SEARCH

SEARCH BY CITATION

Keywords:

  • allergic sensitization;
  • radioallergosorbent test

Abstract

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Conclusion
  7. Acknowledgment
  8. References

Background:  Specific IgE antibodies are often detected without any clinical manifestation of allergies. We aimed to analyse the predictivity of allergic sensitization for incident symptoms of allergic diseases in adults during a 10-year follow-up .

Methods:  In 1994/95 specific IgE antibodies against five common inhalant allergens (grass pollen, birch pollen, house dust mite, cat dander and Cladosporium) were diagnosed by radioallergosorbent test in 4178 adults aged 25–74 years. A subset of 2656 participants could be re-evaluated in 2004/05. Information on socio-economic factors and medical history, including data on atopic diseases, was assessed by a combination of a personal interview and a self-administered questionnaire. Logistic regression models were applied to study associations between allergic sensitization and incident allergic diseases.

Results:  Allergic sensitization was an important predictor for incident hay fever (OR 7.95, CI 95% 4.64–13.62) and asthma (OR 1.82, CI 95% 1.29–2.57). Specific IgE antibodies were mainly related to outdoor allergens (grass and birch pollen) for hay fever and indoor allergens (mite and cat dander) for asthma, while for atopic dermatitis no specific IgE antibodies were identified as major predictors.

Conclusions:  Allergic sensitization not only covers clinically apparent allergies, but indicates a prognostic factor for later allergies, even in adulthood.

Although allergic diseases are very common in both children and adults, epidemiological studies on atopic disorders in adults are less common. Prevalence rates vary between different regions and countries and affect up to 50% of the population (1). The development and severity of atopic diseases depend on a complex interaction between genetic factors, environmental exposure to allergens and nonspecific adjuvant factors such as lifestyle, tobacco smoke, air pollution and infections starting early in life (2). Besides clinical diagnosis of typical symptoms of hay fever, asthma or atopic dermatitis (AD), IgE antibodies as typical markers for atopic sensitization can be diagnosed by two main techniques, indirectly by skin prick test (SPT) and directly by radioallergosorbent test (RAST). Both tests were found to perform better in the negative than in the positive prediction of hay fever (3). RAST determines allergen-specific IgE antibodies in the serum and, in contrast with SPT, gives a quantitative result of detected IgE antibodies. The validity of RAST as indicator for clinical allergy depends on used cut-off points for RAST-classes (3, 4). However, often high sensitization rates and RAST-classes are found without apparent allergies. We aimed to analyse the predictivity of allergic sensitization diagnosed by RAST regarding incident cases of hay fever, asthma and AD in adults in a 10-year follow-up study.

Methods

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Conclusion
  7. Acknowledgment
  8. References

Study population and questionnaire

Study participants were evaluated in 1994/95 and 2004/05 in the framework of the KORA project (Cooperative Health Research in the Augsburg Region), a research platform for population based health research in the fields of epidemiology, health economics and health care research in the City of Augsburg and two adjacent counties (5). The study region has a population of about 600 000 of which 430 000 inhabitants were between 25 and 74 years of age in 1994/95. The sample was drawn in a two-stage procedure where first Augsburg city and 16 communities from the adjacent counties were selected by cluster sampling; then age-sex stratified random sampling was performed within each community (5, 6). The participants were sampled through the registration offices and invited to a specific, medically equipped study center. The KORA studies consist of a combination of extended health examinations and questionnaire-based (personal interview and self-administered) evaluations. Of the 4856 participants of the baseline study S3 in 1994/95, 3006 participated in the 10-year follow-up study F3 in 2004/05. Subjects were considered ineligible for F3 if they had died in the meantime (n = 405, 8%), lived too far outside the study region or were completely lost to follow-up (n = 222, 5%), or had demanded deletion of their address data (n = 270, 6%). Of the remaining 3959 eligible persons, 161 could not be contacted, 295 were unable to come because they were too ill or had no time, and 497 were not willing to participate in this follow-up, resulting in a response rate of 76%. For the present evaluation a subgroup of 4178 adults providing information on RAST-sensitization at baseline in 1994/95 with 2656 who could be re-approached 2004/05 was used. Study characteristics and data on baseline and follow-up are given in Table 1. Baseline information on socio-demographic variables, living conditions, risk factors (smoking, alcohol consumption, physical activity etc.), medical history and family history of chronic diseases, medication use and more was acquired by a standardized face to face interview by medical staff. An additional self-administered questionnaire collected data on present health conditions, including respiratory and allergic diseases. Data on atopic diseases in 2004/05 was assessed by self-administered questionnaire, asking: ‘Did a doctor ever diagnose the following diseases?: asthma, atopic dermatitis, hay fever’.

