Long-term Change in the Risk of Skin Cancer After Organ Transplantation: A Population-Based Nationwide Cohort Study.

Importance: The high risk of skin cancer after organ transplantation is a major clinical challenge and well documented, but reports on temporal trends in the risk of posttransplant cutaneous squamous cell carcinoma (SCC) are few and appear contradictory. Objective: To study temporal trends for the risk of skin cancer, particularly SCC, after organ transplantation. Design, Setting, and Participants: Population-based, nationwide, prospective cohort study of 8026 patients receiving a kidney, heart, lung, or liver transplant in Norway from 1968 through 2012 using patient data linked to a national cancer registry. The study was conducted in a large organ transplantation center that serves the entire Norwegian population of approximately 5.2 million. Exposures: Receiving a solid organ transplant owing to late-stage organ failure, followed by long-term immunosuppressive treatment according to graft-specific treatment protocols. Main Outcomes and Measures: Occurrence of first posttransplant SCC, melanoma, or Kaposi sarcoma of the skin. Risk of skin cancer was analyzed using standardized incidence ratios (SIRs) and, for SCC, multivariable Poisson regression analysis of SIR ratios, adjusting for 5-year time period of transplantation, different follow-up time, age, sex, and type of organ. Results: The study cohort included 8026 organ transplant recipients, 5224 men (65.1%), with a mean age at transplantation of 48.5 years. Median follow-up time was 6.7 years per recipient; total follow-up time, 69 590 person-years. The overall SIRs for SCC, melanoma, and Kaposi sarcoma were 51.9 (95% CI, 48.4-55.5), 2.4 (95% CI, 1.9-3.0), and 54.9 (95% CI, 27.4-98.2), respectively. In those who underwent transplantation in the 1983-1987 period, the unadjusted SIR for SCC was 102.7 (95%, 85.8-122.1), declining to 21.6 (95% CI, 16.8-27.0) in those who underwent transplantation in the 2003-2007 period. Adjusting for different follow-up times and background population risks, as well as age, graft organ, and sex, a decline in the SIR for SCC was found, with SIR peaking in patients who underwent transplantation in the 1983-1987 period and later declining to less than half in patients who underwent transplantation in the 1998-2002, 2003-2007, and 2008-2012 periods, with the relative SIRs being 0.42 (95% CI, 0.32-0.55), 0.31 (95% CI, 0.22-0.42), and 0.44 (95% CI, 0.30-0.66), respectively. Conclusions and Relevance: The risk of SCC after organ transplantation has declined significantly since the mid-1980s in Norway. Less aggressive and more individualized immunosuppressive treatment and close clinical follow-up may explain the decline. Still, the risk of SCC in organ transplant recipients remains much higher than in the general population and should be of continuous concern for dermatologists, transplant physicians, and patients.

Psychiatric disorders and psychological distress in patients undergoing evaluation for lung transplantation: a national cohort study.

OBJECTIVE: We sought to investigate type and prevalence of psychiatric disorders and psychological distress in patients being evaluated for lung transplantation. METHODS: One hundred eighteen patients were assessed [74% with chronic obstructive pulmonary disease (COPD)] with the MINI Neuropsychiatric Interview, the General Health Questionnaire (GHQ), and Hospital Anxiety Depression Scale (HADS). Spirometry and the 6-min walk test (6MWT) assessed lung function with data subject to multivariate regression analyses. RESULTS: Current and lifetime prevalence for mental disorders were 41.5% and 61.0% respectively, with anxiety (39.8% of patients), mood disorders (11.8%), and subsyndromal disorders (8.7%) identified. 15% of patients reported feelings of panic during the last week, 9% reported hopelessness, and 3% felt that life was not worth living. Statistically significant correlates were derived for HADS-depression with lung function (P=.0012) and 6MWT (P=.030) for the entire group (P=.012), and with lung function (P=.030) for COPD patients (P=.045), for whom higher chronic GHQ-scores correlated with poorer lung function (P=.009). In multivariate regression analysis, history of mental disorder was strongest predictor of current distress. CONCLUSIONS: Our findings underline the importance of assessing past, current, and sub-syndromal psychiatric disorders in addition to levels of distress in transplant candidates, with prospective studies needed to investigate impact on long-term outcome after transplantation.

