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ABSTRACT: BACKGROUND: The timing of disease onset may affect the prognosis in chronic lung allograft dysfunction (CLAD). The relationship between the timing of disease onset and the prognosis of CLAD and its sub-types, bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS), was examined. METHODS: Clinical records and pulmonary function data of 597 patients who underwent bilateral lung transplantation from 1996 to 2010 and survived for >3 months were examined. RESULTS: Among 155 patients with a final diagnosis of BOS, patient survival after disease onset was significantly different according to disease-onset timing (BOS onset/post-BOS median survival: overall/1,438 days; <1 year/511 days; 1-2 years/1,199 days; 2-3 years/1,403 days; >3 years/did not reach median survival; p < 0.0001). The prognosis of RAS was generally poorer than that of BOS (overall post-RAS median survival, 377 days). Treating non-CLAD, CLAD, BOS, and RAS as time-dependent covariates, recipient sex-adjusted and age-adjusted Cox regression analysis demonstrated an overall mortality risk of BOS (reference: no CLAD) of 6.7 (95% confidence interval, 4.6-9.9). However, when patients survived 3 years without CLAD, the mortality risk of subsequent BOS was only 1.9 (95% confidence interval, 0.8-4.4) compared with no CLAD. The number of RAS patients was too small to obtain sufficient power to estimate time-dependent mortality risk. CONCLUSION: Late-onset BOS showed a better prognosis than early-onset BOS. Studies that do not distinguish BOS from RAS may overestimate the mortality risk of BOS. Multicenter studies will be required to further elucidate risk factors toward the development of better management strategies for CLAD.
The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 02/2013; · 3.54 Impact Factor
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ABSTRACT: Restrictive allograft syndrome (RAS) is a novel form of chronic lung allograft dysfunction after lung transplantation. RAS is characterized by restrictive physiology and peripheral lung fibrosis. The purpose of the study is to analyze progression patterns of RAS.
Clinical information, pulmonary function test results and radiographic findings were reviewed for 25 RAS patients who received bilateral lung or heart-lung transplantation between January 2004 and December 2009.
Average time from transplantation to RAS onset was 647±544 (mean±SD) days; RAS onset to end of observation (death or re-transplantation) was 490±417 days. RAS patients had 1 to 4 episodes of acute exacerbation (2.48±0.82 episodes/patient) that accompanied acute respiratory deterioration or distress, a sudden drop in pulmonary function, evidence of diffuse alveolar damage (DAD) on biopsies, and patchy or diffuse ground-glass opacities (GGO) with occasional consolidation on computed tomography scan. Patients were most frequently managed by high-dose steroid in combination with empirical antibiotics, with uncertain efficacy. Acute exacerbation was followed by an interval during which resolution of GGO and progression of consolidation, interstitial reticular shadows and traction bronchiectasis were frequently observed. The interval between episodes of acute exacerbation was 238±165 days. In 21 patients, the last episode of acute exacerbation led to death or urgent retransplantation.
RAS shows a "stair-step" pattern of progression. Acute lung injury represented by DAD and GGO is followed by an interval period during which graft fibrosis often progresses.
