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Objective: The purpose of this study was to evaluate the efficacy of sublingual immunotherapy (SLIT) with house dust mite (HDM) on pediatric perennial allergic rhinitis (AR) based on longitudinal assessment of nasal symptoms, laboratory examination, and in vivo biomarkers., Method: The subjects included 40 children with perennial AR who had SLIT with HDM for 2 years. Nasal symptoms, medications, skin prick tests, nasal provocation tests, and peripheral blood tests were evaluated before, 6 months, one year and two years after the onset of SLIT., Results: Total nasal symptom scores, prick test wheal diameter, and peripheral blood eosinophil count decreased in 6 months. Total nasal symptom scores continued to decrease from 6 months to 2 years. Symptom-medication scores and nasal provocation test responses decreased in 1 year. Symptom-medication scores continued to decline from 1 to 2 years. Medication scores and nasal eosinophilia decreased in 2 years. Serum specific IgE to HDM slightly increased transiently and decreased in 2 years. The severity of symptoms and specific IgE to HDM at the baseline, and changes of symptoms and specific IgE to HDM during the first six months and first one year of SLIT were correlated with improvement in symptom scores over two years of SLUT. TNSS at baseline was correlated with that at second year., Conclusion: Longitudinal assessment of symptoms, allergen specific IgE, and in vivo biomarkers showed the effectiveness of SLIT. Symptom scores and allergen specific IgE may also be early predictive factors of SLIT efficacy in children with AR.

We report herein two cases of allergic fungal rhinosinusitis accompanied by bone destruction of the adjacent nasal sinuses. The first case involved a 21-year-old man who presented with left exophthalmos. Computed tomography (CT) showed soft tissue lesions in the left paranasal sinuses and destruction of the left lamina papyraceae, as well as infiltration of the lesion into the orbit. In the second case, a 39-year-old man, CT showed bone destruction of the skull base and medial wall of the left orbit. In both cases, total serum immunoglobulin (Ig)E level was >1000 IU/mL and fungus-specific IgEs were increased. Fungal hyphae were identified within the mucus on histopathological examination in both cases; however, no fungal invasion of the mucosa was apparent. Final diagnosis was allergic fungal rhinosinusitis (AFRS) in both cases. AFRS is a relatively new disease concept that was proposed in the early 1980s, with disease characteristics very similar to eosinophilic rhinosinusitis. Occasionally, AFRS must be differentiated from malignant disease or invasive fungal rhinosinusitis, so an understanding of the clinical features is important.

We studied changes in histamine release from basophil measured by HRT Shionogi kit as laboratory procedure to evaluate immunotherapy of allergic rhinitis. Nine cedar pollinosis patients (ages 12-64 yrs, 3 male and 6 female) that started immunotherapy with standardized cedar pollen extract (Torii Co) in 2001 were evaluated. Histamine release rate was measured before immunotherapy and at 6 months after starting immunotherapy. As a result, the histamine release rate after immunotherapy was suppressed in all cases. The average of histamine release rate was significantly decreased by the stimulation at 3, 30 and 300 ng/ml with cedar pollen antigen (p<0.05). These data suggested that the measurement of histamine release rate was usable for evaluating the efficacy of immunotherapy, and it has a possibility for monitoring in immunotherapy. In addition, a new different mechanism that T lymphocyte or serum does not concern can be considerable, because the procedure by HRT Shionogi kit is measured from basophils at the condition without serum.

We tried to elucidate the relation of age and severity with the efficacy of immunotherapy. The subjects included 51 patients with perennial allergic rhinitis who had immunotherapy for more than a year. Symptom scores, serum total IgE levels, Dermatophagoides pteronyssinus specific IgE, and peripheral blood eosinophils counts were evaluated before, half a year, one year and two years after the onset of immunotherapy. 64% of the children's group and 69% of the adults' group of patients showed significant improvement in their nasal symptoms, showing that age is not a factor influencing the efficacy of immunotherapy. The severity of the disease influenced the clinical efficacy; the more severe the disease, the poorer the efficacy of the immunotherapy. Periphipheral blood eosinophils counts gradually decreased after the onset of immunotherapy. High eosinophil counts before immunotherapy predicted poor efficacy of the immunotherapy.

We studied effects of immunotherapy on mite antigen-induced cytokine production from peripheral blood mononuclear cells in patient with house dust mite allergic rhinitis. In good response group, IL-4 production were lower than that of poor response group. In contrast, IFN-gamma production and the ratio of IFN-gamma to IL-4 synthesis were significant higher than that of poor response group. The production of IFN-gamma significantly correlated with the periods of immunotherapy. These results suggest that the changes of cytokine synthesis have a close relationship to clinical effects of immunotherapy.