Long-term outcomes of thoracic transplant recipients following conversion to everolimus with reduced calcineurin inhibitor in a multicenter, open-label, randomized trial.

The NOCTET study randomized 282 patients ≥1 year after heart or lung transplantation to continue conventional calcineurin inhibitor (CNI) therapy or to start everolimus with reduced-exposure CNI. Last follow-up, at ≥5 years postrandomization (mean: 5.6 years) was attended by 72/140 everolimus patients (51.4%) and 91/142 controls (64.1%). Mean measured GFR remained stable in the everolimus group from randomization (51.3 ml/min) to last visit (51.4 ml/min) but decreased in controls (from 50.5 ml/min to 45.3 ml/min) and was significantly higher with everolimus at last follow-up (P = 0.004). The least squares mean (SE) change from randomization was -1.5 (1.7)ml/min with everolimus versus -7.2 (1.7)ml/min for controls (difference: 5.7 [95% CI 1.7; 9.6]ml/min; P = 0.006). The difference was accounted for by heart transplant patients (difference: 6.9 [95% 2.3; 11.5]ml/min; P = 0.004). Lung transplant patients showed no between-group difference at last follow-up. Rates of rejection, death, and major cardiac events were similar between groups, as was graft function. Pneumonia was more frequent with everolimus (18.3% vs. 6.4%). In conclusion, introducing everolimus in maintenance heart transplant patients, with reduced CNI, achieves a significant improvement in renal function which is maintained for at least 5 years, but an early renal benefit in lung transplant patients was lost. Long-term immunosuppressive efficacy was maintained.

Pulmonary retransplantation in the Nordic countries.

BACKGROUND: The increasing demand for pulmonary retransplantation (re-LTx) raises ethical issues on the correct allocation of the scarce donor pool. Thus, we performed a thorough review of the current results for re-LTx in the Nordic countries. METHODS: Seventy-five patients with a median age of 50 years (range, 22 to 64 years) underwent re-LTx from 1992 until June 2013, of which 53 had single re-LTx, 21 had double re-LTx, and 1 patient underwent a heart-lung retransplantation. Primary graft dysfunction (PGD) was the primary indication in 9 cases, bronchiolitis obliterans syndrome (BOS) in 62 cases, and airway complications in 4 cases. RESULTS: Patients who underwent re-LTx in the period 1992 to 1999 (n = 16) had a 1-year survival of 37.5% (95% confidence interval [CI], 19.9 to 70.6), whereas patients who underwent re-LTx in the period 2000 to 2013 (n = 64) had a 1-year survival of 81.0% (95% CI, 71.5 to 91.8). Corresponding 5-year survival was 25.0% (95% CI, 10.7 to 58.4) in the early era group (1992 to 1999) and 57.2% (95% CI, 44.3 to 73.7) in the more recent era group (2000 to 2013; p = 0.0151). Patients with BOS who underwent re-LTx in the period 1992 to 1999 (n = 13) had a 1-year survival of 38.5% (95% CI, 19.3 to 76.5), whereas patients with BOS who underwent re-LTx in the period 2000 to 2013 (n = 49) had a 1-year survival of 85.4% (95% CI, 75.9 to 96.0). Corresponding 5-year survival was 23.1% (95% CI, 8.6 to 62.3) in the early era group (1992 to 1999) and 56.1% (95% CI, 41.9 to 75.2) in the more recent era group (2000 to 2013; p = 0.0199). The cumulative incidence among patients who underwent re-LTx because of BOS and developed BOS again after re-LTX was analyzed. The cumulative incidence curves for time periods 1992 to 1999 and 2000 to 2013 are not statistically different for repeat BOS (p = 0.5087), but they are highly significant for time periods among patients who died (p = 0.02381). CONCLUSIONS: Results for re-LTx have improved over time, especially when BOS is the primary indication. The cumulative incidence among patients who underwent re-LTx because of BOS and developed repeat BOS after re-LTX showed equal risk between 1992 to 1999 and 2000 to 2013 in the aspect of developing repeat BOS, but in the later era the patients had a significantly higher chance of surviving.

