Bart Luijk

Systemic eosinophil response induced by respiratory syncytial virus.

Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract disease (LRTD) in infants. Eosinophils have been suggested to play a role in the disease pathogenesis of LRTD. Inflammation can induce functional and morphological alterations of peripheral blood granulocytes. In patients with RSV LRTD, we aimed to investigate the eosinophil activation status by analysing surface markers. In vitro stimulation of eosinophils with cytokines leads to up‐regulation of CD11b and priming markers recognized by the recently developed priming markers A17 and A27, whereas interleukin (IL)‐5Rα is being down‐regulated. In 51 patients and 10 controls we examined the expression of these surface markers on eosinophils in moderate to severe RSV‐induced LRTD patients at the time of admission and 6 weeks later during the convalescence phase. RSV‐patients were characterized by a higher eosinophil CD11b expression compared to controls. Although basal A17 and A27 expression was not increased, we observed a significantly higher expression of these priming epitopes on N‐formyl‐methionyl‐leucyl‐phenylalanine (fMLP)‐stimulated cells of RSV patients compared with cells of controls, indicative of prior in vivo priming. Furthermore, IL‐5Rα expression was down‐regulated on peripheral blood eosinophils of these patients. Follow‐up blood samples showed normalization of all markers but CD11b, which was persistently increased. Utilizing cellular markers, we observed that peripheral blood eosinophils from infants with RSV LRTD are in a more activated state compared to eosinophils of controls, which normalizes only partially during convalescence.

An association of particulate air pollution and traffic exposure with mortality after lung transplantation in Europe

Air pollution from road traffic is a serious health risk, especially for susceptible individuals. Single-centre studies showed an association with chronic lung allograft dysfunction (CLAD) and survival after lung transplantation, but there are no large studies. 13 lung transplant centres in 10 European countries created a cohort of 5707 patients. For each patient, we quantified residential particulate matter with aerodynamic diameter ≤10 µm (PM10) by land use regression models, and the traffic exposure by quantifying total road length within buffer zones around the home addresses of patients and distance to a major road or freeway. After correction for macrolide use, we found associations between air pollution variables and CLAD/mortality. Given the important interaction with macrolides, we stratified according to macrolide use. No associations were observed in 2151 patients taking macrolides. However, in 3556 patients not taking macrolides, mortality was associated with PM10 (hazard ratio 1.081, 95% CI 1.000–1.167); similarly, CLAD and mortality were associated with road lengths in buffers of 200–1000 and 100–500 m, respectively (hazard ratio 1.085– 1.130). Sensitivity analyses for various possible confounders confirmed the robustness of these associations. Long-term residential air pollution and traffic exposure were associated with CLAD and survival after lung transplantation, but only in patients not taking macrolides. Long-term residential air pollution/traffic exposure associated with CLAD and survival after lung transplantation http://ow.ly/Izxj304uA5k

Effective Prolonged Therapy with Voriconazole in a Lung Transplant Recipient with Spondylodiscitis Induced by Scedosporium apiospermum

Scedosporium/Pseudallescheria species are frequently seen in cystic fibrosis patients. However, disseminated forms after lung transplantation in these patients are rarely seen, but often with poor outcome. In this case report we describe a lung transplant recipient with cystic fibrosis who developed a spondylodiscitis that was caused by Scedosporium apiospermum. The patient was treated with anti-fungal treatment by voriconazole for over three years with a clinical good response and without the need for surgical intervention. To our opinion this is the first anti-fungal treated case of invasive disease caused by Scedosporium/Pseudallescheria in a cystic fibrosis (CF) patient who underwent lung transplantation that survived.

Soluble CD59 is a Novel Biomarker for the Prediction of Obstructive Chronic Lung Allograft Dysfunction after Lung Transplantation

CD59 is a complement regulatory protein that inhibits membrane attack complex formation. A soluble form of CD59 (sCD59) is present in various body fluids and is associated with cellular damage after acute myocardial infarction. Lung transplantation (LTx) is the final treatment for end-stage lung diseases, however overall survival is hampered by chronic lung allograft dysfunction development, which presents itself obstructively as the bronchiolitis obliterans syndrome (BOS). We hypothesized that, due to cellular damage and activation during chronic inflammation, sCD59 serum levels can be used as biomarker preceding BOS development. We analyzed sCD59 serum concentrations in 90 LTx patients, of whom 20 developed BOS. We observed that BOS patients exhibited higher sCD59 serum concentrations at the time of diagnosis compared to clinically matched non-BOS patients (p = 0.018). Furthermore, sCD59 titers were elevated at 6 months post-LTx (p = 0.0020), when patients had no BOS-related symptoms. Survival-analysis showed that LTx patients with sCD59 titers ≥400 pg/ml 6 months post-LTx have a significant (p < 0.0001) lower chance of BOS-free survival than patients with titers ≤400 pg/ml, 32% vs. 80% respectively, which was confirmed by multivariate analysis (hazard ratio 6.2, p < 0.0001). We propose that circulating sCD59 levels constitute a novel biomarker to identify patients at risk for BOS following LTx.

Emphysema Is Common in Lungs of Cystic Fibrosis Lung Transplantation Patients: A Histopathological and Computed Tomography Study.

