Respiratory illnesses in early life and asthma and atopy in childhood.

BACKGROUND: The relation between respiratory illnesses in early life and the development of asthma and atopy in childhood is incompletely understood. OBJECTIVE: We sought to examine the relationship between respiratory illnesses in early life and atopic diseases at school age. METHODS: We performed a prospective birth cohort study of the relationship between respiratory illnesses in the first year of life and asthma, atopy (sensitization to >or=1 allergen), and allergic rhinitis at school age in 440 children with a parental history of atopy. Logistic regression was used to examine the relationship between respiratory illnesses and asthma, atopy, and allergic rhinitis. The relationship between respiratory illnesses in early life and repeated measures of wheezing between the ages of 1 and 7 years was investigated by using a proportional hazards models. RESULTS: Physician-diagnosed croup (adjusted odds ratio [OR], 0.30; 95% CI, 0.12-0.72) and having 2 or more physician-diagnosed ear infections (adjusted OR, 0.58; 95% CI, 0.35-0.98) in the first year of life were inversely associated with atopy at school age. Physician-diagnosed bronchiolitis before age 1 year was significantly associated with asthma at age 7 years (adjusted OR, 2.77; 95% CI, 1.23-6.22). Recurrent nasal catarrh (>or=3 episodes of a runny nose) in the first year of life was associated with allergic rhinitis at age 7 years (adjusted OR, 2.99; 95% CI, 1.03-8.67). CONCLUSION: The relationship between early-life respiratory illnesses and asthma and atopy is complex and likely dependent on the type of infection and immune response it initiates. CLINICAL IMPLICATIONS: Certain respiratory illnesses in early life modify the risk of atopy and asthma at school age.

Sensitization to aeroallergens and airway hyperresponsiveness at 7 years of age.

STUDY OBJECTIVES: To investigate the relationship between current and early life factors and airway responsiveness to inhaled methacholine in children with a median age of 7.0 years. PARTICIPANTS: Study subjects were a subset of a prospective birth cohort of children in the Boston area at high risk for atopy. METHODS: One hundred thirty-one children underwent both skin-prick testing to a panel of aeroallergens and a methacholine challenge test between 6.5 years and 8.8 years of age. Telephone questionnaires were performed at set intervals, and home dust samples were collected in the first year of life. RESULTS: Of the 131 participating children, 51% (67 patients) had at least one positive skin-prick test response and 28% (37 patients) had airway hyperresponsiveness (AHR) [provocative concentration of methacholine causing a 20% fall in FEV(1) of < 4 mg/mL]. After adjusting for relevant covariates, AHR was strongly associated with sensitization to at least four aeroallergens (odds ratio [OR], 13.41; 95% confidence interval [CI], 3.03 to 59.42). In separate adjusted models, sensitization to cat (OR, 14.73; 95% CI, 3.64 to 59.55), dust mite (OR, 5.13; 95% CI, 1.94 to 13.56), cockroach (OR, 4.00; 95% CI, 1.19 to 13.50), and ragweed (OR, 10.08; 95% CI, 2.31 to 44.10) were significant predictors of AHR. However, no relationship was found with early life exposure to perennial aeroallergens or other perinatal and first-year-of-life factors. CONCLUSIONS: Among young children at risk for atopy, sensitization to specific aeroallergens, but not early life exposures, is associated with increased airway responsiveness.

Mouse exposure and wheeze in the first year of life.

BACKGROUND: Studies have found that exposure to mice is highly prevalent among children with asthma living in urban areas. OBJECTIVE: To examine the relationship between exposure to mice and wheeze in the first year of life. METHODS: We conducted an ongoing prospective birth cohort study of 498 children with a history of allergy or asthma in at least 1 parent living in metropolitan Boston (the Home Allergens and Asthma Study). RESULTS: In a multivariate analysis, infants whose parents reported exposure to mice in the household had nearly twice the odds of developing any wheeze in the first year of life as children without exposure (odds ratio [OR], 1.83; 95% confidence interval [CI], 1.14-2.95; P = .01). Other variables associated with wheeze in the first year of life included low birth weight (OR, 1.77; 95% CI, 1.06-2.95; P = .03), having at least 1 lower respiratory tract illness (OR, 5.59; 95% CI, 3.46-9.04; P < .001), exposure to high levels of endotoxin at age 2 to 3 months (fourth quartile compared with first quartile: OR, 2.32; 95% CI, 1.19-4.54; P = .01), and exposure to cockroach allergen of 0.05 U/g of dust or more at age 2 to 3 months (OR, 1.83; 95% CI, 1.09-3.08; P = .02). CONCLUSION: Among children with a parental history of asthma or allergies, exposure to mice is associated with wheeze in the first year of life, independent of other factors.

