By either measure, frailty correlated more strongly with exercise capacity and grip strength than with lung function. Frail subjects tended to have higher plasma IL-6 and TNFR1 and lower IGF-1 and leptin. Frailty by either measure was associated with greater disability. After adjusting for age, gender, diagnosis and transplant center, both FFP and SPPB were associated with increased risk of delisting/death before lung transplantation (FFP, HR 1.30, 95%CI 1.01-1.67; SPPB, HR 1.53, 95%CI 1.19-1.59 per one point worsening in score). Frailty is prevalent among lung transplant candidates and is independently associated with greater disability and an increased risk of delisting or death.
    American Journal of Respiratory and Critical Care Medicine 08/2015; DOI:10.1164/rccm.201506-1150OC · 13.00 Impact Factor
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    ABSTRACT: Successful lung transplantation for patients with pulmonary fibrosis from telomerase mutations may be limited by systemic complications of telomerase dysfunction, including myelosuppression, cirrhosis, and malignancy. We describe clinical outcomes in 14 lung transplant recipients with telomerase mutations. Subjects underwent lung transplantation between February 2005 and April 2014 at 5 transplant centers. Data were abstracted from medical records, focusing on outcomes reflecting post-transplant treatment effects likely to be complicated by telomerase mutations. The median age of subjects was 60.5 years (interquartile range = 52.0-62.0), 64.3% were male, and the mean post-transplant observation time was 3.2 years (SD ± 2.9). A mutation in telomerase reverse transcriptase was present in 11 subjects, a telomerase RNA component mutation was present in 2 subjects, and an uncharacterized mutation was present in 1 subject. After lung transplantation, 10 subjects were leukopenic and 5 did not tolerate lymphocyte anti-proliferative agents. Six subjects developed recurrent lower respiratory tract infections, 7 developed acute cellular rejection (A1), and 4 developed chronic lung allograft dysfunction. Eight subjects developed at least 1 episode of acute renal failure and 10 developed chronic renal insufficiency. In addition, 3 subjects developed cancer. No subjects had cirrhosis. At data censorship, 13 subjects were alive. The clinical course for lung transplant recipients with telomerase mutations is complicated by renal disease, leukopenia with intolerance of lymphocyte anti-proliferative agents, and recurrent lower respiratory tract infections. In contrast, cirrhosis was absent, acute cellular rejection was mild, and development of chronic lung allograft dysfunction was comparable to other lung transplant recipients. Although it poses challenges, lung transplantation may be feasible for patients with pulmonary fibrosis from telomerase mutations. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.
    The Journal of Heart and Lung Transplantation 05/2015; 34(4). DOI:10.1016/j.healun.2015.05.002 · 6.65 Impact Factor

  • The Journal of Heart and Lung Transplantation 04/2015; 34(4):S256. DOI:10.1016/j.healun.2015.01.712 · 6.65 Impact Factor

  • The Journal of Heart and Lung Transplantation 04/2015; 34(4):S256-S257. DOI:10.1016/j.healun.2015.01.713 · 6.65 Impact Factor
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    The Journal of Heart and Lung Transplantation 04/2015; 34(4):S15. DOI:10.1016/j.healun.2015.01.028 · 6.65 Impact Factor

  • The Journal of Heart and Lung Transplantation 04/2015; 34(4):S148. DOI:10.1016/j.healun.2015.01.398 · 6.65 Impact Factor

