BACKGROUND:Soluble urokinase plasminogen activator receptor (suPAR) is a biomarker elevated in severely ill patients, but its prognostic value in community-acquired pneumonia (CAP) remains unclear. This study aimed to evaluate suPAR's prognostic role for CAP severity compared to other biomarkers and severity scores. METHODS:A total of 204 hospitalised CAP patients were enrolled. C-reactive protein (CRP), procalcitonin (PCT), suPAR, CURB-65 and Pneumonia Severity Index (PSI) scores were measured at admission, and patients were followed for 365 days. The primary outcome was the relationship between suPAR levels and CAP severity based on IDSA/ATS guidelines. Secondary outcomes included time to clinical stability (TTCS), length of stay (LOS) and mortality. RESULTS:Among 204 patients, 174 (85%) had non-severe and 30 (15%) had severe CAP. SuPAR levels were not associated with severe CAP (OR 1.03, 95% CI 0.88-1.21; AUC 0.53). Unlike the PSI and CURB-65 scores, suPAR did not correlate with TTCS (HR PSI 0.80, HR CURB-65 0.86), though all three markers were correlated to LOS (AUC suPAR 0.61). Only suPAR was significantly associated with 30-day mortality (HR 1.51, AUC 0.68). CONCLUSIONS:The prognostic value of suPAR for CAP severity is low, and it does not provide additional prognostic benefit over the CURB-65 or PSI scores in predicting CAP severity. While it has moderate predictive ability for 30-day mortality, its utility for predicting LOS or TTCS is low. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT01964495.

BACKGROUND:Abdominal obesity is associated with reduced lung function. It remains unclear whether this results from mechanical pressure or whether visceral fat also plays a role via inflammation. Our aim was to examine the association between visceral fat and lung function, and the role of inflammation. METHODS:In this cross-sectional analysis, visceral fat was measured by magnetic resonance imaging and lung function by spirometry. We examined the association between visceral fat and lung function, and mediation by CRP, GlycA, FeNO, leptin, and adiponectin. RESULTS:We included 2,266 participants, mean age 56 (6) years and 90 (56) cm2 visceral fat. After adjusting for confounding factors including total body fat and waist circumference, per SD of visceral fat, FEV1 was 3.6% lower (95% CI: -4.9,-2.4), and FVC was 3.6% (-4.6,-2.6) lower. No mediation was observed by GlycA, FeNO and adiponectin. CRP and leptin together mediated 22% of the association with FEV1 and 19% with FVC. CONCLUSION:In a middle-aged general population with a normal lung function, visceral fat was associated with reduced lung function. This association was for 20% mediated by CRP and leptin. Future research should explore the remaining mechanisms underlying the association between visceral fat and lung function. TRIAL REGISTRATION:CT.gov identifier NCT03410316.

Background SuPAR is a prognostic biomarker in severely ill patients. Levels >6 ng/ml are an indicator of high inflammation. We aimed to determine the prognostic value of suPAR for severity and patient outcome in CAP. Methods A total of 204 patients hospitalized with CAP were enrolled. C-reactive protein (CRP), procalcitonin (PCT), suPAR, CURB-65 score and PSI score were determined at admission. Time-dependent receiver-operator characteristic (ROC) curves for time to clinical stability (TTCS, at day 7), length of stay (LOS, at day 14) and in-hospital mortality (at day 30) were calculated. Results The median age was 69 years (IQR 60-80). SuPAR and PCT, but not CRP, were significantly higher in patients with a higher CURB-65 score. SuPAR, but not PCT and CRP, was significantly higher in patients with a higher PSI class. The Area Under the Curve (AUC) of supAR for TTCS was 0.55 (95% CI 0.43-0.67), the AUC for LOS was 0.68 (0.51-0.84) and the AUC for mortality was 0.66 (0.34-0.97). The difference in AUC of suPAR vs. other predictors was not significant for any of the curves, except for suPAR vs. PCT in the ROC curve of mortality (p=0.04). Conclusions SuPAR at admission showed higher correlation with CAP severity scores than PCT and CRP. Predictive ability of suPAR for TTCS, LOS and mortality was moderate and similar to the predictive ability of PCT, CRP, the PSI score and the CURB65-score.

