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Obliterans Syndrome (obliteran + syndrome)
Kinds of Obliterans Syndrome Selected AbstractsMedium-term outcome of fundoplication after lung transplantationDISEASES OF THE ESOPHAGUS, Issue 8 2009P. R. Burton SUMMARY Gastroesophageal reflux disease (GERD) in lung transplant recipients has gained increasing attention as a factor in allograft failure. There are few data on the impact of fundoplication on survival or lung function, and less on its effect on symptoms or quality of life. Patients undergoing fundoplication following lung transplantation from 1999 to 2005 were included in the study. Patient satisfaction, changes in GERD symptoms, and the presence of known side effects were assessed. The effect on lung function, body mass index, and rate of progression to the bronchiolitis obliterans syndrome (BOS) were recorded. Twenty-one patients (13 males), in whom reflux was confirmed on objective criteria, were included, with a mean age of 43 years (range 20,68). Time between transplantation and fundoplication was 768 days (range 145,1524). The indication for fundoplication was suspected microaspiration in 13 and symptoms of GERD in 8. There was one perioperative death, at day 17. There were three other late deaths. Fundoplication did not appear to affect progression to BOS stage 1, although it may have slowed progression to stage 2 and 3. Forced expiratory volume-1% predicted was 72.9 (20.9), 6 months prior to fundoplication and 70.4 (26.8), six months post-fundoplication, P= 0.33. Body mass index decreased significantly in the 6 months following fundoplication (23 kg/m2 vs. 21 kg/m2, P= 0.05). Patients were satisfied with the outcome of the fundoplication (mean satisfaction score 8.8 out of 10). Prevalence of GERD symptoms decreased significantly following surgery (11 of 14 vs. 4 of 17, P= 0.002). Fundoplication does not reverse any decline in lung function when performed at a late stage post-lung transplantation in patients with objectively confirmed GERD. It may, however, slow progression to the more advanced stages of BOS. Reflux symptoms are well controlled and patients are highly satisfied. Whether performing fundoplication early post-lung transplant in selected patients can prevent BOS and improve long-term outcomes requires formal evaluation. [source] Lung transplantation in patients with connective tissue disorders and esophageal dysmotilityDISEASES OF THE ESOPHAGUS, Issue 7 2008Warren J. Gasper SUMMARY., Lung and esophageal dysfunction are common in patients with connective tissue disease (CTD). Recent reports have suggested a link between pathologic gastroesophageal reflux and bronchiolitis obliterans syndrome (BOS) after lung transplant. Because patients with CTD have a high incidence of esophageal dysmotility and reflux, this group may be at increased risk of allograft dysfunction after lung transplantation. Little is known about antireflux surgery in these patients. Our aims were to describe: (i) the esophageal motility and reflux profile of patients with CTD referred for lung transplantation; and (ii) the safety and outcomes of laparoscopic fundoplication in this group. A retrospective review of 26 patients with CTD referred for lung transplantation between July 2003 and June 2007 at a single center. Esophageal studies included manometry and ambulatory 24-h pH monitoring. Twenty-three patients had esophageal manometry and ambulatory 24-h pH monitoring. Nineteen patients (83%) had pathologic distal reflux and 7 (30%) also had pathologic proximal reflux. Eighteen patients (78%) had impaired or absent peristalsis. Eleven of 26 patients underwent lung transplantation. Ten patients are alive at a median follow-up of 26 months (range 3,45) and one has bronchiolitis obliterans syndrome-1. Six patients had a laparoscopic fundoplication, 1 before transplantation and 5 after. All fundoplication patients are alive at median follow-up of 25 months (range 19,45). In conclusion, esophageal dysmotility and reflux are common in CTD patients referred for lung transplant. For this group, laparoscopic fundoplication is safe in experienced hands. [source] Proteomic identification of human neutrophil alpha-defensins in chronic lung allograft rejectionPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 6 2005Gary L. Nelsestuen Abstract Chronic allograft rejection remains a leading cause of morbidity and mortality in lung transplant recipients. Currently, diagnosis is