Table 1.   Baseline study characteristics and comparison of follow-up-participants and -nonparticipants
 Baseline study (S3) 1994/95Follow-up participants (F3) 2004/05Follow-up nonparticipants
  1. *10 years or more.

  2. †IgE positive: at least one RAST ≥ class 1.

Variables, % (n/N)N = 4178N = 2656N = 1522
Age (years)49.4 ± 14.047.3 ± 12.953.0 ± 15.2
Gender (female)50.7 (2119/4178)52.0 (1382/2656)48.4 (737/1522)
Higher parental education*43.4 (1815/4178)48.4 (1285/2656)34.8 (530/1522)
Smoking24.8 (1036/4178)23.5 (624/2656)27.1 (412/1522)
Allergic sensitization†31.6 (1305/4126)32.4 (857/2645)31.7 (480/1513)
Atopic diseases30.7 (1127/3676)30.5 (737/2416)31.0 (390/1260)
 Asthma2.2 (86/3853)2.2 (54/2504)2.4 (32/1349)
 Hay fever 14.5 (560/3866)14.6 (367/2507)14.2 (193/1359)
 Allergies or eczema23.2 (865/3730)23.4 (575/2457)22.8 (290/1273)

Allergen-specific IgE antibodies

During the first examination period in 1994/95, blood sample analyses included the detection of specific IgE antibodies against five common inhalant allergens (grass pollen, birch pollen, house dust mite (Der p1), cat dander (Fel d1) and Cladosporium herbarum). The standard laboratory procedures (RAST-CAP-FEIA; Pharmacia, Uppsala, Sweden) were performed by Pharmacia Diagnostics in Freiburg, Germany. The detection limit for RAST reactivity was set at 0.35 kU/l. Atopic sensitization was defined to be present if at least one of the five specific IgE antibodies was positive (RAST-class >0).

Statistical analyses

Descriptive statistical analyses and multivariate logistic regression modelling were carried out using sas (SAS Institute Inc, Cary, NC, USA), version 9.13. Logistic regression analyses were performed to identify the predictivity of allergic sensitization adjusting for potential confounders such as age, gender, education and smoking. The logistic regression models were applied for incident health outcomes of hay fever, asthma and AD 10 years after evaluating the atopic baseline status by RAST and questionnaire. Afterwards the same models were applied to identify the predictivity of sensitization to single aeroallergens.

Results

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Conclusion
  7. Acknowledgment
  8. References

A total of 4178 adults aged 25–74 years could be recruited for the baseline RAST-evaluation in 1994/95. Four thousand one hundred and twenty-six provided information on all five tested allergens (Table 2). About one-third of the participants were sensitized to any allergen with highest rates for house dust mite and grass pollen. The followed up study population of 2656 adults (Table 1) who were taken further analyses showed similar rates.

Table 2.   Data on allergic sensitization at Baseline (1994/95)
RAST-classes (IgE-levels)House dust miteGrass pollenBirch pollenCat allergenCladosporiumAny allergen
  1. Variables, % (n/N).

