Lung transplantation : studies in candidates and recipients P 1476 Results of a phase 2 b multi-center trial of ALN-RSV 01 in respiratory syncytial virus ( RSV )-infected lung transplant patients (original) (raw)
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Revista Médica de Minas Gerais, 2015
Introduction: patients with advanced lung disease (DPA) exhibit reduced tolerance to an effort, dyspnea, and fatigue. Pulmonary rehabilitation (RP) aims to improve exercising tolerance, controlling symptoms, minimize complications in the pulmonary disease, and improve the quality of life. Objective: to evaluate the effect of RP on exercise capacity, according to the distance traveled in the six-minute walk test (TC6M), in patients with DPA on the waiting list for lung transplantation. Methodology: patients on the waiting list for lung transplantation, referred to RP in the General Hospital of the Federal University of Minas Gerais were submitted to the TC6M, at the beginning and end of RP, and the degree of dyspnea was assessed using the Borg scale. The data were presented as mean and standard deviation of absolute values and compared using the Student's t-test. The p-values < 0.05 were considered statistically significant. Results: between January of 2011 and December of 2012, 17 patients completed the RP. The average age was 42 ± 12 years, 65% were females, the peripheral oxygen saturation on admission was 83 ± 17%, and 35% used oxygen 24 hours/day. Seven patients (41%) presented DPOC, six (35%) had pulmonary fibrosis, and four (24%) other DPA. There was a significant improvement in the distance walked in the TC6M at the end of RP (314 ± 131 m versus 427 ± 111 m; p = 0.0016), with an average increase of 118 m. Conclusion: the RP had a positive impact on the exercise capacity of patients on the waiting list for lung transplantation.
Bone Marrow Transplantation, 2000
In some subsets of these immunocompromised patients, RSV upper respiratory illnesses frequently progress to fatal viral pneumonia. The frequency of progression to pneumonia is higher during the pre-engraftment than during the postengraftment period. Once pneumonia develops, the overall mortality is 60-80%, regardless of the treatment strategy. We performed a pilot trial of therapy of RSV upper respiratory illnesses using aerosolized ribavirin and IVIG (500 mg/kg every other day), with the goal of preventing progression to pneumonia and death. Two dosages of ribavirin were used: a conventional regimen (6 g/day at 20 mg/ml for 18 h/day) and a high-dose short-duration regimen (6 g/day at 60 mg/ml for 2 h every 8 h). Fourteen patients were treated for a mean of 13 days (range: 7-23 days). In 10 (71%) patients, the upper respiratory illness resolved. The other four (29%) patients, three of whom were in the pre-engraftment period, developed pneumonia, which was fatal in two. The most common adverse effect was psychological distress at being isolated within a scavenging tent. In conclusion, prompt therapy of RSV upper respiratory illnesses in BMT recipients with a combination of aerosolized ribavirin and IVIG was a safe and promising approach to prevent progression to pneumonia and death. Bone Marrow Transplantation (2000) 25, 751-755.
Exercise testing parameters associated with post lung transplant mortality
Respiratory Physiology & Neurobiology, 2012
Exercise performance during cardiopulmonary exercise testing (CPET) is a predictor of all-cause mortality in the general population and in patients with coronary heart disease. Mortality beyond one-year after lung transplantation (LTx) is due to multiple causes, is difficult to predict, and has not been fully evaluated in LTx recipients. We hypothesized that, similar to other populations, exercise performance after LTx may be associated with mortality. A retrospective review of all LTx recipients who underwent CPET between 2001 and 2009 was conducted. Chosen endpoint was re-transplantation or death. Survival analysis was performed using Cox proportional-hazard models in 183 patients. After adjusting for bronchiolitis obliterans syndrome (BOS) score, for every 10% increment in percent-predicted peak watts or percent-predicted peak oxygen uptake patients were approximately 23% less likely to experience an endpoint. We conclude that after adjusting for BOS score, lower exercise capacity one-year post LTx is independently associated with mortality. This may imply a protective role of exercise capacity in the LTx population.
