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Superiority of an Intranasal Corticosteroid Compared With an Oral Antihistamine in the As-Needed Treatment of Seasonal Allergic Rhinitis
Scott M. Kaszuba, MD;
Fuad M. Baroody, MD;
Marcy deTineo, BSN;
Lauran Haney, BSc;
Christopher Blair, BSc;
Robert M. Naclerio, MD
Arch Intern Med. 2001;161:2581-2587.
ABSTRACT
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Background The daily use of either intranasal corticosteroids or histamine1 (H1) receptor antagonists has proved to be efficacious
in the treatment of seasonal allergic rhinitis. Most patients, however, use
these medications as needed. Our objective was to compare the effectiveness
of as-needed use of H1 receptor antagonists with that of intranasal
corticosteroids in the treatment of seasonal allergic rhinitis.
Methods We performed a randomized, open-label, parallel-group study comparing
the as-needed use of an H1 receptor antagonist (loratadine) with
that of an intranasal corticosteroid (fluticasone propionate) in the management
of fall seasonal allergic rhinitis in the fall of 1999. Subjects kept a diary
of their daily symptoms and were examined at enrollment into the study and
biweekly for 4 weeks during treatment. Outcome measures were the Rhinoconjunctivitis
Quality of Life Questionnaire score, daily symptom diary scores, and the number
of eosinophils and the levels of eosinophilic cationic protein in nasal lavage
samples.
Results Patients in the fluticasone-treated group reported significantly better
scores in the activity, sleep, practical, nasal, and overall domains (P<.05) of the Rhinoconjunctivitis Quality of Life Questionnaire.
The median total symptom score in the fluticasone-treated group was significantly
lower than that in the loratadine-treated group (4.0 vs 7.0; P<.01). After treatment, the number of eosinophils was significantly
smaller in the fluticasone-treated group compared with the loratadine-treated
group (P = .001). Eosinophilic cationic protein levels
followed the same pattern, with a significant correlation between the levels
of eosinophilic cationic protein and the number of eosinophils (rs = 0.70, P<.01).
Conclusion As-needed intranasal corticosteroids reduce allergic inflammation and
are more effective than as-needed H1 receptor antagonists in the
treatment of seasonal allergic rhinitis.
INTRODUCTION
ALLERGIC RHINITIS affects about 20% of the US population, sparing no
age group.1 It has a negative impact on the
quality of life, and billions of dollars are spent annually on the treatment
of this disease and its associated conditions. Furthermore, its incidence
is increasing, and this will increase health care expenditures.2
The treatment of this common ailment, therefore, is increasingly being subjected
to guidelines, some of which are evidence based.3-4
The typical guidelines recommend the use of histamine1 (H1) receptor antagonists as the first-line treatment of mild disease,
whereas more severe disease is usually treated with daily intranasal corticosteroids.3-4 The rationale for these recommendations
is that H1 receptor antagonists have a rapid onset of action (within
hours) and are, thus, suitable for as-needed treatment when the patient is
seeking immediate relief of symptoms. Fluticasone propionate nasal spray (Flonase),
an intranasal corticosteroid, has an onset of action within 12 hours and a
peak effect that occurs after several days.5
We questioned the logic of these guidelines based on our understanding of
the pathophysiological features of seasonal allergic rhinitis.
Allergic individuals challenged with an appropriate allergen in the
laboratory react within minutes with an early response, characterized by mast
cell degranulation, histamine release, and typical symptoms of sneezing, rhinorrhea,
and congestion.1 This early response is followed
hours later by a cellular influx, including eosinophils, and an increase in
nasal reactivity to further antigen exposure, called priming. The late response,
with congestion as the primary symptom, is less dramatic than the early reaction.
Although histamine is increased during the late reaction, its role is not
clearly defined. Antihistamines have not been shown to reduce eosinophil influx
into the nasal mucosa, block priming, or reduce symptoms of the late reaction.6 In contrast, intranasal corticosteroids have profound
inhibitory effects on the late response.7
We reasoned that those allergic individuals who use medications as needed
would treat themselves after sensing an early reaction. Taking an antihistamine
at this point would not affect the symptoms of the immediate response, because
the symptoms dissipate within minutes and antihistamines do not affect the
late response. In essence, the antihistamine would be effective against the
sneezing and rhinorrhea associated with the next immediate response to antigen
exposure, provided the drug is present at therapeutic levels at that time.