1 (>0.35 kU/l)5.0 (208/4175)3.4 (140/4154)2.2 (90/4128)2.9 (121/4172)1.0 (43/4144)12.7 (522/4126)
2 (>0.7 kU/l)6.6 (275/4175)5.2 (214/4154)3.9 (160/4128)3.4 (141/4172)0.5 (21/4144)15.7 (648/4126)
3 (>3.5 kU/l)3.1 (131/4175)4.8 (201/4154)3.6 (147/4128)1.6 (68/4172)0.1 (3/4144)10.9 (450/4126)
≥4 (>17.5 kU/l)1.1 (44/4175)3.2 (132/4154)3.4 (139/4128)0.7 (27/4172)0.1 (3/4144)6.9 (285/4126)
Total15.8 (658/4175)16.5 (658/4154)13.0 (536/4128)8.6 (357/4172)1.7 (70/4144)31.6 (1305/4126)

The incidence of hay fever from 1994/95 to 2004/05 was 3.9%, being highest among the youngest adults (Fig. 1). In contrast, for asthma, the incidence increased by age with an overall incidence of 6.5% for the 10-year-follow-up period. Allergic sensitization was an important predictor for existing (lifetime prevalence) and incident asthma and hay fever (Table 3, Fig. 2A–C). Rates of atopic diseases were slightly influenced by age and gender with all diseases being more frequent among female adults (Table 3). Hay fever and AD was more common in higher educated adults, while results for asthma were independent from the education. Rates for hay fever were higher among those living in the city of Augsburg.

image

Figure 1.  Age-dependent 10 year incidence of asthma and hay fever.

Download figure to PowerPoint

Table 3.   Logistic regression models for follow-up health outcomes
 Follow-up 2004/05
Lifetime prevalenceIncidence
Adjusted model 1*Adjusted model 2†Adjusted model 1*Adjusted model 2†
ORCI 95%ORCI 95%ORCI 95%ORCI 95%
  1. *Age, gender.

  2. †Age, gender, education, smoking, place of residence (urban vs rural).

  3. AD, atopic dermatitis. Significant values are indicted in bold.

a) Hay fever (doctor-diagnosed)n/N = 317/2294n/N = 76/1960
Sensitization19.9713.75–29.020.8314.27–30.407.704.51–13.178.054.69–13.82
Covariates
 Age0.750.66–0.850.730.64–0.840.680.54–0.850.650.51–0.83
 Gender (female)1.531.17–2.001.591.21–2.101.681.04–2.721.661.02–2.70
 Higher education  2.001.48–2.66  1.390.84–2.31
 Smoking   0.410.29–0.58  0.450.25–0.83
 Place of residence (urban/rural)  1.581.20–2.08  1.921.18–3.12
b) Asthma (doctor-diagnosed)n/N = 178/2294n/N = 145/2245
Sensitization2.081.52–2.852.071.51–2.841.811.28–2.561.821.29–2.57
Covariates
 Age1.261.09–1.461.271.09–1.481.231.05–1.441.211.02–1.44
 Gender (female)1.140.83–1.551.150.84–1.571.130.80–1.591.120.79–1.58
 Higher education  1.020.74–1.40  0.870.61–1.23
 Smoking   1.090.76–1.58  1.080.72–1.62
 Place of residence (urban/rural)  1.220.89–1.66  1.180.84–1.65
c) AD (doctor-diagnosed)n/N = 66/2253n/N = 27/1774
Sensitization1.380.84–2.291.340.81–2.220.750.31–1.790.720.30–1.74
Covariates
 Age0.750.59–0.950.780.61–1.000.870.62–1.240.920.63–1.33
 Gender (female)2.581.48–4.472.621.51–4.582.351.02–5.432.501.08–5.81
 Higher education  1.951.12–3.38  2.190.94–5.11
 Smoking   0.550.28–1.07  0.640.24–1.75
 Place of residence (urban/rural)  1.300.79–2.14  1.470.68–3.19
image

Figure 2.  Incident cases of atopic diseases in adults within a 10-year follow-up. (A) Incident cases of hay fever; (B) incident cases of asthma; (C) incident cases of atopic dermatitis.

