The reasons for the increasing incidence of childhood asthma are unclear. The indoor environment, in particular exposure to house dust mite, is an area of particular concern. 1 Bedding is a significant source of house dust-mite allergen, 2 partly because of proximity to the human airway. For example, airborne Dermatophagoides house dust-mite allergen levels near the face during sleep were reduced more than 10-fold by replacing used bed quilts with new ones. 3 Synthetic pillows contain much higher levels of house dust mite and other indoor allergens compared with feather pillows 4,5,6 and so it is plausible that the previously reported associations between synthetic bedding and adverse respiratory outcomes 7–14 do not simply reflect feather-bedding avoidance measures in the more severe asthmatics. 15,16 Prospective studies are required to examine the link between synthetic bedding and childhood wheeze and to evaluate the role of upper bedding in asthma. 15,16
An association between synthetic bedding and wheeze 7–12 or rhinitis 13,14 has been reported from several cross-sectional studies. A population-based case-control study comparing children with severe or frequent wheeze with children with no wheeze reported that foam pillows were associated with severe wheeze (odds ratio [OR] = 2.8; 95% confidence interval [CI] = 1.9–4.2). 7 This association held even among children whose parents denied making changes to the child's bedroom for reasons related to allergy. 7 Similarly, the association between nonfeather pillow use and perennial rhinitis remained after excluding subjects who changed pillows because of allergy (OR = 2.4; CI = 1.3–5.0). 13 If these observations were causal, one possible mechanism might be that synthetic pillows increase the risk of atopic disease by placing a higher allergen load near the face compared with nonsynthetic bedding. Alternatively, synthetic bedding may have an adverse effect by other means such as chemical emissions 7 or reduced bacterial endotoxin exposure compared with natural materials such as feather. 17 High house dust-mite allergen levels, exposure to chemical emission compounds, and reduced exposure to bacterial endotoxin levels have all been implicated as environmental factors that may contribute to the development of wheeze in childhood. 18–20
Progress on the role of environmental factors in the development of asthma has been hampered by disease misclassification and the lack of prospective data. Asthma is a clinical syndrome reflecting airway inflammation and obstruction. 1 The specific contribution of allergen-induced, irritant-induced and infection-induced wheeze within the broad spectrum of asthma has not yet been clearly identified. Although the overall proportion of population-based childhood asthma attributable to atopy is low (with only approximately 38% attributable), 21 atopic individuals are overrepresented at the severe end of the asthma spectrum. 22–24 Further, although house dust-mite sensitization is only weakly associated with asthma (relative risk [RR] = 1.7), it is strongly associated with frequent wheeze (more than 12 episodes compared with no wheeze over the past year; RR = 19.6). 25 Thus, a focus on severe symptoms such as frequent wheeze should reduce disease misclassification in population-based studies examining house dust-mite–induced airway disease. 25 We now report the first prospective study on the use of synthetic bedding in infancy and subsequent wheeze, taking into account the type and frequency of wheeze in childhood.
The Tasmanian Infant Health Survey
Eligible infants for this birth cohort study represented approximately one-fifth of live births in the state of Tasmania who were scored at birth to be at higher risk of sudden infant death syndrome (SIDS) (Figure 1). From 1988 to 1995, 9,826 (89%) of the eligible infants participated in hospital and home interviews. The eligibility criteria and methods are outlined elsewhere. 26 We defined an at-birth family history of asthma as asthma among the infant's siblings, parents or grandparents reported by interview of the mother during the first postnatal week. We conducted a second interview in the infant's home during the fifth postnatal week. Measurements were carried out on the baby, features of the home were observed, and a structured verbal parental questionnaire was administered. We recorded features of the infant's sleeping environment, including type of pillow, mattress liner, mattress and bed, plus the number and types of upper bedding items that would be used in cold weather.
