Human respiratory syncytial virus (RSV) is the most important cause of severe lower tract disease (LRTD) in young children worldwide. Extensive neutrophil accumulation lungs and occlusion small airways by DNA-rich mucus plugs are characteristic features RSV-LRTD. Activated neutrophils can release extracellular traps (NETs), networks DNA covered with antimicrobial proteins, as part first-line defence against pathogens. NETs trap eliminate microbes; however, abundant NET formation may also...

Abstract Background Activated eosinophils cause major pathology in stable and exacerbating asthma; however, they can also display protective properties like an extracellular antiviral activity. Initial murine studies led us to further explore a potential intracellular activity by eosinophils. Methods To follow eosinophil‐virus interaction, respiratory syncytial virus (RSV) influenza were labeled with fluorescent lipophilic dye (DiD). Interactions visualized confocal microscopy, electron flow...

Eosinophils drive pathophysiology in stable and exacerbating eosinophilic asthma, therefore treatment is focused on the reduction of eosinophil numbers. Mepolizumab, a humanized monoclonal antibody that neutralizes IL-5 efficiently attenuates eosinophils, proved clinically effective severe asthma but not mild asthma.To study effect mepolizumab virus-induced immune responses asthma.Patients with steroid-naive randomized for numbers, received 750 mg intravenously placebo-controlled...

Asthma is a heterogeneous disease with differences in onset, severity, and inflammation. Bronchial epithelial cells (BECs) contribute to asthma pathophysiology.We determined whether transcriptomes of BECs reflect heterogeneity inflammation severity asthma, this was affected from patients severe after their regeneration by bronchial thermoplasty.RNA sequencing performed on obtained bronchoscopy healthy controls (n = 16), mild 17), moderate 5), as well treated untreated airways the latter...

Acute worsening of asthma symptoms (exacerbation) is predominantly triggered by respiratory viruses, with influenza causing the most severe exacerbations. The lack an adequate animal model hampers mechanistic insight and development new therapeutics.We developed characterized a robust, consistent, reproducible mouse exacerbation chronic allergic asthma.Chronic airway inflammation was induced following house dust mite (HDM) sensitization protocol. HDM-sensitized mice controls were infected...

Acute respiratory infections are an important health concern. Traditionally, polysaccharide-enriched extracts from plants, containing immunomodulatory rhamnogalacturonan-I (RG-1), were used prophylactically. We established the effects of dietary supplementation with carrot-derived RG-I (cRG-I, 0–0.3–1.5 g/day) in 177 healthy individuals (18–65 years) on symptoms following infection rhinovirus strain 16 (RV16). Primary outcomes changes severity and duration symptoms, viral load nasal lavage....

Abstract Background Long term macrolide treatment has been found beneficial in bronchiectasis (BE) -pathogical bronchial dilatation- possibly due to a combined anti-bacterial and immunomodulatory effect. The exact mechanism of inflammatory response is unknown. Here, we investigated the effect maintenance on BE. In addition, assessed profile BE relation disease severity. Methods During BAT randomized controlled trial (investigating 1 year azithromycin (AZM) 83 patients), data severity, lung...

Objective Serum prolactin measurements are important in the differential diagnosis of pituitary masses and subfertility. We observed discrepancies serum levels several patients measured with different immunoassays. Despite differences assay results, reference intervals (RIs) derived by manufacturers were similar. In this study, we aimed to investigate re-establish RIs for Methods For comparison, samples collected from men women visiting Amsterdam UMC hospital. Prolactin using Atellica TM IM...

<b>Background:</b> Bronchiectasis is an inflammatory airway disease characterized by pathologic dilatation, but inflammation not well characterized. Macrolide antibiotics are applied in bronchiectasis, their potential anti-inflammatory effects established. <b>Aim:</b> Determine pathways and the effect of macrolide azithromycin sequential sputum samples from bronchiectasis patients BAT trial. <b>Methods:</b> Spontaneous samples, collected sequentially over a year 83 were liquified DTTand...