Multiorgan procurement increases systemic inflammation in brain dead donors.

Organs available for solid organ transplantation are mainly procured from brain dead donors. The inflammation associated with brain death may reduce organ quality and increase organ immunogenicity, thus leading to inferior recipient outcome. We hypothesized that the extensive surgical procedure performed during multiorgan procurement enhances the levels of systemic inflammatory biomarkers. We measured the levels of 27 cytokines and the terminal complement complex (TCC) in plasma samples from brain dead organ donors (n = 34) drawn before and at three specific time points during procurement surgery. Baseline levels of G-CSF, interferon-γ, IL-1ra, IL-4, IL-6, IL-7, IL-8, IL-10, IP-10, MCP-1, macrophage inflammatory protein (MIP)-1ß, platelet derived growth factor (PDGF), regulated upon activation T cell expressed and secreted, and tumor necrosis factor-α were significantly elevated in brain dead donors compared with normal individuals (n = 14), but they were not associated with time on ventilator or any other registered clinical variable. Notably, the secretion of G-CSF, IL1-ra, IL-6, IL-8, IL-10, IP-10, MCP-1, MIP-1ß, PDGF, and TCC, the latter reflecting ongoing complement activation, increased significantly during surgery. None of the biomarker increases were correlated with operation duration. Multiorgan procurement surgery significantly adds to the inflammatory response revealed by both pro- and anti-inflammatory biomarkers associated with brain death. Future studies should determine whether this is associated with inferior recipient outcome.

Long-term follow-up of lung and heart transplant recipients with pre-transplant malignancies.

BACKGROUND: Concern regarding recurrence of pre-transplant (Tx) malignancy has disqualified patients from Tx. Because this has been poorly studied in lung and heart Tx recipients our aim was to investigate the influence of pre-Tx malignancy on post-Tx recurrence and long-term survival, focusing on pre-operative cancer-free intervals. METHODS: From our lung and heart Tx programs (1983 to 2011) we retrospectively identified 111 (lung, 37; heart, 74) of 3,830 recipients with 113 pre-Tx malignancies. The patients were divided into 3 groups by pre-Tx cancer-free interval: Group I, <12 months (n = 24); Group II, ≥12 to<60 months (n = 18); and Group III, ≥60 months (n = 71). RESULTS: Mean age at pre-Tx malignancy was 35±18 years. Mean post-Tx follow-up time was 70±63 months (range, 0-278 months), and malignancy recurrence was 63% in Group I, 26% in Group II, and 6% in Group III. Kaplan-Meier analysis of freedom from post-Tx recurrence revealed the following differences among the groups: Group I vs II, p = 0.08; II vs III, p = 0.002; and I vs III, p<0.001. Overall survival (51 deaths) was significantly poorer in Group I than in Groups II and III (p = 0.044). Survival between Groups II and III did not differ significantly (p = 0.93). CONCLUSIONS: Cancer-free survival of ≥5 years pre-Tx is associated with the lowest recurrence. However, recurrence is related to the time the patients were cancer-free, as seen in Groups I and II.

Airway complications after lung transplantation: long-term outcome of silicone stenting.

