Topical Nasal Spray Research Articles

Análise retrospectiva da toxicidade de gotas otológicas, medicamentos tópicos nasais e orofaríngeos registrada na Grande São Paulo

Retrospective analysis of human toxicity files involving topical medicines for treatment of upper airways diseases (eardrops, topical nasal medicines, lozenges, drops and sprays for oropharyngeal affections). Thirty-four brands of eardrops, 48 of topical nasal medicines and 22 of tablets, lozenges and sprays for oropharyngeal affections were selected, from a total of 104 products available in Brazil. We analyzed the registries in the electronic database from the Poison Control Centre of São Paulo (CCI-Jabaquara), Brazil, for the period from January 1996 through December 2000. The cases related to selected pharmaceuticals were collected. 10,823 cases of human toxicity caused by medicines were voluntarily reported to CCI-Jabaquara. Topical medicines for treatment of upper airways diseases accounted for 291 cases (2.68%), from which 240 (82.5%) represented poisoning; 12 (4.1%) involved ear drops, 268 (92%), topical nasal medicines and 11 (3.9%), topical medicines for oropharyngeal affections. Among topical nasal medicines, vasoconstrictors predominated (233 cases), and among medicines for oropharyngeal affections, it was tetracaine (four cases). Considering age distribution, toxicity predominated significantly in children aged from 1 to 4 years (p=0.0003). The main causes of toxicity were: accidental intake of medicines (43%) and error in drug administration (14.8%). Hypereflexia and vomiting were the most frequent symptoms related to toxicity. There was significant incidence of systemic toxicity due to eardrops, topical nasal and oropharyngeal medicines in children 1 to 4 years-old, whose main cause was accidental intake of these medicines.

Fluconazole Nasal Spray in the Treatment of Allergic Fungal Sinusitis: A Pilot Study

The authors describe a prospective pilot study designed to investigate the use of topical nasal antifungal spray in addition to systemic steroids and itraconazole in the treatment of allergic fungal sinusitis. Sixteen patients with a history of allergic fungal sinusitis were given fluconazole nasal spray and followed for 3 months. Stabilization or improvement of disease without significant side effects was observed in 12 of the 16 patients who were treated with this protocol. These results indicate that topical fluconazole application may help patients with allergic fungal sinusitis; however, a larger multicenter study with longer patient follow-up is required to validate these initial findings.

Lignocaine versus benzocaine as a topical nasal anesthetic

Problem: The effectiveness of 10% lidocaine compared with benzocaine 20% spray in reducing pain perceived by patients undergoing flexible nasolaryngoendoscopy in the ENT clinic was evaluated in a randomized double-blind placebo-controlled study. In addition, patient acceptance of both sprays with reference to taste, smell, and acceptability was evaluated. Methods: Fifty randomly selected subjects undergoing flexible nasolaryngoendoscopy in the ENT clinic were randomly treated with 10% lidocaine spray or 20% benzocaine spray. A nurse in a separate room sprayed the patient and a doctor performed the flexible nasolaryngoendoscopy procedure after 5 minutes had elapsed. Demographic data were collected from the patients: age, sex, and whether they were smokers or nonsmokers. Patients recorded on a form their perception of the pain perceived while the spray was being delivered, of the procedure itself, and of acceptability, taste, and smell on a visual analogue scale. Results: We found that with respect to pain perceived on delivery of the sprays, lignocaine (Xylocaine) was significantly more painful then benzocaine (Hurricaine) with P < 0.05. In reducing the pain of the procedure itself, there was no significant difference between the 2. With respect to taste, smell, and acceptability, benzocaine did significantly better than xylocaine, P < 0.05. There was no significant difference when results were compared with reference to age, sex, or whether one was a smoker. Conclusion: Benzocaine is better tolerated than Lignocaine as a topical intranasal local anesthetic spray. Significance: When possible, choose benzocaine over lignocaine as a topical nasal anesthetic spray. Support: None reported.

A study of intranasal distribution of azelastine hydrochloride aqueous nasal spray with different spray techniques

Topical aqueous nasal sprays are widely used in treating patients with a variety of nasal diseases. Previous studies have suggested that drug delivery to the ciliated mucosa is generally suboptimal. Little is known about the effects of nasal spray delivery technique on intranasal distribution and efficacy of topical nasal drugs. We assessed the intranasal distribution of a nasal spray with two commonly used techniques using azelastine hydrochloride labelled with fluorescein. After spraying, the nasal cavity was photographed endoscopically in two standardized positions, one showing the anterior portion in the region of the nasal valve and one the area of the middle meatus. The photographs were computer analysed to identify the proportion of coverage of fluorescein in each image field. The majority of drug was distributed anteriorly with poor coverage posterior to the nasal valve area. This was the case with both of the positions tested.

