COVID-19 Outcomes in Lung Transplant Recipients Following Pre-Exposure Prophylaxis With Tixagevimab-Cilgavimab During the Omicron BA.5 Surge: A Single Center Analysis.

Lung transplant (LTx) recipients are at high risk for COVID-19 related morbidity and mortality. Data regarding pre-exposure prophylaxis (PrEP) with tixagevimab-cilgavimab in this population are scarce. We therefore evaluated COVID-19 breakthrough infections and COVID-19 related complications after PrEP in a retrospective single-center study, including 264 LTx recipients who received PrEP between June 2022 and December 2022, when Omicron BA.5 was the dominant circulating SARS-CoV-2 variant. PrEP was indicated for fully vaccinated patients with poor seroconversion (anti-S <260 BAU/mL). COVID-19 breakthrough infection after PrEP occurred in 11.0% within the first 3 months, increasing to 17.4% within 6 months. Hospitalization rate rose from 27.6% to 52.9% (p = 0.046), while ICU admissions and COVID-19 mortality remained low, respectively occurring in 6.5% and 4.3% of patients with breakthrough infection within 6 months. COVID-19 breakthrough infection and associated hospitalization remained an important problem during the Omicron BA.5 surge in fully vaccinated LTx recipients with deficient seroconversion, despite PrEP with tixagevimab-cilgavimab. However, ICU admissions and COVID-19 mortality were low. Waning of neutralizing effects of PrEP and changing circulating SARS-CoV-2 variants may explain increases in COVID-19 infections and hospitalizations over time after PrEP, highlighting the need for novel, long-term effective PrEP strategies in these high-risk patients.

Once daily tacrolimus conversion in lung transplantation: A prospective study on safety and medication adherence.

BACKGROUND: Lung transplantation (LTx) requires a calcineurin inhibitor-based immunosuppressive regimen. A once daily (QD) tacrolimus regimen was developed to increase medication adherence. However, data concerning its safety and efficacy in LTx are lacking. METHODS: In this prospective study, stable LTx patients were consecutively converted from twice daily (BID) tacrolimus to QD tacrolimus on a 1 mg:1 mg basis. Trough level (Cmin), renal function, cholesterol, fasting glucose, potassium and lung function were monitored six months before and up to one year after conversion. Adherence and its barriers were assessed by self-reported questionnaires (Basel Assessment of Adherence to Immunosuppressive Medications Scale (BAASIS) and Identification of Medication Adherence Barriers questionnaire (IMAB)) and blood-based assays (mean Cmin and coefficient of variation (CV)). RESULTS: We included 372 patients, in whom we observed a decrease in tacrolimus Cmin of 18.5% (p < 0.0001) post-conversion, requiring subsequent daily dose adaptations in both cystic fibrosis (CF) (n = 72) and non-CF patients (n = 300). We observed a small decrease in eGFR one year post-conversion (p = 0.024). No significant changes in blood creatinine, potassium, fasting glucose, cholesterol or rate of lung function decline were observed. In a subgroup of 166 patients, significantly fewer patients missed doses (8.4% vs. 19.3%, p = 0.016) or had irregular intake post-conversion (19.3% vs. 32.5%, p = 0.019). Mean Cmin and CV, as well as the total number of barriers, also decreased significantly post-conversion. CONCLUSIONS: In LTx, conversion from BID to QD tacrolimus (1 mg:1 mg) requires close monitoring of tacrolimus Cmin. QD tacrolimus after transplantation is safe with respect to renal function, metabolic parameters and allograft function and improves LTx recipient adherence.

How to screen for at-risk alcohol use in transplant patients? From instrument selection to implementation of the AUDIT-C.

BACKGROUND: Given that drinking >2-3 units of alcohol daily might already have adverse health effects, regular screening of at-risk drinking is warranted. We aimed to select and pilot a short instrument to accurately screen for at-risk drinking in transplant patients. METHODOLOGY AND RESULTS: Five consecutive steps were completed: A comprehensive literature review identified 24 possible self-report instruments (step 1). These instruments were scored on six yes/no criteria (ie, length, concept measured, diagnostic accuracy, population, manual available, cost) (step 2). Four nurses piloted three instruments with the highest score and were interviewed on their experiences with using the AUDIT-C, TWEAK, and Five Shot. The AUDIT-C was the easiest to use and score, and items were clear. Cognitive debriefings with 16 patients were conducted to verify clarity of instructions and items, and suggestions were incorporated into a modified version of the AUDIT-C (step 4). A convenience sample of 130 Dutch-speaking heart transplant patients completed the modified AUDIT-C during a scheduled visit (Step 5), revealing that 27.6% of patients showed at-risk drinking. CONCLUSION: The AUDIT-C might be a suitable instrument to identify at-risk drinking in routine post-transplant follow-up. Further validation, however, is indicated.

Azithromycin and early allograft function after lung transplantation: A randomized, controlled trial.

