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Kristina Vermeersch,1 Maria Gabrovska,2 Griet Deslypere,3 Ingel K Demedts,4 Hans Slabbynck,5 Joseph Aumann,3 Vincent Ninane,2 Geert M Verleden,1 Thierry Troosters,1,6 Kris Bogaerts,7,8 Guy G Brusselle,9 Wim Janssens1 On behalf of the BACE Trial Investigators 1KU Leuven, Laboratory of Respiratory Diseases, Department of Clinical and Experimental Medicine, Faculty of Medicine, Leuven, Belgium; 2Department of Pneumology, Centre Hospitalier Universitaire Saint-Pierre, Brussels, Belgium; 3Department of Pneumology, Jessa Ziekenhuis, Hasselt, Belgium; 4Department of Respiratory Medicine, AZ Delta Roeselare-Menen, Roeselare, Belgium; 5Department of Respiratory Medicine, ZNA Middelheim, Antwerpen, Belgium; 6KU Leuven, Department of Rehabilitation Sciences, Faculty of Kinesiology and Rehabilitation Sciences, Leuven, Belgium; 7KU Leuven, Department of Public Health and Primary Care, I-BioStat, Leuven, Belgium; 8Hasselt University, Hasselt, Belgium; 9Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium Background: Long-term use of macrolide antibiotics is effective to prevent exacerbations in chronic obstructive pulmonary disease (COPD). As risks and side effects of long-term intervention outweigh the benefits in the general COPD population, the optimal dose, duration of treatment, and target population are yet to be defined. Hospitalization for an acute exacerbation (AE) of COPD may offer a targeted risk group and an obvious risk period for studying macrolide interventions.Methods/design: Patients with COPD, hospitalized for an AE, who have a smoking history of ≥10 pack-years and had ≥1 exacerbation in the previous year will be enrolled in a multicenter, randomized, double-blind, placebo-controlled trial (NCT02135354). On top of a standardized treatment of systemic corticosteroids and antibiotics, subjects will be randomized to receive either azithromycin or placebo during 3 months, at an uploading dose of 500 mg once a day for 3 days, followed by a maintenance dose of 250 mg once every 2 days. The primary endpoint is the time-to-treatment failure during the treatment phase (ie, from the moment of randomization until the end of intervention). Treatment failure is a novel composite endpoint defined as either death, the admission to intensive care or the requirement of additional systemic steroids or new antibiotics for respiratory reasons, or the diagnosis of a new AE after discharge.Discussion: We investigate whether azithromycin initiated at the onset of a severe exacerbation, with a limited duration and at a low dose, might be effective and safe in the highest risk period during and immediately after the acute event. If proven effective and safe, this targeted approach may improve the treatment of severe AEs and redirect the preventive use of azithromycin in COPD to a temporary intervention in the subgroup with the highest unmet needs. Keywords: COPD, acute exacerbation, macrolide antibiotics, azithromycin, physical activity, RCT

Objectives: Recently a novel subgroup of bronchiolitis obliterans syndrome (BOS) has been described in patients after lung transplantation with high neutrophil counts in broncho-alveolar lavage and recovery of lung functional decline with azithromycin treatment. We aimed to describe the thin-section computed tomography (CT) findings of these neutrophilic reversible allograft dysfunction (NRAD) patients before and after azithromycin.Methods: A cohort of 100 lung transplant recipients with BOS were treated with azithromycin and underwent lung function testing, broncho-alveolar lavage and CT before azithromycin treatment and during follow-up. The 200 CT data sets were scored for bronchial dilatation, mucus plugging, centrilobular abnormalities, airway wall thickening, consolidation, ground glass and end-expiratory air trapping.Results: NRAD was characterized by more centrilobular abnormalities on CT (p = 0.03 for prevalence and p = 0.06 for severity) compared to non-responders. At follow-up NRAD patients showed improvement in all CT abnormalities including air trapping, but the degree of improvement in all CT abnormalities was significantly different between responders and non-responders (who showed progression of bronchus dilatation, consolidation and air trapping).Conclusions: Within BOS patients those with NRAD differ from azithromycin non-responders by more centrilobular abnormalities on CT before azithromycin and improvement in bronchus dilatation, consolidation and air trapping during treatment. [ABSTRACT FROM AUTHOR]

