Cristina Berastegui

Epidemiology and immediate indirect effects of respiratory viruses in lung transplant recipients: a 5 year prospective study.

The epidemiology of respiratory viruses (RVs) in lung transplant recipients (LTRs) and the relationship of RVs to lung function, acute rejection (AR) and opportunistic infections in these patients are not well known. We performed a prospective cohort study (2009–2014) by collecting nasopharyngeal swabs (NPSs) from asymptomatic LTRs during seasonal changes and from LTRs with upper respiratory tract infectious disease (URTID), lower respiratory tract infectious disease (LRTID) and AR. NPSs were analyzed by multiplex polymerase chain reaction. Overall, 1094 NPSs were collected from 98 patients with a 23.6% positivity rate and mean follow‐up of 3.4 years (interquartile range 2.5–4.0 years). Approximately half of URTIDs (47 of 97, 48.5%) and tracheobronchitis cases (22 of 56, 39.3%) were caused by picornavirus, whereas pneumonia was caused mainly by paramyxovirus (four of nine, 44.4%) and influenza (two of nine, 22.2%). In LTRs with LRTID, lung function changed significantly at 1 mo (p = 0.03) and 3 mo (p = 0.04). In a nested case–control analysis, AR was associated with RVs (hazard ratio [HR] 6.54), Pseudomonas aeruginosa was associated with LRTID (HR 8.54), and cytomegalovirus (CMV) replication or disease was associated with URTID (HR 2.53) in the previous 3 mo. There was no association between RVs and Aspergillus spp. colonization or infection (HR 0.71). In conclusion, we documented a high incidence of RV infections in LTRs. LRTID produced significant lung function abnormalities. Associations were observed between AR and RVs, between P. aeruginosa colonization or infection and LRTID, and between CMV replication or disease and URTID.

Biomarkers of Pulmonary Rejection

Immunologic complications after lung transplantation (LT) include acute cellular rejection (ACR), antibody-mediated rejection (AMR), and most forms of chronic allograft dysfunction (CAD). ACR is an inflammatory process in which the reaction is mediated by the T-cell population. Most episodes of ACR fully recover with treatment, but repeated bouts are considered to be a risk factor for CAD. Biomarker cytokines interleukin (IL)-10, IL-15, IL-6, CCL5, CCR2 and IFNγ may play significant roles in this complication. Formerly bronchiolitis obliterans syndrome (BOS) or chronic rejection or most forms of CAD were considered to be immunologic complications not amenable therapeutic measures. CAD, the main limitation for long-term survival in LT, is characterized histologically by airway epithelial cell apoptosis and luminal fibrosis in the respiratory bronchioles causing airflow obstruction and, in some cases, lung parenchymal affectations causing restrictive lung disease. Several biomarkers have been studied in CAD, IL-6, IL-8, IL-17, IL-23, IL-13, IFN γ, and TGF β cytokines, pH, bile acid, and tripsine of gastroesophageal reflux and toll-like receptors of innate immunity. Herein we have reviewed the literature of biomarkers involved in lung rejection.

An association of particulate air pollution and traffic exposure with mortality after lung transplantation in Europe

Air pollution from road traffic is a serious health risk, especially for susceptible individuals. Single-centre studies showed an association with chronic lung allograft dysfunction (CLAD) and survival after lung transplantation, but there are no large studies. 13 lung transplant centres in 10 European countries created a cohort of 5707 patients. For each patient, we quantified residential particulate matter with aerodynamic diameter ≤10 µm (PM10) by land use regression models, and the traffic exposure by quantifying total road length within buffer zones around the home addresses of patients and distance to a major road or freeway. After correction for macrolide use, we found associations between air pollution variables and CLAD/mortality. Given the important interaction with macrolides, we stratified according to macrolide use. No associations were observed in 2151 patients taking macrolides. However, in 3556 patients not taking macrolides, mortality was associated with PM10 (hazard ratio 1.081, 95% CI 1.000–1.167); similarly, CLAD and mortality were associated with road lengths in buffers of 200–1000 and 100–500 m, respectively (hazard ratio 1.085– 1.130). Sensitivity analyses for various possible confounders confirmed the robustness of these associations. Long-term residential air pollution and traffic exposure were associated with CLAD and survival after lung transplantation, but only in patients not taking macrolides. Long-term residential air pollution/traffic exposure associated with CLAD and survival after lung transplantation http://ow.ly/Izxj304uA5k

High intra-individual variability of cyclosporine pharmacokinetics in lung transplant recipients without cystic fibrosis

There has been little study on the variability of CsA pharmacokinetics in stable lung transplant (LT) recipients without cystic fibrosis. This study was conducted to determine the prevalence of high intra‐individual variability of CsA in LT recipients and its implications in CsA monitoring.

