Effect of fluticasone propionate aqueous nasal spray versus oral prednisone on the hypothalamic-pituitary-adrenal axis.

BACKGROUND: Fluticasone propionate is a glucocorticoid with negligible oral bioavailability and very low intranasal bioavailability that is used as an intranasal spray for the treatment of rhinitis. OBJECTIVE: The purpose of this study was to evaluate the hypothalamic-pituitary-adrenal (HPA)axis effects of fluticasone propionate aqueous nasal spray (FP ANS) compared with oral prednisone and placebo by using a 6-hour cosyntropin infusion test. METHODS: In a 4-week, randomized, double-blind, double-dummy, placebo-controlled parallel-group study, 105 adult patients with allergic rhinitis were randomly assigned to receive FP ANS 200 microg once daily, FP ANS 400 microg twice daily, oral prednisone 7.5 mg once daily, oral prednisone 15 mg once daily, or placebo. HPA-axis function was assessed at the screening visit and after 4 weeks of treatment by measuring morning plasma cortisol concentrations and poststimulation concentrations of plasma and urinary cortisol. RESULTS: There was no evidence of altered HPA-axis response to cosyntropin by the end of treatment with FP ANS 200 microg once daily or FP ANS 400 microg twice daily when compared with placebo. In contrast, 4 weeks of treatment with oral prednisone 7.5 or 15 mg once daily was associated with significant (p < 0.05 vs placebo) reduction in HPA-axis function, as evidenced by lower plasma cortisol concentrations (area under the plasma concentration-time curve and peak concentrations) after cosyntropin stimulation and reduced mean 24-hour urinary cortisol excretion. FP ANS 400 microg twice daily and both prednisone regimens were associated with a significant (p < 0.05 vs placebo) reduction in mean morning plasma cortisol concentrations. CONCLUSION: These results indicate that a 4-week course of FP ANS at four times the recommended dose does not suppress adrenal function in response to a 6-hour cosyntropin stimulation test.

The anticholinergic agent, ipratropium bromide, is useful in the treatment of rhinorrhea associated with perennial allergic rhinitis.

The effects of the new ipratropium bromide nasal spray on rhinorrhea associated with perennial allergic rhinitis were studied in 219 patients over eight weeks in a multicenter, randomized, double-blind trial. The purpose of the study was to determine whether the new spray reduces nasal hypersecretion in allergic patients without causing excessive dryness or other potential cholinergic side effects. The investigators compared two doses of the spray (42 or 84 mcg/nostril t.i.d.) to placebo. Two hundred and nineteen patients were admitted to the study; 176 completed it. Study design included one week of screening to confirm a diagnosis of perennial allergic rhinitis with clinically significant rhinorrhea, one week of single-blind treatment with a placebo consisting of the saline vehicle of the spray, an eight-week double-blind treatment-comparison period, and one week of follow-up without treatment. Both doses of ipratropium bromide nasal spray significantly reduced the hypersecretion associated with PAR, compared with placebo. The two doses of active drug were equally effective. Treatment differences were noticeable during the first week and remained relatively stable during the eight-week treatment period. There was no evidence of nasal rebound after discontinuation of treatment. The incidence of side effects was comparable to placebo. The spray was well-tolerated, and was not associated with any significant adverse events.

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.

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.

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.

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.

Asthma symptoms and airway hyperresponsiveness are lower during treatment with nedocromil sodium than during treatment with regular inhaled albuterol.

In a double-blind, double-dummy, multicenter study, 212 patients with asthma whose symptoms were not controlled by as-needed use of inhaled bronchodilators were randomized to receive either 4 mg of nedocromil sodium or 180 micrograms of albuterol four times daily for 12 weeks. Asthma symptom scores (daytime asthma, nighttime asthma, morning chest tightness, and cough) and peak expiratory flow rate were recorded daily on diary cards. Bronchial hyperresponsiveness was assessed by changes in diurnal variation in peak expiratory flow rate and by methacholine inhalation challenge. Statistically significant differences were found between groups favoring nedocromil sodium for relief of day and nighttime asthma and morning chest tightness. Patients treated with nedocromil sodium also had significantly lower diurnal variation in peak expiratory flow rate compared with patients treated with albuterol. Compared with patients treated with albuterol, patients treated with nedocromil sodium showed a greater improvement in cough and a decreased sensitivity to methacholine challenge. Patients in both groups reduced their as-needed albuterol use. Regular treatment with nedocromil sodium therefore led to greater asthma symptom control and reduced bronchial responsiveness compared with regular treatment with albuterol. The study also showed that more frequent use of a beta 2-agonist (for symptom relief or not) did not improve asthma control. Both drugs were well tolerated.