Rationale: Chronic obstructive pulmonary disease (COPD) is characterized by chronic airway inflammation. It is unclear if dendritic cells (DC) participate in this inflammatory process. Objectives: To evaluate the presence of DC in small airways of patients with COPD. Methods: We evaluated DC infiltration in small airways by immunohistochemistry in patients with COPD (stage I-IV), never-smokers, and smokers without COPD. Chemokine ligand 20 (CCL20, the most potent chemokine in attracting DC) was determined in total lung by RT-PCR and in induced sputum by enzyme-linked immunsorbent assay. Chemokine receptor 6 (CCR6, the receptor for CCL20) expression on human pulmonary DC was evaluated by RT-PCR and flow cytometry. Measurements and Main Results: There is a significant increase in DC number in the epithelium (p = 0.007) and adventitia (p = 0.009) of small airways of patients with COPD compared with never-smokers and smokers without COPD. DC number in epithelium and adventitia increases along with disease severity. CCL20 mRNA expression in total lung and CCL20 protein levels in induced sputum are significantly higher in patients with COPD compared with never-smokers (p = 0.034 for CCL20 mRNA and p = 0.0008 for CCL20 protein) and smokers without COPD (p = 0.016 for CCL20 mRNA and p = 0.001 for CCL20 protein). DC isolated from human lung express CCR6 both at mRNA and at protein level. Conclusions: This is the first description of airway infiltration by DC in COPD. Moreover, interaction between CCL20 and CCR6 provides a possible mechanism for accumulation of DC in the lungs in COPD. [ABSTRACT FROM AUTHOR]

RATIONALE: Bronchiolitis obliterans syndrome (BOS) remains the leading cause of death after lung transplantation. Treatment is difficult, although azithromycin has recently been shown to improve FEV(1). The exact mechanism of action is unclear. HYPOTHESES: (1) Azithromycin reduces airway neutrophilia and interleukin (IL)-8 and (2) airway neutrophilia predicts the improvement in FEV(1). METHODS: Fourteen lung transplant patients with BOS (between BOS 0-p and BOS 3) were treated with azithromycin, in addition to their current immunosuppressive treatment. Before and 3 mo after azithromycin was introduced, bronchoscopy with bronchoalveolar lavage (BAL) was performed for cell differentiation and to measure IL-8 and IL-17 mRNA ratios. RESULTS: The FEV(1) increased from 2.36 (+/- 0.82 L) to 2.67 L (+/- 0.85 L; p = 0.007), whereas the percentage of BAL neutrophilia decreased from 35.1 (+/- 35.7%) to 5.7% (+/- 6.5%; p = 0.0024). There were six responders to azithromycin (with an FEV(1) increase of > 10%) and eight nonresponders. Using categorical univariate linear regression analysis, the main significant differences in characteristics between responders and nonresponders were the initial BAL neutrophilia (p < 0.0001), IL-8 mRNA ratio (p = 0.0009), and the postoperative day at which azithromycin was started (p = 0.036). There was a significant correlation between the initial percentage of BAL neutrophilia and the changes in FEV(1) after 3 mo (r = 0.79, p = 0.0019). CONCLUSION: Azithromycin significantly reduces airway neutrophilia and IL-8 mRNA in patients with BOS. Responders have a significantly higher BAL neutrophilia and IL-8 compared with nonresponders and had commenced treatment earlier after transplantation. BAL neutrophilia can be used as a predictor for the FEV(1) response to azithromycin. [ABSTRACT FROM AUTHOR]

Currently, lung transplantation outcome remains inferior compared to other solid organ transplantations. A major cause for limited survival after lung transplantation is chronic lung allograft dysfunction. Numerous animal models have been developed to investigate chronic lung allograft dysfunction to discover adequate treatments. The murine orthotopic lung transplant model has been further optimized over the last years. However, different degrees of genetic mismatch between donor and recipient mice have been used, applying a single, minor, moderate, and major genetic mismatch. This review aims to reassess the existing murine mismatch models and provide a comprehensive overview, with a specific focus on their eventual histopathological presentation. This will be crucial to leverage this model