Substance P is generated in vivo following nasal challenge of allergic individuals with bradykinin

BACKGROUND: Bradykinin, a potent inflammatory mediator, is released during allergic and non-allergic rhinitis and asthma in man. Nasal bradykinin challenge induces a dose-dependent plasma leakage into the nasal cavity and relevant symptoms of rhinitis. OBJECTIVE: We now report on substance P generation during nasal bradykinin challenge in vivo. METHODS: The effect of locally applied bradykinin on substance P generation was studied in nine individuals, allergic to grass pollen and six non-allergic controls. In the allergics TAME-esterase activity, histamine and substance P concentrations were measured in nasal lavages and correlated to the clinical symptoms. RESULTS: Substance P concentrations in nasal lavages increased in a dose-dependent fashion during nasal bradykinin challenge in both groups. In the allergic group Substance P-increases correlated with the production of TAME-esterase activity (r = 0.9, P < 0.05) whereas these allergic individuals did not produce any histamine increases. The generation of substance P and the increase of TAME-esterase activity was associated with the onset of clinical symptoms. Correlation of oedema and hypersecretion to substance P were significant by linear regression analysis (r = 0.88, P < 0.005 and r = 0.89, P < 0.02, respectively). Bradykinin induced irritations like burning and itching were short-term and rare. Serial dilutions of nasal washes produced Substance P-RIA displacement curves that paralleled the standard curve and recovery of standard substance P that was added to nasal washes was 76 +/- 4% (mean +/- SEM), n = 8. CONCLUSION: Bradykinin induces in vivo a dose-dependent plasma leakage into the nasal cavity without affecting mast cells, but stimulates nerve endings resulting in the release of the neuropeptide substance P.     

Cervical actinomycosis. A rare differential diagnosis of parotid tumor]

BACKGROUND: Allergic rhinitis is usually treated with oral antihistamines or nasal steroids. Topically active nasal antihistamine is a new treatment modality for allergic rhinitis. The efficacy in comparison to well established topical treatment alternatives is not fully known. OBJECTIVE: To compare the efficacy of intranasally administered azelastine to budesonide, at their respectively recommended dosage, on the symptoms of perennial rhinitis patients. METHODS: A placebo-controlled, randomized, parallel group study was conducted to compare the efficacy and tolerability of intranasal budesonide aqueous suspension (256 microg once daily) with azelastine hydrochloride nasal spray (280 microg twice daily (560 microg/day)) and with placebo in the treatment of perennial allergic rhinitis. The 195 patients (with at least a 2-year history of perennial allergic rhinitis) recorded individual nasal symptom scores, the degree of symptom control achieved and any adverse events experienced over a 2-week baseline period and a 6-week treatment period. RESULTS: Following treatment, the reductions in mean combined and individual nasal symptom scores from baseline values were significantly greater in the budesonide group compared with the placebo group (P < .0001 for all variables except runny nose P = .01). In patients treated with budesonide, there were also significantly larger reductions from baseline values in combined nasal symptom scores (P < .01) and in scores for all individual nasal symptoms (P < or = .05) compared with those treated with azelastine. The reductions from baseline in both combined and individual nasal symptom scores did not differ between azelastine and placebo. The study medications were well tolerated, producing no unexpected or serious treatment-related adverse events. CONCLUSION: A once-daily dose of 256 microg of intranasal budesonide aqueous suspension is significantly more effective at relieving the symptoms of perennial allergic rhinitis compared with a twice daily dose of 280 microg of azelastine nasal spray.     