The 1995 Tasmanian Asthma Survey
We conducted a cross-sectional survey on all children who turned 7 years of age in Tasmania, identified through primary schools and home-learning and distance-education organizations (Figure 1). 27 Data included sleeping environment and asthma symptoms, using questions from the International Study of Asthma and Allergy in Childhood. 28 Previous validation work has shown that the report of wheeze over the past 12 months has a sensitivity of 0.81 and a specificity of 0.85 for the physician diagnosis of asthma in childhood. 29 In addition, the child's age at onset (in completed years) of wheezy breathing or asthma was obtained. Of the 1,111 who participated in the 1988 TIHS home interview, 863 (78%) also participated in this asthma survey (Figure 1). These studies were approved by the Ethics Committee (Human Experimentation) of the University of Tasmania and parents provided informed written consent, including consent for data linkage between the TIHS and the 1995 Tasmanian Asthma Survey.
Classification of Synthetic Bedding
Pillows reported as foam/sponge/tontine/polyester/Dacron were classified as synthetic. A small number of children in infancy or childhood (1995 cross-sectional study only, N = 23) were excluded because the pillow was described as “antiallergy” but information on composition was not available. A synthetic quilt in infancy was defined as the use of a synthetic quilt over the infant during cold weather. A synthetic quilt in childhood was defined as a polyester or Dacron quilt/doona/duvet over the child. The parental report of infant synthetic-pillow use showed high agreement with nurse observation of infant pillow used in the last night in a 1995 substudy (data not shown). For the present report, synthetic bedding refers to the use of either a synthetic pillow or synthetic overlying quilt. Synthetic-bedding use in childhood was very common (Table 1). The “consistent” use of a bedding item refers to use in both infancy and childhood.
To control simultaneously for multiple confounders and to obtain confidence intervals for relative risk estimates, a generalized linear model with a log-link function and binomial error structure was used for the cross-sectional and prospective analyses. 30,31 We assessed the relation between infant synthetic bedding and age of onset of asthma symptoms using discrete proportional hazard modelling. 32 A log-rank test for the equality of survivor functions was used for analysis of age at onset of asthma or wheezy breathing.
We examined frequent and moderate wheeze over the past year rather than the presence of any wheeze over the past year. Moderate wheeze was defined as 12 or fewer wheeze episodes and frequent wheeze was defined as more than 12 wheeze episodes in the past year. We also examined night wheeze over the past year because bedding was the exposure of interest. Because the data indicated that family history of asthma might be partially determined by exposure (synthetic bedding), family history was not treated only as a confounder; results with and without adjustment for family history are presented. We first evaluated trends by a chi-square test of trend with the categories of synthetic bedding ordered approximately for increasing synthetic upper-bedding volume. A categoric term for increasing number of synthetic items was then used to provide the P-value for trend in the multivariate analyses.
We calculated the etiologic fraction of wheeze attributable to synthetic bedding among those using a synthetic pillow or quilt as P (adjusted relative risk [aRR] − 1)/aRR, where P = the proportion of children with synthetic bedding among those with the wheeze outcome and aRR = the relative risk estimate for synthetic bedding and wheeze, after adjustment for the confounders. 33 We conducted the analyses with Stata 7.0. 34
The Infant Cohort Study
Among children in the 1995 Tasmanian Asthma Survey who were also included in the cohort study that began in 1988, synthetic pillow use at 1 month of age was strongly associated with night wheeze or frequent wheeze at age 7, but not with moderate wheeze (Table 2). The association between synthetic pillow use and frequent wheeze remained after adjustment for the cohort-entry scoring-system components (male sex, exclusive breast feeding, season of birth, multiple birth, duration of second stage of labour, maternal age and birth weight), as either individual factors or as a set, and further adjustment for more than 20 individual confounders including sibling number, dog or cat as a family pet during infancy, air freshener use or hairspray use in infant's bedroom, or infant exposure to active smoking in the same room at 1 month of age. The use during infancy of any pillow or synthetic quilts was not associated with any of the outcomes listed in Table 2.
