J A Golden

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

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Publications (144)914.55 Total impact

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    ABSTRACT: Rationale:Obesity and underweight are contraindications to lung transplantation based on their associations with mortality in studies performed prior to implementation of the Lung Allocation Score (LAS)-based organ allocation system in the United States. Objectives:To determine the associations of the body mass index(BMI) and plasma leptin levels with survival after lung transplantation. Methods:We used multivariable-adjusted regression models to examine associations between (1) BMI and 1-year mortality in 9,073 adults who underwent lung transplantation in the United States between May 2005 and June 2011, and (2) plasma leptin and mortality in 599 Lung Transplant Outcomes Group study participants. We measured body fat and skeletal muscle mass using whole-body dual x-ray absorptiometry in 142 adult lung transplant candidates. Measurements and Main Results: Adjusted mortality rates were similar among normal weight (BMI 18.5-24.9 kg/m2), overweight (BMI 25.0-29.9) and Class I obese (BMI 30-34.9) transplant recipients. Underweight (BMI<18.5) was associated with a 35% increased rate of death (95%CI 10-66%). Class II-III obesity (BMI≥35kg/m2) was associated with a nearly 2-fold increase in mortality (HR 1.9, 95%CI 1.3-2.8). Higher leptin levels were associated with increased mortality after transplant surgery performed without cardiopulmonary bypass (p for interaction=0.03). A BMI≥30 kg/m2 was 26% sensitive and 97% specific for total body fat-defined obesity. Conclusions: A BMI of 30.0-34.9kg/m2 is not associated with 1-year mortality after lung transplantation in the LAS era, perhaps due to its low sensitivity for obesity. The association between leptin and mortality suggests the need to validate alternative methods to measure obesity in candidates for lung transplantation. A BMI ≥30kg/m2 may no longer contraindicate lung transplantation.
    American Journal of Respiratory and Critical Care Medicine 09/2014; · 11.04 Impact Factor
  • The lancet. Respiratory medicine. 05/2014; 2(5):e5.
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    ABSTRACT: Late Breaking AbstractsSESSION TYPE: Slide PresentationPRESENTED ON: Saturday, March 22, 2014 at 09:00 AM - 10:00 AMPURPOSE: Human immunodeficiency virus seropositivity (HIV+) has been considered a contraindication to lung transplantation (LT) primarily due to potential risks of iatrogenic immunosuppression. With the recent passage of the HIV Organ Policy Equity (HOPE) Act on November 21, 2013, the donation of HIV+ organs for transplant in HIV+ recipients is now legal in the USA. As a result there may be an increase in donors for HIV+ recipients. However, there remains only one fully published case report of LT in an HIV+ patient, limiting the evidence base with which to guide medical decision making. We report 3 HIV+ patients at two different medical centers who underwent LT. Based on the experience of two centers, we compiled data for a case series of three HIV+ patients who underwent LT. Data was abtracted from medical records from the lung transplant programs at the University of California, San Francisco and Houston Methodist Hospital. We reviewed charts to investigate: 1.) Does LT affect the course of HIV infection? 2.) Do LT recipients demonstrate an increased risk for HIV-related opportunistic infections or malignancies? 3.) Can drug-drug interactions between immunosuppressive and antiretroviral medications be easily managed? 4.) Are HIV+ LT recipients at higher risk for acute rejection, similar to HIV+ liver and kidney transplant recipients? Patient 1, transplanted for HIV-associated pulmonary arterial hypertension, experienced recalcitrant acute rejection and the rapid development of bronchiolitis obliterans syndrome. Patients 2 and 3, transplanted for idiopathic pulmonary fibrosis, experienced mild acute rejection but remain free from chronic rejection at 3.5 and 1.5 years after transplant, respectively. We observed no instances of HIV-associated opportunistic infections or malignancies in any of the three cases. Drug-drug interactions, although challenging, were manageable. Unexpectedly, all 3 patients showed signs of pulmonary arterial vasculopathy on explant; all three also had at least one episode of acute cellular rejection in the first year after LT. In Patients 2 and 3, rejection was easily managed and did not recur, whereas Patient 1 required a lymphocyte-depleting agent. Based on this limited experience, LT appears feasible in the setting of HIV, although acute rejection appears to be common. As seen in other solid organ transplant populations, LT in the setting of HIV may be associated with good outcomes, but there may be increased rates of acute rejection. The following authors have nothing to disclose: Ryan Kern, Harish Seethamraju, Paul Blanc, Neeraj Sinha, Matthias Loebe, Jeffrey Golden, Jasleen Kukreja, Scott Scheinin, Steve Hays, Kleinhenz Mary Ellen, Leard Lorri, Charles Hoopes, Jonathan SingerNo Product/Research Disclosure Information.