Allergic fungal sinusitis: Diagnosis and management

Clinicians first recognized allergic fungal sinusitis (AFS) as a benign noninvasive condition nearly 2 decades ago because of its similarities to allergic bronchopulmonary aspergillosis (ABPA). AFS has proven to be a distinct clinical entity characterized by atopy, nasal polyposis, distinctive CT scan features, and eosinophilic allergic mucin mixed with fungal elements. Considerable debate still surrounds the immunopathogenesis and the role of the fungus in the disease process. Functional endoscopic sinus surgery with complete extirpation of the allergic mucin and aeration of the obstructed sinuses is the mainstay of treatment. Extensive polyposis and bony erosion from expanding allergic mucin characterize AFS and contribute to the difficulty of obtaining a safe yet thorough resection. Recurrences happen in all patients with underlying, uncorrected immune disease. Desensitization immunotherapy and topical antifungal nasal sprays are two promising new therapeutic approaches.

Unilateral rhinorrhea and nasal obstruction in an adult

choanal atresia is an uncommon malformation, consisting of congenital blockage of one of both choanae. Symptomatology varies according to the type of atresia and the age of the patient. The bilateral, or complete, form presents in newborns as respiratory distress while unilateral, or incomplete, forms present in older children or adults. a 16-year-old girl presented with a lifelong history of right-sided nasal blockage and unilateral watery rhinorrhea. The rhinorrhea increased when the patient bent her head forward. Treatment with antihistamines and topical nasal corticosteroid sprays produced little improvement. The patient's previous medical history was unremarkable except for the expulsion of a coagulated mass through the right nostril a few days after birth, and event that provoked her symptoms. Physical examination was normal except for excoriation of the right external nasal margin. Anterior rhinoscopy revealed watery rhinorrhea, erythematous mucosa in the right nasal cavity and deviated nasal septum. No nasal masses or polyps were found. Physical examination confirmed the absence of ventilation in the right nasal airway and nasal endoscopy indicated right choanal obstruction. skin prick tests with aeroallergens were positive for grass pollen and negative for all other allergens tested (mites, moulds, latex, and epithelia). Total IgE was normal (9 IU/ml). No eosinophilia was detected in the nasal secretion specimen. The results of laboratory tests including complete blood count and differential, erythrocyte sedimentation rate, and biochemical parameters were normal. The glucose level in nasal secretion was 4.6 mg/dl. X-rays of the paranasal sinuses and cavum showed no anomalies. Axial fine-cut computed tomography scans (3 3 mm) revealed choanal obstruction with bony and membranous components. a diagnosis of congenital choanal atresia should be considered in cases of unilateral blockage and rhinorrhea. Nasal endoscopy and computed tomography scans are essential to establish diagnosis.

Dose-dependent effects of budesonide aqueous nasal spray on symptoms in a daily nasal allergen challenge model

It has been difficult to demonstrate dose-dependent clinical effects of anti-allergic glucocorticosteroid drugs in allergic rhinitis. To determine dose-dependent effects on rhinitis symptoms of clinical doses of the glucocorticosteroid budesonide in a standardized daily allergen challenge model. Twenty-five patients with seasonal allergic rhinitis were examined outside the pollen season. The highest 256 microg once daily and lowest 64 microg once daily clinically recommended doses of budesonide aqueous nasal spray and placebo were given in a double-blind, placebo-controlled, randomized, and crossover design with 4 weeks' washout between treatments. After 1 week's treatment, the patients received individually titrated nasal allergen challenges once every morning for 8 days while treatment continued. Nasal symptoms were scored in diary cards. Nasal symptoms from the 6th to the 8th challenge days were used in the analysis. The provocation model produced clinically relevant, and around the clock well tolerable rhinitis symptoms, suggesting that after several days of repeated allergen challenges, a season-like, transient allergic disease condition had been established. Both 64 microg and 256 microg of budesonide aqueous nasal spray reduced nasal symptoms. Budesonide 64 microg reduced total nasal symptoms scores from 5.19 +/- 0.5 to 4.23 +/- 0.53 (P < .05), and budesonide 256 microg reduced total nasal symptoms scores to 3.41 +/- 0.51 (P < .001). A significant difference in nasal symptoms after challenge between budesonide aqueous nasal spray 64 microg and 256 microg (P = .03), indicated a dose-dependent effect. A dose-dependent, symptom-reducing effect of once-daily treatment with topical aqueous nasal sprays of budesonide for two weeks was demonstrated, suggesting that this model is relevant for assessments of dose-dependent effects of anti-inflammatory drugs.