Suppression of human melanoma metastasis following introduction of chromosome 6 is independent of NME1 (Nm23)

BACKGROUND: Nasal immunotherapy with single allergen extracts, following premedication with cromolyn, has been reported to be effective in treating seasonal and perennial allergic rhinitis. METHODS: We conducted a double-blind, placebo-controlled study to assess the efficacy, tolerability, and mechanism of action of nasal immunotherapy for allergic rhinitis caused by weed pollens from three unrelated families. Twenty-seven weed-allergic patients underwent baseline nasal provocation and titrated skin test with a mixed weed extract containing ragweed, sage, and Chenopod extracts. Patients were randomized to receive either mixed weed extract or placebo. Nasal immunotherapy was self-administered daily to alternate nostrils preceded by 5.2 mg intranasal cromolyn. Beginning with 1:2500 wt/vol the concentration was increased to 1:10 wt/vol over an average period of 36 days. The maintenance dose (1:10 wt/vol) was administered daily for 12 to 16 weeks through the weed pollen season. Patients recorded nasal and eye symptoms and the use of rescue medications throughout the study. A nasal lavage for cytokine levels and nasal scraping with Rhinoprobe for nasal cytology were performed at the peak of the weed season. Nasal provocation and titrated skin tests with mixed weed extract were repeated after the weed season. Nasal lavage and scraping were also performed before and 24 hours after the final nasal provocation. RESULTS: During the peak weeks of the weed season the group receiving mixed weed extract by nasal instillation, compared with those treated with placebo, had significantly lower total nasal symptom scores, total eye symptom scores, and symptom medication scores. There were no significant differences in the nasal cytology or cytokines levels between the two groups, except for elevated IL-10 in the nasal lavage in the treated group at the peak of the season. Nasal symptoms and medication use were higher preseasonally in the active treatment group. CONCLUSION: Nasal immunotherapy with aqueous mixed weed extract administered with cromolyn sodium pretreatment for 17 to 21 weeks was effective in reducing both nasal and ocular symptoms of weed pollen-induced allergic rhinitis. There were increased nasal symptoms in the treated group preseasonally.     

Nedocromil sodium 1% nasal spray in the treatment of allergic rhinitis caused by Dermatophagoides pteronyssinus

We have evaluated the efficacy of Nedocromil sodium 1% nasal solution in 36 patients (20 females and 16 males, mean age 29.5 years) suffering from perennial allergic rhinitis caused by Dermatophagoides pteronyssinus. Nedocromil sodium was given four times a day for 2 months. On a daily card patients had to report the severity of the considered symptoms (runny, nose, sneezing, itchy nose and stuffy nose) following an arbitrary score from 0 to 3 (0 = no symptom, 1 = mild, 2 = moderate, 3 = severe). Clinical evaluation was performed after 1 month and at the end of the treatment. We observed a statistically significant decrease of the considered symptoms already after a one month therapy. This improvement was higher after two months (p < 0.001). No side effects have been reported and no concomitant symptomatic therapy was needed. Nedocromil sodium is therefore a safe and efficacious drug in the treatment of allergic rhinitis caused by Dermatophagoides pteronyssinus.     

Levocabastine versus cetirizine for perennial allergic rhinitis in children

OBJECTIVE: To compare the efficacy and safety of levocabastine nasal spray asid cetirizine oral for the treatment of perennial allergic rhinitis in children. MATERIAL AND METHODS: In this randomized, prospective experimental, open clinical trial. We studied 30 children with ages between 6 and 16 years with perennial allergic rhinitis. Group 1, 17 subjects (7 female, 10 male) received cetirizine once daily, 5 mg children weientig less dian 30 k asid 10 mg in children weighing more trw' 30 k during 15 days. Group 2, 13 subjects (7 male, 6 female) received levocabastine 2 puffs BID on each nostril during tbe same time. A nasal symptoms score, nasal peal: flow vid eosinophils in a nasal smear were performed before and after treatment. RESULTS: There were no statistical differences in age, weight, height and arid duration of symptoms. Both groups showed improvement of symptoms via nasal peak flow with no differences between them (intergroup); nasal eosinophils remained unchanged. We for third statistical differences pre vid postreatment in each group (intragroup): Group 1, nasal congestion p = 0.002, ocular itch p = 0.01, sneezing p = 0.007, nasal secretion p = 0.01, nasal itch O = 0.009, total points O = 0.0005. Group 2, nasal congestion O = 0.02, ocular itch p = 0.05, sneezing p = 0.01, nasal secretion p = 0.01, nasal itch p = 0.04, total points p = 0.005. Significant differences were found in nasal peal' flow in Group 1 (p = 0.01) but no differences in eosinophils between file two groups. Side effects: 3 subjects in Group 1 (drowsiness, 1 appetite increase said 1 rhinorrea with epistaxis) vide 1 in Group 2 sensation of facial edema. CONCLUSION: Bofil drugs are effective the clinical relief of symptoms of perennial allergic rhinitis in children vied levocabastine has less side effects.     

