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`1 }Juniper et al., J. Allergy Clin. lmmunol. 83(3):627-633 (1989):
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`T~E~OURNAL OF
`
`.ALLERGY
`
`AND
`
`CLINICAL
`IMMUNOLt>GY
`
`I· .~ALTH SCIENCES UBRAR,
`University of Wisconsin
`.,
`•r~nr-i I i<'rl~~AR' ~tsi~1989/is. 53706
`
`VOL. 83, NO. 3
`MARCH 1989
`
`Table of contents listed on pages 3A, 5A, 7 A, and SA
`
`OFFICIAL PUBLICATION OF
`
`AMERICAN ACADEMY OF ALLER~ AND IMMUNOLOGY
`
`Forty-sixtt, Annual Meeting
`
`March 23-28, 1990
`Baltimore Convention Center
`Baltimore, Md.
`
`Published monthly by The C.V. Mosby Company
`
`ISSN 0091-6749
`
`

`

`r
`
`THE JOURNAL OF
`
`ALLERGY
`
`AND
`
`CLINICAL IMMUNOLOGY
`II Mosby
`
`NUMBER 3
`
`VOLUME 83
`
`Copyright© 1989 by The C.V. Mosby Company
`
`CONTENTS
`March 1989
`
`Original articles
`
`Hymenoptera venom immunotherapy. I. Induction of
`T cell-mediated immunity by honeybee venom immunotherapy:
`Relationships with specific antibody responses
`
`B. Lesourd, MD, PhD, J. Paupe, MD, M. Thiol/et, R. Moulias, MD, J. Sainte-Laudy, MD, and
`P. Scheinmamz, MD, Paris, Frnnce
`
`Hymenoptera venom immunotherapy. II. T proliferative and
`T suppressive activities induced by Vespu/a immunotherapy:
`Effects on long-term antibody responses
`
`B. Leso111"d, MD, PhD, J. Paupe, MD, M. Melani, PhD, J. Sainte-Lar1dy, MD, R. Moulias, MD,
`and P. Scheinmmm, MD, Paris, France
`
`563
`
`572
`
`Contents continued on page 5A
`
`Vol. 83, No. 3, March 1989. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY (ISSN 0091-6749) is published monthly by The C.V.
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`Page 3A
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`

