Including Lung Transplantation Research Articles

Prior immunity to Ureaplasma urealyticum protects against respiratory infection in immunosuppressed mice.

Ureaplasma species can cause systemic infections in immunocompromised hosts, including lung transplant recipients. Here, we investigated the impact of prior exposure to Ureaplasma urealyticum on the risk of U. urealyticum and Ureaplasma parvum infection in mice subjected to an immunosuppression regimen similar to that administered to solid organ transplant recipients. Mice were immunized with three intramuscular injections of U. urealyticum, with control mice injected with adjuvant only. Following immunization, mice received tacrolimus, mycophenolate mofetil, and methylprednisolone, and then were challenged with U. urealyticum or U. parvum intraperitoneally and intratracheally over 6 days. Relative U. urealyticum antibody levels in plasma were assessed over time, and lungs were harvested at sacrifice for bacterial load quantification, assessed using a color-changing unit assay. U. urealyticum antibody levels were higher in immunized compared with control animals (P < 0.0001), even when animals were immunosuppressed. U. urealyticum and U. parvum lung burden was reduced in immunized compared with control mice (~6 log10 reduction for U. urealyticum and <1 log10 reduction for U. parvum; P = 0.008 and 0.046, respectively). In summary, this study shows that prior exposure to live U. urealyticum provides some protection against infection with U. urealyticum.IMPORTANCEUreaplasma-induced hyperammonemia syndrome is a rare but potentially deadly complication of solid organ transplantation, especially lung transplantation. The pathophysiology of this relatively recently recognized condition is poorly understood, and it is unclear what factors may influence patient susceptibility. This study investigates the possible protective effects of prior exposure to Ureaplasma urealyticum in a mouse model subjected to an immunosuppression regimen similar to that given to lung transplant recipients. The findings show that prior exposure could provide protection against Ureaplasma lung infection.

Ceftazidime-avibactam treatment dilemma of blaKPC−2-containing Klebsiella pneumoniae due to the development of co-existence of mixed strains carrying blaKPC−2 or blaKPC−33 in lung transplant recipients

BackgroundCarbapenem-resistant Klebsiella pneumoniae (CRKP) poses a significant threat to immunocompromised populations, including lung transplant recipients. This study investigates mixed CRKP strains carrying either blaKPC−2 or blaKPC−33 following ceftazidime-avibactam (CAZ/AVI) exposure, particularly in the context of lung transplantation. Mixed CRKP strains with shifting resistance phenotypes were frequently identified in patients exposed to CAZ/AVI. We aimed to elucidate the transitional state of blaKPC variants by selecting CAZ/AVI-sensitive and -resistant CRKP strains from a lung transplantation patient.MethodsThe blaKPC-variant-carrying CRKP strains were collected from lung transplant recipients exposed to CAZ/AVI in less than two years. Antibiotic susceptibility testing (AST) was conducted using microbroth dilution, and whole-genome sequencing (WGS) was used to identify genotypes and resistance mechanisms. Limiting dilution, drop-plate, and in vitro induction experiments determined blaKPC-variant changes during CAZ/AVI administration. qPCR primers/probes were designed to identify blaKPC−2 mutations.ResultsAmong 104 lung transplant recipients infected by blaKPC-harboring CRKP strains and receiving CAZ/AVI, 10 (9.6%) experienced changing resistance phenotypes. The limiting dilution method found that Patient 10’s CRKP strains carried either blaKPC−2 or blaKPC−33. The drop-plate experiment showed differing growth patterns on CAZ/AVI mediums. The in vitro induction experiment demonstrated shifting from blaKPC−2 to blaKPC−33.ConclusionsThe study identified a “transitional state” of the mixed CRKP strains carrying either blaKPC−2 or blaKPC−33 in CAZ/AVI-exposed patients. Molecular diagnostics are crucial for identifying mixed strains and the transitional state of blaKPC variants, guiding treatment decisions in this complex landscape.

