Long-term follow-up of patients treated with a three-year course of cat or dog immunotherapy.

BACKGROUND: A 5-year follow-up study was conducted to investigate the duration of the effects of a 3-year course of immunotherapy with standardized cat or dog extracts in 32 children and adults with asthma caused by animal dander. METHODS: Thirty of the subjects could be reached with a questionnaire, 19 underwent bronchial allergen and histamine challenges, and four had only a histamine challenge. Specific IgE and IgG4 levels in serum were measured in those who underwent challenges. RESULTS: Almost all subjects (26 of 30) reported no change (17 subjects) or increased tolerance (9 subjects) on exposure to cats or dogs. In contrast, 17 of the 19 who underwent allergen challenges had increased allergen sensitivity compared with when therapy was stopped (p < 0.01), and the results were no longer significantly different from before therapy was started. Mean provocative concentration of histamine causing a 20% fall in peak expiratory flow was, however, still higher than before therapy in the cat immunotherapy group (p < 0.01) and had not changed significantly during the follow-up period. In the dog immunotherapy group there was no significant change during or after therapy. Specific IgG4 had decreased, and specific IgE in serum had remained low and was comparable to the levels measured at the end of the study period. CONCLUSIONS: Five years after stopping immunotherapy, objectively measured bronchial allergen sensitivity had increased and had approached pretreatment conditions. Asthma symptoms, according to patients' subjective evaluations, had continued to be mild in most patients, and bronchial histamine sensitivity had remained stable. These observations could reflect remaining effects of immunotherapy or the natural history of mild asthma.

Immunotherapy with cat- and dog-dander extracts. IV. Effects of 2 years of treatment.

Thirty-five patients (20 children and 15 adults) with animal-dander asthma completed 2 years of immunotherapy with partly purified and standardized cat- or dog-danger extracts. The first year of the study was performed double-blind with a placebo-treated control group. These 15 patients were transferred to active treatment for a second year. All patients were followed by use of the skin prick test (SPT), allergen and histamine bronchial challenges, and tests for allergen-specific IgE, IgG1, and IgG4 levels. In the group treated with active extracts for 2 years (group A), the previously reported decrease in bronchial responsiveness to cat extract (p less than 0.001) and histamine (p less than 0.01) was even more pronounced after the second year. After 1 year of active treatment in the original placebo group (group B), a significant decrease in the bronchial responsiveness to cat extract was noted (p less than 0.001). The responsiveness to histamine was decreased only in the patients treated with cat-dander extracts (p less than 0.05). A significant decrease in the SPT (p less than 0.001) and an increase in the allergen-specific IgE (p less than 0.001) and IgG4 (p less than 0.001) was also noted in patients (group B) treated with cat-dander extracts. The side effects in the two groups (A and B) were negligible, except for some systemic side effects, especially among the children during the initial phase of immunotherapy. The symptoms were mild and responded promptly to treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy of an oral antihistamine, astemizole, as compared to a nasal steroid spray in hay fever.

The efficacy and side effects of the oral H1-antihistamine, astemizole, were compared with those of nasal beclomethasone in 158 adult birch-pollen allergic hay fever patients. 148 patients completed the 5-week, controlled trial which took place in Stockholm, May 1986, during the birch pollen season. Daily pollen counts were found to be at a rather low level throughout the study period. The effect and tolerability of both drugs were found to be excellent, although beclomethasone reduced nasal symptoms (sneezing, rhinorrhoea, blocked nose) significantly more effectively than astemizole. Eye symptoms were mild and equal in both groups. The results indicate that oral astemizole is an effective non-sedating antihistamine, though less so than nasal beclomethasone, in the treatment of nasal hay fever symptoms.

Immunotherapy with partially purified and standardized animal dander extracts. I. Clinical results from a double-blind study on patients with animal dander asthma.

Forty-one patients (21 adults and 20 children) with cat dander-or dog dander-induced asthma were selected for immunotherapy with standardized and partially purified cat- or dog-dander extracts by use of a double-blind protocol. Based on sex, age, clinical history, results of bronchial challenge, and crossed radioimmunoelectrophoresis studies, the patients were stratified in matched pairs, and the treatment alternatives were distributed randomly among the pairs. Twenty-two patients treated with allergen (15 with cat allergen and seven with dog allergen) and 17 patients receiving placebo therapy completed the first year of treatment. In the cat allergen-treated group, the bronchial sensitivity toward cat and histamine decreased (p less than 0.001 and p less than 0.05, respectively). Measured by bronchial challenge, the cat allergen-treated patients could tolerate 11 times more allergen at the end than at the start of the study, and they also demonstrated a tendency toward less pronounced symptoms after exposure to cat and dog allergens. No significant changes were observed in the dog allergen treated- or placebo-treated groups. The adverse effects in general were negligible except for some systemic side effects during rush hyposensitization, especially among the children, but these were mild and responded promptly to treatment.