Current concepts in the management of paediatric rhinosinusitis.

It is well recognized that adenoid hypertrophy and allergic rhinitis are common in children and that recurrent upper respiratory tract infections are a fact of life. The main causes of symptoms associated with rhinosinusitis in children are rhinorrhoea, nasal obstruction, mouth breathing, hyponasal speech and snoring. Most children grow out of adenoid hypertrophy and recurrent colds by the age of eight to 10 and this means that the main treatment strategy should therefore be conservative and not surgical. An explanation to anxious parents, simple non-invasive measures such as teaching nose-blowing, the use of saline sprays or a trial of allergen avoidance and age-appropriate topical nasal anti-inflammatory sprays should be tried before surgery is even contemplated. Because repeated infections are so common, antibiotics given for chronic nasal discharge often have only short-lived effects. Rhinosinusitis in children is not a surgical disease and 'watchful waiting' is advised. Any treatment should first of all be safe, as even without any intervention the problem usually resolves with time. It is likely that growth and maturation of the immunological response to pathogens play a major role in resolution of the disease. There are few exceptions to this principle: nasal polyps (indicating possible cystic fibrosis), and periorbital cellulitis where an assessment of vision, parenteral antibiotics, and if there is concern about the possibility of a subperiosteal abscess, computerized tomography (CT) and drainage of any pus is indicated.

Changes in Nasal Nitric Oxide Concentration Associated with Symptoms of Common Cold and Treatment with a Topical Nasal Decongestant

Nitric oxide (NO) is known to play a role in the non-specific host defence mechanism. Furthermore, it has been proposed that NO may be important in respiratory defence against the viruses which cause the common cold. Indeed, elevated NO levels have previously been observed in orally expired air during upper respiratory tract infection (URTI). We wanted to investigate further the role of NO in the host response to URTI. Total nasal airway resistance (tNAR) and nasal NO levels were obtained during symptomatic URTI in 97 subjects. Of these, 80 received treatment with either oxymetazoline or a placebo spray. Post-treatment tNAR and NO levels were obtained 60 min after treatment. Measurements of NO were also repeated 4-6 weeks later, when subjects were healthy, (n = 82). NO levels were measured using a chemiluminescence gas analyser whilst tNAR was measured using posterior rhinomanometry. The mean pre-treatment NO level (1063 ± 541 ppb) was shown to be reduced significantly after treatment with oxymetazoline (827 ± 373ppb), p < 0.0001. The mean pre-treatment tNAR, 0.42 Pa cm-3 sec-1, was also reduced significantly to 0.21 Pa cm-1 sec' (p < 0.001) after treatment with oxymetazoline. There was no significant correlation between the change in NO levels and change in tNAR following treatment with oxymetazoline (p, corrected for ties = 0.011, p = 0.98). No significant difference was found between NO levels obtained during URTI (1130 ± 444 ppb) when compared to values obtained when healthy (1197 ± 361 ppb), p =0.25. These results demonstrate that treatment with a topical nasal decongestant spray causes a reduction in nasal NO levels. We propose that this occurs as an indirect consequence of the vasoconstrictor actions of oxymetazoline. Since no change in NO levels was observed during URTI, we propose that the NO synthase responsible for NO production in the nose responds in a different manner to that in the lungs.

Cytokine immunoreactivity in seasonal rhinitis: regulation by a topical corticosteroid.

