J A Golden

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

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Publications (93)639.26 Total impact

  • [Show abstract] [Hide abstract]
    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: 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: OBJECTIVE: Acute clinical deterioration preceding death is a common observation in patients with advanced interstitial lung disease and secondary pulmonary hypertension. Patients with pulmonary arterial hypertension refractory to medical therapy are also at risk of sudden cardiac death (cor pulmonale). The treatment of these patients remains complex, and the findings from retrospective studies have suggested that intubation and mechanical ventilation are inappropriate given the universally poor outcomes. Extracorporeal support technologies have received limited attention because of the presumed inability to either recover cardiopulmonary function in the patient with end-stage disease or the presumed inability to proceed to definitive therapy with transplantation. METHODS: A retrospective review was performed of 31 patients from 2 institutions placed on extracorporeal membrane oxygenation as a bridge to lung transplantation compared with similar patients without extracorporeal membrane oxygenation at the same institutions and comparison groups queried from the United Network for Organ Sharing database. RESULTS: We have transplanted 31 patients with refractory lung disease from mechanical artificial lung support. Of the 31 patients, 19 were ambulatory at transplantation. Pulmonary fibrosis (42%), cystic fibrosis (20%), and pulmonary hypertension (16%) were the most common diagnostic codes and acute cor pulmonale (48%) and hypoxia (39%) were the most common indications for device deployment. The average duration of extracorporeal membrane oxygenation support was 13.7 days (range, 2-53 days), and the mean survival of all patients bridged to pulmonary transplantation was 26 months (range, 54 days to 95 months). The 1-, 3-, and 5-year survival was 93%, 80%, and 66%, respectively. The duration of in-house postoperative transplant care ranged from 12 to 86 days (mean, 31 days). Patients requiring an extracorporeal membrane oxygenation bridge had comparable survival to that of the high acuity patients transplanted without extracorporeal membrane oxygenation support in the Scientific Registry of Transplant Recipients database but were at a survival disadvantage compared with the high-acuity patients (lung allocation score, >50) transplanted at the same center who did not require mechanical support (P < .001). CONCLUSIONS: These observations challenge current assumptions about the treatment of selected patients with end-stage lung disease and suggest that "salvage transplant" is both technically feasible and logistically viable. Widespread adoption of artificial lung technology in lung transplant will require the design of clinical trials that establish the most effective circumstances in which to use these technologies. A discussion of a clinical trial and reconsideration of current allocation policy is warranted.
    The Journal of thoracic and cardiovascular surgery 01/2013; · 3.41 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: 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
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    ABSTRACT: Lung transplantation in mechanically ventilated (MV) patients has been associated with decreased posttransplant survival. Under the Lung Allocation Score (LAS) system, patients at greatest risk of death on the waiting list, particularly those requiring MV, are prioritized for lung allocation. We evaluated whether pretransplant MV is associated with poorer posttransplant survival in the LAS era. Using a national registry, we analyzed all adults undergoing lung transplantation in the United States from 2005 to 2010. Propensity scoring identified nonventilated matched referents for 419 subjects requiring MV at the time of transplantation. Survival was evaluated using Kaplan-Meier methods. Risk of death was estimated by hazard ratios employing time-dependent covariates. We found that pretransplant MV was associated with decreased overall survival after lung transplantation. In the first 6 months posttransplant, ventilated subjects had a twofold higher risk of death compared to nonventilated subjects. However, after 6 months posttransplant, survival did not differ by MV status. We also found that pretransplant MV was not associated with decreased survival in noncystic fibrosis obstructive lung diseases. These results suggest that under the LAS, pretransplant MV is associated with poorer short-term survival posttransplant. Notably, the increased risk of death appears to be strongest the early posttransplant period and limited to certain pretransplant diagnoses.
