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`PROPERTY OF THF..
`NATIONAL
`LIBRARY OF
`MEDICINE
`
`

`

`Vol. 2, No. 1, 2003
`
`Contents
`
`Current Opinion
`
`., .......... , . >
`
`.&.~,, J ' •. ~ ''"F . . , y ··....,·vvA .:•-.· .-;··,·· .s
`Leading Articles
`
`···.,<·.· .• c= ·.
`
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`
`Therapy in Practice
`
`Review Article
`
`OriginCll R~S~Clr~h.Arti~'I~ -
`
`r
`
`. . . ..... ..
`
`.
`
`Adi's otug Ev~IUClti;~-
`
`American Journal of
`
`Respiratory Medicine
`
`Psychiatric Factors in Asthma: Implications for
`Diagnosis and Therapy
`S Rictvcld, TL Creer
`
`1-10
`
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`
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`
`Clinical Usefulness of Inflammatory Markers in Asthma
`PAB Wark, PG Gibso11
`Serotonin Agonists and Antagonists in Obstructive
`Sleep Apnea: Therapeutic Potential
`SC Vcnscy
`C/1/11111ydia pne11111cmiae Infections in Asthma:
`Clinical Implications
`M Ge11cay, M Roth
`
`Optimizing Treatment Outcomes in Severe
`Community-Acquired Pneumonia
`F Rodriguez de Cnstro, A Torres
`
`Comparison of Intranasal Corticosteroids and
`Antihistamines in Allergic Rhinitis: A Review of
`Randomized, Controlled Trials
`LP Nielsen, R Dn/1/
`
`11-19
`
`21-29
`
`31-38
`
`39-54
`
`55-65
`
`-
`
`~~· 67-74 ~
`
`.
`
`··.
`
`. ... 75-107
`
`. ·. .
`
`Inhal~d torh~~ster~id~~With/With~lllt Lo;g~Acting . ·~~ ....
`~-Agonists Reduce the Risk of Rehospitalization and
`Death in COPD Patients
`JB Sorin110, VA Kiri, NB Pride, J Vestbo
`-~- .. -= .... ·. . Cefepi~;: A. Re;i;vV ,()fit; Us~ i11A tl1e M;1~ai~1~ent of -
`Hospitalized Patients with Pneumonia
`TM C/1np111n11, CM Perry
`
`American Journal of Respiratory Medicine is indexed in C/1c111icnl Abstracts. lndexing by all major biomedical databases has been applied for. Individual articles
`are available through the ADONIS document delivery system and arc available on-line via the World Wide Web through lngenta. Further details are available
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`L.a~ 0
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`INTERNATIONAL
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`A Wolters Kluwer Compnuy
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`American Journal of
`Respiratory Medicine
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`International Editorial Board
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`N.C. Barnes, London, England
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`
`REVIEW ARTICLE
`,,...-~ ··LA!✓ -. . /4 _.c.,-
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`
`Am J riospir Med 2003: 2 (I ): 55-65
`l l 75·6.365/03/ 000 1-0055/$:JD.00/0
`
`•··< ~
`
`J>'....,Jc=-.:f
`
`·'.:.i Adls lr1t0rnotionol Um1l0d . All 1lot·11s ,0s0rv0d.
`
`Comparison of Intranasal Corticosteroids and
`Antihistamines in Allergic Rhinitis
`A Review of Randomized, Controlled Trials
`
`Lars P. Nielsen 1,2 and Ronald Dahl2
`
`1 Depurtment of Clinical f'hilrmacology, University of Aarhus, Aurhus, Denmark
`2 Depurtment of Respirntory Diseases, Aarhus University Hospital, Aarhus, Denmark
`
`Contents
`
`, , , , . . , . . . .
`Abstract
`l. Antihistamines . . . . . . . . .
`l . l General Considerations
`l .2 Oral Antihistamines .. .
`l .3
`Intranasal Antihistamines
`2. Corticosteroids
`. . . . . . . .