and tailor it according to specific research needs., Competing Interests: Declaration of competing interest The authors of this review have no conflicts of interest to disclose as described by the American Journal of Transplantation., (Copyright © 2024 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: Chronic lung allograft dysfunction (CLAD) remains a life-threatening complication following lung transplantation. Different CLAD phenotypes have recently been defined, based on the combination of pulmonary function testing and chest computed tomography (CT) scanning and spurred renewed interests in differential diagnosis, risk factors and management of CLAD., Recent Findings: Given their crucial importance in the differential diagnosis, we will discuss the latest development in assessing the pulmonary function and chest CT scan, but also their limitations in proper CLAD phenotyping, especially with regards to patients with baseline allograft dysfunction. Since no definitive treatment exists, it remains important to timely identify clinical risk factors, but also to assess the presence of specific patterns or biomarkers in tissue or in broncho alveolar lavage in relation to CLAD (phenotypes). We will provide a comprehensive overview of the latest advances in risk factors and biomarker research in CLAD. Lastly, we will also review novel preventive and curative treatment strategies for CLAD., Summary: Although this knowledge has significantly advanced the field of lung transplantation, more research is warranted because CLAD remains a life-threatening complication for all lung transplant recipients., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Antimicrobial misuse contributes to antimicrobial resistance in thoracic transplant (TTx) and mechanical circulatory support (MCS) recipients. This study uses a modified Delphi method to define the expected appropriate antimicrobial prescribing for the common clinical scenarios encountered in TTx and MCS recipients., Methods: An online questionnaire on managing 10 common infectious disease syndromes was submitted to a multidisciplinary Delphi panel of 25 experts from various disciplines. Consensus was predefined as 80% agreement for each question. Questions where consensus was not achieved were discussed during live virtual live sessions adapted by an independent process expert., Results: An online survey of 62 questions related to 10 infectious disease syndromes was submitted to the Delphi panel. In the first round of the online questionnaire, consensus on antimicrobial management was reached by 6.5% (4/62). In Round 2 online live discussion, the remaining 58 questions were discussed among the Delphi Panel members using a virtual meeting platform. Consensus was reached among 62% (36/58) of questions. Agreement was not reached regarding the antimicrobial management of the following six clinical syndromes: (1) Burkholderia cepacia pneumonia (duration of therapy); (2) Mycobacterium abscessus (intra-operative antimicrobials); (3) invasive aspergillosis (treatment of culture-negative but positive BAL galactomannan) (duration of therapy); (4) respiratory syncytial virus (duration of antiviral therapy); (5) left ventricular assist device deep infection (initial empirical antimicrobial coverage) and (6) CMV (duration of secondary prophylaxis)., Conclusion: This Delphi panel developed consensus-based recommendations for 10 infectious clinical syndromes seen in TTx and MCS recipients., (© 2024 Wiley Periodicals LLC.)

Background: Assessment and selection of donor lungs remain largely subjective and experience based. Criteria to accept or decline lungs are poorly standardized and are not compliant with the current donor pool. Using ex vivo computed tomography (CT) images, we investigated the use of a CT-based machine learning algorithm for screening donor lungs before transplantation., Methods: Clinical measures and ex situ CT scans were collected from 100 cases as part of a prospective clinical trial. Following procurement, donor lungs were inflated, placed on ice according to routine clinical practice, and imaged using a clinical CT scanner before transplantation while stored in the icebox. We trained and tested a supervised machine learning method called dictionary learning, which uses CT scans and learns specific image patterns and features pertaining to each class for a classification task. The results