nasal airflow and hand preference - -orca
TRANSCRIPT
Nasalairflowandhandpreference:Istherealink?
SubmittedtoCardiffUniversityforthedegreeofMasterofPhilosophy
AnniePriceMBBCh,MRCS(ENT)
CardiffSchoolofBiosciencesCardiffUniversity
Wales,UnitedKingdomNovember2016
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DECLARATIONThisworkhasnotbeensubmittedinsubstanceforanyotherdegreeorawardatthisoranyotheruniversityorplaceoflearning,norisbeingsubmittedconcurrentlyincandidatureforanydegreeorotheraward.Signed:AnniePriceDate:18/11/2016STATEMENT1ThisthesisisbeingsubmittedinpartialfulfillmentoftherequirementsforthedegreeofMPhil.Signed:AnniePriceDate:18/11/2016STATEMENT2This thesis is theresultofmyown independentwork/investigation,exceptwhereotherwisestated,andthethesishasnotbeeneditedbyathirdpartybeyondwhatispermittedbyCardiffUniversity’sPolicy on the Use of Third Party Editors by Research Degree Students. Other sources areacknowledgedbyexplicitreferences.Theviewsexpressedaremyown.Signed:AnniePriceDate:18/11/2016STATEMENT3Iherebygiveconsentformythesis,ifaccepted,tobeavailableonlineintheUniversity’sOpenAccessrepositoryandfor inter-library loan,andfor thetitleandsummarytobemadeavailabletooutsideorganisations.Signed:AnniePriceDate:18/11/2016STATEMENT4:PREVIOUSLYAPPROVEDBARONACCESSIherebygiveconsentformythesis,ifaccepted,tobeavailableonlineintheUniversity’sOpenAccessrepository and for inter-library loans after expiry of a bar on access previously approved by theAcademicStandards&QualityCommittee.Signed:AnniePriceDate:18/11/2016
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SummaryInrecentyears,evidencehasemergedsuggestingthatnasalairflowasymmetryandbrainasymmetrymaybelinked.Thenoseisuniqueinthatitexhibitsasymmetricalairflowwith thedominantairflowalternating fromonenasalpassage to theotherover a periodof hours. The cerebral hemispheres also exhibit both functional andstructural asymmetry, and one of themost obviousmanifestations of this is handpreference.Overtenyearsago,itwassuggestedthatnasalairflowdominanceandhandpreferencewerelinked.Theaimsofthisthesisweretoexploretheliteraturerelating to nasal airflow and brain activity and to conduct a cross-sectionalobservational study looking for a correlation between nasal airflow and handpreferenceinhealthyindividuals.ThemodifiedGlatzelMirrorwasusedtorecordthedominantnasalpassageat15-minuteintervalsovera6-hourperiodin29healthysubjects,ofwhom15wereleft-handed and 14 were right-handed, as measured by the Edinburgh HandednessInventory(ShortForm).As expected based on previous studies, there was considerable variability in thenasal airflow patterns of the individuals observed, but over half demonstrated atleastonedefiniteandsustainedreversalofnasalairflowdominance.Nocorrelationbetweennasalairflowdominanceandhandpreferencewasidentified.Asymmetricalcerebralorganisationmayofferadvantages forcomplexactionssuchasspeechandhandgestures.Nasalairflowiscontrolledbytheautonomicnervoussystemandthefunctionofasymmetricalnasalairflowismostlikelyimmunedefenceand air-conditioning. Having a dominant nasal passage, comparable to having adominanthand,wouldnot thereforebephysiologically advantageous. The resultspresentedhere,alongwithfurtherevidencefromtheliterature,donotsupportthepreviouslyreportedcorrelationbetweenhandpreferenceandnasalairflow.
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ContentsChapter1:IntroductionA(Overview) 11.1:Nasalairflowasymmetry 11.2:Definingthenasalcycle 11.3:Functionofthenasalcycle 41.4:Durationofthenasalcycle 61.5:Controlofnasalairflow 71.6:Sensingnasalairflow 101.7:Measuringnasalairflow 111.8:Factorsthataffectnasalairflow 181.9:Nasalairflowandhandpreference 251.10:Handedness 301.11:Aimsofthesis 32Chapter2:IntroductionB(Nasalairflowandbrainactivity–literaturereview) 342.1:Introduction 342.2:Methods 352.3:Results 352.4:Conclusions 45Chapter3:Methodology 463.1:Ethicalapproval 463.2:Studydesign 463.3:Studypopulationandrecruitment 473.4:Samplesizeandpower 483.5:Measurementofhandedness 483.6:Measurementofnasalairflow 493.7:Trialenvironmentandprocedure 493.8:Blinding 523.9:Statisticalanalysis 52Chapter4:Subjects 534.1:Introduction 534.2:Methods 534.3:Results 544.4:Discussion 58Chapter5:Nasalairflowpatterns 625.1:Introduction 625.2:Methods 635.3:Results 655.4:Discussion 75
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Chapter6:Nasalairflowandhandpreference 816.1:Introduction 81 6.2:Methods 816.3:Results 826.4:Discussion 95Chapter7:FinalDiscussionandConclusions 997.1:Nasalairflowasymmetryandcerebralasymmetry 997.2:Handpreferenceandnasalpassagedominance 1007.3:Limitationsofthisstudy 105References 106Appendix1:Inclusionandexclusioncriteria 116Appendix2:Participantinformationsheet 117Appendix3:Consentform 118Appendix4:EdinburghHandednessInventory(ShortForm) 119
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Chapter1:IntroductionA(Overview)
1.1:Nasalairflowasymmetry
Thenoseisauniqueorganinthatitexhibitsasymmetricalairflowwiththedominant
airflowalternatingfromonenasalpassagetotheotheroveraperiodofhours (1).
Changesinnasalairflowaremediatedbyalternatingdilationandconstrictionofthe
venous erectile tissue in the nasal mucosa, by action of the sympathetic nervous
system(2).Thisalternationofnasalairflowisoftendescribedasa“nasalcycle”asit
canbe regularand reciprocal (1,3-5). The firstdescriptionof thisphenomenon is
attributed toKayser in1895 (6). Sen (1901)documentedobservationsofhisown
nasalmucosa,statingthatthealternatingcongestionanddecongestionofthenasal
erectile tissueoccurredwith“clockwork-like regularity” (7). Morerecentevidence
has suggested that regular periodicities are not always present and that there is
significant inter-individual variation in both reciprocity and rhythmicity (8, 9),
contradictory to the term “cycle”. Patterns of nasal airflow also vary within
individuals,with a lack of reproducibility seenwhenmeasurements of airflow are
repeated on different days (10, 11). Nonetheless, the presence of asymmetrical
nasalairflowthatfluctuatesspontaneouslythroughoutthedayhasbeenestablished
bymultiplestudies(4,8-13).
1.2:Definingthenasalcycle
As mentioned above, there is some confusion in the literature surrounding the
definition of the nasal cycle. Gilbert and Rosenwasser (1987, p.180) suggest that
accordingtotheclassicalideaofreciprocalandregularalternationsofnasalairflow
referredtoasthenasalcycle,“theleftandrightsideshaveidenticalperiods,are180
degreesoutofphase,andhavesimilarmeanairflowandamplitude”(8).However
this isnotnecessarilythecase,andinmanystudiesthetermnasalcycleisusedto
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describe any asymmetries or patterns seen in nasal airflow. Without a clear
definition of what constitutes a nasal cycle, results of research studies can be
difficulttointerpret.ThisissuewashighlightedbyFlanaganandEccles(1997)who
developednumericalparameterstodefinethespontaneouschangesinnasalairway
resistancecommonlyreferredtoasthenasalcycle(13).Thenumericalparameters
suggestedwere the correlation co-efficient (r value) and airflow distribution ratio
(ADR)(13).Thecorrelationco-efficientisameasureofreciprocityrangingfrom-1,
whichwould indicateastrict reciprocal relationship, to+1,whichwould indicatea
strictly in-phase relationship (13). TheADR isameasureof the relativevolumeof
airflowthrougheachnasalpassagecalculatedasapercentageofthetotalvolumeof
airflowoveraneight-hourperiod,witharangeofzerotoone,whereoneindicates
thatthedistributionofairflowbetweenthetwonasalpassageshasbeenequalover
time(13).Theauthorsarguethatinordertobeclassedasanasalcycle,patternsof
nasalairflowshouldexhibitacertaindegreeofreciprocityaswellasequalvolume
distributionbetweenthenasalpassages,anddefinethisasanrvalueabove0.6and
an ADR above 0.7 (13). Using these numerical definitions, only 21% of healthy
subjects demonstrated a nasal cycle, although the majority exhibited a trend
towards reciprocity and equalisation of airflow suggesting some sort of pattern in
nasalairflowchanges(13).
HasegawaandKern (1978)defined thenasal cycle in rhinomanometric termsas a
changeofnasalairwayresistanceof20%ormorecomparingeachnasalpassagefor
two consecutiveobservations at least 15minutes apart (10). Using thisdefinition
theyfoundthat72%of50subjectsobservedovera7-hourperiodhadatleastone
nasalcycle(10).
Huang et al. (2003) defined the nasal cycle as significant negative correlation
between the two nasal passages, but did not specify what they deemed to be
significant(14).Intheiranalysisof10subjects,only5exhibitedanasalcycleasper
thisdefinition(14).
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Kern(1981)suggestedtheterm“non-cyclenose”todescribeindividualswithoutthe
classical features of a nasal cycle (9). After studying nasal airflow patterns in 14
subjectswhodidnothaveanasalcycle,hesuggestedthreecategoriesforthenon-
cyclenose(9):
1. Nochangeinnasalresistance.
2. Moderatefluctuationsinnasalresistanceinonenasalpassagebutnochange
intheoppositeside.
3. Fluctuations in nasal resistance in both nasal passages but no reversal of
dominance i.e. greater airflow from one side to the other (in-phase
relationship).
Gallego et al. (2006) looked at the patterns of nasal airflow in children aged 2-11
yearsandcategorisedthenasalcycleintofourtypes(15):
• Classic–congestioninonenasalpassagewithaccompanyingdecongestionin
the other but no change in the total nasal airway volume, i.e. a reciprocal
relationship.
• Parallel – alternating congestion and decongestion with an in-phase
relationship.
• Irregular – changes in total nasal airway volume but with no discernable
pattern.
• Nopattern–nochangesintheunilateralortotalnasalairwayvolumei.e.no
nasalcycle.
Interestingly, all subjects demonstrated some sort of nasal cycle, but themajority
(50%)hadanirregularpattern(15).Itshouldbenotedhoweverthatthiswasashort
study with a measurement period of only 3 hours, and it could be argued that
patternsmayhaveemergedorchangedoveralongertimeperiod.
Whilstseveralauthorshaveattemptedtodefinewhatconstitutesanasalcycleusing
differentmethods,ageneralconsensushasnotyetbeenreached.Thepresenceof
fluctuatingpatternsofnasalairflowisnotdisputed,buttheterm“cycle”isprobably
notappropriategiventhat inmanyindividualsrhythmicandreciprocalalternations
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in nasal airflow do not occur. For the purposes of brevity and clarity, fluctuating
patterns of nasal airflow will be referred to as the nasal cycle in subsequent
introductorychapters.
1.3:Functionofthenasalcycle
Thenasalpassagesarethenaturalpointofentryforairintotherespiratorytractin
healthyhumans,despitehavingagreaterresistancetoairflowcomparedtotheoral
cavity (16). The principal function of the nose is to prepare inspired air for rapid
gaseousexchangeinthelungs(17).Thisrequirescleaningandfiltering,heatingand
humidification.Howevertheexactpurposeofthenasalcycleremainsunclear.
Since the nasal mucosa continuously comes into contact with pathogens
encounteredininspiredair,Eccles(1996)suggestedthatthenasalcyclemayhavea
role in respiratory defence (18). The nasal mucosa has a rich blood supply, with
arteriesthatemergefromthebonywallsofthenasalcavitytoterminateincapillary
networks situated in the subepithelial layersof themucosa (17). Thesecapillaries
drainintovenoussinusoidswhichformvenousplexusesdeeperinthemucosa(17).
Thevenousplexusesareoftenreferredtoaserectiletissueastheycontainsmooth
muscularwallsandcanbeclosedbysphinctermuscles(17,19).Histologicalstudies
in rabbits revealed the presence of endothelial fenestrations in the subepithelial
venous sinusoids of the nasal mucosa in the regions of the nasal septum and
turbinates (20, 21). Interestingly, these fenestrationswere seen to open towards
theadjacentepithelium,andwerenotpresent in theveins situateddeeper in the
nasalmucosa (21). Based on these findings, Grevers (1993) suggested that these
fenestrated veinswereprobably involved in the regulationofnasal fluid secretion
(21).Theexudationofplasmafromthenasalmucosalvesselsisimportantasafirst
line defence mechanism (22). Not only does the plasma exudate contain
immunoglobulinsandpro-inflammatoryproteins,butinadditiontheflowofexudate
ontothemucosalsurfacecouldhelpwashawaypathogensandforeignmaterial(18).
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The alternating congestion and decongestion of the venous sinusoids, known to
produce the nasal cycle, could in fact be acting as a pump mechanism for the
secretionofplasmaexudate(18).Duringthecongestedphase,hydrostaticpressure
willbe increased inthevenoussinusoidsduetothehigherbloodvolume,andthis
couldaidtheformationofplasmaexudate(18).Followingonfromthis,contraction
ofthesmoothmuscleinthewallsoftheveinsduringthedecongestivephasecould
squeeze the exudate through the fenestrations towards themucosal surface (18).
Thistheoryissupportedbyobservationsofanincreaseintheamplitudeofthenasal
cycleassociatedwithupperrespiratorytractinfection(23),whereintheexaggerated
congestion and decongestion in the venous system could lead to increased
productionofplasmaexudatethatisrichinimmunoglobulinsandpro-inflammatory
proteins(18).
It has also been suggested that thenasal cyclemaybe involved in controlling the
balanceofheatandwaterexchangerequiredtoconditioninspiredairinpreparation
for gaseous exchange in the lungs (16). The nasal airway is lined with liquid,
sometimestermedairwaysurfaceliquid(ASL),whichisderivedfromtheepithelium
andsubmucosalglandsandconsistsofapericiliarylayerwithoverlyingmucus(24).
This fluid is required for thehumidificationof inspiredairand for the transportof
trappedpathogens(24).Effectivemucusclearance,andhenceclearanceoftrapped
pathogens and particles, is inhibited if the ASL becomes dehydrated (25). Using
computermodels,White et al. (2015) demonstrated a possible role for the nasal
cycle in dealing with the difficulties of simultaneously carrying out both of these
important functions, i.e. air-conditioning andmucociliary clearance (26). Efficient
heating and humidification requires higher airflow velocities, whereas efficient
mucociliarytransportrequireslowerairflowvelocities(26).Duringthedecongested
phaseof thenasal cycle, severedehydrationof theASLoccursdue to the greater
airflowthoughthenasalpassage(26).Conversely,duringthecongestedphase,the
reduced airflow results in only minor dehydration of the ASL which leads to
improvedmucociliaryclearance(26).Alternatingthepartitioningofairflowthrough
eachnasalpassageallowsforoneside(thecongestedside)tomaintainitsASLand
carryouteffectivemucociliaryclearance,whilsttheothersidereceivesthegreatest
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proportion of inspired air which can be efficiently heated and humidified but
consequently leadstoASLdehydration(26). Thisthenswitchesover,reducingthe
amountoftimethateachnasalpassageisexposedtodryingconditionsandperhaps
moreefficientlycarryingout theprinciple functionsof thenose– filtering,heating
andhumidificationofinspiredair(26).
1.4:Durationofthenasalcycle
Thereporteddurationofthenasalcyclevarieswidelyintheliterature.Thismayin
part be due to the problems surrounding the definition of the nasal cycle, as
discussedabove.Inadditionthereissignificantvariabilitybothwithinandbetween
individuals, and a lack of reproducible findingswhen the samemeasurements are
repeatedinthesameindividualsbutondifferentdays(10,11).Table1givessome
examples of average nasal cycle durations previously reported in the literature.
There are varying methods of measurement and sampling intervals, which again
couldbeafactorforthesignificantvariabilityseen.AsshowninTable1theshortest
duration recorded is 20minutes (27) and the longest is 7.3 hours (8). The short
duration of 20 minutes was recorded using continuous portable rhinoflowmetry
duringwakefulness,andthedevicewasgiventoparticipantssothatrecordingcould
take place during their normal daily activities (27). A longer cycle duration was
recordedduringsleep(27),whichhasbeenechoedinotherstudies(28).Tahamiler
etal.(2009)recordedanothershortdurationof30minutesusingOdiosoft-Rhino,a
software programme that detects the sounds generated during normal nasal
breathing (29). Their sampling period was 30 minutes, longer than some of the
other studies that failed todemonstrateaperiodicityof less than1hour (10,30).