The effectiveness of antihistamines when given before a nasal challenge with
antigen has been shown repeatedly.8 The antihistamine,
however, would not prevent allergic inflammation and priming from developing.
Thus, as the season progressed, the immediate symptoms in response to further
antigen exposure would increase.
An intranasal corticosteroid, taken after sensing the symptoms of an
immediate response, would be expected to block eosinophil infiltration and
priming, as Anderson and colleagues7 demonstrated
in the laboratory. The intranasal corticosteroid would also be expected to
reduce any contribution of the symptoms of the late reaction to clinical disease,
such as congestion. We also speculated that, as the season progresses, priming
would not occur, and the symptoms experienced by patients on repeated pollen
exposure would be less severe and last for a shorter interval as the pollen
counts dissipated. Therefore, we hypothesized that the as-needed use of intranasal
corticosteroids would reduce allergic inflammation and provide superior symptom
relief compared with the as-needed use of an antihistamine.
As a first step toward testing the stated hypothesis, a parallel, placebo-controlled,
randomized study9 to test whether symptoms
of patients with seasonal allergic rhinitis are reduced by treatment with
as-needed intranasal corticosteroids vs placebo was performed. The results
of that study showed that the as-needed use of an intranasal corticosteroid
(fluticasone) was superior to placebo in reducing eosinophil infiltration
and symptoms while improving the quality of life during the ragweed allergy
season.
SUBJECTS AND METHODS
STUDY DESIGN
We performed a randomized, open-label, parallel-group study. We recruited
88 individuals with fall seasonal allergic rhinitis who were older than 18
years. All subjects had a history of rhinitis during at least the last 2 ragweed
seasons in Chicago, Ill, and a positive puncture skin test result to ragweed
antigen extract. The subjects were in good health except for a few who had
mild asthma. Patients were excluded if they had symptoms or physical signs
suggestive of renal, hepatic, or cardiovascular disease; nasal polyps; a displaced
septum; or perennial rhinitis. Furthermore, patients who had used topical
or systemic corticosteroids, antihistamines, decongestants, or cromolyn sodium
in the preceding 2 weeks or who underwent immunotherapy in the past 2 years
were excluded. Pregnant or lactating women were not permitted to join the
study. Enrollment occurred before and during the ragweed pollen season. Written
informed consent was obtained from all participants, and the Institutional
Review Board of the University of Chicago, Chicago, approved the study.
During their first visit to the nasal physiology laboratory, patients
completed the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), which
is a validated quality-of-life measure for patients with allergic rhinitis.10 Subjects also had their nose lavaged with 10 mL of
lactated Ringer solution. We used the lavage sample to obtain a total eosinophil
count and to measure the level of eosinophil cationic protein (ECP). Each
subject was given either treatment and instructed in its use. Patients who
enrolled before August 15th were instructed not to begin treatment or begin
their diaries until that date. Fluticasone aqueous nasal spray (Flonase),
an intranasal corticosteroid, and loratadine (Claritin), an H1
receptor antagonist, were chosen because they are the market leaders in their
respective categories.
The subjects were randomized in balanced blocks of 4 to receive fluticasone
propionate nasal spray (100 µg/d per nostril) or a loratadine tablet
(10 mg/d) as needed for 4 weeks during the ragweed season. If the patients
had bothersome nasal symptoms, they were instructed to use two 50-µg
sprays in each nostril in the fluticasone-treated group or to take 1 tablet
(10 mg) in the loratadine-treated group, not more frequently than once a day.
If the patients continued to have significant problems, they were asked to
see one of the participating physicians (F.M.B. or R.M.N.). No rescue medications
were allowed. Patients kept a daily symptom and medication diary during the
season in which they recorded the severity, over 12 hours, of episodes of
sneezing, rhinorrhea, itchy eyes, and nasal congestion and medication use.
