Lack of correlation between titers of serum allergen-specific IgE and symptoms in untreated patients with seasonal allergic rhinitis.

In five ragweed seasons and three grass pollen seasons, preseason and postseason ragweed-specific serum IgE and nasal secretory-specific IgE and IgA have been measured in untreated patients with seasonal allergic rhinitis. There was no consistent correlation between severity of rhinitis, as measured by symptom/medication scores during the season, and either absolute or changes in antibody titers. These findings suggest that antibody levels are only one of the factors that determine symptom severity.

Prednisolone disposition in steroid-dependent asthmatic children.

The pharmacokinetics of a 40-mg intravenous dose of prednisolone were determined in 10 steroid-dependent asthmatic children with highly variable prednisone requirements (5 mg every other day to 40 mg a day). Concentrations of prednisolone and cortisol in plasma over a 24-hr test period were measured by high-performance liquid chromatography. Eosinophil concentrations and the concentration-dependent protein binding of prednisolone were also determined. The mean (+/-SD) apparent half-life of prednisolone in these children was 2.5 +/- 0.5 hr. The mean total volume of distribution was 52.8 +/- 14.5 L/1.73 m2 and mean plasma clearance was 246 +/- 62 ml/min/1.73 m2. These pharmacokinetic parameters, as well as the protein binding and eosinopenic response, were similar to values from healthy and steroid-dependent asthmatic adults. The data were also similar in both responsive and relatively resistant patients. The pharmacokinetics and protein binding of prednisolone are not responsible for the highly variable prednisone requirement and clinical response of these children to prednisone therapy.

Local intranasal immunotherapy for ragweed allergic rhinitis. II. Immunologic response.

Local nasal immunotherapy (LNIT) was administered in a double-blind study to 67 subjects. Twenty-three received an unmodified ragweed extract (RW), 24 received a glutaraldehyde polymer of ragweed extract (PRW), and 21 received placebo. Serum ragweed-specific IgE (S-IgE), ragweed-specific nasal secretory (NS-) IgE, secretory IgA (SIgA) and IgG, and NS-albumin were measured. RW therapy caused a significant increase in ragweed-specific S-IgE (p less than 0.005) and NS-SIgA (p less than 0.05). PRW therapy caused a significant rise in ragweed-specific NS-SIgA (p less than 0.001). NS-IgE (p less than 0.05), and NS-IgG (p less than 0.01). Ragweed-specific S-IgG was not affected by any of the treatments. There was no consistent correlation between NS-antibody levels and symptom/medication scores.

Local intranasal immunotherapy for ragweed allergic rhinitis. I. Clinical response.

Local nasal immunotherapy (LNIT) of ragweed allergic rhinitis was studied in a double-blind controlled trial. Sixty-seven subjects were divided into three groups. Twenty-one received unmodified ragweed extract (RW), 24 received a glutaraldehyde polymer of ragweed extract (PRW), and 22 received placebo. Mean symptom/medication scores during the season were 2.12, 2.76, and 3.93 for the RW, PRW, and placebo groups, respectively. Both RW- and the PRW-treated group scores were significantly lower than those of the placebo group (p less than 0.01, and p less than 0.025, respectively). The results of the patients' self-evaluations indicated that therapy was effective in 71%, 59%, and 41% for the RW-, PRW-, and placebo-treated groups, respectively. Adverse reactions to treatment were limited to the upper respiratory tract and were noted by all patients. They were significantly more severe in the RW-treated patients than those in the PRW- or placebo-treated groups. We conclude that LNIT is an effective therapy for ragweed allergic rhinitis. The use of a PRW decreased adverse reactions significantly while slightly decreasing the therapeutic benefit.

Local nasal immunotherapy: efficacy of low-dose aqueous ragweed extract.

In previous studies preseasonal local nasal immunotherapy (LNIT) with moderate doses of aqueous ragweed extract (mean total dose 59 micrograms of AgE and 139 micrograms of AgE) was an effective treatment for ragweed hay fever; however, local adverse reactions during therapy were common. This study evaluated the clinical and immunologic responses to LNIT by use of lower doses of aqueous ragweed extract in order to minimize these adverse reactions. Patients were administered preseasonal LNIT for 7 wk and received a mean total dose of 4.7 micrograms of AgE. During the ragweed season, symptom/medication scores (SMS) of the treated patients were equivalent to SMS of untreated patients. Serum ragweed-specific IgE and nasal secretory ragweed-specific IgA rose slightly in the treated patients but not to the extent observed in previous studies. After the ragweed season treated and untreated patients had a substantial increase in serum ragweed IgE antibody titers. No correlation could be found between antibody responses and SMS. This study indicates that LNIT with lower doses of aqueous ragweed extract is clinically ineffective.

