Barriers to measuring and achieving optimal outcomes in pediatric asthma.

To measure the effectiveness of any therapeutic endeavor, a set of defined outcome measurements must be performed, or the task of determining the effectiveness of any therapeutic step becomes difficult. With asthma, however, in which case it is difficult to establish the initial diagnosis, beginning a program of outcome measurements regarding any therapeutic interaction is nearly impossible. Conventional means are thwarted at the outset. One way of approaching the problem of obtaining reproducible outcomes data is to examine those areas in which measurements can be made and determine the barriers to obtaining the data. Establishing a good medical history is a critical step that, in general, is especially difficult with very young children, and tools that provide objective measurements that are used in the normal evaluation of older children are of little use in the very young child with asthma. Parts of the physical examination are difficult to perform in very young children, and findings associated with asthma can be found in other clinical states. In this age group, diary keeping suffers from the same problems and issues that are related to obtaining an accurate medical history. Barriers also exist to obtaining the best outcomes. The choice of medications for the very young child is limited; there are several typical adherence problems, and information about adverse effects is limited.

Disease management program improves asthma outcomes.

OBJECTIVE: To show that a disease management program that empowers patients with asthma to participate in the management of their condition can improve quality of life and reduce the use of medical services. STUDY DESIGN: Utilization and quality-of-life data were tracked to identify outcome changes in patients with moderate to severe asthma. Baseline measures were used as a control and were compared with measures taken at 6 and 12 months after enrollment. PATIENTS AND METHODS: Study participants were from a single Medicaid managed care plan in western Pennsylvania. Patients' quality of life during their participation in the program was tracked through an outside pharmacoepidemiologic research firm. Utilization data were updated with every interaction between a patient and case management nurse. RESULTS: Both quality-of-life and utilization data show statistically significant improvements at 6 months. Further, 12-month data show improvement that is statistically significant in all measures with the exception of the adult quality-of-life measure, where a small sample size limited the statistical results. CONCLUSIONS: A collaborative, proactive approach to asthma management improves patients' quality of life and reduces use of costly medical services.

Efficacy and safety of ketorolac tromethamine 0.5% and levocabastine 0.05%: a multicenter comparison in patients with seasonal allergic conjunctivitis.

This multicenter, double-masked, randomized, parallel-group study compared the efficacy and safety of ketorolac tromethamine 0.5% ophthalmic solution with levocabastine 0.05% and ketorolac tromethamine vehicle in patients with seasonal allergic conjunctivitis. One drop of ketorolac, levocabastine, or vehicle was instilled in each eye four times daily for 6 weeks. In the majority of efficacy variables, ketorolac produced the greatest improvements, followed by levocabastine and vehicle. Ketorolac was significantly more effective (P < .05) than vehicle in reducing mean itching scores, palpebral hyperemia, bulbar hyperemia, and edema. Patients treated with ketorolac reported significant improvements (P < .05) in their ability to sleep and to concentrate on work, compared with those who received vehicle. No significant differences were noted among the treatment groups in safety or tolerability. Ketorolac tromethamine 0.5% ophthalmic solution instilled four times daily is effective and safe in reducing the signs and symptoms of seasonal allergic conjunctivitis.

Dose-response evaluation of levalbuterol versus racemic albuterol in patients with asthma.

