Background Smoking is a major contributor to respiratory diseases requiring lung transplantation (LTx). Data on smoking after LTx are scarce. Understanding the incidence and determinants of smoking after LTx is crucial for optimizing long-term outcomes. Methods For this prospective observational cohort study done from March 2023 to August 2024 in 11 French transplantation (Tx) centers, LTx and heart-lung transplant (HLTx) recipients completed an anonymous self-administered questionnaire during their routine follow-up. Pre- and post-Tx smoking and sociodemographic characteristics were collected and analyzed centrally. Results Of 946 recipients with complete data on smoking, 524 (55%) reported having smoked before Tx. Among them, approximately 5% smoked after LTx. Smoking after Tx was significantly associated with several demographic and contextual factors, including female sex, younger age, living alone, having cystic fibrosis, prior use of hand-rolled cigarettes, and regular exposure to smokers among family and friends. By multivariate analysis, younger age, living alone, and smoking among family and friends were associated with post-Tx smoking. Due to the anonymous completion of the self-administered questionnaires, associations between post-Tx smoking and clinical outcomes could not be assessed. Conclusions This study provides novel multicenter data about the incidence and determinants of smoking after LTx or HLTx. A small but meaningful proportion of recipients smoked after Tx. We identified several social and demographic risk factors. Our findings highlight the need for targeted smoking-relapse prevention-and-support programs in lung and heart-lung recipients. Further research is warranted to evaluate the impact of smoking after Tx on graft and patient outcomes.

A case of ulcerative colitis-associated bronchiectasis relapse after lung transplantation, with new bronchiectasis and inflammatory airway infiltrates of recipient origin, confirmed by chimaerism analysis and immune repertoire studies https://bit.ly/42z1BDh.

BACKGROUND:The diagnosis of pulmonary antibody-mediated rejection (AMR) remains challenging with lack of specific defining features. This study evaluated the diagnostic and prognostic significance of intragraft anti human leukocyte antigen (HLA) donor-specific antibodies (gDSA) in pulmonary AMR. METHODS:This multicenter prospective study enrolled adult lung transplant recipients (LTR) with serum anti-HLA DSA (sDSA) >1,000 Luminex mean fluorescence intensity (MFI). Transbronchial biopsies (TBBx) were obtained for both standard histologic analysis and cryopreservation to detect anti-HLA class I and II gDSA, using Luminex single-antigen beads assay. Clinical follow-up was conducted over 24 months. An expert pathologist reviewed all TBBx using a predefined checklist. A blinded adjudication panel categorized clinical diagnoses as possible, probable, or definite AMR and non-AMR conditions. The primary objective was to assess gDSA sensitivity and specificity for AMR diagnosis. Additionally, we compared graft outcomes between gDSA+ vs gDSA- patients. RESULTS:Seventy-seven LTR from 5 centers were included from August 2019 to July 2022. Twenty-nine patients were classified as probable or definite clinical/subclinical AMR. Among the cohort, 13 had positive gDSA. gDSA sensitivity, specificity, and positive predictive value for AMR diagnosis were 34.4%, 93.7%, and 76.9%, respectively. gDSA diagnostic performance for AMR was better than sDSA ≥12,500 MFI (sensitivity 37.9%, specificity 85.4%, and positive predictive value 61.1%). Event-free survival analysis (10% forced expiratory volume in 1 second decline or graft loss) showed no significant differences by gDSA positivity. Limited biopsy sampling and spatial heterogeneity may have biased sensitivity and prognostic performances of the technique. CONCLUSIONS:gDSA might offer a specific complementary support for the clinical diagnosis of AMR following lung transplantation.

Background:Pulmonary hypertension (PH) associated with COPD (PH-COPD) exhibits diverse phenotypes, challenging therapeutic management. This study aimed to describe the characteristics of COPD patients with distinct phenotypes, namely end-stage COPD with or without PH (group 1), other COPD patients with mild-to-moderate pre-capillary PH-COPD (group 2) and COPD patients with a pulmonary vascular phenotype (PVP) (group 3). Methods:We performed a retrospective analysis of COPD patients who underwent right heart catheterisation from 2015 to 2022. Results:81 patients were included in group 1, 37 in group 2 and 35 in group 3. The groups differed in terms of clinical, functional, haemodynamic and imaging characteristics. Group 1 had significantly marked lung hyperinflation with increased total lung capacity and residual volume, a feature not observed in group 3. These results were confirmed by analysis of chest CT scans, which confirmed varying degrees of emphysema, as follows: severe in group 1, moderate in group 2 and mild in group 3, with median total emphysema indices of 55% (48-62), 32% (16-49) and 16% (3.4-31), respectively, p<0.0001. Conclusions:Our results highlight the broad spectrum of PH in COPD, from PH associated with end-stage COPD (phenotype/group 1), characterised by predominant alveolar wall damage with severe emphysema, to PVP (phenotype/group 3), mainly due to pulmonary vascular changes. Phenotype/group 2 represents an intermediate state combining features of both. In the current debate on how to distinguish PH-COPD phenotypes, it might be of interest to include quantitative thresholds for emphysema in future diagnostic and management algorithms.