BACKGROUND: Chronic lung allograft dysfunction (CLAD) is the single most important factor limiting long-term survival after lung transplantation (LTx). Azithromycin has been shown to improve CLAD-free and long-term survival, yet the possible impact on early lung allograft function is unclear. METHODS: A prospective, randomized, double-blind, placebo-controlled trial of pre-transplant and prompt post-transplant azithromycin treatment was performed at the University Hospitals Leuven. In each arm, 34 patients, transplanted between October 2013 and October 2015, were included for analysis. Study drug was added to standard of care and was administered once before LTx (1,000 mg of azithromycin or placebo) and every other day from Day 1 until Day 31 after LTx (250 mg of azithromycin or placebo). Primary outcome was an anticipated 15% improvement of forced expiratory volume in 1 second (FEV1, percent predicted) during the first 3 months post-LTx. Secondary end-points included length of intubation, days on ventilator, duration of intensive care unit and hospital stay, prevalence and severity of primary graft dysfunction, acute rejection, infection, and CLAD-free and overall survival. RESULTS: FEV1 was not significantly different between the 2 groups (p = 0.41). Patients treated with azithromycin demonstrated less airway inflammation, with lower bronchoalveolar lavage (BAL) neutrophilia and BAL interleukin-8 protein levels at Day 30 (p = 0.09 and p = 0.04, respectively) and Day 90 (p = 0.002 and p = 0.08, respectively) after LTx. Other secondary outcomes were not significantly different between placebo and azithromycin groups. CONCLUSIONS: Pre-transplant and prompt post-transplant azithromycin treatment was not able to improve early lung allograft function. However, the known anti-inflammatory properties of azithromycin were confirmed (NCT01915082).

Pirfenidone in restrictive allograft syndrome after lung transplantation: A case series.

Pirfenidone may attenuate the decline of pulmonary function in restrictive allograft syndrome (RAS) after lung transplantation. We retrospectively assessed all lung transplant recipients with RAS who were treated with pirfenidone for at least 3 months (n = 11) in our lung transplant center and report on their long-term outcomes following initiation of pirfenidone. Main outcome parameters included evolution of pulmonary function and overall survival. Pirfenidone appears to attenuate the decline in forced vital capacity and forced expiratory volume in 1 second. Notably, 3 patients were bridged to redo-transplantation with pirfenidone for 11 (5-12) months and are currently alive, while 3 other patients demonstrate long-term stabilization of pulmonary function after 26.6 (range 18.4-46.6) months of treatment. Median overall 3-year survival after RAS diagnosis was 54.5%. Subjective intolerance, mainly anorexia and nausea, necessitating pirfenidone dose de-escalation in 55% of patients, as well as calcineurin dose increase requirements with about 20% are important complications during pirfenidone treatment after lung transplantation. Our findings provide further evidence that pirfenidone appears to be safe and may attenuate the rate of decline in lung function in patients with RAS, but the actual clinical benefit cannot be assessed in the context of this study design and requires further investigation in a larger randomized trial.

Recipient selection process and listing for lung transplantation.

Lung transplantation remains the ultimate treatment option for selected patients with end-stage (cardio) pulmonary disease. Given the current organ shortage, it is without any doubt that careful selection of potential transplant candidates is essential as this may greatly influence survival after the procedure. In this paper, we will review the current guidelines for referral and listing of lung transplant candidates in general, and in more depth for the specific underlying diseases. Needless to state that these are not absolute guidelines, and that decisions depend upon center's activity, waiting list, etc. Therefore, every patient should be discussed with the transplant center before any definite decision is made to accept or decline a patient for lung transplantation.

High-dose vitamin D after lung transplantation: A randomized trial.

BACKGROUND: Vitamin D may have innate immunomodulatory functions with potentially beneficial therapeutic effects in lung transplant recipients. METHODS: This was a single-center, double blind, randomized, placebo-controlled, prevention trial of once-monthly oral vitamin D (cholecalciferol; 100,000 IU, n = 44) vs placebo (n = 43) during 2 years in adult lung transplant recipients enrolled from October 2010 to August 2013. Primary outcome was prevalence of chronic lung allograft dysfunction (CLAD) 3 years after transplantation. Secondary outcomes included overall survival, prevalence of acute rejection, lymphocytic bronchiolitis and infection, lung function, pulmonary and systemic inflammation, and bone mineral density. RESULTS: All included patients underwent bilateral lung transplantation and were mostly middle-aged men with prior smoking-related emphysema. Levels of 25-hydroxy vitamin D after 1 year (p < .001) and 2 years (p < .001) were significantly higher in the vitamin D group compared with the placebo group. No difference was observed for CLAD prevalence (p = 0.7) or CLAD-free survival between both groups (p = 0.7). Secondary outcomes were overall comparable between both groups (all p > 0.05). CONCLUSIONS: Once-monthly oral vitamin D supplementation after lung transplantation fails to demonstrate a significant difference in CLAD prevalence, innate immunomodulatory, or a beneficial clinical effect compared with placebo.

Implementing a standardized, evidence-based education program using the patient's electronic file for lung transplant recipients.

CONTEXT: Patient education is crucial to guarantee that transplant recipients are capable of adequate self-management. Until recently, our education program to prepare lung transplant patients for discharge lacked a systematic approach, meaning that it was unclear whether all key information had been provided and whether the patient understood the information. A lack of coordination among the multidisciplinary team members also was apparent. OBJECTIVES: (1) To map out a structured education program, outlining the content, process, and evaluation of education for patients before discharge after lung transplant; (2) to integrate this program into the patient's electronic file and pilot test this new form of education tracking. METHODS: We used the conceptual framework of Lorig and colleagues, as well as the educational leaflets of the International Transplant Nurses Society, to generate the content of our education program. The interdisciplinary lung transplant team decided when and by whom each educational component should be provided, as well as the evaluation criteria. Next, information technology engineers integrated this educational program into the patient's electronic file. Nurses subsequently tested the program, and their feedback was integrated in the next version of the program. RESULTS: Health care providers experienced a higher level of uniformity and transparency. After using the education program, most patients indicated that they felt confident to go home. CONCLUSION: Our electronic educational platform is promising, yet further testing is necessary to evaluate whether patients indeed have sufficient knowledge and show adequate self-management skills in the long term after transplant.