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1.
We studied topical ocular administration of a 4% solution of cromolyn sodium (CS)for treatment of 112 patients with ragweed conjunctivitis in two 8-wk, double-blind, matched-pair studies. During the 1977 and 1978 ragweed seasons, patients instilled a daily total of 12.8 or 19.2 mg CS into each eye, control patients received placebo drops. Treatment efficacy was assessed by daily symptom score diaries, ophthalmic examinations, and a subjective report by the patient at the end of the trials. In the 1977 trial, CS pair members whose preseasonal immunoglobulin E antibody level was <99 ng/ml showed a significant reduction in eye itching (p < 0.01), eye irritation (p < 0.02), visual blurring (p < 0.025), and nasal congestion (p < 0.025) and required less supplemental medication (p < 0.02) during the peak pollen period. In the 1978 trial all patients had IgE antibody levels >100 ng/ml. CS pair members showed a significant reduction in rhinorrhea (p < 0.004) and nasal congestion (p < 0.007) only; no significant reduction in eye symptoms was noted. Transient eye burning was noted by a total of 38 CS and 39 placebo patients from both studies; ophthalmic examinations were unremarkable; and no other side effects were noted. The 4% CS ophthalmic solution provided significant relief of nasal symptoms in both the 1977 and 1978 trials, but significant relief of ocular symptoms was noted only in the 1977 trial and only in those patients with lower preseasonal IgE ragweed antibody levels.  相似文献   

2.
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.  相似文献   

3.
L. C. Laursen    P. Faurschou  E. P. Munch 《Allergy》1988,43(6):420-424
A double-blind, double-dummy comparative study was made of 30 adult birch pollen-allergic outpatients with seasonal rhinoconjunctivitis. They were treated with either topically applied beclomethasone dipropionate 100 micrograms in each nostril twice daily for 4 weeks, placebo, or an injection of 2 ml of a suspension containing 5 mg betamethasone dipropionate and 2 mg betamethasone disodium phosphate per ml (Diprospan) immediately prior to the birch pollen season. Placebo- and topical steroid-treated patients experienced an increase in rhinoconjunctivitis symptoms, i.e. nasal blockage, nasal itching, rhinorrhea, sneezing and eye symptoms, and placebo-treated patients used significantly more antihistamine tablets during the pollen season. Diprospan-treated patients experienced fewer symptoms on all measured parameters. We concluded that one injection of Diprospan immediately prior to the birch pollen season produces significantly fewer rhinoconjunctivitis symptoms than does placebo and topical steroid treatment.  相似文献   

4.
In a double-blind trial thirty-five patients with moderately-severe nasal polyposis were treated with intranasal beclomethasone dipropionate aerosol for 3 weeks. The dose given (400 γg/day) had only local effect on the symptoms. Judged by diary card scores the nasal symptoms were reduced to 52% of the pre-trial level for the whole group. Corrected for the placebo effect the percentage was 68. The reduction of symptoms was equally apportioned to the three symptoms, sneezing, nasal secretion and blockage. The treatment was tolerated well, and it is concluded that intranasal treatment with beclomethasone dipropionate aerosol offers most patients with nasal polyps a good response without any risk of systemic steroid side-effects.  相似文献   

5.
The aim of this study was to evaluate the effect of levocabastine, a new H1-blocking antihistamine for topical use, in comparison with sodium cromoglycate on conjunctival symptoms of birch pollinosis. The two drugs were compared in a randomized double-blind comparative study over 5 weeks in 37 children and adolescents (6-19 years of age) with birch pollen conjunctivitis. Nasal symptoms occurred in 31 of the children and were treated with beclomethasone dipropionate nasal spray. An oral antihistamine was offered as rescue medication for eye symptoms. Initially, the patients received placebo four times a day for a 7-day run-in period. Conjunctival symptoms were recorded daily on diary cards on a 100 mm visual analogue scale. The pollen counts indicated a short but intensive birch pollen season. There was no statistically significant difference between the two treatment groups with regard to eye symptom scores before and during active treatment. However, the patients' evaluation of the efficacy of the therapy was in favour of levocabastine (P less than 0.01). Topical levocabastine, an H1-blocker, applied twice daily, seems to protect from symptoms of allergic conjunctivities as favourably as sodium cromoglycate applied four times a day. There was no difference in number or character of reported adverse reactions between the two treatment groups.  相似文献   