`2. l General Considerations
`2.2
`Intranasal Corticosteroids
`3. Comparing Antihistamines and Intranasal Corticosteroids in Allergic Rhinitis
`3. l Perennial Allergic Rhinitis . . . . . . . . . . . . . . . . . . ... .
`. . . . . . . . . . . . . . . . . . . . . .
`3.2 Seasonal Allergic Rhinitis
`3.3 Combination of Antihistamines and Intranasal Corticosteroids
`3.4 Safety .. . .... .
`3.5 Cost-Effectiveness .
`4. Conclusion . . . . . . . .
`
`55
`56
`56
`56
`56
`57
`57
`57
`58
`58
`58
`60
`60
`61
`61
`
`Abstract
`
`For several years there has been discussion of whether first-line pharmacological treatment of allergic rhinitis
`should be antihistamines or intranasal corticosteroids. No well documented, clinically relevant differences seem
`to exist for individual nonsedating antihistamines in the treatment of allergic rhinitis. Likewise, the current body
`of literature does not seem to favor any specific intranasal corticosteroid. When comparing efficacy of antihis(cid:173)
`tamines and intranasal corticosteroids in allergic rhinitis, present data favor intranasal corticosteroids. Interest(cid:173)
`ingly, data do not support antihistai11ines as superior in treating conjunctivitis associated with allergic rhinitis.
`Safety data from comparative studies in allergic rhinitis do not indicate differences between antihistamines and
`intranasal corticosteroids. Combining irntihistamines and intranasal corticosteroids in the treatment of allergic
`rhinitis does not provide additional beneficial effects to intranasal corticosteroids alone.
`Considering present data, intranasal corticosteroids seem to offer superior relief in allergic rhinitis, when
`compared with antihistamines.
`
`Allergic rhinitis is a disease characterized by nasal obstruc(cid:173)
`tion, rhinorrhea, sneezing and nasal itch and often accompanied
`by conjunctivitis. It is elicited by IgE-mediated allergic inflam(cid:173)
`mation of the nasal mucosa. The disease prevalence is 10-20%
`
`of the population in industrialized countriesl 11 and seems to be
`increasing.1 2-31 Although allergic rhinitis is not a life-threatening
`disease, it can severely affect patients' quality of lifel 4-Cil and can
`cause comorbidity from other diseases, such as asthma, sinusitis,
`
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`

`

`otitis media and conjunctivitis.171 Allergic rhinitis can be either
`seasonal, i.e. present at certain times of the year such as during
`the pollen season, or perennial, i.e. present at all times of the year.
`Applicable therapeutic initiatives in allergic rhinitis are al(cid:173)
`lergen avoidance, allergen immunotherapy and pharmacological
`intervention. This review considers first-line pharmacological
`treatment of allergic rhinitis, in which two main treatment options
`have evolved, i.e. antihistamines and intranasal corticosteroids.
`The choice between these options has been extensively discussed
`since the introduction of intranasal corticosteroid treatment. 181
`Evidence presented in this review considers only data obtained
`in patients with allergic rhinitis. Medical literature including ab(cid:173)
`stracts and randomized trials published in the English language
`during the period 1966-200 I on antihistamines and intranasal
`corticosteroids in the treatment of allergic rhinitis were identified
`using Medline.
`
`1. Antihistamines
`
`l. l General Considerations
`
`Histamine is the major pathophysiological mediator of aller(cid:173)
`gic rhinitis, almost exclusively exerting its action through stim(cid:173)
`ulation of the HI receptor. Whether other histamine receptors
`have any effect in allergic rhinitis remains to be clarified. Anti(cid:173)
`histamines in the treatment of allergic rhinitis are, thus, HI recep(cid:173)
`tor antagonists.I 9, 101 An additional anti-inflammatory effect of H 1
`antihistamines has been proposed, as some newer compounds
`seem to influence cytokinc production, mediator release or in(cid:173)
`flammatory cell flux.I 11 -19! However, other studies have been un(cid:173)
`able to reproduce such findings.1 20-231 Whether antihistamines of(cid:173)
`fer additional and clinically relevant anti-inflammatory effects
`along with their inhibition of histamine action needs further clar(cid:173)
`ification.
