Acupuncture and Loss of Smell

Transcription

Acupuncture and Loss of Smell
142,505-509
Otolaryngology-Headand Neck Surgery i.2010l,
OTOLARYNGOLOGY
ORIGINALRESEARCH-GENERAL
Effectsof traditionalChineseacupuncturein
post-viralolfactory dysfunction
Julia Vent, MD, PhD,Djin-WueWang,MD, andMichaelDamm,MD,
Cologne,Germany
No sponsorshipsor competing interests have been disclosed.for
this article.
ABSTRACT
OBJECTIVE: To date,recoveryof olfactory function after viral
infectionof the upper airway cannot be achicvcdreliably with
pharmacotherapy.
The aim of this studywas to evaluatethe effects
(TCA) on olfactoryfunctionin
of traditionalChineseacupuncture
patientswith persistcntpost-viralolfactorydysfunction(PVOD).
STUDY DESIGN: Historicalcohort study.
SETTING: UnivcrsityMedicalCenter,Departmentof Otorhinolaryngology.
SUBJECTS AND METHODS: A total of l5 patientspresenting to the outpatientclinic with PVOD were treatcdby TCA in 10
weekly, 30-minute sessions.Subjective olfactometry was performed with the Sniffin' Sticks test set. Treatment successwas
defined as an increasein Sniffin' Sticks test scoresof at least six
points.The effectsof TCA, obtainedwith the Xt tcst,were compared with thoseof matchedpairs suffering from PVOD who had
beentreatedwith vitamin B cornplexover l2 weeks.
RESULTS: Eight patientstreatedwith TCA had irrproved olfactory function cornparedwith two treatedwith vitamin B cornplex. 1: test rcvealeda significantlybetteroutcomein olfactory
function in patientsundergoingzlcupuncture
comparedwith patients receiving vitamin B complex (P ....0.02).
CONCLUSION: TCA possiblyoffers a new therapeuticregimen for post-viraldysosmia.More researchirr a larger caseseries
is neededbefore a clearer picture will errerge.
@ 2010 American Academy of Otolaryngology-Headand Neck
Surgery Foundation.All rights reserved.
mong the variouscausesofacquiredolfactorydysfuncf,
.{a.tions are viral upper respiratory tract infections, sinonasaldisease,and trauma after a fall on the back of the
head involving the coup-contrecoupmechanism.lIn the
olfactoryclinic of the Departmentof Otolaryngology,Universityof CologneMedicalCentre,post-viralolfactorydysfunction (PVOD) makes up the largest group of patients,
includingmore than a third of all dysosmicpatients.rThis
distributionof underlyingcausesof dysosmiais comparable
to the populationsreportedby othersmell and tastecenters.
for PVOD;
To date,thereis no validatedpharmacotherapyl2
however.attemDtshavebeenmadeto establisha standardized
tl'eatment.'In the literature,systemicand topicalsteroidsr''las
caroverine,6
alphalipoic
well as vitamin B supplementation,'5
patients.
The
were
used
to
treat
those
acid,7and other drugs
is
to
enhance
regeneration
of
the
Lrnderlying
treatmentstrategy
olfactory epithelium.The olfactory epithelium undergoesa
continuing regeneration,with a balance of apoptosisand
neuro-neogenesis.o
Disturbedbalanceand dominantapoptosis
(asin PVOD) resultin a net lossof olfactoryneuronsand thus
in reducedolfactory function.s The regenerationof olfactory
function can consequentlybe achievedby suppressingcell
deathand inflammation,as well as by promotingregrowthof
However,currently
olfactoryneurons(i.e.,neuro-neogenesis).
no reliabletherapyfor PVOD is available.
The efficacy of alternativeor complementarymedicine is
oftenregardedwith criticismamongacademicsin the Westenr
world. Despitethe increasingpopularityamonglay peopleand
patients,objectivedata about resultsare rarely publishedin
scientificliterature,In the literature,there is only one case
and its methreportof treatmentof anosmiawith acupuncture,
Nevertheless,
a
ods (e.g.,olfactometry)are not standardized."
placebo-controlled
study by Brandt et alro and a large retrorr
spectiveseriesby Hauswaldet al showeda significantimprovementin smell and tastedisordersafter trcatmentwith
acupuncture.
