Onset Of Bronchiolitis Obliterans Syndrome Research Articles

Prognostic value of the 6 min walk test in bronchiolitis obliterans syndrome

Bronchiolitis Obliterans Syndrome (BOS) complicates the course of many lung transplant recipients. It carries significant risk of morbidity and mortality, but its course is difficult to characterize. We evaluated the prognostic utility of the 6min walk test (6MWT) obtained after the onset of BOS in 42 patients. This was compared to the prognostic significance of changes in the FEV(1). The median time between the onset of BOS and the 6MWT was 109 days. The median decline in the FEV(1) from baseline to BOS onset was 25.7%, while the median change over the ensuing 3 months was 12.5%. Neither of these was predictive of subsequent mortality. The 6MWT yielded averages in the resting saturation, lowest saturation, distance walked and maximal Borg scores of 97%, 90.2%, 323m and 2.35, respectively. The best of these parameters in discriminating survival was the distance. Patients who walked further than 330m had a median survival of 1178 days versus 263 days for those who walked less (p<0.0001). We conclude that the 6MWT provides important prognostic information in patients with BOS and might perform better than spirometry. Use of this test might allow different clinical phenotypes to be discerned.

Community-Acquired Respiratory Viral Infections in Lung Transplant Recipients: A Single Season Cohort Study

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. 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. 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. 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.

Prognostic Value of Bronchoalveolar Lavage Neutrophilia in Stable Lung Transplant Recipients

Bronchoalveolar lavage (BAL) neutrophilia may identify patients prone to develop bronchiolitis obliterans syndrome (BOS) after lung transplantation (LTx). This study assessed the predictive value of BAL neutrophilia in stable recipients. Evaluated were 63 consecutive recipients 3 to 12 months after LTx demonstrating no acute rejection (AR) and lymphocytic bronchitis (LB; B < or = 1 without infection; BOS, 0). Recipients were subdivided into never-BOS (follow-up > or = 12 months) and ever-BOS groups (i.e., BOS development > or = 1 after bronchoscopy). The groups were statistically indistinguishable for demographic data and preceding AR and LB episodes. Onset of BOS was at a median of 232 days (range, 87-962) after bronchoscopy. The ever-BOS group (16 patients) demonstrated a significantly higher percentage of neutrophils compared with the never-BOS group (47 patients) at the time of bronchoscopy (33.6% +/- 2.1% vs 9.9% +/- 1.1%, p < 0.05). By Cox regression analysis, a BAL neutrophil percentage of > or = 20% remained a significant predictor for BOS > or = 1 (hazard ratio, 3.57; 95% confidence interval, 1.71-8.40, p < 0.05) distinct from known potential BOS predictor variables. The positive and negative predictive value of BAL neutrophilia of > or = 20% for future BOS was 0.72 and 0.93, respectively (p < 0.05). BAL neutrophilia in stable recipients is of predictive value to identify recipients at risk for BOS. These data warrant prospective confirmation and further studies to evaluate the benefit of preemptive therapy for potential BOS patients.

Effect of Etiology and Timing of Respiratory Tract Infections on Development of Bronchiolitis Obliterans Syndrome

Among the many potential risk factors influencing the development of bronchiolitis obliterans syndrome (BOS), acute cellular rejection is the most frequently identified. Despite the unique susceptibility of the lung allograft to pathogens, the association with respiratory tract infections remains unclear. In this study we analyze the role respiratory tract infections have on the development of BOS after lung transplantation. Data from a single center were analyzed from 161 lung recipients transplanted from November 1990 to November 2005, and who survived >180 days. Univariate and multivariate Cox regression analyses were performed using BOS development and the time-scale was reported with hazard ratios (HRs) and confidence intervals (CIs). Significant findings by univariate analysis per 100 patient-days prior to BOS onset included acute rejection, cytomegalovirus (CMV) pneumonitis, Gram-negative respiratory tract infections, Gram-positive respiratory tract infections and fungal pneumonias. Multivariate analysis indicated acute rejection, Gram-negative, Gram-positive and fungal pneumonias with HRs (CI) of 84 (23 to 309), 6.6 (1.2 to 37), 6,371 (84 to 485,000) and 314 (53 to 1,856) to be associated with BOS, respectively. Acute rejection, CMV pneumonitis, Gram-positive pneumonia and fungal pneumonitis in the first 100 days had HRs (CI) of 1.8 (1.1 to 3.2), 3.1 (1.3 to 6.9), 3.8 (1.5 to 9.4) and 2.1 (1.1 to 4.0), respectively, and acute rejection and fungal pneumonitis in the late post-operative period with HRs (CI) of 2.3 (1.2 to 4.4) and 1.5 (1.1 to 1.9), respectively. In addition to acute rejection, pneumonias with GP, GN and fungal pathogens occurring prior to BOS are independent determinants of chronic allograft dysfunction. Early recognition and treatment of these pathogens in lung transplant recipients may improve long-term outcomes after transplantation.

