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Effectiveness of and compliance to intervention measures in reducing house dust and cat allergen levels
Effectiveness of and compliance to intervention measures in reducing house dust and cat allergen levels
Moira Chan-Yeung MB, FRCPC*; Alexander Ferguson, MB, FRCPC†; Helen Dimich-Ward, PhD*; Wade Watson, MD, FRCPC‡; Jure Manfreda, MD§; and Allan Becker, MD, FRCPC‡
Background: Allergic sensitization is a major risk factor in asthma. Objective: To evaluate the effectiveness of and compliance to intervention measures in reducing levels of house-dust mite and cat allergen in the context of a randomized, controlled study in the primary prevention of asthma. Methods: A total of 545 high-risk families were recruited prenatally and randomly assigned into the intervention group (n ⫽ 278) and the control group (n ⫽ 267). Intervention measures were instituted before birth of the infants and maintained for 12 months afterward in the intervention group and the control group received the usual care from their family physician. Dust samples were collected at six sites in the homes before birth and at specific intervals up to 24 months after birth for analysis of allergens. At 24 months, there were 244 families in the intervention group and 228 in the control group available for followup examination. Results: House-dust mite avoidance measures, consisting of encasement of mattresses, pillows, and duvets, and hot-water washing of bedding were effective in reducing mite allergen in parents’ mattresses to one-third from baseline, significantly lower than the control group, even at 24 months. The use of an acaricide did not reduce mite allergen levels in carpets and upholstered furniture. Seventeen intervention families gave up their cats but six families acquired a new one over a period of 24 months, similar to control families. Cat allergen levels decreased in all sites in the homes of those who removed the cat, similar in both groups. Conclusions: House-dust mite avoidance measures were effective in reducing house-dust mite allergen in mattresses, but not on floors. Reduction in cat allergen levels were evident for those families who got rid of their cats, but the advice to remove pets was not adhered to by most families. Ann Allergy Asthma Immunol 2002;88:52–58.
INTRODUCTION The prevalence of asthma has been rising in many parts of the world.1 * Occupational and Environmental Lung Diseases Unit, Respiratory Division, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada. † Division of Allergy, Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada. ‡ Section of Allergy, Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada. § Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada. Supported jointly by the Respiratory Health, Network of Center of Excellence; NHRDP, Canada, the British Columbia Lung Association, and the British Columbia Children’s Hospital. Received for publication April 10, 2001. Accepted for publication in revised form October 10, 2001.
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There has been an increase in morbidity from the disease in terms of hospitalization and doctor visits for treatment of asthma. The healthcare costs of the disease are high.2,3 Thus, there is considerable interest in the prevention of this disease. Exposure and sensitization to housedust mite is one of the important risk factors in places where mite allergen levels are high.4 Further, a dose-response relationship was found between the level of house-dust mite allergen and the risk of sensitization.5,6 A concentration of Der p1 ⬎2 g/gram of dust has been found to be necessary for sensitization.7 A prospective study of a high-risk cohort of infants has demonstrated that
infants exposed to a high level of house-dust mite allergen during the first year of life had the greatest risk of developing asthma in a followup study at age 11 years.8 The higher the level of exposure in early infancy, the earlier the symptoms of asthma appeared. The results of this study suggest that the early infancy period may be more susceptible to sensitization. We conducted a prenatally randomized, controlled clinical trial on the primary prevention of asthma in high-risk infants in two Canadian cities in 1994. A multifaceted intervention program was initiated shortly before birth and during the first 12 months of life.10 The intervention measures, which included house-dust mite and pet avoidance measures, resulted in a 34% reduction of “possible and probable asthma” in the intervention group compared with the control group. In this report, we examined the effectiveness of avoidance measures in reducing levels of house-dust mite and cat allergens, and the compliance of families to these intervention measures during the first year of life and determined whether there had been changes in allergen levels 12 months after active intervention measures had ceased. METHODS Participants The trial was conducted in two centers, Vancouver and Winnipeg. High-risk infants, defined as those with at least one first-degree relative with asthma or two first-degree relatives with other immunoglobulin (Ig)E-mediated allergic diseases, were identified in prenatal clinics. The method of recruitment of the families and randomization have
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been described in detail elsewhere.10 An equal number of families were recruited in each center. In total, 278 mothers were randomly allocated to the intervention group and 267 to the control (usual care) group. There were 242 families in the control and 252 in the intervention group at 12 months, and 228 and 244, respectively, at 24 months followup. The dropout rate was similar between the control and the intervention group, at 6 and 3%, respectively. Intervention Program The intervention measures were applied for a 12-month period from birth. On each home visit, the research nurse reinforced the importance of avoidance measures and encouraged the families who were assigned to the intervention group to continue with them. Control families did not receive any intervention measures. House-Dust Mite and Pet Avoidance Measures. 1) All mattresses, box springs, pillows, and quilts in parents’ beds were encased with vapor-impermeable covers (Intervent bedding system, WL Gore and Associates, Surrey, England). All mattresses in the infants’ bed were also encased. All covers were provided free of charge and put in place by the research nurse. 2) Parents were instructed to wash all bedding in hot water (55° C) at least fortnightly. 3) Removal of carpets, if at all possible, and especially from bedrooms. 4) Benzyl benzoate (Acarosan powder; Bencard Laboratories/SmithKline Beecham, Philadelphia, PA) was applied by the research nurses on carpets in parents’ and infants’ bedroom and the most commonly used room when their removal was not possible. Benzyl benzoate foam was applied to upholstered furniture in the most commonly used room. These applications were carried out before birth and at 4 and 8 months after the birth of the infants. Powder and foam were left on carpets and furniture for 8 to 12 hours before removal by vacuuming. 5) Parents who had cats, dogs, and other furry pets were counseled to get rid of them. If this was not possible, they were instructed