`

`This material may be protected by Copyright law (Title 17 U.S. Code)
`
`Comparison of beclomethasone dipropionate
`aqueous nasal spray, astemizole, and the
`combination in the prophylactic treatment of
`ragweed pollen-induced rhinoconjunctivitis
`
`E. F. Juniper, MSc, P.A. Kline, RN, F. E. Hargreave, MD, and J. Dolovich, MD
`Hamilton, Ontario, Canada
`
`The clinical efficacy and side effect of (I) beclomethasone dipropiunate aqueous nasal ~pray,
`400 µ,g daily, (2) astemizole, 10 mg daily, and (3) beclomethasone, 400 µ,g, plus astemizole,
`JO mg daily, were compared in a double-blind, randomized, parallel-group trial. Ninety adults
`were matched into groups of three according to sensitivity to ragweed pollen. One uf each of
`the three subjects was assigned to nasal spray alone, one was assigned to astemizole alone, and
`one subject was assigned to both medications. Medications were started 1 week before and
`continued daily until 1 week after the ragweed-pollen season (6 weeks). lf rhinoconjunctivitis
`was inadequately controlled with the trial medications, pressurized steroid nasal ~pray and/or
`antihistamine-decongestant eye drops were used in the minimum dose that would emure relief.
`Nose and eye symptoms and concomitant medicntiun use were recorded daily in·a diary.
`Sneezing, nasal obstruction, and rhinorrhea were significantly better, and less additional nasal
`spray was used in subjects taking beclomethasone alone than in subjects taking astemizole
`alone. Beclomethasone plus astemizole provided no better control of rhinitis than
`beclomethasone alone. Eye symptoms and eye drop use tended to be less in subjects taking
`astemizole alone than in subjects taking beclomethasone alone, but the best control of eye
`~ymptoms was recorded in the subjects taking both trial medications. Side effects were mild or
`transient.(] ALLERGY CLTN [MMUNOL 1989;83:627-33.)
`
`Antihistamine tablets and intranasal steroid spray
`have been used successfully to treat rhinoconjuncti(cid:173)
`vitis induced by seasonal pollens. 1
`2 Most previous
`•
`comparisons have suggested that nasal symptoms may
`be controlled better by steroid nasal sprays, 3
`6 although
`-
`the conclusions are not unanimous, 7 and that con(cid:173)
`junctivitis is treated more effectively by antihista(cid:173)
`mines_ 4-7 These results and the different pharma(cid:173)
`cologic properties of the two types of treatment
`suggest that a combination of nasal steroid and anti(cid:173)
`histamine may be the most effective approach of over(cid:173)
`all treatment.
`In the last few years, effective, nonsedative anti-
`
`From the Departments of Medicine and Paediatrics, St. Joseph's
`Hospital and McMaster University, Hamilton, Ontario, Canada.
`Supported by Glaxo Canada, Inc., Toronto, Ontario, Canada.
`Received for publication April 15, 1988.
`Accepted for publication July 15, 198 8.
`Reprint requests: E. F. Juniper, MSc, Department of Clinical
`Epidemiology and Biostatistics, McMaster University Medical
`Center, 1206 Main St., West, Hamilton, Ontario, Canada
`L&N 325.
`
`histamines have become popular for the treatment of
`seasonal allergic rhinoconjunctivitis. More recently,
`aqueous steroid nasal sprays, with efficacy compa(cid:173)
`rabli, to the original Freon-propelled delivery system,
`but with less nasal bleeding and drying, have been
`introduced. 8 The pharmacologic profile of nasal ste(cid:173)
`roids suggests that the most effective approach to treat(cid:173)
`therefore, an
`ment is regular prophylactic use9
`;
`aqueous delivery system should be effective in achiev(cid:173)
`ing this with a reduced risk of side effects. In this
`study, we have compared the clinical efficacy of
`beclomethasone dipropionate aqueous nasal spray
`(Aq. Beconase; Glaxo Canada, Inc., Toronto, On(cid:173)
`tario, Canada), taken before and continued daily
`throughout the ragweed-pollen season, with that of
`astemizole (Hismanal; Janssen Pharmaceutica, Inc.,
`Mississauga, Ontario, Canada), a nonsedative anti(cid:173)
`histamine whose phannacologic profile also recom(cid:173)
`mends prophylactic and continuous treatment for al(cid:173)
`lergic rhinoconjunctivitis. 10 We have also examined
`whether taking the two medications together produces
`better symptom control than taking either medication
`individually.
`
`627
`
`