TraditionalChinese acupuncture(TCA) is one of the
oldesthealingmethodsin the world, reachingback in history at least 2000 years.TCA mirrors different meridians,
energy lines, and spots of the body that are balancedin a
healthy physique.Traditional Chinesemedicine seeksto
reestablishan equilibrium of forces in the diseasedbody
between the energies of yin and yang (contrary energies
such as fire and water, hot and cold), which are distortedin
the diseasedbody. There are variousmethodsin acupuncture. The traditionalChinesemethod has been modified by
Europeansto laserbeamacupuncturel2
and auricularacupuncture;rr the latter was developedby Nogier from Lyon, France,
in which all body
as a micro systemtechniqueof acupuncture,
pafis are depictedon areasof the conchaauris.l:l
R e c e i v e dO c t o b e r2 ,2 0 0 9 : r e vise dJa n u a r y6 , 2 0 1 0 t a cceptedJanuaryI l . 2010.
0194-5998/[email protected] 2010 American Academy of Otolaryngology-Headand Neck Surgery Foundation.AII rights reserved
doi :1 0 .1 0 1 6 / i . o t o h n s ,2
1 0 .0 1.0 12
506
and Neck Surgery,Vol 142,No 4, April 2010
Otolaryngology-Head
was to assessthe
The aim of this historicalcohort str-rdy
impact of TCA on post-viralhyp- or anosmicpatientsand
comparethem with a control group treatedwith oral administrationof a vitamin B comolex,
Patientsand Methods
In the olfactoryclinic oI the Departmentof Otolaryngology,
patients
Universityof CologneMedicalCenter,consecutive
with post-viral dysosmia were offered sessionsol TCA
from January[o December'2008. Inclusion critelia were
PVOD that failed to improve or resolve for more than six
months underoral administrationof steroids,followed by
topical application of steroid drops to the olfactory cleft.
Exclusioncriteriawere all other conditionsfor smell loss,
previoussurgeryof the noseand the paranasalsinuses,and
acuteor chronicinflammatorynasaldisease.The studywas
approvedby the institutionalreview boardof the University
of CologneMedical Center.
In 2008, I 5 patients(meanage63.I years,range48-73 r'
6.8 years)weretreatedwith acupuncture
for post-viralsrnell
lossand failedto improveunderthe describedstandardized
treatment.The olfactory dysfunctionhad persistedior 4.3
yearsin the mean (range2-10 years).A thoroughmedical
historyof Westernrnedicineand traditionalChinesernedicine (with specialregardto the energy levels) was taken
with standardized
questionnaires.
Additionally,a systen.ratic
otorhinolaryngologicphysical examinationincluding endoscopyof the olfactory cleft was performedto exclude
nasalpathologies(e.g.,acuteand chronic rhinosinusitis).
The acupunclure
treatmentwas carriedor.rtby a Chinese
physician(authorD.-W.W.), who had beentrainedand had
practicedin China for more than a decade.The local puncture points were the lung meridiansnear the sternum,the
life pointsat the radialpulse/wristareabilaterally,and local,
individualpointsindicatedby the ying and yang imbalance.
The needlecould be turnedclockwiseat insertionfor tonization or counterclockwisefor a more sedating effect ol'
those points and energy centers.The following injection
pointswerechosen:DuMai l6 and 20, Di20, Lu 7 and9, Ma
36, and Ni3. The needleswere lelt in placefor 30 minutes,
and the acupLrncture
sessionswere repeatedweekly for l0
weeks.There were l0 insertionpoints of acupunctureneed l e s per s es s ionan d p a ti e n (.
