Wl AM521NN
`1996
`N0.3
`v.10
`c.»1--------SEQ: SR0060761·
`Tl: AMERICAN JOURNAL OF
`RHINOLOG.Y
`
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`
`WINNER OF THE 199S AMERICAN RHINOLOGIC SOCIETY
`BASIC SCIENCE AWARD
`EURONAL HOMEOSTASIS IN MAMMALIAN OLFACTORY EPITHELIUM:
`REVIEW
`J David Holcomb, M.D., Scott Grabam, MD., and Anne L. Calo/, Ph.D.
`UNCTIONAL ENDOSCOPIC SINUS SURGERY, SYMPTOMATIC RELIEF:
`PATIENT PERSPECTIVE
`Louis]. Conte, D.O., and Norman Holzberg, M.D.
`ENDOSCOPIC PITUITARY SURGERY: A MINIMALLY INVASIVE TECHNIQUE
`Dharambir S. Sethi, MD., F.R.CS., F.A.MS. , and Prem K. Pillay, F.R.CS. (Singapore)
`MMUNOHISTOCHEMICAL ANALYSIS OF MONONUCLEAR INFLAMMATORY CELLS IN
`ASAL AND SINUS EPITHELIUM IN CHILDREN WITH SINUSITIS
`Maria Pena, MD., Linda Brodsky, .M.D. , Janet Goifien, MS, and Bemice Noble, Ph.D.
`COMPARISON OF THE RELATIVE ABILITIES OF ACOUSTIC RHINOMETRY,
`HINOMANOMETRY, AND THE VISUAL ANALOGUE SCALE IN DETECTING CHANGE
`N THE NASAL CAVITY IN A HEAL THY ADULT POPULATION
`A. Tomkinson, F.R.CS., and R. Eccles, D.Sc. (United Kingdom)
`COMPARISON OF SYMPTOM SEVERITY IN NATURAL AND EXPERIMENTALLY
`.
`INDUCED COLDS
`Ronald B. Turner, M.D., 1beodore j. Witek, Jr., Dr.P.H., and Donald K. Riker, Ph.D.
`SUBCELLULAR DISTRIBUTION AND PHARMACOLOGICAL IDENTIFICATION OF Ml
`RECEPTORS IN THE SUBMUCOSAL NASAL GLAND ACINAR CELLS OF GUINEA PIGS
`Seiichiro Naluzbayashi, Katsuhisa Ikeda, Akira Shimomura, DaZheng Wu,
`Narihisa Ueda, Masayuki Furukawa, and Tonwnori Takasaka (Japan)
`EFFECTS OF SOME PRESERVATIVE AGENTS ON RAT AND GUINEA PIG TRACHEAL
`AND HUMAN NASAL BEAT FREQUENCY
`Susanna Joki, VeUo Saano, Jubcmi N uutinen, Pasi Virta, Peklia Karttunen,
`Matti Silvasti, and Elina Toskala (Finland)
`MEDICAL THERAPY FOR THE PREVENTION OF RELAPSING NASAL POL YPOSIS: A
`PILOT STUDY ON THE USE OF FUROSEMIDE BY INHALATION
`D. Passclli, L. Bellussi, M. Laurie/lo, A. Ferrara, and j. M. Bernstein (Italy)
`SPECTRUM OF SEASONAL ALLERGIC RHINITIS SYMPTOM RELIEF WITH TOPICAL
`CORTICOID AND ORAL ANTIHISTAMINE GIVEN SINGLY OR IN COMBINATION
`Carter D. Brooks, M.D., Steven F. Francom, Ph.D., Bruce G. Peel, B.S. ,
`Brenda L. Chene, R.N, and Karen A . Klatt, R.N.
`~ ~BS TRAC TS FROM THE WORLD RHINOLOGY LITERATURE
`
`AN
`
`AF
`
`NI
`
`IR
`
`M A
`
`y
`
`u N
`
`E
`
`9
`
`9
`
`6
`
`I
`4.
`
`Th is materia l was copil!'d
`3t.th,e NLM a nd m 3 y t;e
`!:.1 11-,. i.e..-+ 11 -:': i"".ru-,Mr< ial-.+ I .., H,...
`
`

`

`RHINOLOGY AND NASAL ALLERGY
`VEAR BOOK 1 996
`Table of Contents
`
`5.
`
`4.
`
`PUBLISHER'S PREFACE .......................................... xi
`1. Allergic Rhinitis
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
`2. Drug Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
`3.
`Eosinophils/Basophils/Mast Cells in Rhinitis ....................... 77
`Fungal Disease of the Upper Respiratory Tract ..................... 87
`Immunology of the Nose ....................................... 95
`6. Nasal Polyps
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121
`7. Nasal and Sinus Neoplasm/Granuloma ........................... 131
`8. Non-Allergic Rhinitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141
`9. Nasal Physiology and Anatomy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153
`10. Microbiology of Sinusitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167
`11. Miscellaneous . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191
`12. Radiologic Diagnosis of the Nasal Cavity and Paranasal Sinuses
`. . . . . . 225
`13. Rhinitis .................................................... 239
`14. Sinusitis ................................................... 259
`SUBJECT INDEX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 293
`AUTHOR INDEX .................................................. 301
`
`Th is m ated a I w as C'Cpied
`atthe NLM andmay be
`Su<bject USCo,pyright Law s
`
`

