This study reports data on children from birth through 17 years of age collected in round 1 of the KCRHS, which began in 1994 and ended in 1998. Keokuk County was chosen because it is intensely agricultural and entirely rural. A stratified, random sample that identified households from farm, town, and rural nonfarm locations was used. A total of 2,496 eligible households were identified. Details regarding the sampling methodology and survey methods have been reported previously (Merchant et al. 2002). All members of enrolled households were invited to a centrally located research facility for interviews, and all adults and children ≥8 years of age were invited for medical examinations. One adult per household was interviewed by a trained interviewer about the health of all of the children (from birth but < 18 years of age) living in the household.

The childhood respiratory questionnaire chosen for this study was that used in University of Southern California studies of childhood asthma in Los Angeles (Peters et al. 1999). We used four asthma outcomes to estimate asthma prevalence—doctor-diagnosed asthma, asthma/medication for wheeze (doctor-diagnosed asthma and/or medication for wheeze in the last 12 months), current wheeze, and cough with exercise. These four asthma outcomes, severe symptoms consistent with asthma, atopy, an early respiratory illness, and a high-risk birth are fully defined in the definition section of the online version this article. The parent’s response to the questionnaire also provided information regarding parental farm exposures, maternal smoking during pregnancy, household exposure to tobacco smoke, parental education, and household income.

Children ≥8 years of age were invited to complete a medical examination that included skin prick testing (SPT), spirometry, methacholine challenge testing, and height and weight measurements to calculate 95th percentile body mass index (kilograms per square meter) (Must et al. 1991). A total of 18 aeroallergens common to the Midwest, a histamine-positive and normal saline-negative control, were used for SPTs. Common rural aeroallergens included tree pollen mix, grass pollen mix, ragweed pollen, weed pollen mix, cockroach mix, mold mix, insect mix, caddis fly/moth/mayfly mix, cat pelt, dog hair, mouse and rat mix, and dust mite Der f and Der p mix. Farm aeroallergens included grain dust mix or grain smut mix, soybean dust or soybean whole grain, cattle hair, horse hair, chicken feathers, and turkey feathers. Children taking antihistamines and other medications known to affect skin test results, those with histories of past systemic reactions to allergy skin testing, and any participant who might have been pregnant were excluded from skin testing. A wheal ≥3 mm in diameter was defined as a positive reaction; subjects were considered atopic by SPT if they had a positive reaction to any two of the allergens tested. Spirometry was completed on a rolling-seal spirometer that conformed to American Thoracic Society (1995) guidelines. Contraindications to methacholine testing included participants with a baseline forced expiratory volume in 1 sec (FEV₁) of < 70% of predicted or FEV₁ < 1.5 L, pregnancy or suspected pregnancy, lactation, current use of a β-adrenergic blocking agent, and a decline in FEV₁ of ≥15% to the diluent. Methacholine was administered by dosimeter in five serial doses of 0.025, 0.25, 2.5, 10.0, and 25.0 mg/mL, with 3 min between doses (Crapo et al. 2000). Bronchial hyperresponsiveness was defined as having a drop in FEV₁ of ≥20% from the postsaline control (PC20), following inhalation of ≤8 mg/mL of methacholine (Anto 1998; Crapo et al. 2000).

Sera were collected from subjects (n = 217) at the time of SPT and analyzed for total and specific IgE. Total IgE was measured by immunoassay using murine monoclonal anti-human IgE as the capture antibody (CLB, Sanguin Blood Supply Foundation, Amsterdam, the Netherlands), rabbit anti-human IgE as the second antibody (Dako, Corp., Carpinteria, CA), and peroxidase-conjugated donkey anti-rabbit IgG as the labeling antibody (Research Diagnostics, Inc., Flanders, NJ) in a TMB substrate system (Pierce Endogen, Rockford, IL). Standard curves were generated using an IgE CAP system standards (Pharmacia Diagnostics, Uppsala, Sweden) with the standard curve from 0.02 to 10 kU/L. Sera were studied at initial dilutions of 1:20, 1:40, 1:80, and 1:160, with higher dilutions run for high IgE sera. Individuals were considered to be atopic by IgE if their total IgE was ≥60 kU/L (Contreras et al. 2003).

An industrial hygienist visited each household shortly after the clinic visit and completed a home environmental questionnaire and checklist, when applicable a farm environmental questionnaire and farm environmental checklist, and measurement of a limited number of environmental parameters. Details of these environmental assessments have been published previously (Park et al. 2003; Reynolds et al. 1997b). Assessments of specific environmental exposures were taken from these instruments, including several farm operation questions, livestock and antibiotics in animal feed questions, and questions regarding gas stoves, heating with wood, exposure to pesticides, exposure to cats and dogs as pets, and dehumidifier use.

Household type was determined at the time of the child’s birth from the biologic mother’s reproductive history questionnaire and through follow-up phone interviews with the biologic mother regarding residence type (farm, rural nonfarm, or home) at the time of birth. Children’s various farm tasks and the age each task was first performed were determined from a questionnaire on childhood tasks from available KCRHS round 2 data and from follow-up phone administration of this questionnaire to round 1 participants who had not participated in round 2.

Chi-squared tests and analysis of variance were used to evaluate any differences among demographic, personal, and environmental risk factors for farm, rural non-farm, and town households. Univariable logistic regression was used to identify variables that were significant (p < 0.1) for doctor-diagnosed asthma, asthma/medication for wheeze, chronic wheeze, and cough with exercise. Multivariable logistic regression was then used to identify significant (p < 0.05) variables in the final models.

