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Cystic fibrosis transmembrane conductance regulator (CFTR) modulators are drugs that act on the defective CFTR protein in people with cystic fibrosis (pwCF), resulting in improved CFTR protein function and thus improved CF symptoms. Evidence is increasing of their positive impact on extra-pulmonary features of CF, which remains problematic in pwCF post-lung transplantation (LTx). Elexacaftor/tezacaftor/ivacaftor (ele/tez/iva) was licensed in the UK in August 2020. It has been debated since if ele/tez/iva has a role post-LTx for ongoing non-pulmonary CF symptoms. We aim to highlight the practical issues faced when considering this drug in the post-LTx CF population in a single large UK LTx unit. Retrospective analysis of electronic records of pwCF post-LTx with ongoing extra-pulmonary manifestations considered for initiation of ele/tez/iva August 2020-2021, including demographics, potential benefits, contraindications and outcomes. 5 pwCF with LTx have been discussed with their CF physicians to consider initiating ele/tez/iva (some had more than one problem):- sinus (n = 2); bowels (n = 2); weight (n = 2); other (n = 2). All were at least 12 months post-LTx (median 42 months; range 21-191 months). Discussions were initiated by the patient in 1 case, the CF team in 2, and transplant team in 2. 3 were not initiated - 1 due to potential side effects on mental health and 2 were contraindicated with deranged liver tests and ongoing bowel symptoms. 2 were initiated on ele/tez/iva. Of these, one is on tacrolimus, needed no immunosuppression adjustment, but stopped due to drop in FEV1 (CT and biopsy negative for features of rejection) which recovered. The other is on sirolimus, needed significant reduction in immunosuppression (9mg to 4mg) and remains on ele/tez/iva. Extra-pulmonary manifestations of CF are varied and continue post-LTx. With increasing evidence supporting using CFTR modulators to manage extra-pulmonary symptoms, it is important to establish the role these drugs can have in the post-LTx CF population, but also the potential risks. Our experience so far shows mixed results and that discussion between CF and transplant physicians, with patient involvement is vital to ensure correct decisions are taken. Randomised controlled trials are needed to ensure modulator use in pwCF post-LTx is supported by robust evidence. [ABSTRACT FROM AUTHOR]

Purpose The use of awake extracorporeal circulatory support (AECLS) systems, as a means of bridging to lung transplantation, was initiated in the UK at Harefield Hospital in 2011. This centre remains the only UK centre using this approach. Being awake whilst being bridged enables patients to optimize their physical health status pre transplant surgery by engaging in physiotherapy. When the programme was initiated, little was known about the impact of such an approach on the patient's psychological well-being and what psychological support might be beneficial. The aim was to understand the psychological needs of this patient cohort and employ patient feedback to enhance the care delivered to future patients undergoing AECLS. Methods The psychologist collated feedback from the experiences of patients and their relatives of AECLS in the intensive care unit. A framework for the psychological support of this cohort was developed. Engaging key stakeholders, including the physicians, surgical and nursing teams was important. Results The framework for psychological support in AECLS is supported by the team. All patients undergoing AECLS as a bridge to lung transplantation receive regular psychological support. The unit allows open visiting hours for this patient cohort in order to maximize the opportunities for social support and non- clinical activities. The team support "sunshine therapy", where possible, to facilitate a change in environment for these patients. Children are actively encouraged to visit their parent on AECLS and pleasurable activities, such as film watching and painting, are supported with the patient and their children. The prophylactic use of a mood stabilizing medication is discussed with every patient being bridged on AECLS. Conclusion Bridging to lung transplantation via AECLS continues to evolve as a strategy in the UK. Attention to the psychological support required for these patients is paramount in ensuring they are able to engage in the process, thus optimizing their physical health status pre transplant surgery. With good psychological support, patient distress can be minimized at what is clearly a stressful time for them and their family. Patient experience feedback is a valid tool for driving the development of effective psychological care. [ABSTRACT FROM AUTHOR]

Lung transplantation outcomes are limited by chronic lung allograft dysfunction (CLAD). Infection driven loss of graft function is a common cause of CLAD. Extracorporeal photopheresis (ECP) is a salvage therapy post lung transplantation with the indications broadening as experience and availability increases. The therapeutic role of ECP is yet to be explored in infection driven CLAD. A retrospective audit of all lung transplant recipients at a single UK lung transplant centre who received ECP from 2017 to 2021 was performed using electronic records.5 patients with infection driven CLAD treated with ECP were identified. 40% were male with median(range) age 63(30-70) years. Median duration from lung transplant to ECP was 38(13-53)months and median duration of ECP was 14(10-15) months. All 5 patients were responders at 2 months (defined as less than 20 percent FEV1 fall). Median(range) FEV1 percentage change improved from -17% (-20 to+10%) one year pre-ECP to +1%(-1to+10%) one year post-ECP (Figure1). Mycophenolate mofetil was stopped for all patients on initiation of ECP. 4 patients had a reduction in length of stay in hospital (Figure 2). 3 patients were alive 1 year post ECP whilst 2 patients are still within their first year of follow up. ECP can help to stabilize graft function in lung transplant recipients with recurrent infections. It allows for modification of conventional immunosuppression regimens and contributes to improved quality of life by decreasing the length of hospital stay and number of antibiotic days. [ABSTRACT FROM AUTHOR]