Interestingly, they made their recordings by installing the programme on the
subjects’owncomputerssothatagainthetestcouldbecarriedoutinthesubjects’
ownenvironmentratherthan ina laboratory(as isthecaseformoststudies) (29).
They defined a nasal cycle as a statistically significant difference in the values
obtained from each nasal passage (29), which does not take into account the
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reciprocityandregularityusuallyconsideredtobethehallmarksofacycle.
Table1:Examplesofnasalcycledurationsreportedintheliteratureandthedifferentmethodsusedtorecordthem.Study Number
ofsubjects
Agerange(years)
Methodofmeasurement
Durationofmeasurement(hours)
Samplingperiod(minutes)
Cyclelength(hours)Mean S.D. Range
HasegawaandKern1978(10)
50 24 Posteriorrhinomanometry
7 15 2.9 1-6
GilbertandRosenwasser1987(8)
16
18-34 Anteriorrhinomanometry
8 10 4.3 1.3 2.4-7.3
Gilbert1989(31)
9 18-30 Anteriorrhinomanometry
8 5 4.5 1.0 3.5-6
Huangetal.2003(14)
10 18-32 Posteriorrhinomanometry
6 10 3.5 2.3-4.4
Ohkietal.2005(30)
20 Meanage:45.8
Portablerhinoflowmeter
12 Continuous 1.8 - -
Tahamileretal.2009(29)
20 24-30 Odiosoft-Rhino 12 hours on 4differentdays
30 - 0.5-2.5
Rorhmeieretal.2014(27)
20 22-66 Portablerhinoflowmeter
23 Continuous 1.5 0.3-5.6
1.5:Controlofnasalairflow
Changesinnasalairflowaremediatedbyalternatingdilationandconstrictionofthe
venous erectile tissue in the nasal mucosa, by action of the sympathetic nervous
system(2).Thepresenceofavasomotorsupplytothenasalmucosawasfirstnoted
byTschalussowin1913(32).Experimentsoncatsdemonstratedthatstimulationof
thecervicalsympatheticchainledtoimmediatevasoconstrictioninthenasalveins,
indicatingtheoriginofthevasomotorfibres inthecervicalsympatheticchain(33).
Application of topical sympathomimetics causes decongestion of the nose and a
marked increase in nasal airflow (34, 35). Conversely, blockade of the stellate
ganglionor performanceof a cervical sympathectomyare known to cause venous
congestionandreducednasalairflow(36,37). Insummary, increasedsympathetic
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tone causes vasoconstriction of the nasal veins, leading to an increase in nasal
conductance,andreductionorblockadeofsympathetictonecausesvasodilationof
thenasalveins,leadingtoanincreaseinnasalresistance.
Thereisgrowingevidenceforacentralcontrolmechanismofnasalairflow.Studies
onanaesthetisedcatsledtothenotionofcollectionsofsympatheticneuronsinthe
brainstem, so-called “oscillators”, with an asymmetry in sympathetic discharge
between the left and right oscillators resulting in asymmetry of nasal airflow
between the left and right nasal passages (38). The dominance of sympathetic
outputalternatesfromlefttorightandviceversa,causingthereciprocalchangesin
nasal airflow, both spontaneously and in response to electrical stimulation of the
brainstem (38). However ithasbeenpostulated thatoverall controloccursat the
levelofthehypothalamus,asinanimalstudies,electricalstimulationherecausedan
overall increase in sympathetic tone and greater nasal airflow bilaterally (33, 39).
Therefore, with the hypothalamus as the generator of a rhythmic nasal cycle,
increasedordecreasedhypothalamicoutputwillstimulatethebrainstemoscillators
symmetrically, but these brainstem oscillators will influence nasal airflow
asymmetrically due to their reciprocal differences in sympathetic discharge (11).
ThisissummarisedinFigure1.
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Figure1:Modeltoexplainthecontrolofnasalairflow.Theoverallalternationinsympatheticactivityoveraperiodofhoursiscontrolledbythehypothalamusandtheasymmetryinsympatheticoutflowisdeterminedby theactivityofbrainstemoscillatorswhichactasa flip flopmechanism,witheachcentreinhibitingtheactivityoftheothercentreandonlyonecentrehavingdominantactivityatanyonetime.Thesehypothalamicandbrainstemmechanismshavebeenstudiedintheanaesthetisedcat(38,39).
Support for the existence of a central control mechanism determining the
rhythmicity and asymmetry of nasal airflow has been gained from observational
humanstudies.Inastudyofnasalairwayresistanceandaxillarysweatproductionin
7subjects,reciprocalalternatingcycleswiththesameperiodicitywereseenforboth
nasal airflow and axillary sweat production (40). Although not present in every
subject, itwasfoundthatanincreaseinrightaxillarysweatingwasassociatedwith
an increase in left nasal airflow (40). As sweating is controlled by the
thermoregulatory centre in thehypothalamus via the sympathetic nervous system
(41), the authors postulated the presence of a central cycle (40). Galioto et al.
(1991) observed an anomalous or absent nasal cycle in a small cohort of patients
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withKallmansyndrome,adisordercausedbyhypothalamichypoplasia(42).Studies
on patients who had undergone laryngectomy revealed preservation of the
alternations in nasal airflow patterns as seen in healthy individuals but in the
absenceofnasalairflow,reinforcingthenotionofacentralratherthanlocalcontrol
mechanism (43, 44). Although the periodicities of the nasal cyclewere similar in
boththelaryngectomyandcontrolgroups,theamplitudewassignificantlylowerin
theformergroup,andtheauthorshavesuggestedthatnasalairflowreceptorscould
bemodifyingtheunderlyingcentrally-generatedpatternsofnasalairflow(44).
Corticalinfluenceonthehypothalamusandbrainstemintermsofthenasalcycleis
yet to be established, however there is some evidence to support a link between
corticalfunctionsandnasalairflow,whichwillbediscussedindetaillater.
1.6:Sensingnasalairflow
Thesensationofnasalairflowisbelievedtobemainlydeterminedbystimulationof
nasaltrigeminalnerveendingsthataresensitivetotemperaturechanges,especially
cooling of the nasal mucosa, as occurs during inspiration of air (1, 45, 46). This
phenomenonhasbeenreflectedinstudiesontheeffectofmentholonnasalairflow.
Mentholcausedacoolingsensationandasubjectiveimprovementinnasalairflowin
healthy subjects without any change in the total nasal airway resistance (47).
Followingtheapplicationoflocalanaesthetictothenasalmucosa,thesensationof
nasalairflowwasdiminished,aswastheeffectofmenthol(48).Underphysiological
conditions, the spontaneous changes innasal airway resistancebetween thenasal
passages occur without being detected since the total nasal resistance remains
relativelyconstant(18).
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1.7:Measuringnasalairflow
Multipletechniquescanbeusedtomeasurenasalpatency,eitherinclinicalpractice
orforresearchpurposes.Subjectivemethodsincludeuseofavisualanaloguescale
(VAS)toassesstheperceptionofnasalairflow(49),andquestionnairessuchasthe
sino-nasaloutcometest20(SNOT-20)(50).Objectivemethodsincludeevaluationof
nasal cavity anatomy for example with computed tomography or acoustic
rhinometry, andmeasurements of nasal airflow such as rhinomanometry or peak
nasalflowrates(49,51,52).Anobjectivemeasurementofnasalairflowisusefulfor
theclinicianas itwillaid inthediagnosisofnasalobstructionandquantificationof
its severity, as well as in the assessment of treatment outcomes such as topical
decongestantagentsorsurgicalintervention.Itisforthesereasonsthattheability
tomeasuretheairflowthrougheachnasalpassageseparatelyisuseful(53).
Any method used to measure nasal airflow should ideally preserve normal nasal
anatomyandphysiology,beeasytouseandcomfortableforthesubjectorpatient,
measure physiological flow and pressure, and provide reproducible and relevant
results(54,55).Oneofthechallengesencounteredwhenmeasuringnasalairflowis
the physiological variability of resistance that occurs between inspiration and
expiration and between each nasal passage due to the nasal cycle (53). As air is
inspired through the nasal passages, the cartilages are drawn inwards, thereby
increasingtheresistancetonasalairflow.Theoppositeoccursduringexpiration.
The first attempts at objectively measuring nasal airflow were documented by
Zwaardemaker in1889,whousedacoldmirrorplacedhorizontallyunderthenose
tomeasurethecondensationareaproducedbyexpiredairfromeachnasalpassage
(54,56).Thiswasthefirsthygrometricmethodusedtomeasurenasalairflow(57).
Althoughmanymoretechniqueshavesincebeendeveloped,nosinglemethodhas
become commonplace in clinical practice (53). Some examples of othermethods
usedtodaytomeasurenasalpatencyaredescribedbelow.
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Peaknasalinspiratoryflowrate(PNIF)
PNIF is a non-invasive method of measuring nasal airflow during maximal forced
nasalinspiration(51).Itthereforeprovidesanindirectmeasurementofnasalairway
resistance, as an increased resistance alters the peak flow rate achievable (58).
However it isnota reflectionofnasal resistanceduringnormalbreathing (51)and
can miss smaller obstructions to nasal airflow (52). The device used is portable,
relatively simpleand requiresminimal trainingof staff and subjects (58). Another
advantage is the availability of baseline values for adults which can be used for
comparison(52). Subjectcooperation is required,and lackofeffortor fatiguecan
affect the results (58). The subject’s respiratory function and the presence of
secretionscanalsohaveaconfoundingeffect(51,58).
Rhinomanometry
Nasalairflowoccursdue to thepressuredifferencebetween theenvironmentand
the nasopharynx (51, 59). Rhinomanometry measures the pressure and airflow
differences between the anterior and posterior nasal cavity that occur during the
inspiration and expiration of air through the nose (59). These measurements of
nasalairflowandpressurecanthenbeusedtocalculatenasalairwayresistance(58).
Rhinomanometry can provide an assessment of each nasal passage separately or
together,dependingonthetechniqueused. Duringanterior rhinomanometry, the
sensing tube is taped toeachnostril in turnprovidingavalue for thenasalairway
resistance for the left and right nasal passages separately (59). During posterior
rhinomanometry, the sensing tube is placed in the subject’s mouth, providing a
measurement of the total nasal airway resistance (59). This technique requires
subject co-operation and trainingwhich can be difficult (58). Rhinomanometry is
considered to be more sensitive and specific than acoustic rhinometry (52).
However it involves the use of more complex and bulky equipment, which is
expensive, and as such it is more useful in research laboratories than in clinical
practice(51,58).
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Acousticrhinometry
Acoustic rhinometry involves the use of acoustic reflection to demonstrate the
geometry and cross-sectional area of the nasal cavity (60). A sound wave is
transmitted into thenasalpassages,and the reflectedwavepatternsaredetected
andanalysed(58).Variationsinthesizeorcontourofthenasalairway,forexample
septal deviation or the presence of a nasal polyp,will distort the reflected sound
wave (51). Acoustic rhinometry does not require any nasal airflow to obtain
measurementvalues,meaningthatitcanbeusedforthesubjectwithacompletely
occludednose (60). In addition, it doesnot requiremuch subjectparticipationor
cooperation (60) and therefore isuseful in childrenwhocould strugglewithother
methods.Studieshavedemonstratedgoodreproducibility,withalowcoefficientof
variationbetweenrepeatedmeasurements(60).Acousticrhinometrydoeshowever
have several disadvantages. Should an obstruction in the anterior nasal cavity
prevent transmission of sound waves, there is no way of measuring the area
posteriortothatobstruction,thuslimitingtheviewoftheoverallnasalairway(60).
It does not provide information about nasal airflow i.e. a measurement of nasal
function (58), which can be more relevant to the patient and clinician than
anatomicalfindings.Itisalsounabletomeasureeachnasalpassageseparately,but
providesacross-sectionalreflectionofthenasalcavity(52).
Nasalspirometry
The techniqueofnasal spirometrywasdevised in2001asamethodofmeasuring
the distribution of nasal airflow through each nasal passage, termed the nasal
partitioning of airflow ratio (NPR) (61). It provides ameasure of the laterality of
nasalairflow.Adeviceisusedtomeasurethevolumeofairexpiredfromeachnasal
passagefollowingmaximalinspiration(61).Itiseasytousebyboththesubjectand
the investigator, requiringminimal training (62). Otheradvantagesof thismethod
include its good correlation with rhinomanometry (61) and the availability of a
reference range for healthy adults (63). The accuracy and reproducibility of nasal
spirometrywasdemonstrated inastudyusingamodelof thenasalcavity (64). It
has also been used successfully in clinical studies, for example as an objective
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measureofnasal septaldeviation (62) and fordetectingpostural changes innasal
airflowinpatientswithacuterhinitis(65).
ThemodifiedGlatzelMirror(GM)
Following on from the cold mirror method invented in the late 1800s, in 1904,
Glatzel described a metallic mirror marked with four lines that could be used to
quantify nasal airflow. This was modified by Cocks (1915) who added multiple
horizontalcurvedlinesandparallelvertical lines,both1cmapart(66). Toobtaina
measurement,themirrorisheldhorizontallybeneaththenostrils,andthesubjectis
instructedtobreathoutthroughthenosenormally,withthemouthclosed(54,66).
The temperature difference between the nasal cavity and the plate causes
condensation of the vapour in the expired air, producing a brief reflection of the
nasalairwayontheplate(54).
Gertneretal.(1984)describedtheirtechniqueindetail(54),andthereproducibility
ofthismethodspecificallyhasbeenanalysedmorerecently(55).Theplateusedwas
a 10cm x 12cm polished chrome-coated metal plate marked with arches at 1cm
apart(54). Theplatewaspositionedhorizontally immediatelyunderthecollumela
withtheverticalaxisat90degreestowardstheupperlip(54).Thepatientwasthen
askedtoexhalethroughthenoseslowlywiththemouthclosed(54)(seeFigure2).
Theareaofcondensationproducedduringnasalexhalationwasthenmeasured,and
intheabsenceofnasalpathologythiswastypicallyanovalshapedarea7-8cmlong
and4-5cmwide(54)(seeFigure3).
The advantages of this method are immediately obvious; it is easy to use, non-
invasive, quick, inexpensive and does not distort nasal anatomy (54, 55). It does
howeverhavelimitations,forexampletheusertechniquecancausevariabilityinthe
resultsobtained,andthereisnomethodofregulatingairflowwhichcouldalsolead
toerroneousreadings(67).
15
Thisfigurehasbeenremovedbytheauthorforcopyrightreasons.
Figure2:TakenfromGertneretal.’spaper(1984)(54).AphotographofasubjectexhalingthroughthenoseontoamodifiedGM.Thisfigurehasbeenremovedbytheauthorforcopyrightreasons.
Figure 3: Taken fromGertner et al.’s paper (1984) (54). An illustration of the condensation areasexpectedtobeproducedbyanormalindividualwithnonasalpathology.
16
IthasbeensuggestedthattheonlyreliableresultsobtainedbythemodifiedGMare
qualitative in nature, as quantitative values may be unreliable due to potential
variabilitybetweenreadingsandtheshort-livedappearanceofcondensationareas
(49).Howeveronecouldarguethatthereliabilityandusefulnessofresultsdepend
on the purpose, for example a brief view of nasal patency for the purpose of
diagnosingthepresenceandlateralityofnasalobstructioninclinicalpracticecanbe
extremelyuseful.
Brescovici and Roithmann (2008) assessed the reproducibility of themodifiedGM
method in the assessment of nasal patency, specifically utilising the technique
described byGertner et al. (1984) (55). They analysed theminute-by-minute and
hour-by-hour variability of measurements in a cohort of healthy individuals (55).
The mean variation coefficient was found to be less than 15% for unilateral
measurementsandlessthan12%fortotalmeasurementsatdifferenttimeintervals,
whichiscomparabletoothermethodsofmeasuringnasalpatency(55).Itwasalso
abletoreliablydemonstratethechanges innasalairflowcausedbythenasalcycle
(55). Another study comparing the efficacy of themodified GMwith peak nasal
inspiratoryairflowmeasurementsinchildrenidentifiedthemodifiedGMassuperior
inthediagnosisofnasalobstruction(68).
Several factors can affect the reliability and reproducibility of measurements
obtained by use of themodifiedGM. These include patient factors, such as vital
capacity and nasal obstruction, environmental factors such as temperature and
humidity,andpositionalfactorssuchasthepositionoftheplaterelativetothenasal
passages(66). Particularlyforresearchpurposes,thesecanbeminimisedbyusing
anatomical landmarks to correctlyposition theplate,using the sameexaminer for
repeated measurements, and allowing subjects to acclimatise to the room
temperature and humidity for 30minutes prior to takingmeasurements (55). In
addition,usingtheaverageof3-5readingscanimprovereliability(55).