Local intranasal immunotherapy with high-dose polymerized ragweed extract.

Thirty-one ragweed-allergic patients received preseasonal local intranasal immunotherapy (LNIT) with high doses of gluteraldehyde-polymerized ragweed extract (average total dose 544 micrograms antigen E). Minimal side effects were reported during treatment and did not interfere with the dosing schedule. During the ragweed pollen season, LNIT-treated patients had lower symptom scores for sneezing, rhinorrhea and nasal congestion than a comparable group of untreated ragweed-allergic patients. There was no difference in ragweed-induced eye symptoms between the two groups. Secretory ragweed-specific IgA and IgG rose following LNIT treatment. Absolute antibody titers and changes in titers did not correlate with clinical improvement. LNIT with the polymerized ragweed did not block the seasonal rise in serum ragweed-specific IgE. These results suggest that LNIT with high-dose polymerized ragweed extract is a safe, simple and effective form of immunotherapy.

Prednisolone disposition in steroid-dependent asthmatics.

A 40-mg intravenous dose of prednisolone was given as prednisolone phosphate to seven severe steroid-dependent asthmatics and to 13 healthy volunteers to determine if the large prednisone requirements of these patients were a function of the disease, cellular response, or rapid clearance of prednisolone. Plasma concentrations of prednisolone, prednisone, and cortisol were determined by high-performance liquid chromatography over an 8-hr test period. Circulating eosinophil concentrations were monitored concurrently. The apparent half-lifes of prednisolone in the asthmatics and normals were 3.33 +/- 0.71 and 3.25 +/- 0.58 hr (mean +/- SD). The apparent plasma clearances of prednisolone were 201 +/- 54 and 198 +/- 38 ml/min/1.73 m2 and the apparent volumes of distribution were 50.8 +/- 11.7 and 53.5 +/- 13.5 L/1.73 m2 for the asthmatic and normal groups, respectively. When the concentration-dependent binding of prednisolone to plasma protein was examined, no differences in the apparent clearances of unbound drug were found between the two groups. The eosinopenic response to prednisolone was similar in the steroid-dependent asthmatics and healthy normal volunteers. These studies indicate that binding, distribution, and clearance of prednisolone are not responsible for the large prednisone requirement of some steroid-dependent asthmatics. Differences in steroid-receptor sensitivity or in severity or pathophysiology of the disease state more likely account for the need for large prednisone dosages in these patients.

Local nasal immunotherapy for ragweed-allergic rhinitis. III. A second year of treatment.

In 1979, pre-seasonal local nasal immunotherapy (LNIT) was found to be an effective treatment for ragweed hay fever. In 1980, this study was continued to evaluate the clinical and immunologic responses of a second year of LNIT. Patients received either pre-seasonal treatment with an unmodified ragweed extract (RW) or a polymerized ragweed extract (PRW), or no treatment. The results of the second year of treatment were the same as the first year. Adverse reactions were significantly higher in the RW-treated group than in the PRW-treated group (P less than 0.001). Symptom/medication scores (SMS) in the RW-treated group were significantly lower than in the control group (P less than 0.005). Although SMS in the PRW-treated group were lower than in the control group, this difference was not significant. The immunologic response was evaluated by measurements of serum (S) RW-specific IgE and IgG and nasal secretory (NS) RW-specific IgE, IgG, and IgA. After treatment, serum IgE titres and secretory IgA titres rose in the RW-treated patients. Nasal secretory-IgG and NS-IgA titres increased with PRW treatment. The only immunologic response observed in the control group was a rise in S-IgE titres after the ragweed season. There was no substantial difference in immunologic measurements observed in the 1979 and 1980 seasons, except that the pre-treatment NS-IgE level was higher in 1980 (P less than 0.02). No significant correlations were found between antibody response and SMS. This study supports the efficacy of LNIT but does not support the protective role for NS-ragweed-specific IgA or IgG.