Topical nasal decongestant oxymetazoline (0.05%) provides relief of nasal symptoms for 12 hours.

BACKGROUND: Nasal congestion, often referred to as stuffy nose or blocked nose is one of the most prevalent and bothersome symptoms of an upper respiratory tract infection. Oxymetazoline, a widely used intranasal decongestant, offers fast symptom relief, but little is known about the duration of effect. METHODOLOGY: The results of 2 randomized, double-blind, vehicle-controlled, single-dose, parallel, clinical studies (Study 1, n=67; Study 2, n=61) in which the efficacy of an oxymetazoline (0.05% Oxy) nasal spray in patients with acute coryzal rhinitis was assessed over a 12-hour time-period. Data were collected on both subjective relief of nasal congestion (6-point nasal congestion scale) and objective measures of nasal patency (anterior rhinomanometry) in both studies. RESULTS: A pooled study analysis showed statistically significant changes from baseline in subjective nasal congestion for 0.05% oxymetazoline and vehicle at each hourly time-point from Hour 1 through Hour 12 (marginally significant at Hour 11). An objective measure of nasal flow was statistically significant at each time-point up to 12 hours. Adverse events on either treatment were infrequent. The number of subjects who achieved an improvement in subjective nasal congestion scores of at least 1.0 was significantly higher in the Oxy group vs. vehicle at all hourly time-points on a 6-point nasal congestion scale. CONCLUSIONS: This study shows for the first time, that oxymetazoline provides both statistically significant and clinically meaningful relief of nasal congestion and improves nasal airflow for up to 12 hours following a single dose.

Brompheniramine maleate: a double-blind, placebo-controlled comparison with terfenadine for symptoms of allergic rhinitis.

This was a double-blind, randomized, placebo-controlled, multicenter, parallel study comparing the effectiveness, at recommended doses, of an extended-release formulation of brompheniramine maleate and terfenadine in the treatment of allergic rhinitis. Subjects with symptoms of seasonal and/or perennial allergic rhinitis received brompheniramine 12 mg (n = 106), 8 mg (n = 105), terfenadine 60 mg (n = 106), or placebo (n = 53) twice daily for 14 days. On treatment days 3, 7, and 14, symptom severity ratings (i.e., rhinorrhea, sneezing, nasal congestion, itchy nose, eyes or throat, excessive tearing, postnasal drip) were completed by the physician; subjects and physicians each completed a global efficacy evaluation. Brompheniramine 12 mg and 8 mg and terfenadine were more effective than placebo (p < or = 0.05) on the physicians' global: brompheniramine 12 mg was more effective than terfenadine (p < or = 0.05) on days 7 and 14 and brompheniramine 8 mg on day 3. On the subjects' global evaluation, brompheniramine 12 mg and 8 mg and terfenadine were more effective than placebo (p < or = 0.05); brompheniramine 12 mg was more effective than terfenadine (p < or = 0.05) on days 7 and 14 and brompheniramine 8 mg on day 3. In general, brompheniramine 8 mg was comparable to terfenadine. On days 3 and 7, the total symptom and total nasal symptom severity scores for subjects receiving brompheniramine 12 mg were significantly more improved than for placebo (p < 0.05); terfenadine was not different from placebo; brompheniramine 12 mg was significantly better than terfenadine on day 7 (p < 0.05) for reducing total symptom severity and on days 3, 7, and 14 for reducing total nasal symptom severity. Adverse experiences were reported by 155 (41.9%) of the 370 subjects enrolled in the study. The overall rate of adverse experiences in the brompheniramine 12 mg treatment group (57.5%) was significantly greater (p < 0.05) than for brompheniramine 8 mg (38.1%), terfenadine (31.1%), and placebo (39.6%). In conclusion, an extended-release formulation of brompheniramine 12 mg or 8 mg bid alleviates allergic rhinitis symptoms and brompheniramine 12 mg provides significantly better relief of these symptoms than terfenadine 60 mg bid.

Anticholinergic properties of brompheniramine, chlorpheniramine, and atropine in human nasal mucosa in vitro.