based on lung biopsies or the presence of bronchiolitis obliterans syndrome (BOS). To identify a biomarker of rejection we performed a proteome survey of archived bronchoalveolar lavage fluid (BALF) acquired from lung transplant recipients between 1993 and 1996 using mass spectrometry (MS). A total of 126 BALF samples from 57 individuals were tested. Initial MS assessment revealed numerous differences in a majority of individuals who experienced BOS, but three unusually intense peaks at m/z,=,3373, 3444, and 3488. These were identified as human neutrophil peptides 1,3 (HNP). Quantification by enzyme-linked immunoabsorbent assay showed an elevated HNP level (>0.3,ng/µg protein) in 89% of patients who developed BOS2,3 within 15,months, reaching as high as 6% of the total BALF protein. In control patients, 35% demonstrated a slightly elevated HNP level that declined in all who had subsequent BALF available for testing. HNP levels did not correlate with episodes of acute rejection, cytomegalovirus or fungal infection. In conclusion, elevated HNP levels are associated with the onset of BOS and can predate the clinical onset of disease up to 15,months. [source] Obliterative bronchiolitis in lung allografts removed at retransplant for intractable airway problemsRESPIROLOGY, Issue 4 2009Olufemi AKINDIPE ABSTRACT Background and objective: The role of large airway ischaemia, with resultant airway narrowing, in the development of post-lung transplant bronchiolitis obliterans has not been defined. A determination of clinical bronchiolitis obliterans syndrome (BOS), which is defined as a decline in FEV1 from a stable post-transplant baseline, is difficult in the setting of airway complications. The aim of this study was to assess the evidence for histological bronchiolitis obliterans in lung allografts removed during retransplantation for severe recurrent airway narrowing. Methods: Case records and histological findings in allograft lungs removed at retransplantation were retrospectively reviewed. Results: Five lung transplant recipients, who had undergone retransplantation because of severe recalcitrant airway stenosis, were identified. In each case, explant allograft lung pathology revealed evidence of bronchiolitis obliterans. Conclusions: There is a possible link between airway ischaemia, large airway stenosis and the development of bronchiolitis obliterans, which is the most common cause of death in lung transplant recipients after the first year. These findings may provide an impetus for evaluation of the role of bronchial artery revascularization techniques in the prevention of bronchiolitis obliterans. [source] An Unwelcome Guest: Aspergillus Colonization in Lung Transplantation and Its Association with Bronchiolitis Obliterans SyndromeAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2009S. Garantziotis Aspergillus colonization may increase the risk for bronchiolitis obliterans syndrome after lung transplantation. See article by Weigt et al. on page 1903,1911. [source] Immunobiology of Chronic Lung Allograft Dysfunction: New Insights from the Bench and BeyondAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2009R. A. Shilling The first successful human lung transplants were performed in the 1980s. Since that time lung transplantation has been a therapeutic modality for end-stage pulmonary diseases. However, chronic rejection, known as obliterative bronchiolitis (OB)/bronchiolitis obliterans syndrome (BOS), is the key reason why the 5-year survival is only 50%, which is significantly worse than most other solid organ transplants. Recent studies have provided exciting advances that are beginning to be translated into findings in humans. This review will highlight the current advances in understanding the mechanisms of OB/BOS in lung transplant recipients. [source] Aspergillus Colonization of the Lung Allograft Is a Risk Factor for Bronchiolitis Obliterans SyndromeAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2009S. S. Weigt Multiple infections have been linked with the development of bronchiolitis obliterans syndrome (BOS) post-lung transplantation. Lung allograft airway colonization by Aspergillus species is common among lung transplant recipients. We hypothesized that Aspergillus colonization may promote the development of BOS and may decrease survival post-lung transplantation. We reviewed all lung transplant recipients transplanted in our center between January 2000 and June 2006. Bronchoscopy was