Rhinovirus Load Is High despite Preserved Interferon-β Response in Cystic Fibrosis Bronchial Epithelial Cells.

Lung disease in cystic fibrosis (CF) is often exacerbated following acute upper respiratory tract infections caused by the human rhinovirus (HRV). Pathophysiology of these exacerbations is presently unclear and may involve deficient innate antiviral or exaggerated inflammatory responses in CF airway epithelial cells. Furthermore, responses of CF cells to HRV may be adversely affected by pre-exposure to virulence factors of Pseudomonas (P.) aeruginosa, the microorganism that frequently colonizes CF airways. Here we examined production of antiviral cytokine interferon-β and inflammatory chemokine interleukin-8, expression of the interferon-responsive antiviral gene 2'-5'-oligoadenylate synthetase 1 (OAS1), and intracellular virus RNA load in primary CF (delF508 CFTR) and healthy airway epithelial cells following inoculation with HRV16. Parallel cells were exposed to virulence factors of P. aeruginosa prior to and during HRV16 inoculation. CF cells exhibited production of interferon-β and interleukin-8, and expression of OAS1 at levels comparable to those in healthy cells, yet significantly higher HRV16 RNA load during early hours post-inoculation with HRV16. In line with this, HRV16 RNA load was higher in the CFBE41o- dF cell line overexpessing delF508 CFTR, compared with the isogenic control CFBE41o- WT (wild-type CFTR). Pre-exposure to virulence factors of P. aeruginosa did not affect OAS1 expression or HRV16 RNA load, but potentiated interleukin-8 production. In conclusion, CF cells demonstrate elevated HRV RNA load despite preserved interferon-β and OAS1 responses. High HRV load in CF airway epithelial cells appears to be due to deficiencies manifesting early during HRV infection, and may not be related to interferon-β

Implementation and use of mHealth home telemonitoring in adults with acute COVID-19 infection. A scoping review protocol

Dauletbaev N, Kuhn S, Holtz S, et al. Implementation and use of mHealth home telemonitoring in adults with acute COVID-19 infection. A scoping review protocol. BMJ open. 2021;11(9): e053819.INTRODUCTION: mHealth refers to digital technologies that, via smartphones, mobile apps and specialised digital sensors, yield real-time assessments of patient's health status. In the context of the COVID-19 pandemic, these technologies enable remote patient monitoring, with the benefit of timely recognition of disease progression to convalescence, deterioration or postacute sequelae. This should enable appropriate medical interventions and facilitate recovery. Various barriers, both at patient and technology levels, have been reported, hindering implementation and use of mHealth telemonitoring. As systematised and synthesised evidence in this area is lacking, we developed this protocol for a scoping review on mHealth home telemonitoring of acute COVID-19.; METHODS AND ANALYSIS: We compiled a search strategy following the PICO (Population, Intervention, Comparator, Outcome) and PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendation for Scoping Reviews) guidelines. MEDLINE, Embase and Web of Science will be searched from 1 March 2020 to 31 August 2021. Following the title and abstract screening, we will identify, systematise and synthesise the available knowledge. Based on pilot searches, we preview three themes for descriptive evidence synthesis. The first theme relates to implementation and use of mHealth telemonitoring, including reported barriers. The second theme covers the interactions of the telemonitoring team within and between different levels of the healthcare system. The third theme addresses how this telemonitoring warrants the continuity of care, also during disease transition into deterioration or postacute sequelae.; ETHICS AND DISSEMINATION: The studied evidence is in the public domain, therefore, no specific ethics approval is required. Evidence dissemination will be via peer-reviewed publications, conference presentations and reports to the policy makers. © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ

A scoping review of mHealth monitoring of pediatric bronchial asthma before and during COVID-19 pandemic

Dauletbaev N, Oftring Z, Akik W, et al. A scoping review of mHealth monitoring of pediatric bronchial asthma before and during COVID-19 pandemic. Paediatric Respiratory Reviews . 2022.Mobile (m) Health technology is well-suited for Remote Patient Monitoring (RPM) in a patient's habitual environment. In recent years there have been fast-paced developments in mHealth-enabled pediatric RPM, especially during the COVID-19 pandemic, necessitating evidence synthesis. To this end, we conducted a scoping review of clinical trials that had utilized mHealth-enabled RPM of pediatric asthma. MEDLINE, Embase and Web of Science were searched from September 1, 2016 through August 31, 2021. Our scoping review identified 25 publications that utilized synchronous and asynchronous mHealth-enabled RPM in pediatric asthma, either involving mobile applications or via individual devices. The last three years has seen the development of evidence-based, multidisciplinary, and participatory mHealth interventions. The quality of the studies has been improving, such that 40% of included study reports were randomized controlled trials. In conclusion, there exists high-quality evidence on mHealth-enabled RPM in pediatric asthma, warranting future systematic reviews and/or meta-analyses of the benefits of such RPM. Copyright © 2022 Elsevier Ltd. All rights reserved

IFN-β and IL-8 response to sterile filtrates of <i>P</i>. <i>aerigunosa</i> and HRV16.