`

`628 Juniper et al.
`
`TABLE I. Subject characteristics
`
`No.
`Sex (M/F)
`Age (mean, SD)
`Initial ragweed skin sensitivity
`(mean wheal diameter)
`<2.5 mm
`2.5-3.0 mm
`3.0-3.5 mm
`3.5-4.0 mm
`4.0-4.5 mm
`>4.5 mm
`Severity of ragweed rhinocon-
`junctivitis the previous year
`I*
`2t
`3:1:
`4§
`5[1
`History of asthma
`Sensitivity to fungal spores
`Sensitivity to grass pollen
`
`J. ALLERGY CLIN. IMMUNOL.
`MARCH 1989
`
`Astemizole alone
`
`Beclomethasone
`alone
`
`Beclomethasone
`plus astemizole
`
`30
`16/14
`39.8 (13.5)
`
`30
`15/15
`41.3 (11.8)
`
`30
`15/15
`42.2 (13.8)
`
`3
`4
`8
`5
`6
`4
`
`5
`5
`16
`
`3
`5
`5
`18
`
`3
`4
`6
`7
`5
`5
`
`5
`5
`12
`6
`2
`7
`4
`15
`
`3
`4
`7
`6
`6
`4
`
`6
`7
`11
`5
`l
`6
`5
`20
`
`*Symptoms were well controlled with antihistamine or nasal spray.
`tSymptoms were well controlled with antihistamine plus nasal spray or mild symptoms when subject was treated with antihistamine or
`nasal spray.
`:!:Mild symptoms when subject was treated with antihistamine plus nasal spray or moderate symptoms when subject treated with antihistamine
`or nasal spray.
`·
`§Moderate symptoms when subject was treated with antihistamine plus nasal spray or severe symptoms when subject was treated with
`antihistamine or nasal spray.
`·
`IISevere symptoms when subject was treated with antihistamine plus nasal spray.
`
`MATERIAL AND METHODS
`Subjects
`Ninety ragweed pollen-sensitive adults, aged 18 to 70
`years, who were either attending the Firestone Regional
`Chest and Allergy Clinic or who responded to a newspaper
`article, participated in the study. All subjects gave a history
`of rhinoconjunctivitis that required treatment during the pre(cid:173)
`vious ·two ragweed-pollen seasons, and all subjects had a
`positive response to skin prick test with ragweed-pollen
`extract. None of the subjects had perennial rhinitis, and
`none were more than mildly sensitive to the fungal spores
`that are in the air at the same time as ragweed pollen.
`None of the subjects had serious illness other than sea(cid:173)
`sonal rhinitis or asthma. Pregnant and nursing mothers were
`excluded, and women of childbearing potential were ad(cid:173)
`vised to use an effective method of birth control through(cid:173)
`out the study and for 2 months thereafter. None of the
`subjects had taken astemizole, steroid nasal spray, or oral
`steroid within 6 weeks of enrollment. All subjects signed
`an informed consent, which, with the study protocol, had
`been approved by the St. Joseph's Hospital Research
`Committee.
`
`Study design
`The study was designed as a double-blind, random(cid:173)
`ized, p\lfallel-group comparison of (1) beclomethasone
`dipropionate aqueous nasal spray, 50 µ,g per nostril four
`times daily, (2) astemizole, IO mg once daily, and (3)
`beclomethasone dipropionate aqueous nasal spray, 50
`µ,g per nostril four times daily plus astemizole, 10 mg
`daily. A double-dummy technique was used to achieve
`blinding.
`the anticipated start of the
`Three weeks before
`ragweed-pollen season, subjects had duplicate skin prick
`tests with tenfold serial dilutions of ragweed-pollen extract
`(25 to 25,000 Noon units, Bencard Allergy Service, Wes(cid:173)
`ton, Ontario), with single dilutions of Alternaria tenuis and
`Cladosporium (Hormodendrum) (Hollister Steir Laborato(cid:173)
`ries of Canada, Rex.dale, Ontario), and mixed grass-pollen
`extract (Bencard Allergy Service). An allergy history was
`obtained by questionnaire. Severity of rhinoconjunctivitis
`during the previous ragweed season was estimated from
`symptoms and medication requirements (Table I). Subjects
`were matched into groups of three according to skin sen(cid:173)
`sitivity to the ragweed extract, the severity of ragweed
`
`