    Chest 03/2014; 145(3 Suppl):642A. · 7.13 Impact Factor
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    ABSTRACT: Supplementary methods to identify acute rejection and to distinguish rejection from infection may improve clinical outcomes for lung allograft recipients. We hypothesized that distinct bronchoalveolar lavage (BAL) cell profiles are associated with rejection and infection. We retrospectively compared 2939 BAL cell counts and immunophenotypes against concomitantly obtained transbronchial biopsies and microbiologic studies. We randomly assigned 317 subjects to a derivation or validation cohort. BAL samples were classified into four groups: infection, rejection grade ≥A1, both or neither. We employed generalized estimating equation and survival modeling to identify clinical predictors of rejection and infection. We found that CD25(+) and natural killer cell percentages identified a twofold increased odds of rejection compared to either the infection or the neither infection nor rejection groups. Also, monocytes, lymphocytes and eosinophil percentages were independently associated with rejection. A four-predictor scoring system had high negative predictive value (96-98%) for grade ≥A2 rejection, predicted future rejection in the validation cohort and predicted increased risk of bronchiolitis obliterans syndrome in otherwise benign samples. In conclusion, BAL cell immunophenotyping discriminates between infection and acute rejection and predicts future outcomes in lung transplant recipients. Although it cannot replace histopathology, immunophenotyping may be a clinically useful adjunct.
    American Journal of Transplantation 02/2014; · 6.19 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; · 8.38 Impact Factor
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    ABSTRACT: Interstitial Lung Disease Cases ISESSION TYPE: Affiliate Case Report SlidePRESENTED ON: Sunday, October 27, 2013 at 07:30 AM - 08:30 AMINTRODUCTION: Lung transplantation (LT) can be a lifesaving therapy for patients suffering from advanced lung disease due to hypersensitivity pneumonitis (HP). Published data are limited addressing recipient outcomes post-lung transplantation (LT) in HP. In particular, although recurrence of primary disease in the recipient allograft has been described for a number of conditions1 this phenomenon is not well documented in HP. We present a case of recurrent HP in a LT recipient.CASE PRESENTATION: Bilateral LT was performed in 2009 on a 49-year-old woman with advanced fibrotic HP. She initially presented in 1991 complaining of cough and dyspnea, with imaging suggestive of HP and confirmation by surgical biopsy. She had no clear indoor exposure history; the possibility of ambient environmental exposures was considered. Serologic testing demonstrated precipitating antibodies to both bird proteins and fungi. Despite immunosuppressive therapy and potential ambient antigen avoidance by relocating, she had a slow decline in respiratory function and underwent bilateral LT in 2009. She did well for the first 2 years post-LT. By 3 years, however, she developed worsening cough and exertional dyspnea. She had an immune suppressive regimen of prednisone 10 mg daily, mycophenolate mofetil 500 mg bid, and tacrolimus (trough 8-10 ng/mL). CT scanning revealed air trapping; lung function testing showed a declining FEV1. Transbronchial lung biopsies (TBBX) showed non-necrotizing granulomas (culture negative). Repeat TBBXs at 1 month were unchanged. Bronchial alveolar lavage (BAL) showed 29% lymphocytes. The patient noted that pigeons were roosting outside her windows at her new home. Prednisone was increased, the patient again changed residence and her FEV1 stabilized. Subsequent TBBXs show no granulomas; the BAL lymphocytosis has resolved. She now has grade 3/3 bronchiolitis obliterans syndrome. It is unclear whether the recurrent HP contributed to this outcome.DISCUSSION: HP represents an immune reaction to inhaled organic antigens. Despite standard post-LT immunosuppressive regimens, intercurrent or ongoing exposure to an offending antigen may lead to recurrent disease in the allograft. Suggestive findings can include BAL lymphocytosis and non-necrotizing granulomas in the absence of infection.CONCLUSIONS: Our case highlights the importance of antigen recognition and aggressive avoidance or abatement post-LT for HP. This can be particularly problem-ridden if the exposure is poorly characterized. A detailed exposure history not only pre-LT but also at post-LT visits is imperative for this patient population.Reference #1: Collins, J. et al. Frequency and CT findings of recurrent disease after lung transplantation. Radiology 219, 503-509 (2001).DISCLOSURE: The following authors have nothing to disclose: Ryan Kern, Jonathan Singer, Kirk Jones, Kukreja Jasleen, Jeffrey Golden, Steven Hays, Leard Lorriana, Paul BlancNo Product/Research Disclosure Information.
