Flow-dependency of exhaled nitric oxide in children with asthma and cystic fibrosis

The concentration of nitric oxide in exhaled air, a marker of airway inflammation, depends critically on the flow of exhalation. Therefore, the aim of this study was to determine the effect of varying the flow on end-expiratory NO concentration and NO output in children with asthma or cystic fibrosis (CF) and in healthy children. Nineteen children with stable asthma, 10 with CF, and 20 healthy children exhaled from TLC while controlling expiratory flow by means of a biofeedback signal at approximately 2, 5, 10 and 20% of their vital capacity per second. NO was measured in exhaled air with a chemiluminescence analyser. Comparisons between the three groups were made by analysing the NO concentration at the endexpiratory plateau and by calculating NO output at different flows. Exhaled NO decreased with increasing flow in all children. Children with asthma had significantly higher NO concentrations than healthy children, but only at the lowest flows. Asthmatics using inhaled steroids (n=13) tended to have lower median exhaled NO than those without steroids. The slope of linearized (log-log transformed) NO/flow plots was significantly steeper in asthmatics than in healthy controls. CF patients had a significantly lower NO concentration and output over the entire flow range studied, compared to asthmatic and control subjects, with a similar NO/flow slope as control subjects. In conclusion, the nitric oxide concentration in exhaled air is highly flow-dependent, and the nitric oxide-flow relationship differs between asthmatics versus cystic fibrosis patients and control subjects. Assessment of the nitric oxide/flow relationship may help in separating asthmatics from normal children

Puroindolines polymorphism and kernel texture in einkorn (Triticum monococcum)

BACKGROUND: Patients with severe asthma experience problems in different areas of their health status. Identification of these areas will provide insight in the patients needs and perhaps what determines the burden of disease. The Nijmegen Clinical Screening Instrument (NCSI) was recently developed for use in clinical practice in patients with COPD and provides a detailed picture of the patients' physiological functioning, symptoms, functional impairment, and Quality of Life. Main purpose of this study is to evaluate the use of the NCSI as compared to the Asthma Control Questionnaire (ACQ) and Asthma Quality of Life Questionnaire (AQLQ) in patients with severe asthma. METHODS: The NCSI, AQLQ, and ACQ were measured in 167 patients with severe asthma. Pearson correlations were calculated between NCSI sub-domains and the AQLQ domains and the ACQ. RESULTS: The NCSI measures more aspects of health status as compared to the ACQ and AQLQ in patients with severe asthma. Beside symptoms, subjective impairment, and emotions the NCSI also measures general Quality of Life, health related Quality of Life, satisfaction with relations, fatigue, and behavioural impairment. On all NCSI sub-domains proportions of patients with normal, mild, and severe problems were found. Heterogeneity was found on the number and on the combination of sub-domains on which patients reported severe problems. CONCLUSIONS: The NCSI provides a more detailed picture of the individual patient with severe asthma than the ACQ and AQLQ. The use of the NCSI might allow quick identification of the problem areas and possible factors that impair health status

Epithelial IL-6 trans-signaling defines a new asthma phenotype with increased airway inflammation

Background: Although several studies link high levels of IL-6 and soluble IL-6 receptor (sIL-6R) to asthma severity and decreased lung function, the role of IL-6 trans-signaling (IL-6TS) in asthmatic patients is unclear. Objective: We sought to explore the association between epithelial IL-6TS pathway activation and molecular and clinical phenotypes in asthmatic patients. Methods: An IL-6TS gene signature obtained from air-liquid interface cultures of human bronchial epithelial cells stimulated with IL-6 and sIL-6R was used to stratify lung epithelial transcriptomic data (Unbiased Biomarkers in Prediction of Respiratory Disease Outcomes [U-BIOPRED] cohorts) by means of hierarchical clustering. IL-6TS-specific protein markers were used to stratify sputum biomarker data (Wessex cohort). Molecular phenotyping was based on transcriptional profiling of epithelial brushings, pathway analysis, and immunohistochemical analysis of bronchial biopsy specimens. Results: Activation of IL-6TS in air-liquid interface cultures reduced epithelial integrity and induced a specific gene signature enriched in genes associated with airway remodeling. The IL-6TS signature identified a subset of patients with IL-6TS-high asthma with increased epithelial expression of IL-6TS-inducible genes in the absence of systemic inflammation. The IL-6TS-high subset had an overrepresentation of frequent exacerbators, blood eosinophilia, and submucosal infiltration of T cells and macrophages. In bronchial brushings Toll-like receptor pathway genes were upregulated, whereas expression of cell junction genes was reduced. Sputum sIL-6R and IL-6 levels correlated with sputum markers of remodeling and innate immune activation, in particular YKL-40, matrix metalloproteinase 3, macrophage inflammatory protein 1 beta, IL-8, and IL-1 beta. Conclusions: Local lung epithelial IL-6TS activation in the absence of type 2 airway inflammation defines a novel subset of asthmatic patients and might drive airway inflammation and epithelial dysfunction in these patients.Peer reviewe

ARIA 2016: Care pathways implementing emerging technologies for predictive medicine in rhinitis and asthma across the life cycle

The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma a

Anti-leukotriene therapy in asthma

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The effect of a single high dose vitamin D3 on neutrophilic airway inflammation in nonatopic asthma

Rationale: Vitamin D deficiency has been associated with asthma and increased risk of respiratory tract infections. An infectious origin in its turn, has been proposed for nonatopic asthma (Joseph Ann All Asthma Immun 2003) as well as neutrophilic asthma (Simpson Thorax 2007). Vitamin D enhances anti-microbial defence and might thereby influence the inflammatory process in the airways. Therefore, we hypothesized that treatment with high dose vitamin D3 reduces neutrophilic airway inflammation in patients with nonatopic, neutrophilic asthma Methods: 28 nonatopic, neutrophilic (≥53% sputum neutrophils (Spanevello, AJRCCM 2000)) stable asthma patients were included in a randomized doubleblind placebo controlled trial. Patients received 400000 IU vitamin D3 or placebo orally in one dose. All completed questionnaires and underwent blood sampling, lung function tests and sputum induction at baseline and after 8 weeks Results: Baseline characteristics were similar in both arms. Results: see table Conclusion: Treatment with a single high dose vitamin D3 in nonatopic, neutrophilic asthma, does not reduce neutrophilic inflammation, but improves ACQ as compared to placebo Implications: The association between vitamin D and asthma is not explained by its effect on sputum neutrophils. The improvement in asthma control by vitamin D suggests that other beneficial mechanisms might be involved. (Table Presented)