`

`American Journal of Rhinology
`Devored /0 /1111111111ology, Physiology, Biochemisrry,
`a11d Clinirnl Research of rhe Nasophwynx
`95 PITMAN STREET
`PROVIDENCE, RI 02906
`(401) 331-2510
`FAX (401) 331-5138
`
`EDITORIAL BOARD
`Co-editors in Chief
`
`Consulting Editors
`Guy A. Settipane, M.D.
`Clinical Professor of Medicine
`Brown University
`Rhode Island Hospital
`Abstract Editors
`
`Philip Fireman, M.D.
`(Allergy/Immunology)
`Professor & Director
`Department of Pediatrics
`Children's Hospital of Pimburgh
`One Children's Place
`3705 Filth Avenue at DeSoto
`Pittsburgh, PA 15213
`
`john T. Connell, M.D.
`575 Jones Road
`Englewood, NJ 0763 I
`
`Paul V. Williams, M.D., Clinical Professor
`Department of Pediatrics and Environmental Medicine
`University of Washington
`Mount Vernon, WA
`
`Editorial Board
`Valerie J. Lund, M.S.
`University College London
`Rodney P. Lusk, M.D.
`Associate Professor
`St. Louis Children's Hospital
`Richard L. Mabry, M.D.
`Professor
`University of Texas
`Southwestern Medical Center
`Ian S. Mackay, f .R.C.S.
`Consultant, Otolaryngologist
`Brompton and Charing Cross
`Hospitals, London, England
`Robert M. Naclerio, M.D.
`Professor and Chair
`University of Chicago
`Toshia Ohnish, M.D.
`St. Luke's International Hospital, Tokyo
`Gregory S. Weinstein, M.D.
`Assistant Professor
`University of Pennsylvania
`Ernest A. Weymuller, Jr., M.D.
`Professor
`University of Washington
`David M. Yousem, M.D.
`Associate Professor
`University of Pennsylvania
`Allergy/Immunology
`Jean Bousquet, M.D.
`Associate Professor
`University of Montpellier
`Howard M. Druce, M.D.
`Assistant Professor
`New jersey Medical School
`John W. Georgitis, M.D.
`Associate Professor
`Bowman-Gray School of Medicine
`
`Herbert C. Mansmann, Jr., M.D.
`Associate Professor
`Jefferson Medical College
`Kenneth P. Mathews, M.D.
`Professor Emeritus
`Scripps Clinic
`Eli 0. Meltzer, M.D.
`Clinical Professor
`University of California
`San Diego
`Minoru Okuda, M.D.
`Professor
`Nippon Medical Schoold
`John L Seiner, M.D.
`Clinical Professor
`University of Colorado Health
`Science Center
`David P. Skoner, M.D.
`Associate Professor
`Children's Hospital of Pittsburgh
`Raymond Slavin, M.D.
`Professor of Medicine
`University of Colorado
`Health Science Center
`William R. Solomon, M.D.
`Professor of Medicine
`University of Michigan
`Medical School
`Alkis Togias, M.D.
`Assistant Professor
`Johns Hopkins University
`Martha White, M.D.
`Director Allergy Research
`Institute for Asthma & Allergy
`Washington (D.C.) Hospital Center
`
`David W. Kennedy, M.D.
`(Otorhinolaryngology)
`Professor & Chairman
`Department of Otorhinolaryngology
`Head and Neck Surgery
`Universi1y of Pennsylvania Medical Center
`5 Silverstein, 3400 Spruce St.
`Philadelphia, PA 19104
`
`Ralph F. Naunton, M.D., Director
`Communications Sciences & Disorders
`National Institutes of Health
`
`Michael S. Benninger, M.D., Chairman
`Dept. of 01ology, Henry Ford Hospital
`Detroit, Ml
`
`Otolaryngology
`Ronald Amedee, M.D.
`Associate Professor
`Tulane University Medical Center
`Shunkichi Baba, M.D., Professor
`Nagoya City University Medical School
`Andrew Blitzer, M.D., Professor
`College of Physicians & Surgeons of
`Columbia University
`William E. Bolger, M.D.
`Assistant Professor of Surgery
`Uniformed Services University of
`the Health Sciences
`Karen H. Calhoun, M.D.
`Associate Professor & Vice Chair
`University of Texas Medical Branch
`at Galveston
`Charles W. Gross, M.D.
`Professor
`University of Virginia Health
`Sciences Center
`Eugene B. Kern, M.D., Professor
`Mayo Clinic
`Charles f. Koopmann, Jr., M.D.
`Professor
`University of Michigan Medical Center
`Frederick A. Kuhn, M.D.
`Associate Professor
`Medical College of Georgia
`Mary D. Lekas, M.D.
`Professor and Chairman
`Brown University
`Donald W. Leopold, M.D.
`Associate Professor
`Johns Hopkins University
`frank E. Lucente, M.D.
`Professor & Chairman
`Long Island College Hospital
`
`The American Journal of Rhinology (ISSN 1050-6586) is owned and published bimonthly by OceanSide Publications, Inc., 95 Pitman Street, Providence, R.I. 02906. Single copies: $15.00
`(add $S.OO for outside UIA address); Subscriptions: $8S.OO per year, Institution price $115.00 (outside USA add $30.00). Copyright © 1996, OceanSide Publications (401-331-2510; FAX
`401-331-5138). Printed in the U.S.A. Publishing Staff: Cynthia Burke, Carole Fico, Virginia Loiselle.
`
`American Journal of Rhinology
`
`Th is m aterial w asc.o;pied
`at the NLM an<l ma y tie
`S<ubject US Copyright Laws
`
`iii
`
`