The subjects returned in another 2 weeks and underwent a nasal lavage and
completed the RQLQ. Diaries were collected and new ones issued. The patients
continued in the study and returned in 2 weeks for a final visit, in which
the nose was lavaged, an RQLQ was completed, and medications and diary cards
were collected.
POLLEN COUNTS
Ragweed pollen counts for the Chicago area during the study were recorded
by the Grant Hospital Pulmonary Physiology Laboratory by use of the Rotorod
method.
NASAL LAVAGE SAMPLES
Five milliliters of warmed (37°C) lactated Ringer solution was instilled
into each nostril and, after 10 seconds, the subjects expelled the lavage
fluid into a plastic collection vessel. All samples were first vigorously
shaken for homogenization of the mixture of sol and gel phases and were stored
on ice in plastic tubes until cell counts were performed. After the total
cell count was obtained, the samples were centrifuged at 5000g for 15 minutes at 4°C. Aliquots for ECP determination were stored
at -20°C until assayed.
EOSINOPHIL QUANTIFICATION IN NASAL LAVAGE FLUIDS
Total counts of eosinophils recovered from lavage samples were performed
by use of a modification of a previously described method.11
If sufficient cells were present on a slide, 200 cells were counted and a
differential count was obtained. When 200 cells could not be counted, as many
cells as possible were examined for differential determination. If the total
number of cells available for differential estimation was less than 50, the
slide was considered technically inadequate for interpretation, and no value
was available for analysis. If the slide had a sufficient number of cells
to be examined, but no eosinophils were counted among these cells, then 50
was assigned as the number of eosinophils because this was the lowest number
of eosinophils obtained among all the technically adequate specimens.
EOSINOPHILIC CATIONIC PROTEIN
Eosinophilic cationic protein, a marker of eosinophil secretion, was
measured by a commercially available double-antibody radioimmunoassay (Pharmacia
AB, Uppsala, Sweden). The assay has a sensitivity detection limit of 2 µg/L.
Values lower than the detection limit were arbitrarily assigned a value of
1 µg/L.
SYMPTOM DIARIES
Each subject recorded symptom scores in a diary twice daily. Subjects
reported itchy eyes and 3 symptoms for each nostril (rhinorrhea, nasal congestion,
and sneezing) on a scale from 0 to 3 (0 indicates no symptoms; 1, mild symptoms;
2, moderate symptoms; and 3, severe symptoms). Symptom scores were evaluated
separately for each symptom category, and the total symptom score (the sum
of individual symptoms) was also evaluated.
QUALITY-OF-LIFE ASSESSMENT
Quality of life was assessed with the self-administered RQLQ as described
and validated by Juniper and Guyatt.10 In brief,
the RQLQ has 7 domains: sleep, non–nasal/eye, practical, nasal, eye,
emotional, and activity. The average score for each domain was computed and
used for data analysis. The overall quality of life is determined as the average
of the 7 domains on the RQLQ. Higher scores indicate a worse quality of life.
STATISTICAL ANALYSIS
Because the data were not normally distributed, nonparametric statistics
were used for analysis. The primary variable analyzed was the RQLQ score.
The number of subjects to be enrolled was arrived at from a power calculation
based on the results of a previous study9 comparing
as-needed fluticasone with as-needed isotonic sodium chloride solution. We
chose the global score for the RQLQ as the primary variable because it had
the smallest SD. Because Juniper and Guyatt10
define a 0.5 shift as clinically significant in the RQLQ, we chose this level
of difference for our power calculation. Assuming a value of P<.05, a difference of 0.5 in the overall score, and a population
SD of 0.8, having 40 completed patients in each group would have 80% power
of detecting a difference. We assumed a 10% dropout rate.
The secondary variables were the symptom diary scores, ECP levels, total
eosinophil counts, and individual symptom scores. The median total daily symptom
scores were calculated by addition of the individual scores. The difference
between the intranasal corticosteroid– and the H1 receptor
antagonist–treated groups was analyzed for each day of the study by
a Mann-Whitney test. The median total symptom score for all 28 days of treatment
was also calculated and compared between the treatment groups by use of the
Mann-Whitney test. Other symptoms were analyzed similarly. When different
points within a group were analyzed, and if repeated measures were being considered
(eg, total eosinophils on 3 visits for the same treatment group), a Friedman
analysis of variance was first performed. If significant changes were detected,
a post hoc analysis was performed by use of the Wilcoxon signed rank test.
