As of April 2022, the Mater Hospital serves 190 patients who have been the recipient of a lung transplant in Ireland. During the COVID-19 pandemic, solid organ transplant was recognised as a risk factor for progression to severe disease. In January 2022, the European Medicines Agency (EMA) approved the use of Sotrovimab for high risk patients. Sotrovimab is a monoclonal antibody which neutralises SARS-CoV-2 with recent data showing efficacy in reducing the risk of progression to severe disease in high risk patients1. We aim to describe our patient cohort and the rates of COVID-19 infection seen before and after the introduction of monoclonal antibody therapy. While likely reflecting emerging variants resulting in less severe disease, we observe variation in morbidity and mortality in this time. From March 2020 to April 2022, 116 post-lung transplant patients tested positive for COVID-19 infection. This represents 61% of our overall population. Since January 2022, coinciding with the surge of the omicron variant, 57 patients contracted COVID-19. 47 were deemed to be suitable for treatment with 10 presenting outside the window for therapeutic intervention. 3.5% (n=2) required ICU admission and 2 died directly as a result of COVID-19. Prior to this, 58 patients contracted COVID-19, 31 of which (53.5%) required hospital admission with 18 (58%) requiring ICU admission. Overall we saw 13 deaths representing 22.4% of this group and 6.8% of the overall population. 1. Gupta A, Gonzalez-Rojas Y, Juarez E, Crespo Casal M, Moya J, Falci DR, Sarkis E, Solis J, Zheng H, Scott N, Cathcart AL. Early treatment for Covid-19 with SARS-CoV-2 neutralizing antibody sotrovimab. New Englad Journal of Medicine. 2021 Nov18;386(21):1941-50

Introduction: An increased risk of malignancy post-lung transplant (LTx) is established as a complication related to reduced immunosurveillance and patient demographics. Aims: To identify the incidence, risk factors and clinical characteristics of solid-organ malignancy following LTx at The Irish National Lung Transplant Centre. Methods: A retrospective single centre review of all 216 patients transplanted between 2005-2017. Data collected included patient demographics, transplant indication, surgery, smoking status, histological sub-type, TNM staging and outcomes. Results: Nineteen patients were diagnosed with a solid-organ malignancy following LTx during follow-up (8.8%). The median time interval between transplant and cancer diagnosis was 32 months (range 12-133 months). Age at the time of transplant was significantly higher in those who subsequently developed malignancy (p=0.028, mean 58.3 v 49.7 years). Single LTx recipients appear at higher risk compared to double LTx recipients (OR 3.17, 95% CI 1.10-9.14). No single indication for LTx was identified as an independent risk factor. Bronchogenic carcinoma was the most common malignancy (n=11, 5.1%); the majority were identified in the native lung of single transplant recipients (9 of 11). 82% were ex-smokers. Squamous cell carcinoma was the most common subtype (n=5). Five patients were stage IV at diagnosis with an overall 1-year mortality of 82%. Conclusions: Bronchogenic carcinoma is the most common solid organ malignancy post LTx and has a high mortality. Risk factors include older age and single LTx. Despite close prospective monitoring, early detection remains challenging and adequate adequate screening guidelines post-transplant are currently lacking.

Introduction: Identification of risk factors that predict poor survival can aid clinical decision making and allow optimization of any potentially modifiable factors (Stephenson, A.L. et al. J Heart Lung Transplant 2015;34:1139–1145). This may facilitate improved patient selection and ultimately improve overall outcomes. Aims: To describe the Irish experience of co-morbidity post-transplant for cystic fibrosis and to investigate potential non-pulmonary pre-transplant risk factors that could impact on long term survival. Methods: We performed a retrospective review of all 61 patients who received a lung transplant for cystic fibrosis between 2008-2017 at The Irish National Lung Transplant Centre. We recorded patient demographics, co-morbidities and survival. A t-test was used for comparison of mean values. Results: The overall 5-year survival post-transplant is 73.8%. The mean age at transplant is 29.8 years (range 17.8-59.9) with a male predominance (69%). 64% were homozygous ∆F508 genotype. When comparing the 13 patients who have subsequently died to the 48 patients currently alive, the mean age at transplant was significantly lower (25 vs 31 years, p=0.034), mean BMI prior to transplant was lower (19.1 v 20.8, p=0.045) and creatinine clearance prior to transplant was reduced (103 v 136, p=0.031). Of the 48 patients who remain under review, chronic kidney disease is common with 54% of patients having an eGFR <60ml/min. The prevalence of diabetes increased from 38% at listing to 71% at follow–up. Conclusions: There is a high prevalence of non-graft complications post-transplant. Pre-transplant factors that are most predictive poor outcomes in our centre include younger age, lower BMI and reduced renal function.