Abstract Acute respiratory virus infections, such as influenza and RSV, are predominant causes of asthma exacerbations. Eosinophils act a double‐edged sword in exacerbations that they activated by viral infections but also can capture inactivate viruses. Phosphodiesterase type 4 (PDE4) is abundantly expressed eosinophils has been implicated their activation. This exploratory study aims to determine whether these opposing roles activation upon interaction with be modulated selective PDE4...

Defective translocation of the translational repressor TIAR (T-cell internal antigen receptor) in bronchial epithelial cells (BECs) from asthma patients underlies hyperresponsiveness, reflected by an exaggerated production a select panel inflammatory cytokines such as CXCL-8, interleukin (IL)-6, granulocyte colony-stimulating factor, CXCL-10, upon exposure to tumour necrosis factor (TNF) and IL-17A. With this study we aimed clarify whether hyperresponsiveness is consistent finding, changed...

Eosinophils are considered to drive the pathophysiology in asthma and therefore treatment is focused on reducing eosinophil numbers. Mepolizumab, a humanized monoclonal antibody that neutralizes interleukin 5 (IL-5), efficiently attenuates both systemic local eosinophils but proved clinically effective only severe eosinophilic asthma.&nbsp;To study contribution of mild we performed placebo-controlled double-blind trial with mepolizumab after which patients were subjected rhinovirus (RV)16...

<b>Background:</b> Respiratory viral infections in allergic asthmatics promote accumulation of eosinophils and aggravate inflammation locally. Eosinophilic granular constituents exert antiviral activity, suggestive protective properties. Here we report that also display direct anti-viral <b>Approach:</b> To follow eosinophil-virus interaction, respiratory syncytial virus (RSV) influenza were labeled with a fluorescent lipophilic dye (DiD). From mice, examined BALF from house dust...

Viral airway infections cause asthma exacerbation paralleled by accumulation of inflammatory cell subsets in the airways. Here we aim to unravel role IL33-ST2 axis driving immune response a relevant murine model exacerbating asthma. Mice were sensitized i.n. HDM extract for 5 days/week weeks. On day 29, mice infected with influenza A/X31, 3 days before and after X31 infection animals treated (i.p.) mAbs directed against receptors IL33 (T1/ST2) or TSLP (TSLPR). sacrificed at 1, 2, 4, 6, 8...

Abstract Background Long term macrolide treatment has been found beneficial in bronchiectasis (BE) -pathogical bronchial dilatation- possibly due to a combined anti-bacterial and immunomodulatory effect. The exact mechanism of inflammatory response is unknown. Here, we investigated the effect maintenance on BE. In addition, assessed profile BE relation disease severity. Methods During BAT randomized controlled trial (investigating 1 year azithromycin (AZM) 83 patients), data severity, lung...

Loss of asthma control and exacerbations are predominantly triggered by respiratory viral infections characterized eosinophilic airway inflammation increased oxidative stress. Production reactive oxygen species is a key feature activated eosinophils link between stress during thus likely. We investigated whether attenuation eosinophil numbers activation using mepolizumab (anti-IL-5) impacts in stable virus-induced worsening asthma. Patients with mild received one high dose or placebo after...

Eosinophils are considered to drive the pathophysiology in asthma and therefore treatment is focused on reducing eosinophil numbers. Mepolizumab, a humanized monoclonal antibody that neutralizes interleukin 5 (IL-5), efficiently attenuates both systemic local eosinophils but proved clinically effective only severe eosinophilic asthma. To study contribution of mild we performed placebo-controlled double-blind trial with mepolizumab after which patients were subjected rhinovirus (RV)16...

We have shown that activation of granulocytes in airways from asthma patients is not limited to respiratory burst activation. The baseline presence and increase citrullinated histone H3 (CitH3) cell-free eosinophilic granules sputum moderate upon a corticosteroid-withdrawal induced exacerbation suggestive extracellular DNA traps, which may cause airway obstruction. Are these traps also present severe without an exacerbation? In this pilot study, 20 16 samples were analyzed. All used inhaled...