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Background: Exposure to furred pets in early life has been considered to increase the risk of allergic sensitization and consequent development of asthma later in children. However, recently, it has been suggested that early exposure to pets prevents sensitization. The aim of this study was to evaluate the importance of early exposure to pets and other environmental risk factors in asthmatic children.
Methods: This is a follow-up study after 2 years of a previously investigated group of 193 asthmatic children, aged 1–4 years. The study was completed by 181 children, who were clinically examined; serum IgE antibodies were also measured and a questionnaire was answered.
Results: Children with reported exposure to cats during the first 2 years of life were more likely to have developed sensitization to cat by 4 years of age than unexposed children. High levels of cat allergen (Fel d 1≥8 µg/g dust) were associated with an increased risk of sensitization to cat and, in combination with tobacco smoke, also with the development of more severe asthma.
Conclusions: In young asthmatic children, early exposure to cat and tobacco smoke increased the risk of allergic sensitization and further development of more severe asthma later in childhood.
Is early exposure to furred pets a risk factor for development of asthma and sensitization to these animals later in childhood? A recent review on the issue proposed that all exposure to pets in childhood involves a risk of sensitization and recommended that families with atopic members should postpone keeping of pets until the child is at least 2 years old (1). There are, however, entirely discordant views on the issue, since it has been claimed that early exposure to pets is associated neither with an increased risk of childhood asthma nor with development of IgE antibodies to pets; instead, a protective effect has been proposed (2–5). Several studies have clearly shown that atopic sensitization is a risk factor for asthmatic disease, but few have investi-gated the possibility of a stepwise development of sensitization due to allergen exposure and consequent disease (6–11).
In order to evaluate the importance of exposure to various indoor environmental risk factors in early childhood for the development of bronchial asthma, we performed a case-control study in 1990–2, including 193 children with asthma and 318 controls (12). Heredity for asthma, parental smoking, and signs of dampness at home were strongly associated with development of asthma, whereas exposure to cat and/or dog was not. However, the subgroup of asthmatics who were sensitized to cat and/or dog were overexposed to these animals relative to a population-based control group. In an extension of that study, sensitization to both cat and dog was found to be related to exposure to cat in a dose-dependent way. Furthermore, high levels of cat allergen in the home (≥8 µg/g dust), exposure to environmental tobacco smoke (ETS), and signs of home dampness were shown to increase independently the risk of sensitization to both cat and dog (13). Synergistic interaction of the risk factors was indicated in that the risk of sensitization to cat increased 40-fold when all three were present.
This is a 2-year follow-up study of the asthma cases. The aim was to evaluate the importance of early exposure to risk factors for continuous sensitization, mainly to cat and dog, and of disease characteristics, especially severity of asthma.
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The study comprised 138 boys and 43 girls. The mean age at follow-up was 49 months (34–71) (Table 1), or approximately 4 years. Twenty-three percent of the children had IgE antibodies to cat and 27% to dog, as compared to 23% to both cat and dog in study I. During the 2-year period between studies I and II, asthma symptoms had decreased. Thus, the proportion of children with few symptoms (i.e., symptoms of short duration only after allergen exposure or heavy exercise) had increased from 11% in study I to 42% in study II, while the proportion of children with inhaled steroid treatment had increased during the period (data not shown). High-dose exposure to furred pets had decreased; e.g., the keeping of cats fell from 14% to 7%, and the keeping of dogs from 8% to 4%. On the other hand, the reported low-dose exposure to pets, i.e., direct exposure outside the home, had increased. Fifty-six percent of the children were exposed to ETS at home in study I compared to 49% in study II.
Table 1. Background data on 181 asthmatic children from study I and study II, including data on reported exposure to pets and environmental tobacco smoke and IgE levels to cat and dog
| ||Age 0–2 years (study I)||Age 2–4 years (study II)|
|Age (months)||12–47|| || ||34–71|
|Age (months) mean||24|| || ||49|
|Cat at home||26||181||14||12||181||7|
|Cat high (other than at home)||13||181||7||13||181||7|
|Dog at home||14||181||8||7||181||4|
|Dog high (other than at home)||9||181||5||8||181||4|
|Tobacco smoking at home||102||181||56||89||181||49|
|IgE cat, RAST: <0.35 kU/l||124||162||77||110||143||77|
|IgE cat, RAST: 0.35–0.69 kU/l||15||162||9||4||143||3|
|IgE cat, RAST: ≥0.70 kU/l||23||162||14||29||143||20|
|IgE dog, RAST: <0.35 kU/l||120||156||77||101||138||73|
|IgE dog, RAST: 0.35–0.69 kU/L||14||156||9||6||138||4|
|IgE dog, RAST: ≥0.70 kU/l||22||156||14||31||138||23|
Risk factors for sensitization (RAST ≥0.35 kU/l) to cat and dog at the age of 4 years
The exposures for the risk factors under study from studies I and II were related to sensitization to cat and dog at the age of 4 years. As shown in Table 2, the exposure time period was split into two parts, period I – exposure from birth to the time for study I (approximately 0–2 years of age) – and period II – exposure during the time between study I and study II (approximately 2–4 years of age).