Cystic fibrosis (CF) is a life-limiting genetic condition with which often leads to life-threatening respiratory failure requiring lung transplantation. People with CF (PwCF) account for 16% of adult bilateral lung transplants internationally according to a 2016 report of the ISHLT Registry by Yusen et al. With the advent of effective CFTR (cystic fibrosis transmembrane conductance regulator) modulators becoming widely available in recent years, for many PwCF the clinical response has been transformative, and a significant proportion no longer meet criteria for lung transplantation referral and listing. A retrospective analysis was undertaken of the number of PwCF referred in the last 12 months (i.e. since the CFTR modulators tezacaftor/ivacaftor and elexacaftor/tezacaftor/ivacaftor became widely available in the UK) compared to the previous 3 years, for lung transplantation at Harefield Hospital. The impact of CFTR modulators on the Lung Transplant Waiting List at Harefield Hospital was also assessed. As of October 2020, of the 25 PwCF who were assessed for lung transplantation and met criteria for listing at time of assessment, only 7 (28%) remain actively listed. All of the others (n=18; 72%) were suspended after starting a CFTR modulator (of which 12 were suspended in the last 12 months). Median improvement in FEV1(%) after starting a modulator in those who subsequently suspended was 10% (range 0-24%). Referrals of PwCF in the last 12 months was 22 compared with an average of 37 referrals per year over the preceding 3 years. Only 14% (7/49) of the current active waiting list for double lung transplantation are PwCF compared with 26% (19/73) a year ago. The improvement in quality of life and lung function in PwCF eligible for CFTR modulators can be transformative. However, those who continue to decline despite this treatment, are likely to be older, have multiple CF-related comorbidities, and may be more complex surgical candidates. Transplant centres face a changing landscape as transplant lists become increasingly populated with other patient groups. Those continuing to transplant PwCF need to become experienced at managing complex CF comorbidities. [ABSTRACT FROM AUTHOR]

Lung transplant patients are at increased susceptibility to fungal infections. Isavuconazole, a triazole anti-fungal with broad-spectrum activity against medically important fungal pathogens, received a marketing authorisation in the U.K. in 2015. The use of isavuconazole has advantages over voriconazole and posaconazole as it presents a more favourable toxicity profile. There is some, but very limited data appraising its clinical effectiveness, but this is predominantly in the context of anti-fungal prophylaxis. This research looks to review the experience of a single centre by reviewing clinical outcome data in lung transplant patients who received isavuconazole as treatment for invasive fungal infections. We performed a single-centre retrospective study to describe the clinical outcome data from patients commenced on treatment with Isavuconazole for invasive fungal infections between October 2016 and December 2019. We assessed outcomes at 3 months and 6 months post-commencement of treatment including patient reported improvement of presenting symptoms, stability or improvement in lung function (FEV1), radiological improvement or histocytoloical resolution on bronchoscopy (including galactomannan and persistent invasion of fungal hyphae/pseudohyphae or features in keeping with fungal infection). Fifty patients were treated with isavuconazole during the study period. Eleven patients were excluded from analysis (two due to transfer of care to a different centre and nine due to early treatment cessation). Of the thirty-nine patients, twenty-six were treated for possible and thirteen were treated for proven invasive fungal infection. A range of fungal isolates were encountered. Treatment success was observed in 60% (n=24). Isavuconazole was well tolerated by most patients (n = 37). Isavuconazole is well tolerated and appears effective in the management of invasive fungal infection after lung transplantation. The limitations of this study are that it is a single centred, retrospective study, however, is the largest case series to date where clinical effectiveness of Isavuconazole has been appraised. [ABSTRACT FROM AUTHOR]