Polymorphisms in the 5' region of the CD14 gene are associated with eczema in young children.

BACKGROUND: Variants in the CD14 gene (CD14) are hypothesized to be associated with atopic disorders. However, most studies have only investigated one polymorphism in this gene. OBJECTIVE: We sought to study the association of 5 single nucleotide polymorphisms (SNPs) in the 5' flanking region of CD14 with eczema and serum IgE levels in young children. METHODS: We genotyped 5 SNPs in an approximately 6.5-kb region in the 5' region of CD14 in 344 2-year-old white children from 2 birth cohorts in the northeastern United States. We examined the relation of both single SNPs and haplotypes in CD14 with the atopic outcomes. RESULTS: Two SNPs were significantly associated with eczema. In dominant models adjusted for potential confounders, SNP rs2569193 was associated with significantly decreased risk for eczema (odds ratio [OR] for CT/TT vs CC, 0.5; 95% CI, 0.3-0.8), whereas SNP rs2569190 (also reported as the C-159T) was associated with significantly increased risk for eczema (OR for CT/TT vs CC, 2.3; 95% CI, 1.4-3.8). The CT/TT genotypes of SNP rs2569190 also had higher geometric means of serum IgE than the CC genotype (24.6 vs 15 IU/mL, P = .025). Haplotype analyses provided results similar to those of the single SNP analyses. CONCLUSIONS: Our results contradict previous reports that have found a protective effect of the T allele of SNP rs2569190 (C-159T) against atopic disorders. Nevertheless, these results confirm the importance of polymorphisms in CD14 in the development of atopy, and future studies of this gene region will need to account for linkage disequilibrium and environmental exposures unique to the study population.

Variation in total and specific IgE: effects of ethnicity and socioeconomic status.

BACKGROUND: Asthma is common in minority and disadvantaged populations, whereas atopic disorders other than asthma appear to be less prevalent. It is unclear whether the same holds true for objective markers of sensitization. OBJECTIVE: To determine the association of asthma, atopic disorders, and specific sensitization with race and socioeconomic factors. METHODS: We analyzed total and specific IgE among 882 women (577 white, 169 black, and 136 Hispanic) who delivered a child at a large tertiary hospital in Boston, Mass, and who were screened for participation in a family and birth cohort study. Race/ethnicity and other characteristics were obtained from screening questionnaires. Addresses were geocoded, and 3 census-based geographic area socioeconomic variables were derived from block group information from the 1990 US Census. RESULTS: Black and Hispanic women were more likely to come from areas with low socioeconomic indicators and were more likely to have asthma than white women. However, these women were less likely to have hay fever and eczema than their white counterparts. Compared with white women, black women had higher mean total IgE levels; had greater proportions of sensitization to indoor, outdoor, and fungal allergens; and were more than twice as likely to be sensitized to > or =3 aeroallergens. CONCLUSION: The racial/ethnic disparities in atopic disorders may represent either underdiagnosis or underreporting and suggest that allergy testing may be underused in some populations. Differences in total IgE levels and specific allergen sensitization are likely a result of the complex interplay between exposures associated with socioeconomic disadvantage.

Predictors of disease severity in children with asthma in Hartford, Connecticut.