The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 01/2013; 32(1):23-30. · 3.54 Impact Factor
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Efrat Ofek,
Masaaki Sato,
Tomohito Saito,
Ute Wagnetz,
Heidi C Roberts,
Cecilia Chaparro,
Thomas K Waddell, Lianne G Singer,
Michael A Hutcheon,
Shaf Keshavjee,
David M Hwang
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ABSTRACT: We previously described restrictive allograft syndrome as a form of chronic lung allograft dysfunction, demonstrating restrictive pulmonary function decline. However, the histopathological correlates of restrictive allograft syndrome have yet to be satisfactorily described. We hypothesized that pulmonary pleuroparenchymal fibroelastosis, as has recently been described in bone marrow transplant recipients, may also be present in the lungs of patients with restrictive allograft syndrome. Retrospective review of 493 patients who underwent lung transplantation between 1 January 1996 and 30 June 2009, was conducted. Out of 47 patients with clinical features of restrictive allograft syndrome, 16 had wedge biopsy, re-transplant lung explant, or autopsy lung specimens available for review. All lungs showed varying degrees of pleural fibrosis. Fifteen of 16 showed parenchymal fibroelastosis, characterized by hypocellular collagen deposition with preservation and thickening of the underlying alveolar septal elastic network. The fibroelastosis was predominantly subpleural in distribution, with some cases also showing centrilobular and paraseptal distribution. A sharp demarcation was often seen between areas of fibroelastosis and unaffected lung parenchyma, with fibroblastic foci often present at this interface. Concurrent features of obliterative bronchiolitis were present in 14 cases. Another common finding was the presence of diffuse alveolar damage (13 cases), usually in specimens obtained <1 year after clinical onset of restrictive allograft syndrome. The single specimen in which fibroelastosis was not identified was obtained before the clinical onset of chronic lung allograft dysfunction, and showed features of diffuse alveolar damage. In conclusion, pleuroparenchymal fibroelastosis is a major histopathologic correlate of restrictive allograft syndrome, and was often found concurrently with diffuse alveolar damage. Our findings support a temporal sequence of diffuse alveolar damage followed by the development of pleuroparenchymal fibroelastosis in the histopathologic evolution of restrictive allograft syndrome.Modern Pathology advance online publication, 28 September 2012; doi:10.1038/modpathol.2012.171.
Modern Pathology 09/2012; · 4.79 Impact Factor
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ABSTRACT: Normothermic ex vivo lung perfusion is a novel method to evaluate and improve the function of injured donor lungs. We reviewed our experience with 50 consecutive transplants after ex vivo lung perfusion.
A retrospective study using prospectively collected data was performed. High-risk brain death donor lungs (defined as Pao(2)/Fio(2) <300 mm Hg or lungs with radiographic or clinical findings of pulmonary edema) and lungs from cardiac death donors were subjected to 4 to 6 hours of ex vivo lung perfusion. Lungs that achieved stable airway and vascular pressures and Pao(2)/Fio(2) greater than 400 mm Hg during ex vivo lung perfusion were transplanted. The primary end point was the incidence of primary graft dysfunction grade 3 at 72 hours after transplantation. End points were compared with lung transplants not treated with ex vivo lung perfusion (controls).
A total of 317 lung transplants were performed during the study period (39 months). Fifty-eight ex vivo lung perfusion procedures were performed, resulting in 50 transplants (86% use). Of these, 22 were from cardiac death donors and 28 were from brain death donors. The mean donor Pao(2)/Fio(2) was 334 mm Hg in the ex vivo lung perfusion group and 452 mm Hg in the control group (P = .0001). The incidence of primary graft dysfunction grade 3 at 72 hours was 2% in the ex vivo lung perfusion group and 8.5% in the control group (P = .14). One patient (2%) in the ex vivo lung perfusion group and 7 patients (2.7%) in the control group required extracorporeal lung support for primary graft dysfunction (P = 1.00). The median time to extubation, intensive care unit stay, and hospital length of stay were 2, 4, and 20 days, respectively, in the ex vivo lung perfusion group and 2, 4, and 23 days, respectively, in the control group (P > .05). Thirty-day mortality (4% in the ex vivo lung perfusion group and 3.5% in the control group, P = 1.00) and 1-year survival (87% in the ex vivo lung perfusion group and 86% in the control group, P = 1.00) were similar in both groups.
Transplantation of high-risk donor lungs after 4 to 6 hours of ex vivo lung perfusion is safe, and outcomes are similar to those of conventional transplants. Ex vivo lung perfusion improved our center use of donor lungs, accounting for 20% of our current lung transplant activity.
The Journal of thoracic and cardiovascular surgery 08/2012; 144(5):1200-7. · 3.41 Impact Factor
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ABSTRACT: Diffuse alveolar damage (DAD) is a non-specific pathologic diagnosis frequently encountered after lung transplantation. We examined the relationship between DAD and different forms of chronic lung allograft dysfunction (CLAD).
We reviewed the results of 4,085 transbronchial biopsies obtained from 720 lung transplant recipients. DAD detected in biopsies within 3 months and newly detected DAD after 3 months were defined as early DAD and late new-onset DAD, respectively. Among patients with CLAD (FEV(1) <80% baseline), restrictive allograft syndrome (RAS) was defined by a decline in total lung capacity to <90% baseline and bronchiolitis obliterans syndrome (BOS) as CLAD without restrictive allograft syndrome (RAS). Kaplan-Meier analyses and multivariate proportional hazard models were used.
