Clinical evaluation of triamcinolone acetonide nasal aerosol in children with perennial allergic rhinitis

Triamcinolone acetonide aerosol (TAA), a topical corticosteroid, now available for intranasal use, has been shown to be highly effective in the treatment of both seasonal and perennial allergic rhinitis (PAR) in adults. To evaluate the efficacy and safety of TAA in children, 210 patients (ages 4 to 12 years) with PAR were randomly assigned to one of three treatment groups (placebo, TAA 82.5 micrograms/day, or TAA 165 micrograms/day). Medication was given tid over 12 weeks in a double-blind fashion. Response to medication was evaluated using symptom scoring, physician evaluation, and, in 44 patients, nasal airflow determinations by anterior rhinomanometry. The higher dose of TAA (165 micrograms/day) significantly improved rhinitis symptoms relative to placebo: the total nasal symptom score and most individual symptom scores (eg, nasal stuffiness, itch, sneezing) were significantly better, duration of rhinitis symptoms (hours per day) was significantly reduced, and nasal airflow in a subset of patients showed significant improvement. The lower dose of TAA (82.5 micrograms/day) was superior to placebo by the same parameters as the higher dose, but this improvement was not as consistently significant as the higher dose. There were no clinically significant adverse events; nasal irritation and epistaxis were rare with a similar incidence among treatment groups. In conclusion, TAA at 165 micrograms/day was effective in controlling the symptoms of PAR and in improving nasal airflow in pediatric patients; the lower dose (82.5 micrograms/day) was marginally effective. Both doses were safe and well-tolerated in the children studied.     

Efficacy of once-a-day intranasal administration of triamcinolone acetonide in patients with seasonal allergic rhinitis.

A 4-week, double-blind, parallel group study compared the safety and efficacy of once-a-day intranasal administration of triamcinolone acetonide (Nasacort) versus placebo in 304 patients (155 adult and 149 adolescent) with seasonal allergic rhinitis. Patients were randomized to receive triamcinolone acetonide (110, 220, or 440 microgram) or placebo once daily each morning. Daily rhinitis symptoms scores, weekly patient and physician global assessments, and weekly nasal eosinophil smears were obtained. In each triamcinolone acetonide group, significant (P less than .05) improvement over placebo was noted in the nasal index (sum of ratings for stuffiness, discharge, and sneezing) by week 1, the first point of analysis, and maintained throughout the study. Triamcinolone acetonide groups also demonstrated significant (P less than .05) improvement over placebo in all individual rhinitis symptoms evaluated. The greatest improvement in symptoms was observed at the 440 microgram dose. A significant decrease in eosinophil counts paralleled clinical improvement in all triamcinolone acetonide groups. Physicians and patients rated triamcinolone acetonide significantly (P less than .05) more effective than placebo. Responses of adult and adolescent patients were comparable. Adverse experiences, clinical laboratory values, and results of physical examinations were unremarkable and comparable between the triamcinolone acetonide and placebo groups. We conclude that triamcinolone acetonide is safe, well tolerated, and superior to placebo as a once-a-day treatment for seasonal allergic rhinitis.     

Once daily triamcinolone acetonide nasal spray is effective for the treatment of perennial allergic rhinitis

A randomized, double-blind, placebo-controlled, parallel group study was conducted in 11 centers to evaluate the safety and efficacy of a once-a-day regimen of 110 micrograms, 220 micrograms; and 440 micrograms of triamcinolone acetonide intranasal aerosol versus placebo in relieving the symptoms of rhinitis in 305 adult and older pediatric patients with perennial allergic rhinitis. Nasal stuffiness, nasal discharge, sneezing, nasal itching and the nasal index (the sum of the mean scores of the first three symptoms) averaged over the first 6 weeks and second 6 weeks of the study were significantly reduced in patients who received the 220 micrograms/day and the 440 micrograms/day dosages. The 110 micrograms/day group had a reduction in these nasal symptoms, but only the sneezing and nasal index were significantly (P less than .05) better than placebo. During the last 6 weeks of the study, patients were allowed to take oral back-up medication for their nasal symptoms; all three groups receiving triamcinolone nasal aerosol took less back-up medication than did the placebo group. There were no significant adverse effects or laboratory abnormalities noted during this study. Intranasal triamcinolone acetonide 220 micrograms and 440 micrograms, used once-a-day for 12 weeks is clinically and statistically superior to placebo for the treatment of perennial allergic rhinitis.     