Initial data analyses was performed with SAS (version 8; SAS Institute, Inc., Cary, NC) software. SUDAAN software (Research Triangle Institute, Research Triangle Park, NC) was then used to adjust variance estimates for potential intrahousehold correlation resulting from the inclusion of more than one child per household.

The study was approved annually by The University of Iowa institutional review board. A parent or legally authorized representative of each child participant provided written informed consent. Children 8–17 years of age gave their assent.

Of the 2,496 Keokuk County households eligible for this study, 1,675 households (67.1%) initially contacted by letter and telephone agreed to participate immediately or to be contacted at a later date. Enrollment stopped when the goal of 1,000 households was reached. A total of 1,004 households (336 farm, 206 rural non-farm, 462 town households) enrolled and participated in round 1 of the study.

The cohort, which consisted of 644 children (224 farm, 155 rural nonfarm, and 265 town), did not differ in age among household types, was somewhat overrepresented by boys in farm and rural nonfarm households, and was 97.7% Caucasian. Of the 336 farms in the cohort, 109 had children. Complete data on all farming characteristics were available on 89 farms with children and on 172 farms without children. These farms produced primarily corn, soybeans, and hogs but very few other livestock. Farms with children were somewhat smaller (434 total acres in production) than farms without children (468 total acres in production) but were otherwise similar, except that farms with children on average raised more hogs (298 vs. 141, p = 0.03). Fifty percent of farm children were reported by a parent to perform tasks around hogs, compared with ≤16% for rural non-farm or town children, whereas 40% of farm children were reported to perform tasks around cows compared with ≤13% for rural nonfarm or town children.

Ninety-five percent of the children’s data were provided by the child’s biologic mother or female guardian. Complete data on asthma outcomes were available on 610 children. Concordance between the four asthma outcomes varied from strong to weak: doctor-diagnosed asthma (asthma/medication for wheeze κ = 0.81, p < 0.0001; current wheeze κ = 0.31, p < 0.0001; cough with exercise κ = 0.26, p < 0.0001), asthma/medication for wheeze (current wheeze κ = 0.53, p < 0.0001; cough with exercise κ = 0.39, p = 0.11; current wheeze and cough with exercise κ = 0.27, p = 0.73). Only 4.4% of participants were captured by all four asthma outcomes, whereas 33.6% of all 610 participants were captured by at least one asthma outcome. Children with doctor-diagnosed asthma included only a third (8 of 24) of the children with severe symptoms consistent with asthma, whereas children with any one of the four asthma outcomes captured 23 of 24 children with severe symptoms. Of the 394 children 8–17 years of age, 351 (89.1%) had SPT, 347 (88.1%) had pulmonary function tests, and 215 (61.2%) agreed to have blood drawn for sera. Agreement between total individual IgE and SPT results (Aspergillus, cat hair, cockroach, weed mix, tree pollen, Der p, and Der f) ranged from 72.8 to 89.1%.

Children who were born on a farm had a lower prevalence of atopy (IgE), a lower prevalence of diagnosed allergies and a higher forced vital capacity (likely attributable to hyperinflation) (Table 1). Children who currently lived on a farm were somewhat more likely to be boys and somewhat less likely to have diagnosed allergies (Table 1).

A very high proportion of children who lived on a farm at the time of study (currently lives on a farm) were born when their parents lived on a farm (born on a farm) and continued to live on a farm (data for those who lived on a farm during the first year of life or through age 5, or had a parent who continued to work on a farm, were also analyzed but not reported). Because univariable associations were similar for all farm versus nonfarm groups, only comparisons of born on a farm and currently living on a farm exposure results are presented (Table 2). Farm children were consistently exposed to less tobacco smoke but were more often exposed to wood stoves, conditions resulting in dehumidifier use, cats as pets, and application of pesticides outside the home. Farm children’s parents were more often better educated and had a household annual income of ≥$20,000 (Table 2).

Univariable associations among the four asthma outcomes and environmental risk factors are presented in Tables 3 and 4. A weak association was observed between doctor-diagnosed asthma and less parental education. A near significant association was observed between doctor-diagnosed asthma/medication for wheeze and living on a farm raising swine and a significant association with living on a farm that adds antibiotics to feed. No significant association was observed with environmental exposures and current wheeze, but significant negative associations were observed between cough with exercise and exposure to wood smoke and applied pesticides outside home in the last year, significant positive associations were observed with dogs as household pets, and near significant positive associations were observed with living on a swine farm and living on a farm that added antibiotics to feed. Tables 5 and 6 present univariable associations among the four asthma health outcomes and personal and clinical risk factors and health measures, which reveal similar association patterns but a few significant differences.

Multivariable models that included personal or environmental risk factors with univariable significance of p < 0.1 for any of the four asthma outcomes are presented in Table 7. In addition to sex, age, history of allergies, family history of allergies, premature birth, early respiratory infection, and high-risk birth, an interaction term (living on a farm that raised swine and added antibiotics to feed) was independently associated with asthma/medication for wheeze, current wheeze (p = 0.06), and cough with exercise. Of farms that raised swine, 24 of 43 (55.8%) added antibiotics to feed. Of livestock farms that add antibiotics to feed, 24 of 31 farms or 77.4% raise swine. Those farms that add antibiotics to feed were found to have larger mean numbers of livestock than those that did not add antibiotics to feed (750 vs. 392 animals; p = 0.0002). Examination of children who lived on farms raising swine and adding antibiotics to feed found that 55.8% (p = 0.013) reported at least one of the four asthma outcomes (Figure 1).