CHEST Journal, 2011
L ung transplantation results in a dramatic improvement in lung function and may offer prolongation of survival in patients with advanced lung disease. However, its effects on functional outcomes, particularly peak exercise parameters on maximal exercise testing, have not been investigated in detail. Small studies have revealed a peripheral limitation in exercise capacity posttransplant despite a marked increase in pulmonary function. 1 Specifi cally, peak oxygen uptake ( o 2 ) and maximum workload were markedly lower than expected, with peak o 2 ranging between 40% to 60% of predicted values. 2-4 These lower-than-normal values, accompanied by a low peak oxygen pulse, high respiratory exchange ratio (RER), and an early anaerobic threshold, were believed to be potentially consistent with peripheral muscle dysfunction. The most comprehensive method of evaluating exercise outcomes is to use metabolic exercise testing to assess ventilation, exercise capacity, exercise, and metabolic effi ciency. In order to more clearly assess the observed discrepancy between exercise performance Background: Detailed description of functional exercise outcomes before and after lung transplantation is lacking. The objective of this study was to describe and compare posttransplant improvement in lung function and peak exercise parameters in patients with advanced lung disease. Methods: The study included 153 patients who underwent lung transplantation over 7 years who had complete cardiopulmonary exercise testing (CPET) and pulmonary function tests (PFTs) before and after lung transplantation. CPET and PFT within 30 months pretransplant and posttransplant were compared. Results: Pulmonary function markedly improved posttransplant as FVC increased 67%, maximum voluntary ventilation increased 91%, and FEV 1 increased 136%. However, peak oxygen consumption increased only 19%, peak CO 2 production increased 50%, and peak work increased 78%. Although transplant recipients had a 1.5-to 2.0-fold increase in exercise capacity posttransplant, peak exercise capacity remained at 50% of the predicted normal, suggesting a maximal limitation. Subgroup stratifi cation into quartiles based on pretransplant exercise capacity revealed the greatest exercise benefi t to be in the lowest functional pretransplant groups.
The Journal of Heart and Lung Transplantation, 2011
The purpose of this study was to examine the effect of an inpatient rehabilitation program on health-related quality of life (HRQOL) and exercise capacity (EC) in long-term (Ͼ1 year after lung transplantation) survivors (LTSs) in comparison to a control group (CG). METHODS: Sixty LTSs, 4.5 Ϯ 3.2 years after lung transplantation (LTx), were randomly assigned to two equally sized groups that were stratified for gender and underlying disease. Thirty LTSs (age 49 Ϯ 13 years, 13 male and 17 females, 19 double LTxs, 7 BOS Stage Ն1) attended an inpatient rehabilitation program (intervention group, IG) for 23 Ϯ 5 days. The CG (age 50 Ϯ 12 years, 13 males and 17 females, 20 double LTxs, 2 BOS Stage Ն1) received medical standard therapy (physiotherapy). Patients were evaluated by cardiopulmonary exercise testing, 6-minute walk test (6MWT), SF-36, SGRQ and the Quality of Life Profile for Chronic Diseases questionnaire before and after (18 Ϯ 3 days) the program. RESULTS: The groups were statistically indistinguishable in terms of clinical data. Each treatment group significantly improved their sub-maximal EC (6MWT: IG, 493 Ϯ 90 m vs 538 Ϯ 90 m, p Ͻ 0.001; CG, 490 Ϯ 88 m vs 514 Ϯ 89 m, p Ͻ 0.001) and maximal EC (VO 2peak : IG, 17.0 vs 18.5 ml/min/kg, p ϭ 0.039; CG, 18.0 vs 19.5 ml/min/kg, p ϭ 0.005), without reaching statistical significance between the groups. In both study groups, patients HRQOL tended to improve. Significant correlations were found between EC parameters and HRQOL scales. CONCLUSIONS: Our data suggest that structured physical training may improve exercise tolerance in LTS. Our study results did not demonstrate a significant benefit of an inpatient over an outpatient exercise program. J Heart Lung Transplant 2011;30:912-9
Exercise limitation in recipients of lung transplants
Physical therapy, 2004