Influenza is a significant cause of morbidity and mortality following lung transplant. We employ trivalent vaccination as per National Policy in our centre. The trivalent inactivated vaccine (TIV) is not protective against the 2017-18 circulating stain of Influenza B. We reviewed the outcomes in 221 lung transplants recipients post vaccination. All Patients are subject to influenza surveillance. Data include viral swabs, severity of symptoms, history of vaccination, immunosuppression and outcomes for lung transplant patients from November 2017 to date. Ten patients have Influenza DNA detection of which 2 Influenza A and 8 Influenza B. The 10 cases had been vaccinated with the TIV vaccine. The cases presented in January 2018, were stratified as 1) mild, which were discharge home, or 2) severe, which required hospitalisation. All cases were treated with Oseltamivir (nebulised Zanamivir was added in the one of the Influenza B cases). Admission rates from Influenza B were 40%, and 1 patient admitted to intensive care unit died. All Influenza B cases were confirmed as B/Phuket/3073/2013-like (B/Yamagata lineage) virus. The costs for admission were €60,000 as per HSE reimbursement versus a total of €6000 Quadrivalent vaccination (QIV). In our cohort, 80% were infected by Influenza B/Yamagata strain, poorly covered by TIV. Immunocompromised patients may benefit from QIV vaccination leading to a cost benefit by reducing hospitalization, morbidity and mortality.

Alpha1-antitrypsin deficiency (AATD) is characterized by low level of apha-1 antitrypsin, which predispose lung to unprotected proteolytic activity. We observed in our centre that patients with AATD suffer from severe bronchial anastomotic complication. We wanted to determine whether there is difference in post-transplant airway complications between AATD emphysema and emphysema without AATD (EMPH). We performed a retrospective analysis to compare the post-transplantation course of patients with AATD and EMPH. Data collection includes demographic and functional baseline of recipients, primary outcome as bronchial anastomotic complication and secondary end points as survival data. A total of 163 patients were transplanted from January 2005 to May 2016 in our centre, with follow up until August 2016. Out of these, 34 patients had either diagnosis of AATD (35.3%) or EMPH(64.7%). There was a male preponderance of 75% in AATD. Both groups had predominantly double lung transplant. Population with AATD was younger compare to EMPH (mean age 53.5 ± 7.9 vs 60 ± 4.6, p ‹ 0.01). There was no statistical difference in FEV1 pre and post-transplant between groups. 4 (33%) AATD patients had bronchial anastomotic complication (versus 0 in EMPH, p value = 0.011) with median onset 4 months post-transplant, and odd ratio of 1.5 (95%CI, 1.005-2.238). Survival curve showed no difference between both group (p=0.512) with mean survival AATD 29.6 ± 4.3 months and EMPH 44.2 ± 10.8 months. This observation study extends the available knowledge. The findings indicate that AATD patients may have higher risk for developing bronchial anastomotic complication. More robust data and multicentre analysis would be needed for further confirmation.

Introduction In recent years there has been a large increase in rates of lung transplantation for IPF patients. This has driven by the introduction of the Lung Allocation Score in the US, which prioritises patients based on treatment need and benefit. Increasing rates of transplantation have led to older patients being considered for transplant listing. The aim of this study was to assess the survival, functional capacity and quality of life of IPF patients aged over 70 attending our transplant programme. Methods Post-transplant IPF patients aged 70 years or older were identified from the National Lung Transplant Registry. Health-related Quality of Life (HRQL) was assessed using the 36-item Medical Outcomes Survey Short Form (SF-36). Functional status was assessed by exercise tolerance, pulmonary function and level of respiratory support. HRQL was compared to published datasets from randomised clinical trials of drug therapy as well as prospective studies in lung transplant recipients. Results 6 patients met the inclusion criteria, mean age 72.5 ± 0.8 yrs. The mean time from transplant was 3.8 ± 1.5 yrs (range 2.3 – 7.0 yrs). Compared to the BUILD-1 trial (similar age, limited IPF), minimal important clinical differences (MID)1 were seen across many components of the SF-36 score. These MIDs included physical functioning (+7.1), health perception (+29.2) and vitality (+17). Compared to a post-transplant cohort of younger IPF patients (61.0 ± 1.5 yrs)2 the mental component score (MCS) was higher in this study (+12.2). These benefits in MCS were maintained when compared to patients in the IFIGENIA study of N-acetylcysteine and the STEP-IPF study of sildenafil. The mean reported exercise tolerance of our patient group was 1.2 km, and no patient required supplementary oxygen or respiratory support. Compared to pre-transplant status large benefits in function were noted (mean pre-transplant 6MWT was 314 ± 91 m with 6 L oxygen/minute). Conclusion Lung transplantation provides clinically meaningful benefits in HRQL and functional outcomes in patient’s ≥ 70 yrs old. This study highlights that these benefits are comparable to younger IPF patients who receive lung transplant and more beneficial to those reported in drug trials. References 1 Respir Med. 2010;104(2):296–304 2 J Heart Lung Transplant. 2014;33(5):514–520