Data are presented as the median and range or the median with 25th and 75th
percentiles as error bars. Correlation was performed using the Spearman rank
test. A 2-tailed P<.05 was considered to indicate
significance.
RESULTS
The ragweed counts for the 1999 season were typical for the Chicago
area (Figure 1). The number of subjects
enrolled in the study on a particular day is superimposed on this figure.
Most subjects were recruited before or during the beginning of the season,
with all subjects being recruited before peak pollen counts occurred.
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Figure 1. Ragweed counts and number of subjects
enrolled for the duration of the study. The x-axis represents various days
during the ragweed season, and the y-axes represent the number of subjects
enrolled on each day (closed circles) and the ragweed counts on those days
(shaded area). Levels of ragweed less than 40 grains per cubic millimeter
are considered low.
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Eighty-eight subjects were enrolled into the study. There were 44 subjects
randomized to each arm of the study, and, because randomization was blocked
in groups of 4, the number of subjects enrolled at any point was divided equally
between intranasal corticosteroid and H1 receptor antagonist treatments.
The groups were matched for age, sex, race, and skin test sensitivity (Table 1). Two patients from each treatment
group dropped out before completing the protocol. One patient moved away from
Chicago, and 3 were noncompliant with respect to returning for their appointments.
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Table 1. Demographic Characteristics of the Study Population*
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During the 28 days in which subjects were allowed to take their medication,
the intranasal corticosteroid–treated group used medicine on 17.0 (3-28)
days, and the H1 receptor antagonist–treated group used medicine
on 18.0 (5-28) days. The correlation between symptoms and medication use for
each individual patient was rs = 0.34
(-0.44 to 0.82) for fluticasone and rs = 0.39 (-0.26 to 0.79) for loratadine. The overall correlation
for all subjects was rs = 0.41 (P<.001) in the fluticasone-treated group and rs = 0.46 (P<.001) in the loratadine-treated
group.
The RQLQ scores were similar between groups at enrollment into the study.
The intranasal corticosteroid–treated group had significant improvement
on the second and third visits in the activity, sleep, practical, nasal, and
overall domains (P<.05) (Figure 2). Eye symptoms were better in the intranasal corticosteroid–treated
group than in the loratadine-treated group during the second visit.
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Figure 2. The individual domains for the
Rhinoconjunctivitis Quality of Life Questionnaire (A, activity; B, sleep;
C, non–nasal/eye; D, practical; E, nasal; F, eye; G, emotional; and
H, overall). Median responses and 25th and 75th percentiles at each visit
are shown for the 2 treatment groups. The asterisk indicates P<.01 vs the loratadine-treated group; the dagger, P<.05 vs the loratadine-treated group.
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Total symptoms were similar at enrollment into the study. We analyzed
the score based on the day of enrollment, instead of the calendar day; this
permitted ease of matching. Significant differences between the intranasal
corticosteroid– and the H1 receptor antagonist–treated
groups in total symptom scores started to be evident after 5 days of enrollment
and remained significantly different at most points until the 28th day (Figure 3). The median score for the H1 receptor antagonist–treated group during the 28-day duration
of the study was 7.0, whereas the score for the intranasal corticosteroid–treated
group was 4.0, the difference being highly significant (P = .005). The results for the individual symptoms were similar, with
the intranasal corticosteroid–treated group reporting fewer symptoms
than the H1 receptor antagonist–treated group (Table 2).
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Table 2. Individual Nasal Symptoms*
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The number of eosinophils and the level of ECP were not different between
the groups at enrollment. The fluticasone-treated subjects had fewer eosinophils
during visit 3 compared with visit 1 (P = .001) and
during visit 2 compared with visit 1 (P = .005).
