Consensus conference on a composite endpoint for clinical trials on immunosuppressive drugs in lung transplantation.

Background: In lung transplantation, diverse clinical events may impact patient outcome. In clinical trials comparing intervention strategies, single primary endpoints require large populations, or long study durations, whereas composite endpoints (CEPs) do not take into account the respective impact of their components on patient survival. The objective of this study was to propose consensus recommendations on endpoints for clinical trials on immunosuppressants in lung transplantation.

IL-17A mediates early post-transplant lesions after heterotopic trachea allotransplantation in Mice.

Primary graft dysfunction (PGD) and bronchiolitis obliterans (BO) are the leading causes of morbidity and mortality after lung transplantation. Reports from clinical and rodent models suggest the implication of IL-17A in either PGD or BO. We took advantage of the heterotopic trachea transplantation model in mice to study the direct role of IL-17A in post-transplant airway lesions.

Cyclosporine A drives a Th17- and Th2-mediated posttransplant obliterative airway disease.

Calcineurin-inhibitor refractory bronchiolitis obliterans (BO) represents the leading cause of late graft failure after lung transplantation. T helper (Th)2 and Th17 lymphocytes have been associated with BO development. Taking advantage of a fully allogeneic trachea transplantation model in mice, we addressed the pathogenicity of Th cells in obliterative airway disease (OAD) occurring in cyclosporine A (CsA)-treated recipients.

Percutaneous endoscopic jejunostomy in patients with gastroparesis following lung transplantation: feasibility and clinical outcome.

The aim of the present study was to describe success rates, complications, and outcome in patients who underwent percutaneous endoscopic jejunostomy (PEJ) because of gastroparesis due to previous lung transplantation. Between October 2008 and May 2011, 14 attempts at PEJ placement were made in 12 patients in our center. Of the 14 attempts, 11 were successful, giving a technical success rate of 78.

Population pharmacokinetic modelling and design of a Bayesian estimator for therapeutic drug monitoring of tacrolimus in lung transplantation.

Background: Therapeutic drug monitoring of tacrolimus is a major support to patient management and could help improve the outcome of lung transplant recipients, by minimizing the risk of rejections and infections. However, despite the wide use of tacrolimus as part of maintenance immunosuppressive regimens after lung transplantation, little is known about its pharmacokinetics in this population. Better knowledge of the pharmacokinetics of tacrolimus in lung transplant recipients, and the development of tools dedicated to its therapeutic drug monitoring, could thus help improve their outcome.

Bayesian estimation of mycophenolate mofetil in lung transplantation, using a population pharmacokinetic model developed in kidney and lung transplant recipients.

Background And Objectives: The immunosuppressive drug mycophenolate mofetil is used to prevent rejection after organ transplantation. In kidney transplant recipients, it has been demonstrated that adjustment of the mycophenolate mofetil dose on the basis of the area under the concentration-time curve (AUC) of mycophenolic acid (MPA), the active moiety of mycophenolate mofetil, improves the clinical outcome. Because of the high risks of rejections and infections in lung transplant recipients, therapeutic drug monitoring of the MPA AUC might be even more useful in these patients.

Lung transplantation and lung volume reduction surgery.

Since the publication of the last edition of the Handbook of Physiology, lung transplantation has become widely available, via specialized centers, for a variety of end-stage lung diseases. Lung volume reduction surgery, a procedure for emphysema first conceptualized in the 1950s, electrified the pulmonary medicine community when it was rediscovered in the 1990s. In parallel with their technical and clinical refinement, extensive investigation has explored the unique physiology of these procedures.

Chronic allograft dysfunction.

Chronic, progressive, and irreversible loss of lung function is the major medium-term and long-term complication after lung transplantation and the leading cause of death. Over the past decade, progress has been made in understanding the pathogenesis of bronchiolitis obliterans. Alloimmune factors and nonalloimmune factors may contribute to its development.

[Medical complications of lung transplantation].

In 2010, lung transplantation is a valuable therapeutic option for a number of patients suffering from of end-stage non-neoplastic pulmonary diseases. The patients frequently regain a very good quality of life, however, long-term survival is often hampered by the development of complications such as the bronchiolitis obliterans syndrome, metabolic and infectious complications. As the bronchiolitis obliterans syndrome is the first cause of death in the medium and long term, an intense immunosuppressive treatment is maintained for life in order to prevent or stabilize this complication.

[Complications of lung transplantation].

In 2009 lung transplantation is a valuable therapeutic option for a number of patients suffering from end-stage pulmonary diseases. Lung transplantation frequently offers a major improvement in quality of life; however, long-term survival is often limited by the development of the bronchiolitis obliterans syndrome, which is the equivalent of a chronic pulmonary graft rejection. As the bronchiolitis obliterans syndrome is the commonest cause of death in the medium- and long-terms, all patients receive intense immunosuppressive treatment in order to prevent or stabilize this complication.

Gravitational gradients in expiratory computed tomography examinations of patients with small airways disease: effect of body position on extent of air trapping.

Purpose: First, to test the hypothesis that air trapping in diseased patients follows a gravitational gradient and is more extensive in dependent than in nondependent lung regions. Second, to test the hypothesis that the dependent lung regions on combined supine and prone expiratory computed tomography (CT) examinations will show more air trapping than would a supine expiratory CT examination alone.

Materials And Methods: For this ethics committee-approved study, supine and prone multidetector-row CT (4×1 mm collimation, 0.

[Complications of lung transplantation: perioperative complications, acute and chronic rejection].

In 2009 lung transplantation is a valuable therapeutic option for a spectrum of end-stage pulmonary diseases. To many patients who are dying, lung transplantation offers a new and normal life for several years. However, lung transplantation is a major surgical intervention associated with a significant early mortality.