Albuterol, in all marketed forms, is sold as a racemate, composed of a 50:50 mixture of (R)- and (S)-isomers. Racemic albuterol and the single isomer version (R)-albuterol (levalbuterol) were compared in a randomized, double-blind, dose-ranging five-way crossover study in patients (n = 20) with mild persistent to moderate persistent asthma. Placebo, racemic albuterol (2.50 mg), or levalbuterol (0.31, 0.63, or 1.25 mg) were delivered as single, nebulized doses to 5 male and 15 female nonsmoking patients with asthma aged 18-50 years. Serial pulmonary function was assessed at 15-min intervals and mean time to onset of activity and duration of improvement of forced expiratory volume in 1 sec (FEV1) were measured. In addition, blood chemistries, electrocardiogram (ECG) readings, and patient subjective assessment of adverse symptoms were recorded. Levalbuterol was found to provide significant bronchodilatory activity and was well tolerated. Levalbuterol 1.25 mg provided the greatest increase and duration in FEV1 improvement, whereas racemic albuterol (2.50 mg) and levalbuterol 0.63 mg provided comparable effects. The lower doses of levalbuterol were associated with a less marked effect on heart rate and potassium than racemic albuterol or high-dose levalbuterol. These data suggest that 0.63 mg levalbuterol provides bronchodilation equivalent to 2.50 mg racemic albuterol with less beta-mediated side effects.

Lack of subsensitivity to albuterol after treatment with salmeterol in patients with asthma.

The development of tolerance to the bronchodilator effects of beta2-agonists used in asthma therapy has been the subject of debate. We conducted two placebo-controlled crossover studies to assess the bronchodilator response to a short-acting beta2-agonist before and after chronic therapy with salmeterol. Patients in one study were corticosteroid-naive; patients in the other study were using inhaled corticosteroids. Changes in FEV1 after cumulative doubling doses of inhaled albuterol were assessed after a 2-wk beta-agonist washout period, before administering study medication on Day 1, and again after 28 d of therapy. Ipratropium bromide was provided as rapid-relief treatment for asthma, and use of any beta2-agonist except the study treatment was prohibited. On both assessment days for salmeterol, and during placebo administration periods, significant increases from predose FEV1 values were observed beginning with the lowest dose of albuterol and continuing throughout the dose-response assessment (p

A multicenter, placebo-controlled study of twice daily triamcinolone acetonide (800 microg per day) for the treatment of patients with mild-to-moderate asthma.

BACKGROUND: National and international guidelines recommend the use of inhaled antiinflammatory medications in patients with all but the mildest forms of asthma. Twice daily dosing may increase compliance with therapy. OBJECTIVE: We sought to evaluate the safety and efficacy of 400 microg twice daily triamcinolone acetonide (TAA) compared with placebo in adult patients with mild-to-moderate asthma who were poorly controlled by beta2-agonist therapy. METHODS: We performed a multicenter, randomized, double-blind, placebo-controlled study, including a screening visit, a 7- to 21-day pretreatment baseline phase, and a 6-week double-blind treatment phase. Efficacy was measured by weekly spirometry and daily diary recordings of peak flow rates, asthma symptom scores, and albuterol use. Eligible patients used albuterol four or more times per day, had total asthma symptom scores of 15 or greater (possible total, 60) over 5 of 7 baseline days, and had FEV1 measurements of 60% of predicted value or greater. RESULTS: One hundred twenty-one patients were randomized to treatment. TAA was superior to placebo for all efficacy measures, with significant improvements in asthma symptoms, albuterol use, morning and evening peak flow rates, and forced vital capacity evident at Treatment Week 1. Significant improvements in other pulmonary function measurements were observed after 2 or more weeks. All efficacy variables improved progressively throughout the study. CONCLUSIONS: Twice daily TAA (400 microg) decreased asthma symptoms and improved lung function in patients with mild-to-moderate asthma compared with placebo. Therapeutic benefit was evident within 1 week and increased throughout treatment.

Growth in asthmatic children treated with fluticasone propionate. Fluticasone Propionate Asthma Study Group.

