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Maintenance of long-term lung allograft health in lung transplant recipients (LTRs) requires a fine balancing act between providing sufficient immunosuppression to reduce the risk of rejection whilst at the same time not over-immunosuppressing individuals and exposing them to the myriad of immunosuppressant drug side-effects that can cause morbidity and mortality. At present, lung transplant physicians only have limited and rather blunt tools available to assist them with this task. Although therapeutic drug monitoring provides clinically useful information about single time point and longitudinal exposure of LTRs to immunosuppressants, it lacks precision in determining the functional level of immunosuppression that an individual is experiencing. There is a significant gap in our ability to monitor lung allograft health and therefore tailor optimal personalised immunosuppression regimens. Molecular diagnostics performed on blood, bronchoalveolar lavage or lung tissue that can detect early signs of subclinical allograft injury, differentiate rejection from infection or distinguish cellular from humoral rejection could offer clinicians powerful tools in protecting lung allograft health. In this review, we look at the current evidence behind molecular monitoring in lung transplantation and ask if it is ready for routine clinical use. Although donor-derived cell-free DNA and tissue transcriptomics appear to be the techniques with the most immediate clinical potential, more robust data are required on their performance and additional clinical value beyond standard of care. [ABSTRACT FROM AUTHOR]

Intimal granulomatous angiitis is a facet of pulmonary sarcoidosis vasculitis that has almost been forgotten. Its observation may offer new understanding of the various patterns of pulmonary hypertension associated with sarcoidosis. https://bit.ly/3g6Ms76., Competing Interests: Conflict of interest: F. Jeny has received payment or honoraria from Boehringer Ingelheim, outside the submitted work; and support for attending meetings from Oxyvie, outside the submitted work. D. Valeyre has received payment or honoraria from Roche, Boehringer Ingelheim and AstraZeneca, outside the submitted work; and support to attend meetings from Boehringer Ingelheim, outside the submitted work. The remaining authors have nothing to disclose., (Copyright ©The authors 2023.)

Question Addressed by the Study: Do three coronavirus disease 2019 (COVID-19) vaccine doses induce a serological response in lung transplant recipients?, Methods: We retrospectively included 1071 adults (551 (52%) males) at nine transplant centres in France. Each had received three COVID-19 vaccine doses in 2021, after lung transplantation. An anti-spike protein IgG response, defined as a titre >264 BAU·mL -1 after the third dose (median (interquartile range (IQR)) 3.0 (1.7-4.1) months), was the primary outcome and adverse events were the secondary outcomes. Median (IQR) age at the first vaccine dose was 54 (40-63) years and median (IQR) time from transplantation to the first dose was 64 (30-110) months., Results: Median (IQR) follow-up after the first dose was 8.3 (6.7-9.3) months. A vaccine response developed in 173 (16%) patients. Factors independently associated with a response were younger age at vaccination, longer time from transplantation to vaccination and absence of corticosteroid or mycophenolate therapy. After vaccination, 51 (5%) patients (47 non-responders (47/898 (5%)) and four (4/173 (2%)) responders) experienced COVID-19, at a median (IQR) of 6.6 (5.1-7.3) months after the third dose. No responders had severe COVID-19 compared with 15 non-responders, including six who died of the disease., Conclusions: Few lung transplant recipients achieved a serological response to three COVID-19 vaccine doses, indicating a need for other protective measures. Older age and use of mycophenolate or corticosteroids were associated with absence of a response. The low incidence of COVID-19 might reflect vaccine protection via cellular immunity and/or good adherence to shielding measures., Competing Interests: Conflict of interest: None for any authors., (Copyright ©The authors 2023.)