DAD was observed in 320 of 720 (44.4%) patients at least once; early and late new-onset DAD were observed in 264 of 707 (37.3%) and 87 of 655 (13.3%) patients, respectively. Early DAD was associated with significantly higher 90-day mortality (20 of 264 [7.6%] vs 11 of 443 [2.5%]; p = 0.001). Moreover, among 502 bilateral lung transplant recipients who had sufficient pulmonary function tests to distinguish BOS and RAS, early DAD was associated with earlier BOS onset (hazard ratio [HR] 1.24; confidence interval [CI] 1.04 to 1.47; p = 0.017; median time of BOS onset: 2,902 vs 4,005 days). Conversely, treated as a time-varying covariate, late new-onset DAD was a significant risk factor for RAS in a Cox model (HR 36.8; CI 18.3 to 74.1; p < 0.0001).
Early DAD is associated with early mortality and BOS, and late new-onset DAD increases the risk of RAS.
The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 02/2012; 31(4):354-63. · 3.54 Impact Factor
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ABSTRACT: To analyze the outcomes of patients with pulmonary arterial hypertension referred for lung transplantation and determine the changes over time.
All patients with pulmonary arterial hypertension referred for lung transplantation in our program from January 1997 to September 2010 were reviewed. Pulmonary arterial hypertension was classified as idiopathic (n = 123) or associated with congenital heart disease (n = 77), connective tissue disease (n = 102), or chronic thromboembolic disease (n = 14).
After completing their assessment, 61 patients (19%) were found to be unsuitable for lung transplantation, 38 (12%) refused lung transplantation, 65 (21%) were too early to be listed, and 48 (15%) died before their assessment (n = 34) or being listed (n = 14). Of the 100 patients listed for lung transplantation, 57 underwent bilateral lung transplantation, 22 underwent heart-lung transplantation, 18 died while waiting, and 3 were still waiting. The waiting list mortality was the greatest for patients with connective tissue disease-pulmonary arterial hypertension (34% vs 11% in the remaining patients, P = .005). The number of patients admitted to the hospital to be bridged to lung transplantation increased from 7% in the 1997-2004 cohort to 25% in the 2005-2010 cohort (P = .02). After lung transplantation, the 30-day mortality decreased from 24% in the 1997-2004 group to 6% in the 2005-2010 group (P = .007). The 10-year survival was worse for those with idiopathic pulmonary arterial hypertension (42% vs 70% for the remaining patients, P = .01). The long-term survival reached 69% at 10 years in the patients with connective tissue disease pulmonary arterial hypertension.
Lung transplantation is an option for about one third of the patients with pulmonary arterial hypertension referred for lung transplantation. The 30-day mortality after lung transplantation improved significantly over time, but the long-term survival remained similar between the two cohorts. Patients with connective tissue disease-pulmonary arterial hypertension have a high mortality on the waiting list but excellent long-term survival.
The Journal of thoracic and cardiovascular surgery 02/2012; 143(4):910-8. · 3.41 Impact Factor
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ABSTRACT: Bone marrow-derived progenitor cells may play a key role in both lung repair and in fibrogenesis. The contribution of CD45(+)collagen-1(+) fibrocytes to fibrosis has been documented elsewhere and recently identified epithelial-like progenitor cells marked by Clara cell secretory protein (CCSP(+)) may be protective after lung injury. Interplay between these populations has not yet been studied in bronchiolitis obliterans syndrome (BOS) post-lung transplant.
In a cross-sectional design, blood samples were analyzed for CCSP(+) cells and CD45(+)collagen-1(+) fibrocytes by flow cytometry. Plasma cytokines were analyzed by multiplex array.
