Severe preschool asthmatics have altered cytokine and anti‐viral responses during exacerbation

Abstract

Background Preschool asthma/recurrent wheeze is a heterogeneous condition. Different clinical phenotypes have been described, including episodic viral wheeze (EVW), severe intermittent wheeze (SIW), and multiple‐trigger wheeze (MTW). Objective To compare clinical, viral, and inflammatory/immune profiling at exacerbation between MTW, SIW, and EVW phenotypes. Methods Multicenter, prospective, observational cohort (VIRASTHMA‐2). Children (1‐5 years) with preschool asthma were enrolled during hospitalization for a severe exacerbation. History and anamnestic data, plasma, and nasal samples were collected at exacerbation (T1) and at steady state, 8 weeks later (T2), and sputum samples were collected at T1. Results A total of 147 children were enrolled, 37 (25%) had SIW, 18 (12.2%) EVW, and 92 (63%) MTW. They were atopic (47%), exposed to mold (22%) and cigarette smoke (50%), and prone to exacerbations (≥2 in the previous year in 70%). At exacerbation, at least one virus was isolated in 94% and rhinovirus in 75%, with no difference between phenotypes. Children with MTW and SIW phenotypes displayed lower plasma concentrations of IFN‐γ (P = .002), IL‐5 (P = .020), TNF‐α (P = .038), IL‐10 (P = .002), IFN‐β (P = .036), and CXCL10 (P = .006) and lower levels of IFN‐γ (P = .047) in sputum at exacerbation than children with EVW. At T2, they also displayed lower plasma levels of IFN‐γ (P = .045) and CXCL10 (P = .013). Conclusion Among preschool asthmatic children, MTW and SIW, prone to exacerbations, display lower systemic levels of Th1, Th2 cytokines, pro‐ and anti‐inflammatory cytokines, and antiviral responses during severe virus‐induced exacerbation.

Immunology and genetics of asthma, and probiotics in the treatment of atopic dermatitis

“…They conclude by mentioning that bronchiolitis patients had a higher percentage of ILC2 cells in the nasal aspirate and that this population of cells, by providing specific inflammatory signals, could play a significant role in the development of wheezing episodes later in life. Other studies and a review have recently addressed cell‐related mechanisms of asthma and confirm the recent interest in innate‐immunity‐related mechanisms of asthma 6‐8 …”

“…Other studies and a review have recently addressed cell-related mechanisms of asthma and confirm the recent interest in innate-immunity-related mechanisms of asthma. [6][7][8]…”

Immune maturation and modulation in childhood allergies : Aspects of epigenetic, mucosal and systemic immune mediators in allergy development and prevention

“…Thereby this could pave way for allergic disease, and induction of Th1-responses later in childhood could be compensatory in nature, to outweigh Th2-skewing. Furthermore, exacerbations caused by viral respiratory infections are common among asthmatic children 320 , possibly also explaining the induction of these Th1-associated chemokines. (OR=5.3, 95% CI 1.7-16.1, p=0.003) also increased substantially with presence of high concentrations of CCL18 at age 8 ( Figure 11B).…”

Childhood asthma heterogeneity at the era of precision medicine: Modulating the immune response or the microbiota for the management of asthma attack

“…In a cohort of preschool children, IFN-α systemic levels were reduced at the time of RV-induced exacerbation in asthmatics, as compared with healthy controls during an asymptomatic RV infection [30]. In our recently published cohort of preschool asthmatic children with natural virus-induced exacerbation (RV: 73%), the most severe children, who were prone-to-exacerbation, displayed lower plasma concentrations of IFN-β at exacerbation than the others, suggesting a defect of production in response to viruses limited to this sub-population [8]. In another study conducted in older children, we did not observe altered IFN responses in sputum, plasma and cultures of stimulated-PBMC of patients presenting a virus-induced exacerbation, compared with those with a non-virus-induced exacerbation [49].…”

“…During preschool years, these events can be isolated, with few or no interval symptoms, and their persistence despite conventional maintenance treatment, such as inhaled corticosteroids (ICS), is a marker of severity [6,7]. Although viral infections are the main triggers of acute asthma, early and multiple allergic sensitization is a strong risk factor of presenting severe and frequent exacerbations [7,8]. In school-age children and adolescents, acute asthma attacks are usually less frequent, and not only triggered by lung infections, but also by exposure to allergens and pollutants [3,9,10].…”