Impact of Long-Term Atorvastatin Therapy on the Development of Chronic Lung Allograft Dysfunction in Patients with Azithromycin Prophylaxis after Lung Transplantation

ObjectiveTo assess the impact of long-term atorvastatin (ATO) therapy on reducing recipient inflammation and immune response, thus lowering the risk of chronic lung allograft dysfunction (CLAD) in lung transplant recipients. This study aimed to investigate the effects of ATO on overall survival, lung function recovery, and its influence on inflammatory factors alongside azithromycin (AZI) prophylaxis. MethodsThis retrospective single-center study included lung transplant recipients from January 2017 to December 2022. Patients who survival >1 year after lung transplantation and who were receiving AZI prophylaxis for >6 months were selected. Outcome measures involved pulmonary function assessments at various time points after AZI treatment, complete blood cell analysis, and inflammatory factor evaluations. ResultsThe incidence of CLAD was significantly lower in the long-term ATO group compared with those not on ATO (P = .011). Long-term ATO treatment significantly delayed CLAD onset after lung transplantation (850 days vs. 630 days; P = .041), with patients showing notably enhanced lung function recovery within 6 months of AZI therapy compared with the non-ATO group. Neutrophil levels decreased in patients with CLAD, and interleukin-6 concentrations significantly decreased in the AZI + ATO group compared with the AZI group. Overall patient survival was significantly better in the AZI+ATO group than in the AZI group (P = .02). ConclusionIn cases where CLAD develops despite AZI prophylaxis, long-term ATO treatment may lead to short-term improvements in lung function. It could also decrease inflammation levels in lung transplant recipients and enhance overall survival. The combination of AZI and long-term ATO therapy may be beneficial for CLAD prevention.

The Ligament of Marshall: Far From Vestigial!

BackgroundThe ligament of Marshall (LOM) is a vestigial fold of the left atrium that contains the remnant left cardinal vein, muscle bundles, and nerve fibers. Despite its description as an embryologic remnant, the LOM carries significant clinical importance as an important focus for atrial fibrillation propagation as well as a therapeutic target. MethodsIn this review, we discuss the embryologic origins of the LOM, its physiology and importance in atrial fibrillation pathogenesis, as well as the role of targeting and ablating the LOM surgically during concomitant cardiac surgery including lung transplantation. ResultsThe LOM, particularly its distal segment, is an important focus for atrial fibrillation as both a primary trigger as well as an accessory bundle for signal propagation. It is a key target for electrophysiologic therapies including radiofrequency and alcohol-based ablative strategies. The LOM is also a crucial target for surgical ablation while addressing the left atrial lesion sets. This is often performed concomitantly with other cardiac surgical operations and may play an important role in reducing the risk of postoperative atrial fibrillation after lung transplantation. ConclusionsFar from just a vestigial structure, the ligament of Marshall remains an important focus for paroxysmal atrial fibrillation and is a potent therapeutic target for both electrophysiologic and surgical approaches.

Evaluating the efficacy and safety of letermovir compared to valganciclovir for the prevention of human cytomegalovirus disease in adult lung transplant recipients.

Lung transplant recipients are at high risk for severe cytomegalovirus (CMV) disease. Off-label use of letermovir (LET) may avert myelotoxicity associated with valganciclovir (VGCV), but data in lung transplantation are limited. This study aims to evaluate the outcomes of LET prophylaxis among lung transplant recipients. This retrospective, matched cohort study included lung transplant recipients who received LET for primary CMV prophylaxis following VGCV intolerance. Patients were matched 1:1 to historical VGCV controls based on age, serostatus group, and time from transplant. The primary outcome was CMV breakthrough within 1 year post-LET initiation; secondary outcomes included hematologic changes. A total of 124 lung transplant recipients were included per group (32% CMV mismatch, D+R-), with LET initiated a median of 9.6 months post-transplantation. One CMV breakthrough event (0.8%) was observed in the LET group versus four (3.2%) in the VGCV group (p=.370). The median (interquartile range) white blood cell (WBC) count was3.1 (2.1-5.6)at LET initiation which increased to5.1 (3.9-7.2)at the end of follow-up (p <.001). For VGCV controls, WBC was4.8 (3.4-7.2)at baseline and5.4 (3.6-7.2)at the end of follow-up; this difference was not statistically significant (p=.395). Additionally, 98.4% of LET patients experienced ≥1 leukopenia episode in the year prior to LET compared to 71.8% the year after initiation (p <.001). Similar results were observed for neutropenia (48.4% and 17.7%, p <.001). LET prophylaxis was associated with a low rate of CMV reactivation and leukopenia recovery. LET may represent a reasonable prophylaxis option for lung transplant recipients unable to tolerate VGCV.