BACKGROUND: Despite the low rate of bacterial coinfection, antibiotics are very commonly prescribed in hospitalized patients with COVID-19.RESEARCH QUESTION: Does the use of a procalcitonin (PCT)-guided antibiotic protocol safely reduce the use of antibiotics in patients with a COVID-19 infection?STUDY DESIGN AND METHODS: In this multicenter cohort, three groups of patients with COVID-19 were compared in terms of antibiotic consumption, namely one group treated based on a PCT-algorithm in one hospital (n = 216) and two control groups, consisting of patients from the same hospital (n = 57) and of patients from three similar hospitals (n = 486) without PCT measurements during the same period. The primary end point was antibiotic prescription in the first week of admission.RESULTS: Antibiotic prescription during the first 7 days was 26.8% in the PCT group, 43.9% in the non-PCT group in the same hospital, and 44.7% in the non-PCT group in other hospitals. Patients in the PCT group had lower odds of receiving antibiotics in the first 7 days of admission (OR, 0.33; 95% CI, 0.16-0.66 compared with the same hospital; OR, 0.42; 95% CI, 0.28-0.62 compared with the other hospitals). The proportion of patients receiving antibiotic prescription during the total admission was 35.2%, 43.9%, and 54.5%, respectively. The PCT group had lower odds of receiving antibiotics during the total admission only when compared with the other hospitals (OR, 0.23; 95% CI, 0.08-0.63). There were no significant differences in other secondary end points, except for readmission in the PCT group vs the other hospitals group.INTERPRETATION: PCT-guided antibiotic prescription reduces antibiotic prescription rates in hospitalized patients with COVID-19, without major safety concerns.

Background: The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) is causing significant morbidity and mortality. 75% of hospitalized patients develops pneumonia. Long-term effects are currently unknown. We assessed the pulmonary function and radiological improvement in post-COVID-19 patients. Methods: In this combined prospective and retrospective cohort study, we included discharged COVID-19 patients who visited the outpatient clinic for a first follow-up visit between May 2020 and January 2021. Chest X-ray and pulmonary function tests, including spirometry and measurement of carbon monoxide diffusing capacity (DLCO), were performed. Results: 175 consecutive COVID-19 survivors visiting the outpatient clinic were included. The median time to follow-up was 69 (IQR:61-90.5) days. Patients were stratified into critical/severe (n=92) and moderate/mild (n=83) disease based on the WHO classification (Clinical management of COVID-19. WHO/2019-nCoV/clinical/2020.5). Discussion: In the majority of the patients, pulmonary function tests were normal and complete resolution of radiographic consolidations was common. Compared to moderate and mild cases, patients with severe or critical COVID-19 had a significantly lower DLCO, TLC, and FVC and less improvement of radiographic abnormalities. We therefore recommend systematic respiratory follow-up mainly in the more severe cases recovering from COVID-19.

Vitamin D is hypothesized to have a beneficial effect on lung function and respiratory infections. The aim of this study was to assess the relationship of serum 25-hydroxyvitamin D (25(OH)D) concentrations with lung function, airway inflammation and common colds. We performed a cross-sectional analysis in the Netherlands Epidemiology of Obesity (NEO) study, a population-based cohort study. We included participants with measurements of serum 25(OH)D, Forced Expiratory Volume in 1 s (FEV1), Forced Vital Capacity (FVC), Fractional Exhaled Nitric Oxide (FeNO), and data on self-reported common colds (n = 6138). In crude associations, serum 25(OH)D was positively associated with FEV1 and FVC, and negatively with FeNO and the occurrence of a common cold. After adjustment for confounders, however, these associations disappeared. Stratified analyses showed that Body Mass Index (BMI) was an effect modifier in the relationship between serum 25(OH)D and FEV1, FVC and FeNO. In obese participants (BMI ≥ 30 kg/m2), 10 nmol/L higher 25(OH)D was associated with 0.46% predicted higher FEV1 (95% Confidence Interval: 0.17 to 0.75), 0.46% predicted higher FVC (0.18 to 0.74), and 0.24 ppb lower FeNO (−0.43 to −0.04). Thus, in the total study population, 25(OH)D concentrations were not associated with lung function, airway inflammation and common colds. In obese participants, however, higher 25(OH)D concentrations were associated with a better lung function and lower airway inflammation.

