The influence of clinical course after lung transplantation on rehabilitation success.

Pulmonary rehabilitation (PR) is a cornerstone of treatment following lung transplantation (LTx). The aim of this study was to observe the influence of a prolonged postsurgical clinical course on success of a 3-week inpatient PR. LTx recipients were divided according to their clinical course defined by their individual length of stay (LOS) in the transplant center (cohort 1: LOS >; cohort 2: ≤42 days). Peak work rate (PWR), maximum oxygen uptake (VO(2max) ), 6-min walk distance (6-MWD), vital capacity (VC), forced expiratory volume in one second (FEV1), physical activity of daily life (ADL), and health-related quality of life (HRQoL) measured using Short Form 36 questionnaire (SF36) were assessed at beginning and completion of PR. A total of 138 patients were included (LOS >42 days: 30; LOS ≤42 days: 108). At completion, physical functioning (VC, FEV1, PWR, VO(2max) , 6-MWD, ADL), and HRQoL (all SF36 domains) improved in each cohort (P < 0.05). No differences were found in between both cohorts in VC, FEV1, and ADL (n.s.), but in PWR, 6-MWD, and the SF36 domain 'physical functioning' (P < 0.05). A 3-week inpatient PR improves physical functioning despite prolonged hospitalization. HRQoL is close to normal. (ClinicalTrials.gov. identifier: NCT00759538).

Outcome of critically ill lung transplant candidates on invasive respiratory support.

PURPOSE: Lung transplantation (LTx) of patients on mechanical ventilation (MV) or extracorporeal support (ECS) is controversial because of impaired survival. Prognostic factors to predict survival should be identified. METHODS: A retrospective analysis was performed in a single centre of all ventilated LTx-candidates awarded an Eurotransplant (ET) high-urgency (HU) status between November 2004 and July 2009. Clinical data were collected on the first day of HU-status from intubated patients with an approved HU status. Single parameters as well as the lung allocation score (LAS), the Sequential Organ Failure Assessment score (SOFA) and the Simplified Acute Physiology Score (SAPS 2) were calculated. The association of these variables with survival was evaluated. RESULTS: A total of 100 intubated patients (median age 38 years, 56 % female) fulfilled the inclusion criteria, of whom 60 also required ECS. The main indications were cystic fibrosis (25 %) and idiopathic pulmonary fibrosis (24 %). Median time with HU status was 12 days [interquartile range (IQR) 6-21 days]. Sixty patients were transplanted, five were weaned from mechanical ventilation and 38 died while on the wait list. One-year-survival rates were 57, 36 and 5 % for transplanted patients, all candidates and non-transplanted candidates, respectively (p < 0.001). A SAPS score >24 (median 30, IQR 27-35), a procalcitonin level of >0.5 µg/l (median 0.4, IQR 0.1-1.4 µg/l) and any escalation of bridging strategy were independently associated with mortality (p = 0.021, = 0.003, and < 0.001, respectively). The LAS (median 88, IQR 8-90) did not predict survival (p = 0.92). CONCLUSIONS: High-urgency LTx improves survival in critically ill intubated candidates. Higher SAPS scores, escalating therapy and an abnormal procalcitonin level were associated with a poor outcome.

Single-centre experience with oral ribavirin in lung transplant recipients with paramyxovirus infections.

BACKGROUND: Paramyxovirus (PV) infections are increasingly recognized in lung transplant recipients and have been linked to subsequent graft failure and bronchiolitis obliterans syndrome (BOS). Ribavirin represents a possible treatment option although the outcome on graft function and BOS incidence is unknown. METHODS: We analysed outcomes of all PV infections in lung/heart-lung recipients between September 2006 and April 2009 in a single centre. PV-infected recipients treated with oral ribavirin were compared with those unable to receive ribavirin due to contraindications. Recovery of graft function, time to recovery and new development of BOS were compared. RESULTS: A total of 38 patients (ribavirin group) were treated with ribavirin for a median of 9 days (IQR 8-12), whilst 29 patients (non-ribavirin group) received best supportive care including corticosteroids. The median forced expiratory volume in 1 s dropped 20% (IQR 15-32) from baseline in the ribavirin group versus 18% (IQR 13-30) in the non-ribavirin group during infection. In 84% of patients treated with ribavirin and 59% of the non-ribavirin group, graft function recovered within 30 days (P=0.02). New onset of BOS developed within 6 months in 5% of the ribavirin group versus 24% of the non-ribavirin group (P=0.02). CONCLUSIONS: Treatment of PV after lung/heart-lung transplantation with oral ribavirin seems to be associated with earlier recovery of graft function and to prevent BOS.

Endoscopic indicators for obstructive airway complications after lung transplantation.

