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`3}Simpsan, R. J., Ann. Allergy 73(6):497-502 (1994);
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`

`Devoted to the Interests
`of the Practicing Allergist
`December, 1994
`Volume 73, Number 6
`
`CME CREDIT Review Article and Questions-See Pages 457-469
`
`Review Article
`Primary Ciliary Dyskinesia Daniel V Schidlow, MD
`
`Clinical Allergy-Immunology Rounds
`Cardiac Tamponade and Recurrent Upper Respiratory Tract Infections in a 22-Year-Old
`Woman Rohit K Katial, MD; Richard M Hatch, MD; and Michael R Baker, MD
`
`Original Articles
`Outcome of Cough Variant Asthma Treated with Inhaled Steroids Sarah Cheriyan, MD;
`Paul A Greenberger, MD; and Roy Patterson, MD
`Insect Sting Allergy: Analysis of a Cohort of Patients Who Initiated Venom lmmunotherapy
`from 1978 to 1986 David F Graft, MD and William F Schoenwetter, MD
`Lack of Adverse Reactions to Measles, Mumps, and Rubella Vaccine in Egg-Allergic
`Children Bruno Freigang, MD; Tajdin P Jadavji, MB, ChB; and Daniel W Frelgang, MSc
`Psyllium Hypersensitivity Geraldine L Freeman, MD
`Augmented lnterleukin-6 Secretion in Collagen-Stimulated Peripheral Blood Mononuclear
`Cells from Patients with Systemic Sclerosis Mythili Gurram, MD; Savita Pahwa, MD;
`and Marianne Frieri, PhD, MD
`Budesonide and Terfenadine, Separately and in Combination, in the Treatment of Hay
`Fever Richard J Simpson, MB, ChB
`Anaphylaxis due to Limpet Ingestion Teresa Carrillo, MD, PhD;
`Felipe Rodriguez de Castro, MD, PhD; Carlos Blanco, MD; Rodolfo Castillo, MD;
`Joaquin Quiralte, MD; and Manuela Cuevas, MD, PhD
`Use of Nasal Cytology in the Diagnosis of Occult Chronic Sinusitis in Asthmatic
`Children Carol N Jong, MD; Nancy Y Olson, MD; Glen L Nadel, MD;
`Patricia S Phillips, MD; Fred F Gill, MD; and James B Neiburger, MD
`Comparison of Budesonide and Disodium Cromoglycate for the Treatment of Seasonal
`Allergic Rhinitis in Children William G Fisher, MB, ChB
`
`If •.
`.;o -:_:.,.-
`
`