We then examined combined synthetic upper-bedding and pillow use in infancy. The proportion of children with night wheeze at age 7 varied by synthetic upper-bedding use in infancy as follows: no synthetic pillow or quilt, 17%; synthetic quilt only, 17%; synthetic pillow only, 26%; synthetic pillow and quilt, 33% (test for trend:P = 0.006). Feather bedding was not commonly used in infancy (feather pillows, N = 11; feather quilts, N = 11); thus the prospective association between infant feather bedding and child wheeze could not be examined.
Age of onset analysis showed that, among children with asthma, synthetic bedding use in infancy was associated with an earlier onset of asthma symptoms (log-rank test, P = 0.03) (Figure 2). We then further examined the effect of synthetic pillow use on age of onset of asthma symptoms by wheeze episode frequency over the past year. Among children with no wheeze or moderate wheeze, synthetic pillow use did not relate to age of onset (aRR = 1.3 [CI = 0.7–2.2] and aRR =1.3 [CI = 0.8–2.0], respectively). Among children with frequent wheeze, early synthetic pillow use was strongly associated with earlier symptom onset (aRR = 3.6; CI =1.4–9.3). Thus, the earlier onset of asthma symptoms associated with early synthetic bedding use occurred predominantly among children with frequent wheeze, after adjustment for an at-birth family history and the presence of siblings in childhood.
The Cross-Sectional Asthma Survey
The full 1995 cross-sectional sample was similar to the cohort sample with regard to child age, wheeze frequency over the past year, and the proportion of children using synthetic bedding; a lower proportion of children had a history of asthma ever (Table 1). Synthetic bedding use in childhood was associated with a history of asthma ever (aRR 1.3; CI = 1.1–1.6).
Examination of bedding by wheeze frequency found that current synthetic bedding exposure was most strongly related to frequent wheeze (Table 3). There was a significant trend for increased likelihood of wheeze with increasing exposure to synthetic bedding (Table 3). The adjusted associations in Table 3 remained unchanged after further individual adjustment for more than twenty possible confounders. Synthetic quilt use was also significantly associated with night wheeze (aOR = 1.3; CI = 1.1, 1.4). Among children with asthma, synthetic bedding was also associated with an increased frequency of asthma medication use (data not shown), which is consistent with the observation of more severe asthma symptoms in this group. This indicates that the increased in symptoms among children using synthetic bedding could not be attributed to an under-utilization of asthma medications.
We then examined bedding composition in further detail. Comparing synthetic to feather pillows, the aRR for frequent wheeze was 4.4 (CI = 1.1–17.6). Comparing synthetic pillows to other non-feather pillows, the aRR for frequent wheeze was 1.1 (CI = 0.4–2.8). The use of synthetic compared the feather over-bedding related to frequent wheeze (aRR = 1.7; CI =1.1–2.4) but synthetic overbedding was not significantly associated with frequent wheeze compared to other non-feather over-bedding (aRR = 1.2; CI = 0.7, 2.1). Overall feather quilt use was associated with an aRR of 0.6 (CI = 0.4–0.9) for frequent wheeze.
Intriguingly, the importance of the association between sibling number and wheeze also varied by wheeze frequency. For children with moderate wheeze, an increase in household resident number appeared protective (aRR = 0.91; CI = 0.87–0.95) per increase in household resident). However, sibling number appeared less important for children with frequent wheeze (aRR = 1.00; CI = 0.87–1.16) per resident increase. Thus, the protective effect of large family size was only apparent for children with moderate, not frequent wheeze. The percentage of moderate wheeze attributable to synthetic bedding among children exposed to either a synthetic pillow or quilt was low (16%) for moderate wheeze but high for those with frequent wheeze (79%). Thus, it appears that the factors associated with frequent wheeze differ from those associated with moderate wheeze.
Possible Contribution of an At-Birth Family History of Asthma or Early Allergen Avoidance
Among children with asthma at the age of seven, 2% (39/1686) used allergen-occlusive mattress covers. Children with these covers were not more likely to sleep with a synthetic pillow (87% vs. 92% use) or synthetic quilt (47% vs. 48% use). The choice of a non-carpeted bedroom floor was also not associated with synthetic bedding use. These findings suggest that the results in Table 3 do not reflect the parents’ introduction of the synthetic bedding as part of an allergen reduction strategy.