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to keep pets outside the house, or at least outside the infant’s bedroom. Parents without pets were advised not to get one. Dust Collection Home visits were carried out before the birth of the infant (initial) and at 2 weeks, 4, 8, 12, and 24 months after birth. A questionnaire was completed for the intervention group during each visit regarding compliance to various allergen avoidance measures. Dust samples were collected from six sites: infant’s bedroom floor and mattress, parents’ bedroom floor and mattress, the floor of the most commonly used room, and the upholstered furniture in that room. When infants moved out of the parents’ bedroom, dust samples were no longer collected from the parents’ bedrooms. A standard protocol was used for dust collection as described previously.11 Dust samples were collected using a portable vacuum cleaner, with a special sock attachment. The material for the socks had pore sizes approximately 5 m in diameter. The floor, most used upholstered furniture item, and bed mattresses were each vacuumed for 2 minutes. The socks were placed in a ziplocked bag and stored at ⫺20° C until being extracted and analyzed for housedust mite and cat allergens. Large particles were removed by using a 300-m mesh sieve before processing. Samples of dust were extracted in borate-buffered saline in the ratio of 100 mg to 2 mL, left overnight and filtered. Extracts were stored at ⫺20° C until analyzed for allergen levels. Allergen Assay The levels were determined using an ELISA assay with purified monoclonal antibodies against group 1 mite allergens, Dermatophagoides pteronyssinus and Dermatophagoides farinae (Der p 1 and Der f 1) and cat allergen, Fel d 1, respectively.12,13 The extracts of house dust were diluted 1:5, 1:10, and 1:100 for assay in duplicate. The species-specific monoclonal antibodies were used to coat microtiter plates, which were then incubated with the
standard or the extract. Bound allergen was detected using a separate biotinylated monoclonal antibody that recognized a different epitope on Fel d 1 for cat allergen and a common epitope on both Der p 1 and Der f 1 for mite allergen assays, followed by the addition of streptavidin-peroxidase and 2,2⬘-azinobis-(3-ethylbenthiazoline-6sulfonic acid)/H2O2 substrate. The absorbance was read from an ELISA reader at 405 nm. The amount of antigen present in the dust sample was calculated from a standard curve. The lower detection limit for each allergen was 0.5 ng/mL. The total mite allergen (sum of Der p 1 and Der f 1) was reported as g/gram of dust. Statistical Analyses House-dust mite and cat allergen levels were log-normally distributed; the results were reported as geometric means. The analyses were carried out 1) when samples with inadequate dust for ELISA assay were excluded and 2) when samples with insufficient dust were assigned a zero value and included. The results of analyses with samples with inadequate dust excluded are presented in the Results section, unless stated otherwise. Allergen levels of the control and the intervention group were compared at each visit using unpaired t test. Differences between the control and the intervention groups over time were examined with a two-factor ANOVA with repeated measures. Statistical analysis was carried out using SPSS/PC Version 9 for Windows (SPSS 1989 –99, Chicago, IL). Ethics The Ethics Committees of the University of British Columbia and the University of Manitoba approved the study. RESULTS In the intervention group, only 20 (10.9%) of 184 families with carpets in the homes initially managed to remove carpets over a period of 24 months. However, over the same period, 15 (20.8%) of 72 families without carpets in the homes initially had carpets during subsequent visits. Over the 2-year
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period, 154 (32.7%) of the families had changed residence. Table 1 shows the percentage and number of families in the intervention group that had encasement of mattresses, box spring, and pillows, washed bedding in hot water, and applied benzyl benzoate on each occasion after the birth of the infants. Of parents, 94.3% had encasement of mattress, box springs, and pillows. At the end of 12 months, 91.8% continued to use encasement, and at 24 months, the percentage dropped to 86.5. A total of 30 parents in the intervention group removed the encasement from their beds by 24 months. Of infants’ mattresses, 93.4% were encased, and the proportion remained relatively the same for 24 months. Approximately 70% of families had carpets in their homes. For all families with carpets, benzyl benzoate was applied in all three rooms at the time of recruitment and 2 weeks after the birth of the infant. On subsequent occasions, benzyl benzoate was not applied after infants were moved out of the parents’ bedroom. The proportion of families that agreed with the continual application of benzyl benzoate on carpets in bedrooms (parents’ and infants’) remained high at 8 months. The proportion of families that agreed to the application of benzyl benzoate to the upholstered furniture in the most commonly used room, dropped from 100% at the initial
visit to 75 and 70%, respectively, at 4 and 8 months. Using ANOVA for repeated measures, we found significant differences in mite allergen levels between the control and the intervention group over time in parents’ mattresses (P ⬍ 0.001) and the average of the floor samples (P ⬍ 0.01, irrespective of whether the samples with insufficient dust were included as having zero allergen or excluded from the analysis. Figure 1 shows mite allergen levels from samples collected from parents’ and infants’ mattresses, floor samples (average of three rooms), and from the upholstered furniture of the most commonly used room. The number of samples with insufficient dust for assay is presented below the figure; these samples were excluded from this analysis. Among parents’ mattress samples, a significantly higher proportion in the intervention group had samples with insufficient dust compared with the control group at all times after the birth of the infants. No differences were found in mite allergen levels at the onset of the study between the intervention and the control group from all sites. Encasement of mattresses, box springs, and pillows, and hot-water washing of bedding resulted in a reduction of house-dust mite allergen levels in parents’ mattresses to approximately one-third in the intervention group, significantly lower compared
with the control group (P ⬍ 0.01) at all followup visits except for visit 4. Few samples collected from infants’ mattresses had adequate dust for allergen assay. Mite allergen levels were low on samples that were measurable; mite allergen levels were found significantly lower in the intervention group in visit 3 only. The application of benzyl benzoate to carpets and upholstered furniture in the most commonly used room did not lower mite allergen levels significantly in the intervention group, with the exception of floor dust samples collected at visit 6. Table 2 summarizes cat ownership in both groups over the period of 24 months. The number of families in the intervention group that were rid of their cat was similar to those in the control group. A similar number of intervention and control families had acquired a new cat during the period of the study. Of the 33 families who had a cat throughout the 24 months, 3 claimed that the cat was kept outside the home and 22 outside the infant’s bedroom. There were no differences in the initial levels of cat allergen between the intervention and the control group. For families without a cat throughout 24 months, cat allergen levels were lower in parents’ mattress and upholstered furniture in the intervention compared with those in the control group, but were only significantly different at 24 months for samples from upholstered
Table 1. Participation of Families in the Intervention Group 2 weeks Encasement of parent’s bed, N (%) Encasement of infant’s bed, N (%) Hot water wash of bedding, N (%) Parent’s bedroom with carpet* N Acarosan applied, N (%) Infant’s bedroom with carpet N Acarosan applied, N (%) Most commonly used room with carpet N Acarosan applied, N (%) Acarosan applied to upholstered furniture, N (%)
230 (94.3) 228 (93.4) 236 (96.7) 178 178 (100) 174 174 (100) 173 173 (100) 100
4 months 230 (94.3) 230 (94.3) 237 (97.1) 172 171 (99.4) 174 158 (90.9) 169 163 (96.4) 75.0
8 months 225 (92.2) 226 (92.6) 238 (97.6) 157 148 (94.3) 176 159 (90.6) 170 153 (90.0) 69.9
12 months
24 months
224 (91.8) 223 (91.4) 238 (97.6) 134 NA 170 NA 172 NA NA
194 (86.5) 221 (90.6) 234 (95.9) NA NA NA NA
Families in the intervention group (n ⫽ 244) who followed the house dust mite avoidance measures during the 12-month period and their status at 24 months. * When infant moved out of parents’ bedroom, Acarosan was no longer applied to the parents’ bedroom. The number of families where children moved out of parents’ bedroom were 7, 30, and 59 at 4, 8, and 12 months, respectively, some with carpets and some without carpets. N represents the number of families with carpets in parents’ bedroom at the time of the visit. NA indicates that Acarosan was not applied.