`

`ANNALS OF
`ALLERGY
`
`Contents of ANNALS OF ALLERGY Copyright© 1994 by the
`American College of Allergy and Immunology. Published
`monthly by the American College of Allergy and
`Immunology.
`
`Edil~r: R. Michael Sly, MD
`Children's National Medical Center
`111 Michigan Ave. NW
`Washington, DC 20010-2970
`Tel: (202) 884-3136
`Office hours: Mon and Wed:
`7:30 AM to 4 PM SDT
`Thurs: Noon to 4:30 PM
`The Annals of Allergy is the Official
`Publication of the American College of
`Allergy and Immunology and is devoted
`to the interests of the practicing allergist
`
`December. 1994
`
`REVIEW ARTICLE
`
`Primary Ciliary Dyskinesia
`
`Daniel V Schidlow, MD
`
`457
`
`CLINICAL ALLERGY-IMMUNOLOGY ROUNDS
`
`Cardiac Tamponade and Recurrent Upper Respiratory Tract Infections in a 22-Year-Old
`Woman
`Rohit K Katial, MD; Richard M Hatch, MD; and Michael R Baker, MD . . . . . . . . . . . . . . . . . . . 473
`
`ORIGINAL ARTICLES
`
`Outcome of Cough Variant Asthma Treated with Inhaled Steroids
`Sarah Cheriyan, MD;
`Paul A Greenberger, MD; and Roy Patterson, MD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 478
`.
`,
`r
`Insect Sting Allergy: Analysis of a Cohort of Patients Who Initiated Venom lmmunotherapy from 1978 to
`David F Graft, MD and William F Schoenwetter, MD ................................ . 481
`1986
`
`Lack of Adverse Reactions to Measles, Mumps, and Rubella Vaccine in Egg-Allergic
`Bruno Freigang, MD; Tajdin P Jadavji, MB, ChB; and Daniel W Freigang, MSc
`Children
`
`486
`
`Psyllium Hypersensitivity Geraldine L Freeman, MD
`
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 490
`
`Augmented lnterleukin-6 Secretion in Collagen-Stimulated Peripheral Blood Mononuclear Cells from
`Patients with Systemic Sclerosis Mythili Gurram, MD; Savita Pahwa, MD; and
`Marianne Frieri, PhD, MD
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 493
`
`Budesonide and Terfenadine, Separately and in Combination, in the Treatment of Hay
`Fever
`Richard J Simpson, MB, ChB
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 497
`
`Teresa Carrillo, MD, PhD; Felipe Rodriguez de Castro, MD, PhD;
`Anaphylaxis Due to Limpet Ingestion
`Carlos Blanco, MD; Rodolfo Castillo, MD; Joaquin Quiralte, MD; and Manuela Cuevas, MD, PhD . . . . . . . . 504
`
`Use of Nasal Cytology in the Diagnosis of Occult Chronic Sinusitis in Asthmatic
`Children
`Carol N Jong, MD; Nancy Y Olson, MD; Glen L Nadel, MD; Patricla S Phillips, MD;
`Fred F Gill, MD; and James 8 Neiburger, MD
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 509
`
`Comparison of Budesonide and Disodium Cromoglycate for the Treatment of Seasonal Allergic Rhinitis
`in Children William G Fisher, MB, ChB
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 515
`
`For submission of articles, see "Instructions for
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`ANNALS OF ALLERGY, Suite 550
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`
`(Continued on page A-6)
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`This material may be protected by Copyright law (Title 17 U.S. Code)
`
`r f.
`Budesonide and terf enadine, separately and in
`combination, in the treatment of hay fever
`
`RichardJ. Simpson, MB, ChB
`
`Background: While hay fever is a very common experience, its treatment
`in primary care setting has been little reported in controlled studies.
`Objective: This study sought to evaluate the patient's assessment of efficacy
`of an intranasal steroid spray (budesonide) alone or in combination with an
`antihistamine (terfenadine) against terfenadine alone or placebo alone.
`Methods: A double-blind parallel group, placebo-controlled trial design
`was used, comparing the four groups. Each group used an active or placebo
`spray and active or placebo tablets. Symptom scores were recorded daily in
`diaries over a 21-day period.
`Results: Overall assessment of efficacy by the 106 patients was significantly
`greater {P < .05) for budesonide versus terfenadine or placebo alone. There
`was a 40% placebo response. Budesonide was more effective than terfenadine
`for all individual symptom scores, particularly nasal blockage, against which