Effect of nasal triamcinolone acetonide on seasonal variations of bronchial hyperresponsiveness and bronchial inflammation in nonasthmatic children with seasonal allergic rhinitis.

BACKGROUND: Recent evidence suggests that patients with allergic rhinitis have lower airway inflammation and a higher prevalence of bronchial hyperresponsiveness (BHR) regardless of asthma. OBJECTIVE: To investigate markers of lower airway inflammation in nonasthmatic children with seasonal allergic rhinitis (SAR) before and during pollen season and the effect of nasal triamcinolone acetonide on seasonal variations in these parameters. METHODS: Thirty-two nonasthmatic children with SAR in response to grass and/or weed pollens were recruited and separated into 2 groups. Group 1 was treated with triamcinolone acetonide (220 microg once daily) for 6 weeks, and group 2 received no intranasal corticosteroid treatment. Bronchial responsiveness to methacholine [concentration that caused a decrease in forced expiratory volume in 1 second of 20% (PC20)], eosinophil counts in sputum and peripheral blood, and eosinophil cationic protein (ECP) levels in sputum and serum were measured before and during grass pollen season. RESULTS: Twenty-eight patients completed the study. During the pollen season, methacholine PC20 significantly decreased in both groups when compared with the corresponding preseasonal values (P = .01 and P = .003, respectively). The mean percentage of sputum eosinophils increased significantly during the pollen season compared with preseasonal values in group 1 and group 2 (12.7% +/- 2.1% vs 16.5% +/- 2.1%, P = .007, and 11.0% +/- 2.0% vs 20.2% +/- 1.4%, P = .003, respectively). Median [interquartile ranges (IQR)] sputum ECP levels were significantly higher during the pollen season when compared with the preseasonal values in group 1 and group 2 [7.5 microg/L (3.5-36.0 microg/L) vs 35.5 microg/L (13.0-71.7 microg/L), P = .04, and 18.0 microg/L (6.0-36.0 microg/L) vs 69.0 microg/L (39.0-195.0 microg/L), P = .003, respectively], as were the serum ECP levels [6.0 microg/L (2.0-13.0 microg/L) vs 19.0 microg/L (14.0-43.5 microg/L), P = .004, and 6.0 microg/L (3.0-7.0 microg/L) vs 18.0 microg/L (6.0-36.0 microg/L), P = .001, respectively]. Although the mean number of eosinophils in blood increased during the pollen season in both groups, it was only significant in group 2 (70.0 +/- 20.0 vs 161.6 +/- 29.0, P = .02). CONCLUSIONS: Although prophylactic nasal corticosteroid treatment provides significant reduction of nasal symptoms and rescue antihistamine use, there is no significant prevention in the seasonal increase of bronchial inflammation and methacholine BHR.     

Multicenter, double-blind, placebo-controlled trial of triamcinolone acetonide nasal aerosol in the treatment of perennial allergic rhinitis

In a double-blind study involving 205 patients with perennial allergic rhinitis, statistically significantly greater symptomatic improvements were evident following the administration of 200 micrograms/day triamcinolone acetonide aerosol than following placebo. These improvements were evident as early as week 1 and were sustained throughout the 12-week study. They were accompanied by greater reductions in nasal eosinophils. Triamcinolone acetonide aerosol was well tolerated and had no effect on serum cortisol levels.     

Long-term effects of corticosteroid nasal spray on nasal inflammatory cells in patients with perennial allergic rhinitis

BACKGROUND: The effect of long-term topical nasal corticosteroid therapy on nasal inflammatory cells is unclear. OBJECTIVES: To investigate the long-term effect of fluticasone propionate aqueous nasal spray (FPANS) on nasal mucosal inflammatory cells and efficacy in a 1-year study in patients with perennial allergic rhinitis. METHODS: In a 1-year, double-blind, placebo-controlled study of duration we investigated the influence of a topical corticosteroid (FPANS), on Langerhans' cells (CD1a+ cells), T cells, mast cells, eosinophils and macrophages in nasal mucosa in 42 patients with perennial allergic rhinitis. Efficacy was evaluated by nasal symptom score. RESULTS: The FPANS group experienced significantly less sneezing and nasal itching compared with the placebo group. The total symptom score in the FPANS group declined significantly in comparison with baseline (P = 0.007) and placebo group (P = 0.009). After 1 year of active treatment, a significant decrease was seen in the epithelium in numbers of Langerhans' cells, CD3+, CD4+, CD8+ cells, mast cells and eosinophils. In the lamina propria, there was a significant decrease in eosinophils. CONCLUSION: These findings show that FPANS treatment results in a decrease of nasal inflammatory cells. Furthermore, the efficacy of FPANS improves after prolonged treatment.     

