Steven R. Findlay

Cetirizine in patients with seasonal rhinitis and concomitant asthma: prospective, randomized, placebo-controlled trial☆☆☆★★★

OBJECTIVE This study explored the safety and efficacy of cetirizine for treatment of allergic rhinitis and asthma. METHODS Daily treatment for 6 weeks with cetirizine 10 mg (93 patients) was compared with placebo treatment (93 patients) in a randomized, double-blind parallel study of patients with allergic rhinitis and asthma. This multicenter study was started just before onset of the fall pollen season. Rhinitis and asthma symptoms were assessed twice daily; spirometry was performed weekly. RESULTS Placebo-treated patients experienced a worsening of rhinitis symptoms from baseline throughout the study, whereas cetirizine-treated patients had a significant improvement in rhinitis symptoms at week 1, which was maintained after onset of the pollen season. Asthma symptoms in the cetirizine group improved from baseline at week 1; symptoms were significantly better than in the placebo group for 5 of 6 weeks of the study. Pulmonary function did not worsen in patients taking cetirizine or placebo; there were no differences between treatments as determined by spirometry. Albuterol use was less frequent in the cetirizine-treated patients for every week of the study, but differences did not reach significance. Pseudoephedrine use was similar in both groups. More cetirizine-treated patients (90%) completed the trial than did placebo-treated patients (74%). Both treatments were well tolerated. CONCLUSION Cetirizine 10 mg daily is safe and effective in relieving both upper and lower respiratory tract symptoms in patients with seasonal allergic rhinitis and concomitant asthma.

Effect of the oral leukotriene antagonist, ICI 204,219, on antigen-induced bronchoconstriction in subjects with asthma

We studied the effect of a single oral dose of ICI 204,219 on subject response to bronchoprovocation and quantitative skin testing with standardized allergen (cat dander). Cat-allergic male subjects with asthma entered the double-blind, randomized, placebo-controlled, crossover study. Each subject received a 40 mg dose of ICI 204,219 or placebo on study days separated by at least 10 days. After dosing, each subject underwent bronchoprovocation with cat allergen until a provocative dose of allergen caused a 20% decrease in FEV1 or a maximum dose of 30,000 AU/ml was reached. Fifteen subjects entered and 13 completed the study. No significant shift in the dose-response curve of the quantitative skin test occurred in any subject. A mean tenfold increase in the interpolated provocative concentration causing a 20% decrease in FEV1 was observed between ICI 204,219 (6996 +/- 3204 AU/ml) and placebo (460 +/- 98 AU/ml). Eight of 12 subjects required more antigen to provoke a bronchoprovocation response after dosing with ICI 204,219 than that required with placebo (range, threefold to 30-fold), three demonstrated no difference (less than twofold), and one subject required less antigen after ICI 204,219 (sevenfold less). Area under the curve measurements were significantly different (p less than 0.05) between ICI 204,219 and placebo for the fixed time from the end point of the allergen bronchoprovocation to 5 hours after provocation. In conclusion, this trial demonstrates that a single oral dose of ICI 204,219 antagonizes the bronchoconstriction induced by inhaled cat allergen.

Fluticasone propionate given once daily is as effective for seasonal allergic rhinitis as beclomethasone dipropionate given twice daily

Fluticasone propionate was compared with beclomethasone dipropionate for the treatment of allergic rhinitis in a multicenter, double-blind, randomized, placebo-controlled study during the mountain cedar (Juniperus ashei) pollination season in central Texas. Adults (n = 313) with moderate to severe symptoms were treated with fluticasone propionate aqueous nasal spray 200 micrograms once a day or beclomethasone dipropionate aqueous nasal spray 168 micrograms twice a day or placebo for 2 weeks. Fluticasone propionate administered once daily and beclomethasone dipropionate administered twice daily were equally effective as assessed by clinician- and patient-rated scores for nasal obstruction, rhinorrhea, sneezing, and nasal itching throughout the treatment and follow-up periods. Both regimens were more effective than placebo. Adverse events were related to topical administration and were similar in frequency and nature in all three treatment groups. Fluticasone propionate and beclomethasone dipropionate displayed a similar safety profile that did not differ from placebo. We conclude that fluticasone propionate aqueous nasal spray administered as 200 micrograms once daily in the morning is as safe and effective as beclomethasone dipropionate aqueous nasal spray administered as 168 micrograms twice daily for seasonal allergic rhinitis.