  • The Journal of Heart and Lung Transplantation 04/2015; 34(4):S121. DOI:10.1016/j.healun.2015.01.320 · 6.65 Impact Factor
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    ABSTRACT: Background: Hypersensitivity pneumonitis (HP) is an inhaled antigen-mediated interstitial lung disease (ILD). Advanced disease may necessitate the need for lung transplantation. There are no published studies addressing lung transplant outcomes in HP. We characterized HP outcomes compared with referents undergoing lung transplantation for idiopathic pulmonary fibrosis (IPF). Methods: To identify HP cases, we reviewed records for all ILD lung transplantation cases at our institution from 2000 to 2013. We compared clinical characteristics, survival, and acute and chronic rejection for lung transplant recipients with HP to referents with IPF. We also reviewed diagnoses of HP discovered only by explant pathology and looked for evidence of recurrent HP after transplant. Survival was compared using Kaplan-Meier methods and Cox proportional hazard modeling. Results: We analyzed 31 subjects with HP and 91 with IPF among 183 cases undergoing lung transplantation for ILD. Survival at 1, 3, and 5 years after lung transplant in HP compared with IPF was 96%, 89%, and 89% vs 86%, 67%, and 49%, respectively. Subjects with HP manifested a reduced adjusted risk for death compared with subjects with IPF (hazard ratio, 0.25; 95% CI, 0.08-0.74; P = .013). Of the 31 cases, the diagnosis of HP was unexpectedly made at explant in five (16%). Two subjects developed recurrent HP in their allografts. Conclusions: Overall, subjects with HP have excellent medium-term survival after lung transplantation and, relative to IPF, a reduced risk for death. HP may be initially discovered only by review of the explant pathology. Notably, HP may recur in the allograft.
    Chest 11/2014; 147(6). DOI:10.1378/chest.14-1543 · 7.48 Impact Factor
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    ABSTRACT: Lung transplant (LT) aims to extend survival and improve patient-centred outcomes (PCOs) by reducing disability and improving health-related quality of life (HRQL). Few PCO instruments have been validated in LT populations. We aimed to develop and validate a shortened version of the valued life activities (VLA) disability scale specific to LT. We used data from 140 subjects participating in an ongoing cohort study of LT. Subjects completed a survey battery, including VLA items, and physical assessments before LT. To develop a shortened LT-specific VLA (LT-VLA), we iteratively deleted items from a longer 32-item VLA battery, retaining the instrument's conceptual framework, scoring and performance characteristics. We evaluated LT-VLA validity by testing correlations with a HRQL measure (Short Form-12 Physical Function (SF-12 PF) subscale), forced vital capacity % (FVC%) predicted and 6 minute walk distance (6MWD). Responsiveness was evaluated in 84 subjects who completed assessments before and after LT. The 15-item LT-VLA scoring closely matched the longer VLA (correlations ≥0.96) and had excellent internal consistency (Cronbach's α 0.92). The LT-VLA required only 3 min or less to administer. The LT-VLA, measured as mean difficulty in performing each of the 15 activities queried, correlated with FVC% predicted (r=-0.30), 6MWD (r=-0.38) and SF-12 PF (r=-0.47) (all p<0.01). The LT-VLA mean difficulty was responsive to change from before to after LT (63% improvement; effect size=1.60). The LT-VLA is a short, easy to administer, valid and responsive disease-specific PCO instrument that may be useful in clinical and research applications for lung transplantation.
    Thorax 12/2013; 33(4). DOI:10.1136/thoraxjnl-2013-204557 · 8.29 Impact Factor
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    ABSTRACT: Purpose Lung transplant (LT) aims to improve both survival and quality of life (HRQL). To achieve this, a better understanding of the factors determining HRQL is needed. We tested the impact of frailty on HRQL in LT candidates (LTC). Methods and Materials From 2010-12, all patients listed or near listing for LT were asked to complete a phone survey. HRQL was quantified with the EuroQOL-5D (EQ5D) utility instrument (range: -0.11-1.0; higher scores denote better HRQL; 0.06=Minimally Clinically Important Difference [MCID] in EQ5D). Respiratory-specific HRQL was quantified with the revised Airways Questionnaire-20 (AQ20R; range 0-20; lower scores denote better HRQL). Frailty was quantified by the Short Physical Performance Battery (SPPB; walking speed, chair stands, and balance scores integrated into a summary score ranging 0-12; higher scores denote better function). We ascertained frailty prevalence (SPPB≤6) across UNOS diagnostic groups (A:COPD, B:Pulmonary Hypertension, C: Cystic Fibrosis, D: Pulmonary Fibrosis). Using multiple linear regression, we tested sequential models of HRQL to assess the overall explanatory power based on model R2. In Model 1, we tested FEV1% predicted, 6 minute walk distance, age, diagnostic group, and AQ20R as predictors of EQ5D. In Model 2, we added the SPPB to Model 1. Results Of 123 LTC, 37(30%) were frail; frailty prevalence ranged from 25-32% across the 4 diagnostic groups A-D. There was a wide range of SPPB performance (mean 7±3). In regression analyses, the SPPB added significant (p<0.05) explanatory power to models of HRQL (R2=0.46 vs 0.28). In Model 2, adjusting for all covariates, each 1 point increase in SPPB score predicted 0.05 higher EQ5D (95%CI: 0.03-0.08), close to the MCID. Conclusions In summary, almost one third of LTC are frail. Frailty is strongly associated with HRQL, even after accounting for lung function, exercise capacity, and respiratory specific HRQL. Thus, frailty is common and drives HRQL independent of respiratory status. Interventions to improve HRQL in LT should take frailty into account.
    The Journal of Heart and Lung Transplantation 04/2013; 32(4):S43. DOI:10.1016/j.healun.2013.01.912 · 6.65 Impact Factor