Changes in airway inflammation following nasal allergic challenge in patients with seasonal rhinitis

BACKGROUND: Seasonal allergic rhinitis could predispose to the development of chronic bronchial inflammation as observed in asthma. However, direct links between nasal inflammation, bronchial inflammation and airway responsiveness in patients with seasonal allergic rhinitis and without asthma are not fully understood. The aim of this study was to analyse the changes induced by allergic nasal challenge outside the pollen season in airway responsiveness and bronchial inflammation of patients with seasonal allergic rhinitis. METHODS: Nine patients were evaluated after either grass pollens or placebo nasal challenge in a randomized cross-over double-blinded trial. Nasal parameters were recorded hourly and airway responsiveness was assessed by methacholine challenge. Cytological examinations and cytokine measurements were performed in nasal lavage and induced sputum. Eosinophil activation was investigated by eosinophil-cationic protein expression and secretion. RESULTS: Airway responsiveness was increased after allergic nasal challenge. Total eosinophils and eosinophils expressing eosinophil-cationic protein were increased in induced sputum after allergic nasal challenge. Both eosinophil number and eosinophil-cationic protein concentration in induced sputum were correlated to methacholine responsiveness. CONCLUSIONS: These results suggest that eosinophils participate to the bronchial inflammation in patients with seasonal allergic rhinitis following allergic nasal challenge outside the pollen season and might explain changes in airway responsiveness.     

Immunotherapy in allergic rhinitis and lower airway outcomes

Allergic rhinitis and asthma constitute two clinical expressions of a single‐condition, respiratory allergy. Allergen immunotherapy (AIT) is a form of treatment specifically aimed at modifying the response to sensitizing allergens. The inherent potential benefit of AIT is the simultaneous treatment of all clinical expressions of respiratory allergy. Current data support the effectiveness of subcutaneous and sublingual immunotherapy in rhinitis. Studies also provide proof for a beneficial effect in allergic asthma. Even more, substantial evidence points to the preventive effect on the progression from rhinitis to asthma. Despite the current knowledge on the basic mechanisms underlying the immunological effect of AIT is vast, the specific mechanisms for the preventive effect of primary sensitization or new sensitizations are poorly understood. This review aimed to provide a critical overview of the current knowledge on the effectiveness of AIT and its potential role in secondary prevention of respiratory allergy progression.     

Comparative efficacy, safety, and effect on quality of life of triamcinolone acetonide and fluticasone propionate aqueous nasal sprays in patients with fall seasonal allergic rhinitis.

BACKGROUND: The topical potency of fluticasone propionate (FP) is known to be four times greater than that of triamcinolone acetonide (TAA). However, the significance of this difference has not been proven in the clinical treatment of seasonal allergic rhinitis (SAR). OBJECTIVE: To compare the efficacy, safety, and effect on health-related quality of life (HRQL) of FP and TAA aqueous nasal sprays in patients with SAR. METHODS: Single-blind, parallel-group, active-controlled design. Patients were randomized to 3-week treatment with TAA 220 microg (n = 172) or FP 200 microg (n = 180) as two sprays/nostril once daily AM. Twelve-hour reflective symptom evaluations (nasal discharge, stuffiness, itching; sneezing; ocular itching/tearing/redness) were performed AM/PM, beginning at pretreatment baseline period. Incidences of specific treatment-related side effects were collected in daily questionnaires. HRQL was evaluated at baseline and end-of-treatment with a validated disease-specific, quality-of-life instrument. RESULTS: TAA and FP produced similar improvement in daily total nasal symptom scores overall (49.4% and 52.7%, respectively; P = 0.332) and at every weekly time point (P > 0.05). There were no significant differences between TAA and FP in any individual symptom score at any time point except week 2 (FP provided greater reduction in sneezing, P = 0.046). No significant difference was found between groups in overall occurrence of specific treatment-related side effects. Overall Rhinoconjunctivitis Quality of Life Questionnaire scores were similar for TAA and FP at end-of-treatment. CONCLUSIONS: Despite differing molecular potencies, FP and TAA demonstrated comparable efficacy in the treatment of SAR, and produced similar occurrences of specific treatment-related side effects and similar improvements in overall patient HRQL.     

