Mechanisms of asthma and allergic inflammation
Rhinovirus illnesses during infancy predict subsequent childhood wheezing

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Background

The contribution of viral respiratory infections during infancy to the development of subsequent wheezing and/or allergic diseases in early childhood is not established.

Objective

To evaluate these relationships prospectively from birth to 3 years of age in 285 children genetically at high risk for developing allergic respiratory diseases.

Methods

By using nasal lavage, the relationship of timing, severity, and etiology of viral respiratory infections during infancy to wheezing in the 3rd year of life was evaluated. In addition, genetic and environmental factors that could modify risk of infections and wheezing prevalence were analyzed.

Results

Risk factors for 3rd year wheezing were passive smoke exposure (odds ratio [OR] = 2.1), older siblings (OR = 2.5), allergic sensitization to foods at age 1 year (OR = 2.0), any moderate to severe respiratory illness without wheezing during infancy (OR = 3.6), and at least 1 wheezing illness with respiratory syncytial virus (RSV; OR = 3.0), rhinovirus (OR = 10) and/or non–rhinovirus/RSV pathogens (OR = 3.9) during infancy. When viral etiology was considered, 1st-year wheezing illnesses caused by rhinovirus infection were the strongest predictor of subsequent 3rd year wheezing (OR = 6.6; P < .0001). Moreover, 63% of infants who wheezed during rhinovirus seasons continued to wheeze in the 3rd year of life, compared with only 20% of all other infants (OR = 6.6; P < .0001).

Conclusion

In this population of children at increased risk of developing allergies and asthma, the most significant risk factor for the development of preschool childhood wheezing is the occurrence of symptomatic rhinovirus illnesses during infancy that are clinically and prognostically informative based on their seasonal nature.

Section snippets

Study subjects

A total of 289 newborns were enrolled from November 1998 through May 2000 in the Childhood Origins of ASThma (COAST) study as previously described.7, 8, 9 Of these children, 285 were followed prospectively for at least 1 year, and 275 were followed for 3 years.7 To qualify, at least 1 parent was required to have respiratory allergies (defined as 1 or more positive aeroallergen skin tests) and/or a history of physician-diagnosed asthma. The Human Subjects Committee of the University of Wisconsin

Viral isolates

A total of 1668 nasopharyngeal wash specimens were obtained during infancy. The likelihood of viral identification was related to the severity of illness, as measured by the symptom score (Fig 1; P < .0001). Viral identification occurred in 78% (95/122) of the severe (score ≥ 10), 70% (312/444) of the moderate (score = 5-9), and 63% (136/216) of the mild illnesses (score = 1-4; Fig 1). Virus was recovered from 66% (118/179) of the wheezing illnesses. Viral recovery from scheduled well (score = 0)

Discussion

We have used a birth cohort at high risk of developing allergic diseases and/or asthma to define more comprehensively the relationships between specific viral respiratory infections during infancy and the subsequent development of early childhood wheezing. A major advance of our findings is the documentation throughout early childhood of the specific viral pathogens involved in both asymptomatic (ie, at scheduled protocol visits) and symptomatic infections. By using this approach, we

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    Supported by National Institutes of Health grants #1R01HL61879-01 and #1P01HL70831-01.

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