Lorriana Leard

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

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Publications (31)136.91 Total impact

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    ABSTRACT: Background:Hypersensitivity pneumonitis (HP) is an inhaled antigen-mediated interstitial lung disease (ILD). Advanced disease may lead to lung transplantation. There are no published studies addressing lung transplant outcomes in HP. We characterized HP outcomes compared to 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 2000-2013. We compared clinical characteristics, survival, and acute and chronic rejection for lung transplant recipients with HP to IPF referents. 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 to IPF was 96%, 89% and 89% vs. 86%, 67%, and 49%, respectively. HP subjects manifested a reduced adjusted risk of death compared to IPF subjects (HR 0.25, 95% CI 0.08-0.74; p=0.013). Of the 31 cases, the diagnosis of HP was unexpectedly made at explant in 5 (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 of death. HP may be initially discovered only by review of the explant pathology. Notably, HP may recur in the allograft. Hypersensitivity pneumonitis (HP) is an inhaled antigen-mediated interstitial lung disease (ILD). Advanced disease may lead to lung transplantation. There are no published studies addressing lung transplant outcomes in HP. We characterized HP outcomes compared to referents undergoing lung transplantation for idiopathic pulmonary fibrosis (IPF). To identify HP cases, we reviewed records for all ILD lung transplantation cases at our institution from 2000-2013. We compared clinical characteristics, survival, and acute and chronic rejection for lung transplant recipients with HP to IPF referents. 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. 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 to IPF was 96%, 89% and 89% vs. 86%, 67%, and 49%, respectively. HP subjects manifested a reduced adjusted risk of death compared to IPF subjects (HR 0.25, 95% CI 0.08-0.74; p=0.013). Of the 31 cases, the diagnosis of HP was unexpectedly made at explant in 5 (16%). Two subjects developed recurrent HP in their allografts. Overall, subjects with HP have excellent medium-term survival after lung transplantation and, relative to IPF, a reduced risk of death. HP may be initially discovered only by review of the explant pathology. Notably, HP may recur in the allograft.
    Chest 11/2014; · 7.13 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; · 8.56 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. · 5.61 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. · 5.61 Impact Factor
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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; · 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: 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; · 1.49 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. · 5.61 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. · 5.61 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
  • Chest 10/2011; 140(4 Meeting Abstracts):1023A-1023A. · 7.13 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
  • The Journal of Heart and Lung Transplantation 04/2011; 30(4). · 5.61 Impact Factor
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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. · 5.61 Impact Factor
  • Leah Smith, Maggie Hayes, Lorriana Leard
    American Thoracic Society 2010 International Conference, May 14-19, 2010 • New Orleans; 05/2010
  • American Thoracic Society 2010 International Conference, May 14-19, 2010 • New Orleans; 05/2010
  • Michael J. LaFemina, Lorriana Leard
    American Thoracic Society 2010 International Conference, May 14-19, 2010 • New Orleans; 05/2010
  • The Journal of Heart and Lung Transplantation 02/2010; 29(2). · 5.61 Impact Factor
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    ABSTRACT: Single lung transplant recipients with idiopathic pulmonary fibrosis provide an opportunity to study fibrosis in the native lung over time in the setting of pronounced immunosuppression. Lung transplant patients are treated with a regimen of steroids, an antiproliferative agent and a calcineurin inhibitor. This represents a much greater immunosuppression regime than the typical treatment for IPF. To determine whether this regimen of high dose immunosuppression would arrest the progression of fibrosis, the high-resolution chest CT scans (HRCTs) of these patients were reviewed. HRCTs of 21 patients who underwent single lung transplant for IPF between 1/96 and 1/06 were reviewed. Scans were evaluated by two readers at 6 months intervals, beginning within 1-2 months after transplant. Two calculations were made on the native lung: total volume and percentage of lung affected by fibrosis. Baseline pulmonary function test data was correlated with the immediate post-transplant CT. Patients were followed for an average of 35 months after transplant. The mean total volume of the native lung just after transplant was 1120cc. This decreased to 875cc by 2 years and 691cc by 4 years after transplant, representing an average decline of 10.8%/year. Initially, 52% of the native lung was affected by fibrosis compared to 92% at 4 years. Excluding scans with 100% of the lung affected by fibrosis, percentage fibrosis increased 11% per year. Fibrotic disease within the native lung progresses rapidly in single lung transplant recipients with IPF despite prolonged high dose immunosuppression.
    Respiratory medicine 11/2009; 104(3):426-33. · 2.33 Impact Factor
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    ABSTRACT: Lung and esophageal dysfunction are common in patients with connective tissue disease (CTD). Recent reports have suggested a link between pathologic gastroesophageal reflux and bronchiolitis obliterans syndrome (BOS) after lung transplant. Because patients with CTD have a high incidence of esophageal dysmotility and reflux, this group may be at increased risk of allograft dysfunction after lung transplantation. Little is known about antireflux surgery in these patients. Our aims were to describe: (i) the esophageal motility and reflux profile of patients with CTD referred for lung transplantation; and (ii) the safety and outcomes of laparoscopic fundoplication in this group. A retrospective review of 26 patients with CTD referred for lung transplantation between July 2003 and June 2007 at a single center. Esophageal studies included manometry and ambulatory 24-h pH monitoring. Twenty-three patients had esophageal manometry and ambulatory 24-h pH monitoring. Nineteen patients (83%) had pathologic distal reflux and 7 (30%) also had pathologic proximal reflux. Eighteen patients (78%) had impaired or absent peristalsis. Eleven of 26 patients underwent lung transplantation. Ten patients are alive at a median follow-up of 26 months (range 3-45) and one has bronchiolitis obliterans syndrome-1. Six patients had a laparoscopic fundoplication, 1 before transplantation and 5 after. All fundoplication patients are alive at median follow-up of 25 months (range 19-45). In conclusion, esophageal dysmotility and reflux are common in CTD patients referred for lung transplant. For this group, laparoscopic fundoplication is safe in experienced hands.
    Diseases of the Esophagus 06/2008; 21(7):650-5. · 2.06 Impact Factor