were evaluated with donor and recipient clinical measures., Results: Of the 100 lung pairs donated, 70 were considered acceptable for transplantation (based on standard clinical assessment) before CT screening and were consequently implanted. The remaining 30 pairs were screened but not transplanted. Our machine learning algorithm was able to detect pulmonary abnormalities on the CT scans. Among the patients who received donor lungs, our algorithm identified recipients who had extended stays in the intensive care unit and were at 19 times higher risk of developing chronic lung allograft dysfunction within 2 years posttransplant., Conclusions: We have created a strategy to ex vivo screen donor lungs using a CT-based machine learning algorithm. As the use of suboptimal donor lungs rises, it is important to have in place objective techniques that will assist physicians in accurately screening donor lungs to identify recipients most at risk of posttransplant complications., (Copyright © 2023 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Lung transplant (LTx) recipients are at high risk for COVID-19 related morbidity and mortality. Data regarding pre-exposure prophylaxis (PrEP) with tixagevimab-cilgavimab in this population are scarce. We therefore evaluated COVID-19 breakthrough infections and COVID-19 related complications after PrEP in a retrospective single-center study, including 264 LTx recipients who received PrEP between June 2022 and December 2022, when Omicron BA.5 was the dominant circulating SARS-CoV-2 variant. PrEP was indicated for fully vaccinated patients with poor seroconversion (anti-S <260 BAU/mL). COVID-19 breakthrough infection after PrEP occurred in 11.0% within the first 3 months, increasing to 17.4% within 6 months. Hospitalization rate rose from 27.6% to 52.9% ( p = 0.046), while ICU admissions and COVID-19 mortality remained low, respectively occurring in 6.5% and 4.3% of patients with breakthrough infection within 6 months. COVID-19 breakthrough infection and associated hospitalization remained an important problem during the Omicron BA.5 surge in fully vaccinated LTx recipients with deficient seroconversion, despite PrEP with tixagevimab-cilgavimab. However, ICU admissions and COVID-19 mortality were low. Waning of neutralizing effects of PrEP and changing circulating SARS-CoV-2 variants may explain increases in COVID-19 infections and hospitalizations over time after PrEP, highlighting the need for novel, long-term effective PrEP strategies in these high-risk patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest., (Copyright © 2024 Demolder, Schaevers, Lagrou, De Munter, Beeckmans, Verleden, Godinas, Dupont, Van Bleyenbergh, Lorent and Vos.)

Background & Aims: Concomitant respiratory disease is a common finding in patients with hepatopulmonary syndrome (HPS). Among patients who underwent liver transplantation (LT) for HPS, we compared characteristics and outcome of patients with versus without concomitant respiratory disease., Methods: This single center retrospective observational study included patients with HPS who underwent LT between 1999 and 2020., Results: During the study period, 32 patients with HPS received a LT; nine (28%) with concomitant respiratory disease of whom one required a combined lung-liver transplantation. Patients with concomitant respiratory disease had higher PaCO2 (38 vs. 33 mm Hg, p = .031). The 30-day postoperative mortality was comparable, but the estimated cumulative probability of resolution of oxygen therapy after LT in HPS patients with versus those without concomitant respiratory disease was lower: 63% versus 91% at 12 months and 63% versus 100% at 18 months (HR 95% CI .140-.995, p = .040). In addition to the presence of concomitant respiratory disease (p = .040), history of smoking (p = .012), and high baseline 99mTcMAA shunt fraction (≥20%) (p = .050) were significantly associated with persistent need of oxygen therapy. The 5-year estimated cumulative probability of mortality in patients with concomitant respiratory disease was worse: 50% versus 23% (HR 95% CI .416-6.867, p = .463)., Conclusions: The presence of a concomitant respiratory disease did not increase the short-term postoperative mortality after LT in patients with HPS. However, it resulted in a longer need for oxygen therapy., (© 2023 The Authors. Clinical Transplantation published by John Wiley & Sons Ltd.)