BACKGROUND: Airway complications remain a significant cause of morbidity after lung transplantation. The majority of the centres that have published their results have used metal stents. OBJECTIVES: We report the long-term outcome of silicone stenting and subsequent stent removal in lung transplant recipients with stenotic airway complications. METHOD: From 1990 to 2008, 279 patients received 88 single, 170 double, and 21 heart-and-lung transplantations. Of 470 anastomoses at risk, 44 airway complications developed and were treated in 35 patients. Six lesions were treated with Nd:YAG laser and balloon dilatations only. Thirty-two silicone stents of Hood or Dumont type were inserted in 27 patients. RESULTS: Symptoms were relieved and FEV(1) increased in all patients (median 0.7 litres, range 0.1-1.8 litres, p < 0.0001). In 8 patients, stents had to be repositioned or reinserted, in 19 patients only one insertion and one removal procedure were necessary. One patient suffered a serious complication with haemorrhage and pneumonectomy, 3 patients had minor airway wall injuries resolving spontaneously. Six patients died with the stents from causes not related to the airway complications. Twenty-five stents could be removed after a median of 6 months (range 1-22) in 21 patients, and 22 airways remained patent. Median FEV(1) was 2.3 litres immediately after stent removal, and remained 2.3 litres after 24 months. CONCLUSION: Stenotic airway complications after lung transplantation can be successfully treated with silicone stents, which can ultimately be removed, leaving a patent airway.

Improvement in renal function after everolimus introduction and calcineurin inhibitor reduction in maintenance thoracic transplant recipients: the significance of baseline glomerular filtration rate.

BACKGROUND: The NOCTET (NOrdic Certican Trial in HEart and lung Transplantation) trial demonstrated that everolimus improves renal function in maintenance thoracic transplant (TTx) recipients. Nevertheless, introduction of everolimus is not recommended for patients with advanced renal failure. We evaluated NOCTET data to assess everolimus introduction amongst TTx recipients with advanced renal failure. METHODS: This 12-month multicenter Scandinavian study randomized 282 maintenance TTx recipients to everolimus introduction with calcineurin inhibitor (CNI) reduction or standard CNI therapy. The measured glomerular filtration rate (mGFR) was noted at baseline and after 1-year using Cr-ethylenediaminetetraacetic acid clearance. RESULTS: In 21 patients with a baseline mGFR of 20 to 29 ml/min/1.73 m(2), renal function improved in the everolimus group compared with the control group ((ΔmGFR 6.7 ± 9.0 vs -1.6 ± 5.1 ml/min/1.73 m(2); p = 0.03). Amongst 173 patients with moderate renal impairment (mGFR 30-59 ml/min/1.73 m(2)), renal function improvement was also greater amongst everolimus patients than in controls (ΔmGFR 5.1 ± 11.1 vs -0.5 ± 8.7 ml/min/1.73 m(2); p < 0.01). In 55 patients with mGFR 60 to 89 ml/min/1.73 m(2), mGFR did not change significantly in either group. Improvement in mGFR was limited to patients with a median time since TTx of less than 4.6 years and was also influenced by CNI reduction during the study period. CONCLUSIONS: Everolimus introduction and reduced CNI significantly improved renal function amongst maintenance TTx patients with pre-existing advanced renal failure. This beneficial effect was limited to patients undergoing conversion in less than 5 years after TTx, indicating a window of opportunity that is appropriate for pharmacologic intervention with everolimus.

Pregnancy in heart- and heart/lung recipients can be problematic.

OBJECTIVE: The first successful pregnancy after heart transplantation was reported in 1988. Worldwide experience with heart and heart/lung transplanted (H-HLTx) pregnant women is limited. To expand this knowledge the collaborating Nordic thoracic transplant centers wanted to collect information on all such pregnancies from their centers. DESIGN: Information was retrospectively collected on all H-HLTx pregnancies in the Nordic countries. RESULTS: A total of 25 women have had 42 pregnancies and all survived the gestation. Minor complications were increasing incidence of proteinuria, hypertension and diabetes. Major problems were two rejections (early post partum), two severe renal failures, seven pre-eclampsias and 17 abortions. Five women died two to 12 years after delivery. Of 25 live born children, one was born with cancer and one died early after inheriting the mother's cardiomyopathy. CONCLUSION: Pregnancy after H-HLTx can be successful for both mother and child. There are, however, many obstacles which should be addressed. Respecting the couple's desire for children the attitude should be carefully, not too optimistic, after proper pre-pregnant information and counseling. Delivery should preferably take place at the transplant center.