The olfactory function was evaluatedby the Sniffin'
Sticks Testra (BurghartGmbH, Wedel, Germany)before
and after treatment.Odorantswere presentedin felt-tipped
pens; for odor presentation,the cap was removed by the
investigator and the pen's tip was placed in front of the
subject'snostrils for approximately15 seconds.This test
battery assessed
olfactory function bilaterally and involved
subtestsfor odor threshold(T), discrimination(D), and
identification(I). The sum scoreof the subtestresults(TDI
score) was used as a measureof olfactory function, which
allowed groupingof patientsinto anosmic(TDI score= 15),
hyposmic(15 < TDI score< 30), and normosmic(30 < TDI
score)groups.la
The resultsof TCA were comparedwith matchedpairs
suffering from PVOD who had been treatedwith oral vitamin B complex(Br : thiamine,Bo : pyridoxine,andB', :
cobalamine)
over l2 weeks.The outcomeof the participants
were analyzedretrospectivelyas a historicalcohort study
and comparedwith matchedpairs (matchedfor age,initial
olfactoryperformance,and causeof olfactory loss).Treatment successwas definedas an increasein TDI scoresof at
leastsix points.This increasewas previouslydescribedas a
signi{icantchangein olfactory function.r5A X2 test was
usedto comparethe number of patientswho were successfully treatedin both groups.
Statisticalanalysiswas performedwith SPSSversion17
(SPSSInc., Chicago,IL). The resultswere given as means
with SD (-r) in text and tables.The alpha level was set at
0.05.The power analysisshoweda statisticalpower of 0.9.
Results
No harm or adverseevents were encounteredduring and
after the treatmentphasesin either of the two groups.All
patientscompletedthe study.
The meanTD I scoreoi the TC A groupw as 13. - (5- 1 5. 4)
poi ntsbel breundergoi ngtreatmentand 17.9(+ 6. 5) point s
after completionof ilcupuncturetreatment(Table l). The
matchedpairsof the group treatedwith vitamin B complex
i mprovedi n TD I scorefrom 13.01-t 3.5) to 1 5. 81- t -4. 3;
points. According to our definition of treatmentsuccess
(i.e.,increasein TDI scoreol six pointsor more),olfactory
function improved in the acupuncturegroup in eight patients,whereasonly two improvedundervitamin B supplementationflable 2).
The 12 test revealeda significantlybetter outcome in
olfactoryfunctionin patientsundergoingacupuncture
compar-edwith patientsreceivinga vitamin B complex (P :
0.02).Nevertheless,
one patient'solfactoryfunctiondeteriorated after acupunclure.
Discussion
In lhe presentstudy, about half ol the patientssuffering
from PVOD had improvedollactoryfr:nctionafter l0 weeks
of TCA. This study shows the strongpotentialof TCA to
help recoverolfactory functionafter viral dysosmia.
The exact pathogenesisof PVOD remains unclear.r"
Some authorssuggestthat a viral infection(e.g.,influenza
viruses) of the olfactory mllcosa leads to a predominant
apoptosisin the oifactory neuronsand thus to olfactory loss.
Wang et alrT detecteda virus, parainfluenzavirus type 3
(PIV3), in epithelialsamplesof 22 of 25 (88.0Vo)PVOD
patients.Forty percent of these patientswere anosmic and
60 percent were hyposmic by the Cross-CulturalSmell
IdentificationTest (CC-SIT). The high detectionrate of
PIV3 in the turbinateepithelial cells of PVOD patients
suggeststhat PIV3 may be among the causativevirusesof
PVOD. Konstantinidiset alrs showedthat PVOD exhibits
spring seasonality,with peaks in March and May, and
Vent et al
Effectsof traditionalChineseacuouncturein
501
Table 1