The data from the subjects receiving the H1 receptor antagonist
showed that the subjects in this group had an increase in eosinophils during
visit 3 compared with visit 1 (P = .02) and during
visit 2 compared with visit 1 (P = .002). When a
comparison of the number of total eosinophils was performed at each visit
between the 2 treatment groups, the group receiving fluticasone propionate
nasal spray had significantly fewer eosinophils during the second (P = .004) and third (P = .001) visits compared
with the H1 receptor antagonist–treated group (Figure 4). The ECP levels followed the same pattern, with significant
decreases in the intranasal corticosteroid–treated group and significant
increases in the H1 receptor antagonist–treated group (Figure 5). There was a significant correlation
between the levels of ECP and the number of eosinophils (rs = 0.70, P<.01).
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Figure 4. The median numbers of total eosinophils
in nasal lavage samples obtained at each of the 3 study visits are shown.
The asterisk indicates P<.03 vs visit 1; the dagger, P<.01 vs visit 1; and the double dagger, P<.01 vs the loratadine-treated group.
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Figure 5. The median levels of eosinophilic
cationic protein (ECP) in nasal lavage samples obtained at each of the 3 study
visits are shown. The asterisk indicates P = .003
vs visit 1; the dagger, P<.001 vs visit 1; and
the double dagger, P<.02 vs the loratadine-treated
group.
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COMMENT
Although instructed to use intranasal corticosteroids or antihistamines
daily, most patients are probably not compliant. The as-needed use of these
agents has been studied to a limited extent. Juniper and colleagues12 compared regular with as-needed use of intranasal
corticosteroids and found regular use to be superior. In a more recent study13 in which a quality-of-life questionnaire was used,
the differences between as-needed and regular use were statistically significant,
but the researchers found that the degree of improvement with regular use
was not clinically significant compared with as-needed use. Another previous
study9 showed that the as-needed use of intranasal
corticosteroids is more effective than placebo in the treatment of seasonal
allergic rhinitis. To our knowledge, the present study is the first to demonstrate
the superiority of as-needed intranasal corticosteroid use compared with as-needed
H1 receptor antagonist use.
We used multiple subjective and objective outcome variables to support
our conclusion. The difference in the RQLQ scores between the intranasal corticosteroid–
and H1 receptor antagonist–treated groups suggests not only
statistical differences but clinical significance as well.13
Furthermore, the subjects' responses were supported by the measures of eosinophil
counts and the ECP levels. These provide an objective measure and a pathophysiological
explanation for our results.
Whereas a double-blind double-dummy study might have been more elegant,
we doubt that the results would have differed. The lack of availability of
placebo loratadine tablets or data on the pharmacokinetics of the dissolution
of loratadine from opaque capsules precluded that approach. Thus, our study
was more like real life in that each subject was given a medication and instructed
in its use. Because patients knew after randomization which treatment they
were receiving, individual biases could have affected their responses. Our
impression, however, was that biases were equally likely to favor either treatment,
because both are heavily advertised directly to consumers. The consistency
of the results strengthens our observations. Also, the use of blindly assessed
objective measures reinforces our findings.
There was a low dropout rate in both groups and no difference between
them, even though we did not provide any rescue medication. The absence of
rescue medication in our study design made the analysis simpler and the results
more clear-cut.
We reasoned that patients would elect to take their medication after
the antigen caused symptoms. In essence, patients chose to medicate after
the immediate reaction and before eosinophil infiltration and changes in reactivity
occurred. Thus, as the season progressed, subjects receiving fluticasone propionate
nasal spray did not have an eosinophil infiltration or an increase in their
reactivity to antigen and, subsequently, had fewer symptoms and a better quality
of life on exposure to antigen. In contrast, the use of H1 receptor
antagonist did not block eosinophil infiltration and priming and, therefore,
the patients reported more symptoms and a worse quality of life as the season
progressed. The data we collected support this hypothesis.
The study supports the concept of the pathophysiological features of
allergic rhinitis as elucidated through nasal provocation studies. Our study
emphasizes the relative importance of the late reaction over the immediate
response in the contribution to symptoms during seasonal exposure.
Our study does not exclude the benefits of continuous intranasal corticosteroid
use. Researchers14-17
have shown that continuous use of intranasal corticosteroids offers additional
benefits, such as blockage of the early response and reductions of mast cell
migration to the epithelium, IgE synthesis, and the number of dendritic cells
in the nasal mucosa. These components of the allergic cascade could be responsible
for the superiority of regular vs as-needed use of intranasal corticosteroids.