Effect of letermovir initiation on tacrolimus concentrations among lung transplant recipients receiving concomitant azole antifungal prophylaxis.

The antiviral letermovir has been increasingly used as off-label cytomegalovirus prophylaxis in solid organ transplant recipients. Observational studies have reported notable increases in tacrolimus (FK) exposure following letermovir; however, whether a significant interaction occurs in the setting of existing moderate-to-strong CYP3A4 inhibition is unknown. Therefore, the purpose of this study was to evaluate FK trough changes before and after letermovir among lung transplant recipients receiving azole antifungal prophylaxis. This retrospective cohort study included lung transplant recipients newly initiated on letermovir between 2019-2022 following valganciclovir intolerance. Tacrolimus doses and concentrations were collected up to 30 days before and after the letermovir start date. No pre-emptive FK dose adjustments occurred prior to letermovir initiation. Patients admitted to the hospital or lacking an appropriately timed trough in the pre- or post-period were excluded. A total of 78 lung transplant recipients receiving FK (1.5mg median total daily dose) and itraconazole (56.4%), isavuconazole (25.6%) or posaconazole (17.9%) prophylaxis were included. Letermovir was started at a median of 8.4 months post-transplant. The pre-/post-letermovir median FK trough was 9.6/9.0ng/mL (p = .151), median dose-corrected trough was 4.2/4.7ng/mL/mg (+11.9%, p = .032), and median weight-based dose-corrected trough was 362/326 [ng/mL]/[mg/kg/day] (-9.9%, p = .036). There was no significant difference in the proportion of patients within their goal trough range before and after letermovir initiation (62%vs. 72%, p = .229). Empiric FK dose adjustments do not appear warranted before letermovir initiation in lung transplant recipients receiving antifungal prophylaxis with moderate-to-strong CYP3A4 inhibitors.

Clinical characteristics and outcomes of pleural aspergillosis: a review of 13 cases.

Aspergillus pleurisy is a rare complication of invasive pulmonary aspergillosis (IPA), associated with a poor prognosis. The morbidity and mortality of this condition have not been thoroughly studied, and recent research on this topic is limited. The current study included 13 patients diagnosed with Aspergillus pleurisy, with the majority presenting concomitantly with a bronchopleural fistula. Among these patients, nine had a history of thoracic surgery, including lung transplantation and lobectomy. Four patients refused further treatment and were discharged against medical advice, while one patient succumbed to massive hemoptysis 2 years after discharge. This case series provides essential insights into Aspergillus pleurisy and evaluates the therapeutic strategy based on a limited cohort.

Baseline Blood Levels of Mucin-1 Are Associated with Crucial On-Treatment Adverse Outcomes in Patients with Idiopathic Pulmonary Fibrosis Receiving Antifibrotic Pirfenidone.

Mucin-1 is a multi-functional glycoprotein expressed by type II alveolocytes and may be detectable in the circulation following pulmonary fibrosis. The prognostic utility of baseline pre-treatment blood levels of mucin-1 in patients with idiopathic pulmonary fibrosis (IPF) receiving antifibrotics has not yet been fully established. We retrospectively studied a cohort of patients (from two hospitals) with IPF who were receiving pirfenidone for >12 weeks. Baseline blood mucin-1 levels were measured via sandwich enzyme-linked immunosorbent assays. We investigated the performance of mucin-1 levels in longitudinally predicting the risks of acute exacerbation of IPF (AE-IPF) and severe adverse outcomes (SAO), including lung transplantation and death. Seventy patients were included; 20 developed AE-IPF; and 31 had SAO during the follow-up period. Patients with baseline mucin-1 levels ≥2.5 ng/mL had enhanced risks of AE-IPF (adjusted hazard ratio [aHR], 14.07; 95% confidence interval [CI], 4.26-46.49) and SAO within 2 years (aHR, 7.87; 95% CI, 2.86-21.70) and anytime during the follow-up (aHR, 4.68; 95% CI, 2.11-10.39). The risks increased across subgroups with increasing mucin-1 levels. Patients in the "mucin-1 ≥ 2.5" group also exhibited an accelerated decline in DLCO. This study supports baseline blood mucin-1 levels as a biomarker for IPF that predicts adverse outcomes during pirfenidone treatment.

