A. Koivikko

Clinical efficacy and safety of sublingual immunotherapy with tree pollen extract in children

Background:  Subcutaneous immunotherapy has been the principal approach of immunotherapy in the treatment of allergic diseases. Several clinical studies with birch, alder or hazel pollen extract conducted as subcutaneous immunotherapy have been published suggesting a well‐tolerated and clinically effective treatment. Only a few clinical studies of sublingual immunotherapy (SLIT) with these allergens have been published. This study investigated the clinical efficacy, safety and dose–response relationship of SLIT in children suffering from rhinoconjunctivitis with/without asthma.

Airborne birch pollen antigens in different particle sizes

Two particle samplers for ambient air. situated together: a static size–selective bio–aerosol sampler (SSBAS) and a Burkard pollen and spore trap were compared in sampling intact birch pollen grains through one flowering period of Betula (a total of 44 days). The SSBAS trapped pollen grains three times more efficienily than the Burkard trap, but the variations in pollen counts were significantly correlated. In contrast, birch pollen antigenic activity and the pollen count in the Burkard samples were not closely correlated. The antigenic concentration was occasionally high both before and after the pollination period. There was a high birch pollen antigenic activity in particle size classes where intact pollen grains were absent, even on days when the pollen count was very low. Correspondingly, on days with high birch pollen counts in the air, pollen antigenic activity was on several occasions low. indicating that pollen grains were empty of antigenic material. The small particle size classes are especially important to allergic, patients because they are able to penetrate immediately into the alveoli and provoke asthmatic reactions. Therefore, aerobiological information systems based on pollen and spore counts should be supplemented with information concerning antigenic activities–in the air.

Dog hypersensitivity in asthmatic children. A clinical study with special reference to the relationship between the exposure to dogs and the occurrence of hypersensitivity symptoms.

ABSTRACT. The occurrence of dog hypersensitivity in 203 unselected asthmatic children was investigated by means of the skin prick test, the provocation test and RAST. The history of past and present exposure to dogs, symptoms in contact with dogs, and the effects of pet avoidance were examined. The amount of dog dander antigens was analyzed by counter‐immunoelectrophoresis from dust samples from 67 homes. A history of past or present dog hypersensitivity was obtained from 120 subjects (59%). A positive (≧++) prick test reaction was observed in 113 (56%), a positive provocation test result in 84 (41%) and a RAST class ≧ 1 in 140 (69%). The serum levels of IgE antibodies to dog dander correlated significantly with serum total IgE and the frequency of asthmatic attacks. The occurrence of dog allergy was not significantly associated with past or present exposure to dogs at home. However, the children who were exposed to dogs during the first year of life had dog allergy more often than those with late or without exposure. Significant amounts of dog dander antigen were also found in dust samples from homes where dogs have never been kept. Serum samples from previous years were available from 24 patients. Rising or steadily high levels of IgE antibodies to dog dander were observed even in subjects who strictly avoided dogs. The results show that dog hypersensitivity is an important cause of allergic disorders in asthmatic children, and that the common presence of dog dander antigens in our environment may induce dog allergy even without direct exposure to dogs.

Significance of sampling height of airborne particles for aerobiological information

Pollen and spore counts from Burkard traps for routine pollen and spore sampling placed at 15 m above ground and at ground level were compared. Daily counts of most pollen types were higher on the ground than at roof level, but the counts were significantly correlated. The ratios of pollen frequencies at high and low levels varied between 1.0 and 11.5. The most prominent differences were recorded for herbaceous pollen (e.g. Artemisia counts 11 5 and Poaceae counts 4.4 times higher at ground level) and in Botrytis and Ustilaginales spores. Tree pollen grains and basidiomycetous spores were more equally distributed. Wind speed did not affect the variation of pollen frequencies at either height. Large spores are not so unevenly distributed as previously supposed. Artemisia and grass pollen was detected 1 to 2 weeks earlier at ground level than on the roof. It is therefore concluded that especially the beginning of flowering should be monitored at a low level.

Pollen seasons: forecasts of the most important allergenic plants in Finland.

Occurrence of airborne pollen in Finland has been studied for 10 years in Turku (southern Finland), 8 years in Oulu, 4 years in Kuopio (central Finland) and 7 years at Kevo (northern Lapland). Observations on the pollen seasons of alder, birch, grasses and mugwort are presented. All these pollens occur in south and mid‐ Finland in quantities capable of causing allergy symptoms. Except for birch pollen, allergenic pollens occur in far lower concentrations than in central Europe. In northern Lapland only birch and pine pollen concentrations are high. Pollens may occur without signs of local flowering when there are southerly winds. This findings suggests that long‐distance transport is an essential contributing factor to the occurrence of pollens. There are wide year‐to‐year variations in the start of pollen seasons could very much depend on the mean temperature in April. However, a forecasting model based on this and other spring‐time temperature parameters often fails to give sufficiently accurate forecasts.