`
`1.2 Oral Antihistamines
`
`Numerous HI receptor antagonists have been developed over
`the years. For oral use, these can roughly be divided into older,
`first-generation (e.g. chlorpheniraminc, diphcnhydraminc, pro(cid:173)
`mcthazinc and tripolidine) and newer, second-generation antihis(cid:173)
`tamines (acrivastinc, astemizolc, cctirizine, ebastine, fcxofenad(cid:173)
`inc, loratadine, mizolastinc and tcrfcnadinc). This review deals
`with the newer antihistamines, as use of the older drugs in allergic
`rhinitis is limited by their adverse effects, mainly sedation and
`anticholinergic activity.
`All of the newer antihistamines are effective in the treatment
`or allergic rhinitis by decreasing nasal itching, sneezing and rhi(cid:173)
`norrhca, but have a poor effect upon nasal congestion.1 24-31 1 They
`
`are also effective upon conjunctivitis and recent results sccn1 to
`indicate some influence on lower airway symptoms which oftQn
`co-exists with allergic rhinitisY 2,33 1
`Moreover, the pharmacokinctic profile or these drugs is H\.1-
`vantag~ous when compared with that of the older oncs_l:141 TbQy
`have an onset of action within 1-2 hours, lasting for 12-24 hour~,
`except for acrivastine, which has to be given at 8-hour interval;;.
`With the exception of cetirizine and fcxofenadine, which arc c>-i(cid:173)
`crctcd almost unchanged, the drugs in this group arc mctaboliz,:c!
`via the hepatic cytochrome P45O (CYP) system by CYP3A. As a
`number of other compounds (antimycotic conazoles, rnacrolide
`antibacterials and grapefruit juice) are substrates for this enzy1111:,
`this obviously provides a theoretical risk for intcractions.1 35 1 This
`is probably a contributing factor to the occurrence of severe c.,ll'(cid:173)
`diac arrhythmias (such as 'torsade de pointes') and deaths, which
`have been described following treatment with tcrfcnadine anti
`astemizole.136-381 These effects seem to be enabled through u
`quinidine-like action, causing a prolongation of the QT inter(cid:173)
`val.139.401 At present, no clinical evidence has demonstrated car.
`diac adverse effects from other second-generation antihista.
`mines, when considered at therapeutically appropriate levels.
`However, in a consensus statement on the treatment of allergi\::
`rhinitis the European Academy of Allergology and Clinical 1111.
`munology recommends that antihistamines that arc rnetabolizetj
`by CYP45O or have quinidine-like actions be avoided in ris~
`groups, i.e. patients with impaired hepatic function or cardia\::
`arrhythmia.f41 I
`Astemizole can also act as an appetite stimulant and result i11
`increased bodyweight.142.431 The cause of this action remains ob,
`scure, although a CNS-mediated mechanism, such as serotonin an,
`tagonism, could be speculated. However, whether this adverse
`effect is seen exclusively with astemizole remains unclear, as data
`regarding this parameter are lacking for other second-generation
`antihistamines.
`While CNS-related adverse effects were a major charac(cid:173)
`teristic of the first-generation antihistamines, the piperazine/pi(cid:173)
`pcridine-derived structures of the newer generation reduce their
`CNS penetration, although sedative effects have been described
`for some of the compounds, e.g. acrivastinc1441 and cetirizine.1451
`The binding affinity to muscarinic receptors is also decreased.
`With the exception of cardiac adverse effects, this leaves second(cid:173)
`generation antihistamines with a therapeutic index superior to
`that of first-generation antihistamines.