Brompheniramine and chlorpheniramine have anticholinergic activities, but the relative potency of these effects has not been well defined. The anticholinergic properties of brompheniramine, chlorpheniramine, and atropine were assessed in an in vitro model of human nasal mucosal glandular secretion. Methacholine was used as a cholinergic agonist to stimulate glandular secretion of 7F10-mucin. These drugs (0.01-1000 microM) or vehicle (saline) were added to explant cultures with and without 100 microM methacholine. 7F10-mucin concentrations were measured in culture supernatants after 2-hour incubations. The effective dose reducing methacholine-induced secretion (ED50) was determined. ED50 was 0.25 microM for atropine, 4.10 microM for brompheniramine, and 4.63 microM for chlorpheniramine. None of the anticholinergic drugs changed spontaneous glandular exocytosis. Brompheniramine and chlorpheniramine are equipotent anticholinergic agents in human nasal mucosa in vitro. Atropine was 16 to 19 times more potent.

Brompheniramine, loratadine, and placebo in allergic rhinitis: a placebo-controlled comparative clinical trial.

A double-blind, randomized, placebo-controlled, parallel-group, multicenter study was conducted to compare the effectiveness of an extended-release formulation of a classical antihistamine, brompheniramine, and a second-generation compound, loratadine, in the treatment of allergic rhinitis. Subjects with symptoms of allergic rhinitis received brompheniramine 12 mg twice daily (n = 112), loratadine 10 mg once daily (n = 112), or placebo twice daily (n = 114) for 7 days. Study medications were blinded using a double-dummy technique. Subjects completed an overall evaluation of symptom relief on a daily basis and returned on treatment days 3 and 7, at which times the investigator assessed symptom severity. The investigator and subject each completed a global efficacy evaluation, and subjects were interviewed regarding adverse experiences. The primary efficacy variable was the physicians' global efficacy evaluation on day 3. Symptoms also were analyzed as summed severity scores for all symptoms and for the nasal symptom cluster of rhinorrhea, sneezing, and nasal blockage. At all post-baseline evaluations (days 3, 7, and averaged over the two days), brompheniramine was significantly better than loratadine and placebo for both sets of summed symptom scores and all three global assessments. Loratadine was significantly better than placebo for physician ratings of total symptom severity averaged over the two days and for the physician and subject ratings of the nasal cluster on day 3. Central nervous system-related symptoms were the most frequently reported adverse experiences; somnolence was reported most frequently by patients taking brompheniramine, and its occurrence was less frequent as treatment continued. A nonprescription, extended-release formulation of brompheniramine 12 mg twice daily provided significantly better relief of symptomatic allergic rhinitis than loratadine 10 mg once daily.

Efficacy of brompheniramine maleate for the treatment of rhinovirus colds.

We tested the efficacy of brompheniramine maleate in a large randomized, controlled trial of volunteers with experimental rhinovirus colds. Brompheniramine (12 mg) or placebo was administered at 8:00 A.M. and 8:00 P.M. for < or = 4 days after the onset of symptoms (24, 36, or 48 hours after virus challenge). During the first 3 days of treatment (the first 4 days after virus challenge), nasal secretion weights were lower for infected evaluable subjects receiving brompheniramine (n = 113) than for controls (day 1: 4.3 g vs. 6.8 g; day 2: 4.8 g vs. 7.7 g; and day 3: 3.3 g vs. 5.3 g) (P < or = .03), as were rhinorrhea scores (day 1: 0.6 vs. 0.8; day 2: 0.5 vs. 0.8; and day 3: 0.3 vs. 0.5) (P < .03), sneeze counts (day 1: 1.8 vs. 3.6; day 2: 2.1 vs. 5.1; and day 3: 1.3 vs. 3.3) (P < or = .001), and sneeze severity scores (day 1: 0.3 vs. 0.6; day 2: 0.25 vs. 0.7; and day 3: 0.2 vs. 0.4) (P < .001) (n = 112). Cough counts were lower after day 1 of treatment for the brompheniramine group than for controls (4.7 vs. 7.9) (P = .05) (day 2 after virus challenge), and other symptoms were modestly reduced or were unaffected in the brompheniramine group. Total symptom scores were also lower for the brompheniramine group than for controls on treatment days 1 (4.8 vs. 6.0) (P = .03) and 2 (4.1 vs. 5.6) (days 2 and 3 after virus challenge) (P = .003). Treatment with brompheniramine was associated with the adverse effects of somnolence (n = 3) and confusion (n = 1). Brompheniramine was efficacious treatment for the sneezing, rhinorrhea, and cough associated with rhinovirus colds.

Evidence for acute renal cortical vasoconstriction after uninephrectomy.

