Asthma and lower airway disease
Allergen exposure modifies the relation of sensitization to fraction of exhaled nitric oxide levels in children at risk for allergy and asthma

https://doi.org/10.1016/j.jaci.2011.01.066Get rights and content

Background

Studies on airway inflammation, measured as fraction of exhaled nitric oxide (Feno), have focused on its relation to control of asthma, but the contribution of allergen exposure to the increase in Feno levels is unknown.

Objective

We evaluated (1) whether Feno levels were increased in children with allergic sensitization or asthma; (2) whether specific allergen exposure increased Feno levels in sensitized, but not unsensitized, children; and (3) whether sedentary behavior increased Feno levels independent of allergen exposures.

Methods

At age 12 years, in a birth cohort of children with a parental history of allergy or asthma, we measured bed dust allergen (dust mite, cat, and cockroach) by means of ELISA, specific allergic sensitization primarily based on specific IgE levels, and respiratory disease (current asthma, rhinitis, and wheeze) and hours of television viewing/video game playing by means of questionnaire. Children performed spirometric maneuvers before and after bronchodilator responses and had Feno levels measured by using electrochemical detection methods (NIOX MINO).

Results

Feno levels were increased in children with current asthma (32.2 ppb), wheeze (27.0 ppb), or rhinitis (23.2 ppb) compared with subjects without these respective symptoms/diagnoses (16.4-16.6 ppb, P < .005 for all comparisons). Allergic sensitization to indoor allergens (cat, dog, and dust mite) predicted higher Feno levels and explained one third of the variability in Feno levels. Feno levels were highest in children both sensitized and exposed to dust mite. Greater than 10 hours of weekday television viewing was associated with a 0.64-log increase in Feno levels after controlling for indoor allergen exposure, body mass index, and allergic sensitization.

Conclusion

Allergen exposures and sedentary behavior (television viewing/video game playing) might increase airway inflammation, which was measured as the Feno.

Section snippets

Study cohort

Study participants were recruited between September 1994 and August 1996. The screening and recruitment of families have been described in detail elsewhere.18 In brief, eligibility criteria included residence in the Boston metropolitan area, maternal age of 18 years or greater, and a history of hay fever, asthma, or allergies in at least 1 of the child’s parents. Families were not screened if the newborn was hospitalized in the intensive care unit, if his or her gestational age was less than 36

Feno measurement

The median level of Feno was 16.0 ppb (range, 2.0-169 ppb) in all subjects with Feno measurements (Table I). On average, children were 11.7 years of age at the time of Feno quantification (age range, 11-13.9 years). Of the 430 children followed to age 12 years by questionnaire, 277 (64%) had Feno measurements. Children with Feno measurements were more likely to be white and less likely to be Hispanic. Distribution of sex and prevalence of maternal asthma were similar for those with versus

Discussion

The importance of ascertaining specific allergic sensitization when evaluating the clinical significance of allergen exposure on asthma morbidity was highlighted, first in the observational National Inner City Asthma Study21, 22 and then in the subsequent intervention study that was targeted at allergen exposures to which asthmatic children were sensitized.23 Our study highlights the importance of allergic sensitization when evaluating the effects of allergen exposures on subclinical pulmonary

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      Gender has been considered as a factor influencing FeNO levels.7,18 However, other studies are in agreement with the results of the present study, which did not find a significant association between FeNO and gender.4 Atopic dermatitis has been previously considered a condition influencing FeNO levels,3 although our regression model has rejected its relevance.

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      For example, higher FeNO values were recently identified as a strong predictor of exacerbations in the autumn but not the other seasons.9 Furthermore, a recent birth cohort study found that allergic sensitization to indoor allergens, such as cat, dog, and house dust mite, predicted higher FeNO levels in children, but levels were highest in those children who were not only sensitized but also exposed to the allergen during long periods of sedentary behavior.10 Although studies have shown associations among high FeNO levels (ie, ≥50 ppb), current asthma symptoms, and exacerbations,11 clinical trials of FeNO-guided management have yielded conflicting results.

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    Supported by National Institutes of Health grants AI35786 and ES07036.

    Disclosure of potential conflict of interest: D. K. Milton and D. R. Gold have received research support from the National Institutes of Health. The rest of the authors have declared that they have no conflict of interest.

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