Seasonal allergic rhinitis is characterized by the development of nasal mucosal inflammation in response to natural allergen exposure, and is prevented by the administration of topical corticosteroids. Interleukin-4 (IL-4), IL-5, and IL-6 may have important roles in this process, and in vitro the gene transcription for each of these cytokines is inhibited by corticosteroids. In this study we have therefore investigated the effect of seasonal allergen exposure on the expression of immunoreactivity for IL-4, IL-5, and IL-6 in nasal mucosal biopsies, and the effect of regular prophylactic treatment with the topical corticosteroid, fluticasone propionate. Following a nasal mucosal biopsy out of season, patients were randomized double-blind to receive 6 wk of treatment during the pollen season with either topical fluticasone nasal spray (200 micrograms daily) or matching placebo. Each subject underwent a repeat nasal biopsy at the end of the 6-wk treatment period. Seasonal increases in epithelial eosinophils (p = 0.046), submucosal eosinophils (p = 0.001), and epithelial mast cells (p = 0.055) occurred in the placebo--but not the fluticasone-treated patients. Submucosal mast cell numbers did not change in either group. Immunoreactivity for IL-4 and IL-6 was localized predominantly to mast cells while IL-5 was found in both mast cells and eosinophils. Numbers of IL-4+ cells in the nasal submucosa were significantly suppressed by treatment with fluticasone (p = 0.0003 for monoclonal antibody [mAb] 3H4, p = 0.041 for mAb 4D9). In contrast, fluticasone treatment failed to influence the number of IL-5 and IL-6 immunoreactive cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Intranasal Steroids in Rhinology: The Changing Role of Intraturbinal Injection

Intraturbinal injection of repository corticosteroid has been widely used by otolaryngologists for over four decades. The potential for visual loss when retinal embolization or vasospasm complicate this procedure and the introduction of topical nasal steroid preparations have gradually reduced its usage and reshaped the role of intraturbinal steroid injection in the management of a variety of rhinologic disorders. A review by the author of twenty-five years' experience, including over thirteen thousand intraturbinal corticosteroid injections, shows no visual complications in this large series. However, a decline in the use of this procedure was noted, possibly influenced by several factors. Appropriate roles for intraturbinal steroid injection and topical corticosteroid nasal sprays are suggested.

Improvement of Olfaction following Pansinus Surgery

This study involves ten consecutive anosmic patients who underwent pansinus surgery and have been followed and tested a minimum of one year. They all had advanced obstructive bilateral nasal polyposis and pansinusitis. Persistent severe loss of smell was one of the chief complaints in all ten patients. The surgery performed included bilateral nasal polypectomies, bilateral sphenoidethmoidectomies and bilateral nasal antral windows. Post-operatively, all were treated with a topical corticosteroid nasal spray. Seven of these patients were asthmatic and three were also aspirin-sensitive, some being cortisone-dependent. The University of Pennsylvania Smell Identification Test (UPSIT) was administered pre-operatively and then at six-month intervals in the post-operative period. Significant initial improvement in smell acuity occurred in seven of the ten patients. One of the seven, however, developed recurrence of the nasal polyposis and again lost his smell capabilities somewhere between the twelfth and eighteenth post-operative months. Another of the patients who did not improve smell sensitivity post-operatively occasionally is aware of fleeting periods of return.

Intranal 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 amoxicillinlclavulanate postassium 500 mg combined with nasal spray of either 100 yg 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 patients treated with lunisolide 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.

Topical levocabastine compared with orally administered terfenadine for the prophylaxis and treatment of seasonal rhinoconjunctivitis

Background: This study was designed to compare the efficacy and tolerability of a new topical (nasal spray and eye drops) H 1-receptor antagonist, levocabastine, with that of orally administered terfenadine for the prophylaxis and treatment of seasonal allergic rhinoconjunctivitis. Methods: A total of 115 patients with documented birch pollen allergy were enrolled in this randomized, double-blind, double-dummy, parallel-group trial. Treatment was initiated immediately before the birch pollen season started and continued for a total of 8 weeks. Xylometrazoline (Otrivin) nasal spray was permitted as rescue medication. Results: The investigator's evaluation of symptoms showed similar effects for levocabastine and terfenadine. Both the patients' and the investigator's global evaluations of ocular and nasal symptoms disclosed a somewhat higher percentage of good or excellent results for levocabastine, but the differences were not statistically significant. Visual analog scale ratings from the patients' diaries showed better results for levocabastine. Levocabastine was significantly more effective than terfenadine in relieving sneezing, rhinorrhea, lacrimation, itch, and burning sensation ( p < 0.05). For some symptoms, levocabastine was significantly more effective than terfenadine on days when the pollen count was high. There were no statistically significant differences in the use of rescue medication or in the incidence of adverse reactions reported in each treatment group. Conclusions: In the present study topical levocabastine was frequently more effective than orally administered terfenadine for the treatment of seasonal allergic rhinoconjunctivitis. Both drugs were well-tolerated.