Download figure to PowerPoint

When comparing single aeroallergens related to incident cases of hay fever, asthma and AD, clear pictures could be seen for all three diseases. Incident asthma was mainly associated with indoor allergens of house dust mite and cat dander (Fig. 2B), while allergic sensitization did not seem to play any important role for the prediction of AD later in adulthood (Fig. 2C). Incident hay fever was strongly associated with outdoor allergens tested by grass and birch pollen, but additionally seemed to be related to cat sensitization (Fig. 2A). When applying the same logistic regression models to the single aeroallergens as to sensitization in general, outdoor allergens for incident hay fever and indoor allergens for incident asthma remained relevant predictors (Table 4).

Table 4. Single aeroallergens related to incident health outcomes up to 2004/05
 Hay fever (doctor-diagnosed) n/N = 76/1960Asthma (doctor-diagnosed) n/N = 145/2245Atopic dermatitis (doctor-diagnosed) n/N = 27/1774
ORCI 95%ORCI 95%ORCI 95%
  1. Logistic regression models adjusted for age, gender, education, smoking, place of residence (urban vs rural), specific allergens.

Sensitization8.054.69–13.821.821.29–2.570.720.30–1.74
 Grass pollen2.161.11–4.201.160.68–1.972.020.59–6.89
 Birch pollen7.844.16–14.760.990.57–1.710.420.08–2.24
 House dust mite0.720.35–1.461.641.05–2.550.430.09–1.97
 Cat dander1.340.59–3.032.631.59–4.351.190.25–5.59
 Cladosporium1.000.19–5.231.260.44–3.582.470.25–24.41

Discussion

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Conclusion
  7. Acknowledgment
  8. References

Radioallergosorbent test-sensitization has an important impact on the predictivity of incident hay fever and asthma, even in adults. We could demonstrate a clear association of sensitization to outdoor allergens with the development of hay fever and a significantly increased risk of doctor-diagnosed asthma when sensitized to indoor allergens. For the incidence of asthma and hay fever, age-dependent but contrariwise trends can be seen with higher incidence of hay fever the younger and higher incidence of asthma the older the population is. Our results on incidence and age-trends are in line with other studies on incidence and remission of allergic rhinitis (7–9). However in our evaluation, we could not analyse remission rates as for analyses in 2004/05 we asked for ‘Did a doctor ever diagnose the following diseases?: (asthma, atopic dermatitis, hay fever)?’ and not whether the diseases resolved. Overall, longitudinal adult studies on allergic sensitization and outcomes are rare. Most research groups focus on children as in the prevalence and incidence of allergic diseases children still represent the biggest part (10–12). According to some evaluations, the epidemic may have reached a plateau by now (13, 14). Nevertheless, allergic illnesses especially asthma are common and costly diseases (10) and have a substantial impact on children’s and adults’ health.

In the clinical practice, the main method used to diagnose allergic sensitization is the SPT which is a test performed quickly and easily. In contrast with the RAST SPT is not able to give a clear quantitative result of allergen-specific IgE antibodies. Similar to RASTs the SPT can be positive without apparent allergies. In terms of predictivity for an onset of allergic diseases, RAST gives a more evident perspective with higher RAST-classes or IgE-values indicating higher risks for the development of allergic diseases. However, a study of Schäfer et al. (3) pointed out that the capability in predicting hay fever cases depended highly on chosen cut-off points for RAST reactivity with both tests (RAST and SPT) reaching similar power when using a cut-off point of 1.5 kU/l for RAST.