`
`1.3 Intranasal Antihistamines
`
`Azelastine and levocabastine are two newer HI receptor an(cid:173)
`tagonists for topical use. When applied intranasally, both have
`
`,u Adls International Limited, All rights rosorvod
`
`Am J Rospir Mod 2003; 2 (l)
`
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`

`

`Corticosteroids .imi Antihist,1111ines in Allergic Rhinitis
`
`57
`
`proven effective in the treatment of allergic rhinitis, mainly re(cid:173)
`lieving nasal itching and sncczing.14(,.4?1 They act within 15-30
`minutes, which is faster than oral antihistamines. They arc ap(cid:173)
`plied twice daily. No sedative effects have been seen for either
`drug,1 4r,.4 81 whereas the occurrence or a short-lasting perversion
`or taste has been described for azclastinc.H91
`
`2. Corticosteroids
`
`2.1 General Considerations
`
`Inflanunation or the nasal mucosa is the main characteristic
`of allergic rhinitis, and of currently available medications, corti(cid:173)
`costeroids have the most proround effect on this inflammatory
`proccss.1 501 Corticosteroids exert their effect by combining with
`a glucocorticoid receptor localized in target cell cytoplasm. The
`resulting activated glucocorticoid receptor complex interacts
`with cellular DNA, thereby enabling regulation of cellular func(cid:173)
`tions.151-531
`Corticosteroids act on many of the cell types and inflamma(cid:173)
`tory mediators participating in allergic inflammation. Antigen(cid:173)
`presenting Langerhans cells are reduced in number by intranasal
`corticosteroids.1 54,55 1 Moreover, such treatment seems to impair
`their processing of antigen.1 561 Likewise, the migration of baso(cid:173)
`phils and mast cells to the nasal epithelium is inhibited by corti(cid:173)
`costeroidsl57·591 and their release of mediators (i.e. histamine)
`seems to be reducect.1 601 Several pivotal aspects of eosinophil
`function are interfered with by corticosteroid therapy. Apoptosis
`is accentuated and degranulation propensity of cytotoxic pro(cid:173)
`teins, i.e. cosinophil cationic protein and eosinophil peroxidase,
`is inhibited.1 61 J121 In addition, formation of cytokines and
`chemokines vital to eosinophil lifespan is reduced: e.g. interleu(cid:173)
`kin (IL)-5 (l'ormation),163 1 IL-4 (adhesion)1 641 and RANTES (che(cid:173)
`motaxis).1651 Corticosteroids have also been shown to affect lym(cid:173)
`phocytes. In one study, intranasal corticosteroids inhibited
`activated T lymphocytes of nasal epithelium.1661 In two other
`studies, the increase of specific IgE in individuals with pollen
`allergy during the pollen season was abolished.1 67·681
`
`2.2 Intranasal Corticosteroids
`
`Several corticosteroids have been clevelopecl for intranasal
`application, all characterized by a high receptor affinity. Efficacy
`on the symptoms of allergic rhinitis, including nasal congestion,
`has been demonstrated for intranasal beclomethasone dipropion(cid:173)
`ate,1691 budesonide,l701 flunisolicie,l7 1 I fluticasone propionate,1721
`mometasone furoatel 731 and triamcinolone acetonide.1 741 In addi(cid:173)
`tion, some reports have indicated that intranasal corticosteroids
`may have a beneficial effect towards bronchial hyperresponsive-
`
`ness and asthma symptoms which may co-exist with allergic rhi(cid:173)
`nitis.175·801
`It has been generally considered that intranasal corticoste(cid:173)
`roids have a slow onset of action. However, they usually act
`within 12-24 hours.1 81 ·83 1 Recent results have even indicated that
`intranasal buclesonide begins to act after 3 hours.1 8-ll However,
`maximum treatment efficacy occurs after days or even weeks .1851
`Application once daily has proven sufficient to treat most allergic
`rhinitis patients,1 86·901 although severe cases may benefit from a