Background: The published experience of lung transplantation in acute respiratory distress syndrome (ARDS) is limited. The aim of this study was to investigate the contemporary results of lung transplantation attempts in ARDS in major European centres., Methods: We conducted a retrospective multicentre cohort study of all patients listed for lung transplantation between 2011 and 2019. We surveyed 68 centres in 22 European countries. All patients admitted to the waitlist for lung transplantation with a diagnosis of "ARDS/pneumonia" were included. Patients without extracorporeal membrane oxygenation (ECMO) or mechanical ventilation were excluded. Patients were followed until 1 October 2020 or death. Multivariable analysis for 1-year survival after listing and lung transplantation was performed., Results: 55 centres (81%) with a total transplant activity of 12 438 lung transplants during the 9-year period gave feedback. 40 patients with a median age of 35 years were identified. Patients were listed for lung transplantation in 18 different centres in 10 countries. 31 patients underwent lung transplantation (0.25% of all indications) and nine patients died on the waitlist. 90% of transplanted patients were on ECMO in combination with mechanical ventilation before lung transplantation. On multivariable analysis, transplantation during 2015-2019 was independently associated with better 1-year survival after lung transplantation (OR 10.493, 95% CI 1.977-55.705; p=0.006). 16 survivors out of 23 patients with known status (70%) returned to work after lung transplantation., Conclusions: Lung transplantation in highly selected ARDS patients is feasible and outcome has improved in the modern era. The selection process remains ethically and technically challenging., Competing Interests: Conflict of interest: J. Gottlieb reports grants from the German Center for Lung Research (DZL), during the conduct of the study; grants from Deutsche Forschungsgemeinschaft (DFG) and from Breath Therapeutics, personal fees from Novartis, outside the submitted work. Conflict of interest: P.M. Lepper has nothing to disclose. Conflict of interest: C. Berastegui has nothing to disclose. Conflict of interest: B. Montull has nothing to disclose. Conflict of interest: A. Wald has nothing to disclose. Conflict of interest: J. Parmar reports nonfinancial support from Breath Therapeutics, outside the submitted work. Conflict of interest: J.M. Magnusson reports personal fees from GSK, grants and personal fees from Boehringer Ingelheim, outside the submitted work. Conflict of interest: F. Schönrath reports grants from Novartis and Abbott, nonfinancial support from Medtronic, other from AstraZeneca and Orion Pharma, outside the submitted work. Conflict of interest: T. Laisaar has nothing to disclose. Conflict of interest: S. Michel reports grants from the German Center for Lung Research (DZL), during the conduct of the study; grants from Deutsche Forschungsgemeinschaft (DFG), outside the submitted work. Conflict of interest: H. Larsson has nothing to disclose. Conflict of interest: R. Vos reports grants from Research Foundation-Flanders (FWO), outside the submitted work. Conflict of interest: A. Haneya has nothing to disclose. Conflict of interest: T. Sandhaus has nothing to disclose. Conflict of interest: E. Verschuuren has nothing to disclose. Conflict of interest: J. le Pavec has nothing to disclose. Conflict of interest: J. Tikkanen reports personal fees from Astellas Pharma, GSK pharma and CSL Behring, outside the submitted work. Conflict of interest: K. Hoetzenecker reports grants from FWF Austria, personal fees from Medtronic, outside the submitted work., (Copyright ©The authors 2022. For reproduction rights and permissions contact permissions@ersnet.org.)