6.
Nasal resistance to air flow has been used to evaluate the effect of beclomethasone dipropionate aerosol on allergen induced nasal stenosis. Sixteen patients with allergic-rhinitis due to pollen were investigated in a randomized double-blind cross-over study with beclomethasone dipropionate aerosol and placebo aerosol. Only patients reacting to challenge were chosen. The study was carried out in the pollen-free season. After I week on either active or placebo aerosol a basic resistance value was determined followed by allergen challenge. Nasal resistance was determined 15 min and 7 hr after challenge. The aerosols were changed and after another week the procedure was repeated. There was significant preference (P<0.01) for beclomethasone dipropionate aerosol.  相似文献   

7.
In a controlled, double-blind study 20 children and adults, suffering from summer hay fever, were treated intranasally with a daily dose of 200 μg, 300 μg or 400 μg beclomethasone dipropionate (Beconase®, Becotide Nasal®) or with placebo for 2 weeks during the hay fever season. No beneficial effect of the placebo treatment was observed. In patients treated with 200 μg and 300 μg beclomethasone dipropionate a day there was a moderate decrease in nasal symptom scores and in use of antihistamine tablets. As the results indicated 400 μg a day to have the most pronounced effect on nasal symptoms, this dosage is recommended for children as well as adults suffering from summer hay fever.  相似文献   

8.
Fluticasone propionate is a new glucocorticosteroid with potent topical activity. In a double-blind, randomized, parallel-group study, 423 adult patients with moderate to severe seasonal allergic rhinitis received placebo or fluticasone propionate aqueous nasal spray at doses of 25, 100, or 400 micrograms twice daily (b.i.d.) for 2 weeks. Efficacy was evaluated by nasal symptom scores, nasal airflow, nasal cytology, and global evaluation. All doses of fluticasone propionate were significantly better than placebo in reducing symptoms of seasonal allergic rhinitis. Patients receiving the largest dose of fluticasone propionate (400 micrograms b.i.d.) had a slightly greater reduction (not significant) in symptom scores than patients receiving the smallest dose (25 micrograms b.i.d.). Symptom improvement was evident within 3 days of treatment. Nasal airflow improved in the groups treated with fluticasone propionate, 100 and 400 micrograms b.i.d. Examination of nasal cytograms revealed a striking decrease in both eosinophils and basophils in all three groups receiving active treatment compared with placebo. There were few adverse events and no treatment-related abnormalities in laboratory assays or evaluations of hypothalamo-pituitary-adrenocortical axis function. Comparison of treatment groups indicated that fluticasone propionate aqueous nasal spray was as safe as placebo at the doses studied.  相似文献   

9.
BACKGROUND: Unlike many antihistamines, desloratadine can reduce nasal congestion in patients with seasonal allergic rhinitis (SAR). OBJECTIVE: We compared the effects of 5 mg of desloratadine and placebo on nasal airflow and SAR symptoms, including nasal congestion, in response to grass pollen in an allergen-exposure unit. METHODS: In a randomized, double-blind, placebo-controlled, crossover trial, 47 subjects with histories of SAR received desloratadine or placebo every morning for 7 days and, after a 10-day washout period, were crossed over to the other treatment arm for 7 days. Subjects underwent a 6-hour allergen exposure on day 7 of each treatment period. Nasal airflow and nasal secretion weights were measured before and every 30 minutes during allergen exposure; SAR symptoms (including nasal congestion) were scored before exposure and every 15 minutes thereafter. RESULTS: Nasal obstruction, as measured by nasal airflow, was less severe with desloratadine than with placebo (P <.02). Individual and combined SAR symptom severity scores, including nasal congestion and sneezing, were significantly lower with desloratadine than with placebo (all P < or =.003). Within 30 minutes of allergen exposure, less severely decreased nasal airflow (P <.02), less nasal secretions (P <.001), and less severe symptoms, including nasal congestion (P <.002), rhinorrhea, and sneezing, occurred with desloratadine compared with placebo, and this continued throughout (0-6 hours) allergen exposure. Desloratadine was well tolerated, with an adverse event profile similar to that of placebo. CONCLUSION: In subjects with allergen-induced SAR symptoms, desloratadine significantly reduced the severity of nasal obstruction and accompanying complaints of nasal congestion and other SAR symptoms compared with the effects of placebo.  相似文献   

10.
Specific immunotherapy is effective in grass pollen allergy with standardized extracts and formalinized allergoids; but systemic reactions are not uncommon. A high-molecular-weight (greater than 85,000 daltons), formalinized allergoid was investigated in a double-blind, placebo-controlled study to assess its safety and efficacy. Twenty patients received a placebo and 39 the allergoid using a rather aggressive protocol. Five patients developed a mild and transient systemic reaction with high doses of allergoid and one had a more severe reaction requiring treatment. Nasal challenges performed with orchard grass pollen grains showed that the threshold number of grains eliciting nasal symptoms was significantly (p less than 0.01) greater in the treated group. This group had significantly (p less than 0.01) less nasal symptoms during the season and specific IgG levels were significantly (p less than 0.01) elevated. There was a significant (p less than 0.01) correlation between nasal challenges and nasal symptoms during the season but no correlation between IgG and symptoms. There was no dose-dependent effect of allergoids.  相似文献   

