A Short Assessment of Sublingual Immunotherapy (2001)

The WHO has recommended sublingual immunotherapy (SLIT) as the suitable treatment for allergic rhinitis in adults [1]. Our article is based on 20 double-blind, placebo-controlled studies published in peer-reviewed international journals and our own experiences with this therapy in a controlled study with patients allergic to grass pollen [2]. Eighteen studies were performed in patients with rhinitis (table 1), two studies in patients with bronchial asthma [3, 4].In SLIT studies, the medicament is given in drops sublingually for 2 min and then swallowed. In 2 studies the medicament was dropped under the tongue for 2 min and then spat away. The common dose of allergen extracts is 2- to 80-fold higher in SLIT than in subcutaneous therapy. In the SLIT studies, extracts of pollens (grasses, birch, parietaria, ambrosia and olea), house dust mites and cat dander were used. The therapy doses and times of therapy are quite different. Troise et al. [10]and Purello et al. [23]treated their patients for 10 months. The total doses in the study of Purello were 12.7 µg Par j 1, Troise et al. [10]treated with a dose of 6.3 µg Par j 1. The grass studies of Clavel et al. [13], Sabbah et al. [9]and Feliziani et al. [12]were performed for 3 up to 6 months. The cumulative doses are difficult to compare, some authors described the cumulative doses in biological units, others in micrograms of the major allergen Phl p 5.Bagnasco et al. [5]demonstrated with radioactively marked parietaria allergen that 2% of the allergen remained associated with the oral mucosa for 20 h. The radioactivity in the plasma increased after swallowing and peaked after 2 h. The rest of the material leaves the organism very quickly.In most studies in verum-treated groups, the specific IgG4 and the specific IgE increase under the therapy significantly. After a longer time of treatment the specific IgE seems to decrease. Passalacqua et al. [14]found a decrease of ICAM 1 in conjunctival fluid after exposure to allergen in the treated group.They also reported an increase of suppressor cells in the actively treated group but not in the placebo group. Fanta et al. [6]observed a significant decrease of lymphoproliferative response to the complete grass pollen extract (p < 0.001) and to the recombinant Phl p 1 (p < 0.001) after treatment with verum grass pollen extract but no change of Th1/Th2 cell ratio. These data show that SLIT has an effect on the immune system in the actively treated group.The therapeutic effect in the rhinitis studies was measured in scores for symptoms and medicaments recorded from self-assessment of the patients on diary cards. A positive effect was seen in patients with pollen allergy and rhinitis in 11 of 13 studies. Positive results were observed in 2 of 4 studies with house dust mites. The studies of Tari et al. [8]and Passalacqua et al. [14]showed a positive therapeutic effect after treatment for 2 years. Guez et al. [25]noted no effect in the same time of therapy. The therapy with cat dander showed no benefit [18].In seven studies the therapeutic effect was controlled with nasal challenge with the correspondent allergen extracts before and after the treatment. In six studies, a decrease in sensitivity was observed.In the treatment of asthma by SLIT in patients allergic to house dust mites, a clinically positive effect was observed in symptom scores and reduction of use of the medicaments. Bousquet et al. [3]and Pajno et al. [4]treated patients with allergic asthma to house dust mites with sublingual swallow immunotherapy. Bousquet treated double-blind 85 patients for 2 years with a cumulative dose of 4.2 mg Der p 1 and 7.3 mg Der f 1 in the verum group [3]. The results were measured in the frequency of asthma attacks and in the use of medicaments and in the reactivity to methacholine bronchial challenge. A challenge with allergen was not performed. Pajno et al. [4]treated for 2 years 24 children with asthma and allergy to house dust mites. The cumulative doses were not mentioned. The positive results in the verum group were measured in reduction of the asthma attacks and reduction of the use of antiasthmatic drugs.Severe side effects were not reported in the reviewed studies. André et al. [7]found no serious side effects in their review of 8 SLIT studies involving 472 adults and 218 children.SLIT has some effect on the human immune system. The positive clinical results measured in symptom and medication scores show that this therapy may be effective in rhinitis. For treatment of asthma more studies are needed.