Lobe-wise assessment of lung volume and density distribution in lung transplant patients and value for early detection of bronchiolitis obliterans syndrome.

PURPOSE: To evaluate quantitative computed tomography (CT) measurements of the lung parenchyma in lung transplant (LTx) patients for early detection of the bronchiolitis obliterans syndrome (BOS). MATERIALS AND METHODS: 359 CT scans of 122 lung transplant patients were evaluated. Measurements of lung volume and density were performed for the whole lung and separately for each lobe. For longitudinal analysis the difference between the baseline at 6 months after LTx and follow-up examinations was calculated. Patients with and without BOS (matched 1:2) were compared at two different time points, the last examination before the BOS onset and the first examination within one year after BOS onset. RESULTS: 30 patients developed BOS during the follow-up period. Longitudinal changes in the lung volume and lung density measured on CT differed significantly between those patients with and without early BOS, in particular the difference of the inspiratory and expiratory lung volume (p < 0.001), the ratio of the expiratory and inspiratory lung volume (p < 0.001-p = 0.001) and MLD (p < 0.001-p = 0.001), the volume on expiration (p < 0.001-p = 0.007), the MLD on expiration (p < 0.001-p = 0.007), and the percentiles on expiration (p < 0.001-p = 0.002) with an increase of lung volume and a decrease of lung density. Changes were pronounced in the lower lobes. Before BOS onset, patients with and without future development of BOS showed no significant differences. CONCLUSION: Longitudinal changes of lung volume and lung density measured on CT start markedly at BOS onset with increased lung volume and decreased lung density indicating increased inflation levels. Even though this method may help to diagnose BOS at onset it is not useful as a predictor for BOS before disease onset.

Breath volatile organic compounds of lung transplant recipients with and without chronic lung allograft dysfunction.

INTRODUCTION: Chronic lung allograft dysfunction with its clinical correlative of bronchiolitis obliterans syndrome (BOS) remains the major limiting factor for long-term graft survival. Currently there are no established methods for the early diagnosis or prediction of BOS. To assess the feasibility of breath collection as a non-invasive tool and the potential of breath volatile organic compounds (VOC) for the early detection of BOS, we compared the breath VOC composition between transplant patients without and different stages of BOS. METHODS: 75 outpatients (25 BOS stage 0, 25 BOS stage 1 + 2, 25 BOS stage 3) after bilateral lung transplantation were included. Exclusion criteria were active smoking, oxygen therapy and acute infection. Patients inhaled room air through a VOC and sterile filter and exhaled into an aluminum reservoir tube. Breath was loaded directly onto Tenax® TA adsorption tubes and was subsequently analyzed by gas-chromatography/mass-spectrometry. RESULTS: The three groups were age and gender matched, but differed with respect to time since transplantation, the spectrum of underlying disease, and treatment regimes. Relative to patients without BOS, BOS stage 3 patients showed a larger number of different VOCs, and more pronounced differences in the level of VOCs as compared to BOS stage 1 + 2 patients. Logistic regression analysis found no differences between controls and BOS 1 + 2, but four VOCs (heptane, isopropyl-myristate, ethyl-acetate, ionone) with a significant contribution to the discrimination between controls and BOS stage 3. A combination of these four VOCs separated these groups with an area under the curve of 0.87. CONCLUSION: Breath sample collection using our reservoir sampler in the clinical environment was feasible. Our results suggest that breath VOCs can discriminate severe BOS. However, convincing evidence for VOCs with a potential to detect early onset BOS is lacking.

Nasal Nitric Oxide Measurement and a Modified PICADAR Score for the Screening of Primary Ciliary Dyskinesia in Adults with Bronchiectasis.

Background Determining the underlying diagnosis is essential for the targeted and specific treatment of bronchiectasis. Primary ciliary dyskinesia (PCD) is a rare genetic disease, which is characterized by abnormalities in ciliary structure and/or function and which may result in bronchiectasis. The disease is probably underestimated among adults with bronchiectasis due to the fact that extensive diagnostic testing is required and that the recognition of PCD is low. Objective To evaluate a feasible screening algorithm for PCD among adults with bronchiectasis. Methods Data from all patients who presented to our bronchiectasis outpatient clinic from June 2010 until July 2016 were retrospectively analysed from our database. Nasal NO (nNO) and a modified PICADAR score (PrImary CiliAry DyskinesiA Rule) were measured and compared in the two groups of PCD-bronchiectasis and non-PCD-bronchiectasis. Results 185 of 365 patients (75 males, 110 females) had a sufficient measurement of nNO concentration and complete clinical data and were eligible for analysis. The mean (SD) nNO concentration in nL/ml was significant lower in the PCD group compared to the non-PCD group (25 [31] and 227 [112] nL/min, respectively; p < 0.001). A nNO level of 77 nL/min had the best discriminative value to differentiate between the two groups. Patients with PCD had a significant higher modified PIDACAR score than patients without PCD (5 2 and 1 1, respectively [p < 0.001]). Using ROC curve analysis, the modified PICADAR score of 2 had the best discriminative value with a sensitivity of 1.00 and a specificity of 0.89. Conclusions Low nNO concentration and the modified PICADAR score are suitable and cheap screening tests for PCD in adults with bronchiectasis.