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furniture (Fig 2A). There were significantly (P ⬍ 0.01) more mattress samples from parents’ bedrooms excluded because of insufficient dust in the intervention group than in the control group at visits 2 to 5 (Fig 2A). When samples with insufficient dust were included as zero in the analysis, cat allergen levels from parents’ mattresses were significantly lower in the intervention group at all times. For families with a cat throughout 24 months, cat allergen levels at all sites were high initially and in all subsequent visits. For the three families that claimed that they kept the cat outside the home, cat allergen levels were lower in floor samples compared with families with cats inside the home at the onset of the study (average floor level of Fel d 1 of 1.61 vs 6.17 g/ gram of dust) and at all followup visits. However, no differences were found in cat allergen levels in the infants’ bedrooms between families that claimed they kept the cat outside the infants’ room and families that allowed the cat into the infants’ bedrooms. Figure 2B shows cat allergen levels from parents’ and infants’ mattresses, floor (average of three rooms), and upholstered furniture of the most commonly used room from homes with a cat initially and the cat was removed subsequently during one of the followup visits (17 in the intervention and 16 in the control group). Reduction in cat allergen levels was found at all sites in both groups, but the differences between groups were not significant at any time during the 24-month period of observation. For the few families who acquired a cat after the initial visit, cat allergen levels increased with time in parents’ mattress in the control group (data not shown). DISCUSSION In this study, we examined the effectiveness of the intervention measures in reducing house-dust mite and cat allergen levels and the compliance to these measures carried out in the context of a primary prevention of asthma in high-risk infants. Intervention measures were applied, taking into consid-
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Figure 1. House-dust mite allergen levels (g/gram of dust; geometric mean) in control and intervention groups at different visits. Visit 1, before birth; visit 2 at 2 weeks; visit 3 at 4 months; visit 4 at 8 months; visit 5 at 12 months; and visit 6 at 24 months after the birth of the infants. Control group, dashed line; intervention group, solid line. * P ⬍0.05 and ** P ⬍0.01 by paired t tests for differences between the control and the intervention group at each time. The number of samples with adequate dust and the number with inadequate dust are presented below each visit for the control and the intervention group. Table 2. Summary of Cat Ownership over a Period of 24 Months
Intervention Control
No cat throughout
Cat throughout
Gave up a cat
Acquired a cat
No of families at 24 m
187 (77.0) 174 (76.3)
33 (13.6) 31 (13.6)
17 (7.0) 16 (7.0)
6 (2.8) 7 (3.1)
243 (100.0) 228 (100.0)
eration where the infants spent most of the time during early infancy. Thus, we encased mattresses, box springs, pillows, and duvets on parents’ beds as well as on infants’ beds, as most infants were in the parents’ bedroom a great deal of the time during the first 6 to 12 months of life. As the carpet is a major reservoir of house-dust mite, we applied an acaricide, benzyl benzoate, to the carpet in the bedrooms of infants and parents, the most commonly used room, as well as to the upholstered furniture of the most commonly used room. We confirmed that encasement of mattresses, box springs, pillows, and duvets with water-impermeable covers and the use of hot water for washing
bedding were effective in reducing house-dust mite allergen levels as reported in other studies.14 –16 We found that the compliance to encasement was very good. The majority of the families did not remove the covers, which remained robust and effective even after 2 years of use. Compliance to the use of hot water to wash bedding was also excellent. Only 10% of families with carpets initially managed to remove carpets from their homes, but 20% of families without carpets initially had carpets during the followup period of 24 months. Over the 2-year period almost one-third of the families had changed residence. Benzyl benzoate applied every 4 months did not significantly re-
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Figure 2. A. Cat allergen levels (Fel d1 g/gram of dust; geometric mean) in families with no cat throughout 24 months in control and intervention groups at different visits. Visit 1, before birth; visit 2 at 2 weeks; visit 3 at 4 months; visit 4 at 8 months; visit 5 at 12 months; and visit 6 at 24 months after the birth of the infants. Control group, dashed line; intervention group, solid line. No differences in cat allergen levels were found in control and intervention group, except for samples from the most commonly used upholstered furniture at 24 months. B. Cat allergen levels (Fel d 1 g/gram of dust; geometric mean) in families with a cat initially but gave it up during the 24 months of observations in control and intervention groups at different visits. Visit 1, before birth; visit 2 at 2 weeks; visit 3 at 4 months; visit 4 at 8 months; visit 5 at 12 months, and visit 6 at 24 months after the birth of the infants. Control group, dashed line; intervention group, solid line. Significant differences between control and intervention group were not found at any time. There were very few samples with adequate dust for assay of allergen collected from infants’ mattresses for presentation in the figure. The number of samples with adequate dust and the number with inadequate dust are presented below each visit for the control and the intervention group.
duce mite allergen levels in the carpets although, in general, the levels were lower in the intervention group. The ineffectiveness of benzyl benzoate has also been reported previously.16,17 In the earlier study, we found that benzyl benzoate reduced mite allergen levels
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but the period of observation was only 3 months.18 As measures to reduce indoor allergen exposure involved the reduction of dust in the homes, it was sometimes not possible to collect enough dust for assay of allergen levels, especially
from mattresses after encasement. We found that the number of parents’ mattress samples with insufficient dust was significantly higher in the intervention group than the control group in visits 2 to 5. Although insufficient dust probably means low allergen levels,
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one can not be entirely sure. Thus, we have analyzed our data in two ways: samples with insufficient dust were either excluded from the analysis or included in the analysis. Both methods showed significantly lower mite allergen levels in parents’ mattress samples in the intervention group compared with the control group after encasement of mattresses even 24 months later. In this study, cats were kept as pets in 19% of homes. Cat allergen was found not only in the homes of cat owners, but also found at lower levels in homes without cats, as reported in other studies.19,20 Even in homes without a cat for the full 24 months, avoidance measures such as encasement of mattresses are probably useful in reducing cat allergen levels. Removal of cats from homes resulted in reduction of cat allergen levels as expected. Most families, however, treated pets as members of the family and were unwilling to part with them. When removal is not possible, our results based on a small number of families suggests that keeping the cat outside the house is useful in reducing indoor cat allergen levels. One limitation of this study is that we did not collect dust samples from parents’ mattresses when the children moved out of the parents’ bedroom to their own bedroom. However, for those families where we collected samples from parents’ mattresses prenatally, and throughout the 24 months of observation, significantly lower levels of mite allergen levels were also found in the intervention group. There is good evidence that there is a dose-response relationship between the level of exposure to house-dust mite allergen and sensitization.5– 8 However, there is no clear-cut relationship between exposure to cat allergen and sensitization.21,22 The significance of exposure to pet allergens in childhood and the risk for asthma is less clear. The European Community Respiratory Health Study conducted in 16 countries has shown surprising results: childhood exposure to cat was associated with a decrease in sensitization to cat in adulthood, particularly among