Background Lung transplantation is a highly dynamic segment of solid organ transplantation in which gender plays a central role. Our objective was to investigate the causes of outcome differences between women and men all along the lung transplantation pathway. Methods We used data from the French COhort in Lung Transplantation (COLT) study (12 participating lung transplantation centres). Analyses were performed in three phases: baseline clinical characteristics, peri-transplantation period and post-transplantation follow-up. Results Overall, 1710 participants (802 women and 908 men) were included in this study. Women were less likely than men to undergo transplantation (91.6% versus 95.6%; p=0.001) and waited longer before transplantation (115 versus 73 days; p<0.001). Female gender and pre-transplantation class I anti-human leukocyte antigen antibodies were identified as independent factors associated with longer waiting time duration. Female transplant recipients commonly received lungs from height- and sex-matched donors, despite higher female waiting list mortality and a higher proportion of male donors. Importantly, women with oversized lung transplantation (defined by predicted total lung capacity (pTLC) ratio and weight mismatch) did not have worse survival. The overall post-transplantation survival of female recipients was significantly higher than that of male recipients (65.6% versus 57.3%; p<0.001), although the prevalence of specific major lung transplantation outcomes did not differ according to gender. Conclusion Women waited longer and were less likely to undergo transplantation. Women transplanted with an oversized lung did not have worse survival after transplantation, suggesting that size matching criteria based on pTLC ratio and weight mismatch may be less stringent in this context.

Background: Thrombotic microangiopathy (TMA) is a well-recognized complication of solid-organ transplantation that chiefly affects the kidneys. The objective of this study was to describe TMA features and outcomes after lung transplantation. Patients and methods: This retrospective observational study included patients with TMA following lung or heart-lung transplantation at eight French centers in 2006–2023. Univariate and multivariate analyses were done to identify factors associated with outcomes. Results: Of the 4565 patients, 82 (1.8%) experienced TMA, at a median of 19 [6−34] months after transplantation; among them, 79 were included (51% female; median age 50 [33−61] years). Mortality during the median follow-up of 31 [11−66] months was 38/79 (48%). Etiological factors were above-target calcineurin inhibitor (CNI) trough levels (48%), combined CNI and mTOR inhibitor therapy (23%), and infection (9%). CNI was continued in 70 patients and replaced by belatacept in 9 patients. In the belatacept group, renal function at one year was better but death, bacterial pneumonia, and CMV viremia were more common; none of the differences was significant, perhaps given the small sample size. Conclusion: Mortality was high after TMA in lung or heart-lung transplant recipients. CNI monitoring protocols should be improved to minimize the risk of toxicity. Belatacept instead of CNI therapy was associated with better kidney function but also with higher frequencies of adverse events, suggesting a need for great caution. Studies adequately powered to assess the risk/benefit ratio of belatacept therapy according to the dosing regimen, patient features, and concomitant immunosuppressants are needed.

BACKGROUND:Pregnancies in women with lung transplants are considered high-risk due to comorbidities. There is a risk of pregnancy-related antihuman leukocyte antigen alloimmunization, which can potentially lead to antibody-mediated rejection in transplant patients. A few such cases have been reported in women receiving kidney, liver, or heart transplants, but this risk has never been studied in lung transplantation. The aim of our study was to investigate the risk of developing antibody-mediated rejection in the year following pregnancy. METHODS:This is a multicenter retrospective study carried out in 11 French lung transplant centers. We included lung transplant recipients who had a pregnancy between January 1, 2012 and December 31, 2021. RESULTS:Seventy-six pregnancies were included in 52 patients. These were mainly women with double lung transplantation (n = 43; 82.7%). Cystic fibrosis (n = 40; 76.9%) and pulmonary hypertension (n = 11; 21%) were the main underlying diseases for transplantation. Of the 76 pregnancies, 43 (56.6%) resulted in the birth of live children, while the others resulted in abortion (n = 8; 10.5%) or miscarriage (n = 25; 32.9%). Five antibody-mediated rejections (6.6%) were identified in the year following pregnancy, with a mean time of 6.24 ± 6.02 months between the end of pregnancy and rejection. All 5 rejections resulted in graft loss, of which 2 deaths and 3 retransplantations. Nineteen pregnancies (25%) resulted in alloimmunization. When antihuman leukocyte antigen antibodies were de novo donor-specific antibodies (n = 5), antibody-mediated rejection occurred in all cases. CONCLUSIONS:Pregnancy in female lung transplant recipients appears to be at risk of humoral rejection in the year following pregnancy.