Effect of beclomethasone dipropionate nasal aerosol on serum markers of bone metabolism in children with seasonal allergic rhinitis

Thirty-nine children with grass pollen hay fever were randomly treated with nasal inhaled beclomethasone dipropionate (BDP) 200 or 400 microg/day or sodium cromoglycate (SCG) 30 mg/day for 2 months during the pollen season. Serum osteocalcin (OC), parathyroid hormone (PTH), total alkaline phosphatase (AP), bone alkaline phosphatase (BAP) and type I collagen telopeptide (ICTP) were measured immediately before, 1 and 2 months after treatment and 1 week after stopping the therapy. No significant changes in OC, PTH, AP, BAP and ICTP serum level occurred within each group. Minor and probably clinically insignificant between group differences were occasionally found. Our study shows that BDP nasal spray has no significant effect on common markers of bone metabolism.     

Effects of triamcinolone on quality of life in patients with persistent allergic rhinitis.

OBJECTIVE: To study the effects of triamcinolone acetonide on health-related quality of life (HRQL) in adult patients with allergic rhinitis. METHODS: This study was conducted in South Africa as a placebo-controlled, multicenter, randomized, double-blind study. Following a 7-day baseline run-in, patients were treated for 28 days with either triamcinolone or placebo. Interviewer-assisted quality-of-life assessments were conducted using the Juniper Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). Total symptom scores, including nasal congestion, were measured using daily diary cards. RESULTS: A total of 337 patients were recruited and 253 patients completed the study per protocol, of which 55 had seasonal allergic rhinitis (SAR) and 198 had persistent allergic rhinitis (PAR). Improvements in the mean scores per area of the RQLQ were significantly better with triamcinolone compared with placebo for the entire study group for activities (P = .04 at visit 4) and sleep, nasal symptoms, emotional problems, and overall score (P = .002, P = .04, P = .03, and P = .04, respectively, at visit 3). When the patients with SAR were separated from the patients with PAR in the analysis, improvement with triamcinolone was better than placebo only in the PAR patients. The overall investigator and patient assessments of relief favored triamcinolone. CONCLUSIONS: Triamcinolone given for 4 weeks improves symptom scores and HRQL in patients with allergic rhinitis. The ability of triamcinolone to relieve nasal congestion symptoms in PAR patients was correlated with improvements in HRQL.     

Desloratadine reduces nasal congestion in patients with intermittent allergic rhinitis

Nasal congestion is among the most bothersome of the symptoms of intermittent allergic rhinitis (IAR). Decongestants such as pseudoephedrine are often accompanied by adverse effects and should be avoided by patients with hypertension, arrhythmia, and other medical conditions. Most of the currently available antihistamines are ineffective for nasal congestion. Oral desloratadine, a new, potent H1-receptor antagonist, was examined for its ability to relieve nasal congestion/stuffiness in 346 patients (172 in the desloratadine group and 174 in the placebo group) with IAR. Desloratadine, administered once daily at a dose of 5 mg, demonstrated significant improvement in nasal congestion/stuffiness at all time points assessed in the study. This benefit was observed as early as the first patient evaluation on day 2 and continued throughout the 2 weeks of the study. Desloratadine is a new treatment option for patients with IAR and nasal congestion.     