Table 2. Risk of being sensitized to cat at age of 4 years in relation to exposure to cats, ETS, and WPC from 0 to 4 years of age. Exposure time period was split into two parts: period I – exposure from birth to time for study I (approximately 0–2 years of age) – and period II – exposure during time between study I and study II (approximately 2–4 years of age)
|Exposure||Period I||Period II||Sens.||Not sens.||OR crude||CI 95%||ORadjust||CI 95%|
| || || ||n=32*||n=106*|
Among children sensitized to cat, more were boys (OR=3.12, CI 95% 0.78–12.4), and more had heredity for allergy and/or asthma (OR=2.93, 0.85–10.1). Exposure to cat was associated with an increased risk of sensitization to cat. This was true for exposure during period I, but not period II (OR=5.56, 1.06–29.0), and for exposure during both time periods (OR=6.21, 1.55–24.8). The pattern of exposure to ETS showed little change between the time periods. The risk of sensitization to cat was increased when there was exposure to ETS during both time periods compared to when there was none (OR=3.18, 1.11–9.10) (Table 2). Signs of poor ventilation, as indicated by windowpane condensation (WPC) during either of the two periods, were not significantly associated with sensitization to cat (Table 2). An association was found between both degrees of exposure to cat during period I and sensitization to cat at the age of 4 years; OR=3.18, 1.02–9.90 and 3.37, 1.09–10.4 for low- and high-dose exposure to cat, respectively (Table 3). High dust levels of cat allergen (≥8 µg/g Fel d 1 in home floor dust) were associated with a pronounced increased risk of sensitization to cat (OR=5.92, 1.38–25.3). When all the three potential risk factors (high-dose exposure to cat, exposure to ETS, and WPC) had been present during period I, there was an 11-fold increased risk of sensitization to cat (OR=10.8, 1.97–59.6), indicative of a synergistic effect (Table 3).
Table 3. Risk of being sensitized to cat at age of 4 years in relation to exposure to cats, levels of cat allergen, and combination of risk factors (exposure to cats, ETS, and WPC) during period I (approximately 0–2 years of age)
| ||Sens.||Not sens.||OR crude||CI 95%||OR adjust||CI 95%|
| Cat none||10||62||1.00|| ||1.00*|
| Cat low||12||27||2.76||1.06–7.15||3.18*||1.02–9.90|
| Cat high||11||19||3.59||1.32–9.75||3.37*||1.09–10.4|
|Allergen level (Fel d 1)||(n=26)||(n=96)|
|<0.2 µg/g dust||8||58||1.00|| ||1.00*|
|0.2–8 µg/g dust||11||31||2.57||0.94–7.06||2.02*||0.64–6.35|
|>8 µg/g dust||7||7||7.25||2.01–26.1||5.92*||1.38–25.3|
|Cat exposure, ETS and WPC|
| No risk factor present||3||24||1.00|| ||1.00**|
| One risk factor present||7||48||1.17||0.28–4.91||1.11**||0.25–4.92|
| Two risk factors present||15||31||3.87||1.00–14.9||4.38**||1.03–18.6|
| Three risk factors present||8||5||12.8||2.48-66.0||10.8**||1.97–59.6|
Exposure to ETS during both periods was significantly associated with an increased risk of sensitization to dog (OR=2.91, 1.06–8.00), and this was true for reported WPC during both periods as well (OR=3.52, 1.11–11.2). High- or low-dose exposure to dog during period I, but not during period II, tended only to increase the risk of sensitization to dog (OR=3.03, 0.63–14.5). Other combinations of exposure to dog were not associated with an increased risk of sensitization (data not shown).