    American Journal of Transplantation 08/2011; 11(10):2197-204. · 6.19 Impact Factor
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    ABSTRACT: Prior work has shown that transforming growth factor-β (TGF-β) can mediate transition of alveolar type II cells into mesenchymal cells in mice. Evidence this occurs in humans is limited to immunohistochemical studies colocalizing epithelial and mesenchymal proteins in sections of fibrotic lungs. To acquire further evidence that epithelial-to-mesenchymal transition occurs in the lungs of patients with idiopathic pulmonary fibrosis (IPF), we studied alveolar type II cells isolated from fibrotic and normal human lung. Unlike normal type II cells, type II cells isolated from the lungs of patients with IPF express higher levels of mRNA for the mesenchymal proteins type I collagen, α-smooth muscle actin (α-SMA), and calponin. When cultured on Matrigel/collagen, human alveolar type II cells maintain a cellular morphology consistent with epithelial cells and expression of surfactant protein C (SPC) and E-cadherin. In contrast, when cultured on fibronectin, the human type II cells flatten, spread, lose expression of pro- SPC, and increase expression of vimentin, N-cadherin, and α-SMA; markers of mesenchymal cells. Addition of a TGF-β receptor kinase inhibitor (SB431542) to cells cultured on fibronectin inhibited vimentin expression and maintained pro-SPC expression, indicating persistence of an epithelial phenotype. These data suggest that alveolar type II cells can acquire features of mesenchymal cells in IPF lungs and that TGF-β can mediate this process.
    AJP Lung Cellular and Molecular Physiology 04/2011; 301(1):L71-8. · 3.52 Impact Factor
  • Journal of Heart and Lung Transplantation - J HEART LUNG TRANSPLANT. 01/2011; 30(4).
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    ABSTRACT: Venous thromboembolism (VTE) is common after lung transplantation. Enoxaparin is an approved therapy for VTE and anti-factor Xa level can be used to monitor enoxaparin activity. Some studies have demonstrated elevated anti-factor Xa levels are associated with an increased risk of hemorrhage. Having identified a high incidence of supratherapeutic anti-factor Xa levels in lung transplant recipients, we aimed to elucidate the relationship between enoxaparin dose and anti-factor Xa level in this patient population. We identified post-lung transplantation patients with VTE receiving therapeutic enoxaparin who had anti-factor Xa level measured. Standard enoxaparin dosing was defined as 0.9 to 1.1 mg/kg. After identifying a high incidence of supratherapeutic anti-factor Xa levels, we implemented "non-standard" dosing of 0.8 mg/kg. Multivariate linear regression analysis was used to examine the association between enoxaparin dose and anti-factor Xa level; age, body mass index (BMI) and creatinine clearance were included as covariates. In the cohort, 18 patients received standard and 8 patients received non-standard enoxaparin dosing. Twelve of 18 patients (67%; 95% confidence interval [CI]: 43% to 91%) receiving standard dosing had supratherapeutic anti-factor Xa levels vs 0 of 8 patients (0%; 95% CI: 0% to 37%) receiving lower non-standard dosing (p = 0.002). Anti-factor Xa levels were significantly different between the two groups; the mean anti-factor Xa level was 1.3 IU/ml (95% CI: 1.06 to 1.53) in the standard group vs 0.79 IU/ml (95% CI: 0.67 to 0.91) in the non-standard group (p = 0.008). After controlling for covariates, for each 0.1-mg/kg increase in enoxaparin, the mean anti-factor Xa level increased by 0.18 IU/ml (95% CI: 0.05 to 0.31; p = 0.011; model r(2) = 0.53). Standard dosing of enoxaparin in lung transplant recipients is associated with a high incidence of supratherapeutic anti-Xa levels. Further study will be required to correlate this finding with risk of hemorrhage.
    The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 09/2010; 29(9):1009-13. · 3.54 Impact Factor
