IMMUNOTHERAPY WITH STANDARDIZED EXTRACT OF DERMATOPHAGOIDES-PTERONYSSINUS IN BRONCHIAL-ASTHMA - A DOSE-TITRATION STUDY

According to the maximum tolerated dose (MTD) achieved, we assessed th e changes in clinical and laboratory parameters, induced by specific i mmunotherapy (SIT), in a group of 43 asthmatic patients sensitized to Dermatophagoides pteronyssinus, over a period of 18 months. A standard ized extract (100 Bu/ml; 40 mu g/ml of Der p 1; 20 mu g/ml of Der p 2) was used. The patients were divided into two groups: the high-dose im munotherapy (HDI) group (MTD greater than or equal to 4 mu g Der p 1) and the conventional immunotherapy (CI) group (MTD < 4 mu g Der p 1). Changes in clinical severity index, medication, and symptom scores; in cutaneous and conjunctival reactivity; and in the levels of specific IgE, IgG, IgG1, and IgG4 to D. pteronyssinus (Der p 1 and Der p 2) wer e measured (ELISA monoclonal antibodies). Safety was monitored accordi ng to the EAACI guidelines. The range of the MTD was 0.8-16 mu g of De r p 1. Ninety percent of the patients tolerated a dose of 3.2 mu g, bu t only 18% of the patients reached a maintenance dose of 16 mu g. The medians of the accumulated dose were 197 mu g of Der p 1 for the HDI g roup, and 50 mu g for the CI group. Conjunctival and cutaneous reactiv ity was significantly lowered (P < 0.001) after SIT, as were the clini cal severity score and medication score in both groups, without signif icant differences between the groups, except for cutaneous reactivity. Levels of specific IgE decreased significantly (P < 0.01) in both gro ups, again without significant differences between the groups. The ran ge of the increase in medians of specific IgG, IgG1, and IgG4 was 4.4- 120-fold for the HDI group and 3-24-fold for the CI group (P < 0.01). The increase in the levels of Der p 1 and Der p 2 IgG4 were correlated to the changes in cutaneous and conjunctival reactivity (P < 0.01). T hese results show that a maintenance dose of 3.2 mu g Der p 1 (8 BU) c an induce pronounced clinical and immunologic changes with an excellen t safety profile.