Disease-specific approach to lung transplantation.

Purpose Of Review: The present review provides an update on the recent literature regarding disease-specific issues in lung transplantation. Some of the published data will help refine previously published candidate selection criteria and provide evidence-based data for choice of procedures.

Recent Findings: Recent studies on lung transplant outcomes in older patients underline that satisfactory results can be obtained in patients older than 60 years but not in patients older than 70 years.

Effect of lung transplant and volume reduction surgery on respiratory muscle function.

Lung transplantation and lung volume reduction surgery have opened a new therapeutic era for patients with advanced emphysema. In addition to providing impressive clinical benefits, they have helped us better understand how the chest wall and respiratory muscles adapt to chronic hyperinflation. This article reviews the effects of these procedures on respiratory muscle and chest wall function.

Effect of systemic inflammation on inspiratory and limb muscle strength and bulk in cystic fibrosis.

Rationale: Diaphragm thickness is increased in cystic fibrosis (CF), but it shows a marked variability between patients. The variable response of the diaphragm to loading may reflect the combined and opposite effects of training by the respiratory disease and systemic inflammation.

Objectives: To assess the impact of systemic inflammation on diaphragm and limb muscle strength and bulk in adult patients with CF.

Regional heterogeneity of air trapping at expiratory thin-section CT of patients with bronchiolitis: potential implications for dose reduction and CT protocol planning.

Purpose: To prospectively determine whether the regional distribution of air trapping in patients with suspected or overt bronchiolitis is heterogeneous, and to determine the effect that a simulated reduction of computed tomographic (CT) sections and of scanned anatomic regions would have on the assessment of the extent of air trapping.

Materials And Methods: For this Ethical Committee-approved study, multi-detector row CT (collimation, 4 x 1 mm; rotation time, 0.5 second; 140 kVp; and 80 effective mAs) was performed in 47 lung transplant recipients (23 women, 24 men; mean age, 41 years +/- 12 [standard deviation]; 18 without bronchiolitis, 18 with potential bronchiolitis, and 11 with bronchiolitis, as determined by lung function measurements).

Single-breath test in lateral decubitus reflects function of single lungs grafted for interstitial lung disease.

After single-lung transplantation (SLT) for emphysema, heterogeneity of ventilation distribution in the graft can be assessed by measuring the slope of the alveolar plateau, computed from a single-breath test, performed in lateral decubitus with this lung in the nondependent position. We tested the validity of this technique in patients with SLT for interstitial lung diseases (ILD). Twelve patients with SLT for ILD, 12 nontransplanted patients with ILD, and 10 healthy control subjects performed single-breath washouts in right and left lateral decubitus; nitrogen slope (S(N(2))) and the difference between SF(6) and He slopes (S(SF(6))-S(He)) were measured between 75 and 100% of expired volume.

Paradoxical worsening of tuberculosis in a heart-lung transplant recipient.

Unlabelled: We report on a heart-lung transplant recipient who presented with pulmonary tuberculosis (TB) 2.5 months after transplantation and then developed a paradoxical reaction after 4 months of adequate anti-TB treatment. She eventually recovered with anti-TB and high-dose steroid treatments.

Clostridium difficile colitis in cystic fibrosis patients with and without lung transplantation.

Background: Despite a large carriage rate of Clostridium difficile among cystic fibrosis (CF) patients, C. difficile-associated disease (CDAD) is rather rare. In case of lung transplantation, the incidence and clinical aspects of CDAD in this patient population are not well known.

Early detection of chronic pulmonary allograft dysfunction by exhaled biomarkers.

Rationale: Early detection of bronchiolitis obliterans syndrome (BOS) is important because therapies are more likely to be effective if employed early in the disease process.

Objectives: To compare the performance of exhaled NO and CO (which reflect airway inflammation) and the slope of the alveolar plateau for helium (which reflects heterogeneity of ventilation distribution) for detection of BOS stages 0-p and 1.

Methods: Recipients of bilateral (n=64) and single (n=1) lung grafts were prospectively monitored for 1,249 days; the helium slope was derived from single-breath washouts and exhaled NO and CO were measured by chemiluminescence on 933 occasions.

Acute and chronic rejection after lung transplantation.

Over the last decade, improvements in surgical techniques, lung preservation, immunosuppression, and management of ischemia-reperfusion injury and infections have contributed to increase the 1 year patient survival after lung transplantation to 70 to 80%. However, the incidence of acute rejection remains higher than after other types of solid organ transplantation, and long-term survival is threatened by bronchiolitis obliterans, which is thought to be a form of chronic allograft rejection. This article reviews major aspects of clinical presentation, risk factors, diagnosis, and management of acute and chronic rejection after lung transplantation.

Disseminated Scedosporium apiospermum infection in a cystic fibrosis patient after double-lung transplantation.

Scedosporium apiospermum is a saprophytic ubiquitous filamentous fungus. It can cause a wide spectrum of diseases, from localized to invasive infections. S apiospermum has been described as one of the major fungal agents of chronic colonization of airways in cystic fibrosis (CF) patients.

Post-transplant lymphoproliferative disorders after lung transplantation: first-line treatment with rituximab may induce complete remission.

Background: Post-transplant lymphoproliferative disorders (PTLD) are potentially lethal complications of solid organ transplantation. We, here, report on our experience with rituximab, an anti-CD20 monoclonal antibody, as first-line treatment for PTLD in six lung transplant recipients.

Patients And Methods: Two of the patients developed PTLD during the first year after transplantation, while four developed late-onset PTLD.