    Chest 10/2013; 144(4_MeetingAbstracts):432A. · 7.13 Impact Factor
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    ABSTRACT: BACKGROUND: Lung disease is the leading cause of death in systemic sclerosis (SSc). The diagnosis of SSc-related lung disease (SSc-LD) is often a contraindication to lung transplantation (LT) due to concerns that extrapulmonary involvement will yield worse outcomes. We sought to evaluate posttransplantation outcomes in persons with SSc-LD with esophageal involvement compared with persons with nonconnective tissue disease-related interstitial lung disease (nCTD-ILD). METHODS: From 1998 to 2012, persons undergoing LT for SSc-LD were age and gender matched in a 2:1 fashion to controls undergoing LT for nCTD-ILD. Esophageal function was assessed by pH testing and manometry. We defined esophageal dysfunction as the presence of a DeMeester score >14 or dysmotility more severe than "mild nonspecific disorder". The primary outcome was posttransplantation survival. Secondary outcomes included freedom from bronchiolitis obliterans syndrome (fBOS) and rates of acute rejection. Survival and fBOS were estimated with Kaplan-Meier methods. Acute rejection was compared with Student's t test. RESULTS: Survival was similar in 23 persons with SSc-LD and 46 controls who underwent LT (P=0.47). For the SSc-LD group, 1- and 5-year survival was 83% and 76% compared with 91% and 64% in the nCTD-ILD group, respectively. There were no differences in fBOS (P=0.83). Rates of acute rejection were less in SSc-ILD (P=0.05). Esophageal dysfunction was not associated with worse outcomes (P>0.55). CONCLUSIONS: Persons with SSc-LD appear to have similar survival and fBOS as persons transplanted for nCTD-ILD. The risk of acute rejection after transplantation may be reduced in persons with SSc-LD. Esophageal involvement does not appear to impact outcomes.
    Transplantation 04/2013; 95(7):975-980. · 3.78 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; · 1.98 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; · 1.63 Impact Factor
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    ABSTRACT: RATIONALE: Lung transplantation offers great promise for otherwise terminal lung diseases, but the development of bronchiolitis obliterans syndrome (BOS) continues to limit survival. While acute rejection and lymphocytic bronchiolitis have been identified as risk factors for the development of BOS, it is unclear whether large-airway lymphocytic inflammation conveys the same risk. OBJECTIVES: We evaluated lymphocytic bronchitis on endobronchial biopsies as a risk factor for BOS and mortality. METHODS: Endobronchial biopsies were collected and graded during surveillance following lung transplantation. We assessed samples with negative cultures collected in the first 90 days from 298 subjects and compared large-airway lymphocytic bronchitis assessed by a 0 to 2 "E-score" and with standard A and BR pathology scores for acute rejection and small-airway lymphocytic bronchiolitis, respectively. RESULTS: We found surprisingly little association between large- and small-airway lymphocytic inflammation scores from a given bronchoscopy. Endobronchial lymphocytic bronchitis was more prevalent in subjects in BOS stage 0p and BOS stages 1-3 at the time of biopsy. Within 90 days after transplantation, increasing maximum E-score was associated with greater risk of BOS (adjusted hazards ratio 1.76, 95% CI 1.11-2.78, P = 0.02) and in this analysis 90-day maximum E-scores were the only score type predictive of BOS (P < 0.01). CONCLUSIONS: These results would support a multicenter study to evaluate endoscopic biopsies for the identification of patients at increased risk for BOS. The association of endobronchial lymphocytic inflammation and BOS may have mechanistic implications.
