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. 2025 Jun 2;11(3):00675-2024.
doi: 10.1183/23120541.00675-2024. eCollection 2025 May.

Chronic lung allograft dysfunction after lung transplantation: prevention, diagnosis and treatment in 44 European centres

Jens Gottlieb  1   2   3 , Robin Vos  2   4   5 , Peter Jaksch  2   6 , Merel Hellemons  7   8 , Are Martin Holm  9 , Letizia Corinna Morlacchi  10 , Jesper Magnusson  11 , Rodrigo Alonso Moralejo  12 , Víctor M Mora-Cuesta  2   13 , Vera Ennekes  14 , Anna Reed  15 , Claire Merveilleux Du Vignaux  16 , Ina Hettich  17 , David Bennett  18 , Matthias Hecker  3   19 , Alexandra Wald  20 , Svitlana Guk  21 , Andris Skride  22 , Anna Nolde  23 , Christiane Knoop  24 , Federica Meloni  2   25 , Jussi Tikkanen  26 , Hillevi Larsson  27 , Adrien Tissot  28   29 , Peter Riddell  30 , Jérôme Le Pavec  31 , Michael Perch  32   33 , Benjamin Renaud-Picard  34 , François M Carlier  35 , Veronika Müller  2   36 , Jasvir Parmar  37 , Jan Havlin  38 , Rosalía Laporta  39 , Macé Matthew Schuurmans  40 , Matevž Harlander  41 , Slavomir Zenglen  42 , Olivier Brugiere  43 , Nikolaus Kneidinger  3   44   45 , Andrew Fisher  46 , Berta Saez-Gimenez  2   47
Affiliations

Chronic lung allograft dysfunction after lung transplantation: prevention, diagnosis and treatment in 44 European centres

Jens Gottlieb et al. ERJ Open Res. .

Abstract

Background: There are limited data on optimal management of chronic lung allograft dysfunction (CLAD). We aimed to describe the variability of diagnostic and therapeutic practices in Europe.

Methods: A structured questionnaire was sent to 71 centres in 24 countries. Questions were related to contemporary clinical practices for workup, monitoring and treatment of CLAD. The number of lung transplant procedures and patients in follow-up were collected.

Results: 44 centres (62%) responded from 20 countries, representing 74% of European activity. The prevalence of CLAD was estimated at 9.1 cases per million population (25th and 75th percentiles of 4.4, 15.7). Preferred initial workup for probable CLAD consisted of chest computed tomography (CT) (inspiratory 91% and expiratory 74%), donor-specific antibody (DSA) measurement (86%), bronchoalveolar lavage (BAL) (85%) and transbronchial biopsy (81%). For monitoring of definite CLAD, inspiratory CT (67%), DSA (61%) and BAL (43%) were preferred. Body plethysmography was unavailable for 16% of cases. Prophylaxis was based on preventing infections (cytomegalovirus 99%, inhaled antibiotics 70% and antifungals 65%), tacrolimus-based immunosuppression (96%), azithromycin (72%) and universal proton pump inhibitor treatment (84%). First-line treatment of CLAD was based on azithromycin (82%) and steroid augmentation (74%). Photopheresis was used in 26% of cases.

Conclusion: Current European practice CLAD detection is based on spirometry, inspiratory CT and DSA, with limited access to plethysmography and expiratory CT. Prophylactic treatment is based on azithromycin, tacrolimus-based immunosuppression and treatment of risk factors. No single treatment strategy is universally used, highlighting the need for an effective treatment of CLAD. The preferred first-line strategy is azithromycin and steroid augmentation.

