Impact of community respiratory viral infections in urban children with asthma

Abstract

Background: Upper respiratory tract viral infections cause asthma exacerbations in children. However, the impact of natural colds on children with asthma in the community, particularly in the high-risk urban environment, is less well defined.

Objective: We hypothesized that children with high-symptom upper respiratory viral infections have reduced airway function and greater respiratory tract inflammation than children with virus-positive low-symptom illnesses or virus-negative upper respiratory tract symptoms.

Methods: We studied 53 children with asthma from Detroit, Michigan, during scheduled surveillance periods and self-reported respiratory illnesses for 1 year. Symptom score, spirometry, fraction of exhaled nitric oxide (FeNO), and nasal aspirate biomarkers, and viral nucleic acid and rhinovirus (RV) copy number were assessed.

Results: Of 658 aspirates collected, 22.9% of surveillance samples and 33.7% of respiratory illnesses were virus-positive. Compared with the virus-negative asymptomatic condition, children with severe colds (symptom score ≥5) showed reduced forced expiratory flow at 25% to 75% of the pulmonary volume (FEF_25%-75%), higher nasal messenger RNA expression of C-X-C motif chemokine ligand (CXCL)-10 and melanoma differentiation-associated protein 5, and higher protein abundance of CXCL8, CXCL10 and C-C motif chemokine ligands (CCL)-2, CCL4, CCL20, and CCL24. Children with mild (symptom score, 1-4) and asymptomatic infections showed normal airway function and fewer biomarker elevations. Virus-negative cold-like illnesses demonstrated increased FeNO, minimal biomarker elevation, and normal airflow. The RV copy number was associated with nasal chemokine levels but not symptom score.

Conclusion: Urban children with asthma with high-symptom respiratory viral infections have reduced FEF_25%-75% and more elevations of nasal biomarkers than children with mild or symptomatic infections, or virus-negative illnesses.

Figure 1

Comparisons of lung function and exhaled NO (eNO) between the 6 groups of conditions. The virus-negative/high-symptom group (symptom score ≥5, black squares), virus-positive/mild-symptom group (symptom score 1-4, gray squares), virus-positive/asymptomatic (symptom score 0, white squares), virus-negative/high-symptom group (symptom score ≥5, black circles) and virus-negative/mild-symptom group (symptom score 1-4, gray circles) are each compared with the virus-negative/asymptomatic group. A, Changes in lung function (percent predicted) compared with the virus-negative/low-symptom group. Adjusted mean estimates and 95% confidence intervals are shown. B, Changes in eNO (ppb) compared with the virus-negative/no-symptom group. Adjusted odds ratios and 95% confidence intervals are shown.

Figure 2

Comparison of nasal aspirate mRNAs and proteins between the 6 groups of conditions. The virus-negative/high-symptom group (symptom score ≥5, black squares), virus-positive/mild-symptom group (symptom score 1-4, gray squares), virus-positive/asymptomatic (symptom score 0, white squares), virus-negative/high-symptom group (symptom score ≥5, black circles), and virus-negative/mild-symptom group (symptom score 1-4, gray circles) are each compared with the virus-negative/asymptomatic group. A, Differences in log transformed mean mRNA values for CXCL8, CXCL10, IRF7, RIG-I, and MDA5 compared with the virus-negative/low-symptom group. The 95% confidence intervals are also shown (*P < .05). B, TLR3 and IFN-λ1 mRNAs were analyzed as a binary variable (detectable, undetectable). Odds ratios and 95% confidence intervals compared with the virus-negative/low-symptom group are shown (*P < .05). C, Differences in log-transformed mean mRNA values for CXCL8, CXCL10, IL-4, IL-13, sICAM-1, CCL2, CCL4, CCL5, CCL20, and CCL24 compared with the virus-negative/low-symptom group. The 95% confidence intervals are also shown (*P < .05). Abbreviations: CCL, C-C motif chemokine ligand; CXCL, C-X-C motif chemokine ligand; IFN-λ1, interferon λ1; IL, interleukin; IRF7, interferon regulatory factor-7; MDA5, melanoma differentiation-associated protein 5; mRNA, messenger RNA; RIG-I, retinoic-acid-inducible protein 1; sICAM, soluble intercellular adhesion molecule; TLR3, Toll-like receptor 3.

Figure 3

Associations between nasal aspirate biomarkers and rhinoviral RNA. A, Nasal aspirate mRNAs are represented as ln (mRNA +1). Adjusted means and 95% confidence intervals are shown. B, Nasal aspirate proteins represented as ln (protein level +1). Adjusted means and 95% confidence intervals are shown. The association of viral copy number and nasal biomarker was determined using the GEE method (*P < .05). C-G, Individual adjusted correlations of viral copy number and selected nasal aspirate cytokines. Abbreviations: GEE, generalized estimating equations; mRNA, messenger RNA.

Figure 4

The time course of nasal biomarker changes from 28 virus-positive sick period weeks. A, Nasal aspirate mRNAs are represented as ln mRNA. B, Nasal aspirate proteins are represented as ln protein. For easier readability, SD are not shown. Abbreviations: mRNA, messenger RNA; SD, standard deviation.