Title Airway Remodeling Factors During Early-Life Rhinovirus Infection and the Effect of Premature Birth.
Author XuChen, Xilei; Weinstock, Jered; Arroyo, Maria; Salka, Kyle; Chorvinsky, Elizabeth; Abutaleb, Karima; Aguilar, Hector; Kahanowitch, Ryan; Rodriguez-Martinez, Carlos E; Perez, Geovanny F; Gutierrez, Maria J; Nino, Gustavo
Journal Front Pediatr Publication Year/Month 2021
PMID 33718297 PMCID PMC7952989
Affiliation + expend 1.Division of Pediatric Pulmonary and Sleep Medicine, Children's National Hospital, George Washington University, Washington, DC, United States.

Background: Early rhinovirus (RV) infection is a strong risk factor for asthma development. Airway remodeling factors play a key role in the progression of the asthmatic condition. We hypothesized that RV infection in young children elicits the secretion of growth factors implicated in airway remodeling and asthma progression. Methods: We examined the nasal airway production of remodeling factors in children ( </= 2 years old) hospitalized due to PCR-confirmed RV infection. Airway remodeling proteins included: MMP-1, MMP-2, MMP-7, MMP-9, MMP-10, TIMP-1, TIMP-2, EGF, Angiopoietin-2, G-CSF, BMP-9, Endoglin, Endothelin-1, Leptin, FGF-1, Follistatin, HGF, HB-EGF, PLGF, VEGF-A, VEGF-C, VEGF-D, FGF-2, TGF-beta1, TGF-beta2, TGF-beta3, PDGF AA, PDGF BB, SPARC, Periostin, OPN, and TGF-alpha. Results: A total of 43 young children comprising RV cases (n = 26) and uninfected controls (n = 17) were included. Early RV infection was linked to (1) enhanced production of several remodeling factors (e.g., HGF, TGFalpha), (2) lower MMP-9/TIMP-2 and MMP-2/TIMP-2 ratios, and (3) increased MMP-10/TIMP-1 ratios. We also found that relative to term infants, severely premature children had reduced MMP-9/TIMP-2 ratios at baseline. Conclusion: RV infection in young children elicits the airway secretion of growth factors implicated in angiogenesis, fibrosis, and extracellular matrix deposition. Our results highlight the potential of investigating virus-induced airway remodeling growth factors during early infancy to monitor and potentially prevent chronic progression of respiratory disorders in all ages.

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