IgE-, IgA- and IgG-antibody responses to carbohydrate and protein antigens of Candida albicans in asthmatic children

Analysis of IgE, IgA and IgG antibodies directed against Candida albicans antigens in 28 asthmatic children was performed with immunoblotting after SDS‐PAGE. Analysis with the purified eytoplasmic protein fraction revealed a major protein allergen with an MW of 46 kD. In addition to the major allergen, 15 other antigenic bands with molecular weights between 16 and 135 kD bound IgE. Ten of 13 anti‐C. albicans IgE‐positive children had IgE towards the 46 kD major allergen. None of the subjects in the study group or in the non‐atopic controls had IgA or IgG antibodies towards this protein. Analysis of the crude surface extract showed that mannan, a carbohydrate, was an intermediate allergen contrary to being the major antigen in IgA and IgG antibody responses.

IgE, IgA and IgG antibodies and delayed skin response towards Candida albicans antigens in atopics with and without saprophytic growth.

Immunoblotting and RAST were used to analyse IgE, IgA and IgG responses to antigens of Candida albicans. These were compared with the delayed skin response and C. albicans carriage in 40 atopic subjects. The majority of the atopic patients showed a strong IgG and IgA antibody response towards mannan, a carbohydrate, but only occasionally to proteins. Altogether 22 of the 40 patients showed specific IgE towards C. albicans by immunoblotting. The IgE response was mainly towards proteins, particularly to ones with molecular weights of 29 kD and 46 kD, and only in eight out of 22 IgE‐positive subjects towards mannan. The IgG and IgA responses to mannan and the total IgE response towards C. albicans assessed by RAST showed an association with C. albicans carriage, whereas the delayed skin response showed an inverse relationship. The immunological parameters characteristic of C. albicans carriage were found to be C. albicans‐specific depressed delayed skin response and elevated IgE, IgA and IgG responses. This situation in the atopies presenting such parameters may favour simultaneous sensitization and exposure by colonization. The degree of sensitization may be sufficiently high to produce symptomatic allergy, such as asthma, in some individuals during occasional overgrowth of C. albicans, e.g. due to antibiotic therapy.

Cross-Reactivity of Cat and Dog Allergen Extracts

The commercial cat and dog allergen extracts are traditionally prepared from pelt, fur or dander. However, there is increased evidence of the allergenicity of saliva and urine of the animals. We have investigated 25 asthmatic children with a positive cat and/or dog RAST result. All 20 subjects with a positive cat RAST gave a positive skin prick test result to cat saliva, cat urine and cat hair. Analogously, all 20 subjects with a positive dog RAST had a positive skin reaction to dog saliva, urine and dander. In RAST inhibition experiments with dog and cat allergen discs, dog saliva appeared to be at least as potent as a commercial dog dander and hair extract, while cat saliva was less potent than the respective commercial extract. Both dog and cat salivas were clearly more potent than the respective urine. Significant cross-reactivity was observed between cat hair and dog dander in the RAST inhibition, whereas saliva and urine were shown to be more species-specific. An experimental dog dander preparation had about the same specificity as, and even higher allergenic activity than, that of dog saliva or urine. Our results suggest that saliva actually may be the best source of cat and dog allergen preparations. The importance of urine warrants further investigation.

Allergenic cross-reactivity of yeasts.

Yeast allergen extracts of Candida albicans, C. pseudotropicalis, C. krusei, C. parapsilosis, C. tropicalis, C. guilliermondi, C. humicola, C. norwegica, C. utilis, Cryptococcus albidus, Geotrichum candidum, Pityrosporon pachydermatis, P. ovale, Rhodotorula minuta, R. rubra, Saccharomyces cerevisiae, Torulopsis glabrata and Trichosporon cutaneum were investigated regarding their common allergenic properties. The enzyme immunoassay (EIA) using rabbit anti Candida albicans antiserum showed remarkable immunological cross‐reactivity only between the Candida species. However, there was a significant multiple sensitivity to the extracts of C. albicans, C. utilis, Cr. albidus, R. rubra, and S. cerevisiae in skin prick testing in atopic patients, suggesting the possible presence of one or more common skin reactive allergens.

Use of the extended Phadebas RAST® panel in the diagnosis of mould allergy in asthmatic children

The clinical significance of mould allergens in Phadebas RAST® panel was investigated in 121 asthmatic children. They were selected from a total population of 1649 patients. The patients were distributed into four groups, based on the combination of positive or negative skin prick tests (SPT) together with symptoms suggestive or not of mould sensitivity. Mould‐specific IgE antibodies were investigated using the original RAST panel (Alternaria, Aspergilius, Candida, Cladosporium, Mucor and Penicillium) and a set of 10 additional mould‐allergen discs (Aureobasidium, Batrytis, Currularia, Epicoccum, Fusarium, Helminthosporion, Phama, Rhizopus, Stemphylium and Trichoderma). The set of additional RAST dises revealed patients with mould‐reaginic antibodies not found with the original RAST panel. This occurred in four of 49 (8.2%) RAST positive (class 2) patients. The allergens most frequently positive were Cladosporium (in 28% of the patients). Candida (28%) and Helminthosporium (26%). A remarkable degree of simulataneous reactivity to almost all moulds rested was observed. Patients with multiple ( 7) mould sensitization were effectively pinpointed using any duplicate combination of Aureabasidium, Botryts, Candida, Cladesporium, Helminthosporium, Pencillium and Stemphylium.