Background: Extracorporeal life support (ECLS) is not routinely used at our center during sequential single-lung transplantation (LTx), but is restricted to anticipate and overcome hemodynamic and respiratory problems occurring peri-operatively. In this retrospective descriptive cohort study, we aim to describe our single-center experience with ECLS in LTx, analyzing ECLS-related complications., Methods: All transplantations with peri-operative ECLS use [2010-2020] were retrospectively analyzed. Multi-organ and heart-lung transplantation were excluded. Demographics, support type and indications are described. Complications are categorized according to the underlying nature and type. Data are presented as median [interquartile range (IQR)]. Kaplan-Meier was used for survival analysis., Results: The overall use of ECLS was 22% (156/703 patients) with a mean age of 52 years (IQR, 36-59 years). Transplant indications in ECLS cohort were interstitial lung disease (38%; n=60), chronic obstructive pulmonary disease (COPD) (19%; n=29), cystic fibrosis (17%; n=26) and others (26%; n=41). Per indication, 94% (15/16) of pulmonary arterial hypertension patients required ECLS, whereas only 8% (29/382) of COPD patients did. In 16% (25/156) of supported patients, veno-venous extracorporeal membrane oxygenation was initiated, while 77% (120/156) required veno-arterial support, and 7% (11/156) cardiopulmonary bypass. Thirty-day mortality was 6% (9/156). Sixteen percent (25/156) of patients were bridged to transplantation on ECLS and 24% (37/156) required post-operative support. Main reasons to use ECLS were intra-operative hemodynamic instability (53%; n=82), ventilation/oxygenation problems (22%; n=34) and reperfusion edema (17%; n=26). Overall incidence of patients with at least one ECLS-related complication was 67% (n=104). Most common complications were hemothorax (25%; n=39), need for continuous renal replacement therapy (19%; n=30), and thromboembolism (14%; n=22)., Conclusions: ECLS was required in 22% of LTxs, with a reported ECLS-related complication rate of 67%, of which the most common was hemothorax. Larger databases are needed to further analyze complications and develop tailored deployment strategies for ECLS-use in LTx., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-443/coif). The series “Extracorporeal Life Support in Thoracic Surgery” was commissioned by the editorial office without any funding or sponsorship. J.D.B. received PhD Fellowship in Fundamental Research from The Research Foundation Flanders (91152820N). L.G. received consulting fees from Biotest and Janssen as well as honoraria for lecture from Janssen, support for attending a meeting from MSD and Biotest and participates on advisory board of Janssen. R.V. received a research grant from Research Foundation Flanders. E.D.T. received predoctoral grant from the University Hospitals Leuven (KOOR-UZ Leuven). D.F.D. received postdoctoral grant from the University Hospitals Leuven (KOOR-UZ Leuven). G.H. received support from Eurosets for attending a meeting. J.W. received Investigator-initiated grant, speakers fee and support for attending a meeting from MSD, Pfizer and Gilead, participates on advisory board of Gilead and received study medication from MSD. A.P.N. received a grant from KU Leuven (C24/18/0730) and support for attending a meeting and speakers fee from Xvivo. L.J.C. is supported by a KU Leuven University Chair funded by Medtronic, a philantropic grant funded by Gunze, a postdoctoral grant from the University Hospitals Leuven (KOOR-UZ Leuven) and a Research foundation Flanders FWO-grant (G090922N). The authors have no other conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

Lung transplantation (LTx) is a challenging procedure. Following the process of ischemia-reperfusion injury, the transplanted pulmonary graft might become severely damaged, resulting in primary graft dysfunction. In addition, during the intraoperative window, the right ventricle (RV) is at risk of acute failure. The interaction of right ventricular function with lung injury is, however, poorly understood. We aimed to address this interaction in a translational porcine model of pulmonary ischemia-reperfusion injury. Advanced pulmonary and hemodynamic assessment was used, including right ventricular pressure-volume loop analysis. The acute model was based on clamping and unclamping of the left lung hilus, respecting the different hemodynamic phases of a clinical lung transplantation. We found that forcing entire right ventricular cardiac output through a lung suffering from ischemia-reperfusion injury increased afterload (pulmonary vascular resistance from baseline to end experiment P < 0.0001) and induced right ventricular failure (RVF) in 5/9 animals. Notably, we identified different compensation patterns in failing versus nonfailing ventricles (arterial elastance P = 0.0008; stroke volume P < 0.0001). Furthermore, increased vascular pressure and flow produced by the right ventricle resulted in higher pulmonary injury, as measured by ex vivo CT density (correlation: pressure r = 0.8; flow r = 0.85). Finally, RV ischemia as measured by troponin-T was negatively correlated with pulmonary injury ( r = -0.76); however, troponin-T values did not determine RVF in all animals. In conclusion, we demonstrate a delicate balance between development of pulmonary ischemia-reperfusion injury and right ventricular function during lung transplantation. Furthermore, we provide a physiological basis for potential benefit of extracorporeal life support technology. NEW & NOTEWORTHY In contrast to the abundant literature of mechanical pulmonary artery clamping to increase right ventricular afterload, we developed a model adding a biological factor of pulmonary ischemia-reperfusion injury. We did not only focus on the right ventricular behavior, but also on the interaction with the injured lung. We are the first to describe this interaction while addressing the hemodynamic intraoperative phases of clinical lung transplantation.

