Immunotherapy with standardized extract of Dermatophagoides pteronyssinus in bronchial asthma: a dose-titration study.

According to the maximum tolerated dose (MTD) achieved, we assessed the changes in clinical and laboratory parameters, induced by specific immunotherapy (SIT), in a group of 43 asthmatic patients sensitized to Dermatophagoides pteronyssinus, over a period of 18 months. A standardized extract (100 Bu/ml; 40 micrograms/ml of Der p 1; 20 micrograms/ml of Der p 2) was used. The patients were divided into two groups: the high-dose immunotherapy (HDI) group (MTD > or = 4 micrograms Der p I) and the conventional immunotherapy (CI) group (MTD < 4 micrograms 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) were measured (ELISA monoclonal antibodies). Safety was monitored according to the EAACI guidelines. The range of the MTD was 0.8-16 micrograms of Der p 1. Ninety percent of the patients tolerated a dose of 3.2 micrograms, but only 18% of the patients reached a maintenance dose of 16 micrograms. The medians of the accumulated dose were 197 micrograms of Der p 1 for the HDI group, and 50 micrograms for the CI group. Conjunctival and cutaneous reactivity was significantly lowered (P < 0.001) after SIT, as were the clinical severity score and medication score in both groups, without significant differences between the groups, except for cutaneous reactivity. Levels of specific IgE decreased significantly (P < 0.01) in both groups, again without significant differences between the groups. The range 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). These results show that a maintenance dose of 3.2 micrograms Der p 1 (8 BU) can induce pronounced clinical and immunologic changes with an excellent safety profile.