`

`VOLUME 83
`NUMBER 3
`
`Comparison of nasal sprays 629
`
`S»EE2'.ING
`
`o.s
`
`0.7
`
`RUNNY NOSE
`
`0.8
`
`0.7
`
`Ill 0.6
`0::
`0
`0 o.s
`UJ
`~ 0 4
`<(
`•
`0
`z 0.3
`<(
`LIi :; 0.2
`
`0.1
`
`0
`
`0,9
`
`0.6
`
`0.7
`
`0.6
`
`Ill
`a:
`0
`0
`(/J
`~ 0.5
`<(
`0 0.4
`z
`<( 0.3
`LIi :;
`
`0.2
`
`0.1
`
`0
`
`~~
`STUFFY NOSE J
`J ✓-1,
`,,/
`'1
`LJ~f
`
`'1 1--1
`--
`, l
`i ,,,.
`.....
`
`.
`
`BASELINE 1
`2
`3
`TIME (WEEKS)
`
`4
`
`5
`
`\
`
`\
`
`I
`
`I
`
`/
`
`r-r---
`
`BASELINE 1
`2
`3
`TIME (WEEKS)
`
`4
`
`6
`
`~ 0.6
`0
`~ 0.5
`~ <C 0.4
`0
`z 0.3
`<(
`Ill
`:; 0.2
`
`0.1
`
`0
`
`0.9
`o.a
`
`0.7
`
`0.6
`
`0.5
`
`0.4
`
`0.3
`
`Ill a:
`0
`0
`UJ
`
`?J < 0
`z <(
`Ill
`2
`
`3
`2
`BASELINE 1
`Ti'-'IE [WEEKS)
`
`4
`
`5
`
`EVES
`
`L.r
`!l l "-
`
`..._
`
`I
`
`.r
`
`~
`
`I
`
`0.2
`
`0,1
`
`0
`
`3
`2
`BASELINE 1
`TIME (WEEKS)
`
`4
`
`5
`
`FIG, 1. Mean daily nose and eye symptom scores (SEM) before and throughout the ragweed(cid:173)
`pollen season; astemizole alone (o); aqueous beclomethasone nasal spray alone (LI); astemizole
`plus aqueous beclomethasone nasal spray(•).
`
`pollen~induced rhinoconjunctivitis, sensitivity to Alter(cid:173)
`naria and Cladosporium (Hormodendrum), history of
`asthma, grass-pollen sensitivity, and gender. One of each
`of the three subjects was assigned randomly to bec1ometh(cid:173)
`asone alone, one was assigned to astemizole alone, and one
`subject was assigned to the combination of beclomethasone
`and astemizole.
`Subjects started taking the trial medication 1 week before
`ragweed pollen was expected in the air (Monday, August
`10) and continued daily until 1 week after the pollen season
`(Monday, September 21), that is, for a total of 6 weeks.
`Subjects were instructed to take the tablet in the morning
`either 1 hour before or 2 hours after food and to use the
`nasal spray four times per day. If they had difficulty re(cid:173)
`membering to use the spray at regular intervals, they were
`allowed to take two doses in the morning and two in the
`· evening. If, during the season, symptoms were not ade(cid:173)
`quately controlled by the trial medications, subjects were
`instructed to take additional medications in the minimum
`dose that would keep them well controlled. For nasal symp(cid:173)
`toms they used Freon-propelled beclomethasone dipropio(cid:173)
`nate nasal spray, one puff (50 µ,g) into each nostril, when
`it was needed, up to four times a day. Even for subjects
`taking the trial beclomethasone, this additional dose pro•
`vided a total daily amount that was lower than the recom(cid:173)
`mended maximum dose. For eye symptoms, subjects used
`naphazoline HCl and anatazoline ophthalmic drops, one
`
`drop into each eye, when it was needed, up to four times
`per day. If this treatment was insufficient, sodium cromo(cid:173)
`glycate eye drops, up to four times per day, were added.
`Subjects were instructed not to use other medication for
`rhinoconjunctivitis. Nasal spray and eye drops were selected
`over an antihistamine tablet as the concomitant medication
`·SO that nose and eye symptoms could be evaluated sepa(cid:173)
`rately. Subjects with asthma used salbutamol aerosol, 200
`µg, when it was needed, up to four times per day and those
`with more severe asthma took beclomethasone dipropionate,
`100 µg, up to four times per day. No oral steroids were
`used. The provision and rise of standardized concomitant
`medications allowed the efficacy of the trial medications to
`be estimated from the amount of additional medication used,
`prevented subjects dropping out of the study because of
`inadequate symptom c6ntrol, and reduced the risk of sub(cid:173)
`jects using unauthorized hay fever medications.
`Subjects made entries in a diary each morning and each
`evening throughout the study. 11 They recorded the severity
`(0, absent; 1, mild; 2, moderate; and 3, severe) and duration
`(0, absent; 1, a few short episodes; 2, many episodes; and
`3, continuous) of sneezing, stuffy nose, runny nose, eye
`symptoms, and asthma. At the end of each day, they re•
`corded the amount of concomitant medication needed in the
`previous 24 hours.
`Subjects attended the clinic after 1, 3, and 6 weeks of
`treatment. At each visit, symptoms were reviewed to ensure
`
`

