Lack of subsensitivity to loratadine during long-term dosing during 12 weeks.

The development of subsensitivity to first-generation H1 blockers often occurs within days or weeks of treatment. It is manifested by a decrease in efficacy and a waning of the inhibition of skin reactivity to allergen or histamine. Subsensitivity to loratadine was investigated in a double-blind, placebo-controlled parallel group study in 20 allergic subjects (22 to 35 years) who received either placebo or loratadine (10 mg one daily) for 12 weeks. Skin prick tests were done with six threefold increasing concentrations of standardized allergen extracts (orchard grass or mite) and histamine-coated Phazet. Skin tests were done before any treatment and after 7, 28, 56, and 84 days. Wheals and flares were measured. Compliance was monitored strictly during the study. Statistical analysis was done by parallel line bioassay and Wilcoxon W test. Skin test reactivity to histamine or allergen did not change throughout the trial in the placebo-treated group. Patients treated by loratadine had a significantly smaller wheal-and-flare reaction after 7 days. This effect was greater at 28 days and lasted throughout the treatment period. This study demonstrates that subsensitivity to loratadine measured by histamine and allergen skin tests does not develop during a 12-week period.

Double-blind, placebo-controlled immunotherapy with mixed grass-pollen allergoids. III. Efficacy and safety of unfractionated and high-molecular-weight preparations in rhinoconjunctivitis and asthma.

Specific immunotherapy with unmodified formalinized allergoids is effective in grass-pollen allergy, but systemic reactions have been observed. A high-molecular-weight formalinized allergoid (HMW-GOID) was fractionated by gel filtration, retaining molecules of greater than 85,000 daltons in the expectation of improving safety without sacrificing efficacy. HMW-GOID and unfractionated allergoid (GOID) had a similar allergenic activity assessed by RAST inhibition, but the HMW-GOID preparation was 65 times less reactive when it was tested by skin prick test than the GOID preparation. A double-blind, placebo-controlled study was carried out in grass pollen-allergic patients with placebo (14 patients), GOID (15 patients), and HMW-GOID (13 patients). An additional group of 18 patients was treated by a rush schedule with a standardized orchard grass-pollen extract. A similar mean cumulative dose was administered with both allergoids. The fractionated allergoid only elicited minor systemic reactions similar to reactions elicited by placebo, whereas 20% of patients treated by GOID and 5.5% of patients receiving the standardized extract had a severe systemic reaction. For rhinitis, conjunctivitis, and asthma, the HMW-GOID and the standardized extract had a similar efficacy, significantly greater than placebo. GOID was less effective than the other two active treatments but was significantly more effective than placebo treatment for asthma and conjunctivitis.

Specific immunotherapy with a standardized Dermatophagoides pteronyssinus extract. II. Prediction of efficacy of immunotherapy.

House dust mites of the species Dermatophagoides pteronyssinus (Dpt) represent one of the major allergens inducing asthma. However, a strict allergy to Dpt is not always observed in Dpt-allergic patients, since nonallergic and other allergic triggering factors often coexist. It was suggested that specific immunotherapy with house dust-mite extracts is more effective in children than in adults. A controlled study was undertaken in 215 Dpt-allergic patients with asthma ranging in age from 3 to 72 years (mean +/- SD, 28.2 +/- 10.9 years) to investigate parameters that might predict the efficacy of specific immunotherapy before it is started; 171 patients received a rush immunotherapy protocol with a standardized Dpt extract and, subsequently, maintenance injections with 3000 BU of this extract, and 44 patients served as a control group. Before immunotherapy, all patients had a complete evaluation of the severity of asthma by symptom-medication scores and a pulmonary function test, as well as a study of other triggering factors by checking on seasonal and perennial allergens, sinusitis, and other possible causes, such as aspirin intolerance; 196 patients were investigated between 9 and 12 months after the onset of the survey by means of pulmonary function tests and symptom-medication scores. Medications were adapted according to peak flow rates. It was observed that patients with chronic sinusitis, and/or aspirin intolerance, and/or other perennial allergies did not benefit from specific immunotherapy; therefore, the treatment of a major etiologic factor did not demonstrate improvement in the patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Double-blind placebo-controlled study of loratadine, mequitazine, and placebo in the symptomatic treatment of seasonal allergic rhinitis.

Loratadine is a long-acting H1 antagonist devoid of anticholinergic and sedative effects. A double-blind, placebo-controlled, parallel-group study was performed in 69 patients to compare efficacy and safety of loratadine and mequitazine. Patients allergic to grass pollens were randomly assigned to one of the three treatment groups and followed up to 2 weeks during the peak of the pollen season. Symptoms of allergic rhinitis were evaluated at baseline and after 3, 7, and 14 days of treatment by the physician with patients rating their response daily on diary cards. Both loratadine and mequitazine induced a significant relief of nasal symptoms when these were compared to placebo. Loratadine was found to be significantly superior to placebo after 3 days of treatment, whereas a significant improvement was only observed after 7 days in patients treated with mequitazine. For nonnasal symptoms, none of the two anti-H1 antagonist induced a significant improvement, and this lack of effect may be related to low symptoms at baseline. Loratadine did not induce more side effects than placebo. Loratadine can be considered to be an effective and safe anti H1 histamine with a rapid onset of action.

Allergy in long-term hemodialysis. II. Allergic and atopic patterns of a population of patients undergoing long-term hemodialysis.