Lung transplantation in systemic sclerosis: A single center cohort study

OBJECTIVE Lung transplantation (LT) has been proposed as a treatment for advanced interstitial lung disease (ILD) and/or pulmonary hypertension (PH) associated to systemic sclerosis (SSc) but few studies have been reported. The aim of this study was to describe the clinical features, complications and survival of a single-center cohort of patients with SSc that underwent LT and to compare their survival with a group of non-SSc transplanted patients. METHODS Fifteen patients with SSc were transplanted between May 2005 and April 2015. Standard international criteria were used to determine eligibility for LT. The severity of gastroesophageal involvement was not considered as a major contraindication if symptoms were under control. RESULTS Eight (53.3%) patients had diffuse cutaneous SSc. Eleven (73%) underwent bilateral LT. The main indication for LT was ILD, with or associated PH in 4 cases. Acute cellular rejection and infections were the most frequent complications. Functional lung tests tended to keep stable after transplantation. Median survival was 2.4 years (Q1-Q3: 0.7-3.7 years). We did not find differences in survival between patients transplanted with SSc versus those transplanted due to non-SSc ILD or PH. SSc complications were scarce with no patient developing PH after LT. CONCLUSIONS LT was an effective treatment for advanced ILD and/or PH associated to SSc in our study. Gastroesophageal reflux was not a limitation for LT in SSc in this study. Complications and survival did not differ from non-SSc patients undergoing LT.

Lung transplantation after allogeneic stem cell transplantation: a pan-European experience

Late-onset noninfectious pulmonary complications (LONIPCs) affect 6% of allogeneic stem cell transplantation (SCT) recipients within 5 years, conferring subsequent 5-year survival of 50%. Lung transplantation is rarely performed in this setting due to concomitant extrapulmonary morbidity, excessive immunosuppression and concerns about recurring malignancy being considered contraindications. This study assesses survival in highly selected patients undergoing lung transplantation for LONIPCs after SCT. SCT patients undergoing lung transplantation at 20 European centres between 1996 and 2014 were included. Clinical data pre- and post-lung transplantation were reviewed. Propensity score-matched controls were generated from the Eurotransplant and Scandiatransplant registries. Kaplan–Meier survival analysis and Cox proportional hazard regression models evaluating predictors of graft loss were performed. Graft survival at 1, 3 and 5 years of 84%, 72% and 67%, respectively, among the 105 SCT patients proved comparable to controls (p=0.75). Sepsis accounted for 15 out of 37 deaths (41%), with prior mechanical ventilation (HR 6.9, 95% CI 1.0–46.7; p<0.001) the leading risk factor. No SCT-specific risk factors were identified. Recurring malignancy occurred in four patients (4%). Lung transplantation <2 years post-SCT increased all-cause 1-year mortality (HR 7.5, 95% CI 2.3–23.8; p=0.001). Lung transplantation outcomes following SCT were comparable to other end-stage diseases. Lung transplantation should be considered feasible in selected candidates. No SCT-specific factors influencing outcome were identified within this carefully selected patient cohort. Lung transplantation is feasible in selected stem cell transplant recipients http://ow.ly/z4vn30h6gao

BALF cytokines in different phenotypes of chronic lung allograft dysfunction in lung transplant patients

The long‐term success of lung transplantation (LT) is limited by chronic lung allograft dysfunction (CLAD). Different phenotypes of CLAD have been described, such as bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS). The purpose of this study was to investigate the levels of cytokines and chemokines in bronchoalveolar lavage fluid (BALF) as markers of these CLAD phenotypes. BALF was collected from 51 recipients who underwent (bilateral and unilateral) LT. The study population was divided into three groups: stable (ST), BOS, and RAS. Levels of interleukin (IL)‐4, IL‐5, IL‐6, IL‐10, IL‐13, tumor necrosis factor alpha (TNF‐α), interferon‐gamma (IFN‐γ), and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) were measured using the multiplex technology. BALF neutrophilia medians were higher in BOS (38%) and RAS (30%) than in ST (8%) (P=.008; P=.012). Regarding BALF cytokines, BOS and RAS patients showed higher levels of INF‐γ than ST (P=.02; P=.008). Only IL‐5 presented significant differences between BOS and RAS (P=.001). BALF neutrophilia is as a marker for both CLAD phenotypes, BOS and RAS, and IL‐5 seems to be a potential biomarker for the RAS phenotype.