Background: In the last years, there has been interest in the role of small airways abnormalities in asthma. However, the role of small airways functioning in obese asthma patients is not well described. Aim: To explore differences in small-airways functioning between obese and non-obese asthma patients; To explore differences in small-airways functioning between obese asthma patients with and without increased factional exhaled nitric oxide (FeNO). Methods: The Netherlands Epidemiology of Obesity (NEO) study is a population based cohort study in 6671 participants of whom 513 had asthma. 57 patients were excluded due to missing values. Differences in small airways functioning (forced expiratory flow at 25-75% of FVC (FEF25-75)) between obese (BMI≥30 kg/m2) and non-obese asthma patients were explored using linear regression analysis. In the non-obese and obese subgroups FEF25-75 was compared between patients with high (≥25 ppb) and low (<25 ppb) Fe<NO levels. Analyses were adjusted for confounders. Results: Among 465 asthma patients, 51% was obese and 25% had high FeNO levels. The predicted FEF25-75 did not differ between non-obese and obese asthma patients (adjusted mean difference (MD) -0.66 % predicted, 95% CI: -4.6 to 5.9). In non-obese asthma patients, the FEF25-75 did not differ significantly between patients with low and high FeNO (adjusted MD -8.7 %, 95% CI: -17.5 to 0.1). In obese asthma patients, the FEF25-75 was lower in patients with high FeNO compared to patients with low FeNO (adjusted MD -10.7 %, 95% CI -18.9 to -2.5). Conclusions: Obese and non-obese asthma patients do not differ regarding small airways functioning. Small airways functioning was decreased in patients with high FeNO levels, suggesting that FEF25-75 might contribute to the diagnosis of asthma.

Obesity is a risk factor for the development of asthma. In patients with obesity the diagnosis of asthma is often based on symptoms, but without objective measurements. Nevertheless, obesity-associated asthma is recognized as a distinct asthma phenotype. Therefore, this study explores lung function and symptoms in asthma patients with and without obesity.

Background: Obesity increases the risk of asthma. Obesity-related asthma is recognized as a distinct phenotype. More evidence on differences between obese and non-obese asthma patients can help to improve diagnostic accuracy and to optimize treatment. Aim: To explore differences in lung function, inflammation and symptoms between obese and non-obese asthma patients. Method: The Netherlands Epidemiology of Obesity (NEO) study is a population based cohort study in 6671 participants(592 with asthma). Differences in lung function, fractional exhaled nitric oxide(FeNO) and symptoms between obese and non-obese asthma patients were explored using regression analysis, corrected for age, sex, smoking, ethnicity, education, physical activity, inhaled corticosteroids use. Results: Among 592 asthma patients, 318 were obese(BMI≥30 kg/m2). Non-obese asthma patients had better predicted forced expiratory volume in 1s (FEV1%)(100.2±18.6 vs. 96.5±18.1,p=0.026) and forced vital capacity (FVC%)(112.1±18.0 vs. 107.0±15.8,p<0.001) compared with obese patients. They did not differ regarding FeNO(17[12-25] vs. 15[11-24]ppb,p=0.285). Obese patients reported more wheezing than non-obese patients(33.3% vs. 16.9%,p<0.001), but did not differ on other symptoms. Symptoms worsened more during exercise in obese patients compared with non-obese patients(47.0% vs. 31.9%, p<0.001). Conclusions: Non-obese asthma patients have a better lung function than obese asthma patients. Obese patients more often experience wheezing and their symptoms worsen more during activity. Our results suggest that despite similar levels of inflammation as assessed by FeNO, obese asthma patients are more symptomatic and have a lower lung function than non-obese patients.

Background Allergy is often accompanied by infections and lower levels of antimicrobial peptides (AMPs). Vitamin D has been shown to increase expression of selected AMPs. In this study we investigated whether antimicrobial peptide levels in nasal secretions of allergic asthma patients are lower than in healthy controls, and whether administration of the active form of vitamin D (1,25(OH)2D3) affects these antimicrobial peptide levels. Methods The levels of antimicrobial peptides in nasal secretions were compared between 19 allergic asthma patients and 23 healthy controls. The effect of seven days daily oral treatment with 2 μg 1,25(OH)2D3 on antimicrobial peptides in nasal secretions was assessed in a placebo-controlled cross-over clinical study. Results Levels of neutrophil α-defensins (human neutrophil peptides 1–3; HNP1-3) and lipocalin 2 (LCN2; also known as NGAL) were significantly lower in asthmatics, but no differences in LL-37 and SLPI were detected. Treatment with a short-term 1,25(OH)2D3 caused a small increase in HNP1-3, but not when the asthma and control groups were analyzed separately. LL-37, LCN2 and SLPI did not change after treatment with 1,25(OH)2D3. Conclusion Levels of the antimicrobial peptides HNP1-3 and LCN2 are lower in nasal secretions in asthmatics and are not substantially affected by a short-term treatment with active vitamin D.