`

`This material may be protected by Copyright law (Title 17 U.S. Code)
`
`Spectrum of Seasonal Allergic
`Rhinitis Symptom Relief with
`Topical Corticoid and Oral
`Antihistamine Given Singly
`or in Combination
`
`~arter D. Brooks, M.D., Steven F. Francom, Ph.D., Bruce G. Peel, S.S.,
`renda L. Chene, R.N., and Karen A. Klott, R.N.
`
`ABSTRACT
`
`Sixty ragweed-sensitive volunteers participated in a 2-week
`study that co .
`I ,
`.
`.
`. .
`mparec symptom profiles durmg treatment wzth
`ant1/ustamine (l
`t 1.
`ora ac. me, LOR) alone, topical corticoid (be-
`l
`.
`e omethasone BEC) 1
`,
`a one, or the two drugs combmed. For 5
`, I
`days commenci
`l
`,I'
`.
`.
`ng s wrt y a1 ter the begznnmg of the ragweed
`bloom, patient t k
`s oo no treatment while we collected baseline
`.
`th
`data. They we
`re
`en randonuzed to one of the three treat-
`, ti
`meius, receivi
`ng wt treatment for the balance of the 2-week
`f
`study term T •
`· w1ce eac I day they recorded the severity of
`congestion ey, ,
`.
`.
`,
`.
`e symptoms, runnmg and blowing, itching, and
`sneezing. At the end of the study they provided an estimate of
`1. ,I' 1 .
`overall synmtm
`,.
`n re te1 , w uch favored combined treatment (vs
`L?R p == 0.001, vs BEC P == 0.042). To gain an estimate of
`disease ~ev
`·t
`1
`· en Y anc. treatment effectiveness over time, and to
`cl
`.
`.
`1· · 1 d
`smooth out day to l
`· -
`-cay vanatwn, we l 1vu e symptom
`iary
`reports into three segments (days 2-4, 5-7, and 8-10) for
`
`Fro,'.i The Upjohn Research Clinics and Michigan State Uni(cid:173)
`versity College of Hwnan Medicine, Department of Pediatrics
`arzcl Human Development
`Thi~ study was conducted in a clinic wholly supported by The
`UpJohn Company
`Address correspondence and reprint requests to Dr. Carter D.
`i Brooks, Clinical Research Director, 7000 Portage Road,
`Kalamazoo, Ml 49001-0199
`
`analysis. Combined treatment controlled symptoms better than
`antihista,nine alone in nearly all study segments. Corticoid
`alone or combined with antihistamine provided similar control
`of congestion, running and blowing, and eye complaints. Com(cid:173)
`bination therapy controlled itching and sneezing better, espe(cid:173)
`cially through the study segments 1 and 2. Patient preference
`for combined treatment seems to relate to control of itching
`and sneezing and rapid onset of effect. (American Journal of
`Rhinology 10, 193-199, 1996)
`
`I n several previous studies we have examined profiles of
`
`individual symptoms in allergic rhinitis and the selective
`effects of various treatments on these profiles. We showed that,
`compared to placebo, terfenadine suppressed sneeze, itch, and
`eye symptoms, benefitted congestion marginally, and failed to
`improve running and blowing. Of these, only control of sneez(cid:173)
`ing appeared quickly after introduction of the drug in midsea(cid:173)
`son. 1 Another study intended to establish minimal effective
`doses of oral methylprednisolone found, at 6 mg per day,
`significant suppression of congestion, postnasal drainage, and
`eye symptoms, but not itching, sneezing, and nmning.2 These
`findings could be a clinical expression of the reported inability
`of systemic corticoid to prevent release of mediators from
`human mast cells.3
`It appeared that the symptoms most responsive to anti(cid:173)
`histamine treatment responded least well to low dose cor(cid:173)
`ticoid and vice versa, providing a rational basis for combi(cid:173)
`nation of the two drug types for seasonal allergic rhinitis
`
`t American Journal of Rhinology
`
`~
`
`Th i:s m at er ia I w as copied
`
`193
`
`