Background Lung disease in cystic fibrosis (CF) involves excessive inflammation, repetitive infections and development of bronchiectasis. Recently, literature on emphysema in CF has emerged, which might become an increasingly important disease component due to the increased life expectancy. The purpose of this study was to assess the presence and extent of emphysema in endstage CF lungs. Methods In explanted lungs of 20 CF patients emphysema was semi-quantitatively assessed on histology specimens. Also, emphysema was automatically quantified on pre-transplantation computed tomography (CT) using the percentage of voxels below -950 Houndfield Units and was visually scored on CT. The relation between emphysema extent, pre-transplantation lung function and age was determined. Results All CF patients showed emphysema on histological examination: 3/20 (15%) showed mild, 15/20 (75%) moderate and 2/20 (10%) severe emphysema, defined as 0–20% emphysema, 20–50% emphysema and >50% emphysema in residual lung tissue, respectively. Visually upper lobe bullous emphysema was identified in 13/20 and more diffuse non-bullous emphysema in 18/20. Histology showed a significant correlation to quantified CT emphysema (p = 0.03) and visual emphysema score (p = 0.001). CT and visual emphysema extent were positively correlated with age (p = 0.045 and p = 0.04, respectively). Conclusions In conclusion, this study both pathologically and radiologically confirms that emphysema is common in end-stage CF lungs, and is age related. Emphysema might become an increasingly important disease component in the aging CF population.

A Multicenter Study on Long-Term Outcomes After Lung Transplantation Comparing Donation After Circulatory Death and Donation After Brain Death

The implementation of donation after circulatory death category 3 (DCD3) was one of the attempts to reduce the gap between supply and demand of donor lungs. In the Netherlands, the total number of potential lung donors was greatly increased by the availability of DCD3 lungs in addition to the initial standard use of donation after brain death (DBD) lungs. From the three lung transplant centers in the Netherlands, 130 DCD3 recipients were one‐to‐one nearest neighbor propensity score matched with 130 DBD recipients. The primary end points were primary graft dysfunction (PGD), posttransplant lung function, freedom from chronic lung allograft dysfunction (CLAD), and overall survival. PGD did not differ between the groups. Posttransplant lung function was comparable after bilateral lung transplantation, but seemed worse after DCD3 single lung transplantation. The incidence of CLAD (p = 0.17) nor the freedom from CLAD (p = 0.36) nor the overall survival (p = 0.40) were significantly different between both groups. The presented multicenter results are derived from a national context where one third of the lung transplantations are performed with DCD3 lungs. We conclude that the long‐term outcome after lung transplantation with DCD3 donors is similar to that of DBD donors and that DCD3 donation can substantially enlarge the donor pool.

Use of an anti-CD200 antibody for prolonging the survival of allografts: a patent evaluation of WO2012106634A1

Background: Allograft rejection continues to be the biggest hurdle in successful organ transplantation. This application (WO2012106634A1) claims the use of blocking CD200 antibody to achieve long-term survival of allografts. CD200 is the ligand for the inhibitory CD200 receptor (CD200R). Methods: In mouse allograft transplantation models, a blocking CD200 antibody was used to improve renal and cardiac graft survival. Similarly, in humans a blocking CD200 antibody would be administered to the organ recipient in combination with currently used immunosuppressive drugs or even as a monotherapy. Results: In the presented animal experiments, anti-CD200 antibody application to the allograft recipient decreases SHIP expression in splenocytes. This is accompanied by a significant increase in renal or cardiac graft survival. Furthermore, anti-CD200 antibody has an immunosuppressive effect manifested by an increased production of T regulatory and myeloid-derived suppressor cells (MDSC) and a decrease in B cells and activated T cells. Conclusion: In vivo administration of anti-CD200 antibody has a remarkable positive effect on allograft survival. However, since this finding contradicts all previous effects of in vivo CD200 manipulation described in transplantation settings, future development of this invention is highly uncertain.

Pulmonary Nodule Volumetry at Different Low Computed Tomography Radiation Dose Levels With Hybrid and Model-Based Iterative Reconstruction: A Within Patient Analysis.

Objective The aim of the study was to determine the effects of dose reduction and iterative reconstruction (IR) on pulmonary nodule volumetry. Methods In this prospective study, 25 patients scheduled for follow-up of pulmonary nodules were included. Computed tomography acquisitions were acquired at 4 dose levels with a median of 2.1, 1.2, 0.8, and 0.6 mSv. Data were reconstructed with filtered back projection (FBP), hybrid IR, and model-based IR. Volumetry was performed using semiautomatic software. Results At the highest dose level, more than 91% (34/37) of the nodules could be segmented, and at the lowest dose level, this was more than 83%. Thirty-three nodules were included for further analysis. Filtered back projection and hybrid IR did not lead to significant differences, whereas model-based IR resulted in lower volume measurements with a maximum difference of −11% compared with FBP at routine dose. Conclusions Pulmonary nodule volumetry can be accurately performed at a submillisievert dose with both FBP and hybrid IR.

Successful treatment of bronchial stenosis after lung transplantation

Treatment of stenotic anastomosis after lung transplantation can be challenging. In this case report, we present a case in which 3D computed tomography reconstructions guided the clinical decision towards operative bronchoplasty after which our patient was treated successfully.

Images in COPD : Combined Pulmonary Emphysema and Fibrosis with Pulmonary Hypertension

Abbreviations: chronic obstructive pulmonary disease, COPD; forced expiratory volume in 1 second, FEV1; forced vital capacity, FVC; computed tomography, CT; 18-fluorodeoxyglucose, 18-FDG; positron emission tomography, PET; usual interstitial pneumonia, UIP; combined pulmonary emphysema and fibrosis, CPFE; non-specific interstitial pneumonia, NSIP; respiratory bronchiolitis-associated interstitial lung disease, RB-ILD; desquamative interstitial pneumonia, DIP; idiopathic pulmonary fibrosis, IPF Citation: Mohamed Hoesein FA, Voortman M, Kwakkel-van Erp JM, Luijk B, de Jong PA. Images in COPD: Combined pulmonary emphysema and fibrosis with pulmonary hypertension. Chronic Obstr Pulm Dis (Miami). 2017; 4(1):76-80. doi: http://dx.doi.org/10.15326/ jcopdf.4.1.2016.0171 Images in COPD