`double close given twice daily.1 91 1
`The different potencies of intranasal corticosteroids are im(cid:173)
`portant, when considering comparative data. It is well established
`that intranasal fluticasone propionate is twice as potent as intra(cid:173)
`nasal beclomethasone dipropionate.1 721 Regarding other relative
`potencies between intranasal corticosteroids, results have been
`controversial. However, the ,iewer drugs, i.e. fluticasone 'propio(cid:173)
`nate and mometasone furoate, seem to be more potent than oth(cid:173)
`ers_lX21
`Currently available intranasal corticosteroids are generally
`well tolerated. Sneezing caused by nasal hyperreactivity can oc(cid:173)
`cur at the beginning of therapy, but usually disappears with
`time.1 921 Occasionally, mild and transient dryness, crusting and
`blood-stained secretions occur, often responsive to a reduction of
`close.1 85 ,93,941 Septa! perforation has been described as a rare com(cid:173)
`plication.195-961 Atrophy of the mucosa, corresponding to dermal
`atrophy, after prolonged use of intranasal corticosteroids has not
`occurred.197-981
`The risk of systemic adverse effects has been a concern for
`this class of drugs. A proportion of intranasally applied cortico(cid:173)
`steroid ends up in the gastrointestinal tract and thereby is system(cid:173)
`ically absorbed. Likewise, direct absorption across the nasal mu(cid:173)
`cosa could contribute to systemic bioavailability. However, these
`compounds, especially the newer fluticasone propionate and
`mometasone furoate, have low systemic bioavailability, mainly
`because of their massive first-pass metabolism in the liver.1 821
`When used exclusively intranasally at therapeutic close levels, the
`drugs in this class do not seem to exhibit any particular influence
`on the hypothalamic-pituitary-adrenal (HPA) axis.199·1021 Lack of
`I-IPA-axis suppression does not guarantee against other kinds of
`systemic adverse effects. Data demonstrating an inhibitory effect
`on the short-term growth rate of children have been presented for
`intranasal beclomethasone dipropionate and budesonide,1 1o3. io-11
`although the result for intranasal budesonicle was achieved only
`by giving an adult dose of 2OOµg twice daily. Moreover, this could
`not be reconfirmed in a more recent study, in which budesonide
`4OOµg daily was equal to placebo with respect to effect on child
`growth, expressed by lower-leg knemometry.1 1051 Newer intra(cid:173)
`nasal compounds (fluticasone propionate and mometasone furoate)
`
`''J Adis International Limited. All rights reserved.
`
`Th is m ateria I w as. co,p ied
`at the N LM and m ay be
`~u,bject US Copyright Laws
`
`Am J Resplr Med 2003; 2 (1)
`
`

`

`58
`
`Nicl,m & U11/,I
`
`have not shown evidence of any effect on growth rate in children
`when given in therapeutic doses.l 1061 This difference has been
`explained by a difference of bioavailability between the drugs,
`although closing frequency probably plays a major role, thus dis(cid:173)
`favoring beclomethasone dipropionate and budesonide.f 1°61
`However, more data are needed before drawing firm conclusions
`on the superiority of a drug regarding growth suppression. Cur(cid:173)
`rent evidence seems to advocate once-daily administration of the
`minimum effective dose. Other systemic adverse effects that
`have been linked to intranasal therapy, such as cataract, glaucoma
`and dermal thinning, do not seem to occur in patients receiving
`treatment exclusively by the intranasal route.1 1061
`
`3. Comparing Antihistamines and Intranasal
`Corticosteroids in Allergic Rhinitis
`
`3.1 Perennial Allergic Rhinitis
`
`A number of studies have compared antihistamines and intra(cid:173)
`nasal corticosteroids in allergic rhinitis (table I and table II).