Also, the regular use of corticosteroids could be responsible for increased
efficacy by providing a quantitatively superior inhibition of eosinophil influx
and the priming response related to the higher cumulative dose during regular
use.
There have been numerous clinical trials1
demonstrating the efficacy and success of H1 receptor antagonist
in the treatment of seasonal allergic rhinitis. However, in these studies,
H1 receptor antagonist were used continually and, thus, the medication
was in essence given prophylactically. When antihistamines are given in this
manner, our concept of the pathophysiological features of allergic rhinitis
would predict a benefit. Likewise, we would predict a benefit if H1
receptor antagonists were given before exposure, such as before going golfing
or visiting a friend with a pet, or during an environmental chamber antigen
exposure. However, we question the efficacy of intermittent use of H1 receptor antagonists when taken after exposure and the benefit of
this class when used in an as-needed fashion as rescue therapy in clinical
trials.
The major message from our study relates to guidelines for treating
seasonal allergic rhinitis. Our data support the efficacy of fluticasone propionate
nasal spray in the treatment of seasonal allergic rhinitis and the superiority
of its as-needed use compared with that of an as-needed H1 receptor
antagonist. Weiner and colleagues18 reached
a similar conclusion when they performed a meta-analysis comparing the regular
use of intranasal corticosteroids with that of H1 receptor antagonist.18 Thus, it would seem logical to use intranasal corticosteroids
as first-line treatment for seasonal allergic rhinitis. The medication would
be recommended for regular use in patients with severe disease and for as-needed
use in patients with mild disease. This recommendation is not the prescribing
trend, as suggested by the observation that H1 receptor antagonists
outsell intranasal corticosteroids 3 to 1. In addition, a 30-day supply of
nonsedating H1 receptor antagonists costs more than a 30-day supply
of intranasal corticosteroids.19 The reduced
cost and superior efficacy of either continuous or as-needed use of intranasal
corticosteroids compared with nonsedating H1 receptor antagonist
suggests that the cost-benefit ratio favors intranasal corticosteroids. A
change in guidelines would benefit more patients and reduce health care costs.
AUTHOR INFORMATION
Accepted for publication April 9, 2001.
This study was supported in part by a grant from Glaxo Wellcome Inc,
Research Triangle Park, NC; and grant AI 45583 from the National Institutes
of Health, Bethesda, Md.
Corresponding author and reprints: Robert M. Naclerio, MD, Section
of Otolaryngology–Head and Neck Surgery, University of Chicago, 5841
S Maryland Ave, Mail Code 1035, Chicago, IL 60637 (e-mail: rnacleri{at}surgery.bsd.uchicago.edu).
From the Section of Otolaryngology–Head and Neck Surgery, Department
of Surgery, The Pritzker School of Medicine, University of Chicago, Chicago,
Ill.
REFERENCES
| |
1. Naclerio RM, Solomon W. Rhinitis and inhalant allergens. JAMA. 1997;278:1842-1848.
FREE FULL TEXT
2. Evans R. Epidemiology and natural history of asthma, allergic rhinitis, and
atopic dermatitis. In: Middleton E Jr, Reed C, Ellis E, et al, eds. Allergy: Principles and Practice. 4th ed. St Louis, Mo: Mosby–Year
Book Inc; 1993:1109-1136.
3. Dykewicz MS, Fineman S, Skoner DP, et al for the American Academy of Allergy, Asthma, and Immunology. Diagnosis and management of rhinitis: complete guidelines of the Joint
Task Force on Practice Parameters in Allergy, Asthma and Immunology. Ann Allergy Asthma Immunol. 1998;81(pt 2):478-518.
4. van Cauwenberge P, Bachert C, Passalacqua G, et al for the European Academy of Allergology and Clinical Immunology. Consensus statement on the treatment of allergic rhinitis. Allergy. 2000;55:116-134.
FULL TEXT
|
ISI
| PUBMED
5. LaForce CF, Dockhorn RJ, Findlay SR, et al. Fluticasone propionate: an effective alternative treatment for seasonal
allergic rhinitis in adults and adolescents. J Fam Pract. 1994;38:145-152.