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those with a family history of atopy.23,24 The authors postulated that childhood exposure to pets might modulate immunologic mechanisms and reduce sensitization to pets in adulthood. This study has shown that it is possible to reduce mite allergen levels for a prolonged period of time. It is not known at present whether reducing exposure to mite or cat allergen level during early infancy is effective in the primary prevention of asthma. Although there have been reports of a reduction in the prevalence of asthma at the age of 1 and 2 years,5,9,25 there was no significant difference in the prevalence of asthma in later childhood between the intervention and the control group. None of the infants in our cohort was sensitized to house-dust mite at the age of 12 months, and the small percentage of 2.1% (1.8% in the control and 2.4% in the intervention group) were sensitized to cat allergen.6 Because sensitization to aeroallergens usually occurs later in childhood,7 the effectiveness of the intervention measures in preventing sensitization and asthma can not be determined until a later followup study is carried out. CONCLUSION We found that the intervention measures applied were effective in reducing house-dust mite allergen levels in parents’ mattresses but not in the carpets. Compliance to these measures was also good. However, compliance to the removal of cats was poor. Removal of the cat from the household resulted in significant reduction of cat allergen levels. A followup study of our cohort will determine whether the reduction in house-dust mite leads to reduction in sensitization and asthma in these high-risk children. ACKNOWLEDGMENTS The authors acknowledge Bencard Allergy Service/SmithKline Beecham and W.L. Gore for their generous donation of their products for this study. We also thank Michelle Dittrick, Maureen Sigurdson, Joan Brooks, Roxanne Rousseau, Henry Chan, Anne DyBuncio, Connie Bassett, Marilyn Lilley, Les-
ley Stewart, and Judy Passante for their assistance, and all the students that have helped to make this study possible. REFERENCES 1. Burney PG. Epidemiologic trends. In: Barnes PJ, Grunstein MM, Leff AR, Woolcock AJ, editors. Asthma. Philadelphia: Lippincott Raven, 1997: 35– 47. 2. Weiss KB, Gergen PJ, Hodgson TA. An economic evaluation of asthma in the United States. N Engl J Med 1992; 326:862– 866. 3. Krahn MD, Berka C, Langlois P, Detsky AS. Direct and indirect costs of asthma in Canada, 1990. CMAJ 1996; 154:821– 831. 4. Platts-Mills TA, Vervloet D, Thomas WR, et al. Indoor allergens and asthma: report of the Third International Workshop. J Allergy Clin Immunol 1997;100:S2–S24. 5. Lau S, Falkenhorst G, Weber A, et al. High mite-allergen exposure increases the risk of sensitization in atopic children and young adults. J Allergy Clin Immunol 1989;84:718 –725. 6. 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. 7. Rowntree S, Cogswell JJ, Platts-Mills TA, Mitchell EB. Development of IgE and IgG antibodies to food and inhalant allergens in children at risk of allergic disease. Arch Dis Child 1985; 60:727–735. 8. Sporik R, Holgate S, Platts-Mills T, Cogswell J. Exposure to house-dust mite allergen (Der p 1) and the development of asthma in childhood. N Engl J Med 1992;323:502–507. 9. Arshad SH, Matthews S, Gant C, Hide DW. Effect of allergen avoidance on development of allergic disorders in infancy. Lancet 1992;339:1493–1497. 10. Chan-Yeung M, Manfreda J, DimichWard H, et al. A randomized controlled trial on the effectiveness of a multifaceted intervention program in the primary prevention of asthma in high-risk infants. Arch Pediatr Adolesc Med 2000;154:657– 663. 11. Chan-Yeung M, Manfreda J, DimichWard J, et al. Mite and cat allergen levels in homes and severity of asthma. Am J Respir Crit Care Med 1995;152: 1805–1811. 12. Luczynska C, Arruda L, Platts-Mills T,
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et al. A two-site monoclonal antibody ELISA for the quantification of the major Dermatophagoides spp. allergens, Der p 1 and Der f 1. J Immunol Methods 1989;118:227–235. Chapman MD, Aalberse RC, Brown MJ, Platts-Mills TA. Monoclonal antibodies to the major feline allergen Fel d 1. II. Single step affinity purification of Fel d 1, N-terminal sequence analysis, and development of a sensitive two-site immunoassay to assess Fel d 1 exposure. J Immunol 1988;140: 812– 818. Colloff MJ, Ayres J, Carswell F, et al. The control of allergens of dust dust mites and domestic pets: a position paper. Clin Exp Allergy 1992; 22(Suppl):1–28. Marks GB, Tovey ER, Green W, et al. The effect of changes in house dust mite allergen exposure on the severity of asthma. Clin Exp Allergy 1995;25: 114 –118. Custovic A, Simpson BM, Simpson A, et al. Manchester Asthma and Allergy Study: low-allergen environment can be achieved and maintained during pregnancy and in early life. J Allergy Clin Immunol 2000;105:252–258.
17. Huss R, Huss M, Squire E, et al. Mite control with acaricide fails. J Allergy Clin Immunol 1992;94:27–32. 18. Chang JH, Becker A, Ferguson A, et al. Effect of application of benzyl benzoate on house dust mite allergen levels. Ann Allergy Asthma Immunol 1996;77:187–190. 19. Noertjojo K, Dimich-Ward H, Obata H, et al. Exposure and sensitization to cat dander: asthma and asthma-like symptoms among adults. J Allergy Clin Immunol 1999;103:60 – 65. 20. Munir AK, Einarsson R, Schou C, Dreborg SK. Allergens in school dust. I. The amount of the major cat (Fel d 1) and dog (Can f 1) allergens in dust from Swedish schools is high enough to probably cause perennial symptoms in most children with asthma who are sensitized to cat and dog. J Allergy Clin Immunol 1993;91:1067–1074. 21. Quirce S, Dimich-Ward H, Chan H, et al. Major cat allergen (Fel d 1) in the homes of patients with asthma and their relationship to sensitization to cat dander. Ann Allergy Asthma Immunol 1995;75:325–330. 22. Sporik R, Ingram JM, Price W, et al. Association of asthma with serum IgE
and skin test reactivity to allergens among children living at high altitude: tickling the dragon’s breath. Am J Respir Crit Care Med 1995;151: 1388 –1392. 23. Roost HP, Kunzli N, Schindler C, et al. Role of current and childhood exposure to cat and atopic sensitization. European Community Respiratory Health Survey. J Allergy Clin Immunol 1999; 104:941–947. 24. Svanes C, Jarvis D, Chinn S, Burney P. Childhood environment and adult atopy: results from the European Community Respiratory Health Survey. J Allergy Clin Immunol 1999;103: 415– 420. 25. Hide DW, Matthews S, Matthews L, et al. Effect of allergen avoidance in infancy on allergic manifestations at age two years. J Allergy Clin Immunol 1994;93:842– 846. Requests for reprints should be addressed to: Dr. Moira Chan-Yeung Respiratory Division, Department of Medicine 2775 Heather Street Vancouver, BC, Canada V5Z 3J5 E-mail:[email protected]
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Moira Chan-Yeung MB, FRCPC*; Alexander Ferguson, MB, FRCPC†; Helen Dimich-Ward, PhD*; Wade Watson, MD, FRCPC‡; Jure Manfreda, MD§; and Allan Becker, MD, FRCPC‡
Background: Allergic sensitization is a major risk factor in asthma. Objective: To evaluate the effectiveness of and compliance to intervention measures in reducing levels of house-dust mite and cat allergen in the context of a randomized, controlled study in the primary prevention of asthma. Methods: A total of 545 high-risk families were recruited prenatally and randomly assigned into the intervention group (n ⫽ 278) and the control group (n ⫽ 267). Intervention measures were instituted before birth of the infants and maintained for 12 months afterward in the intervention group and the control group received the usual care from their family physician. Dust samples were collected at six sites in the homes before birth and at specific intervals up to 24 months after birth for analysis of allergens. At 24 months, there were 244 families in the intervention group and 228 in the control group available for followup examination. Results: House-dust mite avoidance measures, consisting of encasement of mattresses, pillows, and duvets, and hot-water washing of bedding were effective in reducing mite allergen in parents’ mattresses to one-third from baseline, significantly lower than the control group, even at 24 months. The use of an acaricide did not reduce mite allergen levels in carpets and upholstered furniture. Seventeen intervention families gave up their cats but six families acquired a new one over a period of 24 months, similar to control families. Cat allergen levels decreased in all sites in the homes of those who removed the cat, similar in both groups. Conclusions: House-dust mite avoidance measures were effective in reducing house-dust mite allergen in mattresses, but not on floors. Reduction in cat allergen levels were evident for those families who got rid of their cats, but the advice to remove pets was not adhered to by most families. Ann Allergy Asthma Immunol 2002;88:52–58.