`However, only a few of these have been performed in perennial
`allergic rhinitis. Two 4-week studies compared terfenadine with
`intranasal beclomethasone dipropionatel 1071 and astemizole with
`intranasal budesonide.f 1°81 Both demonstrated intranasal cortico(cid:173)
`steroids to be superior on nasal symptoms. Only one small (n =
`8) nonblind study on astemizole and beclomethasone dipropion(cid:173)
`ate for 12 weeks each, was unable to show differences between
`the two drugs.11091
`Concerning differences between intranasal antihistamines
`and intranasal corticosteroids, azelastine has been compared with
`beclomethasone dipropionate, with no demonstrable differences
`for symptoms, physician's assessment of efficacy or nasal block(cid:173)
`age measured by rhinomanometry.1 1241 However, when azelastine
`Was compared with budesonide in another study, budesonide had
`a significantly superior effect on all nasal symptoms.I 1251 A single(cid:173)
`blind comparison of intranasal levocabastine and intranasal
`bcclomethasone di propionate, which was a follow-up on a double(cid:173)
`blind comparison of levocabastine and placebo, demonstrated a
`better effect of beclomcthasone dipropionate on nasal obstruc(cid:173)
`tion.11261
`
`3.2 Seasonal Allergic Rhinitis
`
`Several comparisons have been done on antihistamines and
`intranasal corticosteroids in patients with seasonal allergic rhini(cid:173)
`tis, almost all being randomized, double-blind studies. Consider(cid:173)
`ing oral antihistamines (table I), results of 15 comparative stud(cid:173)
`ies, in total involving more than 2600 patients, have been
`presented, involving: terfenadine compared with beclometha-
`
`sone dipropionatel 110•111 1 or fluticasone propionate;l 20,11 2. 1 i:i1
`loratadine with beclomethasone dipropionate,1 1141 triamcinolone
`acetonidel 115·1161 or fluticasone propionate;i 117· 1191 astemizoJe
`with beclomethasone dipropionatel 120· 121 I or triamcinolone ace(cid:173)
`tonide;i 1221 and cetirizine with fluticasone propionate.1123 1 With
`the exception of two studies,1 111 ·121 i all were able to demonstrate
`intranasal corticosteroids as significantly more effective than oral
`antihistamines on nasal symptoms. In fact, only one study, corn(cid:173)
`paring astemizole and beclomethasone dipropionate in 74 pa(cid:173)
`tients, showed similar effect on nasal symptoms.l 121 1 A possible
`explanation could be that a very long study period of approxi(cid:173)
`mately 15 weeks for the grass pollen season was used, thereby
`imposing a risk of diluting differences depending on pollen ex(cid:173)
`posure. Actually, the paper lacks pollen data for the last 17 days
`of the study period.
`Although the second exception was unable to disclose dif(cid:173)
`ferences in symptoms, it revealed intranasal corticosteroids as
`superior when applying an objective measure of nasal obstruc(cid:173)
`tion, i.e. rhinomanometry.1 111 1 This difference in nasal obstruc(cid:173)
`tion measured objectively was also seen in one of the studies
`demonstrating difference in nasal symptomatology.1 201 The one
`study in adolescents showed a better effect of fluticasone propi(cid:173)
`onate on nasal peak inspiratory flow rate in a subgroup of pa(cid:173)
`tients.f 1181 Two studies were able to demonstrate significant re(cid:173)
`ductions in the number of nasal mucosa! eosinophils only with
`intranasal corticosteroids.120.1131
`Most studies compare treatments given on a regular daily
`basis . However, a recent randomized, open study compared
`loratadine with fluticasone propionate, when both drugs were
`given as needed throughout the season in patients with ragweed(cid:173)
`induced allergic rhinitis.l 1191 Interestingly, fluticasone propio(cid:173)
`nate, given as needed, seemed superior to loratadine with regard
`not only to nasal symptoms, but also to quality-of-life estimates
`(Rhinitis Quality of Life Questionnaire [RQLQJ) and number of
`eosinophils in nasal lavage.
`Conjunctivitis is often a major problem in seasonal allergic
`rhinitis. One of the reasons for using oral antihistamines rather
`than intranasal corticosteroids has been an expected better effect
`on eye symptoms. Of the previously mentioned studies, only two
`have been able to verify this.I 114,121 J
`The apparent superiority of intranasal corticosteroids over
`oral antihistamines on nasal symptoms was confirmed by a meta(cid:173)
`analysis of 16 studies involving 2 267 subjects,1 1341 which
`showed a better effect of intranasal corticosteroids on nasal ob(cid:173)
`struction, secretion, itching and sneezing as well as total nasal
`symptom score. However, the meta-analysis was unable to
`demonstrate any difference between the two drug classes on oc(cid:173)
`ular symptoms.