The modified GM has been used as an outcome measure in several studies
attemptingtoanalysetheeffectsofnasalsurgery(54,67,69).Gertneretal.(1984)
17
demonstratedthatthemodifiedGMwasusefulinclinicalpractice,asitcoulddetect
differences in nasal airflow before and after septal surgery used to treat nasal
obstruction (54). However another study assessing changes to nasal airflow
followingrhinoplastyprocedureswiththemodifiedGMfailedtoshowasignificant
differenceinthevaluesobtainedpre-andpost-operatively(67).Theauthorsofthis
study commented that this could have been due to the effects of the nasal cycle
(67).Itshouldbenotedhoweverthatthisstudyonlyinvolvedasmallcohortof20
patients who were undergoing cosmetic rhinoplasty, and therefore the aim of
surgerymaynothavebeentoimprovenasalairflow.Aswithothermethods,studies
haveidentifiedapoorcorrelationbetweensubjectivemeasuresofnasalairflow(e.g.
patient questionnaires) and objectivemeasures taken using themodifiedGM (55,
67).
ThemodifiedGM isparticularlyuseful in childrenas it isnon-invasiveandeasy to
use, not requiring any training. It has been used successfully in several studies
involvingchildren (68,70). Thecoldmirrormethodhasevenbeenused inanimal
studies in order to demonstrate the presence of a nasal cycle (71). A coldmetal
mirrorwasplacedunderthenostrilsoftranquilisedratsandrabbits,andthesideof
the nose (left or right) producing the greatest area of condensationwas recorded
(71). Thiswas comparedwithmeasurements of airflow recorded inmillilitres per
minute by collecting air that escaped from each nostril under water following
insufflation into the trachea (71). The cold mirror recordings were shown to
correlatewiththemeasurementsofflow(71),supportingitsreliabilityandaccuracy.
Recently,thecoldmirrormethodhasbeenadaptedfurtherbytheadditionofvideo
technology which is termed the video-rhino-hygrometer (49). This involves the
recording of the condensation areas produced by nasal expiration followed by
computerprocessinginordertoextractmoredetailedquantitativeparameters(49).
When this method was used to evaluate the post-operative outcome following
septoplasty,itwasabletoidentifyanimprovementincomparisontopre-operative
measurements (49). However in the same group of patients, there was no
18
statisticallysignificantcorrelationbetweenmeasurementsobtainedbyvideo-rhino-
hygrometryandthoseobtainedbyanteriorrhinomanometry(49).
1.8:Factorsthataffectnasalairflow
Numerousstudieshavedemonstratedthatnasalairflowcanbe influencedbyboth
pathologic and physiologic conditions. Some significant examples are discussed
below.
Age
Cross-sectional studies of adults aged 16 to 82 years have demonstrated that age
doesnotaffectnasalairflowrate,nasalcross-sectionalareaornasalresistance(72,
73).Howevercross-sectionalstudiesmaynotbereliableduetothehighdegreeof
variabilitybetweensubjectsseeninstudiesofnasalairflow,andtheauthorssuggest
thatchangestothenasalmucosathicknessandelasticityarealikelyconsequenceof
ageing (72). It seems that ageing can affect the rhythmicity and reciprocity in
patternsofnasalairflowtypicallyassociatedwiththenasalcycle. Inastudyof60
subjectsaged18to85years,nasalairflowwasmeasuredevery15minutesover6
hours (74). In subjects under the age of 50 years, 22%exhibited a classical nasal
cycle, defined by the authors as statistically significant negative r values (i.e.
significant reciprocity), compared to 9% of subjects aged over 50 years (74). In
addition,thepresenceofacyclicpatterns,definedasnofluctuationsinnasalairflow
ineithernasalpassage,wasmore likelywithadvancingage (74). Ina longitudinal
studyof a single subject, nasal airflowmeasurementswere takenalmost 40 years
apart, and a significant decline in reciprocity was identified (75). Although the
reasonsfortheseage-associatedchangeshavenotbeenfullyestablished,itislikely
that they are due to age-related changes in the central nervous system, since
fluctuations in nasal airflow patterns are controlled by the hypothalamus and
brainstem(74,75).
19
Posture
Positional changes can affect nasal airflow. Changing from a sitting position to a
recumbentpositioncausesariseinjugularvenouspressure,increasingbloodflowto
thehead, includingthenose (76). Thiswill leadtovasodilationof thenasalveins,
increasing the total nasal airway resistance, and one study identified an 8.4%
increaseinnasalresistancewhenchangingfromasittingtoasupineposition(77).A
pressurestimulustoonesideofthebody,forexamplewheninthelateraldecubitus
position, leads to ipsilateral vasodilation (congestion) and contralateral
vasoconstriction (decongestion) in the nasal passages (78-80). This has been
demonstrated by application of axillary pressure bymeans of a small crutch, and
whenappliedtothesamesideasthedominantnasalpassage,itcausedreversalof
nasal passage dominance within 5 minutes (80). Twelve minutes of lateral
recumbency was shown to induce the same changes in nasal airway resistance,
whichinterestinglywerefoundtocontinueafterthepressurestimuluswasremoved
(79). It has been proposed that this phenomenon is mediated by a reflex arc,
sometimes called the corporo-nasal reflex, involving sensory receptors in the skin
and sympathetic innervation to the nasal mucosa (78). These are likely to be
pressure sensors situated in the thorax, pectoral and pelvic girdles with efferent
fibrestravellingviathecervicalsympatheticchaintothevenoussinusesinthenose
(79).
Sleep
Spontaneousfluctuationsinnasalresistancealsooccurduringsleep(28,81).Sleep
seemstoaffectthenasalcycle,causinganincreasedperiodicitywhencomparedto
wakefulness inthesamesubjects(27,28). Inastudyof20healthysubjects,there
was a significant reduction in thenumberof cycles, i.e. reversals of nasal passage
dominance,thatoccurredduringsleepcomparedtowakefulnesswhennasalairflow
wasmeasured continuously over a 24 hour period (28). In another similar study,
reversalsofnasalpassagedominancewereprecededbyachange inbodyposition
almost 60% of the time (27). There is also an increase in nasal cycle amplitude
during sleep, caused by increased congestion in the congested nasal passage,
howeverthisismorelikelyaresultofrecumbencyratherthansleep,consistentwith
20
theexistenceofthecorporo-nasalreflex(27).Itshouldbenotedhoweverthatboth
of these studies used portable rhinoflowmetry to continuously measure nasal
airflow,whichrequirestheinsertionofnasalprongs intotheanteriornares. Nasal
prongshavebeenshowntosignificantlyincreasenasalairwayresistanceeveninthe
absence of nasal pathology, as they reduce the cross-sectional area of the nasal
passages(82).Thereisalsoachancethattheycouldbecomedislodgedormisplaced
especially during sleep, or cause irritation to the nasalmucosa,which again could
affecttheaccuracyofmeasurements.
There is some evidence to suggest that reversal of nasal passage dominance
predominantlyoccursduringrapideyemovement(REM)sleep(28,83),evenwhen
postural effects are taken into account (28). REM sleep is associated with
sympatheticnervoussystemactivationwhichcouldexplainthisfinding(27).
Exercise
Exercise reduces the total nasal airway resistance, abolishing the asymmetry
betweenthenasalpassages(84,85).Re-breathing(resultinginanelevatedplasma
carbondioxide level)alsoreducesthetotalnasalairwayresistance(84). It is likely
that the increased metabolic demand caused by these scenarios leads to a
sympathetic response resulting in vasoconstriction and reduced nasal airway
resistance(84).
Environment
Onestudyusedacousticrhinometryasanobjectivemeasureofnasalpatencyin50
healthy subjects at two different room temperatures; 30-33°C and 18-22°C, and
found no statistically significant difference caused by the change in room
temperature (86). Ina studyofeighthealthysubjects, ingestionofhotwaterand
nebuliser treatment (i.e. heat and humidification) caused a significant decrease in
thevolumeofthenasalcavitythatwasalreadythemostcongested,althoughthere
wasnochangeintotalnasalcavityvolume,againmeasuredbyacousticrhinometry
(87).Drinkingcoldwaterandplacementofanicepackontheneckdidnothaveany
significanteffect(87).
21
Hormones
There is some evidence to suggest that female reproductive hormones may be
associated with changes in nasal airflow, however conflicting findings have been
reported.Duringpregnancy,itisthoughtthathormonalchangesareresponsiblefor
pregnancy-induced rhinitis, which is relatively common in the later stages of
gestation(88,89).Inthiscondition,nasalsymptomsdevelopduringpregnancyand
resolvespontaneouslysoonafterdelivery(90).Inalongitudinalcohortstudyofover
2000 pregnant women, self-reported “nasal stuffiness” increased throughout
pregnancy,occurringin42%ofwomenat36weeksgestation(91).
This phenomenon led to analyses of the effects of the menstrual cycle and
contraceptivedrugsonnasalairflow. Ina studyof41healthywomen,nasalpeak
expiratory flow rate was found to be significantly lower during menstruation
comparedwiththerestofthemenstrualcycle,indicatingincreasednasalcongestion
at this time (92). It hasbeen suggested that elevated levelsofoestrogenmaybe
responsibleforfluctuationsinnasalcongestionoccurringduringthemenstrualcycle,
however oestrogen levels are lowest during menstruation (92). Using
rhinostereometry, Haeggstrom et al. (2000) observed nasal hyperreactivity during
ovulation(whenoestrogenlevelsarehighest)bychallengingthenasalmucosawith
histamine (93). However when acoustic rhinometry was used to measure nasal
congestion, no significant differences were identified at different phases of the
menstrual cycle (93). The authors suggest therefore that the sensation of nasal
congestionassociatedwithpregnancycouldbedue tohyperreactivityof thenasal
mucosa caused by high oestrogen levels, rather than increased congestion of the
nasalmucosa(93).
Theoppositewas found inanother study,wherenasal resistancewas found tobe
significantlyhigheraroundthetimeofovulationcomparedtothemenstrualphase
asmeasuredbyanteriorrhinomanometry(94).Biopsiesofthenasalmucosataken
duringdifferentphasesofthemenstrualcycleshowednodifferencescomparedto
malecontrols insevenoutoftenwomen(95). Thethreewomenwithhistological
changesdemonstrated increased vascularitywithdilated and congested capillaries
22
and glandular hyperactivity, which the authors suggested may be related to
emotionaldisturbancesinfluencingtheautonomicnervoussystem(95).
A large studyofover300women found thatolfactory sensitivity reached itspeak
during the ovulatory phase of the menstrual cycle and was higher at this stage
compared tocontrols (96). The lowest sensitivitywas foundduring themenstrual
phaseof themenstrual cycle (96). It is thought that changes in oestrogen levels
throughoutthemenstrualcyclecouldbealteringolfactoryfunctionperipherallyand
centrally(96).Thesefindingsareparticularlyinterestinggiventhatsomestudieson
nasalairflowhavesuggestedthatnasalcongestionandhyperreactivityoccuratthe
timeofovulation(93,94),whichwouldusuallyreduceolfactorysensitivity. Clearly
this relationship between female sex hormones, nasal airflow and olfactory
sensitivityiscomplex,anditsdefinitiveexistencehasnotbeenfullyestablished.
Animalstudieshaverevealedthatadministeringoestrogenscausesvasodilationwith
an increase in the size of vascular spaces in the nasal mucosa, with the same
histological changes occurring in pregnancy (97). Similar effects have been
demonstrated in human histological studies. Toppozada et al. (1984) took nasal
biopsiesfrom25womenonthecombinedoralcontraceptivepill,15ofthesewomen
had developed nasal symptoms after starting the drug (98). Although minor
changessuchasglandularhyperactivitywereobservedintheasymptomaticgroup,
the symptomatic group had changes similar to those seen in hypertrophic non-
allergicrhinitis,suchasinterepithelialoedema,glandularhyperplasiaandcongested
capillaries(98).Howeveramorerecentstudyfoundthatthemoderncombinedoral
contraceptivepilldidnothaveanyeffectonnasalairflowasmeasuredbyavariety
ofmethods(99).
It would seem that the effects of hormones such as oestrogen and progesterone
have the potential to cause changes in the nasal mucosa and even symptomatic
rhinitis, however significant variability has been identified in the prevalence,
duration and severity of symptoms. Whether these changes alter nasal airflow is
even more controversial, and conflicting results have been presented in the
23
literature.Evenifthereareminorchangesinnasalairflowoccurringthroughoutthe
menstrual cycleorwithuseof contraceptives, thisdoesnotnecessarilymean that
thenasalcyclewillbeaffected.Equally,thereisevidencetosuggestthatmenhave
agreaternasalairflowratethanwomen(72),mostlikelyduetotheirincreasedvital
capacitywhichshouldnotaffectthenasalcycleduration,onlyit’samplitude.Most
importantly, a relationship between gender and the nasal cycle has not been
identified.Mirzaetal.(1997)measurednasalairflowevery15minutesfora6-hour
periodin60subjectstodeterminefactorsthataffectnasalcyclepatterns,andfound
that gender had no significant effect (74). Tahamiler et al. (2009) found no
significantdifferencesinnasalcyclingbetweenmaleandfemalesubjectswhennasal
airflow was measured every 30 minutes for 12 hours on 4 different days in 20
subjects(29).
Drugs
Many drugs have been shown to affect nasal airflow generally and also alter the
nasal cycle. For example alcohol, known to have vasodilatory effects, has been
shownto increasetotalnasalairwayresistance (100,101). Cigarettesmokingalso
hasaneffect.Inastudyofover2500adults,thosewhowerecigarettesmokershad
lowernasalcavityvolumesandpeaknasalinspiratoryflowvaluescomparedtonon-
smokers,evenafterdecongestion(102).Itislikelythatchronicdamagetothenasal
mucosa caused by cigarette smoke is responsible for these changes (102). Topical
decongestantssuchasadrenalineandxylometazolinecausevasoconstrictionofthe
dilated veins, leading to symmetrical nasal airflow (12, 14). Anti-inflammatory
medicationsuchasanti-histaminesandcorticosteroidsalsodecongest thenoseby
reducinginflammation(103,104).Nasalobstructionandrhinitishavebeenreported
inpatientstakinganti-hypertensivessuchasACE-inhibitors(105)andbeta-blockers
(106).
Disease
Severalpathologicfactorscan influencenasalairflowandthenasalcycle, including
local factors suchasanatomicalobstructionormucosal inflammation,andgeneral
factorssuchasrespiratoryfunction.Anatomicalobstructionsuchasseptaldeviation
24
reduces nasal airflow through the affected nasal passage (54). In a comparative
study, the amplitudeof fluctuation innasal airflowwas greater in thewidernasal
passage in patients with anterior septal deviation compared to those without,
althoughtherewasnochangeinthedurationofthenasalcycle(107).Itispossible
that severe nasal septal deviation can eliminate the nasal cycle i.e. prevent any
reversal in the dominance of nasal airflow (28), although the evidence for this is
weak and as discussed previously the great variation in nasal airflow patterns
generallycouldaccountforthisobservation.
Nasal resistance is increased in allergic and chronic hypertrophic rhinitis (77). In
addition,acuterhinitis,forexampleinupperrespiratorytractinfection,exaggerates
thenasalcycle,causingagreatermaximalnasalairwayresistanceandanincreasein
the amplitude of reciprocal changes between to the two nasal passages (12, 23).
Restrictedorreducedlungmovement leadstoreflexvenousdilatationinthenasal
mucosaandreducednasalairflow(37).
Overthepastdecade,evidencehasemergedtosuggestthatnasalairflowpatterns
arealteredinneurodevelopmentalandpsychiatricdisorders(70,108,109),although
this notion remains controversial with only a few studies published on the topic.
Thisconceptwillbediscussedinmoredetaillater.
Summary
There aremany factors that can influence nasal airflowbutmost of these do not
affectthecharacteristicsofthenasalcycle.Thereareafewexceptions.Asymmetry
between the nasal passages can be abolished by stimulation of the sympathetic
nervoussystem,forexampleduringexercise(84,85)orfollowingtheapplicationof
topical sympathomimetics (12). Increasing age is associated with reduced
reciprocity in the alternating fluctuations of nasal airflow (74, 75). Changes in
posture,specificallyresultinginapressurestimulustolateralaspectsofthebodyfor
exampleduring lateral recumbency, triggera reversal innasalpassagedominance,
such that the greater airflow is observed in thenasal passage contralateral to the
pressurestimulus (78,80). Pathologicalconditionssuchassevereseptaldeviation
25
have the potential to prevent fluctuations in nasal airflow (28), and acute rhinitis
exaggerates the amplitude of reciprocal changes between the two nasal passages
(12,23). These influencesneedtobeconsideredcarefullywhendesigningstudies
thataimtoassessthenasalcycle,andshouldbeadequatelycontrolledforwherever
possible.
1.9:Nasalairflowandhandpreference
The cerebral hemispheres exhibit both functional and structural asymmetry (110).
Perhapsoneof themostobvious signsof cerebral asymmetry is handpreference.
Broca proposed that the hemisphere controlling speech was contralateral to the
dominant hand, suggesting that in most people the left hemisphere is dominant,
however this relationship is actually more complex (111). The majority of the
populationisright-handdominant,hasspeechcontrolledbythelefthemisphereand
visuospatialprocessingcontrolledbytherighthemisphere(110,112).
