Dataset Information

Clinical correlates of rhinovirus infection in preschool asthma.

ABSTRACT:

Background

Investigation of preschool asthma is important since not all children outgrow their illness during this age. Data are scarce on the role of rhinovirus (RV) infections in this patient group.

Objectives

To investigate the role of RV infections in preschool asthma: (i) susceptibility factors, (ii) clinical course, and (iii) medium-term outcome.

Methods

A total of 130 asthmatic children aged 4-6 years from the multinational PreDicta cohort were prospectively followed for a 12-month period. Allergy tests and a standard health questionnaire were carried out at study entry. Respiratory virus presence in nasopharyngeal washes was studied at illness visits and at 3 scheduled visits.

Results

At study entry, mean age of the children was 5.3 years. Of 571 visits, 54% were positive for any virus and 39% for RV. Patient characteristics were only assessed with RV infection due to low number of other viruses. The use of supplementary vitamin D was inversely associated with RV infection (P < .05). RV infection was associated with more severe course of acute illness in terms of more severe nighttime coughing, more sleep disturbances, and more days with runny nose (all P < .05). RV infection was also associated with more severe disease course during the 12-month follow-up in terms of more nights with awakenings and more days of exercise-related symptoms (both P < .05).

Conclusions

Vitamin D supplementation may have an anti-rhinovirus effect. Both short- and medium-term outcomes suggest RV infection to be an important clinical marker of instable preschool asthma.

SUBMITTER: Jartti T

PROVIDER: S-EPMC7818397 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

Clinical correlates of rhinovirus infection in preschool asthma.

Jartti Tuomas T Liimatainen Unna U Xepapadaki Paraskevi P Vahlberg Tero T Bachert Claus C Finotto Susetta S Kowalski Marek L ML Sobanska Anna A Lukkarinen Heikki H Pasioti Maria M Vuorinen Tytti T Zhang Nan N Zimmermann Theodor T Papadopoulos Nikolaos G NG

Allergy 20200721 1

<h4>Background</h4>Investigation of preschool asthma is important since not all children outgrow their illness during this age. Data are scarce on the role of rhinovirus (RV) infections in this patient group.<h4>Objectives</h4>To investigate the role of RV infections in preschool asthma: (i) susceptibility factors, (ii) clinical course, and (iii) medium-term outcome.<h4>Methods</h4>A total of 130 asthmatic children aged 4-6 years from the multinational PreDicta cohort were prospectively followed ...[more]

PMID: 32621330

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Project description:Respiratory viral infections, particularly those caused by rhinovirus, exacerbate chronic respiratory inflammatory diseases, such as asthma and chronic obstructive pulmonary disease (COPD). Airway epithelial cells are the primary site of rhinovirus replication and responsible of initiating the host immune response to infection. Numerous studies have reported that the anti-viral innate immune response (including type I and type III interferon) in asthma is less effective or deficient leading to the conclusion that epithelial innate immunity is a key determinant of disease severity during a rhinovirus induced exacerbation. However, deficient rhinovirus-induced epithelial interferon production in asthma has not always been observed. We hypothesized that disparate in vitro airway epithelial infection models using high multiplicity of infection (MOI) and lacking genome-wide, time course analyses have obscured the role of epithelial innate anti-viral immunity in asthma and COPD. To address this, we developed a low MOI rhinovirus model of differentiated primary epithelial cells obtained from healthy, asthma and COPD donors. Using genome-wide gene expression following infection, we demonstrated that gene expression patterns are similar across patient groups, but that the kinetics of induction are delayed in cells obtained from asthma and COPD donors. Rhinovirus-induced innate immune responses were defined by interferons (type-I, II, and III), interferon response factors (IRF1, IRF3, and IRF7), TLR signaling and NF-κB and STAT1 activation. Induced gene expression was evident at 24 h and peaked at 48 h post-infection in cells from healthy subjects. In contrast, in cells from donors with asthma or COPD induction was maximal at or beyond 72-96 h post-infection. Thus, we propose that propensity for viral exacerbations of asthma and COPD relate to delayed (rather than deficient) expression of epithelial cell innate anti-viral immune genes which in turns leads to a delayed and ultimately more inflammatory host immune response.

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Project description:BackgroundHistamine-releasing factor (HRF) is implicated in allergic diseases. We previously showed its pathogenic role in murine models of asthma.ObjectiveWe aim to present data analysis from 3 separate human samples (sera samples from asthmatic patients, nasal washings from rhinovirus [RV]-infected individuals, and sera samples from patients with RV-induced asthma exacerbation) and 1 mouse sample to investigate correlates of HRF function in asthma and virus-induced asthma exacerbations.MethodsTotal IgE and HRF-reactive IgE/IgG as well as HRF in sera from patients with mild/moderate asthma or severe asthma (SA) and healthy controls (HCs) were quantified by ELISA. HRF secretion in culture media from RV-infected adenovirus-12 SV40 hybrid virus transformed human bronchial epithelial cells and in nasal washings from experimentally RV-infected subjects was analyzed by Western blotting. HRF-reactive IgE/IgG levels in longitudinal serum samples from patients with asthma exacerbations were also quantified.ResultsHRF-reactive IgE and total IgE levels were higher in patients with SA than in HCs, whereas HRF-reactive IgG (and IgG1) level was lower in asthmatic patients versus HCs. In comparison with HRF-reactive IgElow asthmatic patients, HRF-reactive IgEhigh asthmatic patients had a tendency to release more tryptase and prostaglandin D2 on anti-IgE stimulation of bronchoalveolar lavage cells. RV infection induced HRF secretion from adenovirus-12 SV40 hybrid virus transformed bronchial epithelial cells, and intranasal RV infection of human subjects induced increased HRF secretion in nasal washes. Asthmatic patients had higher levels of HRF-reactive IgE at the time of asthma exacerbations associated with RV infection, compared with those after the resolution. This phenomenon was not seen in asthma exacerbations without viral infections.ConclusionsHRF-reactive IgE is higher in patients with SA. RV infection induces HRF secretion from respiratory epithelial cells both in vitro and in vivo. These results suggest the role of HRF in asthma severity and RV-induced asthma exacerbation.

Dataset Information

Clinical correlates of rhinovirus infection in preschool asthma.

Background

Objectives

Methods

Results

Conclusions

Publications

Clinical correlates of rhinovirus infection in preschool asthma.

Similar Datasets

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