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.

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.

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.

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.

Effect of clarithromycin on nasal mucus properties in healthy subjects and in patients with purulent rhinitis.

Erythromycin inhibits mucus glycoconjugate secretion from airway cells in vitro and may increase mucus clearance in patients with asthma or diffuse panbronchiolitis. Because mucus hypersecretion is common in purulent rhinitis, we questioned whether clarithromycin would change the properties of nasal mucus from subjects without sinus disease and from patients with acute purulent rhinitis. Nasal secretions were collected before and after nasal methacholine challenge from 10 adults without nasal symptoms and without methacholine from 10 patients with purulent rhinitis. After 2 wk of oral clarithromycin (500 mg twice daily), secretions were again collected from both groups. Secretions were analyzed for viscoelasticity, cohesion, hydration, and ciliary and airflow (sneeze) transportability. Compared with secretions from healthy subjects, rhinitis secretions had decreased wettability (contact angle on Teflon 100 degrees versus 84.67 degrees; p = 0.001), increased cohesion (36.8 versus 24.3 mm; p = 0.003), decreased sneeze clearability (20.6 versus 32 mm; p = 0.04), and increased percent solids (4.61 versus 2.82%; p = 0.04). After clarithromycin, the rheology, hydration, cohesion, and transportability of the rhinitis secretions were similar to those of the postclarithromycin secretions from the healthy subjects. Secretion volume also decreased (500.1 versus 28.3 mg; p = 0.01), and mucociliary transportability increased by 30% (0.76 versus 0.99; p = 0.005). Although clarithromycin reduced mucus secretion in both rhinitis patients and normal subjects, it did not alter the secretory response to methacholine.

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.

Chronic angio-oedema of the tongue associated with pernicious anaemia and Hashimoto's thyroiditis.

The cause of chronic urticaria and angio-oedema (CUA) often remains undetermined. CUA has been associated with thyroid disease and most recently with thyroid autoimmunity (i.e. elevated titres of thyroid microsomal and/or thyroglobulin antibody). There is growing speculation that in this subset of patients, CUA may represent an autoimmune phenomenon. We describe a case in which chronic angio-oedema of the tongue was the sole presenting complaint in a patient with underlying quiescent pernicious anaemia and Hashimoto's thyroiditis. Awareness of the association of Hashimoto's thyroiditis with pernicious anaemia and CUA resulted in correct diagnosis and treatment of the underlying diseases.

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.

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.

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.

In vivo detection of a novel macrophage-derived protein involved in the regulation of nasal mucus-like glycoconjugate secretion.

BACKGROUND: We recently described a novel 68 kd mucus secretagogue (MMS-68) derived from human monocytes, pulmonary macrophages, and a macrophage hybridoma, clone 63. We detected MMS-68 in monocyte culture supernatants from patients with steroid-dependent asthma and in bronchoalveolar lavage fluid from patients with chronic bronchitis by antigen capture ELISA and in normal lung tissue by immunohistochemistry. METHODS: To determine a role for MMS-68 in the regulation of nasal mucus, we labeled human nasal turbinates with tritiated glucosamine and assayed for the ability of the previously purified MMS-68 (stock solution) to induce mucus-like glycoconjugate release (MLGC). We also performed immunohistochemistry stains with an anti-MMS-68 antibody (1-D-10) on frozen sections (n = 5) of nasal turbinates from patients with allergic and nonallergic rhinitis who were undergoing rhinoplasty and measured MMS-68 levels in nasal lavages from patients who were undergoing topical nasal histamine or methacholine challenge. RESULTS: MMS-68 is a potent nasal MLGC secretagogue causing a dose-dependent increase in MLGC release in vitro. Staining revealed a subepithelial distribution for MMS-68. Antigen capture ELISA of nasal lavages demonstrated mean MMS-68 levels from saline control challenge of 0.9 +/- 0.5 micrograms MMS-68 per milligram of protein (n = 5), 8.6 +/- 1.4 micrograms MMS-68 per milligram of protein from histamine challenge and 20.7 +/- 2.3 micrograms MMS-68 per milligram of protein (n = 5) after methacholine challenge. CONCLUSION: Taken together these data suggest that MMS-68 may play a role in the normal regulation of mucus secretion.

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.