Background: Bronchiolitis obliterans syndrome (BOS) after lung transplantation is characterized by fibrotic small airway remodeling, recognizable on high-resolution computed tomography (HRCT). We studied the prognostic value of key HRCT features at BOS diagnosis after lung transplantation., Methods: The presence and severity of bronchiectasis, mucous plugging, peribronchial thickening, parenchymal anomalies, and air trapping, summarized in a total severity score, were assessed using a simplified Brody II scoring system on HRCT at BOS diagnosis, in a cohort of 106 bilateral lung transplant recipients transplanted between January 2004 and January 2016. Obtained scores were subsequently evaluated regarding post-BOS graft survival, spirometric parameters, and preceding airway infections., Results: A high total Brody II severity score at BOS diagnosis (P = 0.046) and high subscores for mucous plugging (P = 0.0018), peribronchial thickening (P = 0.0004), or parenchymal involvement (P = 0.0121) are related to worse graft survival. A high total Brody II score was associated with a shorter time to BOS onset (P = 0.0058), lower forced expiratory volume in 1 s (P = 0.0006) forced vital capacity (0.0418), more preceding airway infections (P = 0.004), specifically with Pseudomonas aeruginosa (P = 0.002), and increased airway inflammation (P = 0.032)., Conclusions: HRCT findings at BOS diagnosis after lung transplantation provide additional information regarding its underlying pathophysiology and for future prognosis of graft survival., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Lung re-transplantation (re-LTx) is the only therapeutic option for selected patients with advanced allograft dysfunction. This study aims to describe our center's experience to illustrate the feasibility and safety of off-pump re-LTx avoiding clamshell incision., Methods: We performed a retrospective analysis of 42 patients who underwent bilateral re-LTx between 2007 and 2021. Patients were classified according to their surgical approach and extracorporeal life support (ECLS)-use. Demographics, surgical technique, and short- and long-term outcomes were compared between groups. Continuous data were examined with an independent-sample t -test or non-parametric test. Pearson's chi-squared and Fisher's exact were used to analyze categorical data., Results: Twenty-six patients (61.9%) underwent re-LTx by anterior thoracotomy without ECLS. Compared to the more invasive approach (thoracotomy with ECLS and clamshell with/without ECLS, n=16, 38.1%), clamshell-avoiding off-pump re-LTx patients had a shorter operative time (471.6±111.2 vs. 704.0±273.4 min, P=0.010) and less frequent grade 3 primary graft dysfunction (PGD-3) at 72 h (7.7% vs. 37.5%, P=0.038). No significant difference was found in PGD-3 incidence within 72 h, mechanical ventilation, intensive care unit (ICU) and hospital stay, and the incidence of reoperation within 90 days between groups (P>0.05). In the long-term, the clamshell-avoiding and off-pump approach resulted in similar 1- and 5-year patient survival vs. the more invasive approach., Conclusions: Our experience shows that clamshell-avoiding off-pump re-LTx is feasible and safe in selected patients on a case-by-case evaluation., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-64/coif). The series “Extracorporeal Life Support in Thoracic Surgery” was commissioned by the editorial office without any funding or sponsorship. RV is supported as a senior clinical research fellow by the Research Foundation – Flanders (FWO) Belgium. LJC is supported by a KU Leuven University Chair funded by Medtronic and a post-doctoral grant from the University Hospitals Leuven (KOOR – UZ Leuven). LG received consulting fees from Biotest and Janssen as well as honoraria for lecture from Janssen, support for attending a meeting from MSD and Biotest and participates on advisory board of Janssen. APN received a grant from KU Leuven (C24/18/0730) and support for attending a meeting and speakers fee from Xvivo. The authors have no other conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