The efficacy of fluticasone propionate aqueous nasal spray for allergic rhinitis and its relationship to topical effects

Fluticasone propionate aqueous nasal spray is an intranasal corticosteroid for the treatment of patients with allergic rhinitis. This double-masked, double-dummy, parallel-group study was conducted to confirm that the efficacy of fluticasone propionate nasal spray is attributable to topical rather than systemic effects. A total of 304 patients with documented seasonal allergic rhinitis were randomly assigned to receive fluticasone propionate nasal spray 200 micrograms once daily (n = 77), oral fluticasone propionate 5 mg once daily (n = 73), oral fluticasone propionate 10 mg once daily (n = 77), or placebo (n = 77) for 14 days. Plasma fluticasone propionate concentrations were determined at baseline and after 14 days of treatment (day 15). Nasal symptoms were recorded daily by patients and assessed weekly by clinicians. On day 15, more patients in the oral fluticasone propionate 5-mg or 10-mg groups, compared with patients in the fluticasone propionate nasal spray group or the placebo group, had detectable plasma fluticasone propionate concentrations, and mean concentrations were higher in the oral fluticasone propionate groups. Both clinician- and patient-rated total and individual nasal symptom scores for obstruction, rhinorrhea, sneezing, and itching were significantly lower in the fluticasone propionate nasal spray group compared with either of the oral fluticasone propionate groups or the placebo group. With few exceptions, oral fluticasone propionate (5 mg or 10 mg) was not significantly different from placebo on any measures of efficacy. These findings indicate that the efficacy of fluticasone propionate nasal spray (200 micrograms once daily) in the treatment of allergic rhinitis results from direct topical effects rather than from indirect effects after systemic absorption.     

Comparison between nasal and bronchial inflammation in asthmatic and control subjects

Although asthma and rhinitis often coexist, it is still unknown whether they are characterized by a similar inflammatory profile. We studied eosinophilic infiltration, epithelial shedding and reticular basement membrane thickness in nasal and bronchial biopsies of six control subjects, 15 untreated allergic asthmatics with perennial rhinitis, and six corticosteroid-dependent (CSD) asthmatics. In nasal and bronchial biopsies, eosinophils were greater in untreated asthmatics than in control subjects and CSD asthmatics (p = 0.001). In untreated asthmatics, eosinophils were higher in bronchial than in nasal biopsies (p = 0.002). In nasal and bronchial biopsies, reticular basement membrane thickness was greater in untreated and CSD asthmatics than in control subjects (nasal: p < 0.008 and p < 0. 004; bronchial: p < 0.001 and p < 0.008). In untreated and CSD asthmatics, reticular basement membrane thickness was greater in bronchial than in nasal biopsies (p = 0.001; Wilcoxon's W test). Nasal epithelium was not shed in all the study groups. In untreated asthmatics, bronchial epithelium shedding was greater than in control subjects or CSD asthmatics (p < 0.005), and it was greater than nasal epithelium shedding (p < 0.006). This study has shown that, although concomitant, the extent of eosinophilic inflammation of reticular basement membrane thickness and of the epithelium shedding is greater in bronchial than in nasal mucosa of asthmatic patients with perennial rhinitis.     