Early risk factors for current severe asthma
Twelve children fulfilled the criteria for severe asthma (all boys, mean age 45 months), and 162 children those for mild/moderate asthma (124 boys, mean age 49 months) (Table 4). Heredity for asthma and allergy did not differ between the groups. During the first 2 years of life, the children in the group with severe asthma had been exposed more to several of the environmental risk factors studied than the children in the mild/moderate asthma group. Thus, high levels of Fel d 1 in the children's homes tended to increase the risk of severe asthma (OR=3.39, 0.77–14.9), and this was also true for parental smoking (OR=3.01, 0.74–12.2). A combination of the two risk factors resulted in an 18-fold increase of risk (OR=18.0, 3.20–101) (Fig. 1). A greater pro-portion of children in the group with severe asthma exhibited also a RAST level of ≥2 (≥0.70 kU/l) to cat, compared with children in the group with mild/moderate asthma (RAST level ≥2, 33%vs 13%, OR=3.29, 0.86–12.5). Sensitization to dog did not differ between the groups. However, multiple sensitization (more than two positive SPT to allergen extracts) significantly increased the risk of severe asthma (OR=6.99, 1.58–31.0). No significant association was seen of reported exposure to cat or dog with severity of asthma (data not shown)
Table 4. Risk of having current severe asthma (4 years of age) in relation to risk factors during period I (approximately 0–2 years of age)
| ||Mild/moderate asthma||Severe asthma||OR||95% CI||OR adjust||95% CI|
|IgE cat, RAST ≥0.70 kU/l||145||19||13||12||4||33||3.34||0.98–11.6||3.29†||0.86–12.5|
|IgE dog, RAST ≥0.70 kU/l||139||20||14||12||2||17||1.20||0.0–5.31||1.37†||0.27–7.10|
|SPT positive*: 0||160||113||71||12||5||42||1.00|| ||1.00|
|SPT positive*: >2||160||19||12||12||4||33||4.84||1.19–19.7||6.99†||1.58–31.0|
|Fel d 1 <0.2 µg/g dust||135||67||50||12||6||50||1.00|| ||1.00|
|Fel d 1 0.2–8 µg/g dust||135||56||41||12||1||8||0.20||0.02–1.67||0.15**||0.02–1.39|
|Fel d 1 >8 µg/g dust||135||12||9||12||5||42||4.72||1.24–18.0||3.39**||0.77-14.9|
Figure 1. Risk of having current severe asthma (at 4 years of age) in relation to number of risk factors (exposure to Fel d 1 >8 µg/g dust and parental smoking) during period I (approximately 0–2 years of age). OR (odds ratio) values are adjusted for age, heredity, and exposure to cat, dog, parental smoking, and windowpane condensation.
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Current risk factors for current severe asthma
At the mean age of 4 years (study II), severe asthma was still associated with pronounced atopy, i.e., more than two positive SPT (OR=11.8, 2.3–60), RAST of ≥2 (≥0.70 kU/l) to cat (OR=2.8, 0.6–9.9), and now also RAST of ≥2 to dog (OR=2.5, 0.6–10.7). The children in the group with severe asthma were at the time of study II more exposed to cat (reported exposure) and tobacco smoke than children with moderate/mild asthma, although the difference was not statistically significant. No such tendency was observed for exposure to dog (data not shown).
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In this paper, we have focused on early exposure to different environmental factors up to 2 years of age, and on sensitization later in childhood, i.e., at approximately 4 years of age. In addition, the relationship between current exposure factors and current sensitization was investigated. We also investigated the impact of exposure to cat and dog in the process leading to severe asthma. Synergistic associations between early exposure to cat, parental smoking, signs of poor ventilation, and sensitization to cat and dog were found. Exposure to high levels of cat allergen in the home (≥8 µg/g of floor dust), in combination with parental smoking at 2 years of age, was found to be associated both with the development of severe asthma and continued sensitization to cat.
Exposure and sensitization
Early exposure to cat, as indicated by both reported exposure and levels of cat allergen at home, has been shown to increase the risk of sensitization to both cat and dog later in childhood (13–15). In accordance with results from our previous study, we did not find any significant association between early exposure to dog or exposure to levels of dog allergen and sensitization to dog (13). A significant association was found both between early reported exposure to cat and high measured levels of cat allergen at home and current sensitization to cat. In study I, 26 of the 181 children's parents were reported to keep a cat at home compared to 12 in study II. Among the children sensitized to cat (n=33), 11 were exposed at high dose to cat in study I, but only five in study II. This change of exposure to cat may probably be explained by removal of the cat from the home of symptomatic sensitized children and active avoidance of cats outside the home. Similar results were reported by Kuehr et al. in 1992 (16). The same year, Brunekreef et al. (17) reported that the highest prevalence of current allergy and respiratory symptoms among Dutch children aged 6–12 years was found among children from homes where pets were kept in the past but no longer. Active avoidance of allergen, both as a consequence of disease and as a primary preventive effort, complicates interpretation of sensitization during childhood and may very well explain different results in recent studies.
