Clinical and immunological studies of respiratory allergy among farmers : with focus on dust mite allergy

Abstract

Many studies have shown an increase in the prevalence of asthma and rhinoconjunctivitis in most of the industrialised world. In addition, occupational asthma, rhinoconjunctivitis and allergies have increased during the last decade. Earlier studies have demonstrated a high prevalence of respiratory symptoms among farmers and a predominance of storage mites as allergens in rural settings. This thesis focuses on sensitisation and exposure to risk factors for respiratory allergy among farmers as well as evaluation of the clinical and serological relevance of the recombinant major allergens of the storage mites Lepidoglyphus destructor, rLep d 2, and Tyrophagus putrescentiae, rTyr p 2, and the modified derivative of rLep d 2, rLep d 2.6Cys.

An extensive epidemiological 12-year follow-up survey, concerning respiratory symptoms and sensitisation, was conducted in 1996 among farmers on Gotland. Although the overall proportion of fanners with respiratory symptoms was unchanged between 1984 and 1996, a significant increase in the prevalence of asthma (5.2% vs 9.8%), as well as asthma in combination with rhinoconjunctivitis (3.9% vs 7.0%) was found. In spite of the thorough information about health hazards associated with storage mites given in 1984, storage mites remained predominant allergens, more prevalent than animal danders and pollens. Risk factors for sensitisation to common aeroallergens, asthma and rhinoconjunctivitis were assessed, and after adjustments for sex, age and smoking in a multiple regression model, sensitisation to mites (OR=5.8) and pollens (OR=10.3) remained the only significant risk factors for asthma. The corresponding significant risk factors for rhinoconjunctivitis were sensitisation to mites (OR=3.8), pollens (OR=5.8) and in addition working full time (OR=1.9). Although farmers smoked less than the general population, they more frequently had a reduced lung function, measured as FEV1. Dust samples were collected from mattresses and living room carpets for the measurement of cat and dog allergens in 403 farmers' homes. The major cat Fe1 d 1) and dog (Can f 1) allergens were detected in 99. 1 % and 90.6% of the farmers' homes, respectively. Cat allergen levels above the suggested risk threshold for sensitisation were present in 69.2% of the households and the corresponding figure for dog was 42.9%, but only a minority of the farmers were sensitised to the corresponding allergens (cat: 8.4% and dog: 7.4%). However, a significant association between sensitisation to dog and asthma (OR=17.8) and rhinoconjunctivitis (OR=8.0) was found, as well as between sensitisation to cat and asthma (OR=4.9).

To investigate the clinical relevance of rLep d 2 and rTyr p 2, SPTs were performed, and almost all subjects with lgE against the corresponding native allergens were identified. In addition, the SPT reactivity to rLep d 2 and rTyr p 2 correlated well with the lgE and IgG4 reactivity to these allergens. rLep d 2 and rTyr p 2 seem to be useful tools for the diagnosis of dust mite allergy. Evaluation of the modified rLep d 2.6Cys allergen and its unaltered counterpart, rLep d 2, in SPT as well as in skin biopsies obtained 17-20 h after allergen challenge, demonstrated that rLep d 2.6Cys induced fewer and significantly smaller SPT reactions than rLep d 2. In addition, rLep d 2.6Cys, compared to rLep d 2, was significantly less able to trigger mast cell degranulation, induce dermal cell infiltrates, promote an influx of T-cells and activate eosinophils. In the future rLep d 2.6Cys may be a promising candidate molecule for immunotherapy treatment of L. destructor allergic patients.