Intranasal fluticasone propionate is more effective than terfenadine tablets for seasonal allergic rhinitis.

BACKGROUND: We compared the efficacy and tolerability of the intranasal corticosteroid fluticasone propionate with that of the antihistamine terfenadine in patients with seasonal allergic rhinitis. METHODS: Two hundred thirty-two adults and adolescents with seasonal allergic rhinitis received intranasal fluticasone propionate (200 micrograms once daily), terfenadine tablets (60 mg twice daily), or placebo for 2 weeks in a double-blind, randomized, parallel-group study. Main outcome measures were clinician- and patient-rated individual and total nasal symptom scores (based on ratings of nasal obstruction, sneezing, nasal itching, and rhinorrhea); clinician-rated overall response to therapy; changes in nasal inflammatory cell counts; adverse events; and morning plasma cortisol concentrations. RESULTS: Both clinician- and patient-rated total and individual nasal symptom scores were significantly lower in the fluticasone group than in either the terfenadine group or the placebo group at nearly every measured time point throughout the treatment period. After 2 weeks of therapy, clinician-rated total nasal symptom scores decreased by 49% in the fluticasone group compared with 27% in the terfenadine group and 19% in the placebo group. In general, therapy with terfenadine was not statistically distinguishable from that with placebo based on patient-rated total or individual nasal symptom scores. According to clinician ratings, 64% of fluticasone-treated patients compared with 49% and 44% of patients treated with terfenadine and placebo, respectively, experienced significant or moderate improvement. A greater percentage of fluticasone-treated patients compared with either terfenadine- or placebo-treated patients experienced reductions in intranasal eosinophil and basophil counts after 2 weeks of therapy. No unusual or serious drug-related adverse events were reported. Morning plasma cortisol concentrations after 2 weeks of therapy did not differ among groups. CONCLUSION: Fluticasone aqueous nasal spray, a well-tolerated corticosteroid preparation that can be administered once daily, is more effective than terfenadine tablets or placebo in controlling symptoms of seasonal allergic rhinitis.

A double-blind, controlled trial to assess the safety and efficacy of azelastine nasal spray in seasonal allergic rhinitis.

BACKGROUND: Azelastine solution is a topically (nasal) administered antiallergy drug with a preclinical profile suggestive of efficacy in patients with allergic rhinitis. OBJECTIVES: The study was designed to compare the effectiveness and safety of two dosages of azelastine nasal spray (2 sprays per nostril once daily and twice daily) with that of placebo in the treatment of patients with symptomatic seasonal allergic rhinitis. METHODS: Two hundred fifty-one patients (12 years of age or older) were randomized to treatment in this 2-week, double-blind, parallel-group study. Primary efficacy variables were Major Symptom Complex (nose blows, sneezes, runny nose, itchy nose, watery eyes) and Total Symptoms Complex (Major Symptom Complex plus itchy eyes/ears/throat/palate, cough, postnasal drip). RESULTS: Patients treated with azelastine had mean percent improvements in Total and Major Symptom Complex scores that were consistently superior to placebo at each evaluation point. Overall, improvements were statistically significant (p < or = 0.05) in the Total Symptoms Complex for both azelastine groups and in the Major Symptom Complex for the twice daily group with a trend toward statistical significance for the once daily group. Azelastine was superior to placebo in improving all individual rhinitis symptoms. Adverse experiences in the azelastine groups were minor and infrequent. CONCLUSION: The results support the efficacy and safety of azelastine nasal spray in the treatment of seasonal allergic rhinitis.

Fluticasone propionate: an effective alternative treatment for seasonal allergic rhinitis in adults and adolescents.