In 2005, Searleman and colleagues hypothesised the existence of a correlation
betweennasalairflowandhandedness(113).Theydescribedtwoprinciplereasons
forthebasisoftheirhypothesis.First,thereisatendencyforapositivecorrelation
between lateral preferences, including both limb sidedness and sense organ
sidedness,sothat left-handers tendalsotobe left-footed, left-eyedand left-eared
(113). Secondly, there are two separate nasal passages which function
independently. As discussed in detail earlier, airflow through each nasal passage
fluctuatesspontaneouslyoveraperiodofhours(1,3,4),unlikeairflowthroughthe
bronchi and lungs, which under normal circumstances (i.e. in the absence of
pathology) is divided equally between the left and right sides. At any given time
point one nasal passage is decongested, i.e. has greater airflow making it the
dominantside,whilsttheotheriscongested,i.e.haslessairflowthusmakingitthe
non-dominantside.Sincetheexactnatureandpurposeofthesefluctuatingpatterns
26
ofnasalairflowremainelusive,itseemsreasonabletoconsiderstructuralinfluences
suchascerebralorganisationandlateralpreferences.
Searlemanetal. (2005)aimed toanswer twoquestions; is thereadominantnasal
passageand if so, is it consistentwithother lateralpreferences, forexamplehand
dominance(113)?Theypredictedthattheleftnasalpassagewouldbedominantfor
the majority of the time in left-handers, and vice versa in right-handers (113).
Searleman et al.’s (2005) study involved 20 healthymale participants, aged 18-22
years, 11 of whom were right-handed and 9 of whom were left-handed (113).
Women were excluded due to concerns that alterations in hormone levels could
influence nasal airflow (113). Handedness was determined by self-report and
observationofhand-writing(113). Nasalairflowwasmeasuredusingtwohotwire
anemometerspositioned just inside thenares, and themaximumairflow ratewas
used as the measure of nasal passage dominance (113). Measurements were
performedat15-minuteintervalsoveracontinuous6-hourperiod(113).Attempts
were made to minimise potential confounding factors by performing anterior
rhinoscopytoruleoutobstructivenasalpathology,excludingsmokersorthosewith
anabnormalsenseofsmell,ensuringcorrectandconsistentpositioningduringnasal
airflow measurements, and prohibiting exercise and lying down on the test day
(113).
In order to look for a correlation between hand preference and nasal passage
dominance, Searleman et al. (2005) analysed the percentage of time each nasal
passagewasdominant, basedonmaximumairflow rates recorded fromeach side
(113). In left-handers, the leftnasalpassagewasdominant for59.3%of thestudy
period,whereasinright-handers,therightnasalpassagewasdominantfor59.5%of
the studyperiod (113). Thep value forbothof these findingswas less than0.01,
howeverthemethodsofstatisticalanalysiswereunclear(113).Theyalsolookedfor
anycorrelationbetweenthenumberofnasalcyclesandhandedness.Left-handers
had an average of 5.67 nasal cycles in the 6-hour measurement period, whereas
right-handershadanaverageof3(113).Usingthisinformation,theycalculatedthat
the average duration of a nasal cycle was 63.1 minutes in left-handers and 120
27
minutes in right-handers (113). These findings were not statistically significant,
althoughagainthestatisticalmethodsusedwerenotspecified.
Thereareseveral issueswithboththemethodologyanddata interpretation inthis
article:
1. A small sample size of only 20 subjects has been used. As there is no
previoussimilarliterature,powercalculationswouldnothavebeenpossible.
Inaddition,studiesthatrequiremeasurementandanalysisofthenasalcycle
are,bydefinition, timeconsuming,and therefore themajorityofpublished
reportsonlyhaveasmallnumberofsubjects.
2. Themethod of measuring nasal airflow required the insertion of hot wire
anemometers just inside the nares, which could have interfered with the
accuracyofmeasurements.
3. Noformaltestwasusedtodeterminehandednessdespitetheavailabilityof
validatedobjectiveandsubjectivemeasures.Handednessisnotassimpleas
left or right, but is in fact a continuum, with degrees of left and right-
handedness (114). Studies that utilise hand preference as a variable can
thereforebedifficulttointerpret.
4. Dataanalysisandstatisticalmethodshavenotbeendescribedinanydetail,
making itdifficulttoreliably interprettheresults. Itwouldappearthatthe
number of times each nasal passage was dominant during the 6-hour
measurementperiodhasbeencalculatedandusedtoproduceapercentage
value for theamountof timeeach sidewasdominant. A subjecthas then
beendefinedasbeing leftnasalpassagedominant if the leftnasalpassage
hadthegreatestairflowformorethan50%ofthetimepoints,andviceversa
for the right nasal passage. This figure has then been used to show a
correlationwithhandedness.Asthereissignificantinter-andintra-individual
variabilityinnasalairflowpatterns,using50%asthecutofffornasalpassage
dominance could be unreliable. With only a few more measurements,
extending the sampling period to 7 hours for example, the percentage of
timeonenasalpassagewasdominant couldeasily change to just aboveor
justbelow50%,completelyalteringtheoutcomes.
28
5. When calculating the average number of nasal cycles in left-handers and
right-handers, there isnodescriptionordefinitionofwhat ismeantby the
term“nasalcycle”inthecontextofthisdata.
The findingofa correlationbetweennasalairflowandhandpreference isunusual
forseveralreasons. Manydifferentresearchgroupshaveperformedobservational
studiesonnasalairflowinhealthyindividuals,andalthoughtheyhavenotexplicitly
lookedforarelationshipbetweennasalairflowandhandpreference,ithasnotbeen
identified incidentally. Since 90% of the population is right-handed, surely other
studiesofnasalairflowwouldhavenotedthatthemajorityoftheirparticipantshad
rightnasalpassagedominance. Althoughtheexact functionof thenasalcyclehas
not been firmly established, there is evidence to suggest that it has functional
significancewithpotentialrolesinimmunedefenceandairconditioning(18,26).A
correlation between nasal airflow and hand preference would conflict with these
theories by suggesting that nasal airflow patterns were linked with cortical
organisation rather than having a functional role in respiratory defence or
preparationofinspiredairforgaseousexchange.
ThearticlebySearlemanetal.(2005)(113),publishedover10yearsago,istheonly
availableliteratureconcerninghandpreferenceandnasalairflowinhealthysubjects,
anditisnotcommonlycitedinthemorerecentliteraturebaseforthenasalcycle.In
2007,DaneandBalcipublisheda study that comparedhandpreferenceandnasal
airflow patterns in 37 autistic children and 20 healthy controls (70). Autism is a
neurodevelopmental disorder in which cerebral lateralisation is abnormal (70).
Children with autism have a lesser degree of handedness, i.e. are less lateralised
thancontrolsandmorelikelytodemonstratemixedorleft-handedness(70).When
nasalairflowwasmeasured24timesovera12-hourperiodusingthemodifiedGM,
themajorityofautisticchildrendemonstratedleftnasalpassagedominanceforthe
majorityof the timeperiod (70). Of the24measurements, the leftnasalpassage
wasonaveragedominant19.59timesintheautisticgroup,comparedto11.75times
inthecontrolgroup,andthisdifferencewasfoundtobestatisticallysignificant,with
apvalueof0.00(70).Theauthorsdidnotlookspecificallyforacorrelationbetween
29
handpreferenceandnasalpassagedominancebutdidfindthatintheirgroupof37
autisticchildren,therewasahigherprevalenceofleftormixedhandednessandof
leftnasalpassagedominancecomparedtocontrols(70).
Two similar studies investigatednasal airflowpatterns in right-handed adultswith
schizophrenia andmood disorders. ThemodifiedGMwas used tomeasure nasal
airflow every 30minutes over a 12-hour period in 83 patientswith schizophrenia
(108), 26 patients with unipolar depression and 44 patients with bipolar disorder
(109)andcomparedwith64healthycontrols.Psychoticdisordersmaybeassociated
withabnormalbrainasymmetry,andtherehavebeenreportsofincreasedratesof
mixed and left-handedness in patients with schizophrenia (112, 115, 116). All
subjects in thesestudieswere right-handed. In schizophrenicpatients, the rateof
leftnasalpassagedominancewas65.1%,comparedtoarateof22.9%forrightnasal
passagedominance,afindingwithapvalueof0.00.Inhealthycontrols,therateof
leftnasalpassagedominancewas25%, the rateof rightnasalpassagedominance
was21.9%,andthemajorityhadnosignificantlateralisationofnasalairflowoverthe
12-hourmeasurementperiod(108).Patientswithbipolardisorderhadahigherrate
of right nasal passage dominance, whereas those with unipolar depression had a
higher rate of left nasal passage dominance, however these findings were only
significant in female subjects (109). The authors of these studies have suggested
that the altered nasal airflow patterns apparently associatedwith these disorders
may be contributing the hypo- or dys-function in the cerebral hemispheres (108,
109). Specifically,Ozanetal.(2009)proposedthatgreaterairflowthroughtheleft
nasal passage for the majority of the time corresponds to increased sympathetic
tone and therefore reduced electrical activity in the left cerebral hemisphere,
contributingtothelefthemisphericdysfunctionseeninschizophrenia(108).
Theabovefindings inhealthycontrolsubjectsareparticularlyrelevant. Overa12-
hourperiod,53.1%hadnooverall lateralisationofnasalairflow,meaning that the
left and right nasal passages were dominant for roughly equal amounts of time
(108).Therateofleftnasalpassagedominancewas25%,andtherateofrightnasal
passage dominance was 21.9% (108). All subjects were right-hand dominant as
30
measured by the Edinburgh Handedness Inventory, a validated questionnaire for
handedness.TheseresultsdirectlycontradictthefindingsofSearlemanetal.(2005)
(113).
1.10:Handedness
Around 90% of the population is right-handed and 10% is left-handed (117).
Although these figures may vary slightly, right-handers have been predominant
throughouthistoryandacrosstheworld(117).
Handednesscanbedefinedbyeitherpreferenceorskill.Preferenceisasubjective
measurethatisassessedbyaskingsubjectswhichhandtheyuseforaparticulartask
i.e.aquestionnaire,whereasskillstestscompareasubject’sabilitytoperformtasks
witheachhand(118).TheEdinburghHandednessInventoryisthemostwidelyused
preferencequestionnaire(119),inwhichparticipantsareaskedwhichhandtheyuse
foranumberofactivitiessuchaswriting, throwingaballandusingaspoon(120).
Thereisgoodcorrelationbetweenmeasuresofpreferenceandskill,particularlyfor
complexmovementssuchaswriting,howeverwhetherpreferenceprecedesskillor
viceversaisdifficulttoestablish(118).
Somestudies fail todifferentiatemixed-handers from left-or right-handers,which
couldconfoundresults(121).PreferencetestsproduceaJ-shapeddistribution,with
themajorityof individuals showinga clear rightpreference, someshowinga clear
leftpreferenceandhardlyanybeingindifferent(122).
Defininganindividualaseitherright-handedor left-handedmayseemverysimple,
butinactualfactitcanbequitecomplicated.Whenpreferencesforseveraldifferent
actions are observed (i.e. not just hand-writing), the patterns of preference are
surprisingly variable (122). In 1970,Annett (p. 316) suggested that “to talk about
asymmetry intermsof leftandrightmightbe liketalkingaboutheight intermsof
31
“tall”or“short””(122).Handednessisthereforebestviewedasbeingacontinuum,
withmixed handers being part of the left-right continuum rather than a separate
classificationofhandpreference(122).Thatsaid,forthepurposeofresearchacut-
offpointisrequiredinordertoclassifyhandedness.Thedegreeofhandednesscan
bemeasured using laterality indices; questionnaire responses are assigned scores
that are combined, for example a pure right-hander will score +100, a pure left-
handerwillscore-100andanambidextroussubjectwillscorezero(118).
Handednessisoftenregardedasareflectionofcerebralhemispheredominance,and
Broca proposed that the hemisphere controlling speech was contralateral to the
dominanthand(111).Around5-6%ofright-handershavespeechcontrolledbythe
righthemisphere,comparedto30-35%of left-handers,sothecorrelationbetween
cerebralhemispheredominanceandhandednessisactuallymorecomplex(117).It
isimportanttorememberthereforethathandednessdoesnotnecessarilycorrelate
withcerebralhemispheredominance. Inaddition,whilst right-handersareusually
consistent intheirhandpreferencee.g.forperformingdifferenttasks, left-handers
arelessso(123).
There is a fundamental difference in the cerebral organisation of those that are
right-handedandthosethatareleft-handed,howevertheunderlyingreasonforthis
is controversial. Factors other than neural control can influence handedness, and
these include imitation, specific instruction, social prejudice and tool design (124).
Annett(1972)proposedthreepotentialmechanismsthatcouldexplainthevariation
inhandednessseeninhumans(121):
1. Genetics.Afamilialtrendforhandednesshasbeendemonstrated,however
simplegenetictransmissioncannotexplainthesefindings.
2. Translational errors. The accidental effects of minor translational errors
couldleadtovariation.
3. Culturaldifferences.Imitationandpracticecouldaffecthandedness.
Itislikelythatallofthesefactorsareinvolvedtosomeextentinthedevelopmentof
handedness(121).Twinandfamilialstudiessuggestthatageneticfactorisinvolved
32
in the development of handedness, however this cannot be explained by a
Mendelianmodel(118).
Thedifferencesbetweenhumansandanimalswithregardtolateralpreferencesare
interesting. Animalswithbilaterallysymmetrical limbsalsoexhibitpreferences for
the left or right side, however this seems to occur by chance and is not heritable
(125).Bothhumansandanimalsexhibitabell-shapeddistributionofasymmetryof
skill,howeverinhumansthebell-shapedcurveisshiftedtotheright,meaningthat
there isabias towards right-handedness, termedtherightshift (121). If this right
shift was not present, the distribution of hand preference would be the same in
humans andnon-humans; 25%would be left-handed, 25%would be right-handed
and50%wouldhavemixedhandedness(121).Therightshiftfactor,whichisspecific
tohumans,mayberelatedtospeechdevelopmentwhichusuallyoccurs inthe left
hemisphere (121). It is possible that the lateralisation of speech may confer
advantagesforspeechdevelopment(125).Whenacomplexactionoriginatesinthe
brain, theremaybeadvantages tohaving itarise inonlyonehemisphere, suchas
avoiding unnecessary conduction between the hemispheres and duplication of
specialisedareaswhenneuralspaceislimited(119).
1.11:Aimsofthesis
Theprincipleaimofthis thesiswasto lookforacorrelationbetweennasalairflow
andhandpreferenceinhealthyindividuals.Sincehandpreferenceisconsideredto
be a reflection of brain asymmetry, a secondary aim was to conduct a literature
review in order to gain a better understanding of the theories and evidence
suggestingalinkbetweenbrainactivityandnasalairflow.
Overthepastfewdecades,evidencehasemergedfromdifferentresearchgroupsin
different areas suggesting that asymmetrical brain activity may influence
asymmetrical nasal airflow, and vice versa. The research findings have been
33
obtained usingmany differentmethods with numerous variables, and have often
yieldedcontradictoryresults,makingthisfielddifficulttointerpret.Theseideasand
controversiesarepresentedandsummarisedinChapter2.
A possible relationship between nasal airflow and hand preference in healthy
individualswas identified ina single studybySearlemanetal. (2005) (113). Since
then there has been no further specific research in this area. There are several
reasons to doubt the reliability of this study. First, issues with themethodology
wereidentifiedandhavebeendescribedindetailabove(seeChapter1.9).Secondly,
numerous studies have analysed nasal airflow patterns in healthy individuals, and
although90%of thepopulation is right-handed,nonehavecommentedthat there
wasapreponderanceofrightnasalpassagedominance,whichwouldbeexpectedif
Searlemanetal.’s (2005) findings (113)wereapplicable to thegeneralpopulation.
Thirdly,alternatingnasalpassagedominanceappearstohaveafunctionrelatedto
immunedefenceandair-conditioning,bothofwhichwouldrequireequaldivisionof
labourbetweenthe twonasalpassages,and thereforehavinganoveralldominant
nasalpassagewouldnotmakesense.
Using a different method of measuring nasal airflow and analysing the data, this
study aimed to reproduce the experiment conducted by Searleman et al. (2005)
(113) in order to test the theory of a correlation between nasal airflow and hand
preference.ThemethodologyandresultsarepresentedinChapters3to6.
