Peter Jaksch

Zusammenfassung: Seit einigen Jahren wächst der Anteil von Patient:innen mit interstitiellen Lungenerkrankungen (ILD) im Rahmen systemischer Autoimmunerkrankungen, wie rheumatoide Arthritis (RA), systemische Sklerose, systemischer Lupus erythematodes (SLE) oder Mischkollagenosen (MCTD), im Kollektiv der Lungentransplantations(LuTX)-Patient:innen. Gerade diesem Kollektiv eröffnet die LuTX oft die einzige therapeutische Perspektive. Im Vergleich zu Patient:innen mit interstitieller Lungenfibrose wurden in LuTX-Studien im Wesentlichen ähnliche Ergebnisse in Bezug auf Abstoßungsreaktion, Outcome und Überleben erzielt, sodass rheumatologische Grunderkrankungen keine Kontraindikationen zur LuTX darstellen. Vielmehr ist die LuTX in dieser Klientel eine sichere und effektive Behandlungsoption. Mögliche Komorbiditäten, wie gastroösophagealer Reflux und Aspiration, renale Beteiligung, Gefäß- und Hautmanifestationen, sowie ggf. eine erforderliche Immunsuppression aufgrund der Grunderkrankung und spezifische onkologische Risiken stellen besondere Herausforderungen im LuTX-Management dar. Grundsätzlich sind eine frühe Zuweisung in ein Transplantationszentrum, eine multidisziplinäre Abklärung mit Fokus auf extrapulmonale Manifestationen, eine individuelle Anpassung der Immunsuppression, eine interdisziplinäre rheumatologische Betreuung und ein spezifisches Nachsorgeprogramm sinnvoll. Das Wiener LuTX-Programm, eines der größten Zentren Europas, verfügt über eine langjährige Erfahrung in der LuTX-Behandlung, darunter auch Patient:innen mit rheumatischen Erkrankungen. Im vorliegenden Artikel werden die Wiener LuTX-Daten dargestellt, die internationale Literatur kritisch beleuchtet und Empfehlungen für das Management dieser besonderen Patient:innengruppe abgeleitet.

Background: Pulmonary alveolar proteinosis (PAP) is a rare disease. Only a small number of case reports describing lung transplantation (LTx) as a treatment option for PAP have been published. Due to this limited evidence, current guidelines on LTx for PAP remain vague. To address this gap, we collected cases of LTx for PAP worldwide. Methods: 214 centres were approached to contribute any cases of LTx performed for PAP. Re-transplantations and multi-organ transplantations were excluded. Patients were divided into two groups based on the presence of PAP recurrence after LTx. Time-to-event analyses were performed using Kaplan–Meier curves and Cox proportional-hazards modelling was performed with PAP recurrence as a time-dependent covariate. Results: At a response rate of 64%, 31 centres contributed 63 patients. Most had primary PAP (n=20; 39.2%). Six patients with secondary PAP were identified (11.8%), while seven (13.7%) had congenital and 18 (35.3%) unclassified PAP. Aetiology was not specified in 12. Patients underwent transplantation at a median (interquartile range) 11 (3–17) years after initial diagnosis. Nine (15%) patients developed PAP recurrence after LTx. No significant difference was found regarding patient characteristics between the patients with versus without recurrence. Freedom from recurrence was 96.2% (1 year), 83.5% (5 years) and 70.1% (10 years) post-LTx. PAP recurrence as time-dependent covariate was not significantly associated with graft loss (hazard ratio 1.88, 95% CI 0.51–6.91; p=0.342) in a Cox proportional-hazards model. Conclusion: LTx provides excellent peri-operative and long-term outcomes for patients with end-stage PAP and should be recommended in treatment guidelines. Although recurrence of PAP occurs in ∼15% of cases, overall survival appeared unaffected in our limited dataset.

Extracorporeal photopheresis (ECP) is an immunomodulatory therapy currently used as an add-on treatment for the prevention and management of organ rejection in lung transplantation. Thanks to its immunomodulatory properties and its ability to reduce the need for immunosuppressive therapies, ECP presents a promising therapeutic option, especially for high-risk patients with comorbidities, infections, or malignancies. This review provides a comprehensive overview of the current indications, clinical experience, and ongoing research surrounding the use of ECP in lung transplantation. Additionally, it delves into the current understanding of the mechanism of action of ECP, its potential role in lung transplantation, and the limitations identified in existing studies. By highlighting these aspects, the review aims to lay the groundwork for future research, which could further elucidate the mechanisms underlying this promising therapy and contribute to the standardization of therapeutic protocols.

Objective: To determine the impact of prolonged storage of donor lungs at 10 °C for up to 24 hours on outcome after lung transplantation. Background: An increasing body of evidence suggests 10 °C as the optimal storage temperature for donor lungs. A recent study showed that cold ischemic times can be safely expanded to >12 hours when lungs are stored at 10 °C. However, it is currently unknown how long donor lungs can be preserved before they deteriorate in function. Methods: Patients who received a donor lung stored at 10 °C between November 2020 and June 2023 at the lung transplant programs of Toronto, Vienna, and Madrid were included in this retrospective analysis. After excluding ex-vivo lung perfusion cases, recipients were grouped based on the total preservation times of their donor organs (P = 0.493]. Intensive care unit length of stay [6 days (4–14); 8 days (4–23); 8 days (5–32)] and hospital length of stay [32 days (20–48); 29 days (20–50); 26 days (17–50)] were also similar. Furthermore, the length of donor organ preservation had no impact on patient survival (log-rank P = 0.413). Conclusions: Prolonged static preservation of donor lungs at 10 °C for up to 24 hours is safe and does not impair short-intermediate outcomes after lung transplantation.

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.

Background: Lung transplant recipients have the worst long-term outcomes of all solid organs due to acute rejection and chronic lung allograft dysfunction (CLAD). Our objective was to investigate the efficacy of extracorporeal photopheresis (ECP) as a prophylactic treatment to prevent acute cellular rejection (ACR), cytomegalovirus (CMV) infections and reduce the risk of CLAD.Methods: This was a single-centre prospective randomised controlled trial conducted at the Medical University of Vienna (Vienna, Austria) between 2018 and 2020. It included 31 COPD recipients per group. The treatment group underwent ECP in addition to a standard triple-drug immunosuppression protocol after lung transplantation. The control group received standard triple-drug immunosuppressive therapy. The primary outcome was a composite outcome defined as incidence of high-grade ACR, CMV infection or CLAD within 24 months after lung transplantation.Results: In the control group, 19 patients (61.3%) achieved the primary combined end-point compared with only six patients (19.4%) in the treatment group (pversus0.56±0.94; pversus1.0±1.45; p=0.002). The rate of infections was lower in the ECP group with five cases and 67 cumulative hospital days compared with 22 cases and 309 days in the control group (p=0.002). Freedom from CLAD at 3 years was significantly greater in the ECP group (p=0.015).Conclusion: Adding ECP to standard triple immunosuppression resulted in a significant reduction of the number of ACR episodes and significantly lower incidence of CLAD.

Ultralow-dose photon-counting CT yielded appropriate image quality to show anatomic structures and detect interstitial lung abnormalities, thus indicating its usefulness as a tool for long-term follow-up after lung transplant.