Effect of antifibrotic agents on postoperative complications after lung transplantation for idiopathic pulmonary fibrosis.

BACKGROUND: Antifibrotic agents (AFAs) are now standard-of-care for idiopathic pulmonary fibrosis (IPF). Concerns have arisen about the safety of these drugs in patients undergoing lung transplantation (LTx). METHODS: We performed a multi-centre, nationwide, retrospective, observational study of French IPF patients undergoing LTx between 2011 and 2018 to determine whether maintaining AFAs in the peri-operative period leads to increased bronchial anastomoses issues, delay in skin healing and haemorrhagic complications. We compared the incidence of post-operative complications and the survival of patients according to AFA exposure. RESULTS: Among 205 patients who underwent LTx for IPF during the study period, 58 (28%) had received AFAs within 4 weeks before LTx (AFA group): pirfenidone in 37 (18.0%) and nintedanib in 21 (10.2%). The median duration of AFA treatment before LTx was 13.8 (5.6-24) months. The AFA and control groups did not significantly differ in airway, bleeding or skin healing complications (p = 0.91, p = 0.12 and p = 0.70, respectively). Primary graft dysfunction was less frequent in the AFA than control group (26% vs. 43%, p = 0.02), and the 90-day mortality was lower (7% vs. 18%, p = 0.046). CONCLUSIONS: AFA therapy did not increase airway, bleeding or wound post-operative complications after LTx and could be associated with reduced rates of primary graft dysfunction and 90-day mortality.

Risk of Bronchial Complications After Lung Transplantation With Respiratory Corynebacteria. Results From a Monocenter Retrospective Cohort Study.

Corynebacterium spp. are associated with respiratory infections in immunocompromised hosts. A link with bronchial complications after lung transplantation (LTx) has been suggested. We aimed to assess the link between respiratory sampling of Corynebacterium spp. and significant bronchial complication (SBC) after LTx. We performed a single center retrospective study. Inclusion of LTx recipients with at least one respiratory Corynebacterium spp. sample (July 2014 to December 2018). Subjects were matched to unexposed LTx recipients. Primary outcome was SBC occurrence after Corynebacterium spp. isolation. Secondary outcomes were Corynebacterium spp. persistent sampling, chronic lung allograft dysfunction (CLAD) onset and all-cause mortality. Fifty-nine patients with Corynebacterium spp. sampling with 59 without isolation were included. Corynebacterium spp. identification was not associated with SBC occurrence (32.4% vs. 21.6%, p = 0.342). Previous SBC was associated with further isolation of Corynebacterium spp. (OR 3.94, 95% CI [1.72-9.05]). Previous SBC and corticosteroids pulses in the last 3 months were the only factors associated with increased risk of Corynebacterium spp. isolation in multivariate analysis. Corynebacterium spp. sampling was significantly associated with CLAD onset (27.1% vs. 6.9%, p = 0.021). Corynebacterium spp. isolation was not associated with SBC but with higher risk of CLAD. Whether CLAD evolution is affected by Corynebacterium spp. eradication remains to be investigated.

Determinants of survival after lung transplantation in telomerase-related gene mutation carriers: A retrospective cohort.

Carriers of germline telomerase-related gene (TRG) mutations can show poor prognosis, with an increase in common hematological complications after lung transplantation (LT) for pulmonary fibrosis. The aim of this study was to describe the outcomes after LT in recipients carrying a germline TRG mutation and to identify the predictors of survival. In a multicenter cohort of LT patients, we retrospectively reviewed those carrying pathogenic TRG variations (n = 38; TERT, n = 23, TERC, n = 9, RTEL1, n = 6) between 2009 and 2018. The median age at LT was 54 years (interquartile range [IQR] 46-59); 68% were male and 71% had idiopathic pulmonary fibrosis. During the diagnosis of pulmonary fibrosis, 28 (74%) had a hematological disease, including eight with myelodysplasia. After a median follow-up of 26 months (IQR 15-46), 38 patients received LT. The overall post-LT median survival was 3.75 years (IQR 1.8-NA). The risk of death after LT was increased for patients with myelodysplasia (HR 4.1 [95% CI 1.5-11.5]) or short telomere (HR 2.2 [1.0-5.0]) before LT. After LT, all patients had anemia, 66% had thrombocytopenia, and 39% had neutropenia. Chronic lung allograft dysfunction frequency was 29% at 4 years. The present findings support the use of LT in TRG mutation carriers without myelodysplasia. Hematological evaluation should be systematically performed before LT.