Background: Long-term survival after lung transplantation is limited compared with other organ transplants. The main cause is development of progressive immune-mediated damage to the lung allograft. This damage, which can develop via multiple immune pathways, is captured under the umbrella term chronic lung allograft dysfunction (CLAD). Despite the availability of powerful immunosuppressive drugs, there are presently no treatments proven to reverse or reliably halt the loss of lung function caused by CLAD. The aim of the E-CLAD UK trial is to determine whether the addition of immunomodulatory therapy, in the form of extracorporeal photopheresis (ECP), to standard care is more efficacious at stabilising lung function in CLAD compared with standard care alone., Methods and Analysis: E-CLAD UK is a Phase II clinical trial of an investigational medicinal product (Methoxsalen) delivered to a buffy coat prepared via an enclosed ECP circuit. Target recruitment is 90 bilateral lung transplant patients identified as having CLAD and being treated at one of the five UK adult lung transplant centres. Participants will be randomised 1:1 to intervention plus standard of care, or standard of care alone. Intervention will comprise nine ECP cycles spread over 20 weeks, each course involving two treatments of ECP on consecutive days. All participants will be followed up for a period of 24 weeks.The primary outcome is lung function stabilisation derived from change in forced expiratory volume in one second and forced vital capacity at 12 and 24 weeks compared with baseline at study entry. Other parameters include change in exercise capacity, health-related quality of life and safety. A mechanistic study will seek to identify molecular or cellular markers linked to treatment response and qualitative interviews will explore patient experiences of CLAD and the ECP treatment.A patient and public advisory group is integral to the trial from design to implementation, developing material to support the consent process and interview materials., Ethics and Dissemination: The East Midlands-Derby Research Ethics Committee has provided ethical approval (REC 22/EM/0218). Dissemination will be via publications, patient-friendly summaries and presentation at scientific meetings., Trial Registration Number: EudraCT number 2022-002659-20; ISRCTN 10615985., Competing Interests: Competing interests: AJF has received honoraria for speaking at educational meetings organised by Mallinckrodt Pharmaceuticals., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: A new UK Lung Allocation Scheme (UKLAS) was introduced in 2017, replacing the previous geographic allocation system. Patients are prioritised according to predefined clinical criteria into a three-tier system: the super-urgent lung allocation scheme (SULAS), the urgent lung allocation scheme (ULAS) and the non-urgent lung allocation scheme (NULAS). This study assessed the early impact of this scheme on waiting-list and post-transplant outcomes., Methods: A cohort study of adult lung transplant registrations between March 2015 and November 2016 (era-1) and between May 2017 and January 2019 (era-2). Outcomes from registration were compared between eras and stratified by urgency tier and diagnostic group., Results: During era-1, 461 patients were registered. In era-2, 471 patients were registered (19 (4.0%) SULAS, 82 (17.4%) ULAS and 370 (78.6%) NULAS). SULAS patients were younger (median age 35 vs 50 and 55 for urgent and non-urgent, respectively, p=0.0015) and predominantly suffered from cystic fibrosis (53%) or pulmonary fibrosis (37%). Between eras 1 and 2, the odds of transplantation within 6 months of registration were increased (OR=1.41, 95% CI 1.07 to 1.85, p=0.0142) despite only a 5% increase in transplant activity. Median time-to-transplantation during era-1 was 427 days compared with waiting times in era-2 of 8 days for SULAS, 15 days for ULAS and 585 days for NULAS patients. Waiting-list mortality (15% era-1 vs 13% era-2; p=0.5441) and post-transplant survival at 1 year (81.3% era-1 vs 83.3% era-2; p=0.6065) were similar between eras., Conclusion: The UKLAS scheme prioritises the critically ill and improves transplantation odds. The true impact on waiting-list mortality and post-transplant survival requires further follow-up., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The demand for lung transplantation vastly exceeds the availability of donor organs. This translates into long waiting times and high waiting list mortality. We set out to examine factors influencing patient outcomes from the time of listing for lung transplantation in the UK, examining for differences by patient characteristics, lung disease category and transplant centre., Methods: Data were obtained from the UK Transplant Registry held by NHS Blood and Transplant for adult lung-only registrations between 1January 2004 and 31 March 2014. Pretransplant and post-transplant outcomes were evaluated against lung disease category, blood group and height., Results: Of the 2213 patient registrations, COPD comprised 28.4%, pulmonary fibrosis (PF) 26.2%, cystic fibrosis (CF) 25.4% and other lung pathologies 20.1%. The chance of transplantation after listing differed by the combined effect of disease category and centre (p<0.001). At 3 years postregistration, 78% of patients with COPD were transplanted followed by 61% of patients with CF, 59% of other lung pathology patients and 48% of patients with PF, who also had the highest waiting list mortality (37%). The chance of transplantation also differed by height with taller patients having a greater chance of transplant (HR: 1.03, 95% CI: 1.02 to 1.04, p<0.001). Patients with blood group O had the highest waiting mortality at 3 years postregistration compared with all other blood groups (27% vs 20%, p<0.001)., Conclusions: The way donor lungs were allocated in the UK resulted in discrepancies between the risk profile and probability of lung transplantation. A new donor lung allocation scheme was introduced in 2017 to try to address these shortcomings., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)