    American Journal of Respiratory and Critical Care Medicine 12/2012; · 11.04 Impact Factor
  • American Thoracic Society 2012 International Conference, May 18-23, 2012 • San Francisco, California; 05/2012
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    ABSTRACT: Lung transplant recipients (LTR) have an increased risk of cutaneous squamous cell carcinoma (SCC) due to immunosuppressive therapy. Voriconazole, which is associated with phototoxic side effects in some patients, may be an additional risk factor for SCC in this population. To test whether voriconazole is a risk factor for developing SCC in LTR, we evaluated cumulative exposure to voriconazole in 327 adults who underwent lung transplantation at one center between 1991 and 2010. Voriconazole exposure was assessed as a time-varying covariate. We used survival analysis methods to assess the risk of developing SCC over time. Exposure to voriconazole was associated with a 2.6-fold increased risk for SCC. This phenomenon was dose-dependent: the risk for SCC increased by 5.6% with each 60-day exposure at a standard dose of 200 mg twice daily. At 5 years after transplant, voriconazole conferred an absolute risk increase for SCC of 28%. These results suggest that caution should be taken when using voriconazole in LTR because this drug increases the already high risk for SCC in this population.
    The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 04/2012; 31(7):694-9. · 3.54 Impact Factor
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    ABSTRACT: The relationship of mast cells to the pathogenesis of lung fibrosis remains undefined despite recognition of their presence in the lungs of patients with pulmonary fibrosis. This study was performed to characterize the relationship of mast cells to fibrotic lung diseases. Lung tissues from patients with idiopathic pulmonary fibrosis (IPF), chronic hypersensitivity pneumonitis (HP), systemic sclerosis (SSc)-related interstitial lung disease (ILD) and normal individuals were subjected to chymase immunostaining and the mast cell density quantified. Eosinophils were quantified by immunostaining for eosinophil peroxidase. Changes in lung function were correlated with mast cell density. Lung tissue obtained from IPF patients had a higher density of chymase-immunoreactive mast cells than that from patients with HP, SSc-related ILD or normal lungs. IPF lung tissue had a higher density of eosinophils than normal lung. There was no correlation between mast cell density and eosinophil density in IPF lung. IPF patients with high mast cell density had a slower rate of decline in forced vital capacity (FVC) than IPF patients with low mast cell density. Mast cell density in IPF lungs is higher than in other fibrotic lung diseases and normal lungs. Increased mast cell density in IPF may predict slower disease progression.
    Histopathology 03/2012; 61(1):98-106. · 2.86 Impact Factor
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    ABSTRACT: The optimal method of both predicting and preventing cytomegalovirus (CMV) disease in lung transplant recipients remains unclear. In particular, the most appropriate duration of CMV prophylaxis post transplant is unresolved. We report herein our experience with a planned indefinite regimen of valganciclovir prophylaxis and monitoring of quantitative CMV load in bronchoalveolar lavage (BAL) fluid. We performed a single-center observational study with both prospective and retrospective components. The included patients (n = 128) received a planned regimen of indefinite valganciclovir prophylaxis post transplant, regardless of donor (D)/recipient (R) CMV serostatus. Real-time polymerase chain reaction assay for detection of CMV in BAL was prospectively performed over a 1-year period. Clinical data were reviewed retrospectively; median follow-up was 24.8 months (range 1-93 months). Sixty-five patients (50.6%) discontinued valganciclovir prophylaxis, either temporarily or permanently, with a primary cause of mild leukopenia. Six cases of CMV disease were identified (4.7%), with no significant difference between those who were on continuous prophylaxis or not (4.6% vs. 4.9%; P = non-significant [ns]). However, those who discontinued prophylaxis showed an increased incidence of laboratory-detected CMV infection (40.7% vs. 12.7%; P = 0.001). High-risk D+/R- patients did not demonstrate a significantly increased incidence of CMV disease (8.1% vs. 3.3% other serotypes; P = ns). Three patients (2.3%) developed valganciclovir-resistant CMV disease. Molecular detection of CMV in BAL fluid was significantly more sensitive than shell vial culture. However, BAL CMV viral load was not predictive of subsequent disease development. Extended valganciclovir prophylaxis for all lung transplant recipients led to a low incidence of CMV disease and resistance. In such low-incidence populations, routine quantitation of CMV in BAL did not confer significant clinical benefit over non-quantitative methods in prediction of CMV disease onset.