ung transplantation is a viable option for improving survival and quality of life in selected patients with end-stage lung diseases such as chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis, and cystic fibrosis. 1 Following lung transplantation, there are substantial improvements in pulmonary function and a subsequent improvement in exercise capacity; however, peak exercise remains reduced to 40% to 60% of predicted values even up to 2 years after transplantation. Williams et al 2 tested maximal exercise capacity in recipients of a single-lung transplant (SLT) (nϭ6) and in recipients of a double-lung transplant (DLT) (nϭ7) at 3 months and again at 1 to 2 years after transplantation. At 3 months after transplantation, peak oxygen consumption (V o 2 peak) was 46% of predicted values in the SLT group and 50% of predicted values in the DLT group. At 1 to 2 years after transplantation, there was no improvement in maximal oxygen consumption (V o 2 max) or maximal work capacity in either group, despite improvements in lung function and return to regular activities (ie, school or work) in most of the recipients of transplants. Evans et al 3 compared whole-body exercise (cycling) in 9 recipients of SLT who were 5 to 38 months after transplantation versus a control group of subjects without known pathology or impairments. Measurements of V o 2 peak taken during cycling were reduced in the SLT group compared with the control group (PϽ.001) and were only 36.8%Ϯ3.1% (XϮSD) of predicted values in the SLT group. This reduction in exercise capacity poses an interesting challenge to physical therapists. An understanding of the potential factors contributing to exercise limitation in this population, therefore, is imperative to prescribing an exercise program that emphasizes the appropriate body systems and leads to improvement in functional capacity of these people. There are a number of factors that may limit maximal exercise in recipients of lung transplants, including abnormal ventilatory limitation, cardiac and peripheral vascular factors, and impaired oxidative capacity of peripheral skeletal muscle (Table, Figure). A growing body of evidence points to the role
Journal of Heart and Lung Transplantation, 2010
BACKGROUND: Respiratory syncytial virus (RSV) infections in lung transplant recipients (LTRs) have been associated with significant morbidity and mortality. Immunoglobulins, ribavirin, and palivizumab are suggested treatments for both pre-emptive and therapeutic purposes. However, in the absence of randomized, placebo-controlled trials, efficacy is controversial and there is toxicity as well as cost concerns. METHODS: We retrospectively reviewed cases of lower respiratory tract RSV infections in adult LTRs. Diagnosis was based on clinical history, combined with a positive polymerase chain reaction (PCR) and/or viral cultures of bronchoalveolar lavage (BAL) specimens. RESULTS: Ten symptomatic patients were identified (7 men and 3 women, age range 28 to 64 years). All were hospitalized for community-acquired respiratory tract infections. Two patients had a concomitant acute Grade A3 graft rejection, and 1 patient had a concomitant bacterial pneumonia. Eight patients did not receive a specific anti-RSV treatment because of clinical stability and/or improvement at the time of RSV diagnosis. Only 2 patients (1 with Grade A3 allograft rejection and 1 requiring mechanical ventilation) received ribavirin and palivizumab. All patients recovered without complications and with no persistent RSV infection. However, bronchiolitis obliterans (BOS) staging worsened in 6 patients during the mean follow-up of 45 months. CONCLUSIONS: Our data suggest that mild RSV infections in LTRs might evolve favorably in the absence of specific anti-viral therapy. However, this observation needs confirmation in a large clinical trial specifically investigating the development of BOS in untreated vs treated patients.
American Journal of Transplantation, 2008
We investigated the impact of lung transplantation and outpatient pulmonary rehabilitation after lung transplantation on skeletal muscle function and exercise tolerance. Skeletal muscle force (Quadriceps force, QF), exercise tolerance (six minute walking distance, 6MWD) and lung function were assessed in 36 patients before and after lung transplantation. Seventeen male and 19 female patients (age 57 ± 4) showed skeletal muscle weakness before the transplantation. A further 32 ± 21% reduction was seen 1.2 (interquartile range 0.9 to 2.0) months after LTX. The number of days on the intensive care unit was significantly related to the observed deterioration in muscle force after LTX. At this time point 6MWD was comparable to pre-LTX.