Objective: To describe our experience with lung transplantation (LTx) from donors ≥70 years and compare short and long-term outcomes to a propensity-matched cohort of donors <70 years., Background: Although extended-criteria donors have been widely used to enlarge the donor pool, the experience with LTx from older donors (≥70 years) remains limited., Methods: All single-center bilateral LTx between 2010 and 2020 were retrospectively analyzed. Matching (1:1) was performed for the donor (type, sex, smoking history, x-ray abnormalities, partial pressure of oxygen/fraction of inspired oxygen ratio, and time on ventilator) and recipient characteristics (age, sex, LTx indication, perioperative extracorporeal life support, and cytomegalovirus mismatch). Primary graft dysfunction grade-3, 5-year patient, and chronic lung allograft dysfunction-free survival were analyzed., Results: Out of 647 bilateral LTx, 69 were performed from donors ≥70 years. The mean age in the older donor cohort was 74 years (range: 70-84 years) versus 49 years (range: 12-69 years) in the matched younger group. No significant differences were observed in the length of ventilatory support, intensive care unit, or hospital stay. Primary graft dysfunction-3 was 26% in the older group versus 29% in younger donor recipients ( P = 0.85). Reintervention rate was comparable (29% vs 16%; P = 0.10). Follow-up bronchoscopy revealed no difference in bronchial anastomotic complications ( P = 1.00). Five-year patient and chronic lung allograft dysfunction-free survivals were 73.6% versus 73.1% ( P = 0.72) and 51.5% versus 59.2% ( P = 0.41), respectively., Conclusions: LTx from selected donors ≥70 years is feasible and safe, yielding comparable short and long-term outcomes in a propensity-matched analysis with younger donors (<70 years)., Competing Interests: R.V. is supported as a senior clinical research fellow by the Research Foundation Flanders (FWO) Belgium. G.M.V. and D.V.R. are supported by the Broere Charitable Foundation. L.J.C. is supported by a KU Leuven University Chair funded by Medtronic, a post-doctoral grant from the University Hospitals Leuven (KOOR—UZ Leuven) and a research project from the Research Foundation Flanders (FWO) Belgium (G090922N). The remaining authors report no conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease-19 (COVID-19) which can lead to acute respiratory distress syndrome (ARDS) and evolve to pulmonary fibrosis. Computed tomography (CT) is used to study disease progression and describe radiological patterns in COVID-19 patients. This study aimed to assess disease progression regarding lung volume and density over time on follow-up in vivo chest CT and give a unique look at parenchymal and morphological airway changes in "end-stage" COVID-19 lungs using ex vivo microCT., Methods: Volumes and densities of the lung/lobes of three COVID-19 patients were assessed using follow-up in vivo CT and ex vivo whole lung microCT scans. Airways were quantified by airway segmentations on whole lung microCT and small-partition microCT. As controls, three discarded healthy donor lungs were used. Histology was performed in differently affected regions in the COVID-19 lungs., Results: In vivo , COVID-19 lung volumes decreased while density increased over time, mainly in lower lobes as previously shown. Ex vivo COVID-19 lung volumes decreased by 60% and all lobes were smaller compared to controls. Airways were more visible on ex vivo microCT in COVID-19, probably due to fibrosis and increased airway diameter. In addition, small-partition microCT showed more deformation of (small) airway morphology and fibrotic organization in severely affected regions with heterogeneous distributions within the same lung which was confirmed by histology., Conclusions: COVID-19-ARDS and subsequent pulmonary fibrosis alters lung architecture and airway morphology which is described using in vivo CT, ex vivo microCT, and histology., Competing Interests: Conflicts of Interest: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-22-1488/coif). BMV, GGR, WAW, and WJ report funding from KU Leuven (No. C16/19/005). WAW reports funding from Roche, Boehringer Ingelheim, and Galapagos. GMV and DEVR report funding from the Broere Charitable Foundation. LJC reports funding from Medtronic. RV reports funding from UZ Leuven (No. STG15/023). RV, VG, JK, A Vanstapel, TG, MV, and IG report funding from the Research Foundation-Flanders (FWO) (No. 12G8715N to RV, No. 11L9822N to VG, No. 1198920N to JK, No. 1102020N to A Vanstapel, No. 1S73921N to TG, No. 1SE4322N to MV, and No. 11N3922N to IG). MNB reports funding from the Ghent University Special Research Fund for the UGCT Centre of Expertise BOF.EXP.2017.0007. The other authors have no conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