The rate of progression of chronic renal failure (CRF) is similar for many diseases, suggesting a common, perhaps intrinsic, renal signal for its progression. The remnant nephron hypothesis of Bricker suggests that CRF may be the result of persistent compensatory renal growth (CRG). Normally, CRG after unilateral nephrectomy (uniNx) ceases within 1 week. Knowledge of the signals that initiate CRG may therefore shed light on the signals responsible for ongoing CRF. The signals responsible for the initiation of compensatory renal growth after uniNx are unknown. Hemodynamic changes in the remaining renal artery have been observed, but there are as yet no data for the main renal compartment which undergoes hypertrophy, the superficial renal cortex. The noninvasive technique of laser-Doppler flowmetry allows the continuous and independent monitoring of blood velocity and blood volume. The product of the two signals is proportional to tissue blood flow per unit volume of the tissue observed. Under controlled conditions in adult male Sprague-Dawley rats, renal cortical blood velocity increased by 22% within 5 min after uniNx and remained elevated at this level for 60 min. Renal cortical blood volume decreased throughout the experiment. Their product, renal cortical blood flow, increased briefly by 14% 5 min after uniNx but decreased over the time of observation in parallel with renal cortical blood volume. The simultaneous increase in blood velocity and decrease in blood volume in the superficial renal cortex acutely after uniNx suggest that vasoconstriction is an early event in compensatory renal growth.

Comparison of a screening coronal CT versus a contiguous coronal CT for the evaluation of patients with presumptive sinusitis.

BACKGROUND: Computed tomography has greatly improved the accuracy of sinus imaging. While contiguous coronal computed tomography scanning of the sinuses provides detailed imaging as compared with plain sinus radiography, this modality is significantly more expensive and involves exposure of the patient to a higher dose of radiation. It has become increasingly common to obtain screening, or non-contiguous, CT scans of the sinuses when screening for the presence of sinusitis. OBJECTIVE: To calculate the sensitivity and specificity of the screening coronal CT scan of the sinuses in screening for inflammatory disease using the contiguous coronal CT examination of the sinuses as the standard. METHODS: From contiguous coronal computed tomograms of the paranasal sinuses, screening coronal computed tomographic examinations were created for 44 patients. Patients were being screened for the presence of sinusitis in the Comprehensive Sinus Clinic at St. Louis University. The two examinations were reviewed independently and in random order by two neuroradiologists. Using the original examinations as the standard, the sensitivity and specificity of the screening studies were calculated for various situations. RESULTS: Overall, a sensitivity of 93.3% and a specificity of 89.3% for the detection of inflammatory disease of the sinuses by the screening examination was observed. CONCLUSIONS: The screening coronal computed tomogram of the paranasal sinuses may be useful in the evaluation of the patient with possible sinusitis.

Intranasal flunisolide spray as an adjunct to oral antibiotic therapy for sinusitis.

BACKGROUND: The diagnosis of sinusitis is difficult and there are few controlled studies of customary therapies. In particular, the possible role of topical intranasal steroid as an adjunct to antibiotic treatment has not been evaluated. METHODS: The study was a multicenter, double-blind, randomized, parallel trial in which patients aged 14 years or older were recruited from allergy practices. All patients had maxillary sinusitis documented by radiographs. Treatment consisted of amoxicillin/clavulanate potassium 500 mg combined with nasal spray of either 100 micrograms flunisolide or placebo to each nostril three times a day for 3 weeks (phase I) followed by administration of flunisolide or placebo nasal spray alone three times a day for 4 weeks (phase II). RESULTS: Clinical symptoms and signs decreased significantly in both treatment groups during phase I (p < 0.01). There was a trend to greater improvement in the patients treated with flunisolide, but only the decrease in turbinate swelling/obstruction was statistically significant at the end of phase I when compared with placebo (p = 0.041). Patients' global assessment of overall effectiveness of treatment was higher for flunisolide than placebo after phase I (p = 0.007) and after phase II (p = 0.08). Maxillary sinus radiographs showed improvement in both treatment groups during phase I (p < 0.004) with somewhat greater regression of abnormal findings in patients treated with flunisolide after phase II (p = 0.066). However, 80% of radiographs were still abnormal at the end of phase I. All types of inflammatory cells were significantly decreased in nasal cytograms in patients treated with flunisolide in comparison with those treated with placebo. Flare-up of sinusitis during phase II occurred in 26% of with those treated with placebo. Flare-up of sinusitis during phase II occurred in 26% of patients treated with flunisolide and 35% of those treated with placebo and tended to be more severe in the latter, although these differences were not statistically significant. Adverse events, mainly gastrointestinal symptoms and headache, were similar in both groups and more frequent in phase I than in phase II, (42 vs 15 patients); these side effects were probably due to the antibiotic. CONCLUSION: The addition of flunisolide topical nasal spray as an adjunct to antibiotic therapy was most effective in global evaluations, tended to improve symptoms, to decrease inflammatory cells in nasal cytograms, to normalize ultrasound scans, and to aid regression of radiographic abnormalities compared with placebo spray.