Raw numbers of age and olfactory function (presentedas Sniffin' Sticks TDI scorel of patients before and after
treatment, including categoriesof normosmic, hyposmia,or anosmia in both groups (TCA and vitamin B
treatment)
Aftertreatment
Before treatment
TCAgroup
V it am in
B gr oup
Gender
Age
Male
Male
Female
Female
Male
Female
Male
Female
Male
Male
Male
Female
Male
Fe m a l e
Fe m a l e
Fe m a l e
Female
Fe m a l e
Male
Fe m a l e
Male
Fe m a l e
Male
Fe m a l e
Male
Male
Ma l e
Ma l e
Ma l e
F e ma l e
7 3 .0
7 0 .6
6 1.7
6 0 .3
7 0 .1
6 0 .2
6 3 .8
5 9 .9
6 9 ,9
5 6 ,8
6 9 .1
5 9 ,1
6 6 .8
4 8 .0
5 7 .9
4 2 .0
59.4
6 3 .9
6 2 .9
5 8 .0
7 5 .0
5 8 .3
4 8 .9
6 9 .8
5 9 .8
6 8 .3
5 7 .9
5 8 .3
7 4 .0
6 4 .9
TDI
s c o re
Ouantitativea lteration
o f ol factorVfuncti on
9.00
10.00
7.00
'15.50
13.25
11.00
13.50
13.50
9.00
10.00
7,00
17.00
24.54
19.50
22.75
11.75
13.75
12.50
7.00
12.00
12.00
12.50
8.50
14.25
11.25
9.50
16.00
A nosmi a
A nosmi a
A nosmi a
A nosmi a
A nosmi a
A nosmi a
A nosmi a
A nosmi a
A nosmi a
A nosmi a
A nosmi a
H yposmi a
H yposmi a
H yposmi a
H yposmi a
A nosmi a
A nosmi a
A nosmi a
A nosmi a
A nosmi a
A nosmi a
A nosmi a
A nosmi a
A nosmi a
A nosmi a
A nosmi a
H yposmi a
H yposmi a
H yposmi a
H yposmi a
tY.z5
1 8 .5 0
1 6 .2 5
TDI
TDIscore
difference score
8.75
-2.00
9.00
9.75
10.00
7.25
-4.50
11.00
0.00
4.00
9.00
-5.25
-0.50
-0.75
-0.50
-0.25
2.00
2.00
2.O0
2.75
3.00
3.50
5.50
5.50
- U .5U
3.25
6.50
8.25
Ouanti tati vealt er at ion
of olfactory function
17.75
8.00
16.00
25.25
23.25
18.25
9.00
24.50
9.00
25.50
11.00
26.00
19.25
14.00
22.25
11.00
13.25
12.25
9.00
14.00
14.00
15.25
11.50
17.75
16.75
15.00
15.50
22.50
25.00
t4.3U
H ypos m ia
A nosm ia
H ypos m ia
H ypos m ia
H ypos m ia
H ypos m ia
A nosm ia
H ypos m ia
A nosm ia
H ypos m ia
A nosm ia
H ypos m ia
H ypos m ia
A nosm ia
H ypos m ia
A nosm ia
A nosm ia
A nosm ia
A nosm ia
A nosm ia
A nosm ia
A nosm ia
A nosm ia
H yposm ia
H yposm ia
A nosm ia
A nosm ia
H yposm ia
H yposm ia
H yposm ia
IDl, thre sh old(T),dis c r im inat ion( D) ,and ident if ic a t i o n( l ) [ o f o d o r ) ; T C A ,t r a d i t i o n a lC h i n e s ea c u p u n c t u r e .
hypothesized
that possiblecausativefactorswere influenza
and parainfluenza
viruses(type III), respectively.
Harris et alre explainedthe PVOD that occurspredominantly in the elderly as follows: Olfactory epitheliumun-
dergoessignificantchangeswith age.Over time, patchesof
olfactory epithelium are replaced with respiratoryepitheliLrm;the epitheliallayeralsomay becomethinnerand basal
cell proliferation is reduced. Central causes of olfactory
Table 2
Outcome of olfactory function as measured by an increaseof six points in the TDI score
V i tami n B group
T C A g ro u p
B e fo retre a tm e n t
A nos m ic
Hy pos m ic
Nor m os m ic
AT DI > 6
1 1 (73.3%\
4
(26.7%l
0
A fter treatment
B eforetreatment
After treatment
5
10 \66,7% )
0
I (53,3% )
11 (73.3% \
4 (26.t%\
10 ( 66. 7%\
C (J J . J 7 o ,
0
2 (13.3%l
ICA, tra ditio na lChines eac upunc t ur e;I Df t hr es hol d ( T ) ,d i s c r i m i n a t i o n( D ) ,a n d i d e n t i f i c a t i o n( l ) [ o f o d o r ] .
Absolute number and percentageof patientsof both cohortstreatedeither with TCA or vitamin B before and after treatment.The
12 te st re ve ale da s ignif ic ant lybet t er out c om e in th e n u m b e r o f v o l u n t e e r sw i t h a T D I i n c r e a s eo f s i x o r h i g h e r un d e r g o i n g
acupuncturecomparedwith patients receivingvitamin B complex (P : 0.02).