A higher proportion of circulating fibrocytes was measured in patients with BOS Grade ≥1 than in those with BOS Grade 0(p). In parallel, a lower proportion of CCSP(+) cells was found in BOS ≥1 patients compared with BOS 0(p) and non-transplant controls, resulting in an altered cell ratio between the groups. A higher ratio of CD45(+)collagen-1(+) to CCSP(+) cells was associated with greater airflow limitation based on FEV(1) and FEV(1)/FVC ratio. No relationship between cell profiles and time post-transplant was found. Plasma analysis showed an increase in key stem cell and inflammatory cytokines in both groups post-transplant, whereas stromal-derived factor-1 and vascular endothelial growth factor were increased in cases of BOS ≥1 specifically. Plasma stromal-derived factor-1 levels also correlated with fibrocytes post-transplant.
Overall, altered progenitor cell profiles were found in patients who developed advanced BOS, which may be mediated by alterations in circulating cytokines. Ultimately, measurement of progenitor cell profiles may lead to further insight into the pathogenesis of airflow obstruction after lung transplantation.
The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 02/2012; 31(2):222-8. · 3.54 Impact Factor
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ABSTRACT: The main cause of late morbidity and mortality after lung transplantation is bronchiolitis obliterans syndrome (BOS). This study assesses the prevalence of gastroparesis among lung-transplant recipients and its association with BOS. The files of 139 patients who underwent nuclear gastric emptying studies before and/or three and 12 months after lung transplantation were reviewed, and the correlation of gastric emptying time (GET) at each time point with the occurrence of acute rejection or BOS (stage 0p or higher) was evaluated. Delayed gastric emptying (DGE; t(1/2) > 90 min) was documented in 50% of patients before transplantation - 74% at three months and 63% at 12 months. Median pre-transplant t(1/2) was 108 min in patients who acquired BOS and 77 min in BOS-free patients (p = 0.022). Among patients with pre-transplant DGE, 58% were BOS-free at 24 months post-operatively and 37% at 36 months; corresponding rates in patients with normal motility were 78% and 63% (p = 0.084). On multiple regression analysis adjusting for other measures of upper gastrointestinal dysfunction, GET before or three months after transplantation was significantly associated with BOS (OR 1.05 [95% CI 1.01-1.09] and OR 1.001 [1.001-1.005] per minute t(1/2)). Gastroparesis is common in lung-transplant recipients and associated with the development of BOS.
Clinical Transplantation 01/2012; 26(1):133-42. · 1.67 Impact Factor
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ABSTRACT: Pulmonary hypertension (PH) associated with pulmonary fibrosis (PF) is a severe condition with poor outcome. It is unknown whether patients with PF with associated PH (APH) represent a distinct phenotype of the disease. We hypothesized that the lung tissue gene expression pattern of patients with APH has a characteristic profile when compared with patients with PF without APH. We sought to determine if different gene expression signatures in PF could be determined based on pulmonary arterial pressures (PAPs) and to provide new insights into the pathobiology of APH.
Microarray analysis (Affymetrix) was performed after RNA was extracted from explanted lungs in 116 consecutive patients with PF (development set, n = 84; validation set, n = 32) and seven subjects with idiopathic pulmonary arterial hypertension undergoing lung transplant (LTx). PAP were recorded intraoperatively immediately before starting LTx. The development set was divided into three groups according to mean PAP (mPAP): severe PH group (mPAP ≥ 40 mm Hg, n = 17); intermediate PH group (mPAP 21-39 mm Hg, n = 45); NoPH group (mPAP ≤ 20 mm Hg, n = 22).
Distinct gene signatures were observed. Patients in the severe PH group showed increased expression of genes, gene sets, and networks related to myofibroblast proliferation and vascular remodeling, whereas patients in the NoPH group strongly expressed proinflammatory genes. Two-dimensional hierarchic clustering based on 222 differentially expressed genes (severe PH vs no PH) dichotomized subjects into two phenotypes in the intermediate PH group and in the validation set. Real-time polymerase chain reaction confirmed the differential expression of selected genes.
Gene expression profiles distinguish PF phenotypes with and without APH. This observation can have important implications for future trials.
Chest 08/2011; 141(3):661-73. · 5.25 Impact Factor
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ABSTRACT: The BODE index (Body mass index, Obstruction, Dyspnea, Exercise), predicts the risk of death in patients with chronic obstructive pulmonary disease (COPD), and is used to identify candidates for lung transplantation. We hypothesized that a higher BODE index would be associated with worse health-related quality of life (HRQL) in advanced COPD, and with larger improvements in HRQL after transplantation.