Disturbed energy metabolism after lung and heart transplantation.

Overweight, in combination with other cardiovascular risk factors, reduces survival after transplantation. The aim of this prospective study was to observe leptin, adiponectin, and energy intake as predictors of body mass index (BMI) and body composition and as risk factors associated with metabolic syndrome after lung and heart transplantation. After pre-operative baseline investigations, 35 lung and 59 heart recipients were followed and re-investigated two, six, and 12 months after transplantation. Linear regressions were performed to predict BMI and body composition. The lung recipients had a substantial weight gain after transplantation. Leptin increased, especially in the lung recipients and positively predicted BMI. Energy intake predicted BMI before and at two months after transplantation, but not after 12 months. Percentage trunk fat increased and lean mass decreased. Before transplantation, the dominant determinant of lean mass was adiponectin (positively associated), while after it was leptin (negatively associated), controlled for possible confounding variables (including prednisolone). Metabolic syndrome 12 months after transplantation was associated with higher leptin, greater weight gain without increased energy intake. After transplantation, a disturbed energy metabolism is indicated, where adiponectin and especially leptin are involved and a disadvantageous body composition is favored with increased body fat and decreased lean mass.

Two-year outcomes in thoracic transplant recipients after conversion to everolimus with reduced calcineurin inhibitor within a multicenter, open-label, randomized trial.

BACKGROUND: Use of the mammalian target of rapamycin inhibitor everolimus with an accompanying reduction in calcineurin inhibitor (CNI) exposure has shown promise in preserving renal function in maintenance thoracic transplant patients, but robust, long-term data are required. METHODS: In a prospective, open-label, multicenter study, thoracic transplant recipients more than or equal to 1 year posttransplant with mild-to-moderate renal insufficiency were randomized to continue their current CNI-based immunosuppression or convert to everolimus with predefined CNI exposure reduction. After a 12-month core trial, patients were followed up to month 24 after randomization. RESULTS: Of 245 patients who completed the month 12 visit, 235 patients (108 everolimus and 127 controls) entered the 12-month extension phase. At month 24, mean measured glomerular filtration rate had increased by 3.2±12.3 mL/min from the point of randomization in everolimus-treated patients and decreased by 2.4±9.0 mL/min in controls (P<0.001), a difference that was significant within both the heart and lung transplant subpopulations. During months 12 to 24, 5.6% of everolimus patients and 3.1% of controls experienced biopsy-proven acute rejection (P=0.76). There were no significant differences in the rate of adverse events or serious adverse events (including pneumonia) between groups during months 12 to 24. CONCLUSIONS: Converting maintenance thoracic transplant recipients to everolimus with low-exposure CNI results in a renal benefit that is sustained to 2 years postconversion, with significantly improved measured glomerular filtration rate in both heart and lung transplant patients. Despite reductions of more than 50% in CNI exposure, there was no marked loss of efficacy. The safety profile of the everolimus-based regimen was acceptable.

Osteoporosis is a prevalent finding in patients with solid organ failure awaiting transplantation - a population based study.

Post-transplant bone disease is common in solid organ recipients; however, there is limited information on their pre-transplant bone status. We aimed to compare bone mineral density (BMD) in different categories of patients with end-stage organ failure awaiting transplantation (Tx) in Norway. Overall 291 adult patients were enrolled, including 60, 84, 81 and 66 patients with end-stage lung, liver, kidney and heart failure, respectively. Mean age was 51 ± 12 yr with no significant differences between the groups. We measured BMD in lumbar spine, femur, proximal one third and ultra-distal radius by dual energy X-ray absorptiometry. Differences in T- and Z-scores between the groups were compared by ANOVA. Low bone mass was found in all four groups of patients. Both T- and Z-scores differed (p < 0.05) at all measured sites between the groups. Patients with lung failure had the highest prevalence of osteoporosis (67%) and lowest Z-scores, followed by patients with liver (31%), kidney (24%), and heart (23%) failure. Osteoporosis is prevalent in all groups of organ transplant candidates, and poor bone health is remarkably pronounced in patients with chronic lung disease. General practitioners and specialists who care for these patients before they are referred for transplantation should consider measures to prevent osteoporosis at an earlier stage.

