Among children with a history of wheeze at the beginning of the study, an increased risk of asthma was associated with gerbils or hamsters and birds as pets, and a decreased risk was associated with any pest in the home and with mildew (Tables 3–4).
For those associations for which the 95% confidence interval did not include 1.0, each model was further adjusted for baseline BMI, maternal smoking, history of allergies, family history of asthma, membership in an insurance plan, and SES. There was evidence of confounding only among children with a history of wheeze at study entry, for whom the RR associated with pet gerbils or hamsters increased to 3.1 (95% CI = 1.6–6.0), and the RRs associated with a pet bird and mildew decreased to 1.4 (95% CI = 0.8–2.4) and 0.5 (95% CI = 0.3–0.8), respectively.
Our results suggest that there are identifiable indoor environmental exposures that increase the risk of development of asthma among adolescents. Among children with no prior history of wheeze at baseline, there can be little doubt as to the temporal association between exposure and asthma, because children with no history of wheeze were unlikely to have had undiagnosed asthma at study entry. The association with pets, and particularly dogs, is consistent with those of some cross-sectional and case-control studies. 15,29 Other cross-sectional studies, in which allergen in house dust was measured, have found either no association with pet (or any other indoor allergen) exposure in children, 19 or a protective effect. 30 These results might have resulted from families getting rid of pets when the child developed asthma. However, two prospective studies of young children have also not found pets to be associated with asthma. 21,22
One explanation for the inconsistencies among studies might be that pets have different effects at different ages. For example, an exposure early in life to endotoxin associated with pets might result in a protective shift in the immune system from a T-helper-2 cell to a T-helper-1 cell response, 31,32 whereas exposure to pets later in life might be associated with asthma. Other immunologic mechanisms for the development of tolerance at high allergen exposure among children have also been proposed. 33 In adults, a pet in the home has been associated with increased risk of pet-specific sensitization, but pet ownership in childhood has been associated with less atopy and less pet-specific sensitization in adulthood, an observation which would be consistent with different risks of pet exposure for allergic disease at different ages. 34,35 Although we had good information on age of onset of asthma in this study, participants were not asked at what age the child was first exposed to pets.
A potential explanation for the absence of an association of cats with asthma in our study is the misclassification of cat allergen exposure based on questionnaire, because cat allergen is likely to be found in public places and in homes without cats. 36
The increased risk associated with humidifier use, also observed in previous epidemiologic studies of children, 17,37 could have been caused by an increase in house dust mite allergen, which is common in humid homes, 38–41 or by conditions which may favor the growth of mold in the home environment or in the humidifier itself. 41 Clinical and limited laboratory studies have established the potential of humidifiers to grow mold 42 and to exacerbate asthma both in the occupational 43 and in the home environment. 44 Humidifiers have also been associated with endotoxin exposure in the home. 13 We considered the possibility that homes may have had humidifiers to treat symptoms of children with other early respiratory manifestations of asthma, but in whom wheezing had not been recognized or reported at baseline. The association with humidifier use persisted in our study after restricting the analysis to children who did not have a history of other respiratory illness (bronchitis or chronic cough that lasted for more than 3 months in the previous year, or frequent congestion in the chest or production of phlegm) at baseline. In addition, the risk associated with a humidifier in the home in children with newly diagnosed asthma in the first year of follow-up (RR = 1.9), who may have been more likely to have already had asthma at baseline, differed little from that in children diagnosed in later years (RR = 1.6). Therefore, it seems unlikely that a humidifier in the home was an indicator of undiagnosed asthma at baseline.
Although this study is prospective, the temporal relation of observed associations between risk factors and asthma among children with a history of wheezing at study entry may not be clear. Associations with asthma observed in this group may have resulted from families with more symptomatic children at baseline having intervened to reduce exposures which they believed exacerbated wheeze. For example, these families may have substituted unusual pets, such as gerbils, hamsters, or birds, for dogs. The evidence for effect modification by wheeze is not altogether convincing, because the estimated effects of indoor risk factors had wide and overlapping confidence intervals among wheezy and never wheezy children; nonetheless, these results suggest that prospective studies of the primary causes of asthma should examine children with and without wheeze at study entry separately.