In this cohort study (n = 112), we administered the St. George's Respiratory Questionnaire (SGRQ), 36-Item Short Form (SF-36), Visual Analog Scale, Standard Gamble and EuroQol Group 5-Dimension (EQ-5D) index to otherwise healthy COPD patients with a FEV(1) <50% predicted. We compared mean HRQL values across BODE score groups, and tested for linear trends. In patients who received lung transplants during the study period, we compared SGRQ scores before and early (mean 4 months) after transplantation.
BODE was directly associated with SGRQ and inversely related to all other HRQL measures (p < 0.05). Early post-transplant improvements in HRQL were also seen across the spectrum of BODE scores from 5 to 10.
The BODE score is a significant predictor of HRQL in patients with severe COPD. We noted dramatic improvements in HRQL after transplantation, which appeared similar in magnitude for patients with pre-transplant BODE scores of 5 or 6 and 7 to 10, despite the difference in expected survival between these two groups. The association of the BODE score with HRQL further supports its use in identifying potential candidates for lung transplantation.
The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 07/2011; 30(12):1334-41. · 3.54 Impact Factor
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ABSTRACT: Pandemic H1N1 influenza has been associated with a worldwide outbreak of febrile respiratory illness. Although impaired cell mediated immunity, such as that caused by transplant immunosuppression, has been identified as a risk factor for severe infection with this virus, the course of this infection has not been adequately characterized in solid organ transplant (SOT) recipients in comparison with nontransplanted controls. We report our experience with severe pH1N1 infection in transplant recipients and compare this group with nonimmunosuppressed patients.
Data were retrospectively collected on all patients admitted to our institution with proven pH1N1 infection. Clinical characteristics, treatments, and outcomes were compared between SOT recipients and nonimmunocompromised controls.
Seventeen SOT recipients and 49 controls were identified. The control group had higher baseline rates of asthma (P = 0.02) and smoking (P = 0.05) at baseline. No difference in clinical features of H1N1 infection was detected except for a greater prevalence of wheeze in the non-SOT group (P = 0.02). No statistical differences in outcomes could be detected between the groups. Several markers of severity, including use of high frequency oscillatory ventilation, extracorporeal membrane oxygenation, and death were slightly more frequent in the control group.
SOT recipients admitted to hospital with pH1N1 infection did not have significantly more severe outcomes of their infection compared with their nonimmunocompromised counterparts, despite their immune suppressed status.
Transplantation 05/2011; 92(2):230-4. · 4.00 Impact Factor
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Marcelo Cypel,
Jonathan C Yeung,
Mingyao Liu,
Masaki Anraku,
Fengshi Chen,
Wojtek Karolak,
Masaaki Sato,
Jane Laratta,
Sassan Azad,
Mindy Madonik,
Chung-Wai Chow,
Cecilia Chaparro,
Michael Hutcheon, Lianne G Singer,
Arthur S Slutsky,
Kazuhiro Yasufuku,
Marc de Perrot,
Andrew F Pierre,
Thomas K Waddell,
Shaf Keshavjee
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ABSTRACT: More than 80% of donor lungs are potentially injured and therefore not considered suitable for transplantation. With the use of normothermic ex vivo lung perfusion (EVLP), the retrieved donor lung can be perfused in an ex vivo circuit, providing an opportunity to reassess its function before transplantation. In this study, we examined the feasibility of transplanting high-risk donor lungs that have undergone EVLP.
In this prospective, nonrandomized clinical trial, we subjected lungs considered to be high risk for transplantation to 4 hours of EVLP. High-risk donor lungs were defined by specific criteria, including pulmonary edema and a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (PO(2):FIO(2)) less than 300 mm Hg. Lungs with acceptable function were subsequently transplanted. Lungs that were transplanted without EVLP during the same period were used as controls. The primary end point was primary graft dysfunction 72 hours after transplantation. Secondary end points were 30-day mortality, bronchial complications, duration of mechanical ventilation, and length of stay in the intensive care unit and hospital.