Prevalence and clinical significance of potential drug-drug interactions among lung transplant patients.

Background: Drug-drug interactions (DDIs) are a major but preventable cause of adverse drug reactions. There is insufficient information regarding DDIs in lung transplant recipients. Objective: This study aimed to determine the prevalence of potential DDIs (pDDIs) in intensive care unit (ICU) lung transplant recipients, identify the real DDIs and the most frequently implicated medications in this vulnerable population, and determine the risk factors associated with pDDIs. Methods: This retrospective cross-sectional study included lung transplant recipients from January 2018 to December 2021. Pertinent information was retrieved from medical records. All prescribed medications were screened for pDDIs using the Lexicomp® drug interaction software. According to this interaction software, pDDIs were classified as C, D, or X (C = monitor therapy, D = consider therapy modification, X = avoid combination). The Drug Interaction Probability Scale was used to determine the causation of DDIs. All statistical analysis was performed in SPSS version 26.0. Results: 114 patients were qualified for pDDI analysis, and total pDDIs were 4051. The most common type of pDDIs was category C (3323; 82.0%), followed by D (653; 16.1%) and X (75; 1.9%). Voriconazole and posaconazole were the antifungal medicine with the most genuine DDIs. Mean tacrolimus concentration/dose (Tac C/D) before or after co-therapy was considerably lower than the Tac C/D during voriconazole or posaconazole co-therapy (p < 0.001, p = 0.027). Real DDIs caused adverse drug events (ADEs) in 20 patients. Multivariable logistic regression analyses found the number of drugs per patient (OR, 1.095; 95% CI, 1.048-1.145; p < 0.001) and the Acute Physiology and Chronic Health Evaluation II (APACHE Ⅱ) score (OR, 1.097; 95% CI, 1.021-1.179; p = 0.012) as independent risk factors predicting category X pDDIs. Conclusion: This study revealed a high incidence of both potential and real DDIs in ICU lung transplant recipients. Immunosuppressive drugs administered with azole had a high risk of causing clinically significant interactions. The number of co-administered drugs and APACHE Ⅱ score were associated with an increased risk of category × drug interactions. Close monitoring of clinical and laboratory parameters is essential for ensuring successful lung transplantation and preventing adverse drug events associated with DDIs.

Post-Operative Thoracic Epidural Analgesia and Incidence of Major Complications according to Specific Safety Standardized Documentation: A Large Retrospective Dual Center Experience.

(1) Background: Thoracic epidural analgesia is considered the gold standard in post-operative pain management following thoracic surgery. This study was designed to explore the safety of thoracic epidural analgesia and to quantify the incidence of its post-operative complications and side effects in patients undergoing thoracotomy for major surgery, such as resection of lung malignancies and lung transplantation. (2) Methods: This is a retrospective, dual-center observational study including patients that underwent major thoracic surgery including lung transplantation and received concurrent placement of thoracic epidural catheters for post-operative analgesia. An electronic system of referral and documentation of complications was used, and information was retrieved from our electronic critical care charting system. (3) Results: In total, 1145 patients were included in the study. None of the patients suffered any major complication, including hematoma, abscess, or permanent nerve damage. (4) Conclusions: the present study showed that in experienced centers, post-operative epidural analgesia in patients with thoracotomy is a safe technique, manifesting minimal, none-serious complications.

Meet in the middle: Could cell mediated-immunity assays be the answer for ideal Cytomegalovirus prophylaxis after lung transplantation? Observational study from a single center with intermittent antiviral prophylaxis.