Dietary vitamin K2 supplement improves bone status after lung and heart transplantation.

BACKGROUND: Osteoporosis is a problem after transplantation. Studies since the last year indicate that vitamin K plays a role in optimal bone health. The aim of this randomized, double blind, prospective longitudinal study was to investigate the effect of a dietary supplement with vitamin K2 (180 microg menakinon-7) on bone mass, the first year after lung and heart transplantation. METHODS: After preoperative baseline investigation of bone mass and bone-related biochemistry, 35 lung and 59 heart recipients were postoperatively randomized to vitamin K2 or placebo and reinvestigated the following year. RESULTS: In all recipients, 1 year after solid organ transplantation, the difference between vitamin K2 and placebo for the lumbar spine (L2-L4) bone mineral density (BMD) was 0.028 (SE 0.014) g/cm(2), P=0.055 and for L2 to L4 bone mineral content was 1.33 (SE 1.91) g/cm(2) (P=0.5). In lung recipients separately, the difference for bone mineral content was 3.39 g (SE 1.65), P=0.048 and in heart recipients 0.45 (SE 0.02) g, P=0.9 after controlling for baseline measures. In a forward stepwise linear regression analysis fitted to model differences in the L2 to L4 BMD, controlled for possible confounding variables (including use of bisphosphonate), and the only significant predictors were organ (B=-0.065 g/cm(2), P<0.001) and vitamin K2 (B=0.034 g/cm(2), P=0.019). Insufficient vitamin D status was common, and the parathyroid hormone was highest in the K2 group indicating a higher need for vitamin D. CONCLUSIONS: One year of vitamin K2 supplement suggest a favorable effect on lumbar spine BMD with different response in lung and heart recipients. Vitamin D status should receive more attention.

Everolimus with reduced calcineurin inhibitor in thoracic transplant recipients with renal dysfunction: a multicenter, randomized trial.

BACKGROUND: The proliferation signal inhibitor everolimus offers the potential to reduce calcineurin inhibitor (CNI) exposure and alleviate CNI-related nephrotoxicity. Randomized trials in maintenance thoracic transplant patients are lacking. METHODS: In a 12-month, open-labeled, multicenter study, maintenance thoracic transplant patients (glomerular filtration rate > or =20 mL/min/1.73m and <90 mL/min/1.73 m) >1 year posttransplant were randomized to continue their current CNI-based immunosuppression or start everolimus with predefined CNI exposure reduction. RESULTS: Two hundred eighty-two patients were randomized (140 everolimus, 142 controls; 190 heart, 92 lung transplants). From baseline to month 12, mean cyclosporine and tacrolimus trough levels in the everolimus cohort decreased by 57% and 56%, respectively. The primary endpoint, mean change in measured glomerular filtration rate from baseline to month 12, was 4.6 mL/min with everolimus and -0.5 mL/min in controls (P<0.0001). Everolimus-treated heart and lung transplant patients in the lowest tertile for time posttransplant exhibited mean increases of 7.8 mL/min and 4.9 mL/min, respectively. Biopsy-proven treated acute rejection occurred in six everolimus and four control heart transplant patients (P=0.54). In total, 138 everolimus patients (98.6%) and 127 control patients (89.4%) experienced one or more adverse event (P=0.002). Serious adverse events occurred in 66 everolimus patients (46.8%) and 44 controls (31.0%) (P=0.02). CONCLUSION: Introduction of everolimus with CNI reduction offers a significant improvement in renal function in maintenance heart and lung transplant recipients. The greatest benefit is observed in patients with a shorter time since transplantation.