508
Otolaryngology-Head
and Neck Surgery,Vol 142, No 4, April 2010
impairment in the elderly are also supportedby the theory
that aging leads to atrophy of the nasal mucosa,leaving it
susceptibieto infection.The exact locationof the damagein
PVOD is not yet known, even though biopsy findingsby
Welge-Lussen and Wolfensbergerz'rshowed that direct
damageof the olfactoryreceptorcells was very likely.
Althoughthe pathophysiology
of PVODs is not clear,the
methodsof treatmentconsistof cofiicosteroids,
supplementation with vitamin B complex, smell training, and others.2-a
Heilmann et als reported a significant increasein olfactory
function after administrationof topical steroidsand vitamin B
complex for six months.Whereasthe treatmentwith steroids
can reducelocalinflammation,vitamin B complexmight have
a neuro-regenerative
effect on the cranial nerves.The effectsof
vitamin B deficiencywere extensivelystudiedin humansand
animal models by Scalabrino.2rVitamin B deficiency has
negativeeffectson neuro-neogenesis
and myelinization,and
evokeschangesin cytokine,neurotransmitter,
and growth factor productionand secretion,as well as the generationof
myelin sheaths.Nevertheless,
none of the study patientswas
diagnosedwith or suspectedof sufferingfrom vitamin B deficiency,nor hasthis everbeendiagnosedor suspected
in any
patientwith chemosensory
complaintsat this center.
In contrastto the pharmacological
therapies,the aim of
acupuncture
is to restorea physicalbalanceand to bring the
ying and yang forces into an equilibrium.22A recentreview23describesthe importanceof alternativeor complementarymedicine.Sincenearly40 percentof all patientsin
general are using alternativeor complementarymedicine,
this is a rising issuein discussionsof therapeuticoptions
with patients,as well as in public health or monetary aspects. These papers suggestthat TCA shows anti-inflammatory, antioxidant, and anti-allergic properties,although
the mechanismof actionis unclear.
Our resultsare supportedby a study about acupuncture
in idiopathic taste disordersfrom Brandt et al.rO They
treated 17 patients with gustatory dysfunction by whole
body acupunctureadministeredwith needles.The treatment
successwas definedas improvementin a validated,subjective gustatorytest (basedon impregnatedfilter papers,the
so-calledtaste strips2a)by six points as well as improved
quality of life and mood. Gustatoryfunction improved from
11.1to 17.5points in the true acupuncturegroup, whereas
the sham laser acupuncturegroup improved from 1 1.9 to
only 14.7points.In the true acupuncturegroup,64.7percent
of all patients improved with regard to the definition of
treatment successcompared with only 25 percent in the
control shamgroup.rnHowever, the method of acupuncture
appliedby Brandt et alro differed from the methodwe used.
points(Di4, Ma 13,Ma44,
They usedidenticalacupuncture
KG 23, LG 15,MP 6, Ex-KH 3,LG 20,3E 23, OP 4, OP34)
in every patient, whereas in the present study, additional
individual points were selected to improve the ying and
yang balance.With regard to Chinese acupunctureguidelines, it is not feasibleto standardizeacupuncturetreatment;
rather, individualizedtherapy must be offered.
A method of sham acupunctureby a specialneediewas
developed by Streitberger and Kleinhenz.2sThis needle
does not penetratethe skin and can serve as a meansfor
controllingthe effectof acupuncture.
In light of the smallcase
numberin our study,it was not feasibleto useshamacupuncture. However, receiving intense treatment with acupuncture
(which involvesmany personalcontactsbetweenpatientand
doctor) may have a very different placebo quality than even
taking a tablet (vitamin B substitute)that doesnot have side
effects.This outcome must be consideredin this study.
To our knowledge,this is the first controlledcohort study
to investigatethe effect of acupunctureon post-viral hyposmia in a largenumberof patients,althoughthe patientswere
not blinded to the type of therapy received.Blinding could
have been achieved with laser or sham acupuncture(randomly switching laseron and off, using sham needle)but is
not feasiblein TCA. In Chineseacupuncture,every needle
insertion is believed to have an effect; thus, a "mock"
insertionof a needlein some randompositioncould have
negative effects on the energetic balance of the patient.