591: Pretransplant Medication Nonadherence: An Underestimated Predictor of Poor Outcome after Lung Transplantation

Few studies investigated the impact of pre-Tx behavioral factors on post-Tx outcomes. The present study examines, for the first time, whether pre-Tx medication nonadherence (NA) is predictive for mortality, onset of bronchiolitis obliterans syndrome (BOS) and re-Tx up to 5 years after Lung Tx.

Human Metapneumovirus in Lung Transplant Recipients and Comparison to Respiratory Syncytial Virus

Human metapneumovirus is a newly described virus isolated in 2001 from children with acute respiratory viral infection. It has subsequently been reported globally, although there are limited data in lung transplant recipients. To prospectively analyze whether human metapneumovirus was circulating in our adult lung transplant community and assess the morbidity of this infection and to compare the clinical presentation and outcome after intravenous ribavirin of human metapneumovirus with that of respiratory syncytial virus (RSV). Lung transplant patients with clinical features of respiratory viral infection underwent nasopharyngeal aspirates. Patients with a positive specimen for RSV or human metapneumovirus by reverse transcriptase-polymerase chain reaction analysis and graft dysfunction received intravenous ribavirin and pulse steroid therapy. Eighty-nine patients had 199 visits for aspirate studies. A viral cause was determined for 62 visits in 47 patients (19 human metapneumovirus, 18 RSV, 13 parainfluenza, 9 influenza A, 2 adenovirus, and 1 influenza B). A significant percentage of patients with metapneumovirus (63%) and RSV (72%) developed graft dysfunction, with average declines in FEV(1) of 30 +/- 12.4% and 25.9 +/- 11.2%, respectively. In these patients, bronchiolitis obliterans syndrome onset or progression occurred in no patients with human metapneumovirus compared with 5 of 13 (38%) patients with RSV at 6 months. Human metapneumovirus is a leading cause of acute respiratory tract illness in lung transplant recipients. The incidence and clinical spectrum at presentation are similar to RSV, although the latter seems to be associated with a higher risk of chronic rejection. We recommend testing of nasopharyngeal aspirates for human metapneumovirus with polymerase chain reaction to assess local epidemiologic patterns.

Long-term Health-related Quality of Life and Walking Capacity of Lung Recipients With and Without Bronchiolitis Obliterans Syndrome

Outcome after lung transplantation (LTx) is affected by the onset of bronchiolitis obliterans syndrome (BOS) and lung function decline. Reduced health-related quality of life (HRQL) and physical mobility have been shown in patients developing BOS, but the impact on the capacity to walk is unknown. We aimed to compare the long-term HRQL and 6-minute walk test (6MWT) between lung recipients affected or not by BOS Grade > or =2. Fifty-eight patients were prospectively followed for 5.6 +/- 2.9 years after LTx. Assessments included the St George's Respiratory Questionnaire (SGRQ) and the 6MWT, which were performed yearly. Moreover, clinical complications were recorded to estimate the proportion of the follow-up time lived without clinical intercurrences after transplant. Analyses were performed using adjusted linear regression and repeated-measures analysis of variance. BOS was a significant predictor of lower SGRQ scores (p < 0.01) and reduced time free of clinical complications (p = 0.001), but not of 6MWT distance (p = 0.12). At 7 years post-transplant, results were: 69.0 +/- 21.8% vs 86.9 +/- 5.6%, p < 0.05 (SGRQ); 58.5 +/- 21.6% vs 88.7 +/- 11.4%, p < 0.01 (proportion of time lived without clinical complications); and 82.2 +/- 10.9% vs 91.9 +/- 14.2%, p = 0.27 (percent of predicted 6MWT), respectively, for patients with BOS and without BOS. Despite significantly less time lived without clinical complications and progressive decline of self-reported health status, the capacity to walk of patients affected by BOS remained relatively stable over time. These findings may indicate that the development of moderate to severe BOS does not prevent lung recipients from walking independently and pursuing an autonomous life.