BACKGROUND: Obstructive airway complications (OACs) are a significant cause of morbidity after lung transplantation (LTx). Endoscopic evaluation early after LTx may help earlier identification of patients at risk. METHODS: Anastomotic healing process was prospectively evaluated in 169 LTx recipients by bronchoscopy between 2007 and 2009 in a single center. Bronchoscopies were performed on day 7, 14, 21, 90, 180, and 360 after LTx. A scoring system of airway healing was constructed. RESULTS: In 42 of 169 patients (25%), OAC occurred. Dehiscence (P≤0.001), extensive necrosis (P=0.001), fibrinous plug (P≤0.001), and mucosal healing at segmental level (P=0.001) on day 21 after LTx were significantly associated with later occurrence of OAC. The hereby developed Mucosal Airway Score for Healing (0-8 points, cutoff >3 points) proved to predict later OAC in 67 patients of validation phase (sensitivity=0.97; specificity=0.93; positive predictive value=0.85; and negative predictive value=0.96). Substantial interobserver agreement using Mucosal Airway Score for Healing was achieved (κ=0.617). All airway complications were managed with endoscopic intervention, and no surgical treatment was necessary. CONCLUSION: Endoscopic appearance on day 21 after LTx predicts later occurrence of OAC. The resulting scoring system may be used in the early postoperative period as a tool to assess preventive strategies.

Health-related quality of life in long-term survivors after heart and lung transplantation: a prospective cohort study.

BACKGROUND: Health-related quality of life (HRQoL) represents an important outcome measure to assess the success of transplantation in the long term. This study evaluated HRQoL in heart (HTx) and lung (LTx) transplant survivors, and assessed potential outcome-related predictors from before to 5 years after transplantation. METHODS: Study participants (n=170) were prospectively followed up from before to 5 years after HTx (n=82) or LTx (n=88), including HRQoL assessments (pretransplantation, 6, 12, and yearly between 24 and 60 months) using the Short Form-36, employment status index, and monitoring of adverse events. RESULTS: Patient groups (HTx vs. LTx) differed with respect to gender (men 74% vs. 48%; P<0.03) and high-urgency waiting status (72% vs. 45%; P<0.0001). Both cohorts showed the most significant HRQoL improvements within the first year posttransplant (P<0.0001), and relatively stable conditions afterward. Marital (P<0.01) and employment status (P<0.01) impacted HRQoL in both groups. The incidence of bronchiolitis obliterans showed significantly lower HRQoL in LTx patients (29.3%; P<0.005). CONCLUSIONS: HTx and LTx patients benefit from the transplant procedure with respect to HRQoL improvements for at least 5 years posttransplant; however, their trajectories during this time interval differ. Further research on organ-type-related predictors of HRQoL is necessary for the development of tailored psychosocial interventions.

Vibration response imaging (VRI) in lung transplant recipients.

BACKGROUND: In the first 6 months following lung transplantation, the most frequently occurring complications are infection, acute rejection and anastomotic dysfunction. The utility of vibration response imaging (VRI) lung images in assisting with the detection of these complications was evaluated. OBJECTIVES: The study aimed to evaluate if VRI is a good, non-invasive method of detecting clinical problems in lung transplant (LTx) recipients during early follow-up. METHODS: Between 06/2006 and 03/2007 all LTx patients who received transplants during the preceding 6 months at the Hannover Medical School received baseline VRI at enrollment with subsequent reassessment in combination with standard follow-up at 1, 3 and 6 months thereafter. The resulting images were analysed by two blinded reviewers. RESULTS: Fifty-five lung transplant recipients were enrolled in the study, with 49 patients successfully completing follow-up. Device operability and patient participation occurred without significant problems. High numbers of abnormal scans were detected. According to the clinical diagnosis, 29 patients (59.2 %) were stable at all four visits. Twenty clinical problems occurred (e.g., infections, rejections, obstructions, unknown deterioration). Agreement with clinical interpretation of rejections and infections was poor. Central airway obstruction (CAO) was detected in 80% by both reviewers. Accuracy in detecting obstructions was 89%; positive predicted value and negative predicted value were 80% and 90%, respectively. CONCLUSION: The VRI system is a non-invasive easy-to-use method with technical success and good image quality. The high number of abnormal scans makes interpretation following LTx difficult. VRI was unable to detect deterioration in graft function with the exception of ventilation disorders like central airway complications.

Significance of patient self-monitoring for long-term outcomes after lung transplantation.

BACKGROUND: Lung transplant (LTx) recipients' adherence to regular self-monitoring of lung function (SMLF) is important in maintaining health. This study investigated patients' behavior based on electronic monitoring (EM) and compared these findings with self-reported data. METHODS: This single-center study included 269 patients following LTx. Patients reported on adherence regarding SMLF, and data were compared to electronically stored measurements for the last three months prior to self-reporting. RESULTS: Non-adherence was 59.4% based on EM for a total of 22,052 measurements performed. Main reported reasons for non-adherence were forgetfulness (22%), lack of time (19%), and good self-perception of health status (19%). Determinants for non-adherence were patients constraining beliefs (p ≤ 0.0001), low perceived support from the transplant center (p ≤ 0.008), a history of infections (p ≤ 0.014) and rejections (p ≤ 0.043), and bronchiolitis obliterans (p ≤ 0.006). Multiple logistic regression revealed low-perceived support from the transplant center (OR 3.22; 95% CI 1.32-7.83; p < 0.01), and lack of support from patient organizations (OR 2.19; 95% CI 1.02-4.72; p < 0.04) as independent predictors for non-adherence. CONCLUSIONS: LTx recipients had some difficulties maintaining SMLF on a daily basis. Non-adherence regarding lung function monitoring may provide a clinically relevant estimate of suspect cases for critical events impacting outcomes after LTx.