It is likely that synthetic bedding choices will be shared within a family. The cohort data suggested the possibility that synthetic bedding use may have promoted asthma among other family members, such as younger siblings. Among children with no family history at birth, infant synthetic pillow use predicted a positive family asthma history by childhood (RR = 1.5; CI = 1.1–1.9) while among those children who did not use a synthetic pillow, an at-birth family history of asthma was only slightly associated with frequent wheeze (RR = 1.3; CI = 0.5–3.3)). There was no evidence that parents of children with an at-birth family history of asthma were selecting a synthetic pillow as part of a bed allergen reduction strategy. Similarly, there was no indication that they were selectively using a plastic mattress liner (42% vs. 40% use) nor avoiding sheepskins (29% vs. 28% use). Among children with no at-birth family history of asthma, the consistent use of a synthetic pillow (RR = 3.2; CI = 1.0–10.1) or synthetic quilt (RR = 1.9; CI = 1.1–3.2) in both infancy and childhood compared to no use was associated with night wheeze at age seven. Importantly, the associations between bedding and frequent wheeze in Tables 2 and 3 were present with or without further adjustment for family history of asthma.
In the cohort analysis, infant synthetic pillow use was associated with an increased risk of frequent childhood wheeze, independently of later exposure to synthetic bedding. A strong association between current synthetic bedding use and frequent wheeze was also observed. Feather bedding was uncommon in early life so the prospective association between infant feather bedding and childhood wheeze could not be reported. However, the findings that infant synthetic pillow was not associated with childhood feather bedding and that controlling for childhood use did not affect the association between infant synthetic pillow use and frequent wheeze suggest that the prospective association between infant synthetic bedding use and frequent wheeze cannot be readily explained by the use of feather bedding in later childhood. The finding that synthetic infant quilts were not associated with wheeze may be because these items are usually of the coverlet type and thus more frequently washed than pillows or child quilts. We examined non-causal explanations for the striking associations between synthetic bedding and frequent wheeze. The findings argue against a spurious association caused by the selection of synthetic bedding because of asthma or family history. The associations between synthetic bedding and frequent wheeze persisted after adjustment for confounding factors. Several criteria indicative of a causal relationship 33 between synthetic bedding and wheeze were evident, including a high strength of association and dose-response patterns in Table 3. In addition, the prospective measurement here of infant bedding before asthma development and the earlier shift in age of onset with earlier use of synthetic bedding establishes the causal feature of temporality.
These findings add to accumulating evidence that synthetic bedding may be associated with adverse respiratory outcomes. No study to date has shown a lower wheeze prevalence associated with synthetic bedding. Previous cross-sectional studies have shown positive associations for synthetic or non-feather bedding and child wheeze 7–12 or rhinitis. 13–14 Several of the investigators also restricted their analyses to those subjects who did not report that they changed their bedding because of respiratory symptoms or they adjusted for reported allergen avoidance; the positive association between synthetic or non-feather bedding and wheeze or rhinitis persisted. 7–8, 13–14 In addition, a previous study has implicated synthetic bedding in the increasing incidence of asthma over time. Researchers examined the relation between changes in the home environment and the increase in childhood wheeze between 1978 and 1991 among seven to eight-year-olds in the London Borough of Croydon. They found that, of the environmental risk factors examined, the increasing use of non-feather pillows (from 44% in 1978 to 67% in 1991) was the most important factor, accounting for more than half of the 20% increase in current wheeze between 1978 and 1991. 35
