| 1. |
- Scherstén, Henrik, 1956, et al.
(författare)
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Increased levels of endothelin-1 in bronchoalveolar lavage fluid of patients with lung allografts
- 1996
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Ingår i: J Thorac Cardiovasc Surg. - 0022-5223. ; 111:1, s. 253-8
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study was to determine levels of endothelin-1 in bronchoalveolar lavage fluid and in plasma in patients with lung and heart-lung allografts. The aim was based on the hypothesis that levels of endothelin-1 are elevated in the bronchoalveolar lavage fluid of patients with lung allografts. Patients (n = 23) undergoing heart-lung (n = 8), single-lung (n = 10), or bilateral lung (n = 5) transplantation were included in the study. In patients with single-lung allografts, endothelin-1 levels were analyzed in bronchoalveolar lavage fluid from both the transplanted and the nontransplanted, native lung. The level of endothelin-1 was also analyzed in bronchoalveolar lavage fluid from 12 patients who did not undergo transplantation. Transbronchial biopsies and bronchoalveolar lavage were done routinely or when clinically indicated on 64 different occasions, between 2 and 104 weeks after transplantation. The level of endothelin-1 was measured in bronchoalveolar lavage fluid and plasma by radioimmunoassay. Immunoreactive endothelin-1 was detectable in bronchoalveolar lavage fluid from all patients. The concentration of endothelin-1 in bronchoalveolar lavage fluid from transplanted lungs (2.94 +/- 0.30 pg/ml, n = 64) was significantly higher compared with that in bronchoalveolar lavage fluid from patients without allografts (0.86 +/- 0.20 pg/ml, n = 12, p < 0.01). In patients who received single-lung transplantation because of emphysema, the level of endothelin-1 in bronchoalveolar lavage fluid from the transplanted lung was significantly greater than that from the native lung (5.61 +/- 1.9 versus 0.39 +/- 0.05 pg/ml, p < 0.05). Concentrations of endothelin-1 in bronchoalveolar lavage fluid did not correlate with grade of rejection, infection, or time after transplant. Plasma levels of endothelin-1 were unchanged with pulmonary rejection. These results indicate that endothelin-1 is released into bronchi of transplanted human lungs. The release is not associated with rejection or infection. Because of its potent mitogenic properties, endothelin-1 may have a potential impact in the development of posttransplant complications such as bronchiolitis obliterans.
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| 2. |
- Albertsson-Wikland, Kerstin, 1947, et al.
(författare)
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Mortality is not increased in rhGH-treated patients when adjusting for birth characteristics.
- 2016
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 101:5, s. 2149-2159
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This study aimed to investigate whether reported high mortality in childhood recombinant human GH (rhGH)-treated patients was related to birth-characteristics and/or rhGH treatment. Design and Setting: We sought to develop a mortality model of the Swedish general population born between 1973 and 2010, using continuous-hazard functions adjusting for birth characteristics, sex, age intervals, and calendar year to estimate standardized mortality ratio (SMR) and to apply this model to assess expected deaths in Swedish rhGH-treated patients with idiopathic isolated GH deficiency (IGHD), idiopathic short stature (155) or born small for gestational age (SGA). Participants:The general population: Swedish Medical Birth Register (1973-2010: 1 880 668 males; 1 781 131 females) and Cause of Death Register (1985-2010). Intervention Population: Three thousand eight hundred forty-seven patients starting rhGH treatment between 1985 and 2010 and followed in the National GH Register and/or in rhGH trials diagnosed with IGHD (n = 1890), ISS (n = 975), or SGA (n=982). Main Outcome Measures: Death. Results: Using conventional models adjusting for age, sex, and calendar-year, the SMR was 1.43 (95% confidence interval, 0.89-2.19), P = .14, observed/expected deaths 21/14.68. The rhGH population differed (P < .001) from the general population regarding birth weight, birth length, and congenital malformations. Application of an Advanced Model: When applying the developed mortality model of the general population, the ratio of observed/expected deaths in rhGH-treated patients was 21/21.99; SMR = 0.955 (0.591-1.456)P = .95. Model Comparison: Expected number of deaths were 14.68 (14.35-14.96) using the conventional model, and 21.99 (21.24-22.81) using the advanced model, P < .001, which had at all ages a higher gradient of risk per SD of the model, 24% (range, 18-42%; P < .001). Conclusions: Compared with the general Swedish population, the ratio of observed/expected deaths (21/21.99) was not increased in childhood rhGH-treated IGHD, ISS, and SGA patients when applying an advanced sex-specific mortality model adjusting for birth characteristics.