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    ABSTRACT: DSAs prior to lung transplantation (LT) have been associated with adverse outcomes, but the implications of weak DSAs detected by sensitive microarrays remain poorly understood. We examined the incidence of DSAs before transplant and immunodominant DSA (iDSA) profiles after LT.Methods and MaterialsLT recipients (n=66) from a single center with single antigen testing (LABScreen®) before LT, within the first 45 days after LT and at least one subsequent time point were studied. Patients were excluded if they received any desensitization or antibody directed therapy. We defined the iDSA as the DSA with the highest mean fluorescence intensity (MFI). We used iDSA levels pre-LT to categorize subjects into 3 groups: No DSA, iDSA MFI of 500-1000 MFI, and iDSA MFI >1000.ResultsPre-LT, no DSAs were detected in 36 (55%) patients. Of these, 6 (17%) developed iDSA >1000 MFI post-LT (range 1685-6071 MFI). These iDSAs were initially detected 12-32 days after transplant, against HLA Class II, and accompanied by additional DSAs. At the last time point (93-560 days post-LT), the DSAs were below peak levels or were eliminated. Pre-LT iDSAs with MFI 500-1000 were observed in 12 (18%) of patients. Of these, 5 (42%) developed iDSA >1000 MFI post-LT. In 2 of these 5, the post-LT iDSA specificity was different from the pre-LT iDSA. At the last time point, DSA levels were declining or eliminated in 3 recipients. Pre-LT iDSA >1000 MFI were detected in 18 (27%) recipients (range 1023-5246 MFI; 11 Class II, 7 Class I). Post-LT, 4 had no DSA >1000 MFI. The maximum iDSA level after LT was 9659 MFI. In 13 (72%) of these recipients, iDSA specificity pre- and post-LT was identical. Of the 18 recipients, 9 (50%) had all DSA <500 MFI at the last serum, 8 (44%) had DSA declining from peak levels, and 1 was stable.Conclusions Weak DSAs are observed in nearly half of patients pre-LT. While variable, the majority of DSAs decline post-LT. Additional study is needed to determine the impact of weak pre-LT DSAs and declining post-LT DSAs on clinical outcomes.
    The Journal of Heart and Lung Transplantation 04/2013; 32(4):S171. DOI:10.1016/j.healun.2013.01.407 · 6.65 Impact Factor
  • J P Singer · J Chen · P D Blanc · L E Leard · J Kukreja · H Chen ·
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    ABSTRACT: Health-related quality of life (HRQL) has been assessed in various lung transplantation (LT) investigations but never analyzed systematically across multiple studies. We addressed this knowledge gap through a systematic literature review. We searched the PubMed, CINAHL and PsychInfo databases for publications from January 1, 1983 to December 31, 2011. We performed a thematic analysis of published studies of HRQL in LT. Using a comparative, consensus-based approach, we identified themes that consistently emerged from the data, classifying each study according to primary and secondary thematic categories as well as by study design. Of 749 publications initially identified, 73 remained after exclusions. Seven core themes emerged: (1) Determinants of HRQL; (2) Psychosocial factors in HRQL; (3) Pre- and posttransplant HRQL comparisons; (4) Long-term longitudinal HRQL studies; (5) HRQL effects of therapies and interventions; (6) HRQL instrument validation and methodology; (7) HRQL prediction of clinical outcomes. Overall, LT significantly and substantially improves HRQL, predominantly in domains related to physical health and functioning. The existing literature demonstrates substantial heterogeneity in methodology and approach; relatively few studies assessed HRQL longitudinally within the same persons. Opportunity for future study lies in validating existing and potential novel HRQL instruments and further elucidating the determinants of HRQL through longitudinal multidimensional investigation.
    American Journal of Transplantation 02/2013; 13(4). DOI:10.1111/ajt.12174 · 5.68 Impact Factor
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    ABSTRACT: Despite the adoption of antifungal prophylaxis, fungal infections remain a significant concern in lung transplant recipients. Indeed, some concern exists that such prophylaxis may increase the risk of infection with drug-resistant fungal organisms. Here, we describe a case of disseminated Scedosporium prolificans infection, presenting as pericarditis, which developed in a lung transplant patient receiving prophylactic voriconazole for 8 months. The epidemiology and clinical presentation of S. prolificans infections are reviewed, and controversies surrounding antifungal prophylaxis and the development of resistant infections are discussed.
    Transplant Infectious Disease 02/2013; 15(2). DOI:10.1111/tid.12056 · 2.06 Impact Factor
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    ABSTRACT: Background: Community acquired respiratory virus (CARV) infections in lung transplant recipients (LTR) have been associated with adverse outcomes, including acute rejection (AR) and decline in allograft function, in some but not in all studies. Methods: Spirometry and transbronchial biopsy results of LTR diagnosed with CARV infection over a two-yr period were extracted from clinical records. Primary outcomes, studied at 1-2.5 months postinfection, were as follows: (i) incidence of biopsy-proven AR (grade >A0) and (ii) allograft function, defined by forced expiratory volume in one s (FEV(1)). A reference group of biopsies (n = 526) collected during the study period established the baseline incidence of AR. Rhinovirus (RV) and non-rhinovirus (non-RV) infections were analyzed as subgroups. Results: Eighty-seven cases of CARV infection were identified in 59 subjects. Incidences of AR were similar in the post-CARV and reference groups and did not differ significantly after RV vs. non-RV infection. Allograft function declined significantly after non-RV infection, but not after RV infection. Conclusions: In LTR, CARV infections other than RV are associated with allograft dysfunction at 1-2.5 months after infection. However, CARVs do not appear associated with AR at this time point. The impact of specific CARVs on lung allografts, including the development of chronic allograft rejection, merits further study.
    Clinical Transplantation 12/2012; 27(1). DOI:10.1111/ctr.12054 · 1.52 Impact Factor
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    ABSTRACT: Pulmonary venoocclusive disease (PVOD) is a rare cause of pulmonary hypertension characterized by a progressive clinical course and poor outcomes if not treated by early lung transplantation. The pathogenesis of PVOD remains poorly understood. We report PVOD that developed in 2 young women soon after the initiation of oral contraceptives (OCs). The first patient is a 14-year-old girl, with no medical history, who started taking an OC 3 weeks before the onset of symptoms. The second patient is an 18-year-old girl, diagnosed 2 years previously with systemic lupus erythematosus and lupus anticoagulant, who started taking an OC 4 months before the onset of symptoms. Both patients required lung transplantation. Radiographic and histopathologic findings in both patients showed features of PVOD. Only 1 prior patient with PVOD and a handful of unclassified patients with pulmonary hypertension in association with OCs have been documented. The importance of PVOD as the basis of pulmonary hypertension in patients with connective tissue disease has been recently proposed, as well as the role of thrombogenesis, in the development of PVOD. The temporal sequence in these 2 patients suggests the thrombogenic action of OCs may contribute to the development of PVOD, with or without underlying connective tissue disease.
    The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 09/2012; 31(9):1031-6. DOI:10.1016/j.healun.2012.05.007 · 6.65 Impact Factor