Childhood asthma is a major public health problem in the United States, particularly among minority populations. The aim of our study was to examine the relationship among ethnicity, allergen sensitization, spirometric measures, and asthma severity in children with mild to severe asthma who received their medical care in Hartford, Connecticut. Four hundred thirty-eight children aged 4-18 years who were enrolled in an asthma care program (Easy Breathing) in Hartford and who were referred for spirometry and allergy skin testing participated in this cross-sectional study. Risk factors for increased asthma severity as defined by National Asthma Education and Prevention Program (NAEPP) guidelines were determined using multinomial logistic regression. Of 438 children, 383 (87.4%) had mild to moderate asthma, and 292 (66.7%) had at least one positive skin test to allergens. Forced expiratory volume in 1 sec/forced vital capacity (FEV1/FVC) was significantly decreased in children with severe vs. mild asthma (80.7 vs. 87.3, respectively). In a multivariate analysis, predictors of severe asthma included African-American ethnicity (odds ratio (OR)=3.70, 95% confidence interval (CI)=1.10-12.42), Puerto Rican ethnicity (OR=3.55, 95% CI=1.18-10.67), sensitization to cockroach allergen (OR=4.34, 95% CI=1.73-10.86), and decreased FEV1/FVC (OR for every 1% decrease in FEV1/FVC=1.06, 95% CI=1.02-1.11). In conclusion, among children with asthma in Hartford and its surrounding communities, predictors of disease severity included African-American ethnicity, Puerto Rican ethnicity, sensitization to cockroach allergen, and decreased FEV1/FVC. Our findings suggest that FEV1/FVC is a useful indicator of asthma severity in children.

Low-normal gestational age as a predictor of asthma at 6 years of age.

BACKGROUND: Perinatal factors, including gestational age and birth weight, influence the development of atopy in early life. However, the role of these factors in the development of asthma in later life among children who do not develop perinatal respiratory disease remains unclear. METHODS: Four hundred fifty-four infants who had a history of allergy or asthma in at least 1 parent, were born in the 36th week of gestation or later, and did not develop perinatal respiratory distress were monitored for at least 6 years. Associations between predictor variables and asthma and wheeze were assessed with multivariate logistic regression and repeated-event analyses. RESULTS: Although we previously observed a relationship between low birth weight and persistent wheeze in the first 1 year of life, we did not observe similar associations between low birth weight and asthma at 6 years of age (odds ratio [OR]: 1.05; 95% confidence interval [CI]: 0.40-2.73). However, a strong relationship was found between low-normal gestational age and asthma at 6 years of age (OR: 4.7; 95% CI: 2.1-10.5). The effects of low-normal gestational age were significantly greater among boys than among girls (boys: OR: 8.15; 95% CI: 2.98-22.3; girls: OR: 1.90; 95% CI: 0.38-13.83). Longitudinal analysis of the relationship between gestational age and wheeze during the 6 years of observation confirmed these gender differences. CONCLUSIONS: Among children at high risk of developing atopic disease, late prematurity might be an important additional determinant of asthma later in life, and these effects are gender specific.

Endotoxin exposure and eczema in the first year of life.

OBJECTIVE: Exposure to endotoxin in early life has been proposed as a factor that may protect against the development of allergic diseases such as eczema. The objective of this study was to examine the relation between endotoxin exposure in early life and eczema in the first year of life in children with parental history of asthma or allergies. METHODS: This study used a prospective birth cohort study of 498 children who had a history of allergy or asthma in at least 1 parent and lived in metropolitan Boston. A subset of 401 living rooms had house dust samples adequate for analysis of endotoxin. RESULTS: In multivariate analyses adjusting for gender, income, and season of birth, endotoxin levels in the living room at 2 to 3 months of age was inversely associated with physician- or nurse-diagnosed eczema in the first year of life (odds ratio [OR] for each quartile increment: 0.76; 95% confidence interval [CI]: 0.61-0.96). Exposure to a dog in the home at age 2 to 3 months was also inversely associated with eczema in the first year of life, but the CI widened when endotoxin was included in the multivariate model (OR: 0.54; 95% CI: 0.27-1.09). Other variables associated with eczema in the first year of life included paternal history of eczema (OR: 1.91; 95% CI: 1.03-3.55) and maternal specific immunoglobulin E positivity to > or =1 allergen (OR: 1.61; 95% CI: 1.01-2.56). CONCLUSIONS: Among children with parental history of asthma or allergies, exposure to high levels of endotoxin in early life may be protective against eczema in the first year of life. In these children, paternal history of eczema and maternal sensitization to at least 1 allergen are associated with an increased risk of eczema in the first year of life.

Ethnicity and skin test reactivity to aeroallergens among asthmatic children in Connecticut.