Possible mechanisms for the association of synthetic bedding and frequent wheeze include increased exposure to house dust mite or to volatile organic compounds and reduced exposure to endotoxin. Firstly, synthetic bedding may lead to higher allergen exposure. Vacuum extraction studies show synthetic pillows have five to seven-fold higher house dust mite allergen levels compared with feather pillows. 4,5 The higher allergen levels in synthetic bedding have been postulated to reflect a looser weave for the lining of synthetic, compared to feather, bedding, but the internal bedding microclimate with regard to warmth and humidity or electrostatic properties may also be important. In the Tasmanian environment, the mean Dermatophagoides pteronyssinus level in synthetic pillows was 2.7 ug at one month of age 36 and, based on an accumulation study, 37 the levels could reach over 20 ug/g after a further year. It has been suggested that exposure to Dermatophagoides pteronyssinus allergen levels above 2 ug/g may increase the risk of dust mite sensitisation and levels above 10 ug/g may induce respiratory symptoms in house dust mite-sensitized individuals. 38 Previously, three prospective cohort studies have found house dust mite allergen levels in bedding during early life to be predictive of initial house dust mite sensitisation, with a dose-response evident. 39–41 House dust mite exposure among house dust mite-sensitized children increased the risk of developing asthma. 42 Among house dust mite-sensitized children, house dust mite exposure has been associated with bronchial hyper-responsiveness. In an Australian study, bed house dust mite allergen (a composite sample from mattress and upper bedding) was associated with a reduction in minimum morning peak expiratory flow rate, with an increase of one natural log of house dust mite allergen leading to an approximately 15L/min reduction. 43 House dust mite allergen levels in bedroom floors were less important than bed house dust mite allergen levels in determining airway responsiveness 43 or asthma severity. 44 This could partly explain why an association between infant bedroom house dust mite levels and asthma has only been found in one of three studies. 18,45,46 That is, by measuring infant floor dust, rather than infant bedding, these studies may have misclassified inhalational house dust mite allergen exposure during infancy. An inverse association of childhood asthma with farm residence or early life contact with animals, if causal, has been postulated to reflect a higher level of infant exposure to bacterial endotoxins resulting in immune deviation away from atopy. 47 Synthetic pillows may contain fewer bacterial products than feather 17 but further work is required on this issue. In addition, volatile organic compounds released from synthetics might increase mucosal permeability to inhaled allergens. 7 The Oslo birth cohort study found an exposure-response relationship between plasticizer-containing surface materials and risk of bronchial obstruction by age two. 19 Thus, the role of chemical emissions from synthetic bedding also requires further evaluation.
In conclusion, the association between synthetic upper bedding and frequent childhood wheeze in the present studies displayed the features of high strength of association, temporality, dose-response, and consistency. These features, together with findings from previous studies, indicate that the association may be causal in nature. However, to fully exclude the possibility that synthetic bedding is associated with lifestyle or other factors that are causally related to frequent wheeze, randomized controlled trials evaluating alternative bedding are required.
We thank the parents, families, infants, and children who participated in these studies, the research staff for data collection and collation, and the hospitals participating in the infant cohort study. We thank the participating schools, the Department of Education, the Department of Cultural and Community Development and the Catholic Education Office. We also thank the Asthma Foundation of Tasmania for the equipment loan; Carole Goff for data coordination and collection and for exercise testing in 1995; Michael Martin for exercise testing in 1995; and the volunteer staff: Val Walsh, Baden Duffy, Diane Jackson, Von Calvert, Diana Young, and Sharon Clark.
1. Sears MR. Epidemiology of childhood asthma
. Lancet 1997; 350: 1015–1020.
2. Arlian LG, Platts-Mills TA. The biology of dust mites and the remediation of mite allergens in allergic disease. J Allergy Clin Immunol 2001; 107: S406–413.
3. Sakaguchi M, Inouye S, Yasueda H, et al.
Concentration of airborne mite allergens (Der I and Der II) during sleep. Allergy 1992; 47: 55–57.
4. Crane J, Kemp T, Siebers R, et al.
Increased house dust mite
allergen in synthetic pillows may explain increased wheezing. BMJ 1997; 314: 1763–1764.