Rabbit Anti-thymocyte Globulin Induction Therapy Does Not Prolong Survival After Lung Transplantation

Lung transplant survival is limited by the development of bronchiolitis obliterans syndrome (BOS). The strongest risk factor for BOS is acute rejection (AR). We have previously shown that rabbit anti-thymocyte globulin (RATG) induction therapy is associated with a decrease in early AR. Thus, we hypothesized that RATG induction would translate to reduced BOS and improved long-term graft survival. Forty-four lung recipients were prospectively randomized to receive conventional immunosuppression with RATG induction (RATG group) or conventional immunosuppression alone (control group). End-points included graft survival, early and total acute rejection, BOS and treatment complications. There was no difference in graft survival between the groups at 8 years (RATG: 36%; control: 23%; p = 0.48). The RATG group had fewer early rejections compared with the control group (5% vs 41%; p = 0.01). However, the overall rejection incidence did not differ (RATG: 62%; control: 68%; p = 0.52). There was a trend toward a delay in BOS onset among RATG subjects compared with control subjects (2,376 days vs 1,108 days; log rank, p = 0.15). There was no difference in the incidence of infections, but the RATG group had a higher rate of malignancies. Our results suggest that alternative approaches to anti-thymocyte induction should be pursued to reduce BOS and prolong allograft survival.

De Novo Production of K-α1 Tubulin-Specific Antibodies: Role in Chronic Lung Allograft Rejection

Lung transplantation is the treatment option for a variety of end-stage pulmonary diseases. Posttransplant development of Abs against donor HLA and non-HLA Ags have been associated with acute and chronic rejection of transplanted organs. Development of bronchiolitis obliterans syndrome (BOS) following lung transplantation has been correlated with de novo production of anti-donor-HLA Abs. However, only a portion of the patients with BOS demonstrate detectable anti-donor-HLA Abs. Airway epithelium is considered as a major target for lung allograft rejection. In this study we demonstrate that many BOS(+) patients (12 of 36) develop Abs reactive to epithelial cell Ag that are distinct from HLA. Furthermore, de novo production of antiepithelial cell Ab precedes clinical onset of BOS. N-terminal sequencing and blastx analysis as well as blocking with K-alpha1 tubulin-specific Ab identified the epithelial Ag as K-alpha1 tubulin. Binding of the de novo-produced anti-K-alpha1 tubulin Abs to the airway epithelial cells resulted in the increased expression of transcription factors (TCF5 and c-Myc), leading to increased expression of fibrogenic growth factors, activation of cell cycle signaling, and fibroproliferation, the central events in immunopathogenesis of BOS following human lung transplantation.

Activation of Tissue Remodeling Precedes Obliterative Bronchiolitis in Lung Transplant Recipients

Obliterative bronchiolitis (OB) and Bronchiolitis Obliterans Syndrome (BOS) are frequent complications in the lung transplant recipient, and are the leading cause of mortality after transplantation. The mechanisms responsible for OB remain elusive, but inflammatory and tissue remodeling responses are implicated. We hypothesized that alterations in markers of tissue remodeling in BALF of lung transplant recipients could predict development of OB. To test this, we identified 13 lung transplant recipients who developed both BOS and histologic OB (OB group) at median post-operative day (POD) 485 (range 73-2070). Bronchoalveolar lavage fluid (BALF) was obtained at median POD 387 (range 45-2205), which preceded the onset of OB and BOS by a median of 140 days (range 60-365). As a control, BALF was also obtained from a group of 21 stable recipients without OB (non-OB group) at median POD 335 (range 270-395). BALF was examined for gelatinolytic activity, fibronectin gene transcription, and transforming growth factor-beta1 (TGF-beta1) expression. Gelatin zymography of BALF from the OB group showed increased matrix metalloproteinase-9 (MMP-9) activity over that of the non-OB group (p < 0.005). Similarly, BALF from the OB group induced greater fibronectin expression in fibroblasts compared to the non-OB group (p < 0.03). The induction of fibronectin also correlated with the amount of TGF-beta1 protein in BALF (r = 0.71) from the OB group. We conclude that activation of tissue remodeling precedes the onset of OB, and analysis of gelatinolytic and/or fibronectin-inducing activity in BALF can serve as an early, pre-clinical marker for OB.

