Influence of viral infection on the relationships between airway cytokines and lung function in asthmatic children

Abstract

BackgroundFew longitudinal studies examine inflammation and lung function in asthma. We sought to determine the cytokines that reduce airflow, and the influence of respiratory viral infections on these relationships.MethodsChildren underwent home collections of nasal lavage during scheduled surveillance periods and self-reported respiratory illnesses. We studied 53 children for one year, analyzing 392 surveillance samples and 203 samples from 85 respiratory illnesses. Generalized estimated equations were used to evaluate associations between nasal lavage biomarkers (7 mRNAs, 10 proteins), lung function and viral infection.ResultsAs anticipated, viral infection was associated with increased cytokines and reduced FVC and FEV1. However, we found frequent and strong interactions between biomarkers and virus on lung function. For example, in the absence of viral infection, CXCL10 mRNA, MDA5 mRNA, CXCL10, IL-4, IL-13, CCL4, CCL5, CCL20 and CCL24 were negatively associated with FVC. In contrast, during infection, the opposite relationship was frequently found, with IL-4, IL-13, CCL5, CCL20 and CCL24 levels associated with less severe reductions in both FVC and FEV1.ConclusionsIn asthmatic children, airflow obstruction is driven by specific pro-inflammatory cytokines. In the absence of viral infection, higher cytokine levels are associated with decreasing lung function. However, with infection, there is a reversal in this relationship, with cytokine abundance associated with reduced lung function decline. While nasal samples may not reflect lower airway responses, these data suggest that some aspects of the inflammatory response may be protective against viral infection. This study may have ramifications for the treatment of viral-induced asthma exacerbations.Electronic supplementary materialThe online version of this article (10.1186/s12931-018-0922-9) contains supplementary material, which is available to authorized users.

Oxidative Stress-Related Mechanisms in SARS-CoV-2 Infections

“…Apart from iNOS induction in response to viruses and viral components, interferon gamma has been reported as a major cytokine to induce iNOS and NO overproduction in the pathogenesis of virus infection [ 123 , 124 ]. This cytokine is associated to Th1 cell response, as it is acknowledged that antiviral adaptive response is Th1 type [ 125 ]. Nevertheless, some viruses (such as influenza virus and HSV) might inhibit Th1 response through downregulation of interferons production.…”

Cluster analysis of nasal cytokines during rhinovirus infection identifies different immunophenotypes in both children and adults with allergic asthma

“…Children are especially susceptible to acute wheezing episodes caused by RV. To date, most studies in children have examined immune profiles associated with wheeze in the blood [19][20][21][22] , examined nasal gene expression using transcriptomic methods 23,24 , focused on targeted nasal cytokines [24][25][26][27] , or utilized univariate analytical methods. 28 Given that different asthma endotypes are known to exist, we theorized that a comprehensive assessment of nasal mediators was warranted in the context of RV infection, including examination of relationships to viral load, allergic status, and respiratory symptoms.…”

The Impact of Ambient Environmental Exposures to Microbial Products on Asthma Outcomes from Birth to Childhood

“…The researchers observed that wheezing with rhinovirus was associated with asthma at age 13 (OR = 3.3, 95% CI (1.5-7.1), p = 0.02) and sensitization to allergens increased with age [9]. FEV 1 % predicted has also been shown to be lower in asthmatic patients admitted to the hospital with an asthma exacerbation with concurrent rhinovirus infection, compared to children with asthma admitted for an exacerbation but negative for rhinovirus [29,59].…”