Exhaled nitric oxide is a noninvasive measure of airway inflammation that can be detected by a handheld device. Obesity may influence the reproducibility of exhaled nitric oxide measurements, by - for instance – decreased expiratory reserve volume.

Background: Several studies have reported a positive relationship between lung function impairment and the metabolic syndrome. This is most usually explained by abdominal adiposity.We hypothesized that the main determinant of the association between lung function impairment and abdominal obesity is the presence of visceral fat.Methods: The present study is a cross-sectional analysis of 98 non-diabetic men aged between 50 and 70 years with the metabolic syndrome. The amount of visceral and subcutaneous adipose tissue was determined by an MRI scan. The association between visceral fat and measures of lung function (FEV1, FVC, exhaled and NO) was assessed using linear regression.Results: 98 participants were included in this analysis. There was a linear inverse association between visceral fat and both FEV1 and FVC. None of the other different fat-related measurements (subcutaneous fat, waist circumference and BMI) or features of the metabolic syndrome were found to be associated with these lung function measurements.Conclusion: In non-diabetic subjects with the metabolic syndrome and a lung function that is within the normal range, visceral fat is negatively correlated with FEV1 and FVC. (C) 2013 Elsevier Ltd. All rights reserved.

Studies have demonstrated a role for vitamin D in inflammation and host defense against infection. In patients with obstructive lung diseases higher vitamin D levels are associated with a better lung function. We aimed to study the association between vitamin D and lung function (FEV1), and to which extent this association could be explained by exhaled nitric oxide (eNO), as a measure of airways inflammation, in a general population. This is a cross-sectional analysis of the baseline measurements of the Netherlands Epidemiology of Obesity study, a cohort of participants aged 45 to 65 years with an oversampling of BMI≥27kg/m². We used linear regression to study the associations of serum 25-hydroxyvitamin D concentrations with FEV1 and eNO, adjusting for age, sex, ethnicity, month and year, recent cold, asthma and total body fat. After exclusion of participants with missing data (n=166), 5146 adults were included with a mean (SD) age of 56 (6) y, BMI of 30.6 (4.8) kg/m² and total body fat of 37 (9) %. 47 % were men, 6% had asthma and 25% had a cold within the last month. The median (IQR) eNO was 18 (11-22) ppb, 25-hydroxyvitamin D 57 (39-71) nmol/l and the mean (SD) FEV1 was 104 (16) %. Serum 25-hydroxyvitamin D was associated with FEV1 (beta 0.09, 95% CI 0.07-0.10) this attenuated after adjustment for confounding (beta 0.03, 95% CI 0.01-0.05) but did not further change after adjustment for eNO. There was no association of eNO (beta 0.00 95% CI -0.001-0.000) with 25-hydroxyvitamin D, nor with FEV1 (beta 0.00 95% CI 0.000-0.001). Conclusion: In a general population serum 25-hydroxyvitamin D was associated with FEV1. This association was not explained by airways inflammation as assessed by eNO.

In COPD severity of disease is assessed with spirometry and dypnoea score such as CCQ (Clinical COPD Questionaire) or MRC (Medical Research Councel). Dyspnoea scores and spirometry are poorly correlated, dyspnoea may also be the result of other, not pulmonary aspects, especially in COPD GOLD 1 and 2. Questions: 1. What is the predictive value of CCQ and MRC with respect to the degree and cause of exercise limitation in patients with COPD 2. Which factors predict a pulmonary limitation? Methods: 60 symptomatic COPD patients in a stable phase without relevant comorbidity. At baseline they scored CCQ and MRC. A score of > 2 was considered abnormal dyspnoea (D +), others were D -. Exercise limitation in a cardiopulonary exercise test was labelled pulmonary (pulm), cardiac (card) or nonspecific (nonspec). Results: Main exercise limitating factor D– D+ pulm card nonspec pulm card nonspec GOLD 1 2 2 9 0 0 1 GOLD 2 8 0 3 9 3 7 GOLD 3 + 4 6 0 0 10 0 0 D + patients had a higher BMI (p<0.05), lower FEV1% (p <0.01), a lower Wattmax, VO2max and Inspiratory Capacity (p<0.005). In patients with a strict pulmonary limitation dyspnoea was not different from patients without pulmonary limitation. FEV1 and DLCO were significantly different, p<0.0001. Positive predictive value of dyspnoea score for pulmonary or cardiac limitation was 84% in all and 75% in patients with GOLD 1 and 2. Negative predictive value was 35% and 44% respectively. Conclusions: In COPD patients GOLD 1 and 2 exercise limitation was not due to pulmonary factors in 86% and 43% of patients, respectively. Pulmonary or cardiac limitation can be expected at high CCQ or MRC score, and can not be excluded in patients with a low score.