OBJECTIVE: To determine whether inhaled fluticasone propionate has long-term effects on growth in children with persistent asthma. STUDY DESIGN: In a double-blind, randomized, parallel-group, multicenter study, 325 prepubescent children with persistent asthma and normal growth rates were treated with placebo or inhaled fluticasone propionate powder 50 microg or 100 microg administered twice daily by a breath-actuated device for 1 year. Growth was evaluated monthly, whereas other safety variables and pulmonary function were evaluated periodically. RESULTS: The prepubescent patients showed no statistically significant differences in mean height, mean growth velocity, or mean skeletal age between any of the treatment groups at any time. Over a period of 1 year, mean height (+/- SE) increased 6.15 +/- 0.17 cm in the placebo group, 5.94 +/- 0.16 cm in the fluticasone propionate 50 microg group, and 5.73 +/- 0.13 cm in the fluticasone propionate 100 microg group (p = 0.308, overall). CONCLUSIONS: Prepubescent children treated with fluticasone propionate 50 microg and 100 microg administered twice daily for 1 year grew at rates similar to placebo-treated control subjects and at rates equal to expected growth velocity for age.

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.

Neuropsychological and behavioral changes in asthmatic children treated with beclomethasone dipropionate versus theophylline.

OBJECTIVE: Results from previous investigations that examined the psychological side effects of theophylline have been inconsistent, and none have reported about inhaled corticosteroids. The objective of this study was to assess the relative psychological side effects of theophylline and beclomethasone in asthmatic children. METHODS: This was a multicenter, randomized, double-blind, parallel-groups study in which 102 asthmatic patients were assigned to one of two treatments: beclomethasone three times daily or theophylline twice daily. At baseline, 1 month, and 1 year, parents completed standardized behavioral questionnaires while the children received psychometric testing of attention and concentration, memory and learning, and problem-solving. RESULTS: Although power was sufficient to detect meaningful mean score changes, no consistent differential treatment effects were observed. Two significant treatment-by-period interactions were discordant, with one suggesting slightly better attention in the theophylline group, whereas the other indicated a small advantage in attention scores in the beclomethasone group. Numerous significant period effects revealed that behavior and cognitive test performance improved over the 1-year period, regardless of treatment, and confirmed a well established practice effect resulting from repeated administrations of such tests. CONCLUSIONS: Neither theophylline nor beclomethasone should be avoided out of concern for significant psychological side effects. The possibility remains that a subset of asthmatic children may be susceptible to such medication-induced changes; investigators have suggested that preschool children may be at particular risk, although no controlled studies with this age group have been conducted. Parental perceptions of medication side effects can be influenced by temporary effects present at initiation of treatment or by erroneous attribution of the psychological effects of the chronic illness. Reports of psychological changes in response to asthma medications must be addressed respectfully but objectively, with due consideration of available evidence and an awareness of other potential explanations.

Proventil HFA and ventolin have similar safety profiles during regular use.

OBJECTIVE: As a secondary objective to a long-term study evaluating the bronchodilator effectiveness of Proventil HFA (albuterol), to assess the safety of Proventil HFA, Ventolin, and hydrofluoroalkane 134a (HFA-134a) placebo over 12 weeks of regular dosing. DESIGN: Randomized, double-blind, double-dummy parallel group, placebo-controlled, multicenter trial of asthmatics requiring inhaled beta-adrenergic bronchodilators for symptom control. INTERVENTIONS: Treatment with Proventil HFA, Ventolin, or HFA-134a placebo, qid, for 12 weeks. MEASUREMENTS: Adverse events were reviewed at biweekly clinic visits. Between clinic visits, patients recorded morning and evening peak expiratory flow (PEF), asthma symptom and nighttime asthma sleep disturbance scores, and use of rescue beta-adrenergic bronchodilator on diary cards daily. Investigators provided a global assessment of asthma control at weeks 0, 4, 8, and 12. Vital signs were recorded over 6 h after dosing with study drug at weeks 0, 4, 8, and 12. Standard laboratory tests, CBC count, serum chemistries, and urinalysis were obtained at study start and end. RESULTS: Adverse event reporting rates were similar for the three treatment groups. The morning PEF tended to be lower for the Proventil HFA and Ventolin groups than the HFA-134a placebo group, but the evening PEF tended to be higher for the active treatment groups. Daytime asthma symptom scores tended to be lower (better) with active treatment than placebo, but nighttime asthma sleep disturbance scores were similar for all three treatment groups. Use of Ventolin Rotacaps as rescue medication was significantly greater for the HFA-134a placebo group than the Proventil HFA and Ventolin groups. Diary card data did not change within groups over time. Investigator global assessments of asthma scores clustered between fair and good for all three treatment groups throughout the study. Changes in heart rate and BP were small after dosing with study drug and tended to be similar for the active treatments and HFA-134a placebo groups. No clinically meaningful changes in results of standard laboratory tests were found in any treatment group during this study. CONCLUSIONS: Proventil HFA had a similar safety profile as Ventolin during regular use. A dosage of 16 puffs per day of propellant HFA-134a was well tolerated by asthmatics. Regular use of either Proventil HFA or Ventolin did not cause asthma control to deteriorate.