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| 3. |
- Aldred, M. A., et al.
(författare)
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BMPR2 gene rearrangements account for a significant proportion of mutations in familial and idiopathic pulmonary arterial hypertension
- 2006
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Ingår i: Hum Mutat.. ; 27:2
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Tidskriftsartikel (refereegranskat)abstract
- Mutations of the BMPR2 gene predispose to pulmonary arterial hypertension (PAH), a serious, progressive disease of the pulmonary vascular system. However, despite the fact that most PAH families are consistent with linkage to the BMPR2 locus, sequencing only identifies mutations in some 55% of familial cases and between 10% and 40% of cases without a family history (idiopathic or IPAH). We therefore conducted a systematic analysis for larger gene rearrangements in panels of both familial and idiopathic PAH cases that were negative on sequencing of coding regions. Analysis of exon dosage across the entire gene using Multiplex Ligation-dependent Probe Amplification identified nine novel rearrangements and enabled full characterization at the exon level of previously reported deletions. Overall, BMPR2 rearrangements were identified in 7 of 58 families and 6 of 126 IPAH cases, suggesting that gross rearrangements underlie around 12% of all FPAH cases and 5% of IPAH. Importantly, two deletions encompassed all functional protein domains and are predicted to result in null mutations, providing the strongest support yet that the predominant molecular mechanism for disease predisposition is haploinsufficiency. Dosage analysis should now be considered an integral of part of the molecular work-up of PAH patients. (c) 2006 Wiley-Liss, Inc.
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| 4. |
- Johansson, Inger, 1953, et al.
(författare)
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Lower incidence of CMV infection and acute rejections with valganciclovir
- 2013
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Ingår i: BMC Infectious Diseases. - : Springer Science and Business Media LLC. - 1471-2334. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background Cytomegalovirus (CMV) is the most common opportunistic infection following lung transplantation. CMV replication in the lung allograft is described as accelerating the development of bronchiolitis obliterans syndrome (BOS).Finding a strategy to prevent CMV infection is an important issue. Methods We performed a retrospective, single-centre study of 114 lung transplant recipients (LTRs) who underwent lung transplantation from January 2001 to December 2006. In a smaller cohort of 88 CMV seropositive (R+) LTRs, three months of valganciclovir prophylaxis (2004-2006) was compared to three months of oral ganciclovir (2001-2003) with respect to the incidence of CMV infection/disease, the severity of CMV disease, acute rejection, BOS-free 4 year survival and 4 year survival. In the whole group of 114 LTRs the impact of CMV infection on long-term survival (BOS free 4 year survival and 6 year survival) was assessed. Results For the cohort of 88 CMV seropositive LTRs, the incidence of CMV infection/disease at one year was lower in the valganciclovir group compared to the ganciclovir group (24% vs. 54%, p = 0.003). There was a tendency towards reduced CMV disease, from 33% to 20% and a significant lower incidence of asymptomatic CMV infection (22% vs. 4%, p = 0.005). A lower incidence of acute rejection was observed in the valganciclovir group. However, there was no significant difference between the two groups in BOS free 4 year survival and 4 year survival. For the entire group of 114 LTRs, BOS-free 4 year survival for recipients with CMV disease was (32%, p = 0.005) and among those with asymptomatic CMV infection (36%, p = 0.061) as compared with patients without CMV infection (69%). Six year survival was lower among patients with CMV disease, (64%, p = 0.042) and asymptomatic CMV infection (55%, p = 0.018) than patients without CMV infection (84%). Conclusions A lower incidence of CMV infection/disease and acute rejections was observed with valganciclovir (3 months) when compared to oral ganciclovir (3 months). The long-term impact of CMV infection/disease was significant for BOS-free survival and survival.