Bronchoalveolar Lavage Fluid Proteome in Bronchiolitis Obliterans Syndrome: Possible Role for Surfactant Protein A in Disease Onset

Bronchiolitis obliterans syndrome (BOS) affects long-term survival of lung transplant (Tx) recipients (LTRs), with no consistently effective treatment strategy. Identifying early markers of BOS is of paramount importance for improving graft survival. We used 2-dimensional gel electrophoresis and protein identification by mass spectrometry to compare the protein profile of bronchoalveolar lavage fluid (BALf) in two groups of LTRs: one composed of patients with BOS and the other composed of patients with good graft function at >5 years post-surgery (stable LTRs). Based on the hypothesis that only proteins of lung origin could represent reliable BOS markers, we also evaluated paired plasma samples. Proteins of interest were also assessed in the BALf of control subjects and results confirmed by dot- blot analysis. Among 11 differentially expressed proteins, we identified 2 locally produced factors: peroxiredoxin II (PRXII), exclusively expressed in BOS; and surfactant protein A (SP-A), expressed consistently less in BOS patients than in stable LTRs. PRXII expression was never observed in BALf from control subjects, whereas SP-A was present in higher amounts compared with stable LTRs and BOS patients. Finally, the time course of SP-A was studied in 5 LTRs who subsequently developed BOS. A reduction in BALf SP-A content was detectable early after Tx, preceding BOS onset in 4 of 5 patients. Our results suggest that testing SP-A levels in BALf could predict LTR patients who are at higher risk of BOS development.

A Randomized Controlled Trial of Tacrolimus Versus Cyclosporine After Lung Transplantation

The optimal maintenance immunosuppressive regimen after lung transplantation is uncertain. We conducted a randomized controlled trial of tacrolimus versus cyclosporine in combination with azathioprine and prednisone after lung transplantation. Ninety adults were randomized to tacrolimus (n = 44) or cyclosporine (n = 46). The primary end point was a composite of a cumulative acute rejection A score of 3 or higher, a cumulative lymphocytic bronchitis B score of 4 or higher, or the onset of bronchiolitis obliterans syndrome (BOS) stage 0-p. Recipients randomized to cyclosporine were significantly more likely to develop the primary end point than those randomized to tacrolimus. During the study period, the primary end point developed in 39 of 46 cyclosporine subjects compared with 24 of 44 tacrolimus subjects (p = 0.002); acute rejection or lymphocytic bronchitis end points developed in 29 of 46 cyclosporine subjects compared with 18 of 44 tacrolimus subjects (p = 0.036). Furthermore, BOS stage 0-p was more likely to develop in the cyclosporine group than in the tacrolimus group, but this was not statistically significant (log-rank p = 0.1). In addition, there was a trend to a higher incidence of diabetes among those in the tacrolimus group, but there was no significant difference in graft survival or the total number of infections, or in the incidence of hypertension, chronic kidney disease, or cancer between the 2 groups. Tacrolimus is associated with a lower burden of acute rejection and lymphocytic bronchitis and a trend to a greater freedom from BOS stage 0-p than cyclosporine after lung transplantation.

Soluble CD30 levels as a diagnostic marker for bronchiolitis obliterans syndrome following human lung transplantation

The long term survival of human lung allograft is hampered by the occurrence of chronic rejection, Bronchiolitis Obliterans Syndrome (BOS). This end-stage disease is normally diagnosed clinically by using the pulmonary function tests. This results in delay of BOS diagnosis and consequently prevents early intervention. It is generally accepted that alloimmunity plays an important role in chronic rejection of the allograft. In this study we analyzed serial serum samples from BOS+ and BOS− patients for sCD30 levels to determine the role of sCD30 to predict the onset of BOS. In contrast to BOS negative patients and normal subjects, 6 out of 9 BOS+ patients (p<0.05) studied had an increase in the sCD30 levels. Significantly, the rise was noted 7.57±2.63 months before the clinical diagnosis was evident. Therefore, we propose that the rise in serum sCD30 levels can be used as a marker for the detection of patients who are at risk of development of BOS.

Chemokine redundancy in BOS pathogenesis. A possible role also for the CC chemokines: MIP3-beta, MIP3-alpha, MDC and their specific receptors