During the study period, 136 lungs were transplanted. Lungs from 23 donors met the inclusion criteria for EVLP; in 20 of these lungs, physiological function remained stable during EVLP and the median PO(2):FIO(2) ratio increased from 335 mm Hg in the donor lung to 414 and 443 mm Hg at 1 hour and 4 hours of perfusion, respectively (P<0.001). These 20 lungs were transplanted; the other 116 lungs constituted the control group. The incidence of primary graft dysfunction 72 hours after transplantation was 15% in the EVLP group and 30% in the control group (P=0.11). No significant differences were observed for any secondary end points, and no severe adverse events were directly attributable to EVLP.
Transplantation of high-risk donor lungs that were physiologically stable during 4 hours of ex vivo perfusion led to results similar to those obtained with conventionally selected lungs. (Funded by Vitrolife; ClinicalTrials.gov number, NCT01190059.).
New England Journal of Medicine 04/2011; 364(15):1431-40. · 53.30 Impact Factor
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Shahid Husain,
Martha L Mooney,
Lara Danziger-Isakov,
Frauke Mattner,
Nina Singh,
Robin Avery,
Michael Ison,
Atul Humar,
Robert F Padera,
Leo P Lawler,
Andy Fisher,
Richard J Drew,
Kate F Gould,
Amparo Sole,
Sean Studer,
Patricia Munoz, Lianne G Singer,
Margaret Hannan
The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 04/2011; 30(4):361-74. · 3.54 Impact Factor
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Francis X McCormack,
Yoshikazu Inoue,
Joel Moss, Lianne G Singer,
Charlie Strange,
Koh Nakata,
Alan F Barker,
Jeffrey T Chapman,
Mark L Brantly,
James M Stocks, [......],
Gregory P Downey,
Eugene J Sullivan,
Thomas V Colby,
Roy T McKay,
Marsha M Cohen,
Leslie Korbee,
Angelo M Taveira-DaSilva,
Hye-Seung Lee,
Jeffrey P Krischer,
Bruce C Trapnell
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ABSTRACT: Lymphangioleiomyomatosis (LAM) is a progressive, cystic lung disease in women; it is associated with inappropriate activation of mammalian target of rapamycin (mTOR) signaling, which regulates cellular growth and lymphangiogenesis. Sirolimus (also called rapamycin) inhibits mTOR and has shown promise in phase 1-2 trials involving patients with LAM.
We conducted a two-stage trial of sirolimus involving 89 patients with LAM who had moderate lung impairment--a 12-month randomized, double-blind comparison of sirolimus with placebo, followed by a 12-month observation period. The primary end point was the difference between the groups in the rate of change (slope) in forced expiratory volume in 1 second (FEV(1)).
During the treatment period, the FEV(1) slope was -12±2 ml per month in the placebo group (43 patients) and 1±2 ml per month in the sirolimus group (46 patients) (P<0.001). The absolute between-group difference in the mean change in FEV(1) during the treatment period was 153 ml, or approximately 11% of the mean FEV(1) at enrollment. As compared with the placebo group, the sirolimus group had improvement from baseline to 12 months in measures of forced vital capacity, functional residual capacity, serum vascular endothelial growth factor D (VEGF-D), and quality of life and functional performance. There was no significant between-group difference in this interval in the change in 6-minute walk distance or diffusing capacity of the lung for carbon monoxide. After discontinuation of sirolimus, the decline in lung function resumed in the sirolimus group and paralleled that in the placebo group. Adverse events were more common with sirolimus, but the frequency of serious adverse events did not differ significantly between the groups.
In patients with LAM, sirolimus stabilized lung function, reduced serum VEGF-D levels, and was associated with a reduction in symptoms and improvement in quality of life. Therapy with sirolimus may be useful in selected patients with LAM. (Funded by the National Institutes of Health and others; MILES ClinicalTrials.gov number, NCT00414648.).