Prospects for ancillary treatment of sinusitis in the 1990s

The basis for ancillary therapy of sinusitis derives from anecdotal accounts and personal beliefs rather than definitive data. The recent appreciation that noninfectious inflammatory causes predispose to infectious sinusitis has stimulated renewed interest in developing and documenting efficacious ancillary therapies that could supplement or abrogate antibiotic use. Ancillary therapies of sinusitis could be directed toward (1) preventing viral upper respiratory tract infections (immunizations, virucidal-impregnated tissues, and proper hand-washing techniques); (2) blocking rhinoviral replication and suppressing mediator release with supraphysiologic nasal hyperthermia, although contradictory studies exist with regard to efficacy; (3) promoting sinus and nasal ventilation with both topical and oral α-agonists and exercise; (4) improving mucociliary clearance by reducing mucus viscosity and elasticity with saline solution irrigation, mucoregulators ( N-acetylcysteine, S-carboxymethylcysteine, and iodinated glycerol), and ciliary stimulants (adenosine triphosphate); and (5) suppressing/modulating cellular inflammation (eosinophilic, basophilic, and neutrophilic) with topical nasal corticosteroid sprays and mediator antagonists. Recommendations are forwarded for future investigations of promising nonantibiotic ancillary therapies of chronic sinusitis.

Information leaflets in the rhinitis clinic?

Failure to get relief from topical steroid nasal spray is often blamed on poor administration knowledge. In a population of patients referred to the rhinitis clinic who have failed to get relief from topical steroid nasal spray when prescribed by the general practitioner, lack of patient education only accounts for 28 per cent of patient treatment failures and other factors e.g. poor compliance, erroneous diagnosis or severity of rhinitis will be responsible for the rest. Information leaflets are considered to be a good idea by nearly all patients but this study demonstrates that they would only be of therapeutic benefit to a minority of patients.

Alae nasi activation and nasal resistance in healthy subjects.

To investigate the effect of alae nasi (AN) activation on nasal resistance, we monitored AN electromyographic (EMG) activity in 17 healthy subjects using surface electrodes placed on either side of the external nares and measured inspiratory nasal resistance utilizing the method of posterior rhinometry. With CO2 inhalation (6 subj), AN EMG activity increased as nasal resistance fell 23 +/- 5% (P less than 0.01). In the same subjects, voluntary flaring of the external nares also increased AN EMG and decreased nasal resistance by 29 +/- 5% (P less than 0.01). Nasal resistance was altered by nasal flaring and CO2 inhalation even after administration of a topical nasal vasoconstrictive spray (8 subj). In six subjects, voluntary nasal flaring or inhibition with the mouth closed produced a 21 +/- 12% change (P less than 0.01) in total airway resistance as measured by body plethysmography. We conclude that activation of the alae nasi will decrease nasal and total airway resistance during voluntary nasal flaring and during CO2 inhalation and thus should be considered in any studies of upper airway resistance.

Rhinitis medicamentosa.

The diagnosis of rhinitis medicamentosa was made in 130 patients seen over a 10 year period from July 1967 to June 1977. There was an incidence of 1% in our otolaryngological practice. Patients had been taking the causal medication for an average of 21.4 months. There were 73 males and 57 females with the peak incidence in young and middle-age adults. The primary offending medications were decongestant nasal sprays in 85 patients, decongestant drops in 33, and a combination of these drugs in 12 patients. The major reasons for self-medication were 1. deviated nasal septum in 40 patients, 2. an acute upper respiratory infection in 33, 3. allergy in 18, 4. miscellaneous causes in 24 and 5. unknown in 15 patients. The initial management in addition to avoidance of the medication consisted of systemic antibiotics, decongestants, antihistamines, and sedatives depending on the severity of the rhinitis and the presence of secondary infection. Later treatment consisted of correction of the deviated septums, allergic management, and supportive care. Eight patients were considered to have complications of the disease by development of chronic ethmoiditis and nasal polyposis. The pharmacologic properties of the causal agents are thoroughly reviewed as they relate to the pathogenesis of this disease. It is felt that the ready commercial availability and limited clinical value of the topical nasal sprays and drops represents a certain risk to all patients using them.

Intranasal sarcoidosis.

AbstractSarcoidosis is a protean disease which may involve several anatomic sites often examined by the otolaryngologist. Sarcoidosis of the nasal mucosa may cause nasal obstruction, especially in the presence of a concomitant deviated nasal septum. The authors review current knowledge pertaining to the etiology, pathology, diagnosis, and treatment as a background for presentation of two interesting cases which highlight the usefulness of a topical steroid nasal spray to relieve obstruction and congestion. Topical steroid therapy is effective and is recommended especially when systemic steroids are not otherwise warranted.