A clinical trial of ipratropium bromide nasal spray in patients with perennial nonallergic rhinitis

Intranasal ipratropium bromide has been shown to significantly reduce rhinorrhea. Use of a freon-propelled intranasal preparation has resulted in side effects associated with the drying properties of the propellant. The purpose of the present trial was to study the safety and efficacy of a new isotonic aqueous ipratropium bromide nasal spray pump, specifically in patients with perennial nonallergic rhinitis. Two hundred thirty-three patients participated in an 8-week double-blind parallel comparison of ipratropium bromide nasal spray with its vehicle, a saline solution. Treatment with the ipratropium spray resulted in a 30% reduction in rhinorrhea; this reduction was significantly greater than that seen with the saline vehicle. There was a modest reduction in postnasal drip, sneezing, and congestion with both treatments, which may be attributable to the salutary effects of the saline solution. Patients also perceived a significant reduction in the degree to which rhinorrhea interfered with their daily activities and moods. Treatment was well tolerated, with no drug-related systemic adverse events and no evidence of nasal rebound on discontinuation of treatment. Minor, infrequent episodes of nasal dryness and epistaxis were the only significant adverse events reported; these did not limit treatment.

Ipratropium bromide aqueous nasal spray for patients with perennial allergic rhinitis: A study of its effect on their symptoms, quality of life, and nasal cytology☆

Ipratropium bromide is an anticholinergic agent with topical activity that has been studied as a freon-propelled aerosol spray for therapy of nonallergic rhinitis. This is the first report of its use both as an aqueous nasal spray and in perennial allergic rhinitis. In this study 123 patients who had symptoms of perennial allergic rhinitis were randomized to receive ipratropium bromide 21 micrograms or 42 micrograms or placebo, one spray per nostril three times a day for 4 weeks. Patients maintained daily diaries of duration and severity of nasal symptoms and were evaluated weekly. Mean duration and severity of rhinorrhea was decreased in both ipratropium bromide treatment groups by comparison with placebo, with consistently greatest improvement in the group treated with ipratropium bromide 42 micrograms per nostril three times a day. No statistically significant differences occurred among treatment groups in duration or severity of postnasal drip, congestion, or sneezing. Seventy percent of patients treated with 42 micrograms of ipratropium bromide thought it had good or excellent effect on rhinorrhea (p less than 0.05 vs placebo); significantly more patients thought that it had improved the quality of life (p = 0.02). No changes occurred in nasal cytology, and no significant local or systemic adverse events occurred. These data indicate that ipratropium bromide significantly decreases the rhinorrhea of perennial allergic rhinitis.

Effects of budesonide by means of the Turbuhaler on the hypothalmic-pituitary-adrenal axis in asthmatic subjects: A dose-response study

BACKGROUND As a general phenomenon, corticosteroids may suppress the activity in the hypothalamic-pituitary-adrenal (HPA) axis. The adrenal stimulation test is a commonly used method to assess the relative risk of exogenous corticosteroids to induce systemic side effects. OBJECTIVES This clinical trial was performed to assess the effects of budesonide on the HPA axis (at 800, 1600, or 3200 microg/day, given as a twice daily regimen, administered by means of the Turbuhaler) in adult patients with mild, non-steroid-dependent asthma. METHODS Sixty-four asthmatic patients received budesonide or placebo by inhalation or 10 mg/day oral prednisone once daily as a positive control in a double-blind, double-dummy, randomized, placebo-controlled, parallel-group, multicenter study. Plasma cortisol concentration was measured to assess the effect on the HPA axis before and during a 6-hour infusion of synthetic adrenocorticotropic hormone (ACTH), cosyntropin. RESULTS After 6 weeks of treatment, plasma cortisol concentrations after adrenal stimulation by cosyntropin infusion had fallen by 4% in the placebo group; by 13%, 11%, and 27% in the budesonide groups (800, 1600, and 3200 microg/day, respectively); and by 35% in the prednisone group. The decrease was significant only in the 3200 microg/day budesonide (p = 0.03) and prednisone (p = 0.005) groups. Over the same time period, decreases in basal plasma cortisol concentrations were 1% in the placebo group; 19%, 19%, and 34% in the three budesonide groups; and 37% in the prednisone group. Only in the prednisone group was the decrease significant (p = 0.03 vs placebo). CONCLUSIONS In this study budesonide inhaled by means of the Turbuhaler, at doses recommended for clinical use (800 or 1600 microg/day), did not produce any statistically significant suppression of the HPA axis compared with placebo.

Use of ipratropium bromide nasal spray in chronic treatment of nonallergic perennial rhinitis, alone and in combination with other perennial rhinitis medications

To study the long-term safety and effectiveness of ipratropium bromide nasal spray 0.03% in the treatment of nonallergic perennial rhinitis, we administered this medication for 1 year in an open-label trial involving 285 patients. Our intention was to maintain the highest protocol dose possible to gain a clearer picture of the long-term side effect profile of the compound. Ipratropium bromide was well tolerated with no serious side effects in this patient population. It provided a significant improvement in rhinorrhea throughout the year-long trial; only 17 of 285 patients (6%) were considered treatment failures. There was an improvement in patient quality of life, as well as a substantial reduction in the need for other medications (antihistamines, decongestants, and nasal steroids) used to treat perennial rhinitis symptoms.