Bronchiolitis obliterans syndrome (BOS) is one of the most important factors limiting the long-term survival of lung transplant recipients (LTR), however its pathogenesis still remains unclear. We hypothesized that an increased production of certain specific proinflammatory mediators in the first post-transplant year would predispose to BOS.We retrospectively evaluated temporal kinetics of some CC chemokines that have not yet been evaluated, including CCL3/MIP1-α, CCL4/MIP1-β, CCL17/TARC, CCL19/MIP3-β, CCL20/MIP3-α, CCL22/MDC and CCL26/eotaxin, in broncho-alveolar lavage fluid (BAL-f) in the first post-transplant year in a cohort of 8 LTR before the development of BOS (pre-BOS LTR) and 8 LTR with long-term stable clinical conditions (stable LTR). Chemokine levels were assayed by means of a multiplex sandwich ELISA. Furthermore, for those ligands which resulted significantly predictive of BOS onset, we analyzed the expression of specific receptors (CCR) on BAL cells. The proportion of CCR-expressing BAL cells was assessed by flow cytometry.We demonstrated that MIP3-β/CCL19, MIP3-α/CCL20, MDC/CCL22 levels at 6 months post-transplant significantly predicted BOS onset. In addition, the temporal behavior of these factors resulted significantly different in pre-BOS patients as compared to stable LTR. Finally the expression of CCR was documented on BAL lymphocytes and macrophages, and, in some cases, their expression was found to vary between the two groups.Within the complexity of the chemokine network, these three CCL factors could play an additive role in the pathogenesis of the inflammatory process leading to bronchiolar fibro-obliteration.

Quality of life and bronchiolitis obliterans syndrome in patients after lung transplantation

Lung transplantation has become an established and effective treatment for patients with end-stage pulmonary disease. To investigate health-related quality of life in correlation with occurrence and degree of bronchiolitis obliterans syndrome after transplantation. In a cross-sectional study design, 119 consecutive lung transplant recipients (63.9% bilateral and 36.1% single lung transplants) responded voluntarily to a set of standardized questionnaires (12-Item Short-Form Health Survey, Center for Epidemiologic Studies-Depression Scale, Coping With Everyday Life, Beck Anxiety Inventory, Zerssen list of complaints) that covered health-related quality of life and psychological well being. Also, we performed pulmonary function studies to clinically grade bronchiolitis obliterans syndrome in all patients. In this cohort, 41.2% of patients developed bronchiolitis obliterans syndrome at a mean interval of 5.6 years after lung transplantation. Actuarial freedom from bronchiolitis obliterans syndrome was 90.1% +/- 2.3% at 1 year, 79.9% +/- 3.7% at 3 years, and 59.5% +/- 4.8% at 5 years after lung transplantation. Recipients with bronchiolitis obliterans syndrome reported significantly lower well being and quality of life than those without bronchiolitis obliterans syndrome, who scored similar to healthy volunteers. In a subanalysis, body functioning (P < .001) and related areas of coping (P < .001) were mostly affected by bronchiolitis obliterans syndrome. Quality of life was negatively affected by the onset of bronchiolitis obliterans syndrome. However, even patients who develop bronchiolitis obliterans syndrome reported a temporary benefit from lung transplantation. In addition to optimal medical care and efforts in preventing bronchiolitis obliterans syndrome, psychological support of lung recipients seems to be essential, especially when bronchiolitis obliterans syndrome occurs.

Quality of Life and Bronchiolitis Obliterans Syndrome in Patients after Lung Transplantation

Lung transplantation has become an established and effective treatment for patients with end-stage pulmonary disease. To investigate health-related quality of life in correlation with occurrence and degree of bronchiolitis obliterans syndrome after transplantation. In a cross-sectional study design, 119 consecutive lung transplant recipients (63.9% bilateral and 36.1% single lung transplants) responded voluntarily to a set of standardized questionnaires (12-Item Short-Form Health Survey, Center for Epidemiologic Studies-Depression Scale, Coping With Everyday Life, Beck Anxiety Inventory, Zerssen list of complaints) that covered health-related quality of life and psychological well being. Also, we performed pulmonary function studies to clinically grade bronchiolitis obliterans syndrome in all patients. In this cohort, 41.2% of patients developed bronchiolitis obliterans syndrome at a mean interval of 5.6 years after lung transplantation. Actuarial freedom from bronchiolitis obliterans syndrome was 90.1% +/- 2.3% at 1 year, 79.9% +/- 3.7% at 3 years, and 59.5% +/- 4.8% at 5 years after lung transplantation. Recipients with bronchiolitis obliterans syndrome reported significantly lower well being and quality of life than those without bronchiolitis obliterans syndrome, who scored similar to healthy volunteers. In a subanalysis, body functioning (P < .001) and related areas of coping (P < .001) were mostly affected by bronchiolitis obliterans syndrome. Quality of life was negatively affected by the onset of bronchiolitis obliterans syndrome. However, even patients who develop bronchiolitis obliterans syndrome reported a temporary benefit from lung transplantation. In addition to optimal medical care and efforts in preventing bronchiolitis obliterans syndrome, psychological support of lung recipients seems to be essential, especially when bronchiolitis obliterans syndrome occurs.