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    ABSTRACT: Numerous small observational studies have shown that gastro-oesophageal reflux is prevalent among patients with advanced lung disease. The fundamental concern is that reflux is a risk factor for recurrent microaspiration, which may cause lung injury. For example, in lung transplant patients, a molecular marker of aspiration was a risk factor for the bronchiolitis obliterans syndrome in one study. To date, however, there are no large prospective studies measuring the impact of aspiration on clinical outcomes. The major obstacle limiting the study of reflux and aspiration in patients with advanced lung disease is the absence of a reliable diagnostic tool. Proximal oesophageal acid detection by pH monitoring is the only widely available measure of aspiration risk. Impedance monitoring may be a superior measure of aspiration risk as it measures both acid and non-acid reflux episodes. Molecular markers of aspiration, such as pepsin or bile salts in the bronchoalveolar lavage or exhaled breath condensate, may be the optimal diagnostic tests, but they are not currently available outside the research setting. Larger observational studies are needed to determine the following: (1) the clinical significance of aspiration in patients with advanced lung disease and in patients who have had lung transplantation and (2) the diagnostic test that best predicts adverse outcomes.
    Thorax 03/2009; 64(2):167-73. · 8.38 Impact Factor
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    ABSTRACT: Gastroesophageal reflux disease (GERD) is prevalent among patients with end-stage lung disease (ESLD). This disease can lead to microaspiration and may be a risk factor for lung damage before and after transplantation. A fundoplication is the best way to stop reflux, but little is known about the safety of elective antireflux surgery for patients with ESLD. This study aimed to report the safety of laparoscopic fundoplication for patients with ESLD and GERD before or after lung transplantation. Between January 1997 and January 2007, 305 patients were listed for lung transplantation, and 189 patients underwent the procedure. In 2003, routine esophageal studies were added to the pretransplantation evaluation. After the authors' initial experience, gastric emptying studies were added as well. A total of 35 patients with GERD or delayed gastric emptying were referred for surgical intervention. A laparoscopic fundoplication was performed for 32 patients (27 total and 5 partial). For three patients, a pyloroplasty also was performed. Two patients had a pyloroplasty without fundoplication. Of the 35 operations, 15 were performed before and 20 after transplantation. Gastric emptying of solids or liquids was delayed in 12 (92%) of 13 posttransplantation studies and 3 (60%) of 5 pretransplantation studies. All operations were completed laparoscopically, and 33 patients recovered uneventfully (94%). The median hospital length of stay was 2 days (range, 1-34 days) for the patients admitted to undergo elective operations. Hospitalization was not prolonged for the three patients who had fundoplications immediately after transplantation. The results of this study show that laparoscopic antireflux surgery can be performed safely by an experienced multidisciplinary team for selected patients with ESLD before or after lung transplantation, and that gastric emptying is frequently abnormal and should be objectively measured in ESLD patients.
    Surgical Endoscopy 03/2008; 22(2):495-500. · 3.43 Impact Factor
  • Journal of Vascular and Interventional Radiology - J VASC INTERVEN RADIOL. 01/2008; 19(2).
  • Journal of Heart and Lung Transplantation - J HEART LUNG TRANSPLANT. 01/2007; 26(2).
  • Journal of Heart and Lung Transplantation - J HEART LUNG TRANSPLANT. 01/2007; 26(2).
  • Journal of Heart and Lung Transplantation - J HEART LUNG TRANSPLANT. 01/2007; 26(2).
  • Journal of Heart and Lung Transplantation - J HEART LUNG TRANSPLANT. 01/2007; 26(2).
  • Journal of Heart and Lung Transplantation - J HEART LUNG TRANSPLANT. 01/2007; 26(2).
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    ABSTRACT: To evaluate the sensitivity, specificity, predictive values, and accuracy of thin-section computed tomography (CT) for the diagnosis of acute rejection following lung transplantation and to determine whether any individual CT abnormalities are associated with histopathologically proved acute rejection. Thin-section CT studies from 64 lung transplant recipients were retrospectively reviewed. CT studies were temporally correlated with various grades of biopsy-proved acute rejection (n = 34); 30 other CT studies were from a control group with no histopathologic evidence of acute rejection. Acute rejection was diagnosed as present or absent, and the diagnostic was calculated. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of CT for the diagnosis of acute rejection were as follows: 35%, 73%, 60%, 50%, 53%, respectively. No individual CT finding was significantly associated with acute rejection. The sensitivity of CT for the detection of various grades of acute rejection was 17% for grade A1, 50% for grade A2, and 20% for grade A3. The combination of volume loss and septal thickening, with or without pleural effusion, was never seen in the absence of acute rejection. Thin-section CT has limited accuracy for the diagnosis of acute rejection following lung transplantation, and no individual CT finding is significantly associated with this diagnosis.