`

`We have carried out preliminary studies docu(cid:173)
`treat~ent; dditive protection with combined antihistamine/
`, tment and the equivalence of oral and topical
`men_tin~da
`· . •
`.
`'
`trea
`cort1co1
`'d hen given as part of the comb111at1on.
`.
`corticoi wh ve studied symptom control with combined
`a
`Others
`• e/topical corticoid treatment and have reported
`. .
`.
`ant1h1stamm
`fi dings.4-7 Most reported a more modest 111cre-
`.
`1
`· h
`f'
`b' d
`vanab e
`tn
`treatment
`t'ent-perceived bene 1t wit com 111e
`.
`ment o pa 1
`f
`.
`eliminary studies Jed us to expect.
`than our pr
`I Of the study reported here was to compare profile
`.
`The goa
`·t of individual symptoms, and overall patient per-
`I
`h' . .
`.
`11
`and seven y
`f benefit during seasona a erg1c r m1tls treatment
`.
`· Cl
`cepuon °
`h
`Pl
`.
`S h
`· .
`c enng- oug ,
`antm,
`t'h'stamine (loratadme,
`.
`with an I
`.
`'
`I
`I e topical nasal cort1c01d (beclomethasone, Vance-
`.
`LOR) a on,
`Schering-Plough, BEC) alone, and the two dmgs m
`AQ
`b
`·
`J
`'d
`,
`nase
`. . t'on The study d1 not contam a concurrent p ace o
`com 10a 1
`..
`·
`b
`I Oup but all study part1c1pants entered the treatment
`.
`.
`.
`,
`contra gr
`• on from an untreated baselme observation penod.
`compans
`
`.
`
`STUDY DESIGN AND EXECUTION
`
`Subject Selection
`
`. t subjects enrolled in and completed the study. Each
`S
`
`0
`
`ixt!atment group contained 20 people; sex distribution
`in the LOR group was lOM/l0F, whereas the BEC and the
`LOR/BEC groups both had 7M/13F. The three treatment
`u s were roughly comparable in age, height, and weight.
`I h' · ·
`'bl
`f
`oro P
`All had reliable histories o seasona r 1mt1s compatl e
`'th ragweed seasonal allergic rhinitis and strongly positive
`:gweed skin (prick) tes~s. Many had participate? in prev~(cid:173)
`ous studies and had provided records of the seventy of their
`seasonal symptoms. None had evidence of significant com(cid:173)
`plicating disease on history, physical examination, or
`·creenin<> laboratory testing; women had negative preg(cid:173)
`~ancy te;ts on entry and_ again in mid-study._ All alleged that
`they understood the design, demands.' ~nd nsks of the study
`and signed their consent to part1c1pate. The Bronson
`
`Hospital Human Use Committee reviewed and approved the
`study design and documents.
`
`Treatment Schedule
`
`I n this community, ragweed typically begins to bloom
`
`around August 15. Subjects came under study observa(cid:173)
`tion on 18 August (Thursday) and were seen each Monday
`and Thursday through 1 September. From August 18 to 22
`they used no treatment; this provided baseline information
`documenting seasonal allergic rhinitis severity at the begin(cid:173)
`ning of the observation period. After 22 August they used
`their randomly assigned therapy, remaining on the same
`treatment through I September. At all visits we reviewed
`and verified hay fever symptom severity diaries, checked
`apparent study drug consumption, and inquired for possible
`treatment side effects or other medical events.
`Table I shows the pollen counts obtained during the study
`confirming the appearance of reasonable levels by mid-Au(cid:173)
`gust. (James L. McDonald, M.D., provided aeroallergen counts
`obtained from a rotobar sampler located at an elevated urban
`site about one mile from the clinic where we ran the study.)
`Absolute counts never exceeded 169 grains per cubic meter,
`relatively low compared with prior years' experiences. How(cid:173)
`ever, they seemed to provide an adequate allergic stimulus,
`both in study subjects and nonstudy patients under our care.
`
`Experimental Drug Treatment
`
`W e randomly allocated volunteers to three drug treat(cid:173)
`
`ment groups consisting of:
`L Loratadine (Claritin, Schering-Plough) (LOR) 10 mg
`once a day, plus a placebo spray twice a day.
`2. Beclomethasone (Vancenase AQ, Schering-Plough)
`(BEC) two sprays (about 84 mcg) each side of the
`nose twice a day, plus placebo LOR.
`3. BEC twice a day plus LOR once daily.
`During the treatment comparison, subjects took no other
`treatment that might affect their hay fever.
`
`TABLE I
`
`Ragweed Pollen Grain Count in Particles Per CU Meter. Counts Made Using A Rotobar Sampler Running
`Intermittently on a Downtown Rooftop
`Study Segment
`Ragweed Count
`1
`6
`19
`14
`16
`40
`71
`27
`14
`59
`23
`
`1
`2
`2
`2
`3
`3
`3
`
`Date
`August 23
`August 24
`August 25
`August 26
`August 27
`August 28
`August 29
`August 30
`August 31
`September l
`September 2
`
`Ragweed Count
`83
`162
`169
`95
`144
`144
`116
`76
`67
`45
`19
`
`Study Segment
`
`Baseline
`Baseline
`Baseline
`
`Date
`August 12
`August 13
`August 14
`August 15
`August 16
`August 17
`August 18
`August 19
`August 20
`August 21
`August 22
`
`194
`
`Th is mate·rial w as co,pied
`at the NLM .and m ay be
`
`May-June 1996, Vol. 10, No. 3
`
`