Proventil HFA provides bronchodilation comparable to ventolin over 12 weeks of regular use in asthmatics.

OBJECTIVE: To compare the bronchodilator effectiveness of albuterol reformulated in the chlorofluorocarbon-free propellant hydrofluoroalkane (HFA)134a (Proventil HFA) to that of Ventolin and HFA placebo over 12 weeks of regular dosing. DESIGN: Randomized, double-blind, double-dummy, parallel group, placebo-controlled, multi-center trial of asthmatics requiring inhaled beta-adrenergic bronchodilators for symptom control. INTERVENTIONS: Treatment qid with Proventil HFA, Ventolin, or HFA-134a placebo for 12 weeks. MEASUREMENTS: At weeks 0, 4, 8, and 12, spirometry was performed predose and serially over 6 h after dosing with study drug. Bronchodilator efficacy variables, based on FEV1 response to study drug, were proportion of responders, time to onset of effect, peak percent change, time to peak effect, duration of effect, and area under the curve (AUC). RESULTS: Demographic and baseline characteristics were similar for patients randomized to Proventil HFA (193), Ventolin (186), and HFA-134a placebo (186). No significant differences were found between the Proventil HFA and Ventolin treatment groups for any FEV1 efficacy variable, either predose or during 6 h of serial spirometry, at weeks 0, 4, 8, and 12. For all efficacy variables, except time to onset of effect, the Proventil HFA and Ventolin results were significantly greater than placebo. Time to onset of effect for the HFA-134a placebo group is misleading; only 13 patients (7%) were found to be responders in the intent-to-treat database. These efficacy results were found to be consistent across subgroup analyses of inhaled and nasal corticosteroid use, age (18 to 35 and 36 to 66 years), sex, race, weight (<60, 60 to 100, and >100 kg), and baseline FEV1 (< or =55% and >55% predicted). The peak FEV1 effect, duration of FEV1 effect, and AUC for FEV1 were all significantly smaller at weeks 4, 8, and 12 than week 0 for both the Proventil HFA and Ventolin treatment groups. CONCLUSIONS: Proventil HFA provided bronchodilation comparable to Ventolin and superior effects to HFA-134a placebo over 12 weeks of regular dosing. There was a diminution in bronchodilator response to both Proventil HFA and Ventolin after 4 weeks of use.

Response to pneumococcal immunization in children with and without recurrent infections.