Cytomegalovirus (CMV) can cause tissue-invasive disease and indirect effects after lung transplantation (LTx) such as acute rejection episodes and chronic lung allograft dysfunction. Monitoring CMV-specific cell immune recovery (CMV-CIR) after LTx can individualize CMV risks and establish better antiviral approach. This study evaluated the dynamics of CMV-CIR, using QuantiFERON-CMV assay (Qiagen Group), in the first year after LTx. Prospective observational cohort study included lung transplant recipients from December/2015 to December/2016. Universal antiviral prophylaxis with intravenous ganciclovir 5mg/kg/day 3 days/week for 3 months was given for CMV-seropositive recipients (R+) and only CMV-seropositive donor and negative recipient (D+/R-) received a 6-month-prophylaxis with ganciclovir and valganciclovir, on alternate days, in the first 3 months and then, 3 more months of valganciclovir. QuantiFERON-CMV was measured at the same time points of surveillance bronchoscopies. CMV infection was defined as any DNAemia detected and CMV disease with proven biopsy or antigenemia pp65 above 10 cells/300.000 neutrophils. Thirty-eight patients were included. On days 45, 90, and 365 days post-LTx, 60%, 72%, and 81% QuantiFERON-CMV were reactive, respectively. Eleven patients (28.9%) presented CMV-disease and 27 DNAemia/CMV infections. Reactive tests were able to predict CMV disease only at 90 days after LTx (p=.027) but failed on DNAemia/CMV infection (p=.148). Daily prophylaxis, for D+/R- patients (13.2%), remained as an independently associated factor for not achieving reactive QuantiFERON-CMV (adjusted OR .27, 95%CI .12-.60, p=.02). QuantiFERON-CMV may be another diagnostic tool to help stratify CMV-disease risk and individualized antiviral prophylaxis after LTx.

Burnout Syndrome in Lung Transplant Physicians.

Objective: Burnout syndrome is common in physicians, but little is known about burnout in lung transplant physicians specifically. The purpose of this study was to explore burnout and its relationship to job factors and depression in lung transplant physicians.Design: A cross-sectional study that included lung transplant pulmonologists and surgeons was performed via electronic survey.Setting: The lung transplant physicians surveyed practiced worldwide.Methods: The survey incorporated questions about demographics and job characteristics as well as the Maslach Burnout Inventory and Patient Health Questionnaire-2. Burnout was defined by high emotional exhaustion or depersonalization.Participants: Ninety physicians worldwide completed the survey.Results: Of the 90 physicians who completed the entire survey, 44 (48.9%) had burnout with 38 (42.2%) having high emotional exhaustion, 15 (16.7%) having high depersonalization, and 9 (10.0%) with both. Of the respondents, 14 (15.6%) had high risk of depression, and of these, 13 also had high emotional exhaustion. There was a positive correlation between depression score and emotional exhaustion score (P=0.67, P<0.001). Depression was more common in surgeons compared with pulmonologists (35.7% versus 11.8%, P=0.02). There was a trend toward more burnout by emotional exhaustion in physicians with more versus less work experience (68.4% versus 31.6%, P=0.056).Conclusions: Emotional exhaustion is common in lung transplant physicians and is associated with depression and a negative impact on life.

Association of Socioeconomic Position With Racial and Ethnic Disparities in Survival After Lung Transplant

A recent National Academies of Sciences, Engineering, and Medicine study found that transplant outcomes varied greatly based on multiple factors, including race, ethnicity, and geographic location. They proposed a number of recommendations including studying opportunities to improve equity in organ allocation. To evaluate the role of donor and recipient socioeconomic position and region as a mediator of observed racial and ethnic differences in posttransplant survival. This cohort study included lung transplant donors and recipients with race and ethnicity information and a zip code tabulation area-defined area deprivation index (ADI) from September 1, 2011, to September 1, 2021, whose data were in the US transplant registry. Data were analyzed from June to December 2022. Race, neighborhood disadvantage, and region of donors and recipients. Univariable and multivariable Cox proportional hazards regression were used to study the association of donor and recipient race with ADI on posttransplant survival. Kaplan-Meier method estimation was performed by donor and recipient ADI. Generalized linear models by race were fit, and mediation analysis was performed. Bayesian conditional autoregressive Poisson rate models (1, state-level spatial random effects; 2, model 1 with fixed effects for race and ethnicity, 3; model 2 excluding region; and 4: model 1 with fixed effects for US region) were used to characterize variation in posttransplant mortality and compared using ratios of mortality rates to the national average. Overall, 19 504 lung transplant donors (median [IQR] age, 33 [23-46] years; 3117 [16.0%] Hispanic individuals, 3667 [18.8%] non-Hispanic Black individuals, and 11 935 [61.2%] non-Hispanic White individuals) and recipients (median [IQR] age, 60 [51-66] years; 1716 [8.8%] Hispanic individuals, 1861 [9.5%] non-Hispanic Black individuals, and 15 375 [78.8%] non-Hispanic White individuals) were included. ADI did not mediate the difference in posttransplant survival between non-Hispanic Black and non-Hispanic White recipients; it mediated only 4.1% of the survival difference between non-Hispanic Black and Hispanic recipients. Spatial analysis revealed the increased risk of posttransplant death among non-Hispanic Black recipients may be associated with region of residence. In this cohort study of lung transplant donors and recipients, socioeconomic position and region of residence did not explain most of the difference in posttransplant outcomes among racial and ethnic groups, which may be due to the highly selected nature of the pretransplant population. Further research should evaluate other potentially mediating effects contributing to inequity in posttransplant survival.