Study Question: In patients with sarcoidosis, past and ongoing immunosuppressive regimens, recurrent disease in the transplant and extrapulmonary involvement may affect outcomes of lung transplantation. We asked whether sarcoidosis lung phenotypes can be differentiated and, if so, how they relate to outcomes in patients with pulmonary sarcoidosis treated by lung transplantation., Patients and Methods: We retrospectively reviewed data from 112 patients who met international diagnostic criteria for sarcoidosis and underwent lung or heart-lung transplantation between 2006 and 2019 at 16 European centres., Results: Patient survival was the main outcome measure. At transplantation, median (interaquartile range (IQR)) age was 52 (46-59) years; 71 (64%) were male. Lung phenotypes were individualised as follows: 1) extended fibrosis only; 2) airflow obstruction; 3) severe pulmonary hypertension (sPH) and airflow obstruction; 4) sPH, airflow obstruction and fibrosis; 5) sPH and fibrosis; 6) airflow obstruction and fibrosis; 7) sPH; and 8) none of these criteria, in 17%, 16%, 17%, 14%, 11%, 9%, 5% and 11% of patients, respectively. Post-transplant survival rates after 1, 3, and 5 years were 86%, 76% and 69%, respectively. During follow-up (median (IQR) 46 (16-89) months), 31% of patients developed chronic lung allograft dysfunction. Age and extended lung fibrosis were associated with increased mortality. Pulmonary fibrosis predominating peripherally was associated with short-term complications., Answer to the Study Question: Post-transplant survival in patients with pulmonary sarcoidosis was similar to that in patients with other indications for lung transplantation. The main factors associated with worse survival were older age and extensive pre-operative lung fibrosis., Competing Interests: Conflict of interest: J. Le Pavec has nothing to disclose. Conflict of interest: D. Valeyre has nothing to disclose. Conflict of interest: P. Gazengel has nothing to disclose. Conflict of interest: A.M. Holm has nothing to disclose. Conflict of interest: H.H. Schultz has nothing to disclose. Conflict of interest: M. Perch has nothing to disclose. Conflict of interest: A. Le Borgne has nothing to disclose. Conflict of interest: M. Reynaud-Gaubert has nothing to disclose. Conflict of interest: C. Knoop has nothing to disclose. Conflict of interest: L. Godinas has nothing to disclose. Conflict of interest: S. Hirschi has nothing to disclose. Conflict of interest: V. Bunel has nothing to disclose. Conflict of interest: R. Laporta has nothing to disclose. Conflict of interest: S. Harari has nothing to disclose. Conflict of interest: E. Blanchard has nothing to disclose. Conflict of interest: J.M. Magnusson has nothing to disclose. Conflict of interest: A. Tissot has nothing to disclose. Conflict of interest: J-F. Mornex has nothing to disclose. Conflict of interest: C. Picard has nothing to disclose. Conflict of interest: L. Savale has nothing to disclose. Conflict of interest: J-F. Bernaudin has nothing to disclose. Conflict of interest: P-Y. Brillet has nothing to disclose. Conflict of interest: H. Nunes has nothing to disclose. Conflict of interest: M. Humbert has nothing to disclose. Conflict of interest: E. Fadel has nothing to disclose. Conflict of interest: J. Gottlieb has nothing to disclose., (Copyright ©The authors 2021. For reproduction rights and permissions contact permissions@ersnet.org.)

Introduction: Since July 2007, the French high emergency lung transplantation (HELT) allocation procedure prioritises available lung grafts to waiting patients with imminent risk of death. The relative impacts of donor, recipient and matching on the outcome following HELT remain unknown. We aimed at deciphering the relative impacts of donor, recipient and matching on the outcome following HELT in an exhaustive administrative database., Methods: All lung transplantations performed in France were prospectively registered in an administrative database. We retrospectively reviewed the procedures performed between July 2007 and December 2015, and analysed the impact of donor, recipient and matching on overall survival after the HELT procedure by fitting marginal Cox models., Results: During the study period, 2335 patients underwent lung transplantation in 11 French centres. After exclusion of patients with chronic obstructive pulmonary disease/emphysema, 1544 patients were included: 503 HELT and 1041 standard lung transplantation allocations. HELT was associated with a hazard ratio for death of 1.41 (95% CI 1.22-1.64; p<0.0001) in univariate analysis, decreasing to 1.32 (95% CI 1.10-1.60) after inclusion of recipient characteristics in a multivariate model. A donor score computed to predict long-term survival was significantly different between the HELT and standard lung transplantation groups (p=0.014). However, the addition of donor characteristics to recipient characteristics in the multivariate model did not change the hazard ratio associated with HELT., Conclusions: This exhaustive French national study suggests that HELT is associated with an adverse outcome compared with regular allocation. This adverse outcome is mainly related to the severity status of the recipients rather than donor or matching characteristics., Competing Interests: Conflict of interest: A. Roussel has nothing to disclose. Conflict of interest: E. Sage has nothing to disclose. Conflict of interest: G. Massard has nothing to disclose. Conflict of interest: P-A. Thomas has nothing to disclose. Conflict of interest: Y. Castier has nothing to disclose. Conflict of interest: E. Fadel has nothing to disclose. Conflict of interest: F. Le Pimpec-Barthes has nothing to disclose. Conflict of interest: J-M. Maury has nothing to disclose. Conflict of interest: J. Jougon has nothing to disclose. Conflict of interest: P. Lacoste has nothing to disclose. Conflict of interest: J. Claustre has nothing to disclose. Conflict of interest: M. Dahan has nothing to disclose. Conflict of interest: A. Pirvu has nothing to disclose. Conflict of interest: A. Tissot has nothing to disclose. Conflict of interest: M. Thumerel has nothing to disclose. Conflict of interest: G. Drevet has nothing to disclose. Conflict of interest: C. Pricopi has nothing to disclose. Conflict of interest: J. Le Pavec has nothing to disclose. Conflict of interest: H. Mal has nothing to disclose. Conflict of interest: X-B. D'Journo has nothing to disclose. Conflict of interest: R. Kessler has nothing to disclose. Conflict of interest: A. Roux has nothing to disclose. Conflict of interest: R. Dorent has nothing to disclose. Conflict of interest: G. Thabut has nothing to disclose. Conflict of interest: P. Mordant has nothing to disclose., (Copyright ©ERS 2019.)