BACKGROUND: Topical corticosteroids are widely regarded as the reference standard in allergic rhinitis therapy because they are well tolerated and effective against all rhinitis symptoms. We evaluated the efficacy, onset of action, and safety of two dosing regimens of the new corticosteroid fluticasone propionate compared with that of beclomethasone dipropionate in patients with moderate to severe seasonal allergic rhinitis. METHODS: In this double-blind, randomized multicenter trial, 110 adolescents and 128 adults were treated for 4 weeks with one of the following regimens: fluticasone aqueous nasal spray 100 micrograms twice daily or 200 micrograms once daily, beclomethasone aqueous nasal spray 168 micrograms twice daily, or placebo. RESULTS: Patient-rated scores for nasal obstruction, rhinorrhea, and combined nasal symptoms indicated that the two fluticasone regimens were equally effective and that both were superior to beclomethasone during most of the study (P < or = .05) and to placebo throughout the study (P < or = .01). Both fluticasone regimens also demonstrated significant clinical efficacy by 24 hours after the first dose. Clinician-rated mean total nasal symptoms scores for all three active treatments were superior to placebo at most time points but were not significantly different from each other. All treatments were well tolerated, with similar incidence and type of adverse events in all treatment groups and no apparent effects on hypothalamic-pituitary-adrenal (HPA) axis function. CONCLUSIONS: Fluticasone aqueous nasal spray was effective in relieving nasal symptoms in adolescents and adults with seasonal allergic rhinitis. Fluticasone administered once or twice daily was superior to beclomethasone administered twice daily in relieving nasal obstruction and rhinorrhea and in reducing nasal symptoms more quickly.

Fluticasone propionate aqueous nasal spray is safe and effective for children with seasonal allergic rhinitis.

INTRODUCTION: Fluticasone propionate aqueous nasal spray, a new topical corticosteroid preparation, is effective when given as 200 micrograms once daily in patients (> 12 years of age) with seasonal allergic rhinitis. STUDY OBJECTIVE: To evaluate the efficacy and safety of fluticasone proprionate aqueous nasal spray in children aged 4 to 11 years with seasonal allergic rhinitis. STUDY DESIGN: Multicenter, randomized, double-blind, placebo-controlled, parallel-group. PATIENTS: Two hundred fifty children aged 4 to 11 years with moderate-to-severe nasal symptoms, a positive skin test reaction to a late-summer or autumn allergen, a history of seasonal allergic rhinitis, and documentation of an unsatisfactory response to conventional treatment. INTERVENTIONS: Children were randomly assigned to receive fluticasone propionate, either 100 micrograms or 200 micrograms, or placebo, given by intranasal spray once daily in the morning for 14 days. MEASUREMENTS AND RESULTS: Severity of nasal symptoms (obstruction, rhinorrhea, itching, and sneezing) was recorded on visual analog scales by investigators at weekly visits and by patients (or adult guardian) daily in the evening. According to investigator and patient ratings, both fluticasone propionate 100 micrograms/d and 200 micrograms/d lowered total nasal symptom scores when compared with placebo. Both dosages of fluticasone propionate were more effective than placebo on the basis of investigator-rated overall clinical evaluation of efficacy at the end of treatment, with significant improvement (as opposed to moderate or mild improvement, no change or worsening) noted in 21% to 29% of the active-treatment groups vs 9% in the placebo group. There were no significant differences between the two fluticasone propionate dosages in any efficacy measurement. Morning plasma cortisol concentrations and frequency of drug-related adverse events were similar in the fluticasone propionate and placebo groups. CONCLUSION: In children as young as 4 years, 100 micrograms of fluticasone propionate aqueous nasal spray given once daily is as effective as 200 micrograms given once daily, the usual adult dose for the treatment of seasonal allergic rhinitis. Both fluticasone propionate dosages were well tolerated and neither dosage appears to interfere with the hypothalamic-pituitary-adrenal axis in children.

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.

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.

Adrenal function in adult asthmatics during long-term daily treatment with 800, 1,200, and 1,600 micrograms triamcinolone acetonide. Multicenter study.

A study to assess the effect of the long-term use of triamcinolone acetonide (TA) on adrenal function was conducted with 143 male and female patients with asthma who were randomly assigned to receive 800, 1200, or 1,600 micrograms of TA daily for six months. Adrenal function was assessed prior to treatment and after two weeks and one, three, and six months of TA use. The effect of TA was evaluated by measuring plasma cortisol levels just prior to and 30 min after a bolus IV injection of 0.25 mg cosyntropin. Adrenal suppression was assumed if the plasma concentration of cortisol did not increase by at least 7 micrograms/dl from the prestimulation value, and remained below 18 micrograms/dl 30 min after the cosyntropin injection. Urine collected for 24 h prior to each cosyntropin stimulation was assayed for free cortisol and related metabolites to confirm suppression. Although all treatment regimens caused some reduction in the 24-h excretion of corticosteroid products, none of the mean values was below the normal ranges. The mean data indicate that TA had no significant effect on adrenal function at any dose or at any time for the patients overall. Individually, three patients exhibited some reduction in adrenal function.