Many children with recurrent sinopulmonary infections fail to mount an adequate humoral response following immunization with polysaccharide antigens. At present there are no controlled studies comparing responses to pneumococcal immunization in children with recurrent infections and a healthy, age-matched cohort. Immunological evaluation was performed on 66 children with recurrent sinopulmonary infections, aged 2-5 years (mean 3.06 +/- 0.92). A control group included 28 healthy, age-matched controls (mean 3.14 +/- 0.88 years). Both groups were immunized with 23 valent pneumococcal vaccine, and titers were measured before and 4 weeks after immunization. Antibody levels to 12 pneumococcal serotypes were measured via radioimmunoassay. Geometric preimmunization mean titers in the control group were 215.5 +/- 157 ngAbN/ml rising to 989.5 +/- 745 ngAbN/ml compared to 77.71 +/- 38.4 ngAbN/ml increasing to 446.7 +/- 406 ngAbN/ml in the study group (p < .05). Serotypes 3, 4, 7F, 8, 9N, and 18C were the most immunogenic, while serotypes 6A and 14 were the least. Overall, the control group responded to 7.71 +/- 1.24 serotypes versus 5.1 +/- 2.0 in the study group (p < .05), where postimmunization titers at least doubled and rose to > or = 300 ngAbN/ml. All controls responded to at least five or more serotypes, 26/28 responded to 6 or more. In contrast, only 38/66 (57%) of study patients responded to five or more serotypes, and only 27/66 (41%) responded to at least 6 of 12. Preimmunization titers of greater than 300 ngAbN/ml were present in 30% (102/336) of the control serotypes; however, only 53 of these (52%) doubled post immunization; 22% of the elevated titers decreased post immunization. Markedly elevated titers > or = 500 ngAbN/ml were present in 20% (69/336) of the preimmunization serotypes, only 39% of these doubled post immunization. Twenty-three valent pneumococcal vaccine is immunogenic in young, healthy children. A significant percentage of children with recurrent sinopulmonary infections fail to produce adequate serotype specific antibodies following pneumococcal immunization.

Aerosol beclomethasone dipropionate spray compared with theophylline as primary treatment for chronic mild-to-moderate asthma. The American Academy of Allergy, Asthma and Immunology Beclomethasone Dipropionate-Theophylline Study Group.

BACKGROUND: Inhaled corticosteroids and oral theophylline are effective treatments for moderate asthma. OBJECTIVE: We sought to compare the benefits and adverse reactions of theophylline and aerosol beclomethasone spray. METHODS: A multicenter, double-blind, double-placebo, randomized, controlled trial of 1-year duration was performed. Seven hundred forty-seven patients with asthma received either beclomethasone dipropionate aerosol spray (84 microg four times per day) or sustained-release theophylline twice per day in doses adjusted for optimum control of the disease. The main outcome measures were daily diary of symptoms and peak flow rates (recorded on a mark-sense computer-readable form); supplemental bronchodilator use; doctor's office or hospital visits and absence from work or school; spirometry; methacholine testing; adverse experiences; and cortisol blood measurements. RESULTS: Both treatment strategies reduced symptoms promptly and achieved low absenteeism from work or school and low rates of emergency treatment for asthma. Both maintained nearly normal pulmonary function. Beclomethasone was statistically significantly more effective in reducing symptoms, supplemental bronchodilator and systemic glucocorticoid doses, bronchial hyperresponsiveness, and eosinophilia. However, the magnitude of these differences was small. Theophylline caused more headache, nervousness, insomnia, and gastrointestinal distress, and more patients discontinued treatment because of side effects. Beclomethasone caused more oropharyngeal candidiases and hoarseness and reduced morning plasma cortisol levels before and after cosyntropin. It reduced the rate of growth in children. No new cataracts or glaucoma developed. CONCLUSION: Theophylline effectively controlled symptoms at lower than the customarily recommended blood level. The risk/ benefit profiles of these agents suggest that inhaled corticosteroids may be the preferred agent for most adult patients and for some children.

Use of an anti-IgE humanized monoclonal antibody in ragweed-induced allergic rhinitis.