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| 5. |
- Johansson, Åke, 1955, et al.
(författare)
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Detection of chronic rejection by quantitative ventilation scintigrams in lung-transplanted patients: a pilot study
- 2005
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Ingår i: Clin Physiol Funct Imaging. ; 25:3
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Tidskriftsartikel (refereegranskat)abstract
- Summary The suspicion of chronic rejection [bronchiolithis obliterans syndrome (BOS)] is usually based on deteriorating forced expired volume in 1 s. It is however, desirable to develop more sensitive methods as increased anti-inflammatory therapy is thought to stop progression of the rejection. The aim of the present study was to develop quantitative tools based on ventilation scintigrams, to diagnose BOS. Sixteen double-lung-transplanted patients participated, six developing BOS and 10 who did not develop BOS. They were investigated with planar posterior-anterior (99m)Tc-Technegas (Tetley Manufacturing Ltd, Sydney, Australia) ventilation scintigraphy at baseline, 6 months to 1 year post-transplantation, and at a follow-up examination 3-4-year post-transplant or in the BOS patients close to the time of the diagnosis. An automatic region of interest (ROI) was drawn on each lung in the scintigraphic image at baseline and also applied to the follow-up investigation. The area inside the ROI was subdivided into stripes 10.8 mm high and squares 10.8 x 10.8 mm wide. Corresponding stripes and squares in baseline and follow-up were analysed regarding differences in relative retention. The results show that the square analysis is superior. Applying chosen cut-off values for square element differences, 6/6 right and 5/6 left BOS lungs were identified and one left and one right lung of patients not developing BOS were misclassified. We conclude that the square element difference appears to be a promising method to diagnose BOS.
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| 6. |
- Johanssson, Inger, et al.
(författare)
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Cytomegalovirus and long-term outcome after lung transplantation in Gothenburg, Sweden.
- 2010
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Ingår i: Scandinavian journal of infectious diseases. - : Informa UK Limited. - 1651-1980 .- 0036-5548. ; 42:2, s. 129-36
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Tidskriftsartikel (refereegranskat)abstract
- Prophylaxis with ganciclovir has decreased the initially high morbidity related to cytomegalovirus (CMV) after lung transplantation, but the optimal length of prophylaxis and the long-term outcome have not yet been established. The impact of CMV on the short- and long-term outcome was studied in 187 lung transplant recipients in Gothenburg, Sweden, 1990-2002. Among CMV-seronegative patients receiving grafts from seropositive donors (D+/R-), 88% developed CMV disease, 40% if both donor and recipient were CMV-seropositive (D+/R+) and 26% if only the recipient was CMV-seropositive (D-/R+). Among CMV-seropositive recipients (R+) on oral acyclovir prophylaxis, 38% developed CMV disease, as compared with 39% on intravenous ganciclovir for 4 weeks and 28% on oral ganciclovir for 14 weeks. On average, CMV disease appeared at 41 days in the R+ on acyclovir prophylaxis, at 75 days on 4 weeks of i.v. ganciclovir and at 162 days on 14 weeks of oral ganciclovir. CMV disease was associated with a statistically significant increased risk of developing chronic rejection (bronchiolitis obliterans syndrome) at both 1 and 2 y after transplantation. CMV disease also had a significant negative impact on survival, with a 10-y survival of only 32% as compared with 53% after asymptomatic CMV infection and 57% with no CMV.
