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Preschool rhinovirus (RV) wheezing illnesses predict an increased risk of childhood asthma; however, it is not clear how specific viral illnesses in early life relate to lung function later on in childhood.To determine the relationship of virus-specific wheezing illnesses and lung function in a longitudinal cohort of children at risk for asthma.Two hundred thirty-eight children were followed prospectively from birth to 8 years of age. Early life viral wheezing respiratory illnesses were assessed by using standard techniques, and lung function was assessed annually by using spirometry and impulse oscillometry. The relationships of these virus-specific wheezing illnesses and lung function were assessed by using mixed-effect linear regression.Children with RV wheezing illness demonstrated significantly decreased spirometry values, FEV(1) (P = .001), FEV(0.5) (P.001), FEF(25-75) (P.001), and also had abnormal impulse oscillometry measures--more negative reactance at 5 Hz (P.001)--compared with those who did not wheeze with RV. Children who wheezed with respiratory syncytial virus or other viral illnesses did not have any significant differences in spirometric or impulse oscillometry indices when compared with children who did not. Children diagnosed with asthma at ages 6 or 8 years had significantly decreased FEF(25-75) (P = .05) compared with children without asthma.Among outpatient viral wheezing illnesses in early childhood, those caused by RV infections are the most significant predictors of decreased lung function up to age 8 years in a high-risk birth cohort. Whether low lung function is a cause and/or effect of RV wheezing illnesses is yet to be determined.

Factors affecting fractional exhaled nitric oxide (FeNO) in early childhood are incompletely understood.To examine the relationships between FeNO and allergic sensitization, total IgE, atopic dermatitis, rhinitis, asthma, and lung function (spirometry) in children.Children at high risk of asthma and other allergic diseases because of parental history were enrolled at birth and followed prospectively. FeNO was measured by an online technique at ages 6 and 8 years. Relationships among FeNO, various atopic characteristics, and asthma were evaluated.Reproducible FeNO measurements were obtained in 64% (135/210) of 6-year-old and 93% (180/194) of 8-year-old children. There was seasonal variability in FeNO. Children with aeroallergen sensitization at ages 6 and 8 years had increased levels of FeNO compared with those not sensitized (geometric mean; 6 years, 10.9 vs 6.7 parts per billion [ppb], P.0001; 8 years, 14.6 vs 7.1 ppb, P.0001). FeNO was higher in children with asthma than in those without asthma at 8 years but not 6 years of age (6 years, 9.2 vs 8.3 ppb, P = .48; 8 years, 11.5 vs 9.2 ppb, P = .03). At 8 years of age, this difference was no longer significant in a multivariate model that included aeroallergen sensitization (P = .33). There were no correlations between FeNO and spirometric indices at 6 or 8 years of age.These findings underscore the importance of evaluating allergen sensitization status when FeNO is used as a potential biomarker in the diagnosis and/or monitoring of atopic diseases, particularly asthma.

The contribution of viral respiratory infections during infancy to the development of subsequent wheezing and/or allergic diseases in early childhood is not established.To evaluate these relationships prospectively from birth to 3 years of age in 285 children genetically at high risk for developing allergic respiratory diseases.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.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).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.

Background Exposure to furred pets might confer protection against the development of allergic sensitization through a mechanism that is incompletely understood. Objective The objective of this study was to determine the effects of pet exposure and genotype on immunologic development and the incidence of atopic markers and diseases in the first year of life. Methods Pet exposure in the home was compared with cytokine secretion patterns (mitogen-stimulated mononuclear cells at birth and age 1 year) and indicators of atopy (allergen-specific and total IgE, eosinophilia, food allergy, atopic dermatitis) in 285 infants. Interactions with genotype at the CD14 locus were also evaluated in the data analyses. Results Exposure to dogs was associated with reduced allergen sensitization (19% vs 33%, P = .020) and atopic dermatitis (30% vs 51%, P CD14 locus ( P = .006), even after adjusting for exposure to dogs ( P = .003). Furthermore, infants with the genotype −159TT were less likely to develop atopic dermatitis if they were exposed to a dog (5% vs 43%, P = .04). Last, dog exposure was associated with increased IL-10 (117 vs 79 pg/mL, P = .002) and IL-13 (280 vs 226 pg/mL, P = .013) responses at age 1 year. Conclusions Having a dog in infancy is associated with higher IL-10 and IL-13 cytokine secretion profiles and reduced allergic sensitization and atopic dermatitis. These findings suggest that postnatal exposure to dogs can influence immune development in a genotype-specific fashion and thereby attenuate the development of atopy in at-risk children.

Background Allergic diseases have been linked to abnormal patterns of immune development, and this has stimulated efforts to define the precise patterns of cytokine dysregulation that are associated with specific atopic phenotypes. Objective Cytokine-response profiles were prospectively analyzed over the first year of life and compared with the clinical and immunologic expressions of atopy. Methods Umbilical cord and 1-year PBMCs were obtained from 285 subjects from allergic families. PHA-stimulated cytokine-response profiles (IL-5, IL-10, IL-13, and IFN-γ) were compared with blood eosinophil counts and total and specific IgE levels (dust mites, cat, egg, Alternaria species, peanut, milk, and dog) at age 1 year and at the development of atopic dermatitis and food allergy. Results For the cohort as a whole, cytokine responses did not evolve according to a strict T H 1 or T H 2 polarization pattern. PHA-stimulated cord blood cells secreted low levels of IL-5 (2.1 pg/mL), moderate levels of IFN-γ (57.4 pg/mL), and greater amounts of IL-13 (281.8 pg/mL). From birth to 1 year, IL-5 responses dramatically increased, whereas IL-13 and IFN-γ responses significantly decreased. Reduced cord blood secretion of IL-10 and IFN-γ was associated with subsequent sensitization to egg. In addition, there was evidence of T H 2 polarization (increased IL-5 and IL-13 levels) associated with blood eosinophilia and increased total IgE levels by age 1 year. Conclusion These findings demonstrate that cytokine responses change markedly during the first year of life and provide further evidence of a close relationship between T H 2 skewing of immune responses and the incidence of atopic manifestations in children.