Maintenance hemodialysis is widely used throughout the world, and anaphylactic reactions appear to be increasing in number and severity. However, the exact incidence of sensitization and the role of atopy in these reactions are not yet fully understood. All of the 111 patients routinely dialyzed in a center were tested. All patients had a complete investigation of atopy, RAST to chemicals released during the procedure of dialysis (ethylene oxide (Eto), formaldehyde, phthalic anhydride, and toluene diisocyanate), skin tests with the effluent, and the titration of blood eosinophils. The incidence of atopy was found to be lower (13.5%) than in the normal population of the area. Skin tests with either histamine or allergens are significantly (p less than 0.001) smaller than those of nondialyzed subjects, and this method does not appear to be ideal in this population of patients. Eto sensitivity ranked first (5.5%), followed by phthalic anhydride sensitivity (3.6%); 5/6 patients who had a sensitivity to Eto and/or phthalic anhydride presented symptoms during dialysis, but they never were life threatening. Formaldehyde RAST was only found in one patient who had a life-threatening reaction. Finally, three patients presenting pruritus had positive skin prick tests with the effluent of the dialyzer. All patients having a first use syndrome and 80/81 symptom-free patients did not have serum-specific IgE against the released chemicals, 5/17 patients who had a pruritus during dialysis had either positive RAST to released chemicals or skin tests to the effluent, 5/8 patients who suffered from anaphylaxis had positive RAST to released chemicals, but only those who had a positive RAST presented a severe reaction.(ABSTRACT TRUNCATED AT 250 WORDS)

Skin test reactivity to histamine from infancy to old age.

The skin test reactivity to allergen and histamine differs according to the age of the patients, but complete data from infancy to old age are still lacking. Three hundred sixty-five subjects (1 to 85 years of age, 33.9% atopic, and 50.1% male patients) were prick tested with threefold dilutions of histamine hydrochloride (1 to 243 mg/ml). There was a significant (p less than 0.0001; F test) main effect of age on the skin reactivity to histamine. Age groups were defined and statistical analysis were performed by means of parallel line bioassay. All dose-response curves were linear and parallel. There is a significant increase in the mean wheal size between 4 to 5 and 6 to 9 years of age, 10 to 14 and 15 to 20 years. There was almost no difference between 15 to 20 and 21 to 50 years. No difference was observed between 21 to 30, 31 to 40, and 41 to 50 years, and then, the mean wheal sizes decreased significantly to reach a plateau after the age of 60 years. There was no sex difference, and skin tests with histamine were similar in atopic and nonatopic individuals.

Allergy in chronic haemodialysis. 1. Double-blind intravenous challenge with formaldehyde.

Patients undergoing chronic haemodialysis are often exposed to formaldehyde formaldehyde (F) has been reported to cause IgE-mediated anaphylactic shock. Many other patients reported pruritus or anaphylaxis-like symptoms when dialysed with F-sterilized dialysers. Ten patients presenting such symptoms were compared with five control subjects. Intravenous double-blind challenges were performed on six consecutive occasions, with capillary flow dialysers sterilized with or without F. Dialysis was performed by an investigator who was not aware of the sterilization procedure. Among the ten F-sensitive patients, five had symptoms with F-sterilized dialysers and no symptoms with new dialysers, sterilized by ethylene oxide and free of F. Symptoms included pruritus and hypotension. These five patients were subsequently dialysed with new dialysers, not sterilized with F, and symptoms subsided. The five other patients had inconclusive challenges. The five control subjects had no symptoms during challenges. Skin-prick tests with F showed that only one of the five patients who had symptoms with F-dialysers had a strongly positive prick test. RAST to F was titrated with HSA-discs but it was negative in all patients and control subjects. Formaldehyde was shown to cause symptoms in some patients under chronic haemodialysis but an IgE-mediated mechanism was not demonstrated.

Double-blind, placebo-controlled immunotherapy with mixed grass-pollen allergoids. I. Rush immunotherapy with allergoids and standardized orchard grass-pollen extract.

Forty-five grass pollen-allergic patients were randomly assigned to three groups according to their skin test and RAST sensitivities and the severity of seasonal rhinitis. Eleven patients were treated with placebo (group 1), 19 patients (group 2) were treated with a six-mixed grass-pollen allergoid prepared by mild formalinization with a two-step procedure, and 15 other patients were treated with a standardized orchard grass-pollen extract (group 3). Because of a different immunotherapy schedule, only patients placed in groups 1 and 2 received the extracts in a double-blind fashion. Rush immunotherapy was performed in 3 to 6 days, and the maintenance dose was subsequently administered weekly for 4 weeks and every 2 weeks until the end of the grass-pollen season. During the season, a coseasonal treatment was administered. Systemic reactions occurred during the rush protocol in 36.8% of patients treated with allergoid and 20% of patients who received the standardized extract. Only patients treated with allergoid had systemic reactions during maintenance dose. The reactions observed with the standardized extract were more severe. Total doses of allergoid ranged from 2350 to 13,500 protein nitrogen units. Symptoms and medication scores during the peak of the season were analyzed. Patients treated with the standardized allergen had a significant reduction of the number of days of symptoms during the month of June (9.5 +/- 6.7 days; p less than 0.005) and of medication scores (1.3 +/- 1.4; p less than 0.01) compared to patients receiving placebo (19.4 +/- 8.1 days; medication score, 2.8 +/- 2.1).(ABSTRACT TRUNCATED AT 250 WORDS)