Long-term treatment of perennial allergic rhinitis with ipratropium bromide nasal spray 0.06%

The purpose of this study was to assess the safety and efficacy of ipratropium bromide nasal spray 0.06% (aqueous solution), 84 micrograms per nostril three times a day, in reducing nasal hypersecretion in the long-term treatment of patients with perennial allergic rhinitis (PAR). This was an open-label 1-year trial. In the first 6 months all patients were treated with two puffs ipratropium bromide nasal spray 0.06%, 84 micrograms per nostril three times per day, unless they were unable to tolerate the dose. In the last 6 months the dose could be reduced to the lowest amount required to control rhinorrhea. Ninety-six patients entered the trial, and 47 completed it. Sixty-three patients completed more than 6 months of treatment. Patient and physician global evaluation suggested that ipratropium bromide nasal spray 0.06% is effective in controlling rhinorrhea associated with PAR and can contribute to control of congestion, postnasal drip, and sneezing. There was also a trend toward reduction of mucosal edema and improvement in quality of life. The most common drug-related adverse events were nasal dryness, epistaxis/nose bleed, and increased rhinitis. Most adverse events were mild and resulted in drug discontinuation in less than 10% of patients. Ipratropium bromide nasal spray was well tolerated and not associated with serious drug-related adverse events or clinically significant anticholinergic side effects. Use of ipratropium bromide nasal spray alone or with other standard medications should be considered in treating patients with PAR.

Polistes wasp hypersensitivity: Diagnosis by venom-induced release of histamine in vitro☆

Polistes wasps cause a majority of Hymenoptera-induced anaphylactic reactions in Texas. Using the in vitro release of histamine from basophils of patients allergic to Polistes stings, we have studied the cross-reactivity of venoms from three species of Polistes wasps as well as the cross-reactivity among Polistes, honeybee, and Vespula maculifrons (yellow jacket) venoms. Venom collected by an extrusion technique from Pollistes exclamans, Pollistes apachus, and Pollistes carolina caused release of histamine in seven Polistes-sensitive individuals. The dose-response curves from all three Polistes species were quite similar, suggesting extensive cross-reactivity among these species. None of these patients showed significant release of histamine from leukocytes exposed to yellow jacket or honeybee venom. We conclude that a source of Polistes venom is available for further study and possibly for therapy. It appears that any of three local common species of Polistes wasps could be used. Our studies confirmed earlier reports that Hymenoptera sensitivity if often genus-specific.

Comparison of efficacy, safety, and skin test inhibition of cetirizine and astemizole.

BACKGROUND Astemizole, an H1-histamine-receptor antagonist prescribed for seasonal allergic rhinitis, has a slow onset of action and a strong suppressive effect on the wheal and flare reaction, which interferes with skin testing results. The newer antihistamine cetirizine appears to have a rapid onset of action and a low potential to interfere with posttreatment skin testing results. OBJECTIVE To compare the efficacy, safety, and skin test inhibition of astemizole and cetirizine in the treatment of seasonal allergic rhinitis. METHODS In a double-blind, parallel-group study conducted at six sites during ragweed pollination season, 263 subjects were randomized to receive 10 mg of astemizole, 5 mg of cetirizine, or 10 mg of cetirizine daily for 2 weeks. The subjects rated seven allergic rhinitis symptoms daily, the subjects and investigators provided global assessments of the responses to the treatments, and the subjects rated their satisfaction with the treatments. Thirty-nine subjects at one study site underwent quantitative skin testing before and after treatment. RESULTS As measured by reduction from baseline in total symptom severity score, which was the primary efficacy measure in the study, all three treatments significantly relieved the symptoms of allergic rhinitis (P less than .05). This finding was supported by the global ratings and the subject satisfaction ratings. There were no significant differences among the three treatments for reduction from baseline in total symptom severity score. The mean subject satisfaction score with 10 mg of cetirizine was significantly greater than that with astemizole (P less than .05). In the skin tests performed 3, 7, and 14 days after the end of antihistamine treatment, the subjects who had received the cetirizine doses had significantly greater mean sum of wheal and mean sum of erythema values than those who had received the astemizole dose (P less than .05). Sensitivity to ragweed pollen extract returned to 90% of baseline within three days of the end of cetirizine treatment. Both drugs were well tolerated and their adverse event profiles were similar. CONCLUSIONS Astemizole and cetirizine are effective and well tolerated in alleviating the symptoms of ragweed-induced allergic rhinitis. Cetirizine inhibits skin test results to a much lesser extent than does astemizole. Physicians may wish to consider the potential for skin test inhibition when selecting an antihistamine for patients with allergic rhinitis.