To determine the role of cell adhesion molecules, we evaluated the in vivo effects of anti-intercellular adhesion molecule-1 (ICAM-1) monoclonal antibody (1A29) and anti-leukocyte function associated molecule-1 (LFA-1) monoclonal antibody (WT-1) on ovalbumin (OA) sensitized rats. Both sneezing discharges and nasal rubbing movements after nasal OA challenge were significantly inhibited by these monoclonal antibody administrations (control vs treated group; 20.5 +/- 5.0 vs 7.0 +/- 2.9 times/minutes, p < 0.01 and and 56.8 +/- 7.1 vs 26.9 +/- 2.9 times/15 minutes, p < 0.01, for sneezing and rubbing, respectively). The number of eosinophils in nasal mucosa 24 hours after the challenge was also inhibited by the treatment (control vs treatment group; 108.8 +/- 27.3 vs 13.8 +/- 6.9 p < 0.01). These results suggest some pathophysiological roles of ICAM-1 and LFA-1 in nasal allergy.

We evaluated the clinical and pathophysiological efficacy of hyposensitization with house dust extracts to perennial nasal allergy. Fifty-one patients with allergic perennial rhinitis completed 5 months to 15 years with a mean of 2.4 years course of hyposensitization treatment with house dust extracts, and analyzed clinical symptoms, nasal provocation testing, nasal hypersensitivity to histamine, mast cells and eosinophils in nasal scraping, specific IgG and IgG4 antibody in serum, and blood eosinophils and basophils in relation to therapeutic duration. The improvement in nasal symptoms was found in 74.1% in adults and 66.7% in child and the continuation of hyposensitization with house dust extracts for a half to one year showed significant improvement of clinical symptoms. In objective examination, nasal provocation testing, nasal hypersensitivity to histamine, the number of mast cells and eosinophils in nasal scraping, and blood basophils showed significant improvement at 6 to 12 months the same as clinical symptoms. These findings suggest that the continuation of hyposensitization with house dust extracts is recommendable as a basic treatment against perennial nasal allergy.

We treated perennial nasal allergy with specific desensitization in combination with or without Neurotropin injections (NSP) from March 1983 to September 1984, and analyzed blood anti-mite IgG and IgG4 levels in relation to therapeutic efficacy. Desensitization and NSP were given once a week and seventy subjects (33 from the desensitization group and 37 from the desensitization + NSP group) were evaluated at 24, 36 and 48 weeks. 1) In total cases clinical usefulness showed no significant difference between the desensitization group and combined group at 24 weeks, while in "useful or more" cases significantly better results were attained in the latter at 24 weeks and 48 weeks (p less than 0.05, respectively). 2) Dermatophagoides pteronyssinus (D.p.) specific IgG antibody showed no significant difference between both groups as well as in each group during the overall examination period. 3) In total cases both D.p. specific and D. farinae (D.f.) specific IgG4 were significantly higher in the combined group at 24 and 36 weeks (D.p.: p less than 0.01 and D.f.: p less than 0.05, respectively), whereas in "useful or more" cases only D.p. specific IgG4 showed a significant elevation in the combined group at 24 weeks (p less than 0.05). These results suggest that specific desensitization in combination with NSP can promote early production of mite specific IgG4, which tend to rise in correlation with clinical efficacy.

In treating perennial allergic rhinitis sensitive to house-dust (HD)-mite (Dermatophagoides farinae), rush immunotherapy with HD antigen and classical immunotherapy were applied to 2 different patient groups, and the results obtained were compared. The results were as follows. 1. There was no significant difference in clinical efficacy between both groups. 2. The titer of the anti-mite IgE antibody was not changed in both groups during the course of treatment. 3. The titer of the anti-mite IgG4 antibody was increased in both groups during the course of treatment. In rush immunotherapy, the increase began within 3 months after the initiation of treatment, whereas about 6 months after the initiation in classical immunotherapy. 4. In rush immunotherapy, a smaller dose amount of antigen could increase the titer of the anti-mite IgG4 antibody. 5. It was not clear whether the increased anti-mite IgG4 antibody titer exerted clinical effects on allergic symptoms. Patients with perennial allergic rhinitis may receive benefit from rush immunotherapy. The antigen-specific IgG4 antibody seems to be an index in evaluating immunotherapy objectively.