34
Chapter2:IntroductionB(Nasalairflowandbrain
activity–literaturereview)
2.1:Introduction
FormanycenturiestheancientartofyogainIndiahasstudiednasalbreathingand
developed techniques to switch the dominant nasal passage fromone side to the
otherbyuseofayogadandaorsmallcrutchappliedtotheaxilla (126). Theyoga
belief is that nasal airflow influences brain activity and cognition depending on
whetherairflowisdominantthroughtherightorleftnasalpassage,andthereforeby
controllingleftandrightnasalairflowwiththeyogadanda,theyogastudentcould
controlbrainactivity(127).Thistheorymayappearimplausibletoscepticsfromthe
scientificcommunity,howevertheasymmetricaleffectsoftheyogadandaonnasal
airflowhavebeenconfirmedinseveralstudiesindifferentresearchcentresandthis
ancientpracticenowhasscientificsupport.Reciprocalchangesinnasalairflowcan
bereadilycausedbypressureappliedtotheaxillabymeansofasmallcrutch,orby
adoptingthelateralrecumbentposition(78-80),butwhetherthisinturninfluences
brainactivityremainscontroversial.
Over the past few decades, some evidence has emerged suggesting that nasal
airflow asymmetry and brain asymmetry are linked. Different theories have been
proposed,with varying strengths of evidence from human studies. The following
sectionwilldiscusstheevidencethatlinksnasalairflowandbrainactivityinrelation
to two ideas; firstly the proposal that asymmetrical brain activity causes
asymmetrical nasal airflow, and secondly that asymmetrical nasal airflow causes
asymmetricalbrainactivity. Both the theoriesandevidencearecontradictoryand
mustbeinterpretedwithcaution.
35
2.2:Methods
AMedline®searchwasconductedinNovember2015usingthefollowingkeywords:
nasal airflow, nasal cycle, nasal hyperventilation, forced nostril breathing, brain
asymmetry, electroencephalogram (EEG), cerebral activity, cognition, cerebral
lateralisation,epilepsy,autismandschizophrenia.
Referencelistswerehandsearchedforotherarticlesofinterest.
2.3:Results
Doesasymmetricalbrainactivitycauseasymmetricalnasalairflow?
The peripheral control of nasal airflow via the autonomic nervous system is well
documented(2,36),andinvolvesthevasoconstrictorsympatheticnervesthatsupply
the largeveins intheturbinates. Theasymmetry inbrainactivityandsympathetic
toneextendtothebrainstemregionwhereleftandrightoscillatorscausereciprocal
changesinnasalairflow(38).Thehypothalamusmaygivetheoverallrhythmicityto
acycleofreciprocalchangesinnasalairflow,butthereisnoevidenceforasymmetry
at this level (39). Cortical involvement in nasal airflow asymmetry has been
suggested by studies on hand preference (113), lateralisation disorders such as
schizophrenia(112)andautism(70)andultradianrhythmsofcerebralactivity(128),
but the evidence for these influences is weak and this area of research is
controversial.
Fixedcerebralasymmetriesandnasalairflow
In the early 1800s, the widespread belief was that the two cerebral hemispheres
functioned as a single unit (111). However following studies on brain damaged
patients, itbecameapparent thatdifferentareasof thebrainwere specialised for
different functions (111),andnowadays it isknownthat thecerebralhemispheres
exhibit both functional and structural asymmetry (110). In the majority of the
population, the lefthemisphere isdominant for languageandspeechwhereas the
36
right hemisphere is dominant for visuospatial processing (110). Broca suggested
thatthehemispherecontrollingspeechwasoppositetothedominanthand,sothat
inleft-handersspeechiscontrolledbytherighthemisphereandinright-handersitis
controlledbythelefthemisphere(111).Inreality,therelationshipbetweenspeech
and handedness is more complex and can be influenced by brain damage and
neuronalplasticity(111).
Searlemanandcolleagues (2005)hypothesisedacorrelationbetweennasalairflow
andhandedness,basedontheobservationthatthereisoftenaconsistencyinlateral
preferencese.g.left-handerstendtobeleft-footed,left-eyedetc.(113).Giventhe
existing knowledge of the alternations in nasal airflow between the right and left
nasalpassages,theypredictedthattheleftnasalpassagewouldbedominantforthe
majority of the time in left-handers, and vice versa in right-handers. Their study
proved thehypothesis tobecorrect, in that thedominantnasalpassagepositively
correlated with the dominant hand for almost 60% of the time (113). However,
among other issues outlined in section 1.9, the study only involved a small group
monitoredovera short timeperiodandaspreviouslydemonstrated there isgreat
variability inpatternsofnasalairflow (13). It isalsounusual that this relationship
has not been noted in other observational studies of the nasal cycle in healthy
individuals,since90%ofthemwereprobablyright-handed.
Non-right handedness (left-handedness or inconsistent handedness) seems to be
more prevalent than expected in certain neurodevelopmental and psychiatric
disorders such as autism and schizophrenia and this may be related to cerebral
lateralisationabnormalities(70,112,116).Onestudyanalysedhandpreferenceand
nasalairflowinautisticchildren,andfoundthatthemajoritywereleft-handedand
had left nasal passage dominance for most of the time (12-hour measurement
period)(70).Asimilarstudyinright-handedschizophrenicsrevealedthattherewas
a significant increase in leftnasalpassagedominance in thisgroupcomparedwith
controls(108).
37
Handednessisnotassimpleasleftorright,butisinfactacontinuum,withdegrees
ofleftandright-handedness(114).Studiesthatutilisehandpreferenceasavariable
can therefore be difficult to interpret. There are also different methods of
measuring handedness, including objective performance tests and subjective
inventories(129),andthesearenotstandardisedacrossdifferentstudies.Itshould
be noted as well that the aforementioned studies are relatively small and there
couldhavebeenconfoundingfactorsthatwerenotcontrolledfor,suchastheuseof
psychoactivemedication.
Fluctuatingcerebralasymmetriesandnasalairflow
Theideaofrhythmic,spontaneousfluctuationsincerebralhemisphereactivityfirst
appearedinthe1960s.FollowingthediscoveryoftheREM/non-REM(NREM)sleep
cycle(130),Kleitman(1967)proposedthatthisphenomenonwasthenocturnalpart
ofa“BasicRestActivityCycle”(BRAC),whichinvolvesfluctuationsincentralnervous
systemactivityapproximatelyevery90minutes(131).Thesefluctuationsareoften
referred toasultradian rhythms in cerebralactivity. However theexactnatureof
thesechangesinbrainactivityremaincontentious,andconflictingresultshavebeen
presented. A few studies with small numbers of participants have suggested
rhythmic fluctuations inelectroencephalographic (EEG) activity (132) and cognitive
performance in this time frame (133,134), such that verbalperformance isbetter
than spatial performance, switching to the reverse approximately every 90-100
minutes(133).
Several studies have suggested the existence of a correlation between the
alternatingpatternofnasalairflowandcerebralhemisphereactivity(128),thisagain
is based on the regular periodicity associatedwith the BRAC (131) which has not
beenaconsistent finding (133,135). Werntzetal. (1983) reported increasedEEG
activityinthehemispherecontralateraltothedominantnasalpassageasmeasured
bynasalairflow(128).TheEEGactivitywasobservedacrossthecortexratherthan
focussed at the olfactory centres, suggesting a mechanism other than olfactory
stimulation(128).Alternationofthepredominantnasalairflowtotheoppositeside
occurredafteralternationofcerebralhemispheredominance(128). Alargerstudy
38
involving126right-handedparticipantsfoundatendencyforenhancedperformance
in verbal tasks at times of right nasal passage dominance, and enhanced
performance in spatial tasks at times of left nasal passage dominance, i.e. a link
between nasal passage dominance and activity in the contralateral cerebral
hemisphere(136).
Not only do the authors of these articles often reach different conclusions, they
utilisedifferentmethodsoftesting,analysisandreporting,usuallyinsmallgroupsof
subjects,attimesfailingtoconsiderpotentiallyconfoundingfactorssuchasgender
andhandedness.EEGstudiesinparticulararedifficulttointerpretandhavevarying
methodsofanalysis.Thereisalsoahighlevelofinter-individualvariability(132).It
mustbenotedthattheauthorswhohaveidentifiedanultradianrhythmincognitive
performance have supported Kleitman’s theory of the BRAC (131), potentially
introducingbias(128,133).
Modelofhowthebraininfluencesnasalairflow
A model of how the brain influences nasal airflow is illustrated in Figure 4. The
model summarises the evidence and ideas presented in this section and for
simplicity thecontrol isdiscussed fromtheperipheralnervesandmovingupwards
throughthehierarchyofcentralnervouscontrolcentres.Theperipheralcontrolof
nasal airflow via the autonomic nervous system involves the vasoconstrictor
sympathetic nerves that supply the large veins in the turbinates (2, 36). The
asymmetry in brain activity and sympathetic tone extend to the brainstem region
where leftand rightoscillatorscause reciprocal changes innasalairflow (38). The
hypothalamusmay give the overall rhythmicity to a cycle of reciprocal changes in
nasal airflow, but there is no evidence for asymmetry at this level (39). Cortical
involvement in nasal airflow asymmetry has been suggested by studies on
handedness (113), ultradian rhythms of cerebral activity (128) and lateralisation
disorders such as schizophrenia (108) and autism (70), but the evidence for these
influencesisweak.
39
Figure4:Modeltoexplainthe influenceofbrainactivityonnasalairflow.Theoverallalternation insympatheticactivityoveraperiodofhoursiscontrolledfromthehypothalamusandtheasymmetryinsympatheticoutflowisdeterminedbytheactivityofbrainstemoscillatorswhichactasaflipflopmechanism,witheachcentre inhibiting theactivityof theothercentreandonlyonecentrehavingdominant activity at any one time. These hypothalamic and brainstem mechanisms have beenstudied in theanaesthetised cat (38,39). Higher centres in the cerebral cortexmayalso influencenasal airflow leading to asymmetry and most of the supporting evidence for this has come fromexperimentalwork inman(70,113,128). (SNS=sympatheticnervoussystem,+ve=positive,-ve=negative.)
Doesasymmetricalnasalairflowcauseasymmetricalbrainactivity?
Thesensationofnasalairflowisbelievedtobemainlydeterminedbystimulationof
nasaltrigeminalnerveendingsthataresensitivetotemperaturechanges,especially
coolingof thenasalmucosa,whichoccursduring inspirationof air (1, 45, 46). A
40
purely trigeminal stimulus has been shown to increase arousal frequency and
durationduringsleep(137),whereasnoeffectwasseenwithanolfactorystimulus
(138).Therefore, itseemsthatanasalairflowstimuluscan influencebrainactivity,
andfurtherevidenceisdiscussedbelow.
Nasalhyperventilationandepilepticactivity
Ithasbeenknownforsometimethatdeepbreathingcanactivateepileptic foci in
the brain, triggering seizure activity (139). This phenomenon was previously
explainedbyhypocarbia leading to vasoconstriction and cerebral ischaemia, but it
appears that airflow stimulation of the nasal mucosa could be the trigger (139).
Animal studieshavedemonstrated that insufflationofair into thenasal cavity can
triggerepilepticareasinthebrain(139).Instudiesofsomeepilepticpatients,nasal
hyperventilation was more likely than oral hyperventilation to stimulate epileptic
EEG activity, and unilateral nostril breathing had a greater effect on the
abnormalities in the ipsilateral hemisphere (139, 140). This was suppressed
following theapplicationof local anaesthetic to thenasalmucosa in the regionof
thesuperiormeatus(139,141).Theexactmechanismofthisphenomenonhasnot
beenfullyestablished,howevertheauthorsofthesestudieshavesuggestedareflex
involvingstimulationoftheolfactorynervebynasalairflow(139,141).
Unilateralforcednostrilbreathing
Asymmetrical nasal airflowwith unilateral forced nostril breathing (UFNB), where
onenostrilisoccludedeithermanuallybythesubjectorwithcottonwool,hasbeen
used to analyse the influence of asymmetrical nasal airflow on the brain as
measuredbyEEGactivity(142)andcognitiveperformance(136,143).Infact,these
concepts have their basis in ancient yogic practices, and there is a relatively large
literaturediscussingthenostrilbreathingmethodsutilisedinyogaandtheireffects
on mood and cognition, for examples see (144-149). Several studies have
demonstratedaneffectontheautonomicnervoussystem, forexamplechanges in
cardiovascularparameters(150-152)andintraocularpressure(153-155).Inastudy
offivesubjects,UFNBcausedashift inthedominantcerebralhemisphere,defined
byrelativelygreaterEEGactivity,oftenwithintwominutes(142).Whetherandhow
41
thiscorrelateswithcognitiveperformanceremainscontentious.Ingeneral,studies
haveusedhemisphere-specific tasks tomeasure cognitiveperformance, i.e. verbal
taskstoreflectlefthemisphereactivityandspatialtaskstoreflectrighthemisphere
activity. Using these methods, one study identified significant improvements in
verbal test scores with right UFNB and spatial test scores with left UFNB (156).
Others have found that left UFNB significantly improved right hemisphere
performancewhereasrightUFNBhadnoeffect (149,157),but theoppositeeffect
has also been demonstrated, wherein right UFNB improved left hemisphere
performance but left UFNB had no effect (146). One study suggested that UFNB
affectedtaskperformancedifferentlyinmalesandfemales(143),althoughagainthis
findinghasnotbeenreproducible(157).OthershavefailedtoshowthatUFNBhad
anyeffectonEEGmeasurements(158)orcognitiveperformance(128).Ithasbeen
suggested that UFNB can influence mood, and it has been reported to affect
emotionalresponses(159).
Oftenthesestudiesaredifficulttointerpretaccuratelyandhaveconflictingresults.
Criticismsincludesmallnumbersofparticipants(142,143,156),differingmethodsof
UFNB (142, 143, 149), differingmethods of measuring cerebral activity (142) and
cognitive performance (143, 156), and failure to consider potential confounding
factorssuchassex(149)andhandedness(142).
Following their study of nasal airflow patterns in children with autism, Dane and
Balci(2007)suggestedthatautismisassociatedwiththeabsenceofanormalnasal
cycle,theleftnasalpassagebeingdominantforthemajorityofthetime(70).They
have likened this finding to continuous leftUFNB, and suggested that thismaybe
causingcontinuousstimulationoftherightcerebralhemispherewhilstdeprivingthe
left cerebral hemisphere of stimulation, possibly accounting for the delayed
languagedevelopmentoften seen in thisgroup (70). The issuewith this theory is
thatthere isnoevidencethatrightnasalblockage,forexampleseptaldeviationor
nasalpolyposis,leadstodevelopmentaldelay.Inthesepathologicalconditions,the
differencebetweentheamountofairflowineachnasalpassageisfargreaterthan
thedifferencecausedbythenasalcycleunderphysiologicalconditions.
42
Shannahoff-KhalsaandhiscolleagueshavesuggestedinmultiplearticlesthatUFNB
haspotential as anon-invasive treatment for psychiatric disorders (142, 160), and
haverecordedacorrelationbetweenleftnasalpassagedominanceandhallucination
occurrenceinoneschizophrenicfemale(160).ArecentarticlesuggestedthatUFNB
mayhavebeneficialeffectsforrecoveryofspeechinstrokepatients(161).
Howcouldanasalairflowstimulusaffectcerebralactivity?
A proposed mechanism for a correlation between nasal airflow and cerebral
hemisphere activity involves the sympathetic nervous system (128, 142, 157),
supported in part by the other autonomic effects demonstrated to occur during
UFNB(150-152).Asautonomicnervefibresconnectingthenoseandhypothalamus
donotdecussate,vasoconstrictioninthenasalvesselshasbeenpostulatedtoreflect
concurrent vasoconstriction in the ipsilateral cerebral hemisphere, leading to a
decrease in cerebral blood flow ipsilaterally and relative increase contralaterally
(128, 142, 157). In this way, the increased blood flow could improve cognitive
functionasmeasuredbyperformanceinhemisphere-specifictasks(157).
However thephysiologicalbasis for this theory isquestionable. Taskperformance
has been shown to increase overall blood flow to both hemispheres, and more
specifically verbal tasks cause a left lateralisation and spatial tasks a right
lateralisation in right-handed subjects (162, 163). However the effect of the
sympatheticnervoussystemoncerebralbloodflowunderphysiologicconditions is
thought tobeminimaldue to theactionof cerebralautoregulation (164). In fact,
whilst blockade of the stellate ganglion i.e. inhibition of sympathetic activity
increasesbloodflowinextracranialvessles,ithasnoeffectintra-cranially(165).
Thereforeadifferentmechanism for theeffectofnasal airflowonbrainactivity is
proposedhere,incorporatingtheactivatingeffectofanasalairflowstimulusonthe
cerebralcortexviathereticularformation.ThisisillustratedinFigure5.
43
Figure5:Model toexplain the influenceofnasalairflowonbrainactivity. Anasalairflowstimulussuch as UFNB stimulates trigeminal nerve endings on one side of the nose. Trigeminal neuronstransmittingtemperaturesignalssynapseinthespinaltrigeminalnucleusandthencrossthemidline,travelling up to the thalamus through the brainstem. Studies on cats have suggested that via thebrainstem reticular formation, a nasal airflow stimulus could lead to enhanced arousal and brainactivity in both cerebral cortices (166). EEG studies and cognitive performance testing in humansubjectshaveintimatedthatthegreateststimulatingeffectoccursinthehemispherecontralateraltothenasalairflowstimulus(128,156).