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| 7. |
- Riise, Gerdt C., 1956, et al.
(författare)
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Inflammatory cells and activation markers in BAL during acute rejection and infection in lung transplant recipients: a prospective, longitudinal study
- 1997
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Ingår i: Eur Respir J. - 0903-1936. ; 10:8, s. 1742-6
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Tidskriftsartikel (refereegranskat)abstract
- Acute rejection of the transplanted lung is a clinical problem, since it decreases graft survival and predisposes the patient to chronic rejection and obliterative bronchiolitis (OB). In an earlier study, we had indications that eosinophil cationic protein (ECP) from activated eosinophils and hyaluronan (HYA) from fibroblasts were associated with acute pulmonary rejection. This prospective longitudinal study was designed to investigate whether molecules from activated inflammatory cells in bronchoalveolar lavage (BAL) fluid could serve as clinically useful diagnostic markers for acute rejection. BAL fluid from 138 bronchoscopies performed in 10 single lung, four bilateral lung and five heart-lung transplant recipients were analysed. Nine patients were studied for a period of more than 1 yr (mean 13.4 months) after surgery. Differential cell counts were made from the BAL fluid. ECP, myeloperoxidase (MPO), HYA and interleukin-8 (IL-8) were used as indirect markers for activation and attraction of eosinophils, neutrophils and fibroblasts, respectively. Fifty four episodes of acute rejection were diagnosed. Two patients developed OB. Nine episodes of bacterial infection, 13 episodes of cytomegalovirus (CMV) pneumonitis, three of Pneumocystis carinii infection and one of respiratory syncytial virus (RSV) infection were diagnosed. The mean levels of ECP, MPO, HYA and IL-8 were all higher during rejection episodes, but differences were not statistically significant compared to no rejection, when the confounding factors of time, concomitant infection, and repeated measures in the same individual had been accounted for. We could not confirm that measurements of eosinophil cationic protein, myeloperoxidase, hyaluronan and interleukin-8 in bronchoalveolar lavage fluid can be used as diagnostic markers for acute rejection in the postoperative follow-up of lung transplant recipients.
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| 8. |
- Riise, Gerdt C., 1956, et al.
(författare)
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Persistent high BAL fluid granulocyte activation marker levels as early indicators of bronchiolitis obliterans after lung transplant
- 1999
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Ingår i: Eur Respir J. - 0903-1936. ; 14:5, s. 1123-30
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Tidskriftsartikel (refereegranskat)abstract
- The major cause of mortality in the long-term in lung transplant recipients is chronic rejection. This is a fibroproliferative process in the small airways leading to obliterative bronchiolitis and progressive loss of lung function, both constituting the clinical entity bronchiolitis obliterans syndrome (BOS). Granulocyte activation has been implicated as one factor behind BOS. Granulocyte markers in bronchoalveolar lavage (BAL) fluid were prospectively and longitudinally studied in order to identify possible association with BOS. BAL fluid from 266 bronchoscopy procedures performed in twelve single lung, eight bilateral lung and five heart/lung transplant recipients were analysed. The majority (19 of 25) were studied for a period of 2 yrs after surgery. Myeloperoxidase (MPO), eosinophil cationic protein (ECP) and interleukin-8 (IL-8) levels were used as indirect markers of activation and attraction of granulocytes. Five patients developed BOS. Ninety-eight episodes of acute rejection, nine of bacterial infection, 19 of cytomegalovirus pneumonitis, nine of Pneumocystis carinii infection, two of aspergillus infection and two of respiratory syncytial virus infection were diagnosed. BOS patients had significantly higher mean levels of MPO, ECP and IL-8 compared to patients without BOS, irrespective of acute rejection status. Over time, the five patients with BOS had significantly elevated BAL fluid levels of MPO and ECP as well as neutrophil percentages, and in four patients this increase preceded the clinical diagnosis of BOS by several months. Elevated bronchoalveolar lavage fluid neutrophil percentage as well as levels of the granulocyte activation markers myeloperoxidase and eosinophil cationic protein appear to be early signs of development of BOS in lung transplant recipients.
