Background Rhinovirus (RV) has been linked to the pathogenesis of asthma. Prematurity is a risk factor for severe RV infection in early life, but is unknown if RV elicits enhanced pro-asthmatic airway cytokine responses in premature infants. This study investigated if young children born severely premature (<32 weeks gestation) exhibit airway secretion of Th2 and Th17 cytokines during natural RV infections and if RV-induced Th2-Th17 responses are linked to more respiratory morbidity in premature children during the first two years of life. Methods We measured Th2 and Th17 nasal airway cytokines in a retrospective cohort of young children aged 0–2 years with PCR-confirmed RV infection or non-detectable virus. Protein levels of IL-4, IL-13, TSLP and IL-17 were determined with multiplex immunoassays. Demographic and clinical variables were obtained by electronic medical record (EMR) review. Results The study comprised 214 children born full term (n=108), pre-term (n=44) or severely premature (n=62). Natural RV infection in severely premature children was associated with elevated airway secretion of Th2 (IL-4 and IL-13) and Th17 (IL-17) cytokines, particularly in subjects with history of bronchopulmonary dysplasia. Severely premature children with high RV-induced airway IL-4 had recurrent respiratory hospitalizations (median 3.65 hosp/year; IQR 2.8–4.8) and were more likely to have at least one pediatric intensive care unit admission during the first two years of life (OR 8.72; 95% CI 1.3–58.7; p=0.02). Conclusions Severely premature children have increased airway secretion of Th2 and Th17 cytokines during RV infections, which is associated with more respiratory morbidity in the first two years of life

BACKGROUND It is unknown why human metapneumovirus (HMPV) and respiratory syncytial virus (RSV) cause severe respiratory infection in children, particularly in premature infants. Our aim was to investigate if there are defective airway antiviral responses to these viruses in young children with history of prematurity. METHODS Nasal airway secretions were collected from 140 children ≤3 y old without detectable virus (n = 80) or with PCR-confirmed HMPV or RSV infection (n = 60). Nasal protein levels of IFNγ, CCL5/RANTES, IL-10, IL-4, and IL-17 were determined using a multiplex magnetic bead immunoassay. RESULTS Full-term children with HMPV and RSV infection had increased levels of nasal airway IFNγ, CCL5, and IL-10 along with an elevation in Th1 (IFNγ)/Th2 (IL-4) ratios, which is expected during antiviral responses. In contrast, HMPV-infected premature children (< 32 wk gestation) did not exhibit increased Th1/Th2 ratios or elevated nasal airway secretion of IFNγ, CCL5, and IL-10 relative to uninfected controls. CONCLUSION Our study is the first to demonstrate that premature infants have defective IFNγ, CCL5/RANTES, and IL-10 airway responses during HMPV infection and provides novel insights about the potential reason why HMPV causes severe respiratory disease in children with history of prematurity.

Summary. From Sept. 1986 to Jan. 1989, a hospital-based study was conducted on 736 children, under 5 years of age, with acute respiratory infection. Nasopharyngeal secretions were examined for viruses by culture and by immunofluorescence. Viruses were detected in 22% of specimens : respiratory syncytial(5%), parainfluenza (5%), influenza A (4%), influenza B (273, adenovirus (373, measles (3%). The highest rates of detection were with patients diagnosed clinically as pneumonia or upper respiratory tract infection. The case fatality rate was very high (43%) in children with measles virus infection.

Two hundred and thirty children clinically diagnosed as suffering from acute respiratory infection were tested for four major groups of viral aetiological agents, i.e. influenza para-influenza, respiratory syncytial virus (RSV) and adenoviruses using indirect immunofluorescence technique. At least one of the respiratory viruses was identified in 51 (22 per cent) specimens, which included influenza A in 6 (3 per cent), influenza B in 3 (1 per cent), para-influenza type 1 in 3 (1 per cent), para-influenza type 3 in 13 (6 per cent), RSV in 11 (5 per cent) adenovirus in 12 (5 per cent), and dual virus infections in 3 (1 per cent) cases. Maximum number of virus identification was noted in children below 1 year of age, particularly infection with RSV followed by para-influenza and adenoviruses. Value of rapid diagnosis by indirect immunofluorescence technique is stressed.