New England Journal of Medicine 03/2011; 364(17):1595-606. · 53.30 Impact Factor
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ABSTRACT: This study investigated the impact of patient and caregiver gender on caregiver depressive symptoms. Caregivers' use of relationship-focused coping and dimensions of caregiver burden were examined as potential mediators of gender differences in depressive symptoms. Ninety-three organ transplant candidates and their caregivers completed written questionnaires (N = 186). Females providing care to male patients reported significantly higher depressive symptoms than the other caregivers in our sample. Multiple mediation analyses revealed that less support from family members and a greater negative health impact of caregiving helped explain these gender differences. Women caring for men were also perceived as more overprotective, but this did not explain gender differences in depression. Results highlight the benefits of a contextual, dyadic approach to studying caregiver distress.
Journal of Health Psychology 03/2011; 16(5):843-56. · 1.22 Impact Factor
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Masaaki Sato,
Thomas K Waddell,
Ute Wagnetz,
Heidi C Roberts,
David M Hwang,
Ayesha Haroon,
Dirk Wagnetz,
Cecilia Chaparro, Lianne G Singer,
Michael A Hutcheon,
Shaf Keshavjee
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ABSTRACT: Bronchiolitis obliterans syndrome (BOS) with small-airway pathology and obstructive pulmonary physiology may not be the only form of chronic lung allograft dysfunction (CLAD) after lung transplantation. Characteristics of a form of CLAD consisting of restrictive functional changes involving peripheral lung pathology were investigated.
Patients who received bilateral lung transplantation from 1996 to 2009 were retrospectively analyzed. Baseline pulmonary function was taken as the time of peak forced expiratory volume in 1 second (FEV(1)). CLAD was defined as irreversible decline in FEV(1) < 80% baseline. The most accurate threshold to predict irreversible decline in total lung capacity and thus restrictive functional change was at 90% baseline. Restrictive allograft syndrome (RAS) was defined as CLAD meeting this threshold. BOS was defined as CLAD without RAS. To estimate the effect on survival, Cox proportional hazards models and Kaplan-Meier analyses were used.
Among 468 patients, CLAD developed in 156; of those, 47 (30%) showed the RAS phenotype. Compared with the 109 BOS patients, RAS patients showed significant computed tomography findings of interstitial lung disease (p < 0.0001). Prevalence of RAS was approximately 25% to 35% of all CLAD over time. Patient survival of RAS was significantly worse than BOS after CLAD onset (median survival, 541 vs 1,421 days; p = 0.0003). The RAS phenotype was the most significant risk factor of death among other variables after CLAD onset (hazard ratio, 1.60; confidential interval, 1.23-2.07).
RAS is a novel form of CLAD that exhibits characteristics of peripheral lung fibrosis and significantly affects survival of lung transplant patients.
The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 03/2011; 30(7):735-42. · 3.54 Impact Factor
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Proceedings of the American Thoracic Society 09/2010; 7(5):305-11.
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ABSTRACT: Cystic fibrosis (CF) is an inherited condition that causes progressive respiratory failure and is the third most common indication for adult bilateral lung transplantation. Post-transplant hyperlipidemia commonly affects lung transplant recipients, but the impact of lung transplantation on serum lipids in the adult CF population is not well studied. The aim of this study was to examine the impact of lung transplantation on the prevalence of hyperlipidemia in CF adults.
We retrospectively analyzed prospectively collected data in 108 CF adults undergoing bilateral sequential lung transplantation from 1996 to 2007 at our institution.
The prevalence of hypercholesterolemia (>5.2 mmol/liter) and hypertriglyceridemia (>2.2 mmol/liter) increased significantly after lung transplant (14.8% vs 32.4%, p = 0.002; 8.3% vs 41.7%, p < 0.0001, respectively). Cyclosporine A (CsA) use was associated with significantly higher post-transplant total and LDL cholesterol compared with tacrolimus use. Post-transplant calculated Framingham risk score was <10% in all but 1 subject.
Hyperlipidemia was common in our cohort of post-lung transplant CF adults, with a higher prevalence in those receiving CsA. Despite these findings, calculated cardiovascular risk remained low and none of these subjects developed clinically evident cardiovascular disease.
The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 09/2010; 30(2):188-93. · 3.54 Impact Factor
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ABSTRACT: Patient registries are commonly used to track survival and medical outcomes in large cohorts. However, large-scale collection of health-related quality of life (HRQOL) data is more challenging because such data must be collected directly from patients. Internet-based HRQOL questionnaires are a potential solution, allowing home data collection with immediate storage in a central database.