Course of FEV1after Onset of Bronchiolitis Obliterans Syndrome in Lung Transplant Recipients

Bronchiolitis obliterans syndrome (BOS), defined by loss of lung function, develops in the majority of lung transplant recipients. However, there is a paucity of information on the subsequent course of lung function in these patients. To characterize the course of FEV(1) over time after development of BOS and to determine the predictors that influence the rate of functional decline of FEV(1). FEV(1)% predicted (FEV(1)%pred) trajectories were studied in 111 lung transplant recipients with BOS by multivariate, linear, mixed-effects statistical models. FEV(1)%pred varied over time after BOS onset, with the steepest decline typically seen in the first 6 months (12% decline; p < 0.0001). Bilateral lung transplant recipients had significantly higher FEV(1)%pred at BOS diagnosis (71 vs. 47%; p < 0.0001) and at 24 months after BOS onset (58 vs. 41%; p = 0.0001). Female gender and pretransplant diagnosis of idiopathic pulmonary fibrosis were associated with a steeper decline in FEV(1)%pred in the first 6 months after BOS diagnosis (p = 0.02 and 0.04, respectively). A fall in FEV(1) greater than 20% in the 6 months preceding BOS (termed "rapid onset") was associated with shorter time to BOS onset (p = 0.01), lower FEV(1)%pred at BOS onset (p < 0.0001), steeper decline in the first 6 months (p = 0.03), and lower FEV(1)%pred at 2 years after onset (p = 0.0002). Rapid onset of BOS, female gender, pretransplant diagnosis of idiopathic pulmonary fibrosis, and single-lung transplantation are associated with worse pulmonary function after BOS onset.

137: Pre-transplant MICA, HLA class I or II antibodies are associated with earlier onset of bronchiolitis obliterans syndrome in lung transplant recipient

Purpose: We sought to determine whether the presence of MHC Class I chain-related gene A (MICA), HLA Class I or II Abs as determined by solid phase methods (ELISA or Luminex) predicted outcome after LTX.

Bronchiolitis Obliterans Syndrome after Hematopoietic Stem Cell Transplantation: A Retrospective Multicenter Survey of the Late Effect Working Party EBMT.

Aim and Scope: Substantial morbidity and mortality is caused by respiratory complications in 40–60% of patients after HSCT. Bronchiolitis obliterans syndrome (BOS) is reported in 2–13% of patients, occurring within 6–12 months post transplant. The LEWP launched a retrospective survey in 2003 to document the incidence, current practice for the diagnosis, clinical work-up and treatment of BOS after allogeneic HSCT.Patients&Method: Between 2003 – 2005, 31 centers reported 226 patients with BOS. Adjusted BOS criteria were accepted (normal spirometry pretransplant, respiratory symptoms in the absence of an infection and combination of 3/4 items at onset: FEV1 <80% predicted/measured; FEV1/FVC <80% and MMFR <50% predicted/measured and residual volume >120%; HR CAT scan of the thorax. FOB and BAL were used in 60% of centers, but open lung bx.was not recommended by 75%.Results: The median age of the patients was 30.9 years (1–62) and 19% was pediatric. The donors were 64.6% siblings. HSCT indication was hematological malignancy in 92.3% (37% AL, 21% CL). The graft source was BM in 60% and PBSC in 39%. The preparative regimen was myeloablation in 85.8%. The majority of the patients had antecedent GVHD (acute 66%, chronic 89%). The median interval from transplant to onset of BOS was 11.7 mo.s (1–260). Two third of the patients are still alive (22% in remission and 70% still receiving therapy). Median survival is 39.5 mo.s (1–277). The main reasons for high mortality rate are BOS (69%), relapse (15%) and GVHD (14%). The results of the univariate analysis on KM curves are summarized in Table 1.Conclusion: Univariate data showed a negative impact of male gender, early onset (<11.7 mo.s) and MUD transplants. BOS is still an important cause of non-relapse late morbidity and mortality. Diagnosis and treatment are difficult and heterogeneous. The final analysis with multivariate methods should validate current results.Variables tested in univariate analysesVariablesMed. OS, months (95% CI)PSibling/MUDNR75.9 (28.1–123.6)043Male/Female72.5 (47.6–97.4)NR0.038Onset: Early/Late59 (33.3–84.8)NR0.00001Ablative/Non Ablative102.8 (67.7–137.9)NR0.191NR: not reached

Invited commentary

Invited commentary