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Randomized placebo-controlled trials demonstrated the efficacy of antifibrotic treatment in non-IPF progressive fibrosing ILD (fILD). Currently, there is no consensus on how progression should be defined and clinical data of non-IPF fILD patients in a real-world setting are scarce. Non-IPF fILD patients presenting at the University Hospitals Leuven between 2012 and 2016 were included. Different definitions of progression according to the selection criteria of the INBUILD, RELIEF and the uILD study were retrospectively evaluated at every hospital visit. Univariate and multivariate analyses were performed to identify predictors of progression and mortality. The study cohort comprised 120 patients; 68.3%, 54.2% and 65.8% had progressive disease based on the INBUILD, RELIEF and uILD study, respectively. A large overlap of progressive fILD patients according to the different clinical trials was observed. Median transplant-free survival time of progressive fILD patients was 3.9, 3.9, 3.8 years and the median time-to-progression after diagnosis was 2.0, 3.1 and 2.3 years according to the INBUILD, RELIEF and uILD study, respectively. We identified several predictors of mortality, but only an underlying diagnosis of HP and uILD was independently associated with progression. Our data show a high prevalence of progressive fibrosis among non-IPF fILD patients and a discrepancy between predictors of mortality and progression. Mortality rate in fILD is high and the identification of progressive disease is only made late during the disease course. Moreover, future treatment decisions will be based upon disease behavior. Therefore, more predictors of progressive disease are needed to guide treatment decisions in the future., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Physiological lung ageing is associated with a gradual decline in dynamic lung volumes and a progressive increase in residual volume due to diminished elastic recoil of the lung, loss of alveolar tissue, and lower chest wall compliance. However, the effects of ageing on the small airways (ie, airways <2·0 mm in diameter) remain largely unknown. By using a combination of ex-vivo conventional CT (resolution 1 mm), whole lung micro-CT (resolution 150 μm), and micro-CT of extracted cores (resolution 10 μm), we aimed to provide a multiresolution assessment of the small airways in lung ageing in a large cohort of never smokers., Methods: For this cross-sectional study, we included donor lungs collected from 32 deceased never-smoking donors (age range 16-83 years). Ex-vivo CT and whole lung high-resolution CT (micro-CT) were used to determine total airway numbers, stratified by airway diameter. Micro-CT was used to assess the number, length, and diameter of terminal bronchioles (ie, the last generation of conducting airways); mean linear intercept; and surface density in four lung tissue cores from each lung, extracted using a uniform sampling approach. Regression β coefficients are calculated using linear regression and polynomial models., Findings: Ex-vivo CT analysis showed an age-dependent decrease in the number of airways of diameter 2·0 mm to less than 2·5 mm (β coefficient per decade -0·119, 95% CI -0·193 to -0·045; R 2 =0·29) and especially in airways smaller than 2·0 mm in diameter (-0·158, -0·233 to -0·084; R 2 =0·47), between 30 and 80 years of age, but not of the larger (≥2·5 mm) diameter airways (-0·00781, -0·04409 to 0·02848; R 2 =0·0007). In micro-CT analysis of small airways, the total number of terminal bronchioles per lung increased until the age of 30 years, after which an almost linear decline in the number of terminal bronchioles was observed (β coefficient per decade -2035, 95% CI -2818 to -1252; R 2 =0·55), accompanied by a non-significant increase in alveolar airspace size (6·44, -0·57 to 13·45, R 2 =0·10). Moreover, this decrease in terminal bronchioles was associated with the age-related decline of pulmonary function predicted by healthy reference values., Interpretation: Loss of terminal bronchioles is an important structural component of age-related decline in pulmonary function of healthy, non-smoking individuals., Funding: Research Foundation-Flanders, KU Leuven, Parker B Francis Foundation, UGent, Canadian Institutes for Health., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Several case reports and small case series have been published on coronavirus disease 2019 infection after solid organ transplantation; however, thus far there are limited data on coronavirus disease 2019 infections in lung transplant patients. In the present single-center case series we discuss 10 lung transplant patients with a documented