OBJECTIVES Shortage of organ requires to consider older donors of lung transplants, but the consequence of donor age on the outcomes of lung transplant recipients (LTRs) is not clearly established. Our objective was to determine the impact of donor age on LTR survival. METHODS We analysed data from a multicentre cohort of 1191 LTR. The main outcome was the time from transplantation to death. Multivariate Cox regression associated with G-computation were used to obtain confounder-adjusted results. RESULTS Lung graft from donor over 60 years of age are more frequently allocated to older recipients, female recipients, and candidates with chronic obstructive pulmonary disease and cardiovascular comorbidities. The 5-year confounder-adjusted survival of recipients with lung from donor over 60 was lower than that of recipients of transplants from younger donors (62.1% vs 69.3%, respectively, P < .001). The corresponding HR was 1.28 (95% CI, 1.01-1.63). For such a follow-up at 5 years, the mean life expectancy was 46.4 months (95% CI, 44.4-48.3) in the group receiving a younger graft versus 42.6 months (95% CI, 39.6-45.6) in the older group. It corresponded to significant difference of 3.8 months gain in the 5-year life expectancy (P = .028). CONCLUSIONS Donor age over 60 is an independent risk factor for reduced post-transplant survival. The age criterion must be taken into account when accepting a lung graft as a potential impact to the recipient’s survival. CLINICAL TRIAL NOTATION NCT00980967.

Background and Objective EpiGETIF is a web-based, multicentre clinical database created in 2019 aiming for prospective collection of data regarding therapeutic rigid bronchoscopy (TB) for malignant central airway obstruction (MCAO). Methods Patients were enrolled into the registry from January 2019 to November 2022. Data were prospectively entered through a web-interface, using standardized definitions for each item. The objective of this first extraction of data was to describe the population and the techniques used among the included centres to target, facilitate and encourage further studies in TB. Results Overall, 2118 patients from 36 centres were included. Patients were on average 63.7 years old, mostly male and smokers. Most patients had a WHO score <= 2 (70.2%) and 39.6% required preoperative oxygen support, including mechanical ventilation in 6.7%. 62.4% had an already known histologic diagnosis but only 46.3% had received any oncologic treatment. Most tumours were bronchogenic (60.6%), causing mainly intrinsic or mixed obstruction (43.3% and 41.5%, respectively). Mechanical debulking was the most frequent technique (67.3%), while laser (9.8%) and cryo-recanalization (2.7%) use depended on local expertise. Stenting was required in 54.7%, silicone being the main type of stent used (55.3%). 96.3% of procedure results were considered at least partially successful, resulting in a mean 4.1 points decrease on the Borg scale of dyspnoea. Complications were noted in 10.9%. Conclusion This study exposes a high volume of TB that could represent a good source of future studies given the dismal amount of data about the effects of TB in certain populations and situations.

BACKGROUND:The aim of the study was to describe and investigate the effect of pulmonary arterial hypertension (PAH) therapies in a cohort of patients with severe precapillary pulmonary hypertension (PH) associated with chronic obstructive pulmonary disease (COPD; PH-COPD), and to assess factors predictive of treatment response and mortality. MATERIAL AND METHODS:We retrospectively included patients with severe incident PH-COPD who received PAH therapy and underwent RHC at diagnosis and on treatment. RESULTS:From 2015 to 2022, 35 severe PH-COPD patients, with clinical features of pulmonary vascular phenotype, were included. Seventeen (48.5%) patients were treated with combined PAH therapy. PAH therapy led to a significant improvement in hemodynamics (PVR -3.5 Wood Units (-39.3%); p < 0.0001), and in the simplified four-strata risk-assessment score, which improved by at least one category in 21 (60%) patients. This effect was more pronounced in patients on dual therapy. Kaplan-Meier estimated survival rates at 1, 3 and 5 years were 94%, 65% and 42% respectively. Univariate analysis showed a significant reduction in survival in patients with a higher simplified risk score at follow-up (Hazard ratio (HR) 2.88 [1.16-7.15]; p = 0.02). Hypoxemia <50 mmHg was correlated to mortality in multivariate analysis (HR 4.33 [1.08-17.42]; p = 0.04). CONCLUSIONS:Our study confirms the poor prognosis of patients with COPD and a pulmonary vascular phenotype and the potential interest of combined PAH therapy in this population, with good tolerability and greater clinical and hemodynamic improvement than monotherapy. Using the simplified risk score during follow-up could be of interest in this population.