5. Hallam C, Custovic A, Simpson B, et al. house dust mite
allergen in feather and synthetic pillows. Allergy 1999; 54: 407–408.
6. Custovic A, Hallam C, Woodcock H, et al.
Synthetic pillows contain higher levels of cat and dog allergen than feather pillows. Pediatr Allergy Immunol 2000; 11: 71–73.
7. Strachan DP, Carey IM. Home environment and severe asthma in adolescence: a population based case-control study. BMJ 1995; 311: 1053–1056.
8. Duhme H, Weiland SK, Rudolph P, et al.
Asthma and allergies among children in West and East Germany: a comparison between Munster and Greifswald using the ISAAC phase I protocol. International Study of Asthma and Allergies in Childhood. Eur Respir J 1998; 11: 840–847.
9. Strachan D, Carey IM. Reduced risk of wheezing in children using feather pillows is confirmed. BMJ 1997; 314: 518.
10. Zacharasiewicz A, Zidek T, Haidinger G, et al.
Indoor factors and their association to respiratory symptoms suggestive of asthma in Austrian children aged 6–9 years. Wien Klin Wochenschr 1999; 111: 882–886.
11. Karaman O, Uguz A, Uzuner N. Risk factors in wheezing infants. Pediatr Int 1999; 41: 147–150.
12. Yemaneberhan H, Bekele Z, Venn A, et al.
Prevalence of wheeze and asthma and relation to atopy in urban and rural Ethiopia. Lancet 1997; 350: 85–90.
13. Frosch AC, Sandhu G, Joyce R, et al.
Prevalence of rhinitis, pillow type and past and present ownership of furred pets. Clin Exp Allergy 1999; 29: 457–460.
14. Zacharasiewicz A, Zidek T, Haidinger G, et al.
Symptoms suggestive of atopic rhinitis in children aged 6–9 years and the indoor environment. Allergy 2000; 55: 945–950.
15. Fitzharris P, Siebers R, Crane J. Pillow talk: have we made the wrong beds for our patients to lie in? Clin Exp Allergy 1999; 29: 429–432.
16. Custovic A, Woodcock A. Feather or synthetic? That is the question. Clin Exp Allergy 1999; 29: 144–147.
17. Weernink A, Severin WP, Tjernberg I, Dijkshoorn L. Pillows, an unexpected source of Acinetobacter. J Hosp Infect 1995; 29: 189–199.
18. Sporik R, Holgate ST, Platts-Mills TA, et al.
Exposure to house-dust mite allergen (Der p I) and the development of asthma in childhood. A prospective
study. N Engl J Med 1990; 323: 502–507.
19. Jaakkola JJ, Oie L, Nafstad P, et al.
Interior surface materials in the home and the development of bronchial obstruction in young children in Oslo, Norway. Am J Public Health 1999; 89: 188–192.
20. Gereda JE, Leung DY, Thatayatikom A, et al.
Relation between house-dust endotoxin exposure, type 1 T-cell development, and allergen sensitisation in infants at high risk of asthma. Lancet 2000; 355: 1680–1683.
21. Pearce N, Pekkanen J, Beasley R. How much asthma is really attributable to atopy? Thorax 1999; 54: 268–272.
22. Peat JK, Tovey E, Gray EJ, et al.
Asthma severity and morbidity in a population sample of Sydney schoolchildren: part II–importance of house dust mite
allergens. Aust N Z J Med 1994; 24: 270–276.
23. Nelson HS. The importance of allergens in the development of asthma and the persistence of symptoms. J Allergy Clin Immunol 2000; 105: S628–S632.
24. Ponsonby A-L, Gatenby P, Glasgow N, et al.
Which clinical subgroups within the spectrum of child asthma are attributable to atopy? Chest 2002; 121: 135–142.
25. Ponsonby A-L, Kemp A, Dwyer T, et al
. Feather bedding
and house dust mite
sensitisation and airway disease in childhood. J Clin Epidemiol 2002; 55: 556–562.
