Kugler C, Gottlieb J, Dierich M, Haverich A, Strueber M, Welte T, Simon A. Significance of patient self-monitoring for long-term outcomes after lung transplantation. Clin Transplant 2009 DOI: 10.1111/j.1399-0012.2009.01197.x (c) 2009 John Wiley & Sons A/S. Abstract: 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.

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 enrolment 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.

OBJECTIVES: This study was conducted to evaluate whether brain (B-type) natriuretic peptide (BNP) changes during sleep are associated with the frequency and severity of apneic/hypopneic episodes, intermittent arousals, and hypoxia. BACKGROUND: Sleep apnea is strongly associated with heart failure (HF) and could conceivably worsen HF through increased sympathetic activity, hemodynamic stress, hypoxemia, and oxidative stress. If apneic activity does cause acute stress in HF, it should increase BNP. METHODS: Sixty-four HF patients with New York Heart Association functional class II and III HF and ejection fraction <40% underwent a baseline sleep study. Five patients with no sleep apnea and 12 with severe sleep apnea underwent repeat sleep studies, during which blood was collected every 20 min for the measurement of BNP. Patients with severe sleep apnea also underwent a third sleep study with frequent BNP measurements while they were administered oxygen. This provided 643 observations with which to relate apnea to BNP. The association of log BNP with each of 6 markers of apnea severity was evaluated with repeated measures regression models. RESULTS: There was no relationship between BNP and the number of apneic/hypopneic episodes or the number of arousals. However, the burden of hypoxemia (the time spent with oxygen saturation <90%) significantly predicted BNP concentrations; each 10% increase in duration of hypoxemia increased BNP by 9.6%(95% confidence interval: 1.5% to 17.7%, p = 0.02). CONCLUSIONS: Hypoxemia appears to be an important factor that underlies the impact of sleep abnormalities on hemodynamic stress in patients with HF. Prevention of hypoxia might be especially important for these patients.

While numerous studies have explored the mechanisms of reward-based decisions (the choice of action based on expected gain), few have asked how reward influences attention (the selection of information relevant for a decision). Here we show that a powerful determinant of attentional priority is the association between a stimulus and an appetitive reward. A peripheral cue heralded the delivery of reward or no reward (these cues are termed herein RC+ and RC-, respectively); to experience the predicted outcome, monkeys made a saccade to a target that appeared unpredictably at the same or opposite location relative to the cue. Although the RC had no operant associations (did not specify the required saccade), they automatically biased attention, such that an RC+ attracted attention and an RC- repelled attention from its location. Neurons in the lateral intraparietal area (LIP) encoded these attentional biases, maintaining sustained excitation at the location of an RC+ and inhibition at the location of an RC-. Contrary to the hypothesis that LIP encodes action value, neurons did not encode the expected reward of the saccade. Moreover, at odds with an adaptive decision process, the cue-evoked biases interfered with the required saccade, and these biases increased rather than abating with training. After prolonged training, valence selectivity appeared at shorter latencies and automatically transferred to a novel task context, suggesting that training produced visual plasticity. The results suggest that reward predictors gain automatic attentional priority regardless of their operant associations, and this valence-specific priority is encoded in LIP independently of the expected reward of an action.

Lung transplantation in cystic fibrosis is an established therapy, due to the fact that vast majority of adult CF patients will develop respiratory failure. Even adolescents and children can be transplanted successfully today. Lung transplantation in cystic fibrosis requires special consideration concerning candidate selection, surgery and postoperative follow-up care. Due to a donor shortage and increasing waiting time, early referral to transplant centres of potential candidates is crucial. In the process of candidate selection, assumed improvements in quality of life and survival benefit should be weighed against contraindications. Centre-based follow-up and close cooperation with local physicians are key factors for success. During follow-up care, the transplantation team should be contacted immediately in the case of any problem or change in medication.

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.

Although the parietal cortex is traditionally associated with spatial perception and motor planning, recent evidence shows that neurons in the lateral intraparietal area (LIP) carry both spatial and nonspatial signals. The functional significance of the nonspatial information in the parietal cortex is not understood. To address this question, we tested the effect of unilateral reversible inactivation of LIP on three behavioral tasks known to evoke nonspatial responses. Each task included a spatial component (target selection in the hemifield contralateral or ipsilateral to the inactivation) and a nonspatial component, namely limb motor planning, the estimation of elapsed time, and reward-based decisions. Although inactivation reliably impaired performance on all tasks, the deficits were spatially specific (restricted to contralateral target locations), and there were no effects on nonspatial aspects on performance. This suggests that modulatory nonspatial signals in LIP represent feedback about computations performed elsewhere rather than a primary role of LIP in these computations.

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.

BACKGROUND: This study was designed to analyze the role of postoperative donor cell chimerism for the induction and maintenance of transplantation tolerance in a porcine lung transplantation model. METHODS: Left-sided single lung transplantation from major histocompatibility mismatched male donors was performed in 27 female minipigs. All received a 28-day course of pharmacologic immunosuppression using various agents, some in combination with preoperative irradiation. Groups for eventual analysis were strictly defined by outcome, that is, pigs with acute rejection before postoperative day 178 (n=16) were allocated into one group, long-term surviving animals (n=11) into the other. Peripheral blood chimerism was monitored by flow cytometry and real-time polymerase chain reaction. Intragraft chimerism was detected from bronchoalveolar lavage fluid (BALF) by fluorescent in situ hybridization. RESULTS: Blood chimerism peaked 1 hour after transplantation and was significantly higher in the group of long-term survivors at that time. Thereafter chimerism rapidly decreased, but tended to remain higher in long-term survivors. In case of acute rejection donor cells were lost, but remained detectable for up to 36 postoperative months in tolerant animals. In BALF, the percentage of male nuclei was equally high under immunosuppression in both groups. Rejecting animals showed a rapid decrease of Y-bearing cells in BALF after drug withdrawal and an almost complete loss when acute rejection occurred. In tolerant pigs, intragraft chimerism remained detectable throughout the follow-up. CONCLUSIONS: This study demonstrates a clear correlation of donor leukocyte chimerism with long-term allograft survival in a porcine allogeneic lung transplantation model.