Effect of adherence to home spirometry on bronchiolitis obliterans and graft survival after lung transplantation.

BACKGROUND: Patient-controlled home spirometry (HS) after lung transplantation has been shown to be valid and reliable to detect the presence of graft infection and rejection at its earliest onset. Effects of nonadherence to HS on detection of the bronchiolitis obliterans syndrome (BOS) and on graft survival are unknown. METHODS: A 7-year prospective cohort study assessed nonadherence longitudinally using electronic spirometry for 24 months. During follow-up, BOS, retransplantation, and survival were stratified by adherence groups. RESULTS: Electronic monitoring of 226 patients confirmed that 123,487 measures were performed. Period prevalence was 0.76 measures per patient day and decreased significantly over time (P<0.0001). During follow-up, BOS was developed in 32% of patients; 5% received a second transplant, and mortality rate was 19%. Kaplan-Meier event-free analysis showed decreased freedom from BOS time in nonadherers (30%) compared with good (43%) or moderate adherers (19%) (log rank 6.008; P<0.014) and a tendency toward lower retransplantation rates (log rank 3.14; P<0.07). Mantel Cox regression revealed no impact of adherence on patient survival. CONCLUSIONS: This was the first study assessing nonadherence to HS based on electronic monitoring in relation to long-term outcome after lung transplantation. Nonadherers showed decreased freedom from BOS in the largest sample to date, but did not impact survival.

Bronchial epithelial cells as a new source for differential transcriptome analysis after lung transplantation.

OBJECTIVE: The early diagnosis of chronic organ rejection after lung transplantation (LTx) is currently hampered by the lack of reliable diagnostic markers. The present study aims to establish the procedure of gene expression profiling in bronchial epithelial cells for the identification of candidate genes that might prove useful in the early diagnosis. METHODS: Twenty-three patients who underwent lung transplantations were investigated at a time point when no clinical signs of bronchiolitis obliterans syndrome (BOS) were apparent. Bronchial epithelial cells were obtained by bronchial brushing. Gene expression profiles were determined using a human whole-genome cDNA microarray (Stanford Faculty, Stanford, CA, USA). RESULTS: Unsupervised hierarchical cluster analysis revealed that the samples from LTx patients can be clearly distinguished from the comparison group. We also found that the samples from LTx patients with the same underlying disease do not form major clusters of gene expression pattern. Using biostatistical analysis, 'haemoglobin beta', expressed by alveolar type II and Clara cells, and CD99, involved in inflammatory processes, were identified comparing lung transplantation and comparison group. CONCLUSIONS: Thus, global expression analyses of bronchial epithelial cells might be a new approach to identify diagnostic markers, especially if patients with LTx are monitored sequentially and if patients with and without BOS are compared.

Community-acquired respiratory viral infections in lung transplant recipients: a single season cohort study.

BACKGROUND: The impact of community-acquired respiratory virus (CARV) infections on bronchiolitis obliterans syndrome (BOS) and outcome after lung transplantation (LTx) and diagnostic techniques were prospectively evaluated. METHODS: A single-center prospective cohort study was performed in LTx-outpatients between October 31, 2005 and April 30, 2006. Symptoms of respiratory tract infections were recorded and nasopharyngeal and oropharyngeal swabs were obtained. Lower respiratory sampling was performed when indicated. Immunofluorescence testing, cultures, and polymerase chain reaction for 12 different CARV were applied. Patients were followed up until December 31, 2007. New onset and BOS-stage was recorded 1 year after presentation. RESULTS: Three hundred eighty-eight LTx-recipients were screened. Fifty-one percent reported of symptoms of respiratory tract infection. Seven hundred seventy upper and 180 lower respiratory samples were obtained. Thirty-four CARV were detected in 30 patients (7.7%): 12 parainfluenza, 7 respiratory syncytial virus, 6 metapneumovirus, 5 coronavirus, 3 rhinovirus, and 1 influenza virus. At 1 year, 43 new cases of BOS developed. One-year incidence of BOS was 25.0% in CARV-positive versus 9.0% in CARV-negative patients (log-rank P=0.01). Symptomatic CARV-infection proved to be a significant covariate for 1-year BOS-free survival in multivariate analysis (P=0.002, adjusted hazard ratio 4.13). CARV-infection did not influence BOS progression in 88 patients with prior BOS (P 0.45). After paramyxovirus infection, 8 of 24 patients developed new-onset BOS, whereas no case was recorded after rhinovirus and coronavirus infection. DISCUSSION: Surveillance detected CARV in LTx outpatients infrequently. Symptomatic CARV-infection increases the risk for new onset of BOS, but not progression. Risk to develop BOS was especially increased after paramyxovirus infection.