Verrucous squamous cell carcinoma of the larynx: diagnostic and therapeutic considerations

Certain prostaglandins acting as inflammatory mediators have been implicated in the aetiology of perennial allergic rhinitis (PAR). Inhibition of prostaglandin synthesis in the nasal mucosa might therefore influence the symptoms associated with PAR. A randomised, doubleblind, placebo-controlled cross-over trial using 0.1% Diclofenac eye-drops has been conducted to investigate this hypothesis. Diclofenac, a non-steroidal anti-inflammatory drug (NSAID), reduces prostaglandin synthesis through the inhibition of the cyclo-oxygenase pathway. Twenty-five patients with significant PAR and positive skin tests to relevant perennial allergens were recruited and two drops of the given preparation were administered bilaterally q.d.s.. Thirteen patients completed the study. Nasal symptom score (itch, rhinorrhoea, sneezing, and blockage), smell test score, saccharin transit time, total nasal airflow resistance, and nasal inspiratory peak flow measurements were obtained at each of three study visits. No significant treatment effects were found. The daily nasal symptom score over the entire study period showed no significant variation. Adverse effects such as local invitation, dry nose or throat were rare. No untoward changes in haematological, biochemical profiles and urinalysis occurred. In conclusion, topical 0.1% Diclofenac eye-drops applied nasally have no significant effect on PAR. Prostaglandins alone may not play a major role in mediation of symptoms in this condition.     

Stem cell factor mRNA expression and production in human nasal epithelial cells: contribution to the accumulation of mast cells in the nasal epithelium of allergy

BACKGROUND: In allergic rhinitis, mast cells are increased in number in the epithelium of the nasal mucosa and play an important role in the immediate response. However, the mechanism of the accumulation is not known. OBJECTIVE: The purpose of this study was to determine whether the nasal epithelial cells produce stem cell factor (SCF), the mast cell growth and chemoattractant factor, and contribute mast cell hyperplasia in the epithelium of allergic rhinitis. METHODS: We have characterized the cellular localization of SCF using immunohistochemistry, reverse transcribed-PCR, and ELISA; compared SCF production of cultured epithelial cells between patients with allergic rhinitis and nonallergic subjects; and compared the SCF production with the number of mast cells and the histamine content in the nasal epithelial scrapings. RESULTS: Immunohistochemically, SCF was identified in the nasal epithelium of the biopsy specimens and in cultured nasal epithelial cells. SCF mRNA was expressed by cultured nasal epithelial cells not only in patients with allergy but also in subjects with no allergy. However, the SCF/beta-actin mRNA ratio and SCF production in day 7 cultured epithelial cells was significantly higher in allergic than in nonallergic subjects (P =. 0424, P =.0085, respectively). SCF production from nasal scrapings in culture was strongly correlated with the number of mast cells (r = 0.506, P =.0023) and the histamine content (r = 0.480, P =.0040). CONCLUSIONS: These findings demonstrate that nasal epithelial cells produce SCF and may be important in the attraction, proliferation, and activation of mast cells in allergic inflammation in the nose.     

Budesonide and nasal histamine challenge

The possible mode of action of the lately demonstrated steroid effect on the immediate type allergic reaction was investigated. The influence of a topical steroid, budesonide, on the effects that released mediators have on the nasal mucosa was also studied. A nasal histamine challenge study was performed in a double-blind, cross-over fashion, a 1-week pretreatment with budesonide or placebo preceding the challenge. Symptoms were recorded by means of symptom score as well as objectively via rhinomanometry. In contrast to a previous allergen challenge study, the steroid was found to have minimal effect on the histamine-induced nasal symptoms. It is therefore concluded that other modes of steroid action must also be involved in the steroid effect on the immediate type allergic reaction.     