Vitamin D deficiency has been linked to asthma because of the proposed role of vitamin D in inflammation control and host defense against infection. Antimicrobial peptides (AMPs) are effector molecules of the innate immune system, and their expression may be decreased by allergic inflammation. Vitamin D increases expression of AMP in vitro, but its effects on AMPs levels in asthma patients are unknown. Hypothesis: AMP levels in nasal secretions of patients with allergic asthma are lower than those in controls and can be restored by vitamin D substitution. Methods and results: 20 allergic asthma patients and 20 controls (18-45 yrs) were included. The influence of allergic asthma on AMPs was assessed in a case control design, and the effect of 7 days daily oral treatment with 2 mcg 1,25(OH)2D3 active vitamin D (calcitriol) on AMPs was assessed in a placebo-controlled cross-over study. The levels of the AMPs HNP1-3 and NGAL were significantly lower in asthmatics, whereas there was a trend for LL-37 (table 1). Treatment with 1,25(OH)2D3 significantly increased HNP1-3 and there was a trend for an increase in LL-37 and NGAL. Conclusion: Levels of AMPs are lower in nasal secretions in asthmatics, and treatment with active vitamin D increases these levels.

An association between COPD and subclinical atherosclerosis that persisted after adjusting for cardiovascular risk factors has been reported. This may explain the excess cardiovascular mortality seen in patients with COPD. Objective: To investigate the association between lung function and subclinical atherosclerosis in a population of obese adults with a normal lung function. Methods: This is a cross-sectional analysis of the NEO (Netherlands Epidemiology of Obesity) study, a cohort of adults aged 45 to 65 years with a Body Mass Index (BMI) 27≥ kg/m 2 . The association between FEV1 and subclinical atherosclerosis (mean maximal common carotid intima- media thickness [cIMT] measured by ultrasound) was assessed using linear regression. Results: 1115 adults were included with a mean (25th-75th percentiles) age of 56 (51-61) y, BMI of 31 (28-32) kg/m 2 , FEV1 of 104% (94-113) and 48,7% men. One percent FEV1% increase was associated with 0.001 mm (95% CI -0.001, -0.002) decrease in mean maximal cIMT. After adjustment for age, sex, pack years and BMI the β was 0.001 (95%CI -0.001, 0.000). Conclusion: The association between lung function and subclinical atherosclerosis in obese subjects with a normal lung function is weak and a great part of the initial association is explained by confounders. The small association is probably due to residual confounding.

A 53−year−old man, with known Klippel± Trenaunay syndrome (KTS), presented with massive life−threatening gastroin− testinal blood loss. After hemodynamic resuscitation, upper endoscopy and ileo− colonoscopy were performed. These did not reveal the source of bleeding. Video capsule endoscopy was subsequently per− formed using the Given (Yoqneam, Israel) system. This revealed a large number of small−bowel hemangiomas (Figure 1). However, none of the lesions showed signs of active or recent bleeding. The clinical course was favorable, with spon− taneous resolution of the blood loss. It re− mains unclear what may have precipitat− ed the bleeding episode.

Metal-doped semiconductor–metal tunnel junctions for which the tunneling barrier is made of a double Schottky barrier are proposed and studied both experimentally and theoretically. Using the tunneling barrier model, the electron tunneling current is calculated. The junctions are prepared by successive condensation from vapor of a Pb electrode, a CdS layer, and a second Pb electrode. The thickness of the semiconducting layer is varied from 50 to 5000 Å. The I–U characteristics of the junctions are measured at liquid helium temperature and prove to be in good agreement with the theory proposed. Nous avons proposé et étudié tant théoriquement qu'expérimentalement, des jonctions tunnel, métal–semi-conducteur (dopé)-métal, pour lesquelles la barrière tunnel est constituée d'une double barrière Schottky (deux contacts métal–semi-conducteur accolés dos à dos). Nous avons calculé pour ce modèle de barrière le courant tunnel. De telles jonctions ont été réalisées par évaporation thermique, l'épaisseur de la couche semiconductrice (CdS) variant de 50 à 5000 Å. Les caractéristiques électriques de ces jonctions ont été mesurées aux températures de l'hélium liquide. Les résultats expérimentaux sont en accord avec les conclusions de la théorie proposée.