Hepatopulmonary syndrome (HPS) is a rare pulmonary complication of cirrhosis for which the only curative treatment is liver transplantation (LT). Patients with severe HPS prior to LT are at high risk of postoperative complications and mortality, and may develop refractory HPS after LT. To date, no therapeutic strategy has been validated for these patients. To our knowledge, we describe the first case of successful use of high-flow nasal cannula oxygen therapy for severe post-LT hypoxemia in a 23-year-old adult.

IntroductionDue to the COVID-19 pandemic, France underwent several lockdown periods during 2020. Our aim was to evaluate its clinical and social impact on lung transplant (LT) patients treated at Strasbourg University Hospital, by comparing three periods: first lockdown (T1: March-May 2020), end of the first lockdown (T2: May-October 2020), and second lockdown (T3: November-December 2020) and the incidence of COVID-19 infections. A cohort of patients with rare lung disease (RLD) was also studied during T2.MethodsWe used clinical and paraclinical data collected during routine follow-up. A questionnaire was submitted to each patient at each period to assess their lifestyle, adherence to protective measures against COVID-19, contacts with their family and friends, and contagion risk. The incidence of new COVID-19 cases was also assessed.ResultsOverall, 283 LT and 57 RLD patients were included. We observed only eight COVID-19 cases over the three periods (n=4 during T1, n=0 during T2, and n=4 during T3) in LT patients, with 37.5% of patients hospitalized, no ICU transfers, and 100% favorable outcomes. No case of COVID-19 was diagnosed in the RLD cohort. When comparing the three periods in the LT group, fewer patients limited their out-of-home activities during T2 (p<0.0001). The frequency of these activities increased after the first lockdown, for the purchase of basic necessities (p<0.0001), and professional activity continued (p=0.008). We observed a significant increase in unscheduled medical consultations and in the prescription of anti-infective treatments during the end of the lockdown (p=0.0002 and p=0.005, respectively). Adherence to lockdown and to protective measures was high in both groups of patients.ConclusionCOVID-19 incidence remained low in both groups and there were significant lifestyle evolutions in LT patients and in those with RLD between first and second lockdown.

BACKGROUND Lung transplantation (LTx) is a life-extending therapy for specific patients with terminal lung diseases. This study aimed to evaluate the associations and causes of 1-year mortality after lung transplantation at Strasbourg University Hospital, France, between 2012 and 2021. MATERIAL AND METHODS We carried out a retrospective analysis on 425 patients who underwent LTx at Strasbourg University Hospital between January 1, 2012, and December 31, 2021. Pre-transplant, perioperative, and postoperative data were collected from the electronic medical records. RESULTS Among all patients, 94.6% had a LTx, 4.0% a heart-lung transplantation, and 1.4% underwent pancreatic islet-lung transplantation. The median age at transplantation was 57 years, with 55.3% male patients. The main native lung disease leading to LTx was chronic obstructive pulmonary disease in 51.1% of patients; 16.2% needed super-urgent LTx. The 1-year mortality rate was 11.5%. Most deaths were either caused by multi-organ failure or septic shock. In our multivariate analysis, we identified 3 risk factors significantly related to 1-year mortality after LTx: body mass index (BMI) between 25 and 30 kg/m² vs BMI between 18.5 and 25 kg/m² (P=0.032), postoperative extracorporeal membrane oxygenation support (P=0.034), and intensive care unit length of stay after transplantation (P<0.001). Two other factors were associated with a significantly lower 1-year mortality risk: longer hospital stay after LTx (P=0.024) and tacrolimus prescription (P=0.004). CONCLUSIONS Our study reported a 1-year mortality rate of 11.5% after LTx. Although LTx candidates are carefully selected, additional data are required to improve understanding of the risk factors for post-LTx mortality.