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

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

Mometasone furoate. A review of its intranasal use in allergic rhinitis

Mometasone furoate is a synthetic corticosteroid which has been evaluated for intranasal use in the treatment of adults and children with allergic rhinitis. In several large, well-controlled clinical trials, mometasone furoate 200 micrograms administered once daily as an aqueous intranasal spray was significantly more effective than placebo in controlling the symptoms associated with moderate to severe seasonal or perennial allergic rhinitis. Mometasone furoate was as effective as twice-daily beclomethasone dipropionate or once-daily fluticasone propionate in the treatment of perennial allergic rhinitis, and was as effective as twice-daily beclomethasone dipropionate and slightly more effective than once-daily oral loratadine in the treatment of seasonal allergic rhinitis. Mometasone furoate was also as effective as twice-daily beclomethasone dipropionate or once-daily budesonide, and significantly more effective than placebo in the prophylaxis of seasonal allergic rhinitis. The onset of action of mometasone furoate was approximately 7 hours in patients with seasonal allergic rhinitis. Mometasone furoate was as well tolerated as beclomethasone dipropionate, fluticasone propionate and budesonide in clinical trials, with an overall incidence of adverse events similar to placebo. Adverse events were generally mild to moderate and of limited duration. The most common adverse events associated with mometasone furoate therapy were nasal irritation and/or burning, headache, epistaxis and pharyngitis. Intranasal or oral mometasone furoate had no detectable effect on hypothalamic-pituitary-adrenal axis function in studies of < or = 1 year in duration. CONCLUSIONS: Mometasone furoate is a well tolerated intranasal corticosteroid with minimal systemic activity and an onset of action of < or = 7 hours. It is effective in the prophylaxis and treatment of seasonal allergic rhinitis and the treatment of perennial allergic rhinitis in patients with moderate to severe symptoms.     

Diagnostic use of enzymatic RAST skin tests and determination of eosinophils in nasal mucosa in allergic rhinitis

AIMS: Allergic rhinitis is the most frequent disease mediated by immunoglobulin E (IgE). Nasal challenge is the gold standard for the diagnosis of allergic rhinitis. Skin tests (ST) are the most used diagnostic method to detect the presence of specific IgE bind to skin mast cells. The exposition of the nasal mucous membrane to the allergen is followed by an increase of the local eosinophils; the count of eosinophils in nasal mucous (ENM) is a diagnostic test for allergic rhinitis. Enzymatic RAST or enzymatic allergo-sorbent test (ESA) measures the level of serum allergen-specific IgE. OBJECTIVE: To measure the sensitivity, specificity, and diagnostic precision of ST, EAST and ENM in allergic rhinitis. METHOD: We studied 241 individuals, 162 of them had allergic rhinitis, and 79 were healthy controls. They underwent nasal challenge and intradermic ST for Dermatophagoies spp (acarus). Fraxinus americana (Ash-tree), Amaranthus palmieri (quelite), Cynodon Dactylon (capriola) and Felis catus (cat), EAST for Dermatophagoides pteronyssinus (acarus), and ENIVI. Results of ST, EAST and ENIVI were compared with their corresponding nasal challenge, and the prevalence of allergic rhinitis for each allergen was calculated. The best cut point was assessed by means of receiver-operator curves (ROC), and sensitivity, specificity, positive predictive value, negative predictive value, inter-observer concordance coefficient, area under ROC (0), standard error of 0 (SEO), and 95% confidence interval of 0 of each test were calculated using the best cut point. RESULTS: ST and EAST had the best sensitivity and specificity. ENM had the lowest sensitivity and specificity. CONCLUSION: For the diagnosis of Dermatophagoides spp allergic rhinitis ST for Dermatophagoides spp and EAST for Dermatophagoides pteronyssinus have the same diagnostic precision. According to the indexes for diagnostic precision, and inter-observer concordance coefficient, ST and EAST are useful to diagnose allergic rhinitis induced by the evaluated allergens. ENIVI is a test that is not very useful for the diagnosis of allergic rhinitis.     