Effect of allergen immunotherapy on nasal responses in guinea-pigs with allergic rhinitis

Methods We have investigated the effects of allergen immunotherapy on the nasal responses in the guinea-pigs with allergic rhinitis. Thirty-three male Hartley guinea-pigs with allergic rhinitis were divided into three groups; those receiving intradermal injection of saline (Group 1) or 0.1% ovalbumin (Group 2) 6 days after the last intranasal sensitization, and those injected with 0.1% ovalbumin intradermally once daily for 6 consecutive days from the next day after the last intranasal sensitization (Group 3). Results The dye leakage and histamine content into the nasal lavage significantly decreased at 30min after antigen challenge in Group 3, compared with Group 1 or 2. We also observed the change of mast cell numbers in superficial nasal mucosa, lamina propria and injected dorsal skin. The number of mast cells in superficial nasal mucosa significantly decreased in Group 3 compared with Group 1 or 2, but not those in nasal lamina propria or dorsal skin. Conclusions These results suggest that the improvements of nasal responses such as dye leakage and histamine content may be caused by the decrease of mast cell numbers in the superficial mucosal layer after the specific immunotherapy. which may be developing tolerance and one of the mechanisms underlying the beneficial effect of immunotherapy.     

Effect of deep inspiration on airway conductance in subjects with allergic rhinitis and allergic asthma

We measured specific airway conductance ($\text{Gaw}\text{Vtg}$) in a body plethysmograph before and after a deep inspiratory maneuver in 8 subjects with allergic rhinitis and 8 subjects with allergic asthma. In hay fever subjects deep inspiration had no effect on $\text{Gaw}\text{Vtg}$ if it was performed in the control state; however, when methacholine-induced bronchoconstriction was present, deep inspiration transiently increased $\text{Gaw}\text{Vtg}$. In asthmatic subjects deep inspiration was followed by a transient fall in baseline $\text{Gaw}\text{Vtg}$ in the control state; however, when bronchoconstriction was present, deep inspiration was followed by small and variable changes in $\text{Gaw}\text{Vtg}$ in 7 subjects and marked improvement in $\text{Gaw}\text{Vtg}$ in 1 subject. In asthmatic subjects the bronchoconstrictor response to deep inspiration performed in the control state is thought to be due to reflex changes in bronchomotor tone mediated by cholinergic (vagal) nerve pathways. Like asthmatic subjects, hay fever subjects also possess cholinergic-mediated airway hyperreactivity compared with normals. Our results indicate that, in spite of their increased airway reactivity, hay fever subjects respond more like normal subjects than like asthmatic subjects after a deep inspiratory maneuver.     

Relationship between nasal and conjunctival tests in patients with allergic rhinitis

Simultaneous conjunctival and nasal provocation tests, a total of 174 test pairs, were carried out in fifty patients with allergic rhinitis, using serially diluted antigen solutions of birch, Timothy grass and mugwort pollen, as well as cat and dog dander. The nasal mucosa was found to be more sensitive than the conjunctival mucosa in ninety-six test pairs (55 %). This differs from earlier reports. Nasal reaction only was observed in twenty-nine instances (17%). Posterior rhinomanometry was also used to evaluate test reactions, but was found to yield little additional information. In 43 % of nasal provocation tests, which according to other criteria were positive, the rhinomanometric results were negative. Despite a fairly good correlation between the results obtained by nasal and conjunctival challenge, the results point to organ specificity in type I reactions. Provocation tests, if indicated in a thorough allergy evaluation, should be performed in the shock organ. The provocation methods and interpretation of reactions of this study differ from those of earlier reports. Comparison of results is difficult and standardization of methods is needed.     

Variations in histamine concentration in nasal secretion in patients with allergic rhinitis

The histamine concentration and content in nasal secretion and the volume of nasal secretion in nasal washing samples were measured under different conditions in 28 patients with allergic rhinitis sensitive to birch pollen. The mean histamine concentration was significantly lower after intranasal birch pollen challenge (2.08 micrograms/ml) than in prechallenge samples (6.96 micrograms/ml), and was also significantly lower in untreated patients during the birch pollen season (2.30 micrograms/ml) than off-season (7.18 micrograms/ml). The same relationship was found between the histamine content of the secretion samples obtained on these occasions. The mean secretion volume was greater after than before challenge, but not significantly higher during the season than off-season. A partial reversion of the changes in histamine concentration and content that occurred during the season was observed during intranasal corticosteroid therapy. The concentration and content of histamine in nasal secretion from symptomatic patients after intranasal histamine challenge did not differ significantly from those in asymptomatic subjects before challenge. It was concluded that although the histamine level in nasal secretion can be used as a marker of changes in the severity of allergic rhinitis, it is not ideal for this purpose.