Esophageal Inlet Patch: A Clinically Significant Entity in Advanced Pulmonary Disease and Lung Transplant Rejection

Background: Esophageal inlet patch (IP) refers to heterotopic gastric mucosa in the cervical esophagus. Secretions from IP may produce symptoms of laryngopharyngeal reflux (LPR) and accelerate progression of lung disease. We aimed to characterize the significance of IP among patients with advanced pulmonary disease, including lung transplant (LTx) recipients, and to assess outcomes following IP ablation. Methods: We established and reviewed a prospective database of all patients with advanced pulmonary disease referred for GI motility evaluation for presence of IP over 7 years. Total IP size, results of pH testing, incidence of transplant rejection and mortality, and effects of IP ablation on symptoms were analyzed. Results: Twenty-seven (13 LTx recipients) of 440 pulmonary patients referred for upper endoscopy were found to have IPs, and 14 completed IP ablation (mean number of 1.7 sessions to ablate IP). Total IP size correlated with total acid exposure time ( P = .01) and symptoms of cough ( P &lt; .00001), heartburn ( P = .0001), and globus ( P &lt; .00001). Symptom severity of heartburn and dysphagia improved following IP ablation ( P = .04 and 0.008). Eight of 13 LTx patient with IP developed either acute or chronic rejection, with 3 cases of post-LTx mortality occurring in patients who did not undergo IP ablation. Conclusions: IP should be given careful consideration in patients with advanced pulmonary disease and lung transplant recipients, particularly if symptoms of cough, heartburn, or globus are present. Total IP size may be predictive of severity of LPR, and symptom recurrence should prompt re-examination for residual IP.

Effect of Isavuconazonium Sulfate and Posaconazole Delayed Release Tablets on Tacrolimus Dose-to-Concentration Ratios.

Limited evidence exists on the effect of isavuconazonium sulfate and posaconazole delayed release tablets on tacrolimus dose-to-concentration ratios in lung transplant recipients. The purpose of this evaluation was to assess the impact of novel triazoles on tacrolimus dose-to-concentration ratios. This retrospective review included lung transplant recipient ≥18 years of age from January 1, 2017 to October 1, 2020 who received either posaconazole delayed release tablets or isavuconazonium sulfate for. A paired analysis evaluated outcomes pre-triazole and post-triazole initiation. Forty-one patients met evaluation criteria for inclusion. A total of 34 of 41 patients received posaconazole delayed release tablets. Of these patients, 22 of 34 were transitioned from previous triazole to posaconazole delayed release tablets and experienced a 47% reduction in tacrolimus dose-to-concentration ratio. Twelve patients were newly initiated on posaconazole delayed release tablets and experienced a 50% reduction in tacrolimus dose-to-concentration ratios. Although not statistically significant, a 30% reduction in tacrolimus dose-to-concentration ratio was observed when transitioning to isavuconazonium sulfate from previous triazole therapy. Limited data exists to provide guidance on tacrolimus dose adjustments with initiation and conversion of novel triazoles, however, this evaluation provides more knowledge on the drug interaction with novel triazoles and tacrolimus.