Everolimus Versus Mycophenolate Mofetil De Novo After Lung Transplantation: A Prospective, Randomized, Open-Label Trial.

The role of mammalian target of rapamycin (mTOR) inhibitors in de novo immunosuppression after lung transplantation is not well defined. We compared Everolimus versus mycophenolate mofetil in an investigator-initiated single-center trial in Hannover, Germany. A total of 190 patients were randomly assigned 1:1 on day 28 posttransplantation to mycophenolate mofetil (MMF) or Everolimus combined with cyclosporine A (CsA) and steroids. Patients were followed up for 2 years. The primary endpoint was freedom from bronchiolitis obliterans syndrome (BOS). The secondary endpoints were incidence of acute rejections, infections, treatment failure and kidney function. BOS-free survival in intention-to-treat (ITT) analysis was similar in both groups (p = 0.174). The study protocol was completed by 51% of enrolled patients. The per-protocol analysis shows incidence of bronchiolitis obliterans syndrome (BOS): 1/43 in the Everolimus group and 8/54 in the MMF group (p = 0.041). Less biopsy-proven acute rejection (AR) (p = 0.005), cytomegalovirus (CMV) antigenemia (p = 0.005) and lower respiratory tract infection (p = 0.003) and no leucopenia were seen in the Everolimus group. The glomerular filtration rate (GFR) decreased in both groups about 50% within 6 months. Due to a high withdrawal rate, the study was underpowered to prove a difference in BOS-free survival. The dropout rate was more pronounced in the Everolimus group. Secondary endpoints indicate potential advantages of Everolimus-based protocols but also a potentially higher rate of drug-related serious adverse events.

Prolonged Mechanical Ventilation After Lung Transplantation-A Single-Center Study.

This single-center study examines the incidence, etiology, and outcomes associated with prolonged mechanical ventilation (PMV), defined as time to definite spontaneous ventilation >21 days after double lung transplantation (LTx). A total of 690 LTx recipients between January 2005 and December 2012 were analyzed. PMV was necessary in 95 (13.8%) patients with decreasing incidence during the observation period (p < 0.001). Independent predictors of PMV were renal replacement therapy (odds ratio [OR] 11.13 [95% CI, 5.82-21.29], p < 0.001), anastomotic dehiscence (OR 8.74 [95% CI 2.42-31.58], p = 0.001), autoimmune comorbidity (OR 5.52 [95% CI 1.86-16.41], p = 0.002), and postoperative neurologic complications (OR 5.03 [95% CI 1.98-12.81], p = 0.001), among others. Overall 1-year survival was 86.0% (90.4% for LTx between 2010 and 2012); it was 60.7% after PMV and 90.0% in controls (p < 0.001). Conditional long-term outcome among hospital survivors, however, did not differ between the groups (p = 0.78). Multivariate analysis identified renal replacement therapy (hazard ratio [HR] 3.55 [95% CI 2.40-5.25], p < 0.001), post-LTx extracorporeal membrane oxygenation (HR 3.47 [95% CI 2.06-5.83], p < 0.001), and prolonged inotropic support (HR 1.95 [95% CI 1.39-2.75], p < 0.001), among others, as independent predictors of mortality. In conclusion, PMV complicated 14% of LTx procedures and, although associated with increased in-hospital mortality, outcomes among patients surviving to hospital discharge were unaffected.

Assess, compare and enhance the status of Persons with Multiple Sclerosis (MS) in Europe: a European Register for MS.

OBJECTIVES: Persons with multiple sclerosis (PwMS) experience health-related quality of life (HRQoL) problems greatly differing across Europe, and the European Union (EU) faces deep inequalities in MS management from country to country. Through the establishment of a European MS Register (EUReMS), an effective action is proposed to improve the overall knowledge on MS and support effective intervention programmes at EU and national political level. EUReMS aims to achieve consensus on its mission and vision, to define existing data providers, to develop models driving future MS health policies and research, to develop an information technology (IT) infrastructure for a data set, to develop a European shared governance and to secure providers' data provision into EUReMS. MATERIALS AND METHODS: EUReMS is meant to build on a minimum set of core data from existing national and regional population-based MS registries and from PwMS' perspectives. EUReMS' main partner is the European MS Platform (EMSP) acting in collaboration with associated and collaborating European partners. RESULTS: EUReMS was launched in July 2011. A Consensus Statement on purposes, vision, mission and strategies was produced in December 2011, and a comprehensive survey on existing MS data collections in Europe has been performed, and the EUReMS data mask is currently being discussed. CONCLUSIONS: EUReMS will represent a tool to provide up to date, comparable and sustainable MS data through an effective and credible register, which will encourage extensive knowledge building of MS, more equitable policies and higher standards in MS treatment and services.