`

`observations and Evaluations
`
`Sy~~tom Se_verity Diaries r~corded the lev~l ,~r disc~~:
`
`fo, t perceived by the subjects for each of five classes
`of seasonal allergic rhinitis symptoms. The diary has served
`us Wei] in earlier studies.
`A.I! subjects made twice daily entries for the following
`h~Y fever-related problems:
`
`• Congestion
`• Running and blowing
`• Sneezing
`• Itching
`• Eye symptoms
`
`For each symptom the diary contained a scale specifically
`describing five levels of severity. The diary also provided
`space for recording use of study drug, need for any inter(cid:173)
`ct.1rrent medications, possible adverse reactions to the study
`cifllgs, and amount of time spent in air-conditioning.
`
`Global Assessment
`
`Qn th~ final treatment clay, we asked all subjects ~o- rate
`
`theu- response to treatment as excellent, good, fair, or
`poor. Although crude and subjective, this approach has
`clearly differentiated among treatments in past studies.
`
`DATA HANDLING AND STATISTICAL ANALYSIS
`
`W e omitted symptom severity scores from the first and
`last clays, as these typically included half day re(cid:173)
`ports only, as well as the first full treatment day, feeling that
`still reflected a transition day providing questionable data.
`it
`To allow comparison with baseline and perception of de(cid:173)
`~elo~ing trends, we collapsed symptom severity reports into
`four Intervals; days -3 to -1 (pretreatment), and treatment
`days 2--4, 5-7, and 8-10. We averaged AM and PM scores and
`cal~ulatecl change from mean pretreatment score for each
`st1
`bJect and each follow-up day. Each symptom change score
`was analyzed using a repeated measures analysis of variance
`model incorporating factors associated with treatment, subject
`~estecl Within treatment, study day, and treatment by day
`mteraction. In addition, the mean pretreatment response was
`used as a covariate. We used contrast statements to make
`treatment comparisons within each of the 3-day follow-up
`periods. A pooled e1rnr term containing both the within- and
`between-subject errors was used in testing. All analyses were
`clone using SAS (SAS Institute, Cary, NC).
`
`RESULTS
`
`Symptom Severity During Baseline
`
`Table II contains overall mean symptom severity scores
`
`collected during the baseline period. During this in(cid:173)
`terval, the volunteers took no medications to suppress their
`rhinoconjunctivitis. Diaries allowed description of symp(cid:173)
`toms on a discrete scale from l (no symptoms) to 5 (max(cid:173)
`imum symptoms). Baseline values largely between 2 and 3
`suggest that patients experienced mild to moderate symp-
`
`TABLE II
`
`Mean (± STD DEV) Severity Scores By Symptom and
`Treatment Group for the Untreated Baseline Period
`BEC
`LOR
`(BEC & LOR)
`2.78 ± 1.00 2.90 ± 0.77
`2.72 ± 0.61
`2.35 ± 0.89 2.28 ± 0.79
`1.93 ± 0.72
`2.83 ± 1.07 2.28 ± 0.83
`2.62 ± 0.55
`
`Congestion
`Eye symptoms
`Running/
`blowing
`Itching
`Sneezing
`
`2.30 ± 0.79 2.00 ± 0.88
`2.48 + 0.70 2.23 ± 0.69
`
`2.44 ± 0.96
`2.22 ± 0.76
`
`toms during this time and that symptom severity was rea(cid:173)
`sonably homogeneous across the three groups.
`
`Overall Patient Assessment
`
`A t the last clinic visit, on the last day of study-im~osed
`
`therapy, we asked each subject for an overal_l estimate
`of the effectiveness of the treatment they ~ad Just com(cid:173)
`pleted. Their options were excellent, good, fa1r, or poor; we
`did not qualify these further.
`.
`.
`.
`Table III contains results of the patient ratmgs. Com?I(cid:173)
`nation treatment provided superior symptom control ~1th
`19/20 reporting good (8) or excellent ( 11) r~sults. f~e
`combination was significantly superior to topical steroid
`alone (P = 0.042), and to antihistamine alone (P = 0.00 l ).
`BEC alone appeared to protect slightly better _th,~n- LOR
`alone, but statistical testing did not confirm the s1gmf1cance
`of this trend (P = 0.122).
`
`Diary Symptom Seve1·ity Scores
`
`F igures 1 through 5 show mean changes in symptom
`
`severity from pretreatment to the indicated treat~~nt
`segment. We looked for treatment effect ?Y detenm'.1'.n~
`symptom severity decrements fro_m basehne and testmg
`these for significance using the paired t-te~t.-
`.
`The figures show several patterns. Ant'.!11Stamme alone
`(LOR, L) produced relatively modest benefit, _almost a!w,?s
`less than that seen with either of the topical cortlcmcl-
`
`TABLE III
`
`Treatment Result
`
`Overall Patient Assessment of Treatment Effectiveness
`Statistical Testing
`Treatment
`(BEC + LOR)
`11
`8
`
`BEC LOR
`6
`4
`Excellent
`5
`9
`Good
`9
`Fair
`4
`0
`2
`Poor
`(BEC & LOR) vs BEC P = 0.042; (BEC & LOR) vs LOR
`p = 0.001; BEC vs LOR P = 0.122.
`
`(
`
`American Journal of Rhinology
`
`This material wasco~ie<l
`
`195
`
`