Immunotherapy with cat- and dog-dander extracts. II. In vivo and in vitro immunologic effects observed in a 1-year double-blind placebo study.

The effects of immunotherapy on the skin prick test, allergen-specific IgE, and IgG in 39 patients (19 adults and 20 children), treated with partially purified cat- or dog-dander extracts or placebo for 1 year, were studied by use of a double-blind protocol. IgG levels were measured by three different assays: IgG RAST, IgG4 RAST, and Staph A IgG1, 2, and 4. The skin prick test reaction decreased continuously in the allergen-treated patients, the decrease being the first sign of an immunologic effect of the therapy. Allergen-specific IgE levels increased during the first 9 months in both children and adults. The RAST activity during the last 3 months continued to rise for the children, whereas it declined for the adults. IgG levels measured by all three methods demonstrated an increase in the allergen-treated patients and no increase in the placebo-treated patients. The children developed higher values on IgG RAST and IgG4 RAST than the adults. IgG RAST correlated negatively with IgE levels in the cat allergen-treated group. No correlation between skin prick test results, IgE levels, and IgG levels was found, nor was there any correlation between these parameters and the patients' own subjective evaluation or the allergen bronchial challenge test. In summary, the expected change in skin prick test reaction and allergen-specific IgE and IgG levels was found. The children tended to be more immunologically active than the adults.

Immunotherapy with cat- and dog-dander extracts. III. Allergen-specific immunoglobulin responses in a 1-year double-blind placebo study.

An investigation was made of the specific antibody response to individual antigens in 40 patients taking part in a double-blind placebo study of immunotherapy with cat- or dog-dander extracts. Antigen-specific IgE levels were measured by means of CRIE, and the results were expressed as scores. The patients demonstrated IgE specificities toward 1 to 5 antigens. Cat-dander antigens Nos. 4 (cat Ag 1) and 7, and dog antigens Nos. 6 and 13, produced the highest scores, but high IgE binding was also found for dog albumin. After 1 year of treatment, the IgE responses of the two treatment groups (allergen and placebo) were statistically indistinguishable from those before the start of treatment. There was a tendency toward a reduction in score for two of the dander antigens (cat Ag 1 and dog Ag No. 13), and no new IgE specificities appeared. Antigen-specific IgG levels were measured by means of CIE with patient serum incorporated in an intermediate gel, and the results were expressed as plus/minus precipitins. Only two patients had precipitating antibodies before the start of treatment (one against cat albumin and one against cat Ag 1). During the course of treatment, the production of antigen-specific IgGs was observed in 18/22 allergen- and 1/18 placebo-treated patients. For the cat allergen-treated group, the specificities were directed against cat antigens Nos. 2, 3 (cat albumin), 4 (cat Ag 1), and 7, and for the dog allergen-treated group, against dog antigens Nos. 2 (dog albumin), 13, and 20.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunotherapy with alginate-conjugated and alum-precipitated grass pollen extracts in patients with allergic rhinoconjunctivitis.

In order to compare the safety and the efficacy of two grass pollen extracts made from the same starting material, i.e. equal proportions of cocksfoot and timothy, a 3-year study was made on patients with hay fever. One product was a dialysed aqueous extract of pollens which was chemically conjugated to activated sodium alginate ( Conjuvac ). The other was a pyridine-extracted alum-precipitated crude extract (Allpyral). Forty patients with classical hay fever were admitted to the study. All gave positive result to prick and nasal/conjunctival testing with extracts of both cocksfoot and timothy grass. Thirty-five patients completed all 3 years of the study. Seventeen/eighteen Allpyral-treated and 17/17 Conjuvac -treated patients were subjectively improved. There was no significant difference in symptom scores between the two groups. Challenge tests showed a tendency to reduced sensitivity to allergen in the Conjuvac -treated but not in the Allpyral-treated group. The median values for specific IgG and IgE showed the same pattern of reaction as seen in earlier studies of pollen hyposensitization. There was, however, a greater increase of grass-specific IgG in the Conjuvac -treated patients. No serious adverse effects were seen in any of the treatment groups, but there were slightly fewer side effects in the Conjuvac group.

Evaluation of the bronchodilating and antiallergic properties of a beta-adrenoceptor stimulant, KWD 2131, in asthmatic patients.