Endurance or resistance training in primary care after in-patient rehabilitation for COPD?

Resistance (RT) and endurance training (ET) prescribed by a rehabilitation centre and carried out under the supervision of primary care physiotherapists after the completion of 4 weeks of multidisciplinary in-patient pulmonary rehabilitation (IPR) were compared regarding capacity to induce further health effects. After IPR, 40 chronic obstructive pulmonary disease (COPD) patients were allocated to RT or ET twice weekly for 12 weeks. Primary outcome variables were walking capacity (treadmill endurance time, TET; 6-min walking distance, 6MWD), functional status (Glittre ADL-test; Hyrim Physical Activity Questionnaire) and health-related quality of life (HRQOL) (St. George's Respiratory Questionnaire, SGRQ). Body functions variables were included as secondary outcome measures. HRQOL and physical activity were reinvestigated after 1 year. Median attendance rates were not different between RT (21, interquartile range [17;23]) and ET (22 [18;24]). Both groups improved in TET (RT 7.7 min 95% CI {3.6;12}, ET 5.7 min {1.7;9.8}). 6MWD increased significantly after ET (46 m {20;72}). Functional status was unchanged. SGRQ tended to further improve after RT (-3.2{-7.4;1.2}), while ET maintained the improvement gained during IPR. Body functions measures changed according to training modality. After 1 year, a majority of patients in both groups were exercising regularly, but SGRQ was significantly better than pre-IPR only in the RT group (-7.9{-14.3;-1.5}). We conclude that supervised RT or ET twice weekly sustains and improves the effects of IPR. With no large differences detected between the two training modalities, the choice of training may be guided by individual needs, patient preferences and the availability of equipment.

Lung transplantation in patients with chronic obstructive pulmonary disease in a national cohort is without obvious survival benefit.

BACKGROUND: The objective in lung transplantation is to prolong life, but the survival effect in patients with chronic obstructive pulmonary disease (COPD) or alpha1-anti-trypsin deficiency emphysema is still unresolved. This study assesses the impact of diagnosis, single-lung transplantation (SLT) vs bilateral lung transplantation (BLT) and timing of transplantation on survival in a national cohort. METHODS: In 219 consecutive patients accepted onto the lung transplantation waiting list in Norway, 1990 to 2003, we assessed predictors of death: (1) on the waiting list; (2) 90 days after transplantation. For each period we used Cox regression, including age, gender, diagnosis, baseline pulmonary function tests, cardiac catheterization data, exercise capacity and transplant type, as potential predictors. Survival benefit was assessed graphically by combining adjusted survival curves after transplantation with the curve for those waiting, modeling transplantation after 6, 12 or 24 months. RESULTS: Mean patient age was 49 years (SD 10), with 55% women. High forced expiratory volume in 1 second (FEV(1)) percentage predicted death on the waiting list. Diagnoses other than COPD/emphysema and receiving SLT were associated with death 90 days after transplantation. In COPD/emphysema, there was no clear survival benefit from BLT or SLT. For patients in the "Other" group, the data suggest a survival benefit from BLT. CONCLUSIONS: In COPD/emphysema, there was no obvious survival benefit from lung transplantation, which questions prolongation of life as the primary motivation for the procedure.

Performance of long-term CT monitoring in diagnosing bronchiolitis obliterans after lung transplantation.

