Marcy deTineo

Nasal challenge with allergen leads to maxillary sinus inflammation

BACKGROUND Allergic rhinitis and chronic rhinosinusitis are both characterized by chronic inflammation. OBJECTIVE We sought to investigate the effect of nasal allergen challenge on the maxillary sinus and study the effect of premedication with loratadine. METHODS We performed a double blind, crossover, randomized, placebo-controlled study in 20 allergic subjects out of season. After treatment with either placebo or loratadine (10 mg PO daily) for 1 week, a catheter was inserted into one maxillary sinus and used to lavage the cavity. The subjects then underwent nasal challenge with diluent for the allergen extract, followed by 3 concentrations of grass or ragweed. Nasal and ipsilateral sinus lavages were performed after each challenge and then hourly for 8 hours. Sneezes and symptoms were recorded, and the lavage specimens were evaluated for eosinophils and levels of eosinophil cationic protein, albumin, and histamine. Eleven of the subjects underwent a similar challenge with lactated Ringers solution. RESULTS Compared with the lactated Ringers solution challenge, allergen challenge resulted in significant increases in most early- and late-phase nasal parameters. Allergen challenge of the nose also led to a significant increase compared with control values in maxillary sinus eosinophils and the levels of albumin, eosinophil cationic protein, and histamine during the late response. Loratadine resulted in significant inhibition of the nasal early response compared with that seen with placebo (P < .05). CONCLUSION These findings suggest that a neural reflex or systemic allergic inflammation is responsible for the sinus inflammatory response and that this inflammatory response might play a role in the development of rhinosinusitis in allergic subjects.

Fluticasone furoate nasal spray reduces the nasal-ocular reflex: a mechanism for the efficacy of topical steroids in controlling allergic eye symptoms.

BACKGROUND Eye symptoms frequently occur in patients with allergic rhinitis and are among the most bothersome symptoms. Intranasal steroids have been shown to reduce ocular symptoms associated with allergic nasal symptoms, even though they do not reach the eye. OBJECTIVE To elucidate a mechanism to explain these observations. METHODS We performed a double-blind, placebo-controlled, crossover experiment in 20 subjects with seasonal allergic rhinitis. Nasal antigen challenge was performed consecutively for 3 days after 1 week of treatment with either placebo or fluticasone furoate nasal spray (FFNS). Subjects recorded their nasal and ocular symptoms, and nasal secretions were quantified. Nasal scrapings to quantify eosinophils were obtained before each antigen challenge. RESULTS Nasal challenge with antigen led to sneezing, a nasonasal, and a nasal-ocular reflex. Priming in the number of sneezes, contralateral nasal secretion weights, and total eye symptoms were observed. Treatment with FFNS reduced sneezing, the nasonasal and nasal-ocular reflexes, and the amount of eosinophils in nasal secretions. CONCLUSIONS We confirmed that a nasal-ocular reflex follows nasal challenge with allergen and that it can contribute to the ocular symptoms associated with allergic rhinitis. FFNS reduced eosinophil infiltration, priming, and ocular symptoms. Furthermore, our results support a mechanism by which control of eye symptoms can be achieved during nasal administration of an intranasal steroid in patients with seasonal allergic rhinitis.

Nasal ocular reflexes and eye symptoms in patients with allergic rhinitis

BACKGROUND Allergic patients often complain of eye symptoms during the allergy season. A possible mechanism for these eye symptoms is a nasal ocular reflex. OBJECTIVE To demonstrate eye symptoms after nasal allergen challenge. METHODS In a double-blind, placebo-controlled, crossover, clinical trial, 20 patients with seasonal allergic rhinitis were challenged in 1 nostril with antigen, and the response was monitored in both nostrils and in both eyes. Symptoms were recorded. Filter paper disks (intranasally) and Schirmer strips (intraocularly) were used for collecting secretions, which were subsequently eluted for the measurement of histamine and albumin levels. Patients were treated once topically at the site of challenge with azelastine or placebo. RESULTS After placebo treatment, ipsilateral nasal challenge caused nasal symptoms and an increase in secretion weights; both were blocked by treatment with azelastine. Histamine and albumin levels increased only at the site of nasal challenge. Azelastine pretreatment inhibited the increase in albumin but not histamine levels. Symptoms of itchy and watery eyes increased significantly compared with symptoms with sham challenge after nasal allergen and were blocked by azelastine use. Ocular secretion weights increased bilaterally after placebo use and were not inhibited by azelastine use. CONCLUSIONS Nasal allergen challenge releases histamine at the site of the challenge, which probably initiates a nasonasal and a nasal ocular reflex. This reflex is reduced by an H1-receptor antagonist applied at the site of the challenge. The eye symptoms associated with allergic rhinitis probably arise, in part, from a naso-ocular reflex.

