In lung transplant recipients, long-term graft survival relies on the control of inflammation and tissue remodeling to maintain graft functionality and avoid chronic lung allograft dysfunction. ...Although advances in clinical practice have improved transplant success, the mechanisms by which the balance between inflammation and remodeling is maintained are largely unknown.
To assess whether host-microbe interactions in the transplanted lung determine the immunologic tone of the airways, and consequently could impact graft survival.
Microbiota DNA and host total RNA were isolated from 203 bronchoalveolar lavages obtained from 112 patients post-lung transplantation. Microbiota composition was determined using 16S ribosomal RNA analysis, and expression of a set of genes involved in prototypic macrophage functions was quantified using real-time quantitative polymerase chain reaction.
We show that the characteristics of the pulmonary microbiota aligned with distinct innate cell gene expression profiles. Although a nonpolarized activation was associated with bacterial communities consisting of a balance between proinflammatory (e.g., Staphylococcus and Pseudomonas) and low stimulatory (e.g., Prevotella and Streptococcus) bacteria, "inflammatory" and "remodeling" profiles were linked to bacterial dysbiosis. Mechanistic assays provided direct evidence that bacterial dysbiosis could lead to inflammatory or remodeling profiles in macrophages, whereas a balanced microbial community maintained homeostasis.
The crosstalk between bacterial communities and innate immune cells potentially determines the function of the transplanted lung offering novel pathways for intervention strategies.
Allograft rejection is a critical issue following solid organ transplantation (SOT). Immunosuppressive therapies are crucial in reducing risk of rejection yet are accompanied by several significant ...side effects, including infection, malignancy, cardiovascular diseases, and nephrotoxicity. There is a current unmet medical need with a lack of effective minimization strategies for these side effects. Extracorporeal photopheresis (ECP) has shown potential as an immunosuppression (IS)-modifying technique in several SOT types, with improvements seen in acute and recurrent rejection, allograft survival, and associated side effects, and could fulfil this unmet need. Through a review of the available literature detailing key areas in which ECP may benefit patients, this review highlights the IS-modifying potential of ECP in the four most common SOT procedures (heart, lung, kidney, and liver transplantation) and highlights existing gaps in data. Current evidence supports the use of ECP for IS modification following SOT, however there is a need for further high-quality research, in particular randomized control trials, in this area.
Chronic lung allograft dysfunction (CLAD), predominantly manifest as bronchiolitis obliterans syndrome (BOS), is the primary cause of morbidity and death after lung transplantation. We assessed the ...efficacy and safety of 2 de novo immunosuppression protocols to prevent BOS.
This was a multicenter, prospective, international, randomized (1:1) open-label superiority study of de novo enteric-coated mycophenolate sodium (MPS) vs delayed-onset everolimus (RAD), both arms in combination with cyclosporine (CsA) monitored by 2-hour post-dose (C2) levels, and corticosteroids. Target C2 levels were lower in the RAD group because RAD is known to potentiate CsA nephrotoxicity. Cytolytic induction therapy was not used. Patients were stratified at entry for cystic fibrosis. Confirmation of anastomotic healing was required for randomization. Primary efficacy was freedom from BOS Grade 1 on intention-to-treat (ITT) analysis. Secondary efficacy parameters were patient and graft survival and severity of rejection. Treatment failure was defined by graft loss, patient death, drug cessation, or need for other therapy.
The 3-year freedom from BOS Grade 1 was 70% for MPS (n = 80) vs 71% for RAD (n = 84; p = 0.95 by log-rank) in ITT but was lower in the RAD arm of the per-protocol population (p = 0.03). The 3-year survival was 84% (MPS) vs 76% (RAD; p = 0.19 by log-rank). Thirteen patients switched from MPS vs 31 from RAD (p < 0.01). Days on MPS were greater than days on RAD (p < 0.01). Rejection events proven by biopsy specimen were more common on MPS (p = 0.02), as were leucopenia (p < 0.01), diarrhea (p < 0.01), and cytomegalovirus infection (p = 0.04). Venous thromboembolism was more frequent on RAD (p = 0.02). Creatinine at 3 years was 160 ± 112 μmol/1iter in MPS patients vs 152 ± 98 μmol/1iter in RAD patients (p = 0.67).
This 3-year ITT analysis found no significant difference between arms but was underpowered to accept the null hypothesis that RAD and MPS have equivalent efficacy in preventing BOS or death after lung transplantation.
Barriers and motives towards physical activity (PA) in lung transplant (LTx) recipients with cystic fibrosis (CF) are largely unknown. We aimed to explore perceptions towards PA in LTx recipients ...with CF to better understand individuals' needs and preferences.
Participants completed an online survey at two Swiss LTx and one follow-up shared care centre between June and December 2018.
One hundred and eleven individuals completed the survey (87.4% response rate). Overall, survey participants perceive PA as important for their daily life and health. Perceived motives of PA were improving muscle strength, endurance and quality of life (QoL), to feel better, fun, to achieve personal goals and having more energy for everyday life. Fatigue was the most common perceived barrier to PA and associated with poorer QoL (r = -0.43, p<0.001) and health status (r = -0.31, p = 0.001). Participants with lung allograft dysfunction (LAD, n = 20) reported lower habitual PA (p = 0.009) and health status (p = 0.011), and rated shortness of breath, bad weather and concerns regarding lung rejection higher than those without LAD (all p<0.05). When we asked how an optimal training programme should look like, the majority would prefer individual, non-supervised (60%), outdoor (77%), endurance training (90%), once or twice a week (47%) for 40-60 minutes (48%). Only a minority of patients (14%) would be willing to use exercise applications for their home-based training.
LTx recipients with CF value PA as important for their health. People with CF should be encouraged individually by their multidisciplinary transplant team to implement PA in their daily life, potential barriers should be identified and addressed. Overall, knowledge on perceived barriers and motives for PA should be considered in the development of future patient-centred PA programmes.
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