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| 9. |
- Riise, Gerdt C., 1956, et al.
(författare)
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Prediction of BOS by the single-breath nitrogen test in double lung transplant recipients.
- 2011
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Ingår i: BMC research notes. - : Springer Science and Business Media LLC. - 1756-0500. ; 4:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The present study analyses the ability of the alveolar slope of the single-breath nitrogen washout test (N2-slope) to diagnose and predict the development of the bronchiolitis obliterans syndrome (BOS). METHODS: We present a retrospective analysis of 61 consecutive bilateral lung or heart-lung transplant recipients who were followed at regular control visits during a three year follow-up. The operating characteristics of the N2-slope to diagnose BOS and potential BOS (BOS 0-p) and to predict BOS were determined based on cut off values of 95% specificity. RESULTS: The sensitivity of the N2-slope to identify BOS was 96%, and BOS 0-p 100%. The predictive ability to predict BOS with a N2-slope > 478% of the predicted normal was 56%, and if combined with a coincident FEV1 < 90% of the basal value, the predictive ability was 75%. CONCLUSIONS: The predictive ability of either the N2-slope or of FEV1 to diagnose BOS is limited but the combination of the two appears useful. Follow-up protocols of bilateral lung and heart-lung transplant recipients should consider including tests sensitive to obstruction of the peripheral airways.
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| 10. |
- Silverborn, Martin, 1969, et al.
(författare)
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New-onset cardiovascular risk factors in lung transplant recipients
- 2005
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Ingår i: J Heart Lung Transplant. ; 24:10
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cardiovascular disease (CVD) is a common cause of morbidity and mortality after solid-organ transplantation. Both pre-existing cardiovascular risk factors in recipients and immunosuppressive drug toxicity may contribute to CVD. We sought to describe the prevalence of new-onset hypertension, hypercholesterolemia and diabetes mellitus in lung transplant recipients and to identify predisposing factors. METHODS: One hundred twenty-six patients without pre-transplant hypertension, hypercholesterolemia or diabetes were included in a retrospective descriptive study. All patients were initially on cyclosporine-based triple immunosuppression. Cumulative prevalence of new-onset hypertension, hypercholesterolemia and diabetes were calculated. A multivariate Cox regression model was used to identify independent pre-operative predictors. RESULTS: By 3 years after transplantation, 90% of patients had developed at least 1 cardiovascular risk factor and 40% developed > or = 2 risk factors. The cumulative prevalence of new-onset hypertension at 1, 3, 5 and 7 years was 45%, 65%, 67% and 72%, respectively. The corresponding prevalence for hypercholesterolemia was 16%, 33%, 48% and 58%, and for diabetes 6%, 7%, 7% and 10%, respectively. The independent pre-transplant predictors were: for hypertension, diastolic blood pressure (odds ratio: 2.1 per 10 mm Hg [95% confidence interval: 1.3 to 3.5], p = 0.005); for hypercholesterolemia, serum cholesterol level (OR: 1.8 per mmol/liter [95% CI: 1.3 to 2.5], p < 0.001); and, for diabetes, cystic fibrosis diagnosis (OR: 7.4 [95% CI: 1.6 to 35.6], p = 0.01) and blood glucose level (OR 2.2 per mmol/liter [95% CI 1.1 to 4.5], p = 0.02). CONCLUSIONS: The majority of cyclosporine-treated lung transplant recipients develop new-onset hypertension or hypercholesterolemia early after transplantation. Pre-transplant blood pressure, serum cholesterol levels and blood glucose levels are independent predictors of post-transplant hypertension, hypercholesterolemia and diabetes, respectively.
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