`terfenadine was ineffective. Adverse effects were mild and transient for all
`groups.
`Conclusions: Budesonide alone is a highly effective treatment for hay fever
`with few side effects.
`
`INTRODUCTION
`It has been estimated that 10% to
`17% of North Americans experi(cid:173)
`ence allergic rhinitis1 and that hay
`fever, an allergy to pollen resulting
`in rhinitis and conjunctiva} symp(cid:173)
`toms, is one of the most common
`forms of the disease. Following ex(cid:173)
`posure to the allergen, IgE-mediated
`stimulation of mast cells results in
`the release of allergy mediators such
`as histamine, which cause increased
`vascular permeability, mucous se(cid:173)
`cretion, and stimulation of neural
`reflexes {resulting in pruritus and
`sneezing). Late-phase inflammatory
`reactions2 include the attraction and
`infiltration of inflammatory cells,
`such as mast cells, eosinophils, ba(cid:173)
`sophils, neutrophils and lympho-
`
`From the Forth Valley GP Research
`Group, Department of Clinical Psychology,
`University of Stirling, Stirling, UK.
`This study was supported by a grant from
`Astra Draco AB, Lund, Sweden.
`Received for publication February 22,
`1994.
`Accepted for publication in revised form
`July 6, 1994.
`
`cytes into the mucosa.3 The in(cid:173)
`creased irritability of the nose ob(cid:173)
`served during the allergy season is
`largely due to this inflammatory re(cid:173)
`action; The result of these processes
`is the characteristic nasal symptoms
`of hay fever including pruritus, na(cid:173)
`sal congestion, runny nose, and
`sneezmg.
`Treatment of hay fever includes
`antihistamines, decongestants, so(cid:173)
`dium cromoglycate,4 topical {intra(cid:173)
`nasal),5 or systemic6 steroids and
`imm unotherapy. 7 Antihistamines
`are well-established in the treatment
`of hay fever, reflecting the role of
`histamine release in its pathogen(cid:173)
`esis, but their usefulness has until
`recently been limited because of
`their anticholinergic, central nerv(cid:173)
`ous system and sedative side ef(cid:173)
`fects, 8 which are potentiated by sed(cid:173)
`atives, hypnotics, antidepressants,
`and alcohol. More rec{)nt H 1-recep(cid:173)
`tor antagonists produce a much
`lower incidence of sedation8
`; how(cid:173)
`ever, terfenadine, the most widely
`prescribed antihistamine, and a sec(cid:173)
`ond compound in this group, as-
`
`l VOLUME 73, DECEMBER, 1994
`
`l
`
`temizole, have both been shown to
`cause ventricular arrhythmias in
`10 or when used in com(cid:173)
`overdose9
`•
`bination with erythromycin or other
`macrolide antibiotics and the anti(cid:173)
`fungal preparation ketoconazole. 11
`Although clinical trials have shown
`antihistamines to relieve symptoms
`such as sneezing, itchy nose and
`runny nose, in general they are not
`thought to be effective in relieving
`nasal blockage, and thus may be
`formulated in combination with a
`decongestant. 12
`Systemic treatment with corti(cid:173)
`costeroids can be used in hay fever,
`but is usually reserved for the most
`severe and persistent cases because
`of the risk of adverse effects associ(cid:173)
`ated with the long-term use of this
`type of therapy. 13 Intranasal corti(cid:173)
`costeroids, on the other hand, pro(cid:173)
`. vide one of the most potent thera(cid:173)
`14 and their local
`pies for hayfever7
`•
`mode of application avoids the ad(cid:173)
`verse effects associated with sys(cid:173)
`temic corticosteroids while at least
`equalling their efficacy. 15 They also
`lack the sedative effects of antihis(cid:173)
`tamines. The limitations of intra(cid:173)
`nasally applied steroids are that, due
`to their localized action, they may
`not be effective in controlling eye
`symptoms and that some patients
`experience nasal irritation or mild
`epistaxis as a result of using them. 16
`In the current study, the efficacy
`of intranasal budesonide, a corti(cid:173)
`costeroid preparation, was com(cid:173)
`pared with that of terfenadine and a
`combination of the two in the treat(cid:173)
`ment of hay fever, in a double-blind,
`parallel-group, placebo-controlled
`study.
`
`MATERIALS AND METHODS
`Patients
`Men and women aged 15 years or
`
`497
`
`