Allergic diseases have an important influence on the quality of life, social and economic aspects, working absence and mortality (10). A difficult point is to find adequate prevention strategies when knowing that someone is predisposed. Especially as studies are highly discordant concerning influencing factors. In particular related to pet contact, no clear advice can be given as some studies promote the avoidance of pets while other studies indicate that children who grew up in homes with cats and/or dogs developed less atopic diseases as they grew older (11, 12, 15–19). In contrast, avoidance strategies for other allergens (e.g. house dust mite) have shown clinical benefits on preventing asthmatic symptoms (20). The prognostic factors seem to change by age. Overall, most frequently accounted factors are atopy in the family, gender, day-care attendance, siblings, birth weight, breastfeeding, early respiratory infections, living in damp houses, contact with pets, smoking in the family, own smoking, education, environmental conditions and allergic sensitization (7, 12, 18, 19, 21–25). The effect of atopic family history is constant, while several risk factors known for early development of allergic diseases disappear later in childhood or adulthood and the effect of sensitization to specific allergens is leading (12). In line with other studies (26–33), in our study we could find that sensitivity to house dust mite and cat were significant risk factors for asthma. Hay fever not surprisingly was mainly associated with outdoor allergens (28). When looking at the crude association in Fig. 2, cat sensitization showed a strong influence too. These findings are similar to those of Bodtger et al. (8) who only found significant associations between outdoor allergens when looking at rhinitis symptoms to summer pollens (hay fever) while additionally finding associations to cat allergens and house dust mite when extending to associations to allergic rhinitis symptoms in total. For our multivariate analyses we adjusted for each tested allergen to avoid overestimations because of cross-reactivity. That however might have led to an underestimation of single allergens. Additionally, the possible influence of other allergens we did not test for has to be accounted for, e.g. food allergens, dog dander, other mites and cockroach. However, the RAST panel of five allergen-specific antibodies tested for is representative for the most common German allergens. Cockroaches for example are predominant allergens exposed to in the US (27, 34) while they are not in Germany (27, 34–36). In a previous study on house-dust samples (35), cockroach allergens were below detection limit in 93% of the total samples. Similarly, sensitization to Ambrosia, mugwort and storage mite is not common in Germany, while specific IgE antibodies against Cladosporium is, but in <2%. Our study has further limitations. Information on atopic outcomes is exclusively questionnaire-based. Recall bias has to be accounted for. But as we asked for doctor-diagnosed asthma, hay fever and atopic dermatitis a potential overestimation of cases is reduced. Nevertheless, we do not know how much reported hay fever really is hay fever or how much asthma really is attributable to atopy. Some studies describing the association of asthma and atopy (defined by SPT or elevated IgE antibodies) concluded that an average of 30–40% of asthma cases would be attributable to atopy, in both adults and children (37, 38). Main strengths of our study are a considerable population-based sample size covering several adult age-groups, the enclosed broad measurement of the most common specific IgE antibodies and a long follow-up time of 10 years for calculating incidence rates in adults.

Conclusion

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Conclusion
  7. Acknowledgment
  8. References

Radioallergosorbent test-sensitization not only covers clinically apparent allergies, but indicates a prognostic factor for later allergies, even in adulthood. The definition of RAST-classes should endorse and support risk assessment and prevention programmes for allergic diseases.

Acknowledgment

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Conclusion
  7. Acknowledgment
  8. References

The KORA research platform was initiated and financed by the GSF-National Research Center for Environment and Health, which is funded by the German Federal Ministry of Education and Research and by the State of Bavaria.