`

`630 Juniper et aL
`
`J. ALLERGY CLIN. IMMUNOL, a'
`MARCH 1989 ~
`
`m=oesL] · I
`I - "· "'.}
`lrr1,,fJ
`
`~
`
`I
`;,
`
`1.6
`
`?i
`... w
`C 1.2
`... (/)
`► w
`IL 0.8
`0
`IC
`C
`
`0.4
`
`'ii
`~,1
`.~
`-~
`,-.;
`
`·-1
`
`0
`
`5
`
`4
`
`5
`
`I
`I
`I
`I
`I
`
`Tl
`
`J.-
`
`BASELINE 1
`2
`3
`TIME (WEEKS)
`
`1.6
`
`ADDITIONAL NASAL SPRAY
`
`i_J,,t,~,
`\1
`
`\
`
`\
`
`?.i
`C ... ..J 1.2
`
`ii:
`~
`(I)
`
`0 z
`... (I) 0.8
`IL
`IL ::,
`Q.
`
`0.4
`
`0
`
`FIG. 2. Mean daily additional medication use (SEM) before and throughout the ragweed-pollen
`season; astemizole alone (o); aqueous beclomethasone nasal spray alone (l\); astemiwle plus
`aqueous beclomethasone nasal spray(•).
`
`TABLE II. Efficacy results (mean daily score)
`
`Astemizole alone
`
`Beclomethasone
`alone
`
`Beclo methasone
`plus astemizole
`
`Overall (mean of 6 weeks)
`Sneezing
`Stuffy nose
`Runny nose
`Eye symptoms
`Asthma
`Beclomethasone use
`Eye drop use
`Asthama aerosol use
`
`0.395
`0.594
`0.406
`0.424
`0.030
`0.871
`0.707
`0.195
`
`0.193
`0.319
`0.152
`0.563
`O.DIS
`0.206
`1.016
`0.049
`
`0.155
`0.322
`0.192
`0.355
`0.048
`0.241
`0.354
`0.113
`
`that they were adequately controlled and diaries were ex~
`amined for accuracy and completeness. Subjects reported
`all nonrhinoconjunctivitis symptoms that they had experi(cid:173)
`enced since the previous visit, irrespective of whether they
`perceived them as trial-medication related. The nasal spray
`bottles were weighed and tablets were counted for compli(cid:173)
`ance. At all visits except the last, each subject gave a dem(cid:173)
`onstration of the technique of nasal spray application to
`confinn correct use.
`Regular daily ragweed-pollen counts were not available
`throughout this study. However, intermittent counts were
`made with a Hirst volumetric spore trap (Burkard Manu(cid:173)
`facturing Co., Ltd. , Richmansworth, Hertfordshire, En(cid:173)
`gland). These counts suggested that the duration and severity
`of the local ragweed-pollen season of t.he year 1987 was
`very similar to duration and severity of each of the previous
`10 years when regular daily counts were made. 11
`12
`
`•
`
`Analysis
`Mean daily symptoms and medication scores were cal(cid:173)
`culated for each subject for each of the 6 weeks of the study.
`These data were analyzed for treatment effect with a
`
`repeated measures analysis of variance. Differences be(cid:173)
`tween the three treatments were examined with Student's(cid:173)
`Newma_n-Keuls method for multiple comparisons. 11 These
`data demonstrated instability of variance across the time
`periods, and therefore, a square root transformation was
`used to improve their statistical properties. Percent com(cid:173)
`pliance was estimated from the observed and expected
`bottle-weight loss and tablet use. Differences were consid(cid:173)
`ered significant at p < 0.05 (two-tailed).
`
`RESULTS
`Ninety subjects were enrolled, and eighty-nine
`completed the study. One subject withdrew because
`· he could not remember to talce the trial medication -
`Demographic and allergy characteristics were well
`balanced across the three treatment groups (Table 1).
`In all three treatment groups, nose and eye symp(cid:173)
`toms were well controlled, as indicated by the highest
`mean weekly score for any symptom <0.8 (maxis
`mum, 3.0) (Figs. 1 and 2). Nevertheless, aqueous
`beclomethasone was more effective in controlling
`
`