INTRODUCTION The prevalence of asthma has been rising in many parts of the world.1 * Occupational and Environmental Lung Diseases Unit, Respiratory Division, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada. † Division of Allergy, Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada. ‡ Section of Allergy, Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada. § Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada. Supported jointly by the Respiratory Health, Network of Center of Excellence; NHRDP, Canada, the British Columbia Lung Association, and the British Columbia Children’s Hospital. Received for publication April 10, 2001. Accepted for publication in revised form October 10, 2001.
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There has been an increase in morbidity from the disease in terms of hospitalization and doctor visits for treatment of asthma. The healthcare costs of the disease are high.2,3 Thus, there is considerable interest in the prevention of this disease. Exposure and sensitization to housedust mite is one of the important risk factors in places where mite allergen levels are high.4 Further, a dose-response relationship was found between the level of house-dust mite allergen and the risk of sensitization.5,6 A concentration of Der p1 ⬎2 g/gram of dust has been found to be necessary for sensitization.7 A prospective study of a high-risk cohort of infants has demonstrated that
infants exposed to a high level of house-dust mite allergen during the first year of life had the greatest risk of developing asthma in a followup study at age 11 years.8 The higher the level of exposure in early infancy, the earlier the symptoms of asthma appeared. The results of this study suggest that the early infancy period may be more susceptible to sensitization. We conducted a prenatally randomized, controlled clinical trial on the primary prevention of asthma in high-risk infants in two Canadian cities in 1994. A multifaceted intervention program was initiated shortly before birth and during the first 12 months of life.10 The intervention measures, which included house-dust mite and pet avoidance measures, resulted in a 34% reduction of “possible and probable asthma” in the intervention group compared with the control group. In this report, we examined the effectiveness of avoidance measures in reducing levels of house-dust mite and cat allergens, and the compliance of families to these intervention measures during the first year of life and determined whether there had been changes in allergen levels 12 months after active intervention measures had ceased. METHODS Participants The trial was conducted in two centers, Vancouver and Winnipeg. High-risk infants, defined as those with at least one first-degree relative with asthma or two first-degree relatives with other immunoglobulin (Ig)E-mediated allergic diseases, were identified in prenatal clinics. The method of recruitment of the families and randomization have
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been described in detail elsewhere.10 An equal number of families were recruited in each center. In total, 278 mothers were randomly allocated to the intervention group and 267 to the control (usual care) group. There were 242 families in the control and 252 in the intervention group at 12 months, and 228 and 244, respectively, at 24 months followup. The dropout rate was similar between the control and the intervention group, at 6 and 3%, respectively. Intervention Program The intervention measures were applied for a 12-month period from birth. On each home visit, the research nurse reinforced the importance of avoidance measures and encouraged the families who were assigned to the intervention group to continue with them. Control families did not receive any intervention measures. House-Dust Mite and Pet Avoidance Measures. 1) All mattresses, box springs, pillows, and quilts in parents’ beds were encased with vapor-impermeable covers (Intervent bedding system, WL Gore and Associates, Surrey, England). All mattresses in the infants’ bed were also encased. All covers were provided free of charge and put in place by the research nurse. 2) Parents were instructed to wash all bedding in hot water (55° C) at least fortnightly. 3) Removal of carpets, if at all possible, and especially from bedrooms. 4) Benzyl benzoate (Acarosan powder; Bencard Laboratories/SmithKline Beecham, Philadelphia, PA) was applied by the research nurses on carpets in parents’ and infants’ bedroom and the most commonly used room when their removal was not possible. Benzyl benzoate foam was applied to upholstered furniture in the most commonly used room. These applications were carried out before birth and at 4 and 8 months after the birth of the infants. Powder and foam were left on carpets and furniture for 8 to 12 hours before removal by vacuuming. 5) Parents who had cats, dogs, and other furry pets were counseled to get rid of them. If this was not possible, they were instructed
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to keep pets outside the house, or at least outside the infant’s bedroom. Parents without pets were advised not to get one. Dust Collection Home visits were carried out before the birth of the infant (initial) and at 2 weeks, 4, 8, 12, and 24 months after birth. A questionnaire was completed for the intervention group during each visit regarding compliance to various allergen avoidance measures. Dust samples were collected from six sites: infant’s bedroom floor and mattress, parents’ bedroom floor and mattress, the floor of the most commonly used room, and the upholstered furniture in that room. When infants moved out of the parents’ bedroom, dust samples were no longer collected from the parents’ bedrooms. A standard protocol was used for dust collection as described previously.11 Dust samples were collected using a portable vacuum cleaner, with a special sock attachment. The material for the socks had pore sizes approximately 5 m in diameter. The floor, most used upholstered furniture item, and bed mattresses were each vacuumed for 2 minutes. The socks were placed in a ziplocked bag and stored at ⫺20° C until being extracted and analyzed for housedust mite and cat allergens. Large particles were removed by using a 300-m mesh sieve before processing. Samples of dust were extracted in borate-buffered saline in the ratio of 100 mg to 2 mL, left overnight and filtered. Extracts were stored at ⫺20° C until analyzed for allergen levels. Allergen Assay The levels were determined using an ELISA assay with purified monoclonal antibodies against group 1 mite allergens, Dermatophagoides pteronyssinus and Dermatophagoides farinae (Der p 1 and Der f 1) and cat allergen, Fel d 1, respectively.12,13 The extracts of house dust were diluted 1:5, 1:10, and 1:100 for assay in duplicate. The species-specific monoclonal antibodies were used to coat microtiter plates, which were then incubated with the