severe acute respiratory syndrome coronavirus 2 infection, diagnosed with nasopharyngeal swab in 8 and bronchoalveolar lavage in 2. Eight of 10 patients needed hospital admission, of whom 1 was in the intensive care unit. He died after 2 weeks from multiple organ failure. The remaining nine patients recovered. Cell cycle inhibitors were withheld in all patients, whereas the calcineurin inhibitor and corticosteroids were continued at the same dose, with an acceptable outcome., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Long-term survival after lung transplantation (LTx) is hampered by chronic lung allograft dysfunction (CLAD). Our study evaluated the prevalence and prognostic importance of obstructive and restrictive CLAD phenotypes, with or without an identifiable underlying cause, to validate the recently proposed classification system for CLAD., Methods: Data for patients who underwent LTx between 2004 and 2015 with a minimal survival of 180 days post-LTx were retrospectively collected. Double LTx patients with CLAD (defined as a persistent forced expiratory volume in 1 second decline of ≥ 20% compared with baseline) were subsequently classified according to obstructive (forced expiratory volume in 1 second /forced vital capacity [FVC] < 70%, total lung capacity > 90%, and FVC > 80%) or restrictive (total lung capacity ≤ 90% or FVC ≤ 80%) pulmonary function and to the presence of an unknown (bronchiolitis obliterans syndrome [BOS]/restrictive allograft syndrome [RAS]) or known (non-BOS/non-RAS) underlying cause., Results: After a median of 3.2 years, CLAD developed in 39% of double LTx patients (n = 219), of which 20% (n = 43) had an identifiable cause. Survival was worse in patients with restrictive CLAD (26%) compared with obstructive CLAD (64%; p < 0.0001). Non-BOS patients suffered from inferior survival compared with BOS patients (p = 0.0016), whereas there was no significant difference in survival between RAS and non-RAS (p = 0.17). Patients who evolved from an obstructive (BOS) to a restrictive (RAS) phenotype (10%) experienced better survival than RAS patients and a worse outcome compared with BOS patients (p < 0.0001)., Conclusions: Given the differences in outcome, accurate diagnosis of CLAD phenotypes is important, because this helps to inform patients about their prognosis, to reveal underlying pathogenesis, to identify homogenous patient populations for clinical trials, and to guide future therapeutic approaches., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objectives: Anastomotic airway complications give rise to morbidity and mortality after lung transplantation. Knowledge about contributing factors helps in adopting diagnostic and therapeutic strategies. Systematic endoscopic description and classification play a key role., Methods: A retrospective analysis of all bronchial anastomoses between 2005 and 2013 was performed to assess anastomotic complications and associated variables. Treatment modalities and outcome of endobronchial and surgical interventions are reported., Results: The prevalence of anastomotic airway complications in our cohort was 11%. Contributive factors were all recipient-dependent: microbial infection during the first postoperative trimester [odds ratio (OR) 3.4 (2.1-5.5); P < 0.0001], recipient age [OR 3.0 (1.3-7.1); P = 0.01], right-sided anastomosis [OR 2.5 (1.4-3.3); P = 0.001], the presence of microbiological colonization prior to transplantation [OR 1.8 (1.1-3.1); P = 0.02] and [Formula: see text] during the first 72 h after transplantation [OR 1.6 (1.1-2.7); P = 0.04]. Seventy-five percent of cases were managed conservatively, of which 93% evolved clinically favourable during follow-up. Our data support the use of the proposed MDS classification and show that MDS class M3b, D2x, Sxe or higher are associated with an increased intervention rate., Conclusion: Anastomotic airway complications remain an important issue after lung transplantation. The identified risk factors may play a role in the pathophysiology of anastomotic complications. The indication for endobronchial intervention should be carefully considered based on endoscopic classification since most cases resolve or stabilize over time., (© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Acute cellular rejection (AR) after lung transplantation may result in significant morbidity and mortality both on the short and long term. Transbronchial biopsy through flexible bronchoscopy is highly sensitive for the diagnosis of AR, but reproducibility of histopathologic interpretation is less convincing. Probe-based confocal laser endomicroscopy (pCLE), a novel imaging tool in the field of respiratory medicine, enables real-time imaging