Pregnancy after lung and heart-lung transplantation remains rare. This French study deals with change in lung function after a pregnancy and the maternal and newborn outcomes. We retrospectively included 39 pregnancies in 35 women aged >20 years. Data on patients, course of pregnancies and newborns were collected from nine transplantation centres. Mean age at time of pregnancy was 28 years. Cystic fibrosis affected 71% of patients. Mean±sd time between transplantation and pregnancy was 63±44 months. 26 births occurred (67%) with a mean term of 36 weeks of amenorrhoea and a mean birthweight of 2409 g. Prematurity was observed in 11 cases (43%). Forced expiratory volume in 1 s was 83.9% of predicted before pregnancy and 77.3% of predicted 1 year after the end of pregnancy (p=0.04). 10 patients developed chronic lung allograft dysfunction after delivery. Nine patients died at a mean±sd time after transplantation of 8.2±7 years and a mean±sd time after pregnancy of 4.6±6.5 years. These data show that pregnancy remains feasible in lung and heart-lung transplant recipients, with more frequent maternal and newborn complications than in the general population. Survival in this cohort appears to be similar to the global survival observed in lung transplant recipients. Planned pregnancy and multidisciplinary follow-up are crucial., Competing Interests: Conflict of interest: C. Bry has nothing to disclose. Conflict of interest: D. Hubert has nothing to disclose. Conflict of interest: M. Reynaud-Gaubert has nothing to disclose. Conflict of interest: C. Dromer has nothing to disclose. Conflict of interest: H. Mal reports nonfinancial support from Roche, Boehringer, CSL Behring and Novartis, outside the submitted work. Conflict of interest: A. Roux has nothing to disclose. Conflict of interest: V. Boussaud has nothing to disclose. Conflict of interest: J. Claustre has nothing to disclose. Conflict of interest: J. Le Pavec has nothing to disclose. Conflict of interest: M. Murris-Espin has nothing to disclose. Conflict of interest: I. Danner-Boucher has nothing to disclose., (Copyright ©ERS 2019.)

Data on treatment of patients with portopulmonary hypertension (PoPH) are limited, as they are usually excluded from randomised controlled trials with pulmonary arterial hypertension (PAH)-specific therapies. This study investigated the short- and long-term efficacy/safety of bosentan in these patients, as well as its pharmacokinetics. All 34 consecutive patients with PoPH treated with first-line bosentan (December 2002 to July 2009) were retrospectively evaluated. Assessments included the New York Heart Association functional class (NYHA FC), blood tests, haemodynamics, 6-min walk distance (6MWD) and event-free status. The pharmacokinetics of bosentan in five patients with Child-Pugh (C-P) class B cirrhosis were compared with idiopathic PAH patients. Significant improvements from baseline were observed in NYHA FC, 6 MWD and haemodynamics, and were largely maintained during follow-up. Patients with C-P class B cirrhosis (n=9) had significantly larger haemodynamic improvement after mean ± SD 5 ± 2 months. Mean follow-up time was 43 ± 19 months; four patients died and seven patients had significant elevation of liver enzymes (annual rate 5.5%). Plasma concentrations of bosentan were higher in patients with C-P class B cirrhosis than those observed in idiopathic PAH. These data confirm the benefit of bosentan treatment for patients with PoPH. Haemodynamic improvements were particularly pronounced in patients with more severe cirrhosis. The safety profile of bosentan was consistent with previous studies.