`

`S = Congestion
`
`Mean Change
`0.1 ·
`
`-0.6
`
`-0 .1 .L - - - - - - - - - - - - - - - - - - - - - -
`B B+L L Group
`B B+L L
`B B+L L
`1---- 3 - , Segment
`1----2 - '
`·-. - 1 -1
`Figure]. Congestion Mean Change by Treatment Group and Study Segment. B = Beclomethasone alone, L = Loratadine alone, B+L =
`Combined Beclomethasone and Loratadine. Segment 1 = Treatment Days 2-4, Segment 2 = Treatment Days 5-7, Segment 3 = Treatment
`Days 8-10.
`
`Mean Change
`
`S = Eye Symptom
`
`o.oo·· r- 1-
`
`1·
`
`.
`'
`.
`
`-0.02 ·
`-0.04
`-0.06 ·
`-0.08
`-0.10 ·
`-0.12 ·
`-0.14 ·
`-0.16
`-0.18
`-0.20 ·
`-0.22
`-0.24
`-0.26 ·
`-0.28
`-0.30 ·
`-0.32
`-0.34
`-0.36
`-0.38
`-0.40 ·
`-0.42
`-0.44 ·
`-0.46 ·
`-0.48
`
`B B+L L Group
`B B+L L
`B B+L L
`Segment
`1----2 ~ - - 3 ----i
`1----1-1
`Figure 2. Eye Symptoms Mean Change by Treatment Group and Study Segment. Group and Segment as in Figure 1.
`
`contammg regimens. Antihistamine benefitted congestion
`(Fig. 1) slightly in segments I and 2, and not at all in
`segment 3. Eye symptoms (Fig. 2) improved minimally
`though never significantly, while running and blowing
`(Fig. 3) showed no LOR-induced improvement. Itching
`
`(Fig. 4) showed consistent and significant lessening during
`LOR treatment, whereas sneezing (Fig. 5) improved in
`segments 1 and 2, but not 3.
`Comparing among the treatments, three diary entries,
`congestion, eye symptoms, and running/blowing showed
`
`196
`
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`attlhe NLM ancl ma ybe
`'icubject US Ca;py:r ight Laws
`
`May-June 1996, Vol. 10, No. 3
`
`

`

`S=Runnlng
`
`Mean Change
`0.2
`
`0.1
`
`-0.8
`
`-0.9
`
`-1.0j____ _ ______ _______ ______ _
`B B+L L Group
`B B+L L
`B B+L L
`1---- 1 ---1
`f---- 2 -1
`1---- 3 -1 Segment
`Figure 3 R . ·
`.,
`'
`· F'
`· wmmg/Blowing Mean Change by Treatment Group and Study Segment. Group and Segment as m 1gure
`
`J
`·
`
`S=ltchlng
`
`l
`
`Mean Change
`0.0 -
`
`-0.2 -
`
`-0.3
`
`-0.4
`
`-0.5
`
`-0.6
`
`-0.7
`
`-0.8
`
`-0.9
`
`-1.0 j____ ________________ ____ _
`B B+L L Group
`B B+L L
`B B+L L
`1 - 2 -
`-
`, - 3 ----J
`Segment
`1---- 1 - -1
`Figure 4. Itching Mean Change by Treatment Group and Study Segment. Group and Segment as in Figure I.
`
`similar improvement with BEC and BEC/LOR combined
`treatment. Combined treatment benefitted sneezing and
`itching significantly better than BEC alone (see Table IV) in
`n_iost of the treatment segments. With BEC alone suppres(cid:173)
`sion of sneezing increased gradually from Segments l
`
`through 3, though the difference from baseline was sig(cid:173)
`nificant in all segments. With combined BEC/LOR
`sneeze suppression appeared promptly and already was
`maximum in Segment I; by Segment 3, BEC and BEC/
`LOR provided similar suppression of sneezing (albeit
`
`American Journal of Rhinology
`
`Th is materi:a I ,vas c.op,ied
`:it the N LM and m ay be
`:.u±>ject US Cop,yright Laws
`
`197
`
`