One major challenge is that the laterality of cerebral hemisphere stimulation by
nasal airflow isunclear,with somestudies suggestingan ipsilateral response (139,
143),andothersacontralateralresponse(142,156,157).Olfactorynervefibresdo
not decussate and therefore stimulate mostly the ipsilateral cortex, whereas
trigeminal fibres relaying temperature signals cross over in the spinal cord before
passing through the brainstem. The trigeminal nerve detects nasal airflow, but
experimentalinsufflationofairintothenasalpassagescouldstimulatetheolfactory
44
nerve due to the inadvertent presence of an olfactory stimulus. In addition, the
olfactorycortex isunabletosensethelateralityofastimulusunlessthetrigeminal
nerve isalso stimulated (167).Suppressionof theEEGstimulationcausedbynasal
airflow by application of local anaesthetic to the nasal mucosa (141) is more
suggestive of trigeminal nerve involvement. Although sleep studies have
demonstratedarousalsecondarytoatrigeminalnervestimulus,thisstimuluswasan
irritant (carbon dioxide) (137) and is therefore difficult to compare with nasal
inspirationofairaswithUFNB.
It is possible that nasal airflow causes bilateral cortical stimulation,with a greater
effect on one side. Experimental stimulation of the reticular formation in
anaesthetisedcatscausedEEGchangesindicatingincreasedalertness,andatlower
levelsofstimulationthiseffectwasonlyseenintheipsilateralhemisphere(166).It
isunclearwhetherthetrigeminalorolfactorynervesareinvolvedinthismechanism.
Modelofhownasalairflowinfluencesbrainactivity
Amodel of how nasal airflow influences the brain is illustrated in Figure 5. The
model summarises the evidence and ideas presented in this section. Inspired air
stimulatescoldreceptorsinthenasalmucosathatareinnervatedbythetrigeminal
nerve,providingthesensationofnasalairflow.Environmentalsensorystimulisuch
asnoiseorsmellscanenhancearousal,andthiseffect ismediatedbythereticular
formation–anarea in thebrainstem involved inarousal andconsciousness (166).
ExperimentalstimulationofthereticularformationinanaesthetisedcatscausedEEG
changesindicatingincreasedalertness(166).Insufflationofairintothenosehadthe
sameeffectonEEGpatternsi.e.increasedarousal(168).Therefore,anasalairflow
stimulus, for example insufflation of air or UFNB could activate the reticular
formation and increase arousal, leading to EEG changes and possibly improved
cognitive performance. There is evidence to suggest both an ipsilateral (139, 143)
andcontralateral (142,149,156,157)stimulatingeffect. However it ismore likely
that a unilateral nasal airflow stimulus has an activating effect on both cerebral
hemispheres, but with a greater effect on one side. As trigeminal neurons
45
transmitting temperature signals cross themidline in themedulla, it seems logical
thatthegreatesteffectwouldbeseencontralaterally.
2.4:Conclusions
Theancientyogicpracticeof“pranayama”orbreathcontrolexercisesarethoughtto
promotehealth andwell-being, improve circulationandprepare for concentration
(169). Whilst this notionmay have beenmet with scepticism from the scientific
community, it inspired clinical studies into the effects of nasal breathing on
cognition. There is a growing body of evidence to suggest that nasal airflow can
influence brain activity, however the mechanism, extent and significance are
debatable. Considering the evidence from studies in epileptic patients (139, 141)
andarousalduringsleep(137),itseemsthatanasalairflowstimuluspotentiallyhas
somesortofactivatingeffecton thebrain. Putting this intoaneverydaycontext,
stepping outside into a cold environment and inhaling cool air through the nose
often makes us feel more alert, and the cooling effects of menthol on nasal
receptorsmayalsocausearousal(170).SmellingsaltswereusedinVictoriantimes
toreviveunconsciouspatients,andevennowadayssomeathletesusesmellingsalts
as a stimulant prior to competing (171). However the role of higher centres and
cortical organisation remains uncertain, with some conflicting theories suggested.
For example, if nasal airflow dominance correlateswith hand preference (113), it
couldnotalsocorrelatewithfluctuatingultradianrhythmsofcerebralactivity(136),
ashandpreferenceisnormallyfixed.
46
Chapter3:Methodology
3.1:Ethicalapproval
ThestudywasdesignedandconductedaccordingtotheWorldMedicalAssociation’s
Declaration of Helsinki and the International Council for Harmonisation’s Good
Clinical Practice guidelines. Prior to commencement all documentation was
reviewedandapprovedbytheSchoolofBiosciencesResearchEthicsCommitteeand
Cardiff University’s Research Governance Department. The patient information
leafletandinformedconsentformareincludedinAppendices2and3.
3.2:Studydesign
Thestudywasdesignedasaprospectivepilotstudy,basedonthemethodsusedby
Searlemanetal.(2005)(113).Thehandednessofeachsubjectwasrecordedaspart
ofthescreeningprocedure.Followingthis,nasalairflowwasmeasuredat15-minute
intervals over a continuous 6-hour period using a modified GM, as described by
Gertner et al. in 1984 (54). At eachmeasurement, the investigator examined the
condensationareasformedonthemetalplateanddeterminedwhethertheleftor
right nasal passage had produced the largest area, and therefore was dominant.
Thesameinvestigator(AP)carriedoutallmeasurementsinanattempttominimise
uservariation.
AlthoughsimilarindesigntoSearlemanetal.’s2005study(113),adifferentmethod
ofmeasuringnasalairflowwaschosen.Partofthereasonforthiswasrelatedtothe
aim of the study. In order to determine the dominant nasal passage in terms of
airflow,theonlyvariablesofimportanceareleftorright.ThemodifiedGMprovides
a snapshot view of nasal airflow through each nasal passage, allowing the
investigator to instantaneously judgewhichnasal passagehas the greatest airflow
47
andthereforeisdominant.Otheradvantagesofthistechniquearediscussedinthe
introduction(seesection1.7).
3.3:Studypopulationandrecruitment
Participants were recruited from Cardiff University campus by an advertisement
email and posters seeking out normal, healthy, non-smoking adults. Participants
wereexcludediftheyhadahistoryofnasaldiseaseorweretakingmedicationthat
couldaffectnasalphysiology. Incontrast toSearlemanetal.’s (2005) study (113),
womenwereincludedprovidingtheywerenotpregnantorlactating.Thepotential
effects of female sex hormones on nasal airflow were discussed in detail in the
Introduction(seesection1.8),howeverinbrief,duringpregnancyit isthoughtthat
hormonalchangesareresponsibleforpregnancy-inducedrhinitis,whichisrelatively
commoninthelaterstagesofgestation(88,89).Thereissomeevidencetosuggest
thatnasalairwayresistancemaybehigherduringmenstruation,althoughchangesin
thenasalcyclehavenotbeenidentified(92).Inaddition,thereislittleevidenceto
suggest that the contraceptive pill has a significant effect on the nasal cycle (99).
Many other studies specifically analysing the nasal cycle have involved bothmale
andfemaleparticipants,withoutsignificantdifferencesidentified.
Forthefullexclusionandinclusioncriteria,seeAppendix1.
Participants were paid an honorarium of £70 on completion of the study. Those
excludedfromthestudyfollowingthescreeningassessmentwerepaid£5fortheir
time.
48
3.4:Samplesizeandpower
Asthiswasapilotstudy,theaimwastorecruitbetween25and30participants,with
thefinalnumberdependentonthenumberofleft-handedparticipantsincluded.A
powercalculationbasedonthepreviousstudy(113)wasnotpossibleduetolimited
data presented, however statistical significance was reportedly achieved with 20
participants(113).
3.5:Measurementofhandedness
Atestofhandednesswasperformedtoexcludethosecategorisedasmixed-handed
andtoidentifythehandpreferenceofeachparticipant.Thisinvolvedobservationof
handwriting,followedbycompletionoftheEdinburghHandednessInventory(Short
Form) toobtainahandedness categorisation (172) (seeAppendix4). If therewas
any disparity between the participant’s statement of hand preference and
observation of handwriting, the participant was excluded. Participants were also
excludediftheydemonstratedmixedhandedness.
Handedness can either be measured by preference or skill, and there is good
correlationbetweenboth typesof test especially for complexmovements such as
writing(118). Observationofhandwritingaloneasatest forhandednesscanmiss
thosewithmixedhandedness,whichcouldbeaconfoundingfactor.Aquestionnaire
was therefore used to ascertain subjects’ hand preference for several different
activities.TheEdinburghHandednessInventoryisthemostwidelyusedpreference
questionnaire(119),andtheShortFormisarevisedversionthathasbeenshownto
havegoodvalidityandreliability(172).Subjectswereaskedwhichhandtheyprefer
touse for fourdifferentactions;writing, throwing,usinga toothbrushandusinga
spoon. Theywereassignedscores thatwereusedtocalculatewhether theywere
categorisedasleft-handed,right-handedormixed-handed(seeAppendix4).
49
3.6:Measurementofnasalairflow
Nasal airflowwas assessed using themodifiedGM, as described byGertner et al.
(1984)(54).Thismethodallowstheinvestigatortoobtainamomentaryassessment
of nasal airflow by comparing the condensation area formed by expired air from
each nasal passage. The instrument usedwas a polishedmetal platemade from
aluminiummeasuring10cmx12cmandmarkedwitharches1cmapart (seeFigure
6). The plate was positioned horizontally just beneath the columella with the
verticalaxisat90degreestowardstheupperlip.Eachparticipantwasinstructedto
exhalethroughthenoseslowlywiththeeyesandmouthclosed. Thetemperature
differencebetweentheexpiredairandthemetalplateiswhatcausesthevapourto
condense on the plate. By observing which nasal passage produced the largest
condensationarea,thedominantnasalpassagewasrecorded.
Figure6:Aphotographofthemetalplate(i.e.modifiedGM)usedinthestudy.
3.7:Trialenvironmentandprocedure
All visits and testing procedures were carried out at the Common Cold Centre.
Potentialparticipantsattendedforascreeningvisit,wheretheywereprovidedwith
aparticipant information sheet (seeAppendix2) and signeda study consent form
(seeAppendix3).Theywerethenassessedbythestudyclinician(AP)toensureall
50
inclusionandexclusioncriteriaweremet,whichinvolvedelicitingamedicalhistory
and examining the nose by anterior rhinoscopy. Those enrolled onto the study
attendedatalater,convenientdatefortesting.
Everyattemptwasmadetominimisefactorsknowntoaffectnasalairflowthatcould
potentiallyaffectthestudyresults.Sinceupperrespiratorytractinfectionhasbeen
showntoincreasethenasalairwayresistanceandtheamplitudeofthenasalcycle
(23),participantswithcommoncoldsymptomsatthescreeningvisitoronthetest
dayweredelayed for twoweeks toensure resolution. Alcohol ingestion increases
nasal airway resistance (100, 101), therefore participantswere asked not to drink
more than four units of alcohol the night before testing. Exercise effectively
abolishes the reciprocal changes in nasal airway resistance, leading to an overall
increaseinnasalairflow(84),thereforeparticipantswereaskedtorefrainfromany
vigorous exercise such as running, cycling or swimming for three hours prior to
testing.
On the test day, participants arrived 30minutes prior to the start time for nasal
measurements to ensure anyeffects of exertion and theexternal environmenton
the nasal mucosa were eliminated, and to allow for acclimatisation to the
temperature and humidity of the test environment. During the test period,
participantsremainedatrestandinthesameroom,withallowancesforuseofthe
bathroom. Theywerepermitted to read, use their computersorwatch television
butwerenotpermittedtoliedown,aschangesinpostureandpressurestimulican
leadtoalterationofnasalairflow(78,79).Althoughmentholhasnotbeenshownto
affectnasalairwayresistanceperse,itcancauseasubjectivechangeinnasalairflow
(47), therefore participants were not permitted to eat any menthol containing
productssuchasmints.Theywereprovidedwithastandardcoldlunchbetween12
and12.30pm.Nohotdrinkswerepermitted.
RecordingsofthedominantnasalpassageusingthemodifiedGMwereperformedat
15-minuteintervalsovera6-hourperiod,givingatotalof24recordings.Participants
51
were positioned sitting upright with the head in a neutral position. Once sitting
comfortably,theyweregiventhefollowinginstructions:
“Iwillaskyoutotakeadeepbreathinusingthewordinhale.Youwillthenholdthis
breathuntil I informyou toexhale. Whenyouexhale,keepyoureyesandmouth
closedandgraduallybreathoutthroughyournostrils.”
Whilsttheparticipantheldtheirbreath,themodifiedGMwaspositionedunderthe
collumela as described above (see Figure 7). This procedure was repeated three
timesateach15-minuteinterval. Ajudgementwasmadebytheinvestigatorasto
which nasal passage produced the largest condensation area, and was therefore
dominant,andthiswasrecordedaseitherleftorright.Ifitwasunclearwhichnasal
passage had produced the largest condensation area, the result was recorded as
equal.Ofthethreemeasurementstaken,themajorityreadingwasusedasthefinal
result.
Figure7:AphotographofthemodifiedGMinuse.Theparticipantisexhalingthroughthenosewiththe modified GM positioned horizontally just beneath the columella. The condensation areasproduced during exhalation can be seen on the plate and aremarkedwith a dotted line. On thisoccasion the rightnasalpassageproduceda largercondensationarea than the left, indicating rightnasalpassagedominanceatthattime.
A trial runwasperformedduring the 30-minute rest period after eachparticipant
arrivedatthetestcentretoallowthemtobecomefamiliarwiththetestingmethod.
Results from this trial runwere not be recorded or included in the data analysis.
Carewastakentominimisepositionalerrorswhilstrecording. Thesubjectwassat
52
uprightwiththeheadinaneutralpositionandthesameinvestigator(AP)performed
andinterpretedeachmeasurement.
3.8:Blinding
In order to avoid potential investigator bias (given the subjective nature of the
recordings), as much as possible the investigator taking the nasal airflow
measurements (AP) was blinded to the participants’ handedness. Handedness
questionnaireswerecompletedbyparticipantsandcheckedbyanotherresearcher.
Participants were asked not to reveal their hand preference or write when the
investigatorwasintheroom.Throughoutdatacollection,participantdemographics
weremonitoredbyanotherresearcheranddiscussedwiththeinvestigatortoensure
roughly equal numbers of right-handed and left-handed participants and to guide
recruitment. Thereforethe investigatorwasnotblindedtothe lastthreesubjects’
hand preference as only left-handed volunteers were recruited (subject numbers
034, 035and036). Thehandednessof all participantswas revealedonceall data
hadbeencollectedandanalysed.
3.9:Statisticalanalysis
The data collected was compiled into a Microsoft Excel® spreadsheet for further
analysis. In order to define each subject as either left or right nasal passage
dominantbasedonthemeasurementscollected,binomialdistributionwasusedto
lookforconsistentdifferencesineachsubject.
Once all data had been analysed, the hand preference of each participant was
revealed. The Chi-square test was used to look for a statistically significant
correlationbetweennasalpassagedominanceandhandpreference.
53
Chapter4:Subjects
4.1:Introduction
Overthepastfewdecades,manystudieshavefoundthatcertainphysiologicaland
pathological conditions can influence nasal airflow. These include subject factors,
suchasage(74)andnasalpathology(54),positionalfactorssuchasposture(79)and
other influences such as sleep (28) and exercise (84). During recruitment, efforts
weremadetominimisefactorsknowntoinfluencenasalairflowusingstrictinclusion
and exclusion criteria. The test environment and methods used to take
measurementswerealsocarefullyconsidered. The followingsectiondiscusses the
recruitment procedure and subjects in detail with reference to the relevant
literaturethatinformedtheprocess.
4.2:Methods
Volunteersforthestudywererecruitedbyemailandposteradvertisementsplaced
around Cardiff University campus. There were two periods of recruitment and
testingthatcoincidedwithuniversitysemesters,oneintheautumnandanotherin
the spring. The first group of volunteers were recruited and tested between
November 5th 2015 and December 17th 2015 (subject numbers 001 – 019). The
secondgroupwererecruitedandtestedbetweenApril11th2016andMay20th2016
(subjectnumbers020–036).Bothgroupscontainedamixtureofmaleandfemale
subjectsandleft-handedandright-handedsubjects.Allvolunteerswerestudentsat
theUniversity.
Eachsubjectwasrequiredtoattendthetestcentreontwoseparatedays. Onthe
firstday,afterprovidinginformedconsent,subjectswerescreenedforsuitabilityto
takepart.Toensurethatallinclusionandexclusioncriteriaweremet,subjectswere
asked about their medical history and had a nasal examination using anterior
54
rhinoscopy (for full list seeAppendix1). Aconvenientdatewas thenarranged for
thetestday.
4.3:Results
Intotal,36subjectswererecruitedintothestudy.Ofthose,7wereexcluded.The
reasonsforexclusionarelistedinTable2.
Table 2: A summary of the demographics and reasons for exclusion. *Subject 014 was takingisotretinoinforacne,whichcancausedrynessofthenasalmucosa(173).