`

`VOLUME 83
`NUMBER 3
`
`Comparison of nasal sprays 631
`
`TABLE 111. Statistical comparison of tria\ medications (with Student's-Newman-Keuls method for
`multiple comparisons)
`
`Astemizole vs
`beclomethasone
`
`Astemizole vs
`astemizole plus beclomethasone
`
`Beclomethasone vs
`astemizole plus beclomethasone
`
`Symptom~
`Sneezing
`Stuffy nose
`Runny nose
`Eye symptoms
`Asthma
`Concomitant medication
`use
`Nasal spray
`Eye drops
`Asthma aerosols
`
`p < 0.05*
`p < 0.05*
`p < 0.05*
`NS
`NS
`
`p < 0.05*
`NS
`NS
`
`p < o.ost
`P < o.ost
`p < 0.05t
`NS
`NS
`
`p < o.ost
`NS
`NS
`
`NS, Not significant.
`"Beclomethasone alone was better than astemizole alone.
`tAstemizole plus beclomethasone was better than astemizole alone.
`
`TABLE IV. Compliance(% observed/expected)
`
`NS
`NS
`NS
`NS
`NS
`
`NS
`NS
`NS
`
`Astemizole alone
`
`Beclomethasone alone
`
`Pills (mean, SD)
`Nasal spray (mean, SD)
`
`99.3 (2.8)
`91.8 (14.0)
`
`100.2 (4.1)
`94.1 (7.6)
`'
`
`Beclo methasone
`plus astemizole
`
`99.2 (4.7)
`91.3 (12.6)
`
`sneezing, stuffy nose, and runny nose than astemizole
`(p < 0.05), as demonstrated both by lower symptom
`scores and less need for additional nasal spray (Figs.
`1 and 2; Tables II and III). For nasal symptoms, the
`subjects who took both aqueous beclomethasone and
`astemizole were better protected than subjects taking
`astemizole alone but no different from.subjects taking
`nasal spray alone. For each of the 6 weeks of the
`study, sneezing, stuffy nose, and runny nose dem(cid:173)
`onstrated similar treatment differences, suggesting the
`treatments had similar time courses on each of these
`symptoms (Fig. 1). As might have been expected,
`subjects taking astemizole alone had lower eye symp(cid:173)
`tom scores than subjects taking beclomethasone alone,
`but the lowest eye scores and the least need for ad(cid:173)
`ditional eye drops was demonstrated by the subjects
`taking both astemizole and beclomethasone. However,
`these differences for eye symptoms and eye drops did
`not reach statistical significance, possibly as a result
`of poor statistical power, since not all subjects gave
`a history of allergic conjunctivitis. Asthma symptoms
`and medication requirements were similar in the three
`groups.
`Compliance with taking the trial medications was
`very good (Table IV) with no differences between the
`
`three treatment groups. The most common side effect
`was drowsiness, which was reported on one or more
`occasions by nine subjects taking astemizole alone,
`four subjects taking beclomethasone alone, and four
`subjects taking the combined medications (Table V).
`In most cases the drowsiness was mild and transient.
`However, it was troublesome in one subject taking
`astemizole alone, but he elected to continue taking
`the medication because his rhinoconjunctivitis was
`well controlled. The subjects who reported drowsiness
`experienced a wide range of rhinoconjunctivitis se(cid:173)
`verity; therefore, it was not possible to evaluate
`whether the drowsiness was caused by persistent
`symptoms, the trial medications, the direct effect of
`the ragweed, 14 or factors unrelated to the study. Al~
`though some subjects reported hunger during the
`study, none experienced inappropriate weight gain.
`
`DISCUSSION
`The results of this study have demonstrated that
`seasonal allergic rhinitis is more effectively controlled
`by the regular use of beclomethasone dipropionate
`aqueous nasal spray (400 µ,g daily) than by the regular
`use of astemizole (10 .mg daily). Results ha,ve also
`demonstrated that there is no further improvement in
`
`

