118 research outputs found

    Infant tidal flow–volume parameters and arousal state

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    This version is distributed under the terms of the Creative Commons Attribution NonCommercial Licence 4.0. For commercial reproduction rights and permissions contact: [email protected]: Infant lung function can be assessed with tidal flow–volume (TFV) loops. While TFV loops can be measured in both awake and sleeping infants, the influence of arousal state in early infancy is not established. The aim of the present study was to determine whether TFV loop parameters in healthy infants differed while awake compared to the sleeping state at 3 months of age. Methods: From the population-based Scandinavian Preventing Atopic Dermatitis and ALLergies in children (PreventADALL) birth cohort, 91 infants had reproducible TFV loops measured with Exhalyzer® D in both the awake and sleeping state at 3 months of age. The TFV loops were manually selected according to a standardised procedure. The ratio of time to peak tidal expiratory flow (tPTEF) to expiratory time (tE) and the corresponding volume ratio (VPTEF/VE), as well as tidal volume (VT) and respiratory rate were compared using nonparametric tests. Results: The mean (95% CI) tPTEF/tE was significantly higher while awake compared to the sleeping state: 0.39 (0.37–0.41) versus 0.28 (0.27–0.29); with the corresponding VPTEF/VE of 0.38 (0.36–0.40) versus 0.29 (0.28–0.30). The VT was similar, while the respiratory rate was higher while awake compared to the sleeping state: 53 (51–56) breaths·min−1 versus 38 (36–40) breaths·min−1 . Conclusion: Higher tPTEF/tE, VPTEF/VE and respiratory rate, but similar VT while awake compared to the sleeping state suggests that separate normative TFV loop values according to arousal state may be required in early infancy.publishedVersio

    Transcriptome analysis of controlled and therapy-resistant childhood asthma reveals distinct gene expression profiles

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    Background: Children with problematic severe asthma have poor disease control despite high doses of inhaled corticosteroids and additional therapy, leading to personal suffering, early deterioration of lung function, and significant consumption of health care resources. If no exacerbating factors, such as smoking or allergies, are found after extensive investigation, these children are given a diagnosis of therapy-resistant (or therapy-refractory) asthma (SA). Objective: We sought to deepen our understanding of childhood SA by analyzing gene expression and modeling the underlying regulatory transcription factor networks in peripheral blood leukocytes. Methods: Gene expression was analyzed by using Cap Analysis of Gene Expression in children with SA (n = 13), children with controlled persistent asthma (n = 15), and age-matched healthy control subjects (n = 9). Cap Analysis of Gene Expression sequencing detects the transcription start sites of known and novel mRNAs and noncoding RNAs. Results: Sample groups could be separated by hierarchical clustering on 1305 differentially expressed transcription start sites, including 816 known genes and several novel transcripts. Ten of 13 tested novel transcripts were validated by means of RT-PCR and Sanger sequencing. Expression of RAR-related orphan receptor A (RORA), which has been linked to asthma in genome-wide association studies, was significantly upregulated in patients with SA. Gene network modeling revealed decreased glucocorticoid receptor signaling and increased activity of the mitogen-activated protein kinase and Jun kinase cascades in patients with SA. Conclusion: Circulating leukocytes from children with controlled asthma and those with SA have distinct gene expression profiles, demonstrating the possible development of specific molecular biomarkers and supporting the need for novel therapeutic approaches.Peer reviewe
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