Our objectives were to investigate the sociodemographic predictors of Internet use and willingness to convey HRQOL information over the Internet in a Canadian tertiary care patient population and to determine whether Internet use patterns of tertiary care patients differ from those of the general Canadian population. Additionally, we sought to identify the success of home completion of Internet-based HRQOL questionnaires, as well as factors hindering home completion.
We surveyed 644 patients at the Toronto General and St. Michael's Hospitals from November 2003 through July 2006 within a prospective, longitudinal cohort study of HRQOL in patients with lung disease or lung transplants. Using multiple logistic regression, we assessed patient age, gender, rurality, marital status, and employment or education status as potential sociodemographic predictors of having an Internet-accessible home computer, using email at least weekly, and willingness to complete a quality of life questionnaire over the Internet. Patients electing to complete questionnaires over the Internet were followed from September 2005 through March 2008 to assess completion of HRQOL questionnaires from home, identify barriers for noncompletion, and determine sociodemographic predictors for home completion.
Of the 644 patients, the median age was 51 years, with a similar number of males and females. Most were urban Ontario residents, were unemployed, and were married or in a common-law relationship. Having an Internet-accessible home computer was reported by 79.7% (513/644) of patients and use of email at least weekly by 66.5% (414/623) of patients. A majority of patients (57.1% 368/644) were willing to complete HRQOL questionnaires over the Internet via an emailed link. Of the participating 644 patients, 368 elected to complete future questionnaires from home and, as part of a gradual roll-out of the home HRQOL questionnaire, 211 were sent emails inviting them to do so. Of the invited patients, 78% (165/211) completed at least one questionnaire from home. The most common reason for noncompletion was a lack of or an inability to find time to complete the questionnaire. No statistically significant sociodemographic predictors of Internet use were associated with completion or noncompletion of questionnaires from home.
Home, Internet-based HRQOL assessment is feasible in tertiary care patient populations with a high predicted rate of Internet usage based on sociodemographic parameters. A large minority of patients were unwilling or unable to take part in home HRQOL assessments indicating that alternative methods of data collection are still required. However, the majority of patients electing to complete home HRQOL assessments went on to do so over the Internet.
Journal of Medical Internet Research 01/2010; 12(3):e35. · 4.41 Impact Factor
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ABSTRACT: Weight gain and obesity are common after lung transplantation. Despite associations between these conditions and sleep disordered breathing (SDB) in the general population, the prevalence and clinical impact of SDB in lung transplant recipients is unknown. The study objective was to determine the prevalence and clinical correlates of SDB in a cohort of lung transplant recipients.
Single-center cross-sectional study. Overnight polysomnography, sleep questionnaires, and anthropomorphic measurements were conducted on 24 lung recipients transplanted at least one year previously. The primary outcome was the prevalence of SDB, defined as an apnea-hypopnea index (AHI) > or = 10 per hour.
The prevalence of SDB was 63%. Obstructive sleep apnea (OSA) was observed in 38% and central sleep apnea (CSA) in 25%. Among all subjects, the mean AHI was 19.7 +/- 24.4 events/hour and the average weight gained after transplant was 10.5 +/- 12.3 kg. Subjects with SDB had a higher systolic blood pressure (135 +/- 12 vs. 124 +/- 13 mm Hg, p = 0.045), body mass index (BMI) (28.2 +/- 3.7 vs. 24.0 +/- 4.0 kg/m2, p = 0.008) and arousal index (28.0 +/- 26.9 vs. 10.4 +/- 6.4 per hour, p = 0.025) compared to the non-SDB group. Cyclosporine use was associated with CSA (p = 0.006). Recipients with OSA had a greater change (pre to post transplant) in BMI (5.8 +/- 4.6 vs. 2.0 +/- 2.9 kg/m2, p = 0.05) compared with non-SDB subjects.
Sleep disordered breathing is highly prevalent after lung transplantation. Polysomnography should be considered in lung transplant recipients, especially if they have gained weight.
Journal of clinical sleep medicine: JCSM: official publication of the American Academy of Sleep Medicine 10/2009; 5(5):441-7. · 3.23 Impact Factor
