ABSTRACT
BACKGROUND: Genome-wide association studies have identified several risk alleles for early childhood asthma, particularly in the 17q21 locus and in the cadherin-related family member 3 (CDHR3) gene. Contribution of these alleles to the risk of acute respiratory tract infections (ARI) in early childhood is unclear. METHODS: We analyzed data from the STEPS birth-cohort study of unselected children and the VINKU and VINKU2 studies on children with severe wheezing illness. Genome-wide genotyping was performed on 1011 children. We analyzed the association between 11 preselected asthma risk alleles and the risk of ARIs and wheezing illnesses of various viral etiologies. RESULTS: The asthma risk alleles in CDHR3, GSDMA, and GSDMB were associated with an increased rate of ARIs (for CDHR3, incidence rate ratio [IRR], 1.06; 95% confidence interval [CI], 1.01-1.12; P = .02), and risk allele in CDHR3 gene with rhinovirus infections (IRR, 1.10; 95% CI, 1.01-1.20, P = .03). Asthma risk alleles in GSDMA, GSDMB, IKZF3, ZPBP2, and ORMDL3 genes were associated with wheezing illnesses in early childhood, especially rhinovirus-positive wheezing illnesses. CONCLUSIONS: Asthma risk alleles were associated with an increased rate of ARIs and an increased risk of viral wheezing illnesses. Nonwheezing and wheezing ARIs and asthma may have shared genetic risk factors. Clinical Trials Registration. NCT00494624 and NCT00731575.
Subject(s)
Asthma , Respiratory Tract Infections , Humans , Child , Child, Preschool , Alleles , Cohort Studies , Respiratory Sounds/genetics , Genome-Wide Association Study , Asthma/epidemiology , Asthma/genetics , Respiratory Tract Infections/complications , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/genetics , Egg Proteins/genetics , Membrane Proteins/genetics , Pore Forming Cytotoxic Proteins/genetics , Cadherin Related ProteinsSubject(s)
Asthma , Respiratory Tract Infections , Asthma/epidemiology , Asthma/etiology , Asthma/immunology , Asthma/pathology , Child , Female , Humans , Male , Prospective Studies , Respiratory Tract Infections/complications , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/immunology , Respiratory Tract Infections/pathology , Risk FactorsABSTRACT
Background: Rhinovirus (RV) is the most common cause of respiratory tract infections in children but, still, the clinical characteristics of RV-associated pneumonia have not been sufficiently investigated. Methods: We identified children and adolescents younger than 18 years of age treated for community-acquired pneumonia as inpatients at the Turku University Hospital from 2003 to 2014 and analyzed for RV by PCR of a respiratory tract specimen. We collected the data from medical records and compared RV-positive children with RV-negative children. Results: Of the study population of 313 children with pneumonia who were studied for RV, it was detected in 82 (26%). RV-positive children were younger (median age 2.6 years, interquartile range [IQR] 1.1-4.6 vs. 3.5 years, IQR 1.7-8.3, p = 0.002) and they had more often a history of preterm birth (16% vs. 5%, adjusted odds ratio 2.89, 95% confidence interval 1.21-6.92, p = 0.017) than RV-negative children. RV-positive children had a higher median white blood cell count than RV-negative children at presentation with pneumonia. The signs, symptoms, and severity of pneumonia were mostly similar in RV-positive and RV-negative children. Conclusions: RV was frequently detected in young children hospitalized with community-acquired pneumonia. We identified premature birth as a factor associated with RV-positive pneumonia. The clinical features of pneumonia did not clearly differ between RV-positive and RV-negative children. Further studies are needed to clarify the clinical significance of detection of RV in children with pneumonia.