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

• Published in: Respiratory research Vol. 19; no. 1; pp. 228 - 13
• Main Authors: Lewis, Toby C, Metitiri, Ediri E, Mentz, Graciela B, Ren, Xiaodan, Carpenter, Ashley R, Goldsmith, Adam M, Wicklund, Kyra E, Eder, Breanna N, Comstock, Adam T, Ricci, Jeannette M, Brennan, Sean R, Washington, Ginger L, Owens, Kendall B, Mukherjee, Bhramar, Robins, Thomas G, Batterman, Stuart A, Hershenson, Marc B
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 21-11-2018; BioMed Central; BMC
• Subjects: Air flow; Air pollution; Airways; Analysis; Asthma; Asthma - diagnosis; Asthma - metabolism; Asthma - virology; Biomarkers; Biomarkers - metabolism; Bronchitis; Carbon tetrachloride; Care and treatment; CCL20 protein; CCL4 protein; Chemokine; Child; Child health; Child, Preschool; Children; Correlation analysis; CXCL10 protein; Cytokine; Cytokines; Cytokines - metabolism; Data collection; Female; FEV1; FVC; Health aspects; Humans; Illnesses; Infections; Inflammation; Inflammatory response; Influence; Interleukin 13; Interleukin 4; Longitudinal Studies; Lung - physiology; Lung - virology; Lungs; Male; mRNA; Nasal Lavage - methods; Proteins; Questionnaires; Respiratory diseases; Respiratory function; Respiratory tract; Respiratory Tract Infections - diagnosis; Respiratory Tract Infections - metabolism; Respiratory Tract Infections - virology; Risk factors; Studies; Surveillance; Viral infections; Virus Diseases - diagnosis; Virus Diseases - metabolism; Viruses; Detroit Michigan; United States > US; Chemokine; Urban; FVC; Cytokine; Viral; FEV1; Children; Asthma; Rhinovirus
• ISSN: 1465-993X; 1465-9921; 1465-993X; 1465-9921
• DOI: 10.1186/s12931-018-0922-9

Few 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.
Children 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.
As anticipated, viral infection was associated with increased cytokines and reduced FVC and FEV
. 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 FEV
.
In 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.