BACKGROUND: Increased serum levels of antigen-specific IgE are often associated with allergic respiratory disorders. RhuMAb-E25, a recombinant humanized monoclonal antibody, decreases free serum IgE by forming biologically inactive immune complexes with free IgE. OBJECTIVE: We hypothesized that rhuMAb-E25 would decrease total serum IgE and reduce symptoms. METHODS: Two hundred forty subjects were enrolled into five groups to determine the safety, tolerance, and efficacy of repeated administration of rhuMAb-E25 in adults with ragweed-induced allergic rhinitis and to explore the pharmacodynamic relationship of rhuMAb-E25 and IgE. One hundred eighty-one subjects received an initial intravenous loading dose (day 0, 1 month before ragweed season), followed by administration of rhuMAb-E25 (in mg/kg body weight) of 0.15 mg/kg subcutaneously, 0.15 mg/kg intravenously, or 0.5 mg/kg intravenously on days 7, 14, 28, 42, 56, 70, and 84. A subcutaneous placebo group and an intravenous placebo group were included. The total evaluation time included the 84-day treatment period, followed by a 42-day observation period. RESULTS: Adverse events were mild, and no differences were observed in the rates between the three active and two placebo treatment groups. Ragweed-specific IgE levels correlated with symptom scores. RhuMAb-E25 decreased serum free IgE levels in a dose- and baseline IgE-dependent fashion. However, only 11 subjects had IgE levels that were suppressed to undetectable levels (< or = 24 ng/ml), a sample too small to demonstrate significant differences and clinical efficacy. Thus the case for efficacy was not proven. Nonetheless, the study confirms that it is safe to repeatedly administer rhuMAb-E25 over a period of months. CONCLUSIONS: Because rhuMAb-E25 decreased serum free IgE in a dose-dependent fashion and because symptom scores correlated with antigen-specific IgE levels, the results suggest that if given in adequate doses, rhuMAb-E25 should be an effective therapy for allergic diseases.

Retention of asthmatic patients in a longitudinal clinical trial.

BACKGROUND: Prevention of study patient attrition and assessment of its impact on outcome data are problems that receive little attention despite their obvious importance in asthma research. OBJECTIVE: The medical, demographic, and psychologic characteristics of asthmatic children and adults who dropped out of a yearlong medication trial were assessed to determine whether this group differed from those who completed the study, potentially introducing bias into the data set and interfering with completion of the study's objectives. METHODS: Profiles of 362 adult and pediatric asthmatic patient dropouts from the multicenter trial were contrasted with profiles of those who completed the study. Despite a 1-month prerandomization screening, 24% of patients failed to complete the trial for varied reasons, which largely included noncompliance and treatment dissatisfaction. RESULTS: Although attrition rates were equal among adults and children, dropout-completer differentiation was not. Adult completers did not differ from dropouts in any variables. However, pediatric dropouts were more likely than completers to be female (67% and 36%, p = 0.008) and to have more reactive airways (PD20, 2.29 +/- 1.32 and 5.2 +/- 1.23, p = 0.05), to have reduced scores on tests of intelligence (Full Scale IQ, 102.2 +/- 2.6 and 112.5 +/- 1.6, p = 0.002) and problem solving (Wisconsin Card Sorting Test Error Scores, 39.8 +/- 4.1 and 29.1 +/- 2.0, p = 0.01), and to have increased behavioral problems (Child Behavior Checklist Total Problem Score, 60.7 +/- 2.5 and 53.6 +/- 1.1, p = 0.003). CONCLUSION: These findings demonstrate the potential of patient attrition to bias outcome in clinical trials and underscore the necessity of: (1) preventing its occurrence, (2) correctly assessing its causes, and (3) determining its ultimate impact on study results. Strategies for each of these three tasks should be implemented at the study's initial planning stages.

Results of the first U.S. double-blind, placebo-controlled, multicenter clinical study in asthma with pranlukast, a novel leukotriene receptor antagonist.

Pranlukast (SB 205312; ONO-1078), a potent, orally active selective cysteinyl-leukotriene receptor antagonist (LTRA), was developed in Japan for the treatment of asthma. This article reports results of the initial U.S. clinical evaluation of pranlukast. The primary objective of this multicenter study was to evaluate the safety and tolerability of pranlukast administered at doses of 337.5 mg b.i.d. and 450 mg b.i.d. in 65 patients with mild to moderate asthma. Pranlukast, a novel LTRA, is safe and well tolerated at doses of 337.5 mg b.i.d. and 450 mg b.i.d. Pranlukast has demonstrated clinical activity in patients with asthma.

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.