AIM: The purpose of the study was to evaluate the ability of CT, including expiratory scans with minimum intensity projection in predicting the development of bronchiolitis obliterans syndrome after lung transplantation. MATERIALS AND METHODS: Forty consecutive patients, 29 bilateral and 11 single lung transplanted, were followed-up with regular scans for a median of 36 months. Air trapping was evaluated on expiratory scans constructed from two short spiral scans with minimum intensity projection-technique, one at the level of the carina and the other midway between the right diaphragm and the carina. Air trapping was scored on a 16-point scale. Bronchiolitis obliterans syndrome was diagnosed according to established clinical criteria and quantified spirometrically. RESULTS: Bronchiolitis obliterans syndrome developed in 17 patients (43%) after a median of 12 months. Air trapping and bronchiectasis was seen before the diagnosis of bronchiolitis obliterans syndrome in only two and one patient, respectively. Interobserver agreement for air trapping score was good (kappa = 0.65). Air trapping scores performed significantly better than that achieved by chance alone in determining the presence of bronchiolitis obliterans syndrome (P = 0.0025). An air trapping score of 4 or more provided the best results with regard to sensitivity and specificity in diagnosing bronchiolitis obliterans syndrome. The sensitivity, specificity, positive and negative predictive values of an air trapping of 4 or more in the diagnosis of bronchiolitis obliterans syndrome were 77, 74, 68 and 81%, respectively. CONCLUSION: Expiratory CT scans with minimum intensity projection-reconstruction did not predict the development of bronchiolitis obliterans syndrome in most patients. The findings seriously limit the clinical usefulness of long-term CT monitoring for diagnosing bronchiolitis obliterans syndrome after lung transplantation.

A field test of functional status as performance of activities of daily living in COPD patients.

Patients with chronic obstructive pulmonary disease (COPD) frequently experience activity restrictions and discomfort during activities of daily living (ADL). Functional status refers to the capacity to perform ADL. Available tests only partly measure this domain. Our aim was therefore to establish an assessment tool for functional status in COPD, the Glittre ADL-test. This field test includes a standardised set of ADL-like activities: Walking stairs, carrying, lifting objects, bending down and rising from a seated position. The primary variable was time to complete the test (ADL-time). Validity was investigated in 57 COPD patients by correlating ADL-time to pulmonary function, 6-min walking distance (6MWD) and questionnaires addressing health-related quality of life. Responsiveness was investigated in another 40 patients comparing ADL-time before and after rehabilitation. Median ADL-time was 4.16 min (range 2.57-14.47). Spearman rho=0.93 for test-retest reliability. ADL-time correlated with forced expiratory volume in 1s (rho=-0.61), St. George's Respiratory Questionnaire activity subscore (rho=0.43), dyspnoea during ADL (rho=0.35) and hospitalisation rate (rho=0.35). Despite a close overall correlation with 6MWD (rho=-0.82), variability was substantial, particularly for the more disabled patients. ADL-time improved significantly after rehabilitation. Glittre ADL-test yields information complementary to 6MWD. It is a valid and reliable measure of functional status, useful for assessment of individual patients and rehabilitation programs.

The influence of underweight and dietary support on well-being in lung transplant candidates.

BACKGROUND: Quality of life has been found to be a significant predictor of survival in lung transplantation candidates. The aim of this study was to investigate associations between underweight, dietary support and well-being. METHODS: A self-administered questionnaire for perceived well-being was administered to underweight (n=42) and normal-weight (n=29) candidates for lung transplantation before and after dietary intervention in which the underweight patients received dietary support for weight gain. RESULTS: Underweight compared with normal-weight, independent of lung function, was associated with low well-being in several of the measured dimensions. Improvements were observed after dietary intervention compared with baseline in the underweight patients, for scores in the dimension of tiredness 29.2 (4.2) vs. 26.2 (6.0), P<0.01; general satisfaction 4.7 (1.5) vs. 4.0 (1.4), P=0.01; social life 16.7 (3.9) vs. 15.0 (4.4), P=0.02) (mean (sd) before and after dietary intervention respectively), but not in the normal-weight patients. The underweight patients achieved the goal for energy intake and protein intake and experienced a significant weight gain. Regression analyses showed that none of the well-being improvements was associated with weight gain or change in body composition. However, an association between less tiredness and an increase in protein intake was indicated (b=-0.305, P=0.055). CONCLUSION: Underweight compared with normal-weight was associated with more impaired quality of life in candidates for lung transplantation and some benefit from dietary support in terms of well-being was indicated.