References

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Conclusion
  7. Acknowledgment
  8. References
  • 1
    Bousquet J, Van Cauwenberge P, Khaltaev N. Allergic rhinitis and its impact on asthma. J Allergy Clin Immunol 2001;108(Suppl. 5):S147S334.
  • 2
    Halken S. Prevention of allergic disease in childhood: clinical and epidemiological aspects of primary and secondary allergy prevention. Pediatr Allergy Immunol 2004;15(Suppl. 16):432.
  • 3
    Schaefer T, Hoelscher B, Adam H, Ring J, Wichmann HE, Heinrich J. Hay fever and predictive value of prick test and specific IgE antibodies: a prospective study in children. Pediatr Allergy Immunol 2003;14:120129.
  • 4
    Haahtela T, Jaakonmaki I. Relationship of allergen-specific IgE antibodies, skin prick tests and allergic disorders in unselected adolescents. Allergy 1981;36:251256.
  • 5
    Holle R, Happich M, Loewel H, Wichmann HE et al. KORA - A research platform for population based health research. Gesundheitswesen 2005;67(Suppl. 1):519525.
  • 6
    Chambless L, Cairns V, Herbold M, Dbring A, Filiprak B, Schneller H et al. MONICA Augsburg Survey Sampling. GSF-Bericht 1986;31/86.
  • 7
    Bodtger U, Linneberg A. Remission of allergic rhinitis: an 8-year observational study. J Allergy Clin Immunol 2004;114:13841388.
  • 8
    Bodtger U, Poulsen LK, Linneberg A. Rhinitis symptoms and IgE sensitization as risk factors for development of later allergic rhinitis in adults. Allergy 2006;61:712716.
  • 9
    Nihlen U, Greiff L, Montnemery P, Lofdahl CG, Johannisson A, Persson C et al. Incidence and remission of self-reported allergic rhinitis symptoms in adults. Allergy 2006;61:12991304.
  • 10
    O’Connell EJ. The burden of atopy and asthma in children. Allergy 2004;59(Suppl. 78):711.
  • 11
    Perzanowski MS, Ronmark E, Platts-Mills TA, Lundback B. Effect of cat and dog ownership on sensitization and development of asthma among preteenage children. Am J Respir Crit Care Med 2002;166:696702.
  • 12
    Baecklund AB, Perzanowski MS, Platts-Mills T, Sandstrom T, Lundback B, Ronmark E. Asthma during the primary school ages–prevalence, remission and the impact of allergic sensitization. Allergy 2006;61:549555.
  • 13
    Robertson CF, Roberts MF, Kappers JH. Asthma prevalence in Melbourne schoolchildren: have we reached the peak? Med J Aust 2004;180:273276.
  • 14
    Zoellner IK, Weiland SK, Piechotowski I, Gabrio T, Von Mutius E, Link B et al. No increase in the prevalence of asthma, allergies, and atopic sensitisation among children in Germany: 1992-2001. Thorax 2005;60:545548.
  • 15
    Liu AH, Murphy JR. Hygiene hypothesis: fact or fiction? J Allergy Clin Immunol 2003;111:471478.
  • 16
    Ownby DR, Johnson CC, Peterson EL. Exposure to dogs and cats in the first year of life and risk of allergic sensitization at 6 to 7 years of age. JAMA 2002;288:963972.
  • 17
    Almqvist C, Egmar AC, Hedlin G, Lundqvist M, Nordvall SL, Pershagen G et al. Direct and indirect exposure to pets - risk of sensitization and asthma at 4 years in a birth cohort. Clin Exp Allergy 2003;33:11901197.
  • 18
    De Meer G, Janssen NA, Brunekreef B. Early childhood environment related to microbial exposure and the occurrence of atopic disease at school age. Allergy 2005;60:619625.
  • 19
    Hesselmar B, Aberg N, Aberg B, Eriksson B, Bjorksten B. Does early exposure to cat or dog protect against later allergy development? Clin Exp Allergy 1999;29:611617.
  • 20
    Arshad SH, Bateman B, Matthews SM. Primary prevention of asthma and atopy during childhood by allergen avoidance in infancy: a randomised controlled study. Thorax 2003;58:489493.