OBJECTIVES: To examine the relationship between ethnicity and sensitization to allergens among children with asthma living in urban and suburban areas of Connecticut. STUDY DESIGN: Cross-sectional study. STUDY POPULATION: A total of 791 children with mild-to-severe asthma who received their medical care in the city of Hartford. RESULTS: Puerto Rican ethnicity was associated with skin test reactivity (STR) to cockroach (odds ratio [OR], 3.3; 95% confidence interval [CI], 1.7 to 6.4), STR to dust mite (OR, 1.7; 95% CI, 1.2 to 2.4), STR to mixed grass pollen (OR, 1.7; 95% CI, 1.1 to 2.7), and STR to mugwort/sage (OR, 2.4; 95% CI, 1.4 to 4.1). African-American ethnicity was associated with STR to four outdoor allergens (ie, mixed tree pollen [OR, 2.3; 95% CI, 1.3 to 3.9], mixed grass pollen [OR, 2.7; 95% CI, 1.6 to 4.8], mugwort/sage [OR, 3.1; 95% CI, 1.6 to 6.0], and ragweed [OR, 2.1; 95% CI, 1.2 to 3.8]). Among all children, STR to outdoor allergens was strongly associated with the extent of allergen sensitization. As an example, children sensitized to mixed grass pollen had 34.7 times higher odds of having at least four positive skin tests to other allergens than nonsensitized children (95% CI for OR, 15.6 to 77.0). CONCLUSIONS: Our findings suggest that Puerto Rican ethnicity is associated with an increased risk of sensitization to indoor and outdoor allergens among children with asthma, and that allergy skin testing should be performed more often as part of the management of asthma in African-American children and in Puerto Rican children in the United States.

The relevance of maternal immune responses to inhalant allergens to maternal symptoms, passive transfer to the infant, and development of antibodies in the first 2 years of life.

BACKGROUND: Asthma and other atopic diseases are strongly hereditary. Although the mother might play a special role, the mechanisms for such an effect are not clear. OBJECTIVE: We sought to investigate the influence of maternal immune responses to cat and mite allergens on (1) maternal symptoms, (2) the development of immune responses in the infant, and (3) the development of allergic disease during the first 3 years of life. METHODS: In sera from 465 mothers and 424 infants (cord blood), as well as in sera from 230 of the children at age 2 to 3 years, total IgE and IgE antibodies were measured by using CAP testing; IgG and IgG4 antibodies for the cat allergen Fel d 1 were measured by means of radioimmunoprecipitation. RESULTS: In both mothers and children, approximately 15% of sera contained IgG antibodies to Fel d 1 without IgE antibodies to cat. The strongest predictor of the maternal IgG antibody response was exposure to greater than 8 microg of Fel d 1/g of dust. Thus approximately 70% of children living in a house with a cat had received IgG antibodies from their mothers. In many cases the infant received IgG and IgG4 antibodies to Fel d 1 from a nonallergic mother. Maternal IgE antibodies were consistently associated with asthma; by contrast, the IgG antibody was not independently related to asthma but was related to rhinitis in the mothers (odds ratio, 2.6; 95% CI, 1.1-6.2) and to eczema in children. At age 3 years, 13 of 230 sera contained IgE antibodies to mite, but only 5 had IgE antibodies to cat. CONCLUSIONS: A significant proportion (approximately 15%) of mothers and children exposed to high concentrations of cat (but not mite) allergens have serum IgG antibodies without IgE antibodies. This IgG antibody is freely transferred to the infant and might influence IgG antibody production in the child. The results indicate the importance of understanding the mechanisms of tolerance to cats and raise questions about the independent role of the mother in the inheritance of allergy.

Day care attendance in early life, maternal history of asthma, and asthma at the age of 6 years.

Among children not selected on the basis of a parental history of atopy, day care attendance in early life is inversely associated with asthma at school age. We examined the relation between day care in the first year of life and asthma, recurrent wheezing, and eczema at the age of 6 years and wheezing in the first 6 years of life among 453 children with parental history of atopy followed from birth. Among all study participants, day care in the first year of life was inversely associated with eczema (odds ratio [OR] = 0.3, 95% confidence interval [CI] = 0.1-0.8). Day care attendance in early life was associated with a decreased risk of asthma (OR = 0.3, 95% CI = 0.1-0.7) and recurrent wheezing (OR = 0.3, 95% CI = 0.1-0.9) at the age of 6 years and with a decreased risk of any wheezing after the age of 4 years only among children without maternal history of asthma. Among children with maternal history of asthma, day care in early life had no protective effect on asthma or recurrent wheezing at the age of 6 years but was instead associated with an increased risk of wheezing in the first 6 years of life. Our findings suggest that maternal history of asthma influences the relation between day care-related exposures and childhood asthma.