A qualitative exploration of people living with idiopathic pulmonary fibrosis experience of a virtual pulmonary rehabilitation programme

BackgroundPulmonary rehabilitation (PR) is recommended in the treatment of people with idiopathic pulmonary fibrosis (IPF). Little is known about the experiences of people with IPF of PR. Due to Covid-19 there has been a rapid shift of PR services to remote/virtual delivery.ObjectiveTo explore people living with IPFs experience of a virtual PR (VPR) programme.MethodsAll patients with a diagnosis of IPF in a stable phase of the disease were invited to participate in virtual PR: a 10 week exercise programme delivered twice-weekly for one hour. One-to-one semi- structured interviews were conducted within one week following the programme. All interviews were recorded, transcribed and analysed using Braun and Clarke thematic analysis by two independent assessors.ResultsN=13 participants took part in the semi-structured interviews, mean (standard deviation (SD)) age 69.5(10.4) years; 7M:6F. Mean (SD) FEV1 2.6(0.3)L, FVC 2.9(0.4)L. Four key themes were identified: 1) The impact of VPR on health and outlook, (2) The reality of VPR, (3) Being active after VPR and (4) Living with IPF during the COVID-19 Pandemic. Participants reported high levels of enjoyment and engagement with the programme regardless of the health benefits experienced. Most participants expressed a desire for a longer programme. Participants expressed different levels of maintenance with exercise since finishing the programme, specific motivators and strategies for maintenance included lung transplant, the maintenance of benefits from the programme and social support. COVID-19 and the restrictions imposed had some negative impacts on some participants lives, engaging with PR helped overcome some of these.ConclusionDespite the progressive nature of IPF, all participants expressed high levels of enjoyment with the programme. Future research should explore strategies for maintenance post PR and the optimum duration of PR for people with IPF.

Impact of Cytomegalovirus DNAemia Below the Lower Limit of Quantification: Multistate Model in Lung Transplant Recipients

Background Cytomegalovirus (CMV) infections following transplantation lead to significant morbidity. Identification of CMV DNAemia continually improves and now viral loads below the lower limit of quantification (LLOQ) are detectable. However, the clinical course of positive CMV qPCR &lt;LLOQ is unknown. Methods This retrospective study included lung transplant recipients experiencing their first episode of positive CMV qPCR &lt;LLOQ with all qPCR assays conducted using COBAS® AmpliPrep/COBAS® TaqMan®. A Markov-like multistate model was utilized to describe the course of CMV DNAemia &lt;LLOQ. A multivariable model was employed to identify predictors of transitioning to a positive, quantifiable state. Results 100 patients with a CMV &lt;LLOQ result were included, encompassing 1,248 transitions in the six months following first episode of CMV qPCR &lt;LLOQ. There was an 97.8% probability of remaining &lt;LLOQ or undetectable and a 2.2% probability of transitioning to a positive, quantifiable qPCR state. The multivariable regression model identified treatment for rejection, increasing body mass index, valganciclovir therapy, and increasing CMV qPCR viral load as being predictive of transitioning from CMV qPCR undetectable or &lt;LLOQ into a positive, quantifiable CMV qPCR state. Conclusions Most patients did not transition into a positive, quantifiable CMV qPCR state following a first episode of positive CMV qPCR &lt;LLOQ in this cohort of lung transplant recipients.

When immunosuppression and COVID-19 intersect: An exploratory qualitative study of young lung transplant recipient perceptions of daily life during a pandemic.

BackgroundThe COVID‐19 pandemic poses an increased risk of infection, severe illness, hospitalization and mortality for young people who are immunosuppressed, including lung transplant (LTx) recipients. The aim of this study was to explore the intersection between immunosuppression and COVID‐19, through the impacts of the pandemic upon the daily lives of young LTx recipients residing in the Australian state of Victoria.MethodsAn exploratory qualitative research study was undertaken via consumer engagement. A purposive sample of 11 LTx recipients, residing in Victoria, was recruited during the first year of the COVID‐19 pandemic. Semi‐structured interviews were conducted to gain insights into their daily life and healthcare experiences, including the impacts of the COVID‐19 pandemic. Data were interpreted using thematic analysis.ResultsFour major themes were identified: (1) occupational deprivation due to the intersection of COVID‐19 and lung transplant; (2) resilience and acceptance of restrictions; (3) infection control and vigilance about risk; and (4) care experiences of telehealth.ConclusionsOccupational deprivation emerged as a common theme, specifically in the context of loss of access to meaningful everyday activities of developmental significance. However, participants also commonly reflected upon their ability to flexibly adjust to changing socially regulated community and healthcare environments. A high degree of acceptance and compliance with public health orders was self‐reported, may be indicative of this cohort's long‐term experience of chronic illness and their understanding of the importance of minimizing infection risks. Youth‐informed healthcare strategies were identified as keystone to engaging them in institutional change and program adaptation during a pandemic.