Determinants of One-Year Mortality in Lung Transplants Recipients Readmitted to Intense Care Unit

Introduction There are few data on determinants of long-term outcomes among lung transplant (LTx) patients who require readmission to Intensive Care Unit (ICU). Objectives Our aim was to describe the variables associated with one-year mortality in LTx recipients who require readmission to ICU beyond the postoperative period. Methods Single-center observacional retrospective analysis of a prospectively assessed cohort of LTx patients who were readmitted to ICU over 6-year period (2011-2016). We have included those LTx patients who required readmission beyond 30 days after transplantation. Patient were followed up to one year after ICU readmission. Demographic data, transplantation-related aspects, and ICU-related variables were collected. Data were expressed as mean (standard deviation), median (interquertile range) or frequency (percentage). Differences between categorical variables were assessed by chi-square or Fisher exact test when necessary.Continuous variables were compared using the Student t test or Mann-Whitney test, as appropriate. To determine which variables were independently associated whith one-year mortality, a backward stepwise logistic regression analysis was performed. Variables with p<0.1 in the univariate analysis were introduced intro the multivariate model. Continuous variables were categorized for this analysis using the observed mean in the overall cohort. A two-sided p value of 0.05 or less was considered statistically significant. Results During the study period 342 LTx were performed and 84 LTx recipients requiered ICU readmission, with a total of 100 episodes of ICU readmissions. Patients had a mean age of 53 (12) years old and the mean APACHE II score was 16 (6). The main reason for ICU admission was respiratory failure (70% of the readmissions) and the main respiratory failure etiology was lower respiratory tract infection (59.6% of the respiratory failure episodies). Fifty-four (64.3%) patients died during the follow-up period. APACHE II,SOFA at ICU readmission, need for mechanical ventilation (MV) during their course in the ICU, previous lower respiratory tract infection (LRTI), presence of chronic lung allograft dysfunction (CLAD) and FEV1(1%) reported value prior ICU readmission were included in the multivariate logistic regression analysis. The model showed an association between previous LRTI (OR 17.71 (95%CI 3.52 - 89.15); p<0.001), presence of CLAD (OR 5.46 (95%CI 1.34-22.25),p=0.018), and need for MV during their course in ICU (OR 17.97 (95%CI 4.85-66.64);p<0.001). In this sense, patients who had been diagnosed of LRTI and CLAD prior their ICU readmission and who need MV during their course in the ICU had a predicted probability of one-year mortality of 97%. Conclusion LTx patients who require ICU readmission present a high-risk of death during the subsequent year after their readmission. Previous LRTI and CLAD as well as need for MV during ICU stay are independent predictors of one-year mortality.

The role of transbronchial cryobiopsy in lung transplantation

Lung transplant monitoring is usually performed with forceps transbronchial biopsies. These types of biopsy show limited reliability and a high degree of variability, owing to insufficient material and compression artefact, which lead to misinterpretation and, eventually, inappropriate treatment of the transplanted patients. The following study was undertaken to assess the diagnostic yield, histological quality and safety of cryobiopsy (CB) in comparison with conventional forceps biopsy (FB) for sampling lung tissue in transplant recipients.

Case Report: Successful Lung Transplantation from a Donor Seropositive for Trypanosoma cruzi Infection (Chagas Disease) to a Seronegative Recipient

The increasing shortage of organs for transplantation has prompted transplant programs to investigate the use of extended criteria donors, such as those with transmissible infectious diseases. Successful cases of organ transplantation (mostly kidney and liver) from Trypanosoma cruzi seropositive donors to seronegative recipients have been reported. We present a case of lung transplantation from a donor serologically positive for Chagas disease to a seronegative recipient, and provide a review of the literature. Left single lung transplantation was performed in a 44-year-old Spanish woman presenting with interstitial lung disease in February 2016. The deceased donor was a Colombian immigrant living in Spain who was serologically positive for Chagas disease. Oral administration of 5 mg/kg/day benznidazole divided in three doses for 60 days was given for specific Chagas disease prophylaxis after transplantation. Periodic follow-up with serological reverse transcription polymerase chain reaction to detect T. cruzi DNA were performed until 6 months after the end of treatment. All results were negative, indicating that transmission of T. cruzi had not occurred. In a review of the literature, two similar cases were identified in Argentina and the United States. In both cases T. cruzi infection was detected posttransplant in the recipients, after which they were treated with benznidazole. The course of the patient described herein confirms that lungs from donors with chronic T. cruzi infection can be used successfully as allografts, and that posttransplant prophylaxis with benznidazole may reduce the probability of transmission of T. cruzi to the recipient.