Subjectnumber
Age(years)
Gender Handpreference Reasonforexclusion
001 22 M Left Significantnasalseptaldeviation
014 18 F Left Concominantconfoundingmedication*
016 19 F Left Rhinitis
017 19 M N/A Mixedhandedness
021 22 M N/A Mixedhandedness
026 27 F Right Significantnasalseptaldeviation
029 20 M N/A Mixedhandedness
Efforts were made to recruit roughly equal numbers of left- and right-handed
subjects andmalesand females (seeTables5and6). Of those included,14were
maleand15werefemale.Theaverageagewas20.8years,witharangeof18–30
years. Fifteen subjects were left-hand dominant (LHD), including 6 males and 9
females,and14wereright-handdominant(RHD),including8malesand6females.
ThedemographicsofallincludedpatientsarelistedinTable3.
55
Table3:Demographicsofallincludedsubjects.
Subjectnumber
Age(years) Gender Handdominance Significantmedicalhistory
Concominantmedication
002 19 Female Right None None003 19 Male Left Seasonalrhinitis–
asymptomaticduringstudyperiod
None
004 18 Female Left None None005 19 Female Left None None006 18 Female Left None Progesterone–only
contraceptivepill007 20 Female Left Mildasthmaduring
childhood–asymptomaticfor8years
None
008 20 Female Left None Combinedoralcontraceptivepill
009 18 Female Left Cholecystectomyforgallstones
Combinedoralcontraceptivepill
010 20 Female Left Mildasthmaduringchildhood–asymptomaticfor8years
Combinedoralcontraceptivepill
011 20 Male Left Seasonalrhinitis–asymptomaticduringstudyperiod
None
012 21 Female Left Mildasthmaduringchildhood–asymptomaticfor4years
None
013 20 Male Right None None015 21 Female Left None None018 21 Female Right Appendicectomy None019 19 Female Right None Contraceptiveimplant(slow
releaseprogesterone)020 21 Female Right None Contraceptiveimplant(slow
releaseprogesterone)022 20 Female Right None Combinedoralcontraceptive
pill023 23 Male Right None None024 25 Male Right None None025 21 Male Right Depression Sertraline(selectiveserotonin
reuptakeinhibitor)027 21 Female Right None Combinedoralcontraceptive
pill028 20 Male Right None None030 22 Male Right None None031 30 Male Right None None032 21 Male Left None None033 25 Male Right None None034 21 Male Left None None035 22 Male Left None None036 19 Male Left Migraine None
56
Table4:Summaryofincludedsubjects.
Summaryofincludedsubjectdemographics
Averageage(years) 20.8
Medianage(years) 20
Agerange(years) 18-30
Numberofmales 14
Numberoffemales 15
Maletofemaleratio 1:1.07
Numberofleft-handers 15
Numberofright-handers 14
Lefttoright-handedratio 1:0.93
Table5:Comparisonofbasicdemographicsformaleandfemalesubjects.
Malesubjects Femalesubjects
Numberofsubjects 14 15
Averageage(years) 22 19.7
Medianage(years) 21 19
Agerange(years) 19–30 18–21
Numberofleft-handers 6 9
Numberofright-handers 8 6
Table6:Comparisonofbasicdemographicsforleft-andright-handedsubjects.
Left-handers Right-handers
Numberofsubjects 15 14
Averageage(years) 19.8 21.9
Medianage(years) 20 21
Agerange(years) 18–22 19–30
Numberofmales 6 8
Numberoffemales 9 6
57
During screening, all subjects were asked specifically about any history of nasal
problems in the past and concurrent nasal symptoms. No subject reported
concurrentorrecent(precedingonemonth)nasalsymptomssuchasnasalblockage,
rhinorrheaorchangeinsenseofsmell.Thiswascheckedasecondtimeonthetest
day to ensure no subject had a concurrent or recent history of rhinitis that had
developed between the screening and test days. Anterior rhinoscopy was
performed on all subjects during screening, and those with significant septal
deviation (n=2)or signsof rhinitis (n=1)wereexcluded. Noothernasalpathology
wasdetectedduringscreening.
Themajority of subjects (20/29) reported no significant previousmedical history.
Twosubjectshadahistoryofseasonalrhinitishowevertheywerebothtestedduring
theautumnperiodanddeniedanyrecentnasalsymptoms.Theydidnothavesigns
of rhinitis on anterior rhinoscopy. Three subjects reported mild asthma during
childhood however they had been asymptomatic and had not required any
treatmentforat leastfouryears. Twosubjectshadpreviouslyrequiredabdominal
surgery in the form of an appendicectomy (n=1) and a cholecystectomy (n=1)
however they had fully recovered from these procedures. One male subject
reportedahistoryofmilddepressionandanotherreportedahistoryofmigraines,
bothofwhichweredeemedunlikelytoaffecttheresultsofthestudy.
Nine subjects were taking prescribed medication at the time of the study. The
majority of these subjects were females taking contraception in the form of the
combined oral contraceptive pill (n=5), the progesterone implant (n=2) and the
progesterone-only contraceptive pill (n=1). One subject was taking sertraline, a
selective-serotoninreuptakeinhibitorusedtotreatdepression.
58
4.4:Discussion
During screening and testing, efforts were made to minimise factors that could
influence nasal airflow. Potential influencing factors are discussed below, with
referencestoevidencefromtherelevant literature. Thedemographicsof the left-
andright-handedgroupsweresimilar.
Subjectfactors
Theaverageageofthiscohortwas20.8years,witharangeof18–30years. The
averageageofright-handedsubjectswasslightlyhigherat21.9years,comparedto
19.8years in left-handedsubjects. Studieshavesuggestedthatadvancingagecan
affect patterns of nasal airflow, however changes seem to be more likely in
individualsagedover50years(74,75)andthereforetheagerangeinthisgroupis
unlikelytobeapotentialconfoundingfactor.
Although BMIwas notmeasured specifically, none of the recruited subjectswere
overweight.
Bothmaleandfemalesubjectswereincludedinthestudy.Searlemanetal.(2005)
only includedmalesduetoconcernsthatchanges infemalesexhormonelevelsas
part of the menstrual cycle could affect nasal airflow (113). However conflicting
results have been published regarding this theory,with one study reporting nasal
congestionduringmenstruation (92)and another reportingnodifference innasal
airflow throughout different phases of the menstrual cycle (93). Perhaps more
importantly,twootherstudiesthatmeasurednasalairflowoverseveralhoursusing
differentmethods found that gender did not significantly affect nasal airflow (29,
74).Enquiringaboutphaseofthemenstrualcycleinfemalesubjectswastherefore
consideredunnecessary.Femalesubjectswereaskedwhethertheywerepregnant,
howeverformaltestingwasnotcarriedoutasthestudydidnotinvolveanyrisksto
pregnantwomen (suchasmightbe thecasewithadrug trial). Whilstpregnancy-
inducedrhinitisisrelativelycommon,itpredominantlyoccursinthelatterstagesof
59
pregnancy and is associatedwith symptoms such as nasal stuffiness (88, 89). All
subjects were asked specifically about nasal symptoms and examined by anterior
rhinoscopytoexcludethosewithrhinitis.
Most subjects had no significant past medical history. Of note, three subjects
reportedmildchildhoodasthmabuthadbeenasymptomaticforatleastfouryears
andwerenottakinganyinhalers.Theirrespiratoryfunctionthereforewasassumed
to be normal. Twopatients reported seasonal rhinitis, however theywere tested
during the autumn and were asymptomatic with normal anterior nasal
examinations.
Anteriorrhinoscopywasperformedoneachsubject inordertoexcludethosewith
nasal pathology such as nasal polyps or septal deviation, which can affect nasal
airflow (28, 54, 107). A more detailed nasal examination in the form of nasal
endoscopywasdeemedunnecessaryasitisaninvasiveprocedureandonlysubjects
withnohistoryofnasalproblemsorconcurrentnasalsymptomswererecruitedinto
thestudy.
Eightoutoffifteenfemalesubjectsweretakingsomeformofcontraception,either
progesterone-only(n=3)orcombinedoestrogenandprogesterone(n=5).Although
there have been concerns that oestrogens can cause nasal congestion (92, 97), a
studyontheeffectofthemoderncombinedcontraceptivepillfailedtoshowthatit
alterednasalairflow (99). Therefore itwasdeemedunlikely thatcontraceptionof
anykindwouldinfluencetheresultsofthisstudy. Allothersubjectsdeniedtaking
anyregularprescribedorover-the-countermedication,apartfromonemalesubject
who was taking sertraline, a selective-serotonin reuptake inhibitor used to treat
depression,whichhasnonasal sideeffects listed in theBritishNationalFormulary
(173).
Positionalfactors
Changesinpostureareknowntoaffectnasalairflow.Sometimesreferredtoasthe
corporo-nasal reflex, stimulation of pressure sensors in the thorax, pectoral and
60
pelvic girdles leads to ipsilateral nasal congestion and contralateral nasal
decongestion(78-80).Changingfromasittingtoasupinepositionwillincreasenasal
airwayresistanceviaanincreasedbloodflowtothenasalvessels(76,77).Inorder
to avoid these effects, subjects were not permitted to lie down during the
measurement period. Positional factors can also affect the reliability of
measurementsobtainedusingthemodifiedGM(66)andthereforecarewastaken
to ensure that each subject sat up straight with their head in a neutral position
during measurements. To ensure continuity in the measurement technique, all
measurements were performed by one investigator, and anatomical landmarks
(columellaandupperlip)wereusedtomaintainthesamepositioningoftheplateat
eachmeasurement.
Environmentalfactors
Recruitment and testing took place in two groups, 15 subjects were tested in
NovemberandDecember2015,and14weretestedinAprilandMay2016.Testing
was performed in a laboratory, and all subjects spent the 6-hour measurement
periodinthesameroom,withallowancesfortoiletbreaksasrequired.Althoughthe
exact temperature andhumidity level in the laboratorywerenot recorded, itwas
alwayskeptatacomfortablelevel.Roomtemperaturedifferenceswerenotshown
to affect nasal airflow when acoustic rhinometry was performed at room
temperaturesof18-22°Cand30-33°C(86).Duringthefirsttestperiod,theaverage
maximumoutdoor temperaturewas12°C, theaverageminimumtemperaturewas
10°Candtheaveragehumiditywas88%(174). Duringthesecondtestperiod, the
average maximum outdoor temperature was 12°C, the average minimum
temperaturewas8°Candtheaveragehumiditywas77%(174).Whilsttheoutdoor
environmentwas slightlydifferent foreachsubject, importantly theyweregivena
30-minuterestperiod inthetestenvironmentpriortostartinganymeasurements,
allowingacclimatisationtotheindoorenvironment,assuggestedinapreviousstudy
usingthemodifiedGM(55).Asingestionofhotwaterhasbeenshowntoincrease
nasal congestion (87), subjectswere not permitted to drink hot drinks or eat hot
food during the test period. No such effect was foundwith cold drinks (87) and
61
thereforesubjectswerepermittedbottledwaterthroughoutthedayandweregiven
astandardisedcoldmealatmidday.
Temperatureandhumiditychangesalsohavethepotentialtoreducethereliability
of themodified GM (55, 66). In order to prevent heating of the plate, excessive
handling was avoided and a different plate was used for each of three
measurementsperformedateachtimepoint.Thisalsoensuredthattherewereno
remainingcondensationareas left fromthepreviousmeasurementandallowedall
threemeasurementstobeperformedinquicksuccession.Theplateswerekeptin
thesameroomas thesubjectduring the testingperiodandcleanedat theendof
eachtestday.
Otherfactors
Sleepwasnotpermittedduring the testperiodas sleephasbeen shown toaffect
nasalairflowpatterns,irrespectiveofpostureinsomeinstances(27,28).Duringthe
testperiod,subjectswereaskedtoremainatrestbutwerepermittedtostudy,read
orwatchtelevision. Subjectswereaskedtoavoidstrenuousexercise, forexample
swimming,cyclingorrunninginthethreehourspriortothestartofthestudy.This
was necessary as studies have shown that exercising abolishes the asymmetry of
airflowbetweenthenasalpassages,increasingtheoverallnasalairflowtomeetthe
increasedmetabolic demand (84, 85). Subjectswere askednot to consumemore
thanfourunitsofalcoholinthe12hourspriortothetestperiodduetotherisksof
increasingnasalcongestion(100,101). Ascigarettesmokingcandamagethenasal
mucosa(102),onlynon-smokerswererecruitedintothestudy.
62
Chapter5:Nasalairflowpatterns
5.1:Introduction
Multiple observational studies of nasal airflow patterns have been published over
thelastcenturye.g.(3,5,8-11,13).Whatisclearfromthesestudiesisthatagreat
dealofvariabilityexistsamongstnasalairflowpatterns,notonlybetweenbutalso
withinindividuals(8-11).Thishasledtocontroversyovertheuseoftheterm“nasal
cycle”,as thekey featuresof regularityand reciprocityhavenotbeenconsistently
demonstrated(13).
Nevertheless,somesimilaritiesinpatternsofnasalairflowhavebeenobserved.For
example,severalstudieshavenotedsomedegreeofreciprocitybetweenthenasal
passages, defined as congestion on one sidewith accompanying decongestion on
theotherwithoutachangeintheoverallnasalairwayvolume(13,15).Othershave
observed a parallel or in-phase relationship, with fluctuations in nasal airflow
occurringinbothnasalpassageswithnoreversalofnasalairflowdominance(9,15).
In some individuals, fluctuations in nasal airflow have been observed butwithout
any discernable pattern (8, 15). Kern (1981) used the term “non-cycle nose” to
describeindividualswithouttheclassicalfeaturesofanasalcycle(9).Hesuggested
threecategories;nochangeinnasalresistance,changesinonenasalpassagebutnot
intheother,andanin-phaseorparallelrelationship(9).
This sectiondiscusses thenasalairflowpatternsobserved in thiscohortofhealthy
individuals.
63
5.2:Methods
In order to obtain an overall description of the nasal airflow patterns for each
subject, the nasal airflow patternswere put into different categories according to
the definitions listed below. This part of the data analysis was done prior to
unblindingtohandpreference.
Category1:
Subjectswithdefinitechangesinnasalairflowdominancethatweresustained,i.e.a
changeinthedominanceofnasalairflowfromthelefttotherightnasalpassageor
vice versa. A sustained change was defined as at least four consecutive
measurementsofdominance inone side,which then switched tobecomeat least
four consecutivemeasurementsofdominance in thecontralateral side (seeFigure
8). Aperiodofuncertaintybetweenthechangewasallowed,specificallynomore
than two equal measurements (see Figure 9). Although the time period of four
measurementswaschosenarbitrarily,itwasthoughttobereasonableasitreflected
aonehourperiodoutofthesixhourtotalmeasurementperiod.
Figure8:AnexampleofasubjectwhosenasalairflowpatternfitsintoCategory1.
64
Figure9:AsecondexampleofasubjectwhosenasalairflowpatternsfitintoCategory1.
Category2:
Subjectswithlittleornochangeinnasalairflowdominance,definedasconsecutive
readings of dominance in one nasal passage throughout themeasurement period
(see Figure 10) with the exception of no more than three readings that indicate
dominance inthecontralateralnasalpassage(seeFigure11). Equalreadingswere
disregardedinthisgroup.
Figure10:AnexampleofasubjectwhosenasalairflowpatternfitsintoCategory2.
65
Figure11:AsecondexampleofasubjectwhosenasalairflowpatternfitsintoCategory2.
Category3:
Subjectswithvariationsinthepatternsofnasalairflowdominancethatdidnotfitin
witheitheroftheabovetwocategories(seeFigure12).
Figure12:AnexampleofasubjectwhosenasalairflowpatternfitsintoCategory3.
5.3:Results
Table 7 shows the categorisation of subjects into the groups described above.
Sixteensubjects(55%)exhibitedatleastonedefiniteandsustainedreversalofnasal
airflowdominanceduring the6-hourmeasurementperiodand could thereforebe
describedasinCategory1(seeFigures13-15).Eightsubjects(28%)hadlittleorno
changeinnasalpassagedominance(seeFigures16and17).Onlyfivesubjects(17%)
66
had nasal airflow patterns that were highly variable and therefore could not be
groupedintoCategory1or2(seeFigure18).
Table7:Subjectsgroupedintocategoriesaccordingtotheirpatternsofnasalairflow.
Category1 Category2 Category3
002 022 005 003
004 023 007 006
009 025 008 015
012 028 010 027
013 031 011 030
018 032 024
019 034 033
020 035 036
67
Figure13:NasalairflowpatternsofsubjectsinCategory1.
68
Figure14:NasalairflowpatternsofsubjectsinCategory1,continued.
69
Figure15:NasalairflowpatternsofsubjectsinCategory1,continued.
70
Figure16:NasalairflowpatternsofsubjectsinCategory2.
71
Figure17:NasalairflowpatternsofsubjectsinCategory2,continued.