`

`Mean Change
`0.0
`
`S=Sneezing
`
`-0.1
`
`-0.3
`
`-0.4
`
`-0.5
`
`-0.6
`
`-0.7 ·
`
`-0.8
`
`-0.9 ·
`
`- - - -- -- - - - - - - - - - - - -
`-1.0-'---
`B B+L L Group
`B B+L L
`B B+L L
`t - - 3 - - 1 Segment
`f------ 1 -
`1 - - 2 -----1
`- 1
`5 S'i·ieezin" Mean Change by Treatment Group and Study Segment. Group and Segment as in Figure I.
`"
`.
`
`.
`Figure
`
`TABLE IV
`Probability of BEC vs BEC + LOR Difference for
`Indicated Symptom Severity and Study Segment.
`(BEC vs LOR Showed a High Probability of
`Difference for all Segments and Symptoms
`Except Itching, Segment 1.)
`Segments
`
`Symptom
`
`Congestion
`Eye symptoms
`Running/blowing
`Itching
`Sneezing
`
`1
`
`0.4461
`0.0474
`0.0923
`0.0532
`0.0001
`
`2
`
`0.4461
`0.0550
`0.0244
`0.0001
`0.0001
`
`3
`
`0.6649
`0.2778
`0.6659
`0.0400
`0.0589
`
`still testing statistically different at a 0.0589 level). With
`itching, BEC/LOR provided significantly greater sup(cid:173)
`pression than BEC alone in all segments. Unlike sneez(cid:173)
`ing, control of itching with BEC alone did not increase
`progressively nor approach that achieved with combina(cid:173)
`tion treatment. The difference in itching intensity be(cid:173)
`tween LOR and LOR/BEC, although suggestive in seg(cid:173)
`ment l, tested less than significant (P = 0.1298). With
`segments 2 and 3, and every other symptom, combined
`therapy performed highly significantly better than anti(cid:173)
`histamine alone (P < 0.00 l ).
`
`DISCUSSION
`
`I n analyzing studies of seasonal allergic rhinitis treatment,
`
`0
`
`we have compared symptom responses day by day, or
`alternatively looked at an integrated response over the entire
`study. Both approaches have presented problems. Lookino
`at days individually produces a great deal of variation and
`more data than is really necessary to compare effectiveness
`of several treatments. It will allow insight into developing
`trends and is necessary if one wishes to correlate symptom
`severity with something peculiar to that day, such as
`weather conditions. A single integrated symptom severity
`score representing the typical experience of subjects on a
`given treatment may suffice to compare treatments, but it
`cannot sense differences in the profile of development of
`symptom control over time, Trying to benefit from the
`strengths of each of these approaches, we divided this study
`into 3-day segments, which provided satisfactory indication
`of temporal patterns while smoothing out day-to-clay
`variation.
`We had originally noted that low dose corticoid primarily
`symptoms,
`benefitted congestion, drainage, and eye
`whereas antihistamine affected primarily itching and sneez(cid:173)
`2 This led us to postulate that combination of these
`ing. 1
`•
`drug types would benefit more symptoms but not provide
`improved control of individual parts of the syndrome. In
`fact, our results suggest additive symptom suppression al(cid:173)
`most across the board. With itching and sneezing, which
`showed the greatest increment of benefit from combination
`treatment, the data suggest that both drugs contributed some
`
`198
`
`Th is m ate,ria I ,.,.as copied
`at the NLM and ma ybe
`:.ui>ject US Copyright Laws
`
`May-June 1996, Vol. 10, No. 3
`
`