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Conflict of interest statement

Conflict of interest: J. Gottlieb reports grants from Deutsche Forschungsgemeinschaft, Zambon and the German Center of Lung Research (DZL); personal fees from Novartis, AstraZeneca, CSL Behring, Sanofi and Moderna, all outside the submitted work. He served as a member of the SCAN CLAD Study data safety monitoring board as a nonfinancial disclosure. Conflict of interest: R. Vos reports grants from Research Foundation-Flanders, Cystic Fibrosis Foundation and AstraZeneca; nonfinancial support from Incyte, Zambon and Sanofi; and personal fees from AstraZeneca, GlaxoSmithKline, Zambon, Takeda, Shionogi and Sanofi, all outside the submitted work. Conflict of interest: M. Hellemons is an associate editor of this journal. Conflict of interest: J. Magnusson reports personal fees from Boehringer Ingelheim, AstraZeneca, GlaxoSmithKline, Takada Pharma, Vicore Pharma and Mallinckrodt, outside the submitted work. Conflict of interest: V. Ennekes reports personal fees from Astra Zeneca outside the submitted work. Conflict of interest: P. Riddell is an associate editor of this journal. Conflict of interest: M. Perch reports personal fees from Zambon, Takeda, AstraZeneca, TFF and PulmonX; other support from Therakos; and support from Ryme medical, all outside the submitted work; and is a member of the steering committee of the eCLAD study. Conflict of interest: F.M. Carlier reports travel grants from Takeda outside the present work. Conflict of interest: A. Fisher reports grants and personal fees from Therakos, other support from Sanofi, and grants from Chiesi, all outside the submitted work. Conflict of interest: B. Saez-Gimenez reports institutional research grants from Janssen Pharmaceuticals; fees for consultancy from Janssen Pharmaceuticals and Chiesi Spain; speaker fees from Janssen Pharmaceuticals and CareDx; and travel grants from Chiesi Spain. All disclosures are unrelated to the current work. Conflict of interest: The other authors have nothing to disclose.

Figures

FIGURE 1
FIGURE 1
Diagnostic tests for evaluation of possible chronic lung allograft dysfunction (CLAD) patients (n=44 centres). CT: computed tomography; 6MWT: 6-min walk test.
FIGURE 2
FIGURE 2
Technical monitoring of patients with definite chronic lung allograft dysfunction (CLAD) (n=44 centres). CT: computed tomography; 6MWT: 6-min walk test.
FIGURE 3
FIGURE 3
Options used for prophylaxis of chronic lung allograft dysfunction (CLAD) (n=44 centres). CMV: cytomegalovirus; D: donor; R: recipient; PPI: proton pump inhibitor; GERD: gastro-oesophageal reflux disease.
FIGURE 4
FIGURE 4
Options used for treatment of chronic lung allograft dysfunction (CLAD) (n=44 centres). LTOT: long-term oxygen therapy; LABA: long-acting β-agonists; LAMA: long-acting muscarinic agonist; ATG: anti-thymocyte globulin; JAK: Janus kinase; ROCK: Rho-associated protein kinase; mTOR: mechanistic target of rapamycin.
See this image and copyright information in PMC

References

    1. Chambers DC, Perch M, Zuckermann A, et al. . The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: Thirty-eighth adult lung transplantation report - 2021; Focus on recipient characteristics. J Heart Lung Transplant 2021; 40: 1060–1072. doi:10.1016/j.healun.2021.07.021 - DOI - PMC - PubMed
    1. Verleden GM, Glanville AR, Lease ED, et al. . Chronic lung allograft dysfunction: definition, diagnostic criteria, and approaches to treatment-a consensus report from the Pulmonary Council of the ISHLT. J Heart Lung Transplant 2019; 38: 493–503. doi:10.1016/j.healun.2019.03.009 - DOI - PubMed
    1. Ruttens D, Verleden SE, Demeyer H, et al. . Montelukast for bronchiolitis obliterans syndrome after lung transplantation: a randomized controlled trial. PLoS ONE 2018; 13: e0193564. doi:10.1371/journal.pone.0193564 - DOI - PMC - PubMed
    1. Corris PA, Ryan VA, Small T, et al. . A randomised controlled trial of azithromycin therapy in bronchiolitis obliterans syndrome (BOS) post lung transplantation. Thorax 2015; 70: 442–450. doi:10.1136/thoraxjnl-2014-205998 - DOI - PMC - PubMed
    1. Le Pavec J, Valeyre D, Gazengel P, et al. . Lung transplantation for sarcoidosis: outcome and prognostic factors. Eur Respir J 2021; 58: 2003358. doi:10.1183/13993003.03358-2020 - DOI - PubMed

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