11.
Background: Antihistamines have been shown to have a variety of therapeutic effects in asthma. Although nasal obstruction may play an important role in modulating lower airway function, no prior trial has used a decongestant in combination with an antihistamine in patients with allergic rhinitis and concomitant asthma.Objective: We sought to determine the efficacy and safety of loratadine (5 mg) plus pseudoephedrine (120 mg) (L/P) twice daily in patients with seasonal allergic rhinitis and mild asthma.Methods: We conducted a randomized, double-blind, placebo-controlled trial of L/P in 193 subjects during the fall allergy season. Nasal and chest symptoms, albuterol use, and peak expiratory flow rates were recorded daily for 6 weeks. Spirometry was measured at baseline and after 1, 2, 4, and 6 weeks of therapy, and health-related quality of life was rated at the beginning and end of the study.Results: Total rhinitis and asthma symptom severity scores were significantly reduced in patients receiving active therapy compared with those receiving placebo throughout the 6-week study. Peak expiratory flow rates improved significantly in patients treated with L/P during weeks 2 through 6 (peak effect [mean ± SEM]: L/P, 26.23 ± 4.64 L/min vs placebo, 8.52 ± 3.53 L/min, p = 0.002) as did FEV1 (peak effect [mean ± SEM]: L/P, 170 ± 53 ml vs placebo, 20 ± 40 ml, p = 0.01) at all clinic visits. In addition, select measures of asthma-specific quality of life improved significantly relative to placebo.Conclusions: L/P significantly improved nasal and asthma symptoms, pulmonary function, and quality of life in patients with seasonal allergic rhinitis and concomitant mild asthma. (J Allergy Clin Immunol 1997;100:781-8)  相似文献   

12.
Nineteen patients with perennial rhinitis were studied in a double blind crossover trial of 8 weeks duration using a 2% solution of sodium cromoglycate and placebo. Nasal smears, blood counts and serum IgE levels were carried out to determine whether any changes occurred with either the active or placebo formulations. Clinically, thirteen patients were greatly improved with the active solution, four showed no change and two became worse. Eosinophils in the nasal secretions were generally reduced during the administration of active solution but remained unchanged with the placebo.  相似文献   

13.
Fluticasone propionate aqueous nasal spray (FPANS) contains fluticasone propionate, which is a new topically active glucocorticoid with approximately twice the potency of beclomethasone dipropionate. In this European multicentre study, 143 children with seasonal allergic rhinitis were recruited: 47 received FPANS 100 jag once a day (od), 46 received FPANS 200 μg od, and 50 patients received placebo od, for 4 weeks. Treatment efficacy was assessed using diary card nasal symptom scores for sneezing, rhinorrhoea, blockage and itching, and eye watering/irritation. Patients receiving FPANS 100 μg or FPANS 200 μg demonstrated statistically significant improvements in median nasal symptom scores in all the symptoms recorded, when compared with placebo. There were no statistically significant differences between the FPANS 100 μg and FPANS 200 μg groups in improvement in nasal symptom scores. There was no effect on eye watering/irritation symptoms which could be attributed to either FPANS 100 μg or FPANS 200 μg when compared with placebo. Use of rescue antihistamine medication was significantly reduced in the FPANS 100 μg group when compared with placebo. The adverse events profile was similar in all three treatment groups, and the events reported were generally mild and related to the patients' rhinitis.  相似文献   