of the pulmonary acini., Methods: We performed 105 bronchoscopies in lung transplant recipients, combining both transbronchial biopsies and pCLE. We conducted an observational survey for pCLE findings in AR., Results: Calculations for cellularity showed a median cell count (ACA) of 50 (IQR 18 to 120) cells per microscopic field for AR and 10 (IQR 0 to 15) cells per microscopic field for matched controls (p = 0.0004). Cellular autofluorescence in the AR group was 1,163 (± 157) units and 489 (± 101) units for the matched controls (p = 0.0009). Autofluorescent cells were present in 73% (± 10) of the recorded frames in the AR group and in only 42% (± 9) of the recorded frames in the control group (p = 0.03). Contingency analysis for the presence/absence of ACA in the AR group versus the control group showed a sensitivity of 0.93 and a specificity of 0.46 (relative risk = 6.5 [95% CI 0.94 to 44.8], p = 0.01). The consecutive application of 3 pCLE criteria resulted in a sensitivity of 0.93 and a specificity of 0.83 for detection of AR., Conclusion: Our observational survey suggests the existence of specific pCLE characteristics in patients with AR. Further efforts are necessary to validate these findings prospectively., (Copyright © 2014 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Approximately half of all patients who underwent a lung transplantation suffer from bronchiolitis obliterans syndrome (BOS), the clinical correlate of chronic rejection, within 5 years after transplantation. This prevalence is much higher than for other solid organ transplantations, possibly due to the lung's direct contact with the environment. The authors assessed the association between proximity of the home to major roads and BOS and mortality in a cohort of patients after lung transplantation., Methods: The authors calculated hazard ratios for BOS and mortality in relation to proximity of the home to major roads, adjusting for relevant covariables, in 288 patients after lung transplantation at the Leuven University Hospital between 1997 and 2009 and with follow-up until August 2009. Inflammatory parameters in plasma and bronchoalveolar lavage were assessed in 207 patients., Results: During follow-up, 117 (41%) patients developed BOS and 61 (21%) died. Patients who lived within 171 m of a major road (lowest tertile) were 2.06 (95% CI 1.39 to 3.05) times more likely to develop BOS and 2.20 (1.25 to 3.86) times more likely to die than patients living farther away. The adjusted hazard ratios of BOS and mortality were 0.57 and 0.72 for each 10-fold increase in distance from major roads. Proximity to a major road was inversely associated with plasma C-reactive protein levels, neutrophil percentage and interleukin-6 concentration in bronchoalveolar lavage., Conclusion: Traffic-related air pollution appears to constitute a serious risk of BOS and mortality after lung transplantation.

Lung transplantation is a life-saving treatment option in carefully selected patients with end-stage lung disease. Life expectancy after this form of treatment has progressively increased with a current survival of 90% after 1 year, 70% after 5 years, and 50% after 10 years in experienced centers. Apart from a survival benefit, this treatment aims to improve the quality of life. Bilateral lung transplantation is the type of operation that is performed most frequently because of superior survival results, especially when chronic rejection develops. Single lung transplantation is now reserved for older patients with pulmonary fibrosis. Heart-lung transplantation is rarely done, only in patients with Eisenmenger's syndrome or complex congenital heart disease. Belgium is one of the world leaders in terms of number of deceased organ donors with a lung recovery rate of about 35%. With a total of 8.3 lung transplants per million population, Belgium is currently the number 1 in the world. The procedure nowadays is performed in 4 University Hospitals (UA-KUL-ULB-UCL) in the country. Between 1983 and 2009, nearly 1000 proedures were performed. The most common indication was emphysema, followed by cystic fibrosis, pulmonary fibrosis, pulmonary arterial hypertension, and Eisenmenger's syndrome. Further application of this treatment option is hampered by several problems such as donor organ shortage, primary graft dysfunction, chronic rejection presenting as bronchiolitis obliterans syndrome, and side effect of chronic immunosuppression. In the Laboratory for Experimental Thoracic Surgery and the Laboratory for Pneumology at the Katholieke Universiteit Leuven, intensive research is done by our group looking for new methods to increase the lung donor pool and to prevent and to treat chronic rejection.

