Neutrophil Activation, Infiltration And Damage To Airways In Bronchiolitis Is Independent Of Viral Etiology

Rationale: Bronchiolitis remains one of the leading causes of infant morbidity and hospital admissions. Hospitalization with bronchiolitis has been linked to the development of chronic wheeze and asthma in children, with viral etiology and severity of the acute inflammatory response potential contributing factors. Previously we demonstrated that airway neutrophil infiltration is reduced in breastfed infants during the acute phase of the disease and subsequent development of wheezing illness is decreased up to 3 years of age. From these studies we hypothesized that the influx of activated neutrophils in response to viral induction of inflammatory mediators results in pronounced epithelial damage, which is a substantive contributor to both acute and chronic morbidity. Objective: To examine the effect of viral etiology on inflammatory neutrophil infiltration and associated inflammation and tissue injury in the upper airways of infants hospitalized with bronchiolitis. Methods: Nasopharyngeal aspirates (NPA) were collected from hospitalized children, Flinders Medical Centre, Adelaide, Australia, between June and September 2013. PCR evaluated the presence of eight viral respiratory pathogens. Airway injury and inflammation was assessed via measurement in NPA of urea, protein and cellular infiltrate, and of interleukin (IL)-8, IL-6 and myeloperoxidase (MPO) by ELISA. Results: Consecutive NPA were collected from 228 bronchiolitic infants and 14 non-bronchiolitic hospitalized controls. Human rhinovirus (HRV) was the most prevalent (38%), followed by respiratory syncytial virus (RSV; 36%), adenovirus (10%) and human metapneumovirus (hMPV; 6%), with 25% positive for 2 or more viruses and 25% negative for all viruses. All 14 controls were negative for all viruses. Groups with less than 10 subjects were excluded for statistical analyses. Neutrophil infiltrate was increased in NPA from all virus positive infections above control and negative NPA, and also corresponded with increased markers of tissue injury (urea and protein) (p<0.05). Positive correlations were found between neutrophil infiltrate, and both IL-8 and MPO (r2 0.267 and 0.364, p<0.001). No significant difference was found with virus etiology for any parameter, nor were any significant additive effects of multiple virus infection found. Conclusion: Infants presenting with detectable respiratory virus in the upper airways during hospitalization with bronchiolitis demonstrate elevation in markers of upper airway tissue inflammation and injury with associated evidence of chemokine mediated neutrophil infiltration and activation. This response does not appear to be dependent on viral etiology and therefore provides support for the neutrophil as a target for therapeutic intervention for the treatment of viral bronchiolitis in infants.