14.
BACKGROUND: Azelastine hydrochloride is an H1-receptor antagonist with antiinflammatory properties that is available in the US as Astelin Nasal Spray for the treatment of seasonal allergic rhinitis. The symptoms of seasonal allergic rhinitis can initially be treated with monotherapy using either an antihistamine or an intranasal corticosteroid. Patients whose symptoms do not respond adequately are often prescribed a combination of both an antihistamine and an intranasal corticosteroid. OBJECTIVE: Three multicenter, randomized, double-blind studies were conducted to determine whether patients with moderate-to-severe symptoms of seasonal allergic rhinitis who had responded inadequately to monotherapy with either an oral antihistamine or an intranasal corticosteroid, and who were candidates for combination therapy with both an oral antihistamine and an intranasal corticosteroid, could be effectively treated with azelastine nasal spray monotherapy. METHODS: Following a 1- to 2-week washout period, patients were randomized to 7 days of double-blind treatment with either azelastine nasal spray (2 sprays per nostril bid, 1.1 mg/day) monotherapy or combination therapy with oral loratadine (Claritin, one 10-mg tablet/day) plus intranasal beclomethasone dipropionate monohydrate (Beconase AQ, 2 sprays per nostril bid, 336 microg/day). Efficacy was determined at the end of the study by both a physician assessment of the need for additional anti-rhinitis medication and a patient global evaluation of therapeutic effectiveness. The three studies were conducted at 71 investigational sites during the 1998 spring allergy season. Three separate studies were conducted to verify the reproducibility of the new study design. RESULTS: In all three studies a total of 1,070 patients were randomized to double-blind treatment. There were no statistically significant differences in the percentage of patients treated with azelastine nasal spray versus patients treated with a combination of loratadine tablets and beclomethasone nasal spray who did not require additional anti-rhinitis medication (32% to 45% and 39% to 46%, respectively). The patient global evaluation indicated that 77% to 84% of the patients treated with azelastine nasal spray had symptomatic improvement and 85% to 90% of the patients treated with loratadine tablets and beclomethasone nasal spray had symptomatic improvement. The most commonly reported adverse experience with azelastine nasal spray was a transient aftertaste (8%), while the most commonly reported adverse experience with loratadine tablets and beclomethasone nasal spray in combination was headache (6%). CONCLUSIONS: Based on the percentage of patients not requiring additional antirhinitis medication and the patient assessment of efficacy, azelastine nasal spray monotherapy was as effective as the combination of oral loratadine plus intranasal beclomethasone in treating moderate-to-severe symptoms of seasonal allergic rhinitis.  相似文献   

15.
This international, multicentre, randomized, double-blind, double-dummy, parallel-group trial was undertaken to compare the efficacy and tolerability of once-daily astemizole-D (10mg astemizole plus 240 mg pseudoephedrine) with beclomethasone nasal spray (0.05mg/ml) two puffs/nostril administered twice daily in a total of 204 patients with seasonal allergic rhinitis. Treatment duration was 4 weeks, Although investigator assessments of symptom severity were generally comparable in the two treatment groups throughout the trial, statistically significant differences in favour of astemizole-D for sneezing and ocular symptoms were apparent at the end of the 4-week treatment period (P < 0.05). Patient diary data support these findings, with significant differences in favour of the antihistamine/decongestant combination reported for ocular symptoms after 2 weeks of treatment (P < 0.05) and non-significant trends for sneezing after 2 weeks and ocular symptoms over the entire treatment period (P= 0.07). Use of rescue medication for ocular symptoms was also significantly lower in the astemizole-D treatment group (P < 0.05). A wide range of adverse experiences were reported, however, there were no statistically significant differences in the type or incidence of those between the two treatment groups. In conclusion, astemizole-D appears to be at least as effective and well tolerated as intranasal beclomethasone in the treatment of seasonal allergic rhinitis, providing at least comparable relief from all nasal symptoms including congestion and significantly greater relief from ocular symptoms than the topical steroid.  相似文献   

16.
The currently available beclomethasone dipropionate (BDP) metered-dose nasal aerosol spray is considered uncomfortable by some patients because of the force of delivery. It was compared for efficacy and acceptability in a double-blind study with a new aqueous suspension BDP spray for the treatment of seasonal allergic rhinitis in 44 symptomatic patients aged 12 to 43 years. After 7 days of baseline evaluation, every patient was given both an aerosol canister and an aqueous spray bottle each containing either BDP, 42 mcg per spray, or placebo (P). For 15 days the patient sprayed each nostril twice a day with one spray of suspension (BDP or P) followed 5 minutes later by one spray of aerosol (P or BDP). Patients were evaluated before the study medications were started (day 1) and on days 4, 8, and 15 for nasal and eye symptoms. Nasal cytologic specimens were examined on days 1 and 15, and rhinomanometry was performed on days 1, 8, and 15 of the study. Topical BDP by both methods of delivery was rapidly effective in decreasing mean nasal obstruction, rhinorrhea, sneezing, and itching symptoms as well as mean eye symptoms with no statistically significant differences between them. Nasal airflow increased with both treatments; rhinomanometry significantly correlated with subjective nasal obstruction scores. Of 34 patients with nasal eosinophils, 74% had fewer eosinophils after treatment. Most patients (84%) preferred the aqueous spray over the pressurized aerosol.  相似文献   

