Abstract:
BACKGROUND: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. METHODS: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. RESULTS:As 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. CONCLUSIONS: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.
journal_name
Respir Resjournal_title
Respiratory researchauthors
Lewis TC,Metitiri EE,Mentz GB,Ren X,Carpenter AR,Goldsmith AM,Wicklund KE,Eder BN,Comstock AT,Ricci JM,Brennan SR,Washington GL,Owens KB,Mukherjee B,Robins TG,Batterman SA,Hershenson MB,Community Action Against Asthma Sdoi
10.1186/s12931-018-0922-9subject
Has Abstractpub_date
2018-11-21 00:00:00pages
228issue
1eissn
1465-9921issn
1465-993Xpii
10.1186/s12931-018-0922-9journal_volume
19pub_type
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