    Transplant Infectious Disease 03/2012; 14(3):248-58. · 1.98 Impact Factor
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    ABSTRACT: Cutaneous squamous cell carcinoma (cSCC) is the most common malignancy after solid organ transplantation, with an increased risk of recurrence and metastasis over the general population. The newly updated 7th edition American Joint Committee on Cancer (AJCC) staging system for cSCC is based on consensus expert opinion and requires validation in large cohort studies and in specific patient subpopulations. Our objective was to evaluate the risk of cSCC recurrence in a high-risk population of heart and lung transplant recipients, based on the 7th edition AJCC staging system. We performed a 10-year retrospective cohort study of all primary cSCC diagnosed in heart and lung transplant recipients at a tertiary care academic dermatology center. The cumulative incidence of local recurrence was 4% for cSCC in situ and 19% for stage I cSCC at 5 years, and 54% for stage II cSCC at 3 years. Stage II tumors had a 10-fold greater risk of recurrence than stage I, and a 43-fold greater risk of recurrence than in situ tumors. This study is limited to a specific patient subgroup at a tertiary care center, and may not be generalizable to all populations. Heart and lung transplant recipients are at high risk for local recurrence of cSCC. These data substantiate the prognostic accuracy of the newly updated 7th edition AJCC staging system for stage 0, I, and II cSCC in this population and demonstrate the aggressive behavior of this cancer in immunosuppressed patients.
    Journal of the American Academy of Dermatology 01/2012; 67(5):829-35. · 4.91 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. · 3.54 Impact Factor
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    ABSTRACT: Several reviews exist describing the safety of bronchoscopy in lung transplant recipients. However, the incidence of bronchoscopic complications in lung transplant recipients in relation to trainee involvement, and clinical characteristics such as pre-transplant diagnosis and transplant type, has not been described. We performed a retrospective cohort study of all lung transplant recipients undergoing flexible fiberoptic bronchoscopy (n = 259) at the University of California, San Francisco, between January, 2003, and June, 2009. Complications included bleeding, pneumothorax, aspiration, oversedation, and hypoxemia. From 2003 to 2009, 3734 flexible fiberoptic bronchoscopies were performed, including 2111 (57%) with transbronchial biopsies. Trainees were involved in 2102 bronchoscopies (56%), including 1046 transbronchial biopsies (49.5%). Complications occurred in 27 bronchoscopies [0.7% (95% Confidence Interval [CI]: 0.4-1.0)], with 10 involving a trainee (37%). Twenty (74%) occurred during bronchoscopies with transbronchial biopsies. Six of these involved a trainee, while 14 involved an attending alone (P = 0.03). We did not find differences in pre-transplant diagnosis, transplant type, lung, or renal function between subjects who suffered a complication and those who did not (P ≥ 0.30). The involvement of trainees, pre-transplant diagnosis, and transplant type do not significantly impact the rate of bronchoscopic complications in lung transplant recipients.
