James A. Nickelsen

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 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.

Local nasal immunotherapy: Efficacy of lowdose 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.

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.

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.