`

`over at entry were recruited from a
`primary care setting into the trial.
`All patients had experienced symp(cid:173)
`toms of hay fever between May 1
`and August 3 l for at least 2 years
`preceding the study, and at the time
`of recruitment were suffering from
`two or more of the following symp(cid:173)
`toms: blocked nose, runny nose,
`itching nose, or sneezing. Any pa(cid:173)
`tients who were taking oral corti(cid:173)
`costeroids, were suffering from res(cid:173)
`piratory tract infections (bacterial,
`viral, or fungal) at the time of re(cid:173)
`cruitment, had taken desensitiza(cid:173)
`tion therapy during the previous 12
`months or who suffered hay fever
`symptoms outside
`the specified
`period were excluded from
`the
`study, as were pregnant women.
`The nature and purpose of the
`study were explained to the patients
`in both oral and written form, and
`their written consent to participa(cid:173)
`tion in the study was obtained. The
`study was approved by the local eth(cid:173)
`ics committee and was performed
`in accordance with the Declaration
`of Helsinki.
`Study Procedures
`Patients visited their general practi(cid:173)
`tioner on entry to the study, at
`which time demographic details and
`the patient's assessment of hay fever
`symptoms during the previous 24
`hours were recorded. The symp(cid:173)
`toms assessed were blocked nose,
`runny nose, itchy nose, sneezing
`bouts, runny eyes, and sore eyes.
`Symptoms were scored using a 4-
`point system where O = no symp(cid:173)
`toms, l = mild symptoms (present
`but not troublesome), 2 = moderate
`symptoms (some discomfort expe(cid:173)
`rienced), and 3 = severe symptoms
`(discomfort
`experienced during
`most of the waking hours). A mini(cid:173)
`mum score of 2 was required for
`entry into the study.
`On entry to the study, patients
`were randomized to one of four
`parallel groups receiving (1) intra(cid:173)
`nasal budesonide (Rhinocort, Astra
`Draco AB, Lund, Sweden), 200 µg
`bid, plus
`terfenadine (Triludan,
`Marion Merren Dow, Uxbridge,
`
`Middlesex, UK), 60 mg bid; (2) ter(cid:173)
`fenadine, 60 mg bid, plus a placebo
`nasal spray (identical to the bude(cid:173)
`sonide nasal spray but delivering
`propellant and lubricant only); (3)
`intranasal budesonide, 200 µg bid,
`plus placebo tablets identical in ap(cid:173)
`pearance to the terfenadine tablets;
`and ( 4) placebo nasal spray plus pla(cid:173)
`cebo
`tablets. Patients were
`in(cid:173)
`structed to deliver two puffs from
`the nasal spray into each nostril
`morning and evening, and to take
`one tablet in the morning and one
`in the evening, for 21 days. The use
`of other medications for hay fever,
`particularly oral corticosteroids and
`antihistamines, was forbidden but
`in the event of troublesome eye
`symptoms patients were permitted
`to use xylometazoline or metazoline
`eye drops.
`Patients were supplied with diary
`booklets and asked to record, at the
`end of each day, symptom scores
`experienced during the day for
`blocked nose, runny nose, sneezing,
`itchy nose, runny eyes and sore eyes,
`using the same scoring systerri as on
`entry to the study. The number of
`eye drops used during each 24 hours
`was also recorded, as were any com(cid:173)
`ments about the symptoms or treat(cid:173)
`ment.
`Patients visited their general prac(cid:173)
`titioner after seven days' treatment,
`and were reminded of their option
`to withdraw from the study if the
`previous week's treatment had been
`ineffective. The diary booklets were
`checked for accuracy and complete(cid:173)
`ness, and any comments made by
`the patients were recorded. At the
`final yisit, after 21 days of treat(cid:173)
`ment,· comments by either the pa(cid:173)
`tient or the physician were recorded,
`any inconsistencies in the diary
`booklets clarified, and patients were
`asked tQ make a global assessment
`of the efficacy of treatment accord(cid:173)
`ing to a 4-point scale where O =
`ineffective, 1 = slightly effective, 2
`= noticeably effective, and 3 = very
`effective.
`Statistical Analysis
`Mean weekly symptom scores for
`
`each patient who completed the
`study were determined from the di(cid:173)
`ary booklets and overall means for
`each treatment group calculated
`from these. One-way analysis of var(cid:173)
`iance (using pooled variance) was
`carried out on the 3-week treatment
`mean, the last week of treatment
`and weeks 1, 2, and 3 separately.
`Where statistically significant treat(cid:173)
`ment differences were indicated by
`the F-ratio, linear contrasts were
`used to determine the statistical sig(cid:173)
`nificance of individual treatment
`differences.
`Global assessment and eye drop
`use were subjected
`to Kruskal(cid:173)
`Wallis one-way analysis of variance
`followed by the Wilcoxon rank
`sum-W test where appropriate.
`
`RESULTS
`Efficacy
`One hundred forty-three patients re(cid:173)
`porting to their general practitioner
`with symptoms of hay fever were
`recruited into the study. Records
`from six patients were unusable be(cid:173)
`cause of confused numbering (five
`patients) and lost data (one patient).
`Twenty patients withdrew because
`of lack of treatment efficacy, the
`majority of these (12) being in the
`placebo group A further three pa(cid:173)
`tients withdrew as a result of adverse
`events and five patients failed to
`return for assessment on one or
`more occasions. Three patients se(cid:173)
`verely violated the protocol during
`the trial, and were withdrawn. Table
`1 shows demographic characteristics
`and symptom severity at baseline
`for the 106 patients who were eval(cid:173)
`uated for efficacy. On entry to the
`study, the four treatment groups
`were well matched with respect to
`symptom severity and demographic
`characteristics, with the exception of
`the placebo group which had a
`higher proportion of men than the
`other groups.
`Figure 1 shows the results of the
`patients' overall assessment of the
`efficacy of treatment, whereas Fig(cid:173)
`ure 2 shows the analysis of individ(cid:173)
`ual symptom scores derived from
`
`498
`
`ANNALS OF ALLERGY
`
`!.
`
`I
`J
`
`