26. Dwyer T, Ponsonby A-L, Newman NM, et al. Prospective cohort
study of prone sleeping position and sudden infant death syndrome. Lancet 1991; 337: 1244–1247.
27. Ponsonby A-L, Couper D, Dwyer T, et al.
The relation between infant indoor environment and subsequent asthma. Epidemiology 2000; 11: 128–135.
28. Worldwide variation in prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and atopic eczema: ISAAC. The International Study of Asthma and Allergies in Childhood (ISAAC) Steering Committee. Lancet 1998; 351: 1225–1232.
29. Jenkins MA, Clarke JR, Carlin JB, et al.
Validation of questionnaire and bronchial hyperresponsiveness against respiratory physician assessment in the diagnosis of asthma. Int J Epidemiol 1996; 25: 609–616.
30. Breslow NE, Day NE. Statistical Methods in Cancer Research. Volume 2: The Design and Analysis of Cohort Studies
. Lyon: International Agency for Research on Cancer, 1987.
31. McCullagh P, Nelder JA. Generalised Linear models. London: Chapman and Hall, 1989.
32. Jenkins SP. Easy estimation methods for discrete-time duration models. Oxf Bull Econ Stat 1995; 57: 129–138.
33. Rothman KJ, Greenland S. Modern Epidemiology. 2nd ed. Philadelphia: Lippincott-Raven, 1998.
34. Stata Statistical Software: Release 7.0. College Station, TX: Stata Corporation, 2001.
35. Butland BK, Strachan DP, Anderson HR. The home environment and asthma symptoms in childhood: two population based case-control studies 13 years apart. Thorax 1997; 52: 618–624.
36. Couper D, Ponsonby A-L, Dwyer T. Determinants of dust mite allergen concentrations in infant bedrooms in Tasmania. Clin Exp Allergy 1998; 28: 715–723.
37. Rains N, Siebers R, Crane J, et al. House dust mite
allergen (Der p 1) accumulation on new synthetic and feather pillows. Clin Exp Allergy 1999; 29: 182–185.
38. Platts-Mills TAE, Thomas WR, Aalberse RC, et al.
Dust mite allergens and asthma: report of a second international workshop. J Allergy Clin Immunol 1992; 89: 1046–1060.
39. Kuehr J, Frischer T, Meinert REA, et al.
Mite allergen exposure is a risk for the incidence of specific sensitization. J Allergy Clin Immunol 1994; 94: 44–52.
40. Munir AK, Kjellman NI, Bjorksten B. Exposure to indoor allergens in early infancy and sensitization. J Allergy Clin Immunol 1997; 100: 177–181.
41. Wahn U, Lau S, Bergmann R, et al.
Indoor allergen exposure is a risk factor for sensitization during the first three years of life. J Allergy Clin Immunol 1997; 99: 763–769.
42. Dotterud LK, Van TD, Kvammen B, et al.
Allergen content in dust from homes and schools in northern Norway in relation to sensitization and allergy symptoms in schoolchildren. Clin Exp Allergy 1997; 27: 252–261.
43. Jalaludin B, Xuan W, Mahmic A, et al.
Association between Der p 1 concentration and peak expiratory flow rate in children with wheeze: a longitudinal analysis. J Allergy Clin Immunol 1998; 102: 382–386.
44. Chan-Yeung M, Manfreda J, Dimich-Ward H, et al.
Mite and cat allergen levels in homes and severity of asthma. Am J Respir Crit Care Med 1995; 152: 1805–1811.
45. Hide DW, Matthews S, Tariq S, et al.
Allergen avoidance in infancy and allergy at 4 years of age. Allergy 1996; 51: 89–93.
46. Lau S, Illi S, Sommerfeld C, et al.
Early exposure to house-dust mite and cat allergens and development of childhood asthma
: a cohort
study. Multicentre Allergy Study Group. Lancet 2000; 356: 1392–1397.
47. Lewis SA. Animals and allergy. Clin Exp Allergy 2000; 30: 153–157.