  • 21
    Becker AB. Is primary prevention of asthma possible? Can Respir J 1998;5(Suppl. A):45A49A.
  • 22
    Bergmann RL, Edenharter G, Bergmann KE, Lau S, Wahn U. Socioeconomic status is a risk factor for allergy in parents but not in their children. Clin Exp Allergy 2000;30:17401745.
  • 23
    Linneberg A, Nielsen NH, Madsen F, Frolund L, Dirksen A, Jorgensen T. Factors related to allergic sensitization to aeroallergens in a cross-sectional study in adults: the Copenhagen Allergy Study. Clin Exp Allergy 2001;31:14091417.
  • 24
    Melen E, Wickman M, Nordvall SL, Hage-Hamsten M, Lindfors A. Influence of early and current environmental exposure factors on sensitization and outcome of asthma in pre-school children. Allergy 2001;56:646652.
  • 25
    Surdu S, Montoya LD, Tarbell A, Carpenter DO. Childhood asthma and indoor allergens in Native Americans in New York. Environ Health 2006;5:22.
  • 26
    Sears MR, Herbison GP, Holdaway MD, Hewitt CJ, Flannery EM, Silva PA. The relative risks of sensitivity to grass pollen, house dust mite and cat dander in the development of childhood asthma. Clin Exp Allergy 1989;19:419424.
  • 27
    Gehring U, Heinrich J, Jacob B, Richter K, Fahlbusch B, Schlenvoigt G et al. Respiratory symptoms in relation to indoor exposure to mite and cat allergens and endotoxins. Indoor Factors and Genetics in Asthma (INGA) Study Group. Eur Respir J 2001;18:555563.
  • 28
    Sears MR, Burrows B, Flannery EM, Herbison GP, Holdaway MD. Atopy in childhood. I. Gender and allergen related risks for development of hay fever and asthma. Clin Exp Allergy 1993;23:941948.
  • 29
    Leung TF, Lam CW, Chan IH, Li AM, Ha G, Tang NL et al. Inhalant allergens as risk factors for the development and severity of mild-to-moderate asthma in Hong Kong Chinese children. J Asthma 2002;39:323330.
  • 30
    Lewis SA, Weiss ST, Platts-Mills TA, Burge H, Gold DR. The role of indoor allergen sensitization and exposure in causing morbidity in women with asthma. Am J Respir Crit Care Med 2002;165:961966.
  • 31
    Lau S, Illi S, Platts-Mills TA, Riposo D, Nickel R, Gruber C et al. Longitudinal study on the relationship between cat allergen and endotoxin exposure, sensitization, cat-specific IgG and development of asthma in childhood–report of the German Multicentre Allergy Study (MAS 90). Allergy 2005;60:766773.
  • 32
    Lau S, Illi S, Sommerfeld C, Niggemann B, Bergmann R, Von Mutius E 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;356:13921397.
  • 33
    Peat JK, Tovey E, Toelle BG, Haby MM, Gray EJ, Mahmic A et al. House dust mite allergens. A major risk factor for childhood asthma in Australia. Am J Respir Crit Care Med 1996;153:141146.
  • 34
    Rosenstreich DL, Eggleston P, Kattan M, Baker D, Slavin RG, Gergen P et al. The role of cockroach allergy and exposure to cockroach allergen in causing morbidity among inner-city children with asthma. N Engl J Med 1997;336:13561363.
  • 35
    Fahlbusch B, Heinrich J, Gross I, Jager L, Richter K, Wichmann HE. Allergens in house-dust samples in Germany: results of an East-West German comparison. Allergy 1999;54:12151222.
  • 36
    Gehring U, Bischof W, Fahlbusch B, Wichmann HE, Heinrich J. House dust endotoxin and allergic sensitization in children. Am J Respir Crit Care Med 2002;166:939944.
  • 37
    Pearce N, Pekkanen J, Beasley R. How much asthma is really attributable to atopy? Thorax 1999;54:268272.
  • 38
    Arshad SH, Tariq SM, Matthews S, Hakim E. Sensitization to common allergens and its association with allergic disorders at age 4 years: a whole population birth cohort study. Pediatrics 2001;108:E33.