ECMO support as a bridge to lung transplantation is an independent risk factor for bronchial anastomotic dehiscence.

BACKGROUND: Airway complications are frequent after lung transplantation (LT), as they affect up to 23% of recipients. The implication of perioperative extracorporeal membrane oxygenation (ECMO) support and haemodynamic instability has never been specifically assessed. The first aim of this study was to explore the impact of perioperative ECMO support on bronchial anastomotic dehiscence (BAD) at Day 90 after LT. METHODS: This prospective observational monocentric study analysed BAD in all consecutive patients who underwent LT in the Bichat Claude Bernard Hospital, Paris, France, between January 2016 and May 2019. BAD visible on bronchial endoscopy and/or tomodensitometry was recorded. A univariate analysis was performed (Fisher's exacts and Mann-Whitney tests), followed by a multivariate analysis to assess independent risk factors for BAD during the first 90 days after LT (p < 0.05 as significant). The Paris North Hospitals Institutional Review Board approved the study. RESULTS: A total of 156 patients were analysed. BAD was observed in the first 90 days in 42 (27%) patients and was the main cause of death in 22 (14%) patients. BAD occurred during the first month after surgery in 34/42 (81%) patients. ECMO support was used as a bridge to LT, during and after surgery in 9 (6%), 117 (75%) and 40 (27%) patients, respectively. On multivariate analysis, ECMO as a bridge to LT (p = 0.04) and septic shock (p = 0.01) were independent risk factors for BAD. CONCLUSION: ECMO as a bridge to LT is an independent risk factor for BAD during the first 90 days after surgery. Close monitoring of bronchial conditions must be performed in these high-risk recipients.

Patient-important outcomes in lung transplantation: A systematic review.

BACKGROUND: Patient-important outcomes (PIOs) have emerged in respiratory medicine, in order to place the patient at the center of research. Mortality is a debated PIO in lung transplantation (LTx). The use of PIO in this specific setting has never been studied. We aimed to systematically review the use of PIOs in LTx research. METHODS: MEDLINE, Cochrane Library and Embase databases were searched to include prospective studies published in 2019, involving adult LTx recipients. We excluded articles reporting non-prognostic studies, letters, reviews, commentaries, or case reports. PIOs considered were mortality, pain, physical function, pulmonary, gastrointestinal, neuropsychological, cardiac, sleep or sexual symptoms and quality of life. This systematic review was prospectively registered in the PROSPERO register (CRD42020163425). RESULTS: Among 1048 references retrieved, 51 were finally included in the analysis. In total, 26 (51%) studies investigated at least one PIO, as a primary outcome in 12 (23.5%) and secondary outcome in 21 (41.2%). In 15 (29.4%) studies, mortality was the most frequently reported PIO; 11 (21.5%) studies evaluated at least one PIO other than mortality, quality of life being this PIO in 6. CONCLUSIONS: PIOs were described in half of prospective articles dealing with adult LTx recipients published in 2019. Outcomes other than mortality were insufficiently considered. A core outcome set of PIOs in LTx should be developed with patient input to guide future research in LTx.

Acute worsening of native lung fibrosis after single lung transplantation for pulmonary fibrosis: two case reports.

BACKGROUND: In patients receiving single lung transplantation for idiopathic pulmonary fibrosis, worsening of fibrosis of the native lung is usually progressive over time, with no significant effects on gas exchange. CASE PRESENTATION: Here, we describe the cases of two Caucasian male recipients of single lung transplants for idiopathic pulmonary fibrosis, 65 and 62 years of age, who exhibited acute worsening of lung fibrosis after an episode of serious viral infection (cytomegalovirus primo-infection in one case and COVID-19 in the other). In both cases, along with opacification of the native lung over several days, the patients presented acute respiratory failure that required the use of high-flow nasal oxygen therapy. Eventually, hypoxemic respiratory failure resolved, but with rapid progression of fibrosis of the native lung. CONCLUSION: We conclude that acute worsening of fibrosis on the native lung secondary to a severe viral infection should be added to the list of potential complications developing on the native lung after single lung transplantation for idiopathic pulmonary fibrosis.