Nasal blood flow.

Although the assessment of allergic reactions was subjective for many years, it is now possible to evaluate nasal blockage objectively by measuring nasal airway resistance. To explore the pathophysiology of nasal blockage, however, it is necessary to analyze the separate components of obstruction, including secretions, cellular infiltrates, and microcirculatory parameters. The preferred techniques for measuring nasal mucosal blood flow are laser-Doppler velocimetry and radioactive xenon washout. Laser-Doppler velocimetry allows the measurement not only of blood flow but also of blood volume, red blood cell speed, and pulsatility of flow. It also permits continuous measurement of microcirculatory parameters over time. This technique has been used to assess the nasal microvascular response to neurohormones, antigenic challenge, and histamine challenge with and without antihistamine pretreatment.

The use of intranasal anticholinergic agents in the treatment of nonallergic perennial rhinitis.

Nonallergic perennial rhinitis is a heterogenous disorder. Although the underlying cause is unknown, there is evidence of an autonomic imbalance with parasympathetic hyperreactivity in affected persons. We review this evidence and the role of ipratropium bromide, an anticholinergic drug with topical activity, in the management of nonallergic perennial rhinitis. The pharmacologic features, safety, and efficacy of ipratropium bromide are reviewed.

Diagnosis of sinusitis in adults: history, physical examination, nasal cytology, echo, and rhinoscope.

The symptoms of sinusitis are common and overlap other diseases ranging from common colds to perennial rhinitis. When symptoms are prolonged and interfere with daily living, an appropriate set of investigations are indicated. The workup is designed to detect both the presence and extent of any disease in the paranasal sinus cavities. In chronic sinusitis, a constellation of nonspecific symptoms such as facial pressure, headache, nasal obstruction, and drainage may occur. Physical examination is important to exclude anatomic causes of symptoms. A negative physical examination does not rule out the diagnosis. Adjunctive tests in selected cases include nasal cytologic studies, ultrasound studies, and the use of flexible or rigid nasal endoscopes, in addition to imaging tests such as radiology and computed tomography.

Double-blind study of intranasal ipratropium bromide in nonallergic perennial rhinitis.

We undertook this trial to determine whether ipratropium bromide nasal spray 0.03% (IB) reduced the nasal hypersecretion associated with nonallergic perennial rhinitis (NAPR) without causing excessive dryness or irritation of the nasal mucosa. We compared two drug doses of IB (21 micrograms and 42 micrograms per nostril) to a placebo, administered as two sprays to each nostril twice daily. The study design consisted of a 1-week screening period without treatment, a 1-week single-blind placebo period, a 4-week double-blind treatment comparison period, and a 1-week follow-up period without medication to evaluate nasal rebound. One hundred fifty-two patients were entered and 140 completed the trial. Both doses of IB reduced the severity and duration of rhinorrhea compared with placebo (P = .05 and .03, respectively). Treatment differences were noticeable during the first week of therapy, continued to widen during the second week, and then remained stable throughout the next 2 weeks. There was no evidence of nasal rebound observed during the week after treatment. The drug was well tolerated with side effects limited to infrequent nasal adverse events of nasal dryness, blood-tinged mucus, and epistaxis occurring in 2% to 6% of patients. We conclude that IB is a safe and effective therapy for control of rhinorrhea associated with NAPR.

Allergic rhinitis.

Allergic rhinitis is a common disease with characteristic symptoms affecting the eyes, ears, and face as well as the nose. A detailed history is the foundation of a correct diagnosis. Laboratory tests may be needed to supplement this in atypical presentations. A combination of pharmacotherapy, immunotherapy, and environmental control may be required to control and prevent symptoms.