<p>(<b>A</b>) and (<b>B</b>) Primary healthy (h) and CF (cf) HBE cells were pre-incubated for 18 hours with sterile filtrates of <i>P</i>. <i>aeruginosa</i> (Pfilt; 1: 100 dilution) in experimental culture medium (BEGM without hydrocorticortisone or antibiotics). Then, cells were inoculated for 24 hours with HRV16 (HRV) at an MOI of 0.1 in the presence of Pfilt. Afterwards, production of IFN-β (<b>A</b>) and IL-8 (<b>B</b>) was quantified in cell supernatants by respective ELISAs. Data are presented as box-and-whisker plots (medians, interquartile ranges, and min-max values) of absolute values of IFN-β and IL-8 production. n = 8 cultures per group. * p < 0.05. (<b>C</b>) and (<b>D</b>) The above cells were lysed, and expressions of mRNA of IFN-β (<b>C</b>) and IL-8 (<b>D</b>) were quantified by qPCR. Expression in basal cells (i.e., without exposure to Pfilt or HRV16; not shown) was assumed as 1. Numbers on the plot represent the medians of IFN-β mRNA up-regulation over basal in Pfilt-stimulated cells; other data are presented as box-and-whisker plots of fold up-regulation over basal. n = 8 cultures per group. * p < 0.05 and ** p < 0.01.</p

Up-regulation of <i>OAS1</i> expression by HRV16.

<p>(<b>A</b>) Primary healthy (h) and CF (cf) HBE cells were pre-incubated for 18 hours with experimental culture medium (BEGM without hydrocorticortisone or antibiotics) and subsequently inoculated for 24 hours with HRV16 (HRV) at an MOI of 0.1. Afterwards, expression of <i>OAS1</i> mRNA was quantified by qPCR. Numbers on the plot represent <i>OAS1</i> expression in basal cells, assumed as 1. Other data are presented as box-and-whisker plots (medians, interquartile ranges, and min-max values) of fold up-regulation over basal. n = 8 cultures per group. ** p < 0.01 and *** p < 0.001. (<b>B</b>) Primary healthy (h) and CF (cf) HBE cells were pre-incubated as above and subsequently inoculated for 2 hours with HRV16 (HRV) at the MOI of 0.1. Then, virus-containing cell supernatants were removed, cells were rinsed twice with experimental culture medium to deplete extracellular virus, and incubated for 22 hours without HRV16. Afterwards, expression of <i>OAS1</i> mRNA was quantified by qPCR. Numbers on the plot represent <i>OAS1</i> expression in basal cells, assumed as 1. Other data are presented as box-and-whisker plots of fold up-regulation over basal. n = 6–7 cultures per group. * p < 0.05 and ** p < 0.01.</p

IFN-β production stimulated by 24-hour inoculation with HRV16, with or without prior cell exposure to sterile <i>P</i>. <i>aeruginosa</i> filtrates.

<p>Footnote: Data are presented as median (min–max) pg/ml of secreted IFN-β. hHBE: healthy HBE cells; cfHBE: CF HBE cells; Pfilt: sterile filtrates of P. aeruginosa culture. None of the tested differences were significantly different.</p><p>IFN-β production stimulated by 24-hour inoculation with HRV16, with or without prior cell exposure to sterile <i>P</i>. <i>aeruginosa</i> filtrates.</p

Schematic representation of continuous and short-term inoculation with HRV, and the tested outcomes.

<p>(<b>A</b>) Continuous inoculation with HRV16. Cells were incubated with culture medium for 18 hours and subsequently inoculated for 24 hours with the human rhinovirus (HRV) 16 at a Multiplicity Of Infection (MOI) of 0.1. Afterwards, IFN-β and IL-8 production was quantified in cell supernatants by ELISA, whereas expression of IFN-β and IL-8 mRNAs, and the interferon-responsive antiviral gene <i>OAS1</i> was assessed in cell lysates by qPCR. Parallel cells were incubated with diffusible virulence factors of <i>P</i>. <i>aeruginosa</i> (“bacterial stimuli”) prior to and during inoculation with HRV16. (<b>B</b>) Short-term inoculation with HRV16. Cells were treated as in (<b>A</b>) prior to inoculation for 2 hours with HRV16 at an MOI of 0.1. Then, cell supernatants were removed, and cells were rinsed twice with culture medium to deplete extracellular virus. Subsequently, the cells were incubated for 22 hours without HRV16, and with or without virulence factors of <i>P</i>. <i>aeruginosa</i>. Afterwards, IFN-β and IL-8 (protein and mRNA) response, and expression of the interferon-responsive antiviral gene <i>OAS1</i> were quantified as in (<b>A</b>). (<b>C</b>) Quantification of intracellular HRV RNA load after a short-term inoculation with HRV16. Primary healthy and CF HBE cells were treated and inoculated as in (<b>B</b>). Then, cells were incubated without HRV16, and with or without diffusible virulence factors of <i>P</i>. <i>aeruginosa</i>. Cell lysates were collected at 10, 22, and 34 hours post-inoculation with the virus. HRV16 RNA copy numbers were quantified by qPCR.</p