Genotype-Guided Voriconazole Prescribing in Lung Transplant Recipients

<h3>Purpose</h3> Voriconazole (VRC) is the treatment of choice for Aspergillus in lung transplant recipients. VRC undergoes metabolism via CYP2C19, a polymorphic enzyme that has varying metabolic activity. Patients with either CYP2C19 ultrarapid metabolizer (URM) or rapid metabolizer (RM) phenotypes are less likely to achieve therapeutic VRC levels, which is predictive of treatment failure. Determining CYP2C19 variations can help tailor VRC therapy for lung transplant recipients. <h3>Methods</h3> This prospective cohort study included lung transplant recipients who received VRC between January 1, 2016, to November 30, 2019. Participants were excluded if they did not read or speak English, did not have access to email or internet, and did not provide consent to pharmacogenomic testing. The frequency of various CYP2C19 genotypes in this cohort was identified. <h3>Results</h3> Forty-three VRC exposures occurred in 34 participants who completed pharmacogenomic testing. Twenty-one percent (7/34) had URM or RM phenotypes, 74% (25/34) had normal (NM) or intermediate (IM) metabolizer phenotypes, and 6% (2/34) had poor metabolizer (PM) phenotype. Participants with URM or RM phenotypes required an average of 40 days to reach first therapeutic VRC levels, compared to 13 days and 9 days in the NM or IM and PM phenotypes, respectively. Eight cystic fibrosis participants were included in this cohort. Cystic fibrosis participants with URM or RM phenotypes required 77 days to reach first therapeutic VRC levels, while NM or IM and PM phenotypes required 27 days and 14 days, respectively. <h3>Conclusion</h3> The time required to achieve therapeutic VRC levels was widely variable based on CYP2C19 genotype and the corresponding phenotype in our study cohort. Participants with URM or RM phenotypes are at high risk for treatment failure due to prolonged time to therapeutic VRC levels. CYP2C19 polymorphism may further reduce likelihood of achieving target VRC levels in cystic fibrosis patients.

Tolerability of Extended Multi-Drug Fungal Prophylaxis After Lung Transplant

<h3>Purpose</h3> Lung transplant patients are at risk of fungal infections post-transplant and require anti-fungal prophylaxis (AFP). However, utilization and duration of these agents can be limited by adverse effects. The purpose of this evaluation was to assess the tolerability and duration of AFP post-lung transplant at a large academic medical center. <h3>Methods</h3> This single-center retrospective review included lung transplant patients transplanted from August 2017 to August 2018 who received at least 7 days of AFP and were followed for three years. Patients received a combination of an azole anti-fungal agent, inhaled amphotericin B lipid complex (iABLC), and nystatin suspension immediately post-transplant. Pre-transplant colonization rates, prior fungal infections, transplant indication and baseline characteristics were collected. The primary outcome was tolerability of AFP. Secondary outcomes assessed were adherence and duration of AFP. <h3>Results</h3> Forty patients were included and one patient was excluded from the azole analysis due to a history of liver hyperplasia precluding therapy (Table 1). Patients remained on an azole, iABLC, and nystatin therapy a median of 13.9, 36.6, and 32 months post-transplant, respectively. The most common reason for AFP discontinuation was provider decision to end prophylaxis coverage (Table 2). Seven (19.4%) patients in the azole group, one (4.8%) patient in the iABLC group, and one (4.3%) patient in the nystatin group discontinued therapy due to intolerable side effects and adverse reactions. Patient reported adherence rates were highest in the azole group (87.2%), followed by iABLC (67.5%) and lowest with nystatin (45%). <h3>Conclusion</h3> Despite an extended duration of broad AFP, most patients tolerated therapy without limiting adverse effects. Oral AFP of shorter duration yielded the highest patient reported adherence.