The incidence of newly reported asthma at 2.4% per year is substantial. It may be compared with the cumulative incidence of 12.0% observed among a slightly younger cohort of children followed between ages 6 and 11 in Tucson, Arizona. 8 In a 25-year follow-up, self-reported asthma during the previous 12 months was reported by 10.8% of adults who had no history of asthma or wheezy illness at age 7. 6 However, in other studies of adolescents considerably lower incidence of asthma has been found. 2,45,46 As different methods have been used for ascertainment of asthma in these various studies, it is difficult to determine whether reported differences reflect the true variation in asthma incidence in the various populations.
The many indoor exposures evaluated were selected because they have been reported to be associated with prevalent asthma, or with incident asthma at young age. 14,16,17 The cross-sectional associations of history of wheeze at study entry with pets, pests, and other indicators of indoor allergens, as well as current maternal smoking and the use of wood for heating, suggest that there may be associations of these risk factors with a history of undiagnosed asthma in this population. In contrast, we identified relatively few predisposing indoor risk factors for the new diagnosis of asthma in adolescence. It may be that indoor environment is less important in the etiology of asthma in adolescence than it is in younger years, or it may be that power was too limited because of a small number of new diagnoses. For many risk factors examined in this study, very large (or small) proportions of children were exposed (for example, to carpet and gas stoves), limiting the power to detect an increase in asthma. In addition, the measurement of exposures to indoor pollutants by questionnaire may be relatively imprecise. 19 However, it is likely that the result of questionnaire assessment of indoor exposure in this study would have been nondifferential (at least among parents of children with no history of wheeze at baseline), and it is possible that more precise measurement of exposure would have identified additional associations or strengthened the observed associations.
Another limitation to this study is potential misclassification of asthma, which could be affected by access to care and differences in diagnostic practice between physicians, 47 or by poor reporting by children or parents. However, subject report of physician-diagnosed asthma has been widely used in epidemiologic studies of children, 28 and the validity as assessed by repeatability of response is good. 48,49 Self-report has been found to reflect what physicians actually reported to patients, at least in adults, 50,51 and physician assessment of asthma has been recommended as the gold standard for this disease, for which a more precise diagnosis is not available. 52 Nevertheless, it is also possible that classification of individuals based on measurement of physiologic responses characteristic of asthma, such as bronchial hyperreactivity, or based on a standardized clinical examination, might have strengthened observed associations with indoor risk factors. When we limited the analysis to those cases of asthma for which an inhaler was reportedly used (and which may, therefore, have been more severe, or more likely to be true cases of asthma), the observed associations with indoor risk factors were, in general, stronger. The RRs increased slightly for presence of dogs (to 1.6) and humidifier use (to 2.1) among children without wheeze.
The strength of this study was the ability to identify indoor risk factors for the development of asthma among adolescents with no baseline history of wheezing. This population is also one for which there are few previous prospective studies that could identify risk factors amenable to preventive efforts. Among children without wheeze, there was an increased risk of asthma associated with a humidifier or a pet, especially a dog, in the home. These potentially remediable causes of childhood asthma were common in this population; thus, 32% of asthma among children with no history of wheeze at baseline was attributable to pets, a proportion similar to that estimated from a recent analysis of the Third National Health and Nutrition Examinations Survey. 15
We thank David Bates for his advice and thoughtful comments, and the External Advisory Committee, composed of Morton Lippmann, Jonathan Samet, John Spengler, Frank Speizer, James Whittenberger, Arthur Winer, and Scott Zeger, for its input. We acknowledge the hard work of the study field team and the cooperation of the 12 communities, the school principals, the many teachers, the students, and their parents. Programming support was provided by Isabelo Manila.
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