  • The Journal of Heart and Lung Transplantation 04/2012; 31(4):S176. DOI:10.1016/j.healun.2012.01.516 · 6.65 Impact Factor
  • D.M. Sayah · J.L. Koff · L.E. Leard · J.A. Golden · J.P. Singer ·

    The Journal of Heart and Lung Transplantation 04/2012; 31(4):S238. DOI:10.1016/j.healun.2012.01.707 · 6.65 Impact Factor

  • The Journal of Heart and Lung Transplantation 04/2012; 31(4):S70. DOI:10.1016/j.healun.2012.01.858 · 6.65 Impact Factor
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    ABSTRACT: In lung transplant recipients (LTRs), tacrolimus is often utilized as a core component of immunosuppressive regimens. Although tacrolimus can be delivered orally or intravenously, oral tacrolimus is associated with fewer adverse effects. Various reports have suggested that sublingual tacrolimus may be used as an alternative to oral tacrolimus; however, information regarding converting between routes is limited. We aimed to identify a dose conversion ratio between oral and sublingual tacrolimus in LTRs. We identified adult LTRs at the University of California, San Francisco, who transitioned between oral and sublingual tacrolimus between 2005 and 2010 (n = 34). For tacrolimus, we obtained steady-state blood concentrations and total daily doses before and after the route conversion. Blood concentrations divided by daily doses were calculated for each route. The conversion ratio was then defined as: (blood concentration(sublingual)/daily dose(sublingual))/(blood concentration(oral)/daily dose(oral)). This ratio was tested in inpatient vs outpatient settings and in the presence of impaired gastric emptying. Adverse effects, including nephrotoxicity, hepatotoxicity and anaphylaxis, were evaluated. The conversion ratio of sublingual to oral tacrolimus was 0.46 ± 0.20 (mean ± SD). The ratio was not associated with hospital setting (p = 0.82) or with impaired gastric emptying (p = 0.31). When comparing sublingual to oral tacrolimus administration, there were no differences in serum creatinine, liver function tests or anaphylaxis. Tacrolimus administered sublingually at approximately half of the oral dose achieves therapeutic blood concentrations and is safe in LTRs. Delivery via the sublingual route using this conversion ratio may aid clinicians in maintaining therapeutic tacrolimus blood concentrations while avoiding the need for intravenous administration.
    The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 12/2011; 31(2):127-32. DOI:10.1016/j.healun.2011.10.015 · 6.65 Impact Factor