17.
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.  相似文献   

18.
D. Wang  F. Duyck  J. Smitz  P. Clement 《Allergy》1998,53(4):375-382
We studied the effect and onset of action of fluticasone propionate aqueous nasal spray (FPANS) on mediator release and eosinophil accumulation in nasal secretions and on nasal symptoms of patients with seasonal allergic rhinitis after nasal allergen challenge (NAC). At the end of the pollen season, 28 patients were randomized in a double-blind and crossover design to receive 7 days' treatment with FPANS (200 μg, once daily) and matching placebo. NACs were performed before and at 6 h and 1. 2. 3. and 7 days during treatment with FPANS or placebo. Nasal secretions were collected for a quantitative determination of mediators and eosinophil count before and 5 min after each challenge. Nasal symptoms were assessed by scales grading the severity of symptoms at the same time. Results showed that for mediator concentrations there was a significant decrease of leukotriene C4 (P<0.001) at 7 days after the first administration of FPANS as compared to placebo. Two days after FPANS. both eosinophil counts and eosinophil cationic protein (ECP) concentrations were lower than those of placebo (eosinophils; f=0.032; ECP; F=0.038). The onset became even more important at day 7 (eosinophils; P=0.001; ECP; P=0.009) during the FPANS treatment period. For the subjective nasal symptoms, a significant reduction of symptom scores for nasal obstruction occurred also at day 3 (F=0.017) and for sneezing at day 7 (f=0.003). There was not yet any significant improvement of the objective nasal airway resistance after the different NACs during the study period. In conclusion, this study demonstrated that topical fluticasone propionate is effective in the treatment of mucosal inflammation induced by NAC. For optimal control of nasal symptoms induced by repeated maximal allergen challenges, a treatment period of more than 1 week is required.  相似文献   

19.
BACKGROUND: Allergic rhinitis (AR) is considered a major predisposing factor for the development of acute bacterial rhinosinusitis. How AR augments a bacterial infection is unknown. OBJECTIVE: Our purpose in this study was to test whether an H1 receptor antagonist, desloratadine, could reduce the augmented effect of an ongoing allergic reaction on acute bacterial rhinosinusitis. METHODS: Three groups of infected and ovalbumin (OVA)-sensitized mice were studied: (1) infected and allergic mice treated with desloratadine, (2) infected and allergic mice treated with placebo, and (3) infected mice. A fourth group of uninfected, non-sensitized mice served as a control for the cellular changes. BALB/c mice were sensitized by two intraperitoneal injections of OVA given 8 days apart. One day after the second injection, the mice were nasally exposed daily to 6% OVA (the groups treated with desloratadine or placebo) or phosphate-buffered saline (PBS) (the infection-only group) for 5 days. After the second OVA exposure, the mice were intranasally inoculated with Streptococcus pneumoniae. Desloratadine or placebo was given daily throughout the OVA exposure period. Nasal allergic symptoms were observed by counting of nasal rubbing and sneezing for 10 min after OVA or PBS nasal challenge. On day 5 post-infection, nasal lavage culture was done, and the inflammatory cells in the sinuses were evaluated by flow cytometry. RESULTS: Mice that were made allergic, infected, and treated with placebo showed more organisms and phagocytes than did only infect mice. They also manifested allergic nasal symptoms and eosinophil influx into the sinuses. Desloratadine treatment during allergen exposure reduced allergic symptoms and reduced sinonasal infection (P<0.05). There tended to be less myeloid cell and neutrophil influx (P=0.09 both), but not eosinophil influx (P=0.85) compared with that in the placebo-treated group. CONCLUSION: Desloratadine treatment during nasal challenge inhibited allergic symptoms and reduced sinonasal infection, suggesting that histamine via an H1 receptor plays a role in the augmented infection in mice with an ongoing allergic reaction.  相似文献   

20.
P. Salomonsson    L. Gottberg    H. Heilborn    K. Norrlind    K.-O. Pegelow 《Allergy》1988,43(3):214-218
The efficacy and side effects of the oral H1-antihistamine, astemizole, were compared with those of nasal beclomethasone in 158 adult birch-pollen allergic hay fever patients. 148 patients completed the 5-week, controlled trial which took place in Stockholm, May 1986, during the birch pollen season. Daily pollen counts were found to be at a rather low level throughout the study period. The effect and tolerability of both drugs were found to be excellent, although beclomethasone reduced nasal symptoms (sneezing, rhinorrhoea, blocked nose) significantly more effectively than astemizole. Eye symptoms were mild and equal in both groups. The results indicate that oral astemizole is an effective non-sedating antihistamine, though less so than nasal beclomethasone, in the treatment of nasal hay fever symptoms.  相似文献   

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