Intranasal azelastine. A review of its efficacy in the management of allergic rhinitis

Azelastine, a phthalazinone compound, is a second generation histamine H1 receptor antagonist which has shown clinical efficacy in relieving the symptoms of allergic rhinitis when administered as either an oral or intranasal formulation. It is thought to improve both the early and late phase symptoms of rhinitis through a combination of antihistaminic, antiallergic and anti-inflammatory mechanisms. Symptom improvements are evident as early as 30 minutes, after intranasal administration of azelastine [2 puffs per nostril (0.56mg)] and are apparent for up to 12 hours in patients with seasonal allergic rhinitis (SAR). The effect on nasal blockage is variable: in some studies objective and/or subjective assessment showed a reduction in blockage, whereas in other studies there was no improvement. Intranasal azelastine 1 puff per nostril twice daily is generally as effective as standard doses of other antihistamine agents including intranasal levocabastine and oral cetirizine, ebastine, loratadine and terfenadine at reducing the overall symptoms of rhinitis. The relative efficacies of azelastine and intranasal corticosteroids (beclomethasone and budesonide) remain unclear. However, overall, the corticosteroids tended to improve rhinitis symptoms to a greater extent than the antihistamine. Azelastine was well tolerated in clinical trials and postmarketing surveys. The most frequently reported adverse events were bitter taste, application site irritation and rhinitis. The incidence of sedation did not differ significantly between azelastine and placebo recipients and preliminary report showed cardiovascular parameters were not significantly altered in patients with perennial allergic rhinitis (PAR). Conclusion: Twice-daily intranasal azelastine offers an effective and well tolerated alternative to other antihistamine agents currently recommended for the symptomatic relief of mild to severe SAR and PAR in adults and children (aged > or = 12 years in the US; aged > or = 6 years in some European countries including the UK). The rapid onset, confined topical activity and reduced sedation demonstrated by the intranasal formulation of azelastine may offer an advantage over other antihistamine agents, although this has yet to be confirmed.     

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

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

Acoustic rhinometry in the study of the acute nasal allergic response

Acoustic rhinometry is a recently developed method for the objective assessment of nasal patency. In this study, acoustic rhinometry was used to measure changes in nasal cavity dimensions in the immediate response to nasal allergen challenge in eight pollen-sensitive subjects. Acoustic rhinometric changes were compared with subjective symptoms, as well as histamine in nasal secretions, cytology of nasal mucosal scrapings, and changes in olfactory function. A significantly greater decrease in nasal airway caliber occurred following allergen challenge as compared to buffer diluent challenge in the same individuals (70% +/- 7% versus 22% +/- 5%). During an allergic response, a strong correlation was found between the minimum cross-sectional area and the volume of the nasal cavity measured by acoustic rhinometry (r = .9). However, no correlation was observed between nasal airway caliber and concomitant subjective congestion reported by the subjects. A modest decrease in olfactory function was seen following allergen challenge (3.1 +/- 1.4 fewer odors identified correctly out of 20; p = .08). However, the alterations of olfactory function did not correlate with changes in nasal patency. The results presented in this study demonstrate that acoustic rhinometry has great potential as a reproducible method for the objective assessment of nasal obstruction occurring in nasal allergen challenge studies.     