Furthermore,the good resultsare explainedby the individualized therapy. However, this individualizedtreatment
makesthe acupuncturetechniqueless comparableor scientifically valuable.We must understandthat TCA is not
basedon the same scientific,rigid rules used in Western
medicine;thus,theserules may not accuratelyevaluatethe
the
treatmenteffectsof TCA. Hauswaldet alir investigated
effect of acupunctureon 80 patientswith olfactory dysfunction of various causes;however, of the 42 patientstreated
with infectiousolfactory dysfunction (i.e., POVD patients),
only 12 were anosmic and 30 were hyposmic. Hyposmic
patients tend to have a better prognosis in recovery of
olfactory dysfunction.The authorsreporteda recovery rate
of 70 percentof all patientsand also recommendacupuncture as a treatmentfor PVOD.
A key findingof this historicalcohortstudy is that TCA
seemsto be beneficialin treatingsteroid-reluctantpost-viral
hyposmiaand is superiorto the administrationof vitamin B
complexsuppiementation.
Conclusion
The presentstudy was conductedto gatherpilot data.About
half of our patientsimproved their olfactory function under
TCA. Further investigationsin a largerpopulationwill have
to confirm this effect of acupuncturein PVOD. Nevertheless,the observedhigh responserate of about 50 percentfor
TCA was superior to that of vitamin B complex or that of
spontaneous
remissionand offers a possiblenew therapeutic
regimenin post-viraldysosmia.
Author Information
From the Departmentof Otorhinolaryngology,Head and Neck Surgery,
University of Cologne Medical Center, Cologne, Germany
Vent et al
Effectsof traditionalChineseacupuncturein
Conespondingauthor: Julia Vent, MD, PhD, Departmentof Otorhinolaryngology, Head and Neck Surgery,University of Cologne Medical Center,
Kelpener Str. 62, 50924 Cologne, Germany.
E-nrail address:[email protected]
Data were partially and orally presentedat the Annual Meeting of the
Germany Academy of Otolaryngology, Head and Neck Surgery, Bonn,
Germany, May 3, 2008.
Author Contributions
Julia Vent, study design and conduct, data retrieval, manuscriptpfcparation; Djin-Wue Wang, acupuncture,data retrievalt Michael Damm, study
desi g n ,s t a t i s t i c aal n a l ysis,m a n u scr ip pt r e p a r a tio n .
Disclosures
Competing interests: None.
Sponsorships: None.
References
l. D a m m M , T e m m el A, We lg e - L u sse n
A, e t a l. Olla cto r yd ysfuncti ons.
Epidemiologyand therapyin Germany,Austria and Switzerland.HNO
2004.52:l12-20.
2. Hummel T, Rissom K, Reden J, et al. Effects of olfactory training in
patientswith olfactory loss. Laryngoscope2009;l 19:496-9.
3. Heilmann S, Huettenbrink KB, Hummel T. Local and systemic administrationof corticosteroidsin the treatrnentof ollactory loss. Anr J
R h i n o l 2 0 0 4 :| 8 : 2 9 - 3 3 .
4. S t e n n e rM , V e n t J , Hu e tte n b r in kKB, e t a l. T o p ica lth e r a p yi n anosnri a:
relevanceof steroid-responsiveness.
Laryngoscope2008;I I 8: | 68 l-6.
5. Heilmann S, Just T, Goktas O, et al. lEffects of systcmic or topical
administrationof corticosteroidsand vitamin B in patientswith olfactory lossf . LaryngorhinootoloEie 20O4:83:129 -3 4.
6. Q u i n t C , T e m m e l A F , Hu m m e l T , ct a l. 1 ' h e q u in o xa linederi vati ve
caroverinein the treatmentof sensorineuralsn.relldisorders:a proofof-conceptstudy. Acta Otolaryngol 2002 122:811- 8 | .
7. H u m r n e lT , H e i l m a n nS, Hu tte n b r in kKB. L ip o ic a cid in the LreaLrnent
of smell dysfunctionfollowing viral infection of the uppcr respiratory
tract. Laryngoscope 2O02,| 12:20'76 * 8O.