Background Interstitial lung abnormalities (ILAs) reflect imaging features on lung CT scans that are compatible with (early) interstitial lung disease. Despite accumulating evidence regarding the incidence, risk factors, and prognosis of ILAs, the histopathologic correlates of ILAs remain elusive. Purpose To determine the correlation between radiologic and histopathologic findings in CT-defined ILAs in human lung explants. Materials and Methods Explanted lungs or lobes from participants with radiologically documented ILAs were prospectively collected from 2010 to 2021. These specimens were air-inflated, frozen, and scanned with CT and micro-CT (spatial resolution of 0.7 mm and 90 μm, respectively). Subsequently, the lungs were cut and sampled with core biopsies. At least five samples per lung underwent micro-CT and subsequent histopathologic assessment with semiquantitative remodeling scorings. Based on area-specific radiologic scoring, the association between radiologic and histopathologic findings was assessed. Results Eight lung explants from six donors (median age at explantation, 71 years [range, 60-83 years]; four men) were included (unused donor lungs, n = 4; pre-emptive lobectomy for oncologic indications, n = 2). Ex vivo CT demonstrated ground-glass opacification, reticulation, and bronchiectasis. Micro-CT and histopathologic examination demonstrated that lung abnormalities were frequently paraseptal and associated with fibrosis and lymphocytic inflammation. The histopathologic results showed varying degrees of fibrosis in areas that appeared normal on CT scans. Regions of reticulation on CT scans generally had greater fibrosis at histopathologic analysis. Vasculopathy and bronchiectasis were also often present at histopathologic examination of lungs with ILAs. Fully developed fibroblastic foci were rarely observed. Conclusion This study demonstrated direct histologic correlates of CT-defined interstitial lung abnormalities. © RSNA, 2022 Supplemental material is available for this article. See also the editorial by Jeudy in this issue.

COPD and α-1 antitrypsin deficiency emphysema remain one of the major indications for lung transplantation. If all other treatment possibilities are exhausted or not possible (including rehabilitation, oxygen therapy, noninvasive ventilation, lung volume reduction), patients may qualify for lung transplantation. Strict selection criteria are implemented with a lot of relative and absolute contraindications. Because of an ongoing donor shortage, only a minority of endstage COPD patients will finally get transplanted. The procedure may involve a single or a double lung transplantation, dependent on the experience of the centre, the waiting list, the availability of donor lungs and the patient's risk-benefit ratio. In general, the life expectancy as well as the health-related quality of life after lung transplantation for COPD are usually increased, and may be somewhat better after double compared with single lung transplantation. Several specific complications can be encountered, such as the development of solid organ cancer and chronic lung allograft dysfunction, which develops in up to 50% of patients within 5 years of their transplant and has a major impact on long-term survival, because of the current inefficient treatment modalities., Competing Interests: Conflict of interest: the authors have nothing to disclose., (Copyright ©The authors 2023.)

Fungal exposure and sensitization negatively affect outcomes in various respiratory diseases, however, the effect of fungal sensitization in lung transplant (LTx) recipients is still unknown. We performed a retrospective cohort study of prospectively collected data on circulating fungal specific IgG/IgE antibodies, and their correlation with fungal isolation, chronic lung allograft dysfunction (CLAD) and overall survival after LTx. 311 patients transplanted between 2014 and 2019 were included. Patients with elevated Aspergillus fumigatus or Aspergillus flavus IgG (10%) had more mold and Aspergillus species isolation ( p = 0.0068 and p = 0.0047). Aspergillus fumigatus IgG was specifically associated with Aspergillus fumigatus isolation in the previous or consecutive year (AUC 0.60, p = 0.004 and AUC 0.63, p = 0.022, respectively). Elevated Aspergillus fumigatus or Aspergillus flavus IgG was associated with CLAD ( p = 0.0355), but not with death. Aspergillus fumigatus , Aspergillus flavus or Aspergillus niger IgE was elevated in 19.3% of patients, but not associated with fungal isolation, CLAD or death. Mold isolation and Aspergillus species isolation from respiratory cultures were associated with CLAD occurrence ( p = 0.0011 and p = 0.0005, respectively), and Aspergillus species isolation was also associated with impaired survival ( p = 0.0424). Fungus-specific IgG could be useful in long-term follow-up post-LTx, as a non-invasive marker for fungal exposure, and thus a diagnostic tool for identifying patients at risk for fungal-related complications and CLAD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Beeckmans, Van Roy, Kaes, Sacreas, Geudens, Vermaut, Willems, Jin, Bos, Vanstapel, Van Slambrouck, Orlitova, Vanaudenaerde, Ceulemans, Van Raemdonck, Neyrinck, Godinas, Dupont, Verleden and Vos.)