`

`Table 1. Demographic Characteristics and Baseline Mean Symptom Scores(± SD) of Patients
`Assessed for Efficacy
`
`Demographic characteristics
`Number of patients
`Men/women.(%)
`Age, yr (mean± SD)
`Mean symptom scores
`Blocked nose
`Sneezing bouts
`Nasal itching
`Runny nose
`Sore eyes
`Runny eyes
`
`Treatment Group
`
`Placebo
`
`Budesonide Ter1enadine Budesonide +
`Ter1enadine
`
`21
`71/29
`27.7 (± 12.2)
`
`23
`30
`43/57
`53/47
`26.8 (± 12.4) 29.7 (± 11.7)
`
`32
`41/59
`25.7 (± 7.8)
`
`1.6 ± 1.1
`2.3 ± 0.6
`1.1 ± 1.1
`2.0 ± 0.9
`1.8 ± 1.2
`1.5 ± 1.3
`
`1.9 ± 0.9
`2.1 ± 0.8
`1.2 ± 1.0
`1.9±1.1
`1.8 ± 1.1
`1.5 ± 1.2
`
`1.6 ± 1.2
`1.9 ± 1.1
`1.4±1.1
`1.7 ± 1.2
`1.7 ± 1.1
`1.3 ± 1.2
`
`1.8±1.0
`1.9 ± 0.7
`1.2±1.1
`1.6 ± 0.8
`1.3 ± 1.3
`1.3 ± 1.1
`
`J
`
`100
`
`P< 0.05
`
`D Noticeably effective
`-
`Very effective
`
`80
`
`c
`<lJ
`(.)
`oi 60
`.3
`$
`~ 40
`-~
`a..
`
`20
`
`0
`
`Placebo
`n= 21
`
`Tertenadine Budesonlde Combination
`n = 23
`n = 30
`n = 32
`Figure I. Patients' overall assessment of the efficacy of treatment. Percentage of patients in
`each treatment group who reported the global efficacy of their treatment at week 3 as noticeably·
`effective or very effective, with statistical comparison between groups (Wilcoxon rank sum•W
`test). NS= not significant.
`
`patient booklets. Forty percent of
`patients in the placebo group and
`46% of patients treated with terfen(cid:173)
`adine alone rated the overall effi(cid:173)
`cacy of their treatment as noticeably
`effective or very effective, in com(cid:173)
`parison to 85% of patients receiving
`budesonide alone or in combination
`with terfenadine (Fig 1). A compar(cid:173)
`ison between groups showed statis(cid:173)
`tically significant (P < .05) differ(cid:173)
`ences in the patients' overall assess(cid:173)
`ment of treatment efficacy between
`budesonide versus terf enadine and
`budesonide versus placebo, but no
`significant difference was observed
`between terfenadine versus placebo
`
`or between budesonide alone versus
`budesonide in combination with
`terfenadine.
`Figure 2 shows that treatment
`with terfenadine alone resulted in
`statistically significant (P < .05) re(cid:173)
`ductions in symptom· scores for
`runny nose and itchy nose as com(cid:173)
`pared with placebo. Terfenadine,
`however, had no effect on nasal
`blockage. Treatment with budeson(cid:173)
`ide alone reduced all mean nasal
`symptom scores as compared with
`placebo, the differences being statis(cid:173)
`tically significant (P < .05). Bude(cid:173)
`sonide also reduced mean symptom
`scores more than terfenadine for all
`
`f VOLUME 73, DECEMBER, 1994
`h l
`
`the difference
`nasal symptoms,
`being statistically significant in the
`case of nasal blockage. The combi(cid:173)
`nation of budesonide and terfena(cid:173)
`dine produced symptom scores sim(cid:173)
`ilar to budesonide alone for blocked
`nose, itchy nose and runny nose,
`and reduced the mean sneezing
`score by more than either terfena(cid:173)
`dine or budesonide alone, the differ(cid:173)
`ences being statistically significant
`(P < .05). Figure 3 :Shows changes
`in mean total nasal symptom scores
`during the first week of treatment.
`Terfenadine used alone achieved its
`maximum efficacy within one to
`two days. After two to three days,
`the symptom scores with budeson(cid:173)
`ide were lower than with terfena(cid:173)
`dine, and symptoms continued to
`improve over days 3 to 7. Budeson(cid:173)
`ide and terfenadine combination
`treatment produced a similar effect
`to treatment with budesonide alone.
`Analysis of diary records of eye
`symptoms and eye drop use re(cid:173)
`vealed that there were no statisti(cid:173)
`cally significant differences in eye
`symptom scores between treatment
`groups, although the scores tended
`to be lower in the active treatment
`groups than in the placebo-treated
`patients. Eye drop use
`in all
`groups remained relatively constant
`throughout the study; although use
`in the budesonide group was higher
`than that in the terfenadine group,
`this did not reach statistical signifi(cid:173)
`cance.
`Safety
`The six patients whose records were
`lost or confused were excluded from
`the safety assessment. Nineteen of
`the 137 patients evaluated for safety
`experienced adverse events. These
`events were generally mild and tran(cid:173)
`sient, the most common being local
`effects related to use of the nasal
`spray, such as sneezing and nasal
`irritation after its use. One patient
`treated with combined budesonide
`and terfenadine experienced palpi(cid:173)
`tations one hour after taking the
`tablets, as she had previously when
`taking chlorpheniramine maleate
`(Piriton}
`tablets. Three patients
`
`499
`
`