`
`''J Adis International Limited. All rights reserved.
`
`Am J Respir Med 2003; 2 ( 1)
`
`Th is mate-ria I w as cap,ied
`3t.t:he NLM and mav he
`
`

`

`~
`Ul
`
`t
`}
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`r
`l
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`-
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`::::;
`'f.
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`\
`
`FP > cetirizine
`
`TA> astemizole
`
`NS
`
`BOP > astemizole
`
`FP > loratadine
`
`FP > loratadine
`
`FP > loratadine
`
`TA> loratadine
`
`TA> loratadine
`
`BOP > loratadine
`
`FP > terfenadine
`
`FP > terfenadine
`
`NS
`
`BOP > terfenadineb
`
`FP > terfenadine
`
`3
`
`4
`
`15
`
`5
`
`4
`
`4
`
`4
`
`4
`
`4
`
`3
`
`2
`
`6
`
`8
`
`4
`
`4
`
`NS
`
`BUD > astemizole
`
`BOP > terfenadine
`
`2 X 12
`
`4
`
`2x4
`
`Cetirizine 1 0mg/FP 200µg
`
`Astemizole 10mg/TA 220119
`
`209
`
`Astemizole 1 0mg/BDP 400119
`
`Astemizole 1 0mg/BDP 400r1g
`
`Loratadine 10mg prn/FP 200µg prn
`
`Loratadine 1 0mg/FP 200µg
`
`Loratadine 1 Omg/FP 200µg
`
`Loratadine 1 0mg/T A 220µg
`
`Loratadine 1 0mg/T A 220µg
`
`Loratadine 1 Omg/BDP 400µg
`
`Terfenadine 120mg/FP 200µg
`
`Terfenadine 120mg/FP 200µg
`
`Terfenadine 120mg/BDP 400rIg
`
`Terfenadine 120mg/BDP 400µg
`
`Terfenadine 120mg/FP 200µg
`
`BOP 200-400µ9
`Astemizole 10-30mg/BDP 400µg,
`
`Astemizole 1 0mg/BUD 400µg
`
`Terfenadine 120mg/BDP 400µg
`
`18
`
`49
`
`Difference8
`
`Duration (w)
`
`Active treatment (daily dose)
`
`prn = as needed; r = randomized; TA = triamcinolone acetonide; > indicates significantly better than.
`BDP = beclomethasone dipropionate; BUD = budesonide; co = crossover; db = double-blind; FP = fluticasone propionate; NS = not significant; o = open; pc= placebo-controlled;
`c Adolescents.
`
`a Statistically significant difference between active medications for one or more nasal symptoms.
`
`b During high exposure.
`
`238
`
`74
`
`158
`
`88
`
`240°
`
`114
`
`274
`
`348
`
`60
`
`232
`
`214
`
`348
`
`8
`
`67
`
`18
`
`r, db
`
`r, db
`
`r, db
`
`r, db
`
`r, o
`
`r, db
`
`r, db
`
`r, db
`
`r, db
`
`r, db
`
`r, db, pc
`
`r, db, pc
`
`r, db
`
`r, db
`
`r, db
`
`o,co
`
`r, db
`
`Vervloet et al.11231
`
`Bernstein et al.11221
`
`Wood11211
`
`Salomonsson et al.11201
`
`Kaszuba et al. 11191
`
`Jordana et ai.11181
`
`Gehanno & Desfougeresl1171
`
`Schoenwetter & Lim11161
`
`Condemi et al.11151
`
`Frolund11141
`
`van Bavel et alJ1131
`
`Darnell et al.11121
`
`Lancer et al.11111
`
`Beswick et al.11101
`
`Bronsky et al.1201
`
`Seasonal allergic rhinitis
`
`Sibbald et al.11091
`
`Bunnag et al.11081
`
`r, db, co
`
`Robinson et al.11071
`
`Perennial allergic rhinitis
`
`No. of patients
`
`Design
`
`Study
`
`Table I. Comparative studies of oral antihistamines and intranasal corticosteroids in allergic rhinitis
`
`-·-·---···---
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