standard or the extract. Bound allergen was detected using a separate biotinylated monoclonal antibody that recognized a different epitope on Fel d 1 for cat allergen and a common epitope on both Der p 1 and Der f 1 for mite allergen assays, followed by the addition of streptavidin-peroxidase and 2,2⬘-azinobis-(3-ethylbenthiazoline-6sulfonic acid)/H2O2 substrate. The absorbance was read from an ELISA reader at 405 nm. The amount of antigen present in the dust sample was calculated from a standard curve. The lower detection limit for each allergen was 0.5 ng/mL. The total mite allergen (sum of Der p 1 and Der f 1) was reported as g/gram of dust. Statistical Analyses House-dust mite and cat allergen levels were log-normally distributed; the results were reported as geometric means. The analyses were carried out 1) when samples with inadequate dust for ELISA assay were excluded and 2) when samples with insufficient dust were assigned a zero value and included. The results of analyses with samples with inadequate dust excluded are presented in the Results section, unless stated otherwise. Allergen levels of the control and the intervention group were compared at each visit using unpaired t test. Differences between the control and the intervention groups over time were examined with a two-factor ANOVA with repeated measures. Statistical analysis was carried out using SPSS/PC Version 9 for Windows (SPSS 1989 –99, Chicago, IL). Ethics The Ethics Committees of the University of British Columbia and the University of Manitoba approved the study. RESULTS In the intervention group, only 20 (10.9%) of 184 families with carpets in the homes initially managed to remove carpets over a period of 24 months. However, over the same period, 15 (20.8%) of 72 families without carpets in the homes initially had carpets during subsequent visits. Over the 2-year
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period, 154 (32.7%) of the families had changed residence. Table 1 shows the percentage and number of families in the intervention group that had encasement of mattresses, box spring, and pillows, washed bedding in hot water, and applied benzyl benzoate on each occasion after the birth of the infants. Of parents, 94.3% had encasement of mattress, box springs, and pillows. At the end of 12 months, 91.8% continued to use encasement, and at 24 months, the percentage dropped to 86.5. A total of 30 parents in the intervention group removed the encasement from their beds by 24 months. Of infants’ mattresses, 93.4% were encased, and the proportion remained relatively the same for 24 months. Approximately 70% of families had carpets in their homes. For all families with carpets, benzyl benzoate was applied in all three rooms at the time of recruitment and 2 weeks after the birth of the infant. On subsequent occasions, benzyl benzoate was not applied after infants were moved out of the parents’ bedroom. The proportion of families that agreed with the continual application of benzyl benzoate on carpets in bedrooms (parents’ and infants’) remained high at 8 months. The proportion of families that agreed to the application of benzyl benzoate to the upholstered furniture in the most commonly used room, dropped from 100% at the initial
visit to 75 and 70%, respectively, at 4 and 8 months. Using ANOVA for repeated measures, we found significant differences in mite allergen levels between the control and the intervention group over time in parents’ mattresses (P ⬍ 0.001) and the average of the floor samples (P ⬍ 0.01, irrespective of whether the samples with insufficient dust were included as having zero allergen or excluded from the analysis. Figure 1 shows mite allergen levels from samples collected from parents’ and infants’ mattresses, floor samples (average of three rooms), and from the upholstered furniture of the most commonly used room. The number of samples with insufficient dust for assay is presented below the figure; these samples were excluded from this analysis. Among parents’ mattress samples, a significantly higher proportion in the intervention group had samples with insufficient dust compared with the control group at all times after the birth of the infants. No differences were found in mite allergen levels at the onset of the study between the intervention and the control group from all sites. Encasement of mattresses, box springs, and pillows, and hot-water washing of bedding resulted in a reduction of house-dust mite allergen levels in parents’ mattresses to approximately one-third in the intervention group, significantly lower compared
with the control group (P ⬍ 0.01) at all followup visits except for visit 4. Few samples collected from infants’ mattresses had adequate dust for allergen assay. Mite allergen levels were low on samples that were measurable; mite allergen levels were found significantly lower in the intervention group in visit 3 only. The application of benzyl benzoate to carpets and upholstered furniture in the most commonly used room did not lower mite allergen levels significantly in the intervention group, with the exception of floor dust samples collected at visit 6. Table 2 summarizes cat ownership in both groups over the period of 24 months. The number of families in the intervention group that were rid of their cat was similar to those in the control group. A similar number of intervention and control families had acquired a new cat during the period of the study. Of the 33 families who had a cat throughout the 24 months, 3 claimed that the cat was kept outside the home and 22 outside the infant’s bedroom. There were no differences in the initial levels of cat allergen between the intervention and the control group. For families without a cat throughout 24 months, cat allergen levels were lower in parents’ mattress and upholstered furniture in the intervention compared with those in the control group, but were only significantly different at 24 months for samples from upholstered
Table 1. Participation of Families in the Intervention Group 2 weeks Encasement of parent’s bed, N (%) Encasement of infant’s bed, N (%) Hot water wash of bedding, N (%) Parent’s bedroom with carpet* N Acarosan applied, N (%) Infant’s bedroom with carpet N Acarosan applied, N (%) Most commonly used room with carpet N Acarosan applied, N (%) Acarosan applied to upholstered furniture, N (%)
230 (94.3) 228 (93.4) 236 (96.7) 178 178 (100) 174 174 (100) 173 173 (100) 100
4 months 230 (94.3) 230 (94.3) 237 (97.1) 172 171 (99.4) 174 158 (90.9) 169 163 (96.4) 75.0
8 months 225 (92.2) 226 (92.6) 238 (97.6) 157 148 (94.3) 176 159 (90.6) 170 153 (90.0) 69.9
12 months
24 months
224 (91.8) 223 (91.4) 238 (97.6) 134 NA 170 NA 172 NA NA
194 (86.5) 221 (90.6) 234 (95.9) NA NA NA NA
Families in the intervention group (n ⫽ 244) who followed the house dust mite avoidance measures during the 12-month period and their status at 24 months. * When infant moved out of parents’ bedroom, Acarosan was no longer applied to the parents’ bedroom. The number of families where children moved out of parents’ bedroom were 7, 30, and 59 at 4, 8, and 12 months, respectively, some with carpets and some without carpets. N represents the number of families with carpets in parents’ bedroom at the time of the visit. NA indicates that Acarosan was not applied.