    Radiology 11/2001; 221(1):207-12. · 6.34 Impact Factor
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    ABSTRACT: Our objective was to study the steady-state plasma and intrapulmonary orally administered ethambutol concentrations in healthy volunteers and subjects with AIDS. Ethambutol (15 mg/kg of body weight) was administered orally once daily to 10 men with AIDS, 10 healthy men, 10 women with AIDS, and 10 healthy women. The mean (+/-standard deviation [SD]) CD4 cell count for the 20 subjects with AIDS was (350 +/- 169) x 10(6) cells per liter. Blood was obtained for drug assay 2 h after the last dose and at the completion of bronchoalveolar lavage, performed 4 h after the last dose. Standardized bronchoscopy was performed without systemic sedation. The volume of epithelial lining fluid (ELF) was calculated by the urea dilution method. The total number of alveolar cells (AC) was counted in a hemocytometer, and differential cell counting was performed after cytocentrifugation. Ethambutol was measured by a new, sensitive and specific liquid chromotography-mass spectrometry method. The presence of AIDS, as defined in this study, or gender was without significant effect on the concentrations of ethambutol in plasma at 2 or 4 h or in ELF at 4 h following the last dose. Plasma drug concentrations (mean +/- SD) at 2 and 4 h were 2.1 +/- 1.2 and 2.1 +/- 0.8 microg/ml, respectively, and both values were not significantly different from the concentration of ethambutol in ELF at 4 h (2.2 +/- 1.1 microg/ml). The concentration of ethambutol was significantly greater in AC in all four groups (range, 44.5 +/- 15.6 to 82.0 +/- 39.4 microg/ml) than in ELF or plasma and was approximately 30 to 240 times the reported MIC for ethambutol-susceptible strains of Mycobacterium tuberculosis. The AC ethambutol concentration (mean +/- SD) in the smoking women (97.2 +/- 32.1 microg/ml) was more than twice the concentration in all other nonsmoking subjects (45.2 +/- 16.8 microg/ml) combined (P < 0.05). Two- and 4-h concentrations of ethambutol in plasma were not affected by AIDS status or gender. The high AC/plasma and AC/ELF concentration ratios suggest that substantial antimycobacterial activity resides in these cells. The data confirm earlier observations of active transport ex vivo of ethambutol into pulmonary macrophages.
    Antimicrobial Agents and Chemotherapy 10/2001; 45(10):2891-6. · 4.57 Impact Factor
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    ABSTRACT: To evaluate the accuracy of thin-section computed tomography (CT) with expiratory scans in diagnosing early bronchiolitis obliterans after lung transplantation. Thin-section CT scans were reviewed by two observers blinded to the diagnoses in seven consecutive lung transplant recipients with histopathologically proved bronchiolitis obliterans (group A) and 21 with normal biopsy findings (group B). All patients had normal biopsy and stable pulmonary function test (PFT) results 2-36 weeks prior to CT. Patients with normal biopsy results were placed into subgroups based on abnormal (group B1) or stable (group B2) PFT results. Air-trapping extent on expiratory scans was scored on a 24-point scale. The mean air-trapping score in group A (6.6) was not significantly different from that in group B (4.5, P =. 17). The air-trapping score was significantly higher in groups A and B1 than in group B2 (6.2 and 2.6, respectively; P =.03). The frequency of an air-trapping score of 3 or more in groups A and B1 was significantly higher than that in group B2 (P =.03). By using a score of 3 or more to indicate air trapping, the sensitivity of expiratory CT was 74%, specificity was 67%, and accuracy was 71%. Thin-section CT, including expiratory scans, is of limited accuracy in diagnosing early bronchiolitis obliterans after lung transplantation.
    Radiology 09/2000; 216(2):472-7. · 6.34 Impact Factor

Publication Stats

2k Citations
639.26 Total Impact Points

Institutions

  • 1983–2014
    • University of California, San Francisco
      • • Division of Hospital Medicine
      • • Department of Surgery
      • • Cardiovascular Research Institute
      • • Department of Epidemiology and Biostatistics
      San Francisco, California, United States
  • 1991
    • Howard Hughes Medical Institute
      Maryland, United States