KWD 2131 (1-(3,5-dihydroxyphenyl)-(1,1dimethyl-2-hydroxyethyl-amino/ethanol sulphate) is a beta-adrenoceptor stimulating compound that has been shown to be equipotent to terbutaline with regard to inhibition of anaphylactic histamine release from guinea pig lung tissue but less potent than terbutaline as a cardioaccelerator in this species. In the present study KWD 2131 was found to be about 5-10 times less potent than terbutaline as a cardioaccelerator, tremorogenic and bronchodilator agent on subcutaneous (s.c.) injection in man. S.c. injection of KWD 2131 in a subthreshold dose for bronchodilation, i.e. 0.3 mg or 0.6 mg, given prior to a bronchial provocation test with specific allergen had no protective effect on the changes in specific airway conductance and peak expiratory flow in a double-blind cross-over study in 12 patients with allergic asthma. It is concluded that KWD 2131 probably has a less selective antiallergic activity in man as compared to guinea pig and that the methodology employed for the evaluation is useful for the characterization of antiallergic drugs with bronchodilator properties.

Anti-anaphylactic and bronchodilating action of a beta-adrenoceptor stimulator, KWD 2131, in human lung tissue.

The beta-adrenoceptor stimulating agent KWD 2131 has been studied with regard to inhibitory effect on allergen-induced histamine release from passively sensitized human lung tissue and relaxing effect on contracted small (diameter = 1 mm) and large (diameter greater than 3 mm) isolated human bronchi. The dose for 50% inhibition of the allergen-induced histamine release was 2 x 10(-11) M. The potency of KWD 2131 was approximately 0.15 times that of terbutaline and 0.05 times that of isoprenaline in this respect. The bronchodilating potency of KWD 2131 was 0.02-0.03 times that of terbutaline. The data indicate that KWD 2131 is a compound with preferably anti-anaphylactic potency in the human lung.

Antibodies to synthetic ACTH in asthmatic and rheumatic patients.

The prevalence of antibodies against synthetic ACTH preparations and porcine gamma globulin was investigated in 29 asthmatic patients, in 28 rheumatic patients, and in 63 normal subjects of both sexes. Agglutinating antibodies were examined by a passive haemagglutination test and IgE antibodies by a radio-immuno assay. The incidence of agglutinating reactions against Synacthén and porcine gamma globulin was significantly higher in the asthmatic and rheumatic groups than in the group of normal subjects. Titres were generally low, attaining supposedly pathological levels (larger than or equal to 1/200) in about 10 per cent of the asthmatic patients and in 20-40 per cent of the rheumatic patients. In asthmatic patients, the incidence of ACTH specific IgE was higher than that in the normal group. This difference was not statistically significant in patients on routine treatment but it became satistically significant after ACTH booster treatment. In rheumatic patients the incidence of IgE antibodies against ACTH was insignificantly lower than that in the normal group. The incidence of agglutinating antibodies against vasopressin in asthmatic and rheumatic patients was also increased as compared with that in normal subjects and the titres were positively correlated to those against ACTH.

Immune responses to treatment with natural and synthetic ACTH in bronchial asthma.

Two comparable groups of asthmatics each with 10 patients were treated during 2 years at scheduled intervals with either natural or synthetic ACTH up to a total dose of 2000-95-- IU. All patients had previously been given the natural but never the synthetic hormone. Intradermal tests with natural and synthetic ACTH were performed before treatment and after 1, 12 and 24 months. Serum samples were also taken on these occasions and analysed for antibodies against ACTH, vasopressin and porcine gamma-globulin. No sign of clinical allergy to ACTH was noted in any of the patients during the 2-year period. The incidence of intradermal reactions against natural ACTH was high at the onset of treatment but was not increased by treatment with either synthetic or natural ACTH, while the reactivity rate against synthetic ACTH was increased after both types of treatment. The incidence of IgE reactions against synthetic ACTH at the 20 U/ml level was significantly increased after 12 months' treatment with either natural or synthetic hormone. A high incidence of low-titered agglutinating antibodies against natural or synthetic ACTH was demonstrated before treatment in both the groups, but no significant change in incidence or mean titre against natural or synthetic ACTH or porcine gamma-globulin was noted during treatment with the natural or the synthetic preparation. A few patients, however, did display an increased agglutinating titre against ACTH after 12 months' treatment. Rather unexpectedly, most sera reacting with ACTH were found to react also with vasopressin and a significant increase of the incidence of these reactions and of the titres occurred during the treatment with synthetic as well as with natural ACTH. Two cases have been examined in detail, one because of a fulminant shock after synthetic ACTH and the other because of very high antibody titres without clinical symptoms of ACTH allergy.