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.

Comparison of histamine release effects of ionic and non-ionic radiographic contrast media.

Histamine release may underline the side effects (particularly anaphylactoid) of radiographic contrast media. To study the histamine-releasing properties of radiographic contrast media, this study measured the in vitro release of histamine from human basophils incubated with diatrizoate, a standard ionic radiographic contrast agent, and with iopamidol, a newly developed non-ionic contrast agent. The basophils were separated from blood obtained from 16 patients scheduled for coronary angiography. For both diatrizoate and iopamidol, the concentration of histamine released varied as the concentration of radiographic contrast agent was increased from 0.075 M to 0.50 M. At the higher concentrations tested, the percent of histamine released by iopamidol was about half that released by diatrizoate (p less than 0.05). These data suggest that the use of non-ionic contrast media may involve less patient risk from the histamine-mediated allergic and/or hemodynamic side effects associated with radiographic contrast procedures.

Immunotherapy in cat-induced asthma. Double-blind trial with evaluation of in vivo and in vitro responses.

The efficacy of immunotherapy in cat-induced asthma was studied by use of a purified fraction of cat-pelt extract and a double-blind protocol. Nine active-treatment subjects who received a mean cumulative dose of cat allergen, 1 of 10.9 units, and eight placebo-treatment subjects completed the study. Active treatment resulted in significant reductions in bronchial sensitivity (p less than 0.05) and prick test titer (p less than 0.01). In addition, active treatment resulted in a significant delay in the onset of ocular (p less than 0.05) and pulmonary (p less than 0.02) symptoms on exposure to living cats. Significant increases in IgG antibody to cat allergen 1 (p less than 0.001) and cat albumin (p less than 0.01) also occurred with active treatment. There was no significant change in bronchial reactivity to methacholine or in the sensitivity of circulating basophils. These results confirm the validity of immunotherapy in allergic asthma where there is careful patient selection and well defined treatment preparations.

Radiographic contrast media-induced noncardiogenic pulmonary edema: case report and review of the literature.

Adverse reactions are a frequent complication of exposure to radiographic contrast media (RCM). These reactions are most often anaphylactoid in nature and are characterized by the occurrence of urticaria, angioedema, bronchospasm, and shock. In patients who have had an anaphylactoid reaction to RCM and in whom reexposure is indicated, various pretreatment protocols have been developed to mitigate the risk for recurrence. We report the case of a 46-year-old man who, while undergoing cardiac catheterization, developed noncardiogenic pulmonary edema. This is the first reported case of the occurrence of noncardiogenic pulmonary edema secondary to RCM documented with Swan-Ganz data. In addition, our patient developed noncardiogenic pulmonary edema despite pretreatment with prednisone and diphenhydramine, administered because of a past history of a similar reaction. Potential mechanisms for such a reaction are discussed.

In vitro basophil histamine release induced by mannitol in a patient with a mannitol-induced anaphylactoid reaction.

Anaphylactoid reactions in man are associated with the infusion of diagnostic and therapeutic agents. The etiology of such reactions remains unknown, but clinically they have the signs and symptoms that mimic those associated with in vivo histamine release. We report that the leukocytes of a patient who suffered an anaphylactoid reaction associated with the infusion of mannitol repeatedly released histamine in vitro when the leukocytes were challenged with low concentrations of mannitol (less than 0.1 M). In 44% deuterium oxide buffer, the patient's cells were tenfold more reactive to mannitol as compared to normal leukocytes and were pharmacologically modulated in a fashion similar to IgE-dependent release. The temperature optimum for this nonhyperosmolar (less than 0.1M) mannitol-induced, deuterium oxide-dependent release was the same as that for IgE-dependent release. Desensitization of the patient's cells with anti-IgE completely suppressed release induced by low concentrations of mannitol but did not affect the hyperosmolar (greater than 0.1M) mannitol-induced release of basophil histamine. These studies suggest that patients experiencing anaphylactoid reactions may be identified by use of in vitro basophil histamine release.