Bacteraemia Is Associated with Increased ICU Mortality in the Postoperative Course of Lung Transplantation.

We aimed to describe the prevalence, risk factors, morbidity and mortality associated with the occurrence of bacteraemia during the postoperative ICU stay after lung transplantation (LT). We conducted a retrospective single-centre study that included all consecutive patients who underwent LT between January 2015 and October 2021. We analysed all the blood cultures drawn during the postoperative ICU stay, as well as samples from suspected infectious sources in case of bacteraemia. Forty-six bacteria were isolated from 45 bacteraemic patients in 33/303 (10.9%) patients during the postoperative ICU stay. Staphylococcus aureus (17.8%) was the most frequent bacteria, followed by Pseudomonas aeruginosa (15.6%) and Enterococcus faecium (15.6%). Multidrug-resistant bacteria accounted for 8/46 (17.8%) of the isolates. The most common source of bacteraemia was pneumonia (38.3%). No pre- or intraoperative risk factor for bacteraemia was identified. Recipients who experienced bacteraemia required more renal replacement therapy, invasive mechanical ventilation, norepinephrine support, tracheotomy and more days of hospitalization during the ICU stay. After adjustment for age, sex, type of LT procedure and the need for intraoperative ECMO, the occurrence of bacteraemia was associated with a higher mortality rate in the ICU (aOR = 3.55, 95% CI [1.56-8.08], p = 0.003). Bacteraemia is a major source of concern for lung transplant recipients.

Coping strategies, anxiety and depression related to the COVID-19 pandemic in lung transplant candidates and recipients. Results from a monocenter series.

BACKGROUND: The COVID-19 pandemic has been associated with an increase in anxiety and depression symptoms in people. We investigated the impact of the pandemic on coping strategies and anxiety and depression in lung transplantation (LT) recipients and patients with end-stage chronic lung disease awaiting LT. METHODS: We retrospectively investigated coping strategies by using the Coping Inventory for Stressful Situations questionnaire and anxiety and depression symptoms by the Hospital Anxiety and Depression scale in 115 LT candidates and recipients. RESULTS: Overall, 63 participants (20 women; median age 59 years [interquartile range 52•65]) answered one or both questionnaires (49 LT recipients and 14 LT candidates). The preferred coping strategy was task-focused for 51 (86.4%) participants, with no difference between LT recipients and candidates nor according to the main anamnestic and clinical data. Eleven patients had suspected or proven depression symptoms, and 18 had suspected or proven anxiety symptoms. Coping strategies related to COVID-19 did not differ by presence of anxiety or depression symptoms. CONCLUSION: In the current pandemic, healthcare professionals should consider these results to provide relevant psychological help to these fragile populations and promote a systematic and wide multidisciplinary assessment of LT recipients and candidates.

Harmful neutrophil subsets in patients with ischemic stroke: Association with disease severity.

Objective: To better understand the functional state of circulating neutrophils in patients with ischemic stroke (IS) for planning future clinical trials. Methods: We analyzed by flow cytometry activation state of circulating neutrophils and the distribution of neutrophil peripheral subsets in 41 patients with acute IS less than 6 hours before admission and compared them with 22 age-matched healthy controls. Results: Our results demonstrated continuous basal hyperactivation of circulating neutrophils during acute IS, characterized by lower l-selectin expression and higher CD11b expression at the cell surface, increased ROS production by neutrophils, and greater circulating levels of neutrophil elastase. Neutrophil hyperactivation was associated with deregulation of the equilibrium between apoptotic and necrotic. Patients also had higher percentages than controls of the overactive senescent (CXCR4bright/CD62Ldim) neutrophil subset and increased percentage of neutrophils with a reverse transendothelial migration (CD54highCXCR1low) phenotype. Importantly, neutrophil alterations were associated with the clinical severity of the stroke, evaluated by its NIH Stroke Scale score. Conclusion: Altogether, our results indicate that during acute IS, the inflammatory properties of circulating neutrophils rise, associated with the expansion of harmful neutrophil subsets. These changes in neutrophil homeostasis, associated with disease severity, may play an instrumental role by contributing to systemic inflammation and to the blood-brain barrier breakdown. Our findings highlight new potential therapeutic approaches of stroke by rebalancing the ratio of senescent to immunosuppressive neutrophils or decreasing reverse neutrophil transmigration or both.