    Transplant International 12/2011; 25(2):172-8. · 3.16 Impact Factor
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    ABSTRACT: Information is scant assessing outcomes in lung transplantation (LT) in advanced occupational lung diseases (OLD). To analyse survival after LT for OLD. Using data from the US Organ Procurement and Transplantation Network Registry (OPTN-R), we identified subjects aged ≥ 18 years transplanted for OLD from 2005 to 2010. OPTN-R selected referents of corresponding age, sex and body mass index (BMI) who underwent LT for other diagnoses were also identified. Post-LT survival time was estimated with Cox proportional hazard models. Baseline age, BMI, forced expiratory volume in 1 s, creatinine, lung allocation score, donor age, donor lung ischaemic time and transplant type (single versus bilateral) were included as covariates. Time-dependent covariates were used to model differences in relative risk over time. Thirty-seven males underwent LT for silicosis (n = 19) or other OLD (n = 18) during the analytic period (0.5% of all LTs). For non-silicotic OLD, 6-month and 1- and 3-year survival estimates were 66, 55 and 55%, compared with the silicotic group (86, 86 and 76%) and referent group (89, 84 and 67%). During the first year post-transplant, those with OLD (silicosis and others combined) manifested an overall 2-fold increased mortality risk [hazard ratio (HR) 2.3, 95% CI 1.3-4.4; P < 0.05] compared to referents. In stratified analysis, this increased risk of death was restricted to those with non-silicotic OLD (HR 3.1, 95% CI 1.5-6.6; P < 0.01). Poorer survival was limited to the first year post-LT. Subjects undergoing LT for OLD other than silicosis may be at increased risk of death in the first year post-transplantation.
    Occupational Medicine 11/2011; 62(2):134-7. · 1.45 Impact Factor
  • Don Hayes, Jeffrey A Golden, Charles W Hoopes
    The Annals of thoracic surgery 11/2011; 92(5):1905. · 3.45 Impact Factor
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    ABSTRACT: Background: Invasive aspergillosis (IA) is an important cause of morbidity and mortality among lung transplant recipients. It is unclear which agent should be used for the prevention of IA in this population. We evaluated the impact of two prophylactic strategies to prevent IA among lung transplant recipients. Methods: We retrospectively reviewed medical records for all lung transplants performed between 2000 and 2007 at the University of California at San Francisco. Each patient was prescribed one of two fungal prophylactic regimens, a) inhaled prophylaxis only or b) any systemic prophylaxis (e.g. voriconazole) for 12 weeks plus inhaled amphotericin. We performed surveillance bronchoscopies at 2, 4, 6 and 8 weeks post transplantation. We performed brushings, washings and biopsies of suspicious lesions, examined patients and reviewed chest CT scans at the time of bronchoscopies. Using multivariable analyses, we explored the individual impact of either prophylactic strategy (inhaled only versus systemic) on incident IA post transplantation. Results: Between October 2000 and May 2007, 251 men and women underwent lung transplantation. Of these, 159 received inhaled while 92 received additional systemic mould prophylaxis . Of those who received inhaled prophylaxis, 17% were diagnosed with IA; 9% of those receiving systemic mould prophylaxis had IA. The median time to the onset of IA was 31 weeks (IQR 14-90). In multivariable analysis, there was a relationship between IA and female sex (OR 4.8, 95% CI 1.6-14, P<0.01), but no evidence for a role of systemic mould prophylaxis (versus inhaled agents only), use of induction agents, age, CMV disease and rejection (P>0.20). Conclusion: A voriconazole strategy as primary prophylaxis in lung transplant recipients was not associated with a decline in the incidence of IA compared with inhaled amphotericin. Continued surveillance over time is needed to determine whether these effects are sustained and whether the burden of disease due to non Aspergillus mould will increase.
    Infectious Diseases Society of America 2011 Annual Meeting; 10/2011

Publication Stats

3k Citations
914.55 Total Impact Points

Institutions

  • 1983–2014
    • University of California, San Francisco
      • • Department of Surgery
      • • Department of Epidemiology and Biostatistics
      • • Division of Hospital Medicine
      • • Cardiovascular Research Institute
      San Francisco, California, United States
  • 2010
    • CSU Mentor
      Long Beach, California, United States
  • 1991
    • Howard Hughes Medical Institute
      Ashburn, Virginia, United States