Background: Cystic fibrosis related diabetes (CFRD) is commonly associated with declining lung function and nutritional status. We aimed to evaluate the pulmonary impact of early glucose abnormalities by using 2-h standard oral glucose tolerance testing (OGTT) and continuous glucose monitoring (CGM) in people with cystic fibrosis (PwCF). Methods: PwCF aged >= 10 years old without known CFRD were included in a five-year prospective multicentre study. Annual evaluation of nutritional status, lung function, OGTT and CGM was set up. Associations between annual rate changes (A) in lung function, AFEV1 (forced expiratory volume in 1 s) percentage predicted (pp) and AFVC (forced vital capacity) pp., and annual rate changes in OGTT or CGM variables were estimated with a mixed model with a random effect for subject. Results: From 2009 to 2016, 112 PwCF (age: 21 +/- 11 years, BMI (body mass index) z-score: -0.55 +/- 1.09, FEV1pp: 77 +/- 24 %, 2-h OGTT glucose: 122 +/- 44 mg/dL, AUC (area under curve) >140 mg/dL: 1 mg/dL/day (0.2, 3.0) were included. A total of 428 OGTTs and 480 CGMs were collected. The participants presented annual decline of FVCpp and FEV1pp at -1.0 % per year (-1.6, -0.4), p < 0.001 and - 1.9 % per year (-2.5, -1.3), p < 0.001 respectively without change in BMI z-score during the study. Variation of two-hour OGTT glucose was not associated with declining lung function, as measured by AFEV1pp (p = 0.94) and AFVCpp (p = 0.90). Among CGM variables, only increase in AUC >140 mg/dL between two annual visits was associated with a decrease in AFVCpp (p < 0.05) and AFEV1pp (p < 0.05). Conclusions: This prospective study supports the fact that early glucose abnormalities revealed by CGM predict pulmonary function decline in PwCF, while 2-h standard OGTT glucose is not associated with pulmonary impairment.

BACKGROUND: Respiratory syncytial virus (RSV) infection in lung transplant recipients is associated with high morbidity. This study evaluated the RSV fusion inhibitor presatovir in RSV-infected lung transplant recipients. METHODS: In this international Phase 2b, randomized, double-blind, placebo-controlled trial (NCT02534350), adult lung transplant recipients with symptomatic confirmed RSV infection for <= 7 days received oral presatovir 200 mg on day 1 and 100 mg daily on days 2 to 14, or placebo (2:1), with follow-up through day 28. There were 2 coprimary endpoints: time-weighted average change in nasal RSV load from day 1 to 7, calculated from nasal swabs, in the full analysis set ([FAS]; all patients who received study drug and had quantifiable baseline nasal RSV load) and time-weighted average change in nasal RSV load from day 1 to 7 in the subset of patients with pretreatment symptom duration at the median or shorter of the FAS. Secondary endpoints were changes in respiratory infection symp-toms assessed using the Influenza Patient-Reported Outcomes questionnaire and lung function mea-sured by spirometry. RESULTS: Sixty-one patients were randomized, 40 received presatovir, 20 placebo, and 54 were included in efficacy analyses. Presatovir did not significantly improve the primary endpoint in the FAS (treatment difference [95% CI], 0.10 [-0.43, 0.63] log10 copies/ml; p = 0.72) or the shorter symptom duration subgroup (-0.12 [-0.94, 0.69] log10 copies/ml; p = 0.76). Secondary endpoints were not different between presatovir and placebo groups. Presatovir was generally well tolerated. CONCLUSIONS: Presatovir treatment did not significantly improve change in nasal RSV load, symptoms, or lung function in lung transplant recipients. J Heart Lung Transplant 2023;42:908-916 (c) 2023 The Author(s). Published by Elsevier Inc. on behalf of International Society for Heart and Lung Transplantation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

To cite: Guibert N, Mazières J, Moreno B, et al. Thorax Epub ahead of print: [please include Day Month Year]. doi:10.1136/ thorax-2022-219954 Pulmonology, University Hospital Centre Toulouse, Toulouse, France Thoracic Oncology, CHU Toulouse, Hôpital Larrey, Toulouse, France AnatomikModeling, Toulouse, France Department of Thoracic Oncology, Pleural Diseases and Interventional Pulmonology, Assistance PubliqueHôpitaux de Marseille (APHM), Hopital Nord, Marseille, France Pulmonology, CHU Toulouse, hopital Larrey, Toulouse, France Pneumology, CHU de Strasbourg, Strasbourg, France