8. K e r n R C , C o n l e yDB, Ha in e sGK, Ill, e t a l. Pa th o lo g yo f the ol l actory
mucosa:implications for the treatmentof olfactory dysfunction. Laryngoscope2004t1| 4:219 - 85.
509
9. Michael W. Anosmia treatedwith acupuncture.Acupunct Med 2003:
2l :153-4.
I0. Brandt H, Hauswald B, langer H, et al. Efficacy of acupuncturein the
heatmentof idiopathic tastedisorders.Dt Ztschr f Akup 2008;5I :24-3 L
ll. Hauswald B, Tiinzer K, Huettenbrink KB. Acupucture: results in
patientswith an- and hyposmia.Booklet of the symposiumof the 2nd
acupuncturesymposiumof Mainz, I 998. GermanSocietyof Acupuncture. March 21. 1998.
12. Pothman R, Yeh HL. The effects of treatmentwith antibiotics,Iaser
and acupunctureupon chronic maxillary sinusitis in chiidren. Arn J
C hi n Med 1982;10(l -,1):55-8.
I3. Tanaka O, Mukaino Y. The effect of auricular acupunctureon olfactory acuity. Am J Chin Mecl 19991.27(l):19-24.
14. H url mel T, K obal G, Gudzi ol H , et al . N ormati vedatafor the "S ni ffi n'
S ti cks"i ncl udi ngtestsof odor i denti l l cati on,odor drscri mi nati on,
and
olfactory thresholds:an upgradebasedon a group of more than 3,000
subjects.Eur Arch Otorhinolaryngol 200'7;264:237- 43.
I5. R edenJ, MLrel l erA , Muel l er C , et al . R ecoveryof ol fa c toryfunc ti on
following closcd head injury or infections of the upper respiratory
tract.A rch Otol aryngolH ead N eck S urg 2006;132:26 5-9.
16, Mul phy C , S chubertC R , C rui ckshanksK J, et al . P reva l enc of
e ol fac tory i rnpai rmenti n ol der adul ts.JA MA 2002;288:230 1-12.
17. Wang JH , K w on H J, Jang Y J. D etecti onof parai nfl u enz a
v i rus 3 i n
turbi nateepi thel i alcel l s of postvi ral ol factory dysfunc ti onpati ents .
Laryngoscope2007: | 17: | 445-9.
I 8. K onstanti ni diI,
s H aehnerA , Frasnel lJ,
i et al . P osti nfecti ousol fac tory
dysfunctioncxhibits a seasonalpattern. Rhinology 200644:.135-9.
19. H arri s R , D avi dsonTM, Murphy C , et al . C l i ni cal ev al uati onand
synlptoms of chemosensoryimpairment: one thousand consecutive
casesfror.nthe Nasal Dysfunction CIinic in San Diego. Am J Rhinol
2006:20:l 0l -8.
20. Welge-LussenA, WolfensbergerM. Olfactory disordersfollowing upper
rcspiratory tract i nfections. Adv Otorhinolaryngol 2006:63: 125-32.
21. S cal abri noG. I'he mul ti -facetedbasi s of vi tami n B I2 (c obal ami n)
neurotrophismin adult centralnervoussystem:lessonslearnedfrom its
dcliciency. Prog Neurobiol 2O09:88:203-20.
22. ZhactXX, Wang XX, Zhao Z, et al.Talk about nomenclatureof twelve
rncridians liom quantitative yin-yang theory. Zhongguo Zhen Jiu
2009:29:227-30.
23. Mainaldi T, Kapoor S, Bielory L. Complen.rentaryand alternativc
s vi tami nsand thei r i mmunol ogi c
nredi ci ne:herbs,phytochemi cal and
efl'ects.J A)lergy Clin lrnmunol 2009:123:283-94.
24. Landis I3N, Welge-LuessenA, BramersonA, et al. "Taste Strips"-a
rapid, lateralized,gr.rstatorybedside identification test based on impregnatedlilter papers.J Neurol 2009:256:242-8.
25. S trei tbergelK , K l ei nhenzJ. l ntroduci nga pl acebone edl ei nto ac upunctureresearch.Lancet I9981352:364-5.