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/$36.00@ 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

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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

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Effectsof traditionalChineseacuouncturein

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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).

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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.

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