Comparison of the combinations of fexofenadine-pseudoephedrine and loratadine-montelukast in the treatment of seasonal allergic rhinitis

BACKGROUND Antihistamine-decongestant combinations are used routinely for the treatment of seasonal allergic rhinitis. Recently, the combination of an antihistamine and a leukotriene receptor antagonist has been shown to be efficacious. OBJECTIVE To compare the 2 combinations in the treatment of seasonal allergic rhinitis. METHODS This was a randomized, double-blind, double-dummy, parallel study in which patients with seasonal allergic rhinitis received either fexofenadine, 60 mg, and pseudoephedrine, 120 mg, twice daily, or loratadine, 10 mg, and montelukast, 10 mg, once daily, for 2 weeks. The Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) was completed at the beginning and end of the study. Patients recorded nasal symptoms and measured nasal peak inspiratory flow (NPIF) twice daily. Baseline measurements were obtained before initiation of treatment. RESULTS Compared with baseline, both treatments resulted in statistically and clinically meaningful reductions of overall and individual RQLQ domain scores (P < .01) except for the sleep domain, for which only loratadine-montelukast led to significant improvement. There was a significant reduction in total symptoms (P < or = .05) compared with baseline on most treatment days in patients receiving both combinations. When the change from baseline was analyzed, there were no statistically significant differences in total symptoms between fexofenadine-pseudoephedrine and loratadine-montelukast (median, -28.5 vs -22.5; P = .33). There was a significant improvement in NPIF from baseline on all treatment days in both groups (P < .05), with no significant difference between treatments. CONCLUSIONS Fexofenadine-pseudoephedrine and loratadine-montelukast have comparable efficacy in improving symptoms, RQLQ scores, and nasal obstruction in seasonal allergic rhinitis. The lack of improvement in sleep in the fexofenadine-pseudoephedrine group is probably related to insomnia, a known adverse effect of pseudoephedrine.

Oxymetazoline adds to the effectiveness of fluticasone furoate in the treatment of perennial allergic rhinitis

BACKGROUND In clinical trials, only about 60% of subjects report an excellent response to intranasal steroids, suggesting a need to add therapies to intranasal steroids to provide additional efficacy. OBJECTIVE To determine whether the combination of fluticasone furoate and oxymetazoline is more efficacious than either agent alone, and to determine whether rhinitis medicamentosa develops after treatment. METHODS We performed a double-blind, double-dummy, randomized, placebo-controlled parallel study. Sixty patients with perennial allergy were randomized to 4 weeks of once-a-night treatment with fluticasone furoate, oxymetazoline hydrochloride, the combination, or placebo. They were monitored during treatment and for 2 weeks posttreatment. RESULTS The total nasal symptom score over the 4 weeks of treatment was lower with the combination (median, 143; range, 30-316) compared with treatment with placebo (262; 116-358) and oxymetazoline alone (219; 78-385; ANOVA, P = .04). When acoustic rhinometry was compared between the groups at the end of 4 weeks of treatment, the combination resulted in significantly higher nasal volume (mean + SEM, 15.8 + 1.1 mL; P< .03) compared with both placebo (12.1 + 0.9 mL) and oxymetazoline (12.4 + 0.8 mL) alone. The quality of life data showed no significant differences among the groups. Peak flow showed a nonsignificant improvement with the groups on fluticasone furoate. There was no evidence of rhinitis medicamentosa. CONCLUSION The addition of oxymetazoline adds to the effectiveness of fluticasone furoate in the treatment of perennial allergic rhinitis. The lack of development of rhinitis medicamentosa suggests the need for a large multicenter study to develop a once-a-day combination of an intranasal steroid and a long-acting topical decongestant.

Effects of Intranasal Azelastine on the Response to Nasal Allergen Challenge

Objectives/Hypothesis Azelastine, a second‐generation H1‐receptor antagonist, is available for topical administration. The aim of the study was to evaluate the effects of topical intranasal azelastine on the early‐phase and the late‐phase allergic responses and on nasal hyper‐responsiveness to methacholine.

Elucidating the mechanism underlying the ocular symptoms associated with allergic rhinitis.

Ocular symptoms occur in approximately 40% of patients with allergic rhinitis. The purpose of this study was to determine whether nasal challenge with antigen induces a nasal-ocular reflex. We performed a double-blind crossover trial in 20 subjects. A nasal challenge with antigen was performed in one nostril, and the response was assessed in both nostrils and both eyes. Subjects were treated before challenge with either placebo or azelastine, an H(1)-antihistamine. Nasal challenge with antigen led to a nasonasal reflex and a nasal-ocular reflex as manifested by an increase in symptoms and secretion weights. Treatment with azelastine reduced both reflexes. A nasal-ocular reflex follows nasal challenge with antigen and probably contributes to the ocular symptoms associated with allergic rhinitis.

Effect of the addition of montelukast to fluticasone propionate for the treatment of perennial allergic rhinitis.