During the past decade, the outcome after lung transplantation has improved due to a substantial reduction in the immediate postoperative and perioperative mortality that resulted from better surgical techniques, anaesthetic and perioperative management and more intense antibiotic, antifungal and antiviral prophylaxis. However, according to the International Society for Heart and Lung transplantation (ISHLT) Registry, the long-term survival has not improved much in recent years and mortality is most often due to the development of chronic allograft dysfunction, infections, posttransplant lymphoproliferative disorders and other tumours. Although treatment options have improved for most of these issues, therapy for chronic allograft dysfunction has been very disappointing. Recent observations using azithromycin and antireflux surgery may shed more light on the pathophysiology and perhaps the outcome of this debilitating condition. We hope that better prevention and treatment of chronic allograft dysfunction will result in better long-term survival after lung transplantation.

Emphysema is a disabling disease, for which there is no curative therapy available today. Lung transplantation offers a valuable option for a very selected number of patients, however, due to the enormous organ shortage, only few patients can be offered such a therapy. Recently there has been important resurgence of interest in lung volume reduction surgery and as a consequence, we have embarked in such a program since may 1997. We have now performed unilateral lung volume reduction surgery in 29 emphysema patients (25 on the right and 4 on the left side). Twenty-four patients were already discharged home. There has been no perioperative mortality. The mean hospital stay was 19.8 +/- 11.4 days (range, 8-47 d). Twenty patients of whom we already have follow-up data during 6 months (m) form the further basis of this report. Six weeks after the procedure the FEV1 increased from 0.82 +/- 0.28 L (28 +/- 8%) to 1.05 +/- 0.39 L, a mean increase of 28%. There was a further increase of the FEV1 to a maximum of 1.06 +/- 0.42 L at 6 m, a mean maximum increase of 29% (p = 0.0046, ANOVA). Similarly, the FVC increased from 2.80 +/- 1.10 L to 3.15 +/- 1.00 L, a mean increase of 12.5%. A further increase was also obtained at 6 m and was 19.6% (3.35 +/- 1.05 L, p = 0.014, ANOVA). The maximum decrease in RV was obtained at 3 m (from 5.91 +/- 1.37 L to 4.37 +/- 0.85 L (p = 0.0001, ANOVA), a mean decrease of 26%. The maximum TLC decrease was demonstrated at 3 m (from 8.71 +/- 1.71 L to 7.60 +/- 1.56 L (p = 0.002, ANOVA), a mean decrease of 12.8%. Afterwards there was again a gradual raise of the TLC. The six minute walking distance increased from 231 +/- 31 m to 272 +/- 34 m (p = NS) after pulmonary rehabilitation and to 416 +/- 77 m at 3 m and 415 +/- 18 m at 6 m (p = 0.0002, ANOVA) after the operation. The quality of life (measured with a standardized questionnaire, the Nottingham Health Profile) improved significantly in several domains (e.g. mobility, pain, energy, emotions and social) at 3 m postoperatively. There was one late death (at 6 m) due to an unknown cause. The actuarial survival rate was therefore 100% at 3 m and 95% at 12 m. In conclusion, unilateral thoracoscopic lung volume reduction surgery is a new and safe treatment modality for patients suffering from severe end-stage emphysema. The objective and subjective improvement is marked and the mortality is very low. Rigid selection criteria are, however, necessary to be able to guarantee an optimal result.