`

`3
`
`~ 2
`0 g
`[ii
`Q)
`2
`
`1
`
`0
`
`3
`
`2
`
`0
`
`Q)
`
`8
`"' C ro
`:;;:
`
`Q)
`
`-
`
`-
`
`-
`
`-
`
`D Budesonide n "" 30
`Placebo n"' 21
`Terienadine n"' 23 0 Combination n"' 32
`
`(a} Blocked nose
`
`(b) Runny ·nose
`
`D Budesonide n "' 30
`Placebo n"' 21
`Terienadine n"' 23 D Combination n"' 32
`
`(c) Itchy nose
`
`(d) Sneezing
`
`Figure 2. Assessment of nasal symptom scores at week 3 as derived from patients' diary
`booklets. * Statistically significant difference versus placebo (P < .05). t Statistically significant
`difference versus terfenadine (P < .OS). t Statistically significant difference versus budesonide (P
`< .05).
`
`~
`0
`
`0 "'
`
`C
`«l
`Q)
`2
`
`8
`
`6
`
`4
`
`2
`
`0
`E
`
`~---------(cid:173) ---- ------ -----Placebo
`
`2
`
`3
`
`4
`Days
`
`5
`
`6
`
`7
`
`Figure 3. Changes in mean total nasal symptom scores in each treatment group during the
`first week of treatment.
`
`withdrew from the study as a result
`of adverse events; these were one
`placebo-treated patient who s4f(cid:173)
`fered from nausea after taking the
`tablets, one budesonide-treated pa(cid:173)
`tient who suffered from fatigue, and
`one patient on combination therapy
`who experienced intolerable sneez-
`
`ing and headache after using the
`nasal spray. A summary of adverse
`events is shown in Table 2.
`
`DISCUSSION
`The current study demonstrates that
`both intranasal budesonide and oral
`terfenadine were more effective
`
`than placebo in the treatment of hay
`fever symptoms. This confirms pre(cid:173)
`vious studies with budesonide17 and
`terfenadine. 18 Budesonide, how(cid:173)
`ever, was found to control all nasal
`symptoms of hay fever whereas ter(cid:173)
`fenadine did not significantly affect
`nasal blockage. The lack of efficacy
`of terfenadine against nasal block(cid:173)
`age has been observed in other
`studies 19
`20 and is likely to be clini(cid:173)
`•
`cally significant, as 59% of patients
`in the present study complained of
`nasal blockage. Scores for eye symp(cid:173)
`toms were similar on treatment with
`budesonide or terfenadine, sepa(cid:173)
`rately or in combination, and lower
`than scores in the placebo group,
`although the difference was not sta(cid:173)
`tistically significant. More xylome(cid:173)
`tazoline or metazoline eye drops
`were used by patients in the bude(cid:173)
`sonide group, which may indicate
`better control of eye symptoms with
`terfenadine.
`Budesonide was found to be con(cid:173)
`siderably more effective than terfen(cid:173)
`adine, according to the overall as(cid:173)
`sessment of treatment effect by the
`patients. In the budesonide group,
`85% of patients rated their treat(cid:173)
`ment as noticeably effective or very
`effective compared with 46% in the
`terfenadine group and 40% in the
`placebo group, a level of placebo
`response that emphasizes the im(cid:173)
`portance of adequate control groups
`in hay fever studies. Indeed, placebo
`nasal spray can produce a substan(cid:173)
`tial reduction in symptoms.21 Al(cid:173)
`though the scores for individual na(cid:173)
`sal symptoms tended to be lower
`with combined budesonide and ter(cid:173)
`fenadine treatment than with either
`drug used alone, the global assess(cid:173)
`ments of combination therapy and
`budesonide alone were very similar,
`indicating that the lower scores for
`individual symptoms were not per(cid:173)
`ceived by patients as improvements
`in their overall condition. Terfena(cid:173)
`dine, budesonide, and combination
`therapy all had a good safety profile;
`adverse effects were minor and in(cid:173)
`frequent with all treatments, and
`patients on active treatments expe-
`
`500
`
`ANNALS OF ALLERGY
`
`