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furniture (Fig 2A). There were significantly (P ⬍ 0.01) more mattress samples from parents’ bedrooms excluded because of insufficient dust in the intervention group than in the control group at visits 2 to 5 (Fig 2A). When samples with insufficient dust were included as zero in the analysis, cat allergen levels from parents’ mattresses were significantly lower in the intervention group at all times. For families with a cat throughout 24 months, cat allergen levels at all sites were high initially and in all subsequent visits. For the three families that claimed that they kept the cat outside the home, cat allergen levels were lower in floor samples compared with families with cats inside the home at the onset of the study (average floor level of Fel d 1 of 1.61 vs 6.17 g/ gram of dust) and at all followup visits. However, no differences were found in cat allergen levels in the infants’ bedrooms between families that claimed they kept the cat outside the infants’ room and families that allowed the cat into the infants’ bedrooms. Figure 2B shows cat allergen levels from parents’ and infants’ mattresses, floor (average of three rooms), and upholstered furniture of the most commonly used room from homes with a cat initially and the cat was removed subsequently during one of the followup visits (17 in the intervention and 16 in the control group). Reduction in cat allergen levels was found at all sites in both groups, but the differences between groups were not significant at any time during the 24-month period of observation. For the few families who acquired a cat after the initial visit, cat allergen levels increased with time in parents’ mattress in the control group (data not shown). DISCUSSION In this study, we examined the effectiveness of the intervention measures in reducing house-dust mite and cat allergen levels and the compliance to these measures carried out in the context of a primary prevention of asthma in high-risk infants. Intervention measures were applied, taking into consid-
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Figure 1. House-dust mite allergen levels (g/gram of dust; geometric mean) in control and intervention groups at different visits. Visit 1, before birth; visit 2 at 2 weeks; visit 3 at 4 months; visit 4 at 8 months; visit 5 at 12 months; and visit 6 at 24 months after the birth of the infants. Control group, dashed line; intervention group, solid line. * P ⬍0.05 and ** P ⬍0.01 by paired t tests for differences between the control and the intervention group at each time. The number of samples with adequate dust and the number with inadequate dust are presented below each visit for the control and the intervention group. Table 2. Summary of Cat Ownership over a Period of 24 Months
Intervention Control
No cat throughout
Cat throughout
Gave up a cat
Acquired a cat
No of families at 24 m
187 (77.0) 174 (76.3)
33 (13.6) 31 (13.6)
17 (7.0) 16 (7.0)
6 (2.8) 7 (3.1)
243 (100.0) 228 (100.0)
eration where the infants spent most of the time during early infancy. Thus, we encased mattresses, box springs, pillows, and duvets on parents’ beds as well as on infants’ beds, as most infants were in the parents’ bedroom a great deal of the time during the first 6 to 12 months of life. As the carpet is a major reservoir of house-dust mite, we applied an acaricide, benzyl benzoate, to the carpet in the bedrooms of infants and parents, the most commonly used room, as well as to the upholstered furniture of the most commonly used room. We confirmed that encasement of mattresses, box springs, pillows, and duvets with water-impermeable covers and the use of hot water for washing
bedding were effective in reducing house-dust mite allergen levels as reported in other studies.14 –16 We found that the compliance to encasement was very good. The majority of the families did not remove the covers, which remained robust and effective even after 2 years of use. Compliance to the use of hot water to wash bedding was also excellent. Only 10% of families with carpets initially managed to remove carpets from their homes, but 20% of families without carpets initially had carpets during the followup period of 24 months. Over the 2-year period almost one-third of the families had changed residence. Benzyl benzoate applied every 4 months did not significantly re-
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Figure 2. A. Cat allergen levels (Fel d1 g/gram of dust; geometric mean) in families with no cat throughout 24 months in control and intervention groups at different visits. Visit 1, before birth; visit 2 at 2 weeks; visit 3 at 4 months; visit 4 at 8 months; visit 5 at 12 months; and visit 6 at 24 months after the birth of the infants. Control group, dashed line; intervention group, solid line. No differences in cat allergen levels were found in control and intervention group, except for samples from the most commonly used upholstered furniture at 24 months. B. Cat allergen levels (Fel d 1 g/gram of dust; geometric mean) in families with a cat initially but gave it up during the 24 months of observations in control and intervention groups at different visits. Visit 1, before birth; visit 2 at 2 weeks; visit 3 at 4 months; visit 4 at 8 months; visit 5 at 12 months, and visit 6 at 24 months after the birth of the infants. Control group, dashed line; intervention group, solid line. Significant differences between control and intervention group were not found at any time. There were very few samples with adequate dust for assay of allergen collected from infants’ mattresses for presentation in the figure. The number of samples with adequate dust and the number with inadequate dust are presented below each visit for the control and the intervention group.
duce mite allergen levels in the carpets although, in general, the levels were lower in the intervention group. The ineffectiveness of benzyl benzoate has also been reported previously.16,17 In the earlier study, we found that benzyl benzoate reduced mite allergen levels
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but the period of observation was only 3 months.18 As measures to reduce indoor allergen exposure involved the reduction of dust in the homes, it was sometimes not possible to collect enough dust for assay of allergen levels, especially
from mattresses after encasement. We found that the number of parents’ mattress samples with insufficient dust was significantly higher in the intervention group than the control group in visits 2 to 5. Although insufficient dust probably means low allergen levels,
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one can not be entirely sure. Thus, we have analyzed our data in two ways: samples with insufficient dust were either excluded from the analysis or included in the analysis. Both methods showed significantly lower mite allergen levels in parents’ mattress samples in the intervention group compared with the control group after encasement of mattresses even 24 months later. In this study, cats were kept as pets in 19% of homes. Cat allergen was found not only in the homes of cat owners, but also found at lower levels in homes without cats, as reported in other studies.19,20 Even in homes without a cat for the full 24 months, avoidance measures such as encasement of mattresses are probably useful in reducing cat allergen levels. Removal of cats from homes resulted in reduction of cat allergen levels as expected. Most families, however, treated pets as members of the family and were unwilling to part with them. When removal is not possible, our results based on a small number of families suggests that keeping the cat outside the house is useful in reducing indoor cat allergen levels. One limitation of this study is that we did not collect dust samples from parents’ mattresses when the children moved out of the parents’ bedroom to their own bedroom. However, for those families where we collected samples from parents’ mattresses prenatally, and throughout the 24 months of observation, significantly lower levels of mite allergen levels were also found in the intervention group. There is good evidence that there is a dose-response relationship between the level of exposure to house-dust mite allergen and sensitization.5– 8 However, there is no clear-cut relationship between exposure to cat allergen and sensitization.21,22 The significance of exposure to pet allergens in childhood and the risk for asthma is less clear. The European Community Respiratory Health Study conducted in 16 countries has shown surprising results: childhood exposure to cat was associated with a decrease in sensitization to cat in adulthood, particularly among