`

`632 Juniper et al.
`
`1
`
`J. ALLERGY CLIN. IMMLir-iOL.·'
`MARCH 1989
`
`TABLE V. Number of subjects reporting adverse experiences
`
`Adverse experience
`
`Astemizole alone
`
`Bec/omethasone alone
`
`Beclomethasone plus
`astemizole
`
`Drowsiness
`Hunger
`Dry
`nose/lips I mouth/ throat
`Nasal bleeding
`Headache
`Thirst
`Skin irritation/ rash
`Nausea
`
`9
`3
`3
`
`0
`I
`0
`0
`0
`
`4
`3
`2
`
`2
`1
`2
`2
`0
`
`4
`4
`2
`
`3
`3
`1
`I
`2
`
`nasal symptoms when astemizole is added to the be(cid:173)
`clomethasone. For eye symptoms, astemizole alone
`tended to be more effective than beclomethasone
`alone, but the addition of beclomethasone to the as(cid:173)
`temizole provided even lower eye scores.
`The prophylactic and continuous use of steroid na(cid:173)
`sal sprays has been limited in the past by nasal dryness
`and bleeding, apparently induced by the Freon(cid:173)
`propelled aerosol delivery system. 9 However, the
`aqueous delivery system appears to have reduced the
`side effects without loss of efficacy/ thus permitting
`optimal use of this medication. In the present study,
`care was taken to instruct subjects in the correct use
`of the aqueous nasal spray because the technique of
`application appears to be a little more subject to error
`than the Freon-pressurized delivery system. Each sub(cid:173)
`ject's technique was checked regularly, and the spray
`bottles were weighed to ensure that maximum efficacy
`was being achieved.
`Comparisons between the the new nonsedative anti(cid:173)
`histamines have demonstrated that astemizole is one
`of the most effective fo controlling symptoms of sea(cid:173)
`sonal allergic rhinoconjunctivitis. 12
`15
`16 It has a slow
`•
`•
`onset of action, not reaching steady-state serum levels
`
`for l to 2-, weeks .1Q Therefore, it would be expected
`to achieve maximum therapeutic effed when it was
`used in a schedule similar to that for steroid nasal
`spray, namely, started before · and continued daily
`throughopt the pollen season.
`·
`·. -Previous comparisons of antihistamines and steroid
`nasal sprays have suggested that nasal symptoms are
`contro1led more effectively by nasal spray's, but the
`results are not unanimous. Two studies have suggested
`that the nasal sprays are more effective for controlling
`nasal blockage but similar to antihistamines for sneez(cid:173)
`4 One study suggested that sneez(cid:173)
`ing and rhinorrhea._3
`•
`i~g and: rhinorrhea are controlled better by steroid
`nasal spray but similar for n_f(sal blockage. 0 Another
`study suggested that all nasal symptoms, except sneez-
`
`ing, are better with nasal spray treatment. 5 One study
`concluded that nasal spray and antihistamines are
`of similar effectiveness for all nasal symptoms. 7
`Differences in conclusions may have occurred as a
`result of variation in the types of trial medications and
`differences in dosing schedules. In this study, when
`both trial medications were used in a manner that
`would appear optimal for their pharmacologic prop(cid:173)
`erties, the aqueous beclomethasone nasal spray was
`significantly more effective than astemizole for all
`three nasal symptoms monitored. The results also
`demonstrated that subjects who used both astemizole
`and beclomethasone had less nasal symptoms than
`subjects receiving astemizole alone. This conclusion
`is in agreement with Wihl et al. 17 who demonstrated
`that, even after subjects had demonstrated symptom(cid:173)
`atic improvement with astemizole, further improve(cid:173)
`ment could be a~hieved by. adding beclomethasone
`dipropionate nasal spray. The results of the pre.sent
`study add the further observation that beclomethasone
`nasal spray filone is just as effective as beclomethasone
`plus. astemizole for nasal symptoms, suggesting 'that
`nasal spray alone may be· sufficient for the optimal
`·
`treatment of symptoms.
`Astemizqle was more effective than the. aqueous
`nasal spray at controlling eye symptoms:. However, it
`was interesting to observe that the best control of eye
`symptoms was achieved by the subjects taking the' two
`medications together. The same observation has been
`made with another aqueous . steroid nasal spray,
`budesonide,4 but the mechanism by which this may
`occur is unclear. It may be that, by keeping the nasal
`passages clear, nasolacrimal duct drainage and eyelid
`venous congestio~ are improved. It could be that so~e
`nasal spray _reaches the- eye through the n.,asolacrimal
`duct, ~ut t~is appears unlikely, and, at present, there
`is no evidence to ·support this hypothesis. It may also
`be that, if nasal symptoms are minimal, psychologi(cid:173)
`cally the patient is hot so troubled by eye symptoms
`
`

`

`VOLUME 83
`NUMBER 3
`
`Comparison of nasal sprays 633
`
`and records lower scores. However, these are only
`speculations, and further studies will be required to
`confirm the finding and determine the mechanism.
`
`We thank all the subjects for their diligent participation
`in the study, Professor Robin Roberts for statistical advice,
`and Mrs, Laurie Whitely for assisting in the preparation of
`the manuscript. We thank Iolab Pharmaceuticals for sup(cid:173)
`plying Vasocon-A eye drops and Fisons Pharmaceuticals for
`Opticrom eye drops.
`
`REFERENCES
`
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`·
`17. Wihl J-A, Petersen BN, Petersen LN, Gundersen G, Bresson
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`
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