Introduction and Objectives Idiopathic pulmonary fibrosis (IPF) is a chronic, fibrosing interstitial pneumonia of unknown aetiology. Its clinical course is unpredictable but invariably leads to progressive respiratory failure and death. Median survival from time of diagnosis, without transplant, is 2–3 years. IPF patients referred for transplantation often suffer from poor outcomes, due to organ shortage and rapid disease progression. In America, the introduction of the lung allocation score has greatly benefited the IPF cohort. Furthermore, an increasing proportion of these transplants have occurred in patients over the age of 65 - an age group that had previously been associated with high post-transplant mortality. Recent data has however contradicted this, showing that surgical outcomes and survival are satisfactory in this age group. In a condition with no disease modifying medical therapy, we reviewed the survival benefit of lung transplantation in age-stratified groups to see if our data matched those seen internationally and to encourage further transplantation in this older population. Methods All patients with IPF who received lung transplantation in Ireland, since the beginning of the transplant service in 2005, were included (n = 30). Data collected included patient demographics, lung function, transplant details and survival data. Survival data was compared with IPF patients who had died while awaiting a transplant over the past 3 years (n = 20). Results For those patients on the lung transplant waiting list, who did not receive a transplant, survival was unfortunately poor (75% at 6 months, 30% at 12 months, and 15% at 18 months). However, following transplantation, all-age survival was 96.6% at 1 year, 90.1% at 2 years and 78.9% at 5 years. The 5 year survival for those transplanted over the age of 65 was 88.9% (n = 9). Conclusion As patients who suffer from IPF commonly present in their 7th decade, the consideration of patient age is pertinent when referring for transplantation. Although, many centres view age greater than 65 as a relative contraindication to lung transplantation, we feel that this data reinforces the alternative viewpoint - that age should not be a limiting factor, in carefully selected candidates.

Background Osteoporosis after a lung transplant is common, with reported vertebral fracture rates of up to 30% [1]. Bisphosphonates, and calcium and vitamin D supplements may be less effective in patients who remain on steroid treatment [2]. Corticosteroids are more detrimental to spinal bone mineral density than to the hip [2]; however risk prediction systems use hip T-scores to predict risk and make treatment recommendations [3, 4]. We reviewed the prophylaxis of osteoporosis in a cohort of patients at the time of listing and up to 6 years post-transplant. Purpose We wished to identify: any potential for improvement in prescribing risk factors for clinically significant lumbar fractures the utility of currently available osteoporosis risk algorithms in this cohort. Materials and Methods We conducted a retrospective chart review (n = 27). Patients’ risk of fracture at the time of listing for transplant was calculated using three different methods including WHO charts and American College of Rheumatology algorithm for steroid-treated patients. We attempted to create a model to predict fracture in transplant recipients using known risk factors. Results At time of listing, all patients were taking at least 5 mg of prednisolone daily plus a bisphosphonate and appropriate calcium and vitamin D supplementation. Many already had osteoporotic T scores at this point. Fracture rates in our cohort are in line with published data, but substantially higher than those predicted from algorithms. Improvised algorithms using lumbar T scores were better at predicting risk than published methods. The only risk factor in our cohort that predicted subsequent fracture was lumbar spine T-score (Mean −1.2 versus −2.65 in the fracture group (P = 0.009)). Conclusions Current algorithms underestimate risk, new charts should be created using lumbar T-scores. Our results emphasise that current prophylaxis strategies are not successful in preventing fractures in those who have osteoporosis and remain on prednisolone. Early osteoporosis prophylaxis and alternative treatments are essential to prevent fractures. References Cohen A, Shane E, (2003). Osteoporosis after solid organ and bone marrow transplantation. Osteoporos Int 14, 617–30. Weinstein RS, (2011). Glucocorticoid-Induced Bone Disease. N Engl J Med 365, 62–70. World Health Organization Collaborating Centre for Metabolic Bone Diseases, University of Sheffield, UK. Online risk prediction tool. http://www.shef.ac.uk/FRAX/tool.jsp?country=1 (accessed 3 Nov 2011). Grossman JM, et al, (2010). American College of Rheumatology 2010 recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Care Res 62, 1515–26. No conflict of interest.