ISI
| PUBMED
6. Baroody FM, Lim MC, Proud D, Kagey-Sobotka A, Lichtenstein LM, Naclerio RM. The effects of loratadine and terfenadine on the induced nasal allergic
reaction. Arch Otolaryngol Head Neck Surg. 1996;122:309-316.
FREE FULL TEXT
7. Anderson M, Anderson P, Pipkorn U. Topical glucocorticosteroids and allergen-induced increase in nasal
reactivity: relationship between treatment time and inhibitory effect. J Allergy Clin Immunol. 1988;82:1019-1026.
FULL TEXT
|
ISI
| PUBMED
8. Naclerio RM, Baroody FM. H-1 receptor antagonists: antiallergic effects in vivo. In: Simons FER, ed. Histamine and H1-Receptor
Antagonists in Allergic Disease. New York, NY: Marcel Dekker Inc; 1996:145-174.
Kaliner MA, ed. Clinical Immunology and Allergy Series.
9. Jen A, Baroody F, deTineo M, Haney L, Blair C, Naclerio R. As-needed use of fluticasone propionate nasal spray reduces symptoms
of seasonal allergic rhinitis. J Allergy Clin Immunol. 2000;105:732-738.
FULL TEXT
|
ISI
| PUBMED
10. Juniper EF, Guyatt GH. Development and testing of a new measure of health status for clinical
trials in rhinoconjunctivitis. Clin Exp Allergy. 1991;21:77-83.
FULL TEXT
|
ISI
| PUBMED
11. Lim MC, Taylor RM, Naclerio RM. The histology of allergic rhinitis and its comparison to nasal lavage. Am J Respir Crit Care Med. 1995;151:136-144.
ABSTRACT
12. Juniper EF, Guyatt GH, O'Byrne PM, Viveiros M. Aqueous beclomethasone dipropionate nasal spray: regular vs "as required"
use in the treatment of seasonal allergic rhinitis. J Allergy Clin Immunol. 1990;86:380-386.
FULL TEXT
|
ISI
| PUBMED
13. Juniper EF, Guyatt GH, Archer B, Ferrie PJ. Aqueous beclomethasone diproprionate in the treatment of ragweed pollen–induced
rhinitis: further exploration of "as needed" use. J Allergy Clin Immunol. 1993;92:66-72.
FULL TEXT
|
ISI
| PUBMED
14. Pipkorn U, Proud D, Lichtenstein LM, Kagey-Sobotka A, Norman PS, Naclerio RM. Inhibition of mediator release in allergic rhinitis by pretreatment
with topical glucocorticoids. N Engl J Med. 1987;316:1506-1510.
ABSTRACT
15. Juliusson S, Holmberg K, Karlsson G, Enerback L, Pipkorn U. Mast cells and mediators in the nasal mucosa after allergen challenge:
effects of four weeks' treatment with topical glucocorticoid. Clin Exp Allergy. 1993;23:591-599.
FULL TEXT
|
ISI
| PUBMED
16. Naclerio RM, Adkinson NF Jr, Moylan B, et al. Nasal provocation with allergen induces a secondary serum IgE antibody
response. J Allergy Clin Immunol. 1997;100:505-510.
FULL TEXT
|
ISI
| PUBMED
17. Holm AF, Fokkens WJ, Godthelp T, Mulder PG, Vroom TM, Rijntjes E. Effects of 3 months' nasal steroid therapy on nasal T cells and Langerhans
cells in patients suffering from allergic rhinitis. Allergy. 1995;50:204-209.
ISI
| PUBMED
18. Weiner JM, Abramson MJ, Puy RM. Intranasal corticosteroids versus oral H1 receptor antagonists
in allergic rhinitis: systematic review of randomized controlled trials. BMJ. 1998;317:1624-1629.
FREE FULL TEXT
19. Mometasone furoate nasal spray for allergic rhinitis. Med Lett Drugs Ther. 1999;41:16-17.
ISI
| PUBMED
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.05 vs
the loratadine-treated group; the dagger, P