`

`Table 2. Number of Patients Reporting Adverse Events
`
`Event
`
`Placebo
`(n = 36)
`
`Terfenadine
`(n = 29)
`
`Budesonide
`(n = 35)
`
`Budesonide +
`Terfenadine
`(n = 37)
`
`Nasal adverse events
`Sneezing after use of
`Nasal spray
`Nasal irritation•
`CNS adverse events
`Headache
`Fatigue
`Other adverse events
`Nausea
`Dry mouth
`Palpitations
`
`3
`1
`
`0
`0
`
`1
`0
`0
`
`• Described as stinging, itching, or irritation.
`
`rienced no more adverse effects than
`those taking placebo.
`The lack of efficacy of terfenadine
`and other antihistamines in the
`treatment of nasal congestion in hay
`fever may be an indication of the
`inflammatory nature of the late(cid:173)
`phase response in allergic rhinitis;
`anti-inflammatory agents such as
`corticosteroids could be considered
`as a more rational solution than an(cid:173)
`tihistamines for the nasal symptoms
`of hay fever, especially given the
`excellent safety profile when applied
`intranasally. Budesonide has been
`shown to be more effective than
`beclomethasone dipropionate in the
`treatment of hay fever2 2
`23 and thus
`,
`represents an excellent choice for
`the treatment of this condition.
`In conclusion,
`symptoms of
`runny or itchy nose and sneezing
`could be improved by terfenadine
`or budesonide administered alone
`or in combination, but blocked nose
`was only improved when budeson(cid:173)
`ide was included in the treatment
`regime. Budesonide, alone or in
`combination with terfenadine, was
`perceived by patients as being sig(cid:173)
`nificantly more effective in alleviat(cid:173)
`ing symptoms
`than
`terfenadine
`alone.
`
`ACKNOWLEDGMENTS
`The author would like to acknowl(cid:173)
`edge the work of the General Prac(cid:173)
`titioner members of the Forth Val(cid:173)
`ley GP Research Group, and the
`
`2
`0
`
`0
`0
`
`0
`D
`D
`
`2
`1
`
`0
`2
`
`1
`D
`0
`
`2
`1
`
`2
`D
`
`D
`1
`1
`
`assistance of Mrs V. Swanson, Re(cid:173)
`search Administrator.
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`
`501
`
`

`

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`
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`
`Request for reprints should be addressed to:
`Richard J Simpson, MB, ChB
`Forth Valley GP Research Group
`Dept. Psychology
`University of Stirling
`Stirling FK9 4LA UK
`
`LONG-IBRM TREATMENT OF CHILDREN WITH INHALED
`BUDESONIDE IMPROVES CONTROL OF ASTI-IMA WITI-I NO
`ADVERSE EFFECT UPON GROWTH
`
`To evaluate effects of inhaled budesonide the authors studied 278
`children with mild or moderate asthma at initial ages of 3 to 11 years.
`After having been followed for 1-3 years during which they received no
`corticosteroid for more than 2 weeks per year, 216 children received inhaled
`budesonide, 800 µg/day via Nebuhaler for 6 to 8 weeks. After establishment
`of optimal control the dosage was gradually by reduced 25 % at monthly
`intervals as tolerated. These children continued to receive inhaled bude(cid:173)
`sonide fo