`

`symptom cont. I , d -J
`•
`.
`•
`10
`t 1e improvement seen with the comb1-
`, .
`<111
`.
`n<1tion result I t·
`rom addition of the effects of the component
`ec
`·
`d
`I
`.
`f' .
`'bl
`ti
`rugs. This sug1rests
`· · o 1er poss, e avenues o rnqmry: w 1at
`·
`d·t·i·
`o
`1 erent dru ,
`.
`•
`h·
`g mcc <1111sms affect a given symptom; what about
`I .
`.
`c ose-res
`ponse relationships with the component drugs?
`W
`, e have examined both single dnws and the combination
`.
`"'
`111 an acute
`I
`nasa allergen challenge model looking only at
`I. .
`.
`' •
`.
`• _.
`c mica! en I
`c P0 mts. For sneczmg and secretion, cornbrned
`.
`t
`.•
`reatrnent h cl
`a no more eHect than corticoid alone. However
`'
`II
`.
`.
`, d
`a ergen-ind
`r'.ses 111 measured nasal airway resistance
`uce
`show _ d
`~ no protection from antihistamine alone partial sup-
`'
`.
`.
`pression witl
`1 cort1co1d alone and total suppression with the
`.
`·
`, ·
`s
`corn
`b
`mation. Adding antihistamine which typically affects
`'
`.
`. ,,
`measured
`n~isal resistance or perceived congestion very
`little
`' to topical steroid seemed to facilitate its antiobstruc-
`t.
`1ve effect . h
`111 t e acute challenge model but seemed to affect
`,
`.
`ti
`f I
`1at p·1rt
`t 1e real disease minimally.
`0
`'
`0
`.
`thers hw
`' e exam111ecl combination treatment and typically
`·
`.
`.
`1eported a I d
`. ' no est mcrement of benefit with combined com-
`,
`· 1
`PMed with
`smg e drug treatment. D'Souza found similar num-
`b
`t·
`ers of sympt
`om- ree days with nasal steroid or nasal steroid
`. .
`I
`.
`.
`.
`· A .
`P us antih1st
`1etrospect1ve patient Jucl1rement on suc-
`amme.
`.
`"'
`cess 111 cont 11·
`ro mg nasal symptoms yielded 76.6% for steroid
`, 1
`a one and 85 5<flo 1'01· t·I
`·
`·
`b'
`·11·
`'cl/
`t
`7
`1e s ero1 ant, 1stam111e corn 111at1011.
`·
`Th
`ere was a .
`·1
`' sim1 ar, modest increment for eye symptoms and
`'
`h
`eadache Ba kh
`6
`c ouse et al. found a substantial increment of
`·
`t-
`b
`ene t ·
`1 111 all symptoms examined comparing antihistamine
`, 1
`.
`a one to •mt'h ·
`' 1 istamme plus nasal steroid. That study did not
`. 1
`·c1
`me ude a st
`· ero1 -alone ann.
`.
`f
`In a stud
`Y o astem,zole, beclomethasone and the two
`d
`'
`s
`·
`rugs comb· d
`found that beclomethasone
`me , Ju111per et al.
`I
`.
`I
`Pus astem·
`1zo e provided no better control of rhinitis than
`b
`I
`I
`ec ometha ·
`included
`'sone a one. Symptoms examined
`.
`.
`.
`.
`.
`sneezing r
`' unny_ nose, stuffy nose, and eye complamts. They
`d.d f'
`'f'
`1 md a ··
`' sign, 1cantly higher use of rescue medication for
`e
`ye _proble1~s among those taking nasal steroid alone.
`Simpson compared placebo, budesonide, terfenadine,
`.
`"
`'d ;
`and budes
`looking at severity scores for
`0 111 e ter1enachne
`'
`nasal bl k
`oc age, runny nose, nasal itching, and sneezing.
`A
`moi~g these, only sneezing showed better control with the
`.
`th
`comb111·1tio
`11
`an with budesonide alone Patients' overall
`'
`.
`.
`.
`d d f"
`assessment sh
`e mite preference for the budeso111de-
`owe
`.
`. .
`.
`. b
`.
`conta111ing r
`eg1mens, ut essentially no difference between
`.
`.
`cortic?id alone and combined with terfenadine.
`Splitting our patient responses into early, mid, and late
`segments allowed us to smooth out short-term variability
`nd
`gauge therapeutic effects that take some time to de(cid:173)
`a
`velop. Symptoms that showed gradual onset of control with
`BEC alone included sneezing and possibly itching and eye
`symptoms (Figs. 5, 4, and 2 respectively). These same
`s~mptoms showed rapid development of maximum control
`with combined BEC/LOR treatment. Several articles have
`looked at the effect of topical corticoid treatment on nasal
`muco:"al mast cell populations, and all have agreed that over
`a penod of time such as we studied here total mast cell
`numbers changed little.9· 10 One group found decreased his-
`
`tamine content in the steroid-treated nasal mucosa without
`accompanying change in mast cell numbers. This suggested
`to them that the topical corticoid had decreased the mast cell
`histamine pool. 9 Others found no changes in overall num(cid:173)
`bers but a corticoid-associated reduction in numbers of
`formalin-sensitive mast cells, indicating differential effects
`on mast cell subpopulations. 10 Sneezing responds quickly to
`antihistamine treatment, 1 and we have felt that it largely
`represents the effects of locally elaborated histamine. The
`pattern of control of sneezing seen in this study may reflect
`the gradual onset of corticoid influence on the local mast
`cell population in the BEC alone group, and this effect plus
`immediate histamine blockade in those getting both corti(cid:173)
`coid and antihistamine.
`This study confirms the overall effectiveness of com(cid:173)
`bined corticoid/antihistamine treatment for ragweed sea(cid:173)
`sonal allergic rhinitis and shows that some symptoms remit
`better and sooner when combined trea