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those with a family history of atopy.23,24 The authors postulated that childhood exposure to pets might modulate immunologic mechanisms and reduce sensitization to pets in adulthood. This study has shown that it is possible to reduce mite allergen levels for a prolonged period of time. It is not known at present whether reducing exposure to mite or cat allergen level during early infancy is effective in the primary prevention of asthma. Although there have been reports of a reduction in the prevalence of asthma at the age of 1 and 2 years,5,9,25 there was no significant difference in the prevalence of asthma in later childhood between the intervention and the control group. None of the infants in our cohort was sensitized to house-dust mite at the age of 12 months, and the small percentage of 2.1% (1.8% in the control and 2.4% in the intervention group) were sensitized to cat allergen.6 Because sensitization to aeroallergens usually occurs later in childhood,7 the effectiveness of the intervention measures in preventing sensitization and asthma can not be determined until a later followup study is carried out. CONCLUSION We found that the intervention measures applied were effective in reducing house-dust mite allergen levels in parents’ mattresses but not in the carpets. Compliance to these measures was also good. However, compliance to the removal of cats was poor. Removal of the cat from the household resulted in significant reduction of cat allergen levels. A followup study of our cohort will determine whether the reduction in house-dust mite leads to reduction in sensitization and asthma in these high-risk children. ACKNOWLEDGMENTS The authors acknowledge Bencard Allergy Service/SmithKline Beecham and W.L. Gore for their generous donation of their products for this study. We also thank Michelle Dittrick, Maureen Sigurdson, Joan Brooks, Roxanne Rousseau, Henry Chan, Anne DyBuncio, Connie Bassett, Marilyn Lilley, Les-
ley Stewart, and Judy Passante for their assistance, and all the students that have helped to make this study possible. REFERENCES 1. Burney PG. Epidemiologic trends. In: Barnes PJ, Grunstein MM, Leff AR, Woolcock AJ, editors. Asthma. Philadelphia: Lippincott Raven, 1997: 35– 47. 2. Weiss KB, Gergen PJ, Hodgson TA. An economic evaluation of asthma in the United States. N Engl J Med 1992; 326:862– 866. 3. Krahn MD, Berka C, Langlois P, Detsky AS. Direct and indirect costs of asthma in Canada, 1990. CMAJ 1996; 154:821– 831. 4. Platts-Mills TA, Vervloet D, Thomas WR, et al. Indoor allergens and asthma: report of the Third International Workshop. J Allergy Clin Immunol 1997;100:S2–S24. 5. Lau S, Falkenhorst G, Weber A, et al. High mite-allergen exposure increases the risk of sensitization in atopic children and young adults. J Allergy Clin Immunol 1989;84:718 –725. 6. 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. 7. Rowntree S, Cogswell JJ, Platts-Mills TA, Mitchell EB. Development of IgE and IgG antibodies to food and inhalant allergens in children at risk of allergic disease. Arch Dis Child 1985; 60:727–735. 8. Sporik R, Holgate S, Platts-Mills T, Cogswell J. Exposure to house-dust mite allergen (Der p 1) and the development of asthma in childhood. N Engl J Med 1992;323:502–507. 9. Arshad SH, Matthews S, Gant C, Hide DW. Effect of allergen avoidance on development of allergic disorders in infancy. Lancet 1992;339:1493–1497. 10. Chan-Yeung M, Manfreda J, DimichWard H, et al. A randomized controlled trial on the effectiveness of a multifaceted intervention program in the primary prevention of asthma in high-risk infants. Arch Pediatr Adolesc Med 2000;154:657– 663. 11. Chan-Yeung M, Manfreda J, DimichWard J, et al. Mite and cat allergen levels in homes and severity of asthma. Am J Respir Crit Care Med 1995;152: 1805–1811. 12. Luczynska C, Arruda L, Platts-Mills T,
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et al. A two-site monoclonal antibody ELISA for the quantification of the major Dermatophagoides spp. allergens, Der p 1 and Der f 1. J Immunol Methods 1989;118:227–235. Chapman MD, Aalberse RC, Brown MJ, Platts-Mills TA. Monoclonal antibodies to the major feline allergen Fel d 1. II. Single step affinity purification of Fel d 1, N-terminal sequence analysis, and development of a sensitive two-site immunoassay to assess Fel d 1 exposure. J Immunol 1988;140: 812– 818. Colloff MJ, Ayres J, Carswell F, et al. The control of allergens of dust dust mites and domestic pets: a position paper. Clin Exp Allergy 1992; 22(Suppl):1–28. Marks GB, Tovey ER, Green W, et al. The effect of changes in house dust mite allergen exposure on the severity of asthma. Clin Exp Allergy 1995;25: 114 –118. Custovic A, Simpson BM, Simpson A, et al. Manchester Asthma and Allergy Study: low-allergen environment can be achieved and maintained during pregnancy and in early life. J Allergy Clin Immunol 2000;105:252–258.
17. Huss R, Huss M, Squire E, et al. Mite control with acaricide fails. J Allergy Clin Immunol 1992;94:27–32. 18. Chang JH, Becker A, Ferguson A, et al. Effect of application of benzyl benzoate on house dust mite allergen levels. Ann Allergy Asthma Immunol 1996;77:187–190. 19. Noertjojo K, Dimich-Ward H, Obata H, et al. Exposure and sensitization to cat dander: asthma and asthma-like symptoms among adults. J Allergy Clin Immunol 1999;103:60 – 65. 20. Munir AK, Einarsson R, Schou C, Dreborg SK. Allergens in school dust. I. The amount of the major cat (Fel d 1) and dog (Can f 1) allergens in dust from Swedish schools is high enough to probably cause perennial symptoms in most children with asthma who are sensitized to cat and dog. J Allergy Clin Immunol 1993;91:1067–1074. 21. Quirce S, Dimich-Ward H, Chan H, et al. Major cat allergen (Fel d 1) in the homes of patients with asthma and their relationship to sensitization to cat dander. Ann Allergy Asthma Immunol 1995;75:325–330. 22. Sporik R, Ingram JM, Price W, et al. Association of asthma with serum IgE
and skin test reactivity to allergens among children living at high altitude: tickling the dragon’s breath. Am J Respir Crit Care Med 1995;151: 1388 –1392. 23. Roost HP, Kunzli N, Schindler C, et al. Role of current and childhood exposure to cat and atopic sensitization. European Community Respiratory Health Survey. J Allergy Clin Immunol 1999; 104:941–947. 24. Svanes C, Jarvis D, Chinn S, Burney P. Childhood environment and adult atopy: results from the European Community Respiratory Health Survey. J Allergy Clin Immunol 1999;103: 415– 420. 25. Hide DW, Matthews S, Matthews L, et al. Effect of allergen avoidance in infancy on allergic manifestations at age two years. J Allergy Clin Immunol 1994;93:842– 846. Requests for reprints should be addressed to: Dr. Moira Chan-Yeung Respiratory Division, Department of Medicine 2775 Heather Street Vancouver, BC, Canada V5Z 3J5 E-mail:[email protected]
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