72
Figure18:NasalairflowpatternsofsubjectsinCategory3.
Tointerpretthisdata,onemustconsiderthephysiologicalbasisforthesepatterns.
Ineachfigure,thenasalpassagewiththedominanti.e.thegreatestnasalairflowis
representedbyadiamondateachtimepoint.Thisisequivalenttowhichevernasal
passageproducedthegreatestcondensationareaonthemodifiedGM,andinmost
caseswas judged to be either the left or the right nasal passage. The degree of
differencebetweenthecondensationareaswasnotrecorded,onlywhetheronewas
larger than the other, and therefore this is a crude method of evaluating nasal
passagedominance.
73
Whenanasalpassageisdominant,itreceivesthegreatestsympatheticoutputfrom
the brainstem, leading to vasoconstriction of the nasal veins, reduced nasal
congestion and therefore greater nasal airflow (38). At the same time, the non-
dominantnasalpassagereceiveslesssympatheticoutput,resultingindilationofthe
nasal veins, increased nasal congestion and therefore reduced nasal airflow. A
change in nasal passage dominance fromone side to the other indicates that the
balance of sympathetic output has shifted from one side of the brainstem to the
other. In most subjects, it is likely that changes in sympathetic output occurred
frequentlythroughouttheday,leadingtochangesinnasalairflow.Howeverifthis
change was not large enough to cause a complete reversal of nasal passage
dominance,itwouldnothavebeendetected.
In some instances, it was not possible to decide whether the left or right nasal
passagehadproducedthegreatestcondensationareaastheyappearedtobeequal,
for example measurements 8, 12, 14, 16 and 23 in Subject 006 (see Figure 12).
There are two possible explanations for this finding. First, it could be due to the
methodused.ThemodifiedGMdidnotprovidequantitativevaluesfortheamount
of nasal airflow in each nasal passage. Instead, the dominant nasal passage was
decided subjectively by the investigator by observing the differences in the
condensation areas produced by each side. It is possible therefore that subtle
differences could have been missed, preventing the investigator from making a
judgment on which nasal passage was dominant and leading to a recording of
“Equal”forthattimepoint.Alternatively,itcouldbethatsympatheticoutputfrom
the brainstem was divided equally between the nasal passages, leading to equal
venouscongestionandthereforeequalnasalairflow.
Ateach15-minutetimeinterval,threemeasurementsofnasalairflowweretakenin
quick succession, as taking an average of three measurements has been
recommendedtoimprovereliability(55).Iftherewasuncertaintyastowhichnasal
passage had produced the largest condensation area, this measurement was
recorded as “Equal”. Therefore there were three possible outcomes at each
measurement;“Left”,“Right”or“Equal”.Themajorityresultateachtimepointwas
74
takentobethecorrectmeasurement.Forexample,iftwoormoremeasurements
were “Left”, the result at that timepointwas recorded as “Left”. If twoormore
measurementswere“Equal”,theresultatthattimepointwasrecordedas“Equal”.
If onemeasurementwas “Left”, onewas “Right”, and the otherwas “Equal”, the
resultwasrecordedas“Equal”.
Table8:Summaryofmeasurementsthroughoutthe6-hourtimeperiodforeachsubject.
Subjectnumber
Timepointswhenall3readingsthesame
Timepointswhen2/3readingsthesame
Timepointswhenall3readingsdifferent
Totalnumberof“Equal”readingsthroughoutmeasurementperiod
/24 % /24 % /24 % /72 %002 20 83 3 13 1 4 6 8
003 21 88 3 13 0 0 0 0
004 22 92 2 8 0 0 2 3
005 16 67 7 29 1 4 7 10
006 12 50 11 46 1 4 14 19
007 12 50 11 46 1 4 12 17
008 16 67 7 29 1 4 5 7
009 24 100 0 0 0 0 0 0
010 17 71 7 29 0 0 5 7
011 24 100 0 0 0 0 0 0
012 22 92 2 8 0 0 1 1
013 18 75 6 25 0 0 5 7
015 16 67 6 25 2 8 4 6
018 22 92 1 4 1 4 1 1
019 22 92 1 4 1 4 2 3
020 17 71 7 29 0 0 1 1
022 18 75 6 25 0 0 3 4
023 19 79 4 17 1 4 4 6
024 20 83 4 17 0 0 3 3
025 18 75 6 25 0 0 6 8
027 19 79 3 13 2 8 3 4
028 23 96 1 4 0 0 1 1
030 20 83 4 17 0 0 0 0
031 20 83 4 17 0 0 4 6
032 24 100 0 0 0 0 0 0
033 24 100 0 0 0 0 0 0
034 24 100 0 0 0 0 0 0
035 20 83 3 13 1 4 6 8
036 23 96 1 4 0 0 1 1
Onaverage,allthreemeasurementsgavethesameresultateachspecifictimepoint
82%ofthetime(20/24).Twooutofthreemeasurementsgavethesameresult16%
(4/24)of the timeonaverage,whereas all threemeasurementsweredifferent an
averageof2%(0.5/24)ofthetime. Acrossallmeasurementsfortheentire6-hour
75
period,theaveragenumberofequalreadingsrecordedwas3/72(4.5%).Therewas
howeveralotofvariabilityseenhere,withtwosubjectsrecording12and14equal
readings and seven subjects recording none. In general however, the investigator
was able to make a judgment as to whether the left or right nasal passage was
dominant. Considering all 29 subjects had three measurements taken 24 times,
giving a total of 72 measurements for each subject and 2,088 measurements
altogether, a dominant nasal passage was recorded 1,992 times i.e. in 95% of
measurements.ThissuggeststhatthemodifiedGMwasanappropriatemethodfor
measuringnasalpassagedominance.
5.4:Discussion
Consideringevidencefrompreviousstudies,itisclearthatthedatapresentedabove
isconsistentwith findings in the literature. There isconsiderablevariability in the
nasalairflowpatternsobserved.Overhalfofthesubjectsdemonstratedatleastone
definiteandsustainedreversalofnasalairflowdominance, indicatingsomedegree
ofreciprocity. Thosewhodidnotexhibitadefiniteandsustainedreversalofnasal
airflow dominance either had no reversal of nasal passage dominance or had
fluctuations in nasal passage dominancewithout any obvious pattern, i.e.without
clearreciprocityorregularity.
Unlike other methods of measuring nasal airflow such as rhinomanometry, the
modifiedGMmethod used in this study did not provide quantitative values. It is
possiblethereforethatsomereversalsofnasalpassagedominancecouldhavebeen
missedifthedifferencebetweennasalairflowoneachsidewassmall.Inaddition,it
is difficult to know exactly what was happening with regard to nasal airflow
fluctuations for subjects in Category 2, i.e. with no reversal of nasal passage
dominance during the measurement period. There are several possibilities here.
Themeasurementperiodof6hourscouldhavebeentooshorttocaptureareversal
ofnasalpassagedominance,asthereissomeevidencefromtheliteraturethatthe
76
durationofthenasalcyclecanbeaslongas6or7hours(8,10).Alternatively,there
mayhavebeennofluctuationsinnasalairflow,assuggestedbyKern(1981)(9).The
most likely explanation however, given that in most studies fluctuations in nasal
airflowoveraperiodofhourshavebeenobservedtosomedegree,isthatchanges
innasal airflowdidoccur,but that thesechangeswerenot largeenough to cause
reversalofnasalpassagedominance.
Thepatternsofnasalairflowobtainedinthisstudyhavebeencomparedwiththose
from a previous study of a different group of subjects inwhich nasal airflowwas
measuredhourlyoveran8-hourperiodusinganterior rhinomanometry (175). As
shown inFigures19-22,verysimilarpatternscanbeseen. Thisdemonstratesthat
whilst there is clear inter-individual variation, some consistent patterns in nasal
airflowcanbefoundwhencomparingdifferentsubjects. Inaddition,themodified
GMhassuccessfullydetectedthesepatterns.
77
Figure19:Comparisonofnasalairflowpatterns. Topgraph:hourlymeasurementsofnasalairflowobtained using anterior rhinomanometry fromone subject over 8 hours (175). Bottom graph: 15-minutemeasurementsofnasalairflowobtainedusingthemodifiedGMinadifferentsubjectover6hours. Therightnasalpassageisrepresentedbytheblueline,theleftnasalpassageisrepresentedbytheredline.Thepatternobservedisalmostidenticalinthatthereisonereversalofnasalpassagedominance,thisoccursfromlefttorightinthetopgraphandfromrighttoleftinthebottomgraph.Usingrhinomanometry(topgraph),fluctuationsinnasalairflowaredemonstratedateachtimepoint,however it is only on one occasion that the fluctuation is great enough to cause reversal of nasalpassagedominance.FluctuationsthatdidnotleadtoareversalofnasalpassagedominancearenotdemonstratedbythemodifiedGM(bottomgraph),asquantitativevalueswerenotobtained.
78
Figure20:Comparisonofnasalairflowpatterns. Topgraph:hourlymeasurementsofnasalairflowobtained using anterior rhinomanometry fromone subject over 8 hours (175). Bottom graph: 15-minutemeasurementsofnasalairflowobtainedusingthemodifiedGMinadifferentsubjectover6hours. Therightnasalpassageisrepresentedbytheblueline,theleftnasalpassageisrepresentedby the red line. The patterns observed are similar, in that fluctuations in nasal airflow occurthroughoutthemeasurementperiodleadingtoseveralreversalsofnasalpassagedominance.
79
Figure21:Comparisonofnasalairflowpatterns. Topgraph:hourlymeasurementsofnasalairflowobtained using anterior rhinomanometry fromone subject over 8 hours (175). Bottom graph: 15-minutemeasurementsofnasalairflowobtainedusingthemodifiedGMinadifferentsubjectover6hours. Therightnasalpassageisrepresentedbytheblueline,theleftnasalpassageisrepresentedby the red line. Onceagain, thenasalairflowpatternsareverysimilar. Inbothsubjects, the rightnasal passage has remained dominant throughout the measurement period. Using anteriorrhinomanometry, small fluctuations in nasal airflowwere detected, whereas this was not possiblewiththemodifiedGM.Howevernoneofthesefluctuationsweregreatenoughastoresultinreversalofnasalpassagedominance.
80
Figure22:Comparisonofnasalairflowpatterns. Topgraph:hourlymeasurementsofnasalairflowobtained using anterior rhinomanometry fromone subject over 8 hours (175). Bottom graph: 15-minutemeasurementsofnasalairflowobtainedusingthemodifiedGMinadifferentsubjectover6hours. Therightnasalpassageisrepresentedbytheblueline,theleftnasalpassageisrepresentedby the red line. Again, thenasal airflowpatterns are very similar. In both subjects, the left nasalpassage has remained dominant throughout the measurement period, with small fluctuationsdetectedbyanteriorrhinomanometrybutnotbythemodifiedGM.
81
Chapter6:Nasalairflowandhandpreference
6.1:Introduction
Theprincipleaimofthisstudywastolookforanycorrelationbetweennasalpassage
dominanceandhandpreference.Theexistingliteratureinthisfieldisverylimited,
withonlyonepublishedstudyspecificallydesignedtoanswerthisresearchquestion
inhealthyindividuals.
Theverynotionofthisrelationshipmayseemunusual,asonecouldquestionhow
andwhynasal airflowwould be related to handedness. However humanshave a
tendency for lateral preferences (113), and the nose is considered to be two
separatepassagesratherthanasingleentity.Thereforeifpeoplecanbeleft-handed
andleft-eyed,couldtheyalsobeleft-nosed?
Searlemanetal. (2005) reported thathealthy individualsdidexhibitnasalpassage
dominance, justastheyexhibithandandeyedominance,andthatthisdominance
didcorrelatewithhanddominance(113). However,thereliabilityofthisfinding is
questionable(seesection1.9formoredetail).
Thefollowingsectionspresentnewevidenceanddiscussthesefindingsinrelationto
the previously proposed link between hand preference and nasal passage
dominance.
6.2:Methods
As part of the screening process, the hand preference of each subject was
ascertained by observation of handwriting and completion of the Edinburgh
HandednessInventory(ShortForm).
82
The dominant nasal passage was recorded using the modified GM at 15-minute
intervalsovera6-hourperiodononeday(seeChapter3fordetailedmethodology).
Oncealldatahadbeencollected, itwasanalysed inorderto lookforacorrelation
between hand preference and nasal passage dominance. Several methods of
analysis were used. Similarly to Searleman et al. (2005) (113), the percentage of
timeeachnasalpassagewasdominantwascalculatedforeachsubjectandthiswas
compared in left- and right-handed subjects. Next, left-handed and right-handed
subjects were compared according to their nasal airflow patterns, which were
categorisedasdescribedinChapter5.Theresultswerethencompareddirectlywith
those presented by Searleman et al. (2005) (113). A different method of
determiningoverallnasalpassagedominancewasusedand followingclassification
ofsubjectsaseitherleft-orright-nasalpassagedominant,achi-squaretestwasused
tolookforacorrelationbetweennasalpassagedominanceandhandpreference.
6.3:Results
Nasalairflowpatternswereanalysedin14right-handedsubjectsand15left-handed
subjects. Tables 9 and 10 show the percentage of time each nasal passage was
dominant in left-handed and right-handed subjects respectively. As shown, there
was considerable variability within each group of subjects. In left-handers, the
percentage of time that the left nasal passage was dominant ranged from 0% to
100%.Likewiseinright-handers,thepercentageoftimethattherightnasalpassage
wasdominantrangedfrom4.2%to95.8%.
83
Table9:Nasalpassagedominanceinleft-handedsubjects.Thepercentageoftimeeachnasalpassagewasdominantforeachleft-handedsubject isshown. Notethatthepercentagesdonotalwaysaddup to100%, this isbecause in somesubjects (e.g. Subject005) therewere timepointswhennasalairflowwasrecordedasbeingequallydividedbetweenthenasalpassagesandthereforeadominantnasalpassagecouldnotbedeterminedatthattimepoint.Subjectnumber
%oftimerightnasalpassagedominant
%oftimeleftnasalpassagedominant
003 25.0 75.0
004 58.3 41.7005 75.0 12.5
006 58.3 20.8007 75.0 8.3
008 12.5 79.2009 37.5 62.5
010 0.0 100.0
011 100.0 0.0012 50.0 50.0
015 70.8 16.7032 50.0 50.0
034 45.8 54.2
035 37.5 54.2036 0.0 100.0
Table 10:Nasal passage dominance in right-handed subjects. The percentage of time each nasalpassagewas dominant for each right-handed subject is shown. As above, the percentages do notalwaysaddupto100%forthesamereason.Subjectnumber
%oftimerightnasalpassagedominant
%oftimeleftnasalpassagedominant
002 41.7 45.8013 66.7 29.2
018 62.5 33.3
019 45.8 50020 41.7 58.3
022 50 50023 37.5 58.3
024 95.8 4.2025 29.2 66.7
027 29.2 62.5
028 58.3 41.7030 33.3 66.7
031 33.3 62.5033 4.2 95.8
84
Figure 23:Nasal passage dominance in left- and right-handers. Graph demonstrates the averagepercentageoftimeeachnasalpassagewasdominantinleft-handedandright-handedsubjects.Thereason that the percentages displayed do not total 100% is that in some subjects, nasal passagedominancewasdividedequally(50%and50%)betweenbothsides.
In left-handers, the left nasal passage was dominant for more 50% of the
measurementperiodin7outof15subjects(47%).Inright-handers,therightnasal
passagewasdominantformorethan50%ofthemeasurementperiodin7outof14
subjects(50%). In left-handers,theleftnasalpassagewasdominantanaverageof
11.6 times out of 24, or 48.3% of the time, whereas the right nasal passagewas
dominant for 46.4% of the time (see Figure 23). In right-handers, the right nasal
passagewas dominant an average of 10.8 times out of 24, or 44.9% of the time,
whereastheleftnasalpassagewasdominantfor51.8%ofthetime(seeFigure23).
Justfromthissimpleanalysis,noclearcorrelationbetweennasalpassagedominance
andhandpreferencecanbedemonstrated.
Next,left-andright-handedsubjectswerecomparedaccordingtothecategorisation
of their nasal airflow patterns (see Table 7). Of the 15 left-handers, 6 were in
Category1,6wereinCategory2and3wereinCategory3.Ofthe14right-handers,
10weregroupedtoCategory1,2wereinCategory2and2wereinCategory3(see
Figure 24). There appears to be a trend towards right-handers having definite
changes innasalpassagedominancewithmorevariabilityofnasalairflowpatterns
48.3 46.4 51.8
44.9
0
10
20
30
40
50
60
70
80
90
100
Le2 nasal passage Right nasal passage
% o
f ?m
e na
sal p
assa
ge d
omin
ant
Le2 handers
Right handers
85
seen in left-handers. However,usingthechi-squaretest,nostatisticallysignificant
correlationbetweenhandpreferenceand categoriesofnasal airflowpatternswas
found(p=0.21).
Figure24:Graphtodemonstratethecategorisationofleft