Bronchiolitis in Early Infancy
Predictive factors for post-bronchiolitis wheezing

By Kirsi Nuolivirta
April 2012
Tampere University Press
Distributed by Coronet Books Inc.

ISBN: 9789514486920
148 pages

$82.50 Paper original

Bronchiolitis is the leading cause of infant hospitalization in developed countries, especially in the age group of <6 months. Susceptibility to both severe bronchiolitis and post-bronchiolitis wheezing has been discovered to be multifactorial including factors related to the host, environment and the virus itself. The aim of this prospective study was to evaluate genetic, microbial and other early-life factors as risk factors for disease severity and subsequent wheezing in children hospitalized for bronchiolitis at <6 months of age and prospectively followed up until 1.5 years of age. The aim was to evaluate (1) if the polymorphisms of interleukin (IL)-10 –1082 G/A, IL-18 –137 G/C, toll-like receptor (TLR) 4 +896 A/G, and interferon-gamma gene (IFNG) +874 T/A, and polymorphisms in the mannose-binding lectin (MBL)2 gene are associated with the presence of bronchiolitis and the viral etiology of bronchiolitis; (2) if these polymorphisms are associated with recurrent wheezing and infections during the first 1.5 years of life; (3) how often viral infections, respiratory syncytial virus (RSV) infections in particular, are mixed with Bordetella pertussis infections in infants with bronchiolitis and how co-infection with B. pertussis influences the clinical picture and outcome of bronchiolitis; and (4) how birth weight, weight gain in infancy and overweight assessed by weight for length (WFL) at age 1-2 years influence the risk for wheezing after hospitalization for bronchiolitis.

This prospective study was conducted at the Department of Pediatrics, Tampere University Hospital during three infectious seasons from 2001 to 2004. Infants <6 months of age hospitalized for bronchiolitis were eligible for this study. One hundred and thirty-nine infants were eligible and 129 participated in the follow-up visit. The microbiological diagnosis was confirmed by polymerase chain reaction (PCR) for viruses and B. pertussis. Polymorphisms of the selected genes were studied by PCR from DNA extracted from blood samples. The control group for the gene polymorphism analysis, excluding the MBL2 polymorphisms, consisted of 400 healthy Finnish blood donors. The demographic data and clinical characteristics were recorded during hospitalization. The clinical outcomes during the follow-up period were collected by diaries filled in by parents. The data were supplemented by interviewing the parents at the follow-up visit, and when the children were examined, at which point the weights and heights were measured and the WFLs were calculated. In the statistical analyses of the data, univariate and multivariate models were used as appropriate.

The viral etiology of bronchiolitis was most often associated with RSV (69.8%), followed by human rhinovirus (HRV) (6.5%) and influenza A virus (IVA) (4.3%). The infants hospitalized with non-RSV bronchiolitis were more likely to be homozygous for the A allele at –1082 of IL-10 than were blood donors (p<0.0001). MBL2 gene polymorphisms A/O or O/O were associated with multiple viral etiologies of bronchiolitis (p=0.047). The polymorphism at IFNG +874 T/A (homozygosity for A at +874) was associated with post-bronchiolitis wheezing, and the A allele was associated with less need for corticosteroid therapy (aOR=0.23). Conversely, the MBL2 A/O or O/O genotypes were associated with the need for corticosteroid therapy during post-bronchiolitis wheezing (p=0.016). TLR4 +896 A/G (G allele carriers, p=0.012 vs. non-carriers) and IL-10 –1082 A/G (G allele carriers, p=0.030 vs. non-carriers) were associated with repeated otitis media assessed by tympanostomy tube insertions. B. pertussis diagnosed by PCR was common (8.6%) in unvaccinated or partially vaccinated infants. Two-thirds of the cases had mixed infections with RSV; although the clinical characteristics were rather similar, B. pertussis was associated with coughing spells. Both high birth weight >4000 g (aOR 3.21) and overweight WFL >110% (aOR 4.63) during the follow-up visit were associated with recurrent post-bronchiolitis wheezing.

The results of this study confirm that the most common viral finding in young infants with bronchiolitis is RSV, and that B. pertussis co-infections comprise 8–10% of cases. Preliminary evidence was found that birth weight and overweight at 1–2 years are risk factors for recurrent wheezing after hospitalization for bronchiolitis. The main result of the study was that gene polymorphisms may have some association with the severity of bronchiolitis, post-bronchiolitis wheezing and recurrent infections after bronchiolitis. Greater understanding of the interaction between genes and viruses increases the potential for identifying at-risk infants, in whom preventing infections or tailoring anti-inflammatory treatments could alter the presentation of recurrent wheezing, recurrent infections and even later asthma.


Acta Universitatis Tamperensis No. 1696


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