Wahn et al. showed significantly higher concentrations of cat allergen in the homes of sensitized children (up to 3 years of age) compared to those in homes of unsensitized children (14). This is consistent with our previous findings, while several other studies have failed to show any association between exposure to pets (cat included) and sensitization (18–21). In two recent studies, it has been proposed that childhood exposure to cats is associated with a decreased risk of sensitization to cats later in life (2, 5). Such cross-sectional retrospective studies may be liable to recall bias, which may, at least in part, explain the results. In this study, more than half of the families got rid of the cat between study I and study II, when the children were approximately 2–4 years of age, and our data are in good agreement with those of Brunekreef et al. Different results may partly be explained by exposure outside home, e.g., exposure to cat and dog allergen at schools, at day-care centers, and in the homes of friends and relatives. Furthermore, such exposures may also lead to the contamination of homes and consequent hidden exposure.
The association between WPC and sensitization to dog and cat (although not statistically significant) might be explained by the fact that reduced air exchange may lead to indoor trapping of allergens and consequent enhancement of the actual allergen exposure. Further-more, a synergistic effect was found between exposure to cat, parental smoking, and signs of poor ventilation, thus increasing the risk of sensitization. The presence of WPC and indoor vapor contribution (>3 g/m3) has been associated with poor ventilation, although these indicators may not always reflect the true indoor climate (22). Development of atopic disease has also been found to be associated with WPC and poor indoor climate (23), although the mechanism behind these observations may still not be fully understood.
Recently, several studies of domestic allergens in public places have shown that allergens from cat and dog are ubiquitous, even in environments without such animals, and may be present in levels sufficient to induce sensitization and/or worsen symptoms in sensitized individuals (15, 24–27). This contribution to the allergen load must be considered in estimations of an individual's exposure at home and at other places. In this study, we have tried to estimate the children's exposures to pets by detailed questionnaire and allergen measurements. Most importantly, we found that indirect exposure and low to moderate levels of cat allergen in the homes were associated with a considerably increased risk of sensitization to cat. Such a degree of exposure may be an important confounder in the previously discussed studies (2, 5). However, this study was not population based. There is a possibility of a selection bias, and the results need not be applicable to all children. Misclassification of questionnaire data cannot be ruled out but must be expected to be evenly distributed in the group. The time period between the occurrence of the exposures and the collection of data was short, below years; thus, there should be little risk of recall bias. However, since this is a case study in which the children and parents were given an asthma diagnosis, there is a risk of misclassification of data due to influence of the development of the child's asthmatic disease. For instance, a recall bias for the associations of atopic family history and atopy in children must be considered, and this has been shown to be indeed relevant (28).
Development of asthma requiring continuous treatment
Severe asthma at the age 4 years was in this study associated with exposure to high levels of cat allergen at home, parental smoking, and early sensitization, as indicated by either more than two positive SPT or RAST of ≥0.70 kU/l to cat at the age of 2 years. The link between early sensitization and severity of asthma is of great importance, indicating that atopy in early life is a negative prognostic factor in wheezing children. In this respect, our data are in close agreement with those of others (4, 8).
A number of studies have demonstrated that current atopic status, assessed as either positive SPT or positive RAST, is an important factor for current asthma status. Zimmerman et al. found the number of positive SPT to be associated with increasing severity of asthma (29). Two other recent studies by Sarpong & Karrison have shown that sensitivity to cat increased the risk of having more severe asthma, and this was probably an important determinant for asthma hospitalization in children (6, 7). Furthermore, increased bronchial hyperresponsiveness among children with asthma has been associated with sensitization to dog or cat dander (30). Thus, there are convincing data on a positive association between sensitization to various allergens and asthma severity. This is an important background in the context of our findings of an association between early allergen exposure and sensitization.
A recent meta-analysis study on the health effects of passive smoking concluded that among children with established asthma, parental smoking was associated with more severe disease, a finding which is consistent with our findings (31). Parental smoking in early life among children with wheezing bronchitis has also been shown to be a significant risk factor for asthma at 10 years of age (4).
This follow-up study brings additional information about sensitization and asthma outcome to the current discussion of pet exposure in early life and the development of asthma. Our data clearly indicate that wheezy children should not live in homes where pets are kept. Furthermore they should preferably not have lived in such a home during their first few years, particularly not if the pet was a cat and a parent a smoker.