The effect of BAY u 3405, a thromboxane receptor antagonist, on prostaglandin D2-induced nasal blockage

BACKGROUND: Nasal lavage and challenge studies in allergic rhinitis implicate prostaglandin (PG) D2 in the genesis of nasal blockage. PG D2 is known to act via at least two receptors, the thromboxane prostanoid receptor and the PG D2 prostanoid (DP) receptor; the lower airway effects are mediated chiefly by the TP receptor. The receptor involved in the genesis of PG D2-induced nasal blockage is unknown. BAY u 3405 is a potent selective competitive TP receptor antagonist, which inhibits the lower airway response to PG D2, and shifts the dose-response curve to the right by up to 16-fold. METHODS: The efficacy of a single oral dose of 20 mg of BAY u 3405 was examined in comparison with PG D2 nasal insufflation in a randomized, double-blind, placebo-controlled crossover study, with objective measurement of nasal resistance by active posterior rhinomanometry. RESULTS: BAY u 3405 afforded no protection against PG D2-induced nasal blockage. CONCLUSIONS: This suggests that PG D2-induced nasal blockage may be mediated by the DP receptor rather than the TP receptor and that TP receptor antagonists are unlikely to be of benefit in the treatment of allergic rhinitis. In vivo investigation with specific potent DP receptor antagonists is awaited.     

The role of partial splenectomy in children with thalassemia

AIM OF THE STUDY: To study the changes in nasal reactivity in patients with rhinitis medicamentosa during treatment with placebo or fluticasone propionate, in order to better understand the mechanisms of nasal congestion in such patients. STUDY DESIGN: A parallel, double-blind study. Twenty patients with rhinitis medicamentosa were randomized to either placebo or fluticasone treatment during 14 days. MATERIAL AND METHODS: Nasal mucosa reactivity was studied with a histamine challenge model using three concentrations of histamine to challenge the nasal mucosa (1, 2 and 4 mg histamine/ml). Recordings of the nasal mucosa response were made 5 min after each challenge, using rhinostereometry and acoustic rhinometry, before and after the period of treatment. RESULTS: The fluticasone group had a significantly increased histamine sensitivity after treatment, unlike the placebo group who had an unchanged or slightly decreased histamine sensitivity after treatment. CONCLUSIONS: The results of this study support the theory that the nasal obstruction in rhinitis medicamentosa is due to interstitial oedema rather than to vasodilatation. On the first day of vasoconstrictor withdrawal, the inferior concha was congested and oedematous with a limited capacity to respond to histamine challenge. However, after 14 days of treatment with a corticosteroid nasal spray, the oedema was reduced and the increase in histamine sensitivity reflected the persistence of nasal hyperrreactivity. In the placebo group, histamine sensitivity remains unchanged with the measuring technique we used. This probably indicates that oedema was still present after treatment.     

The effect of terfenadine on unilateral nasal challenge with allergen

To investigate the role of H1 receptor-mediated effects in allergic rhinitis, we challenged 12 allergic volunteers with allergen 2 hours after administration of either placebo or 60 mg of terfenadine. Filter paper discs were used for the unilateral administration of allergen and the collection of nasal secretions. Secretion weights, levels of histamine in recovered nasal secretions, and nasal airway resistance (NAR) were measured for each nostril separately, and the number of sneezes was counted. After placebo treatment, allergen challenge led to significant increases in ipsilateral and contralateral secretion weights, ipsilateral histamine levels, ipsilateral NAR, and sneezing. Contralateral histamine levels were not elevated. H1 antagonism with terfenadine markedly reduced the number of sneezes and partially decreased ipsilateral and contralateral secretion weights, without affecting the increase in NAR. Terfenadine premedication also lowered the amount of histamine in ipsilateral secretions after allergen challenge. Performing identical nasal challenges with a 10-fold lower dose of antigen produced similar results. Previous studies showed that terfenadine had no effect on methacholine provocation and completely abolished ipsilateral and contralateral secretion weights after histamine challenge. We conclude that sneezing after allergen challenge is caused almost exclusively by a reflex initiated through H1 receptors and that H1 antagonism has no influence on allergen-induced increases in NAR. Unilateral allergen challenge leads to bilateral increases in secretion weights, which are only partially inhibited by terfenadine, suggesting the involvement of mediators other than histamine in the nasonasal reflex. As reported earlier, terfenadine also decreases allergen-induced histamine release after challenge with the highest dose of antigen.