BACKGROUND Guidelines for the treatment of patients with allergic rhinitis (AR) recommend intranasal corticosteroids as first-line therapy. In clinical trials, however, only 50% of patients obtain excellent symptom control. OBJECTIVE To evaluate the effectiveness of montelukast add-on therapy in patients with perennial AR (PAR) who have incomplete relief of symptoms after 2 weeks of treatment with intranasal fluticasone propionate. METHODS We performed a 4-week parallel, randomized, double-blind, placebo-controlled trial. One hundred two patients with a history of PAR and a positive skin test reaction to perennial allergens were recruited. They completed the Rhinitis Quality of Life Questionnaire (RQLQ) and were given intranasal fluticasone propionate, 200 microg daily. They were asked to complete symptom diary cards twice daily. After 2 weeks of treatment, patients with a mean total nasal symptom score of at least 4 during the past week (n = 54) were randomized to receive either montelukast (n = 28) or placebo (n = 26) in addition to the continued use of fluticasone propionate. At weeks 3 and 4, the RQLQ was completed again and symptom diary cards were collected. RESULTS Compared with baseline, there were significant improvements in almost all domains of the RQLQ while taking fluticasone propionate (P < .001). A similar trend was observed for nasal symptom scores. After randomization to receive montelukast or placebo, there were no significant differences in RQLQ measures or nasal symptom scores between the groups during the 2 weeks of combination therapy. CONCLUSION The addition of montelukast to an intranasal corticosteroid for the treatment of PAR with residual symptoms is no more effective than is placebo.

Low Dose Clemastine Inhibits Sneezing and Rhinorrhea During the Early Nasal Allergic Reaction

BACKGROUND Clemastine (1 mg) is currently available over-the-counter for the treatment of allergic rhinitis. OBJECTIVE To evaluate the efficacy of half the standard dose of clemastine (0.5 mg) in inhibiting the nasal response to allergen and the cutaneous response to histamine. METHODS Double-blind, placebo-controlled, crossover study of 20 allergic subjects out of season. The subjects received placebo or clemastine administered one, four, and six hours before the challenges. Filter paper discs were used both to challenge the nasal mucosa with diluent and allergen and collect generated secretions. Sneezes, secretion weights, nasal and ocular symptoms, and albumin levels in nasal secretions were monitored for the nasal challenge. Intradermal skin testing was performed with diluent followed by histamine and the wheal and flare reactions were measured. RESULTS There was a significant reduction in the number of sneezes after clemastine administered one, four, and six hours prior to challenge compared with placebo (P < .01). Clemastine administered four and six hours before challenge reduced sneezing significantly more than clemastine administered one hour before challenge (P < .05). Antigen-induced increases in secretion weights and symptoms of rhinorrhea were significantly reduced compared with placebo only when clemastine was administered four and six hours prior to challenge (P < .05). Pretreatment with clemastine had no significant inhibitory effects on other nasal symptoms or on albumin levels in nasal secretions, an objective index of increased vascular permeability. Pretreatment with clemastine did not inhibit the histamine-induced wheal skin reaction but showed a tendency, when administered six hours prior to the intradermal challenge, to reduce the flare reaction induced by the lowest dose of histamine (P = .05). CONCLUSIONS The data show that clemastine, given at half the usual dose four and six hours prior to allergen challenge, provides relief for sneezing and rhinorrhea and suggests that this dose might be useful in the treatment of allergic rhinitis.

Evidence of Maxillary Sinus Inflammation in Seasonal Allergic Rhinitis

Objective. Allergic rhinitis has been frequently associated with both acute and chronic sinusitis. Previous studies have shown an influx of eosinophils into the maxillary sinus after nasal challenge with allergen. The objective of this study was to determine, in humans, if the development of seasonal allergic inflammation, secondary to natural allergen exposure, leads to similar inflammation within the maxillary sinus. Study Design. Prospective, longitudinal study. Setting. Academic medical center and research laboratory. Subjects and Methods. Eighteen subjects were evaluated in and out of the ragweed allergy season using subjective measures (nasal symptoms, quality of life), nasal secretory response to methacholine challenge, and evaluation of biomarkers in nasal and sinus lavages. Results. The subjects became symptomatic during the season and reported worse quality of life and increased nasal reactivity to methacholine. The total number of eosinophils obtained by nasal lavage during the season (median= 35,691) was significantly higher compared with out of season (median = 2811, P ≤ .02). Similarly, there were significantly more eosinophils, albeit to a lesser magnitude, in the maxillary sinus during the season (median = 4248) compared with the out-of-season samples (median = 370, P ≤ .02). Conclusion. The authors provide evidence that natural exposure to pollen during an individual’s allergy season leads to both nasal and sinus inflammation, strengthening the association between allergic rhinitis and sinusitis. The mechanism of this inflammatory response needs to be elucidated.