performed according to a surveillance protocol and when clinically indicated. Aspergillus colonization was defined as a positive culture from bronchoalveolar lavage or two sputum cultures positive for the same Aspergillus species, in the absence of invasive pulmonary Aspergillosis. We found that Aspergillus colonization was strongly associated with BOS and BOS related mortality in Cox regression analyses. Aspergillus colonization typically preceded the development of BOS by a median of 261 days (95% CI 87,520). Furthermore, in a multivariate Cox regression model, Aspergillus colonization was a distinct risk factor for BOS, independent of acute rejection. These data suggest a potential causative role for Aspergillus colonization in the development of BOS post-lung transplantation and raise the possibility that strategies aimed to prevent Aspergillus colonization may help delay or reduce the incidence of BOS. [source] Targeting Allograft Injury and Inflammation in the Management of Post-Lung Transplant Bronchiolitis Obliterans SyndromeAMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2009A. G. N. Robertson Chronic allograft dysfunction, manifesting as bronchiolitis obliterans syndrome (BOS), is the major cause of morbidity and mortality in human lung transplant recipients. While alloimmunity has a definite role, there is increasing interest in overall allograft injury and subsequent inflammation and remodeling. This review deals with nonalloimmune factors that may potentiate alloimmune injury. We discuss infection and reflux/aspiration as examples of allograft injury, which may lead to chronic loss of graft function and BOS. Surgical and nonsurgical treatments aimed at preventing these insults and improving survival are considered. The need for further evidence, including randomized-controlled trials, to evaluate the role of medical and surgical therapies is emphasized by the current literature. [source] Immunohistochemical Study of HLA-G Expression in Lung Transplant RecipientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2009O Brugičre Human leukocyte antigen-G (HLA-G), a nonclassical HLA class I protein, promotes immune tolerance of solid-organ allografts, yet its role in lung transplantation (LTx) is unknown. We examined the expression of HLA-G in lung allografts through immunohistochemistry by a cross-sectional study of 64 LTx recipients, classified into four groups (stable patients, acute rejection [AR], bronchiolitis obliterans syndrome [BOS] and symptomatic viral shedders). A marked expression of HLA-G in bronchial epithelial cells (BEC) was frequently observed in stable recipients (n = 18/35 [51%]), but not in patients with AR (n = 14) or with BOS (n = 8). HLA-G was also expressed by 4 of 7 symptomatic viral shedders. In addition, HLA-G-positive patients from the stable group (n = 35) experienced lower incidence of resistant AR and/or BOS during long-term follow-up, as compared with their HLA-G-negative counterparts. Finally, in vitro data showed that interferon-,, a cytokine present in lung allograft microenvironment, upregulated HLA-G mRNA and protein expression in primary cultured human BEC. We conclude that HLA-G expression in the bronchial epithelium of lung allograft is elevated in some LTx recipients in association with their functional stability, suggesting a potential role of HLA-G as a tolerance marker. [source] Posttransplant Bronchiolitis Obliterans Syndrome Is Associated with Bronchial Epithelial to Mesenchymal TransitionAMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2009S. Hodge Bronchiolitis obliterans syndrome (BOS) compromises lung transplant outcomes and is characterised by airway epithelial damage and fibrosis. The process whereby the normal epithelial configuration is replaced by fibroblastic scar tissue is poorly understood, but recent studies have implicated epithelial mesenchymal transition (EMT). The primary aim of this study was to assess the utility of flow cytometry in detecting and quantifying EMT in bronchial epithelial cells. Large airway brushings were obtained at 33 bronchoscopies in 16 BOS-free and 6 BOS grade 1,3 patients at 2,120 months posttransplant. Flow cytometry was used to assess expression of the mesenchymal markers ,SMA, S100A4 and ED-A FN and HLA-DR. TGF ,1 and HGF were measured in Bronchoalveolar lavage (BAL). Expression of all three mesenchymal markers was increased in BOS, as was HLA-DR. BAL HGF, but not TGF ,1 was increased in BOS. Longitudinal investigation of one patient revealed a 100% increase in EMT markers concurrent with a 6-fold increase in BAL TGF ,1 and the diagnosis of BOS at 17 months posttransplant. Flow cytometric evaluation of bronchial epithelium may provide a novel and rapid means to assess lung allografts at risk of BOS. [source] Follicular Bronchiolitis: A Rare Cause of Bronchiolitis Obliterans Syndrome After Lung Transplantation: A Case ReportAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2009R. Vos This case report is the first confirmed case of follicular bronchiolitis (FB), a rare bronchiolar disorder characterized by peribronchiolar lymphoid follicles, in a series of over 400 lung transplantations performed in our center. It is to our knowledge, the first publication describing FB after lung transplantation (LTx), presenting as chronic allograft dysfunction or bronchiolitis obliterans syndrome (BOS). [source] Airway Epithelial Cell Senescence in the Lung AllograftAMERICAN JOURNAL OF TRANSPLANTATION, Issue 7 2008S. M. Parker Chronic lung allograft dysfunction, manifesting as bronchiolitis obliterans syndrome (BOS), is characterized by airway epithelial injury, impaired epithelial regeneration and subsequent airway remodeling. Increased cellular senescence has been reported in renal and liver allografts affected by chronic allograft dysfunction but the significance of cellular senescence in the airway epithelium of the transplanted lung is unknown. Thirty-four lung transplant recipients, 20 with stable graft function and 14 with BOS, underwent transbronchial lung biopsy and histochemical studies for senescence markers in small airways. Compared to nontransplant control lung tissue (n = 9), lung allografts demonstrate significantly increased airway epithelial staining for senescence-associated beta galactosidase (SA ,-gal) (p = 0.0215), p16ink4a (p = 0.0002) and p21waf1/cip (p = 0.0138) but there was no difference in expression of these markers between stable and BOS affected recipients (p > 0.05). This preliminary cross-sectional study demonstrates that cellular senescence occurs with increased frequency in the airway epithelium of the lung allograft but does not establish any association between airway epithelial senescence and BOS. A prospective longitudinal study is required to better address any potential causal association between airway epithelial senescence in stable allograft recipients and the subsequent development of BOS. [source] Minimal Acute Rejection after Lung Transplantation: A Risk for Bronchiolitis Obliterans SyndromeAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2005Anthony P. Khalifah Bronchiolitis obliterans syndrome (BOS) is a major cause of lung allograft dysfunction. Although previous studies have identified mild to severe rejection (grade ,A2) as a risk factor for BOS, the role of minimal rejection (grade A1) remains unclear. To determine if A1 rejection by itself is a risk factor for BOS, we performed a retrospective cohort study on 228 adult lung transplant recipients over a 7-year period. Cohorts were defined by their most severe rejection episode (none, A1 only, and ,A2) and analyzed for the subsequent development and progression of BOS using univariate and multivariate time-dependent Cox regression analysis. In the univariate model, the occurrence of isolated minimal rejection was a risk factor for all stages of BOS. Similarly, multivariate models that included HLA mismatch, cytomegalovirus pneumonitis, community acquired viral infection, underlying disease and type of transplant demonstrated that A1 rejection was a distinct risk factor for BOS. Furthermore, the associated risk with A1 rejection was slightly greater than the risk from ,A2 and treatment of A1 rejection decreased the risk for subsequent BOS stage 1. We conclude that minimal rejection is associated with an increased risk for BOS development and progression that is comparable to A2 rejection. [source] Clinical Impact of Community-Acquired Respiratory Viruses on Bronchiolitis Obliterans After Lung TransplantAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2005Deepali Kumar Community-acquired viral respiratory tract infections (RTI) in lung transplant recipients may have a high rate of progression to pneumonia and can be a trigger for immunologically mediated detrimental effects on lung function. A cohort of 100 patients was enrolled from 2001 to 2003 in which 50 patients had clinically diagnosed viral RTI and 50 were asymptomatic. All patients had nasopharyngeal and throat swabs taken for respiratory virus antigen detection, culture and RT-PCR. All patients had pulmonary function tests at regular intervals for 12 months. Rates of rejection, decline in forced expiratory volume (L) in 1 s (FEV-1) and bacterial and fungal superinfection were compared at the 3-month primary endpoint. In the 50 patients with RTI, a microbial etiology was identified in 33 of 50 (66%) and included rhinovirus (9), coronavirus (8), RSV (6), influenza A (5), parainfluenza (4) and human metapneumovirus (1). During the 3-month primary endpoint, 8 of 50 (16%) RTI patients had acute rejection versus 0 of 50 non-RTI patients (p = 0.006). The number of patients experiencing a 20% or more decline in FEV-1 by 3 months was 9 of 50 (18%) RTI versus 0 of 50 non-RTI (0%) (p = 0.003). In six of these nine patients, the decline in FEV-1 was sustained over a 1-year period consistent with bronchiolitis obliterans syndrome (BOS). Community-acquired respiratory viruses may be associated with the development of acute rejection and BOS. [source] The Safety and Efficacy of Total Lymphoid Irradiation in Progressive Bronchiolitis Obliterans Syndrome After Lung TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2005Andrew J. Fisher Total lymphoid irradiation (TLI) has been used to control renal and cardiac allograft rejection. Data evaluating TLI in bronchiolitis obliterans syndrome (BOS), the physiological manifestation of chronic lung allograft rejection, is very limited. We present our single center experience of the safety and efficacy of TLI in controlling progressive BOS in a retrospective study. Over 12 years, 37 lung recipients (16 M:21 F) who had undergone 13 single; 12 bilateral and 12 heart-lung transplants were treated with TLI for progressive BOS. Grades at time TLI given were BOS 1 (n = 7) BOS 2 (n = 14) BOS 3 (n = 16). Twenty-seven (73%) completed >8/10 fractions, 10 (27%) failed to complete TLI. Two died from advanced BOS during treatment, 8 stopped early (range 3,7 fractions) due to marrow suppression (6) or infection (2). In the 27 recipients who completed >8/10 fractions, decline in FEV1 was 122.7 mls/month pre-TLI and 25.1 mls/month post-TLI, p = 0.0004, mean (95% CI) change in rate of decline was 97.5 (48.2,146.7) mls/month. TLI significantly reduces the rate of decline in graft function associated with BOS. TLI is well tolerated and associated with few serious complications and is an appropriate immunosuppressive approach in progressive BOS. [source] A review of the potential applications and controversies of non-invasive testing for biomarkers of aspiration in the lung transplant populationCLINICAL TRANSPLANTATION, Issue 3 2010C.S. Davis Davis CS, Gagermeier J, Dilling D, Alex C, Lowery E, Kovacs EJ, Love RB, Fisichella PM. A review of the potential applications and controversies of non-invasive testing for biomarkers of aspiration in the lung transplant population. Clin Transplant 2010: 24: E54,E61. © 2010 John Wiley & Sons A/S. Abstract:, Despite improvements in one-yr survival following lung transplantation, five-yr survival lags significantly behind the transplantation of other solid organs. The contrast in survival persists despite advancements in anti-rejection regimens, suggesting a non-alloimmune mechanism to chronic lung transplant failure. Notably, markers of aspiration have been demonstrated in bronchoalveolar lavage (BAL) fluid concurrent with bronchiolitis obliterans syndrome (BOS). This recent evidence has underscored gastroesophageal reflux (GER) and its associated aspiration risk as a non-alloimmune mechanism of chronic lung transplant failure. Given the suggested safety and efficacy of laparoscopic anti-reflux procedures in the lung transplant population, identifying those at risk for aspiration is of prime importance, especially concerning the potential for long-term improvements in morbidity and mortality. Conventional diagnostic methods for GER and aspiration, such as pH monitoring and detecting pepsin and bile salts in BAL fluid, have gaps in their effectiveness. Therefore, we review the applications and controversies of a non-invasive method of defining reflux injury in the lung transplant population: the detection of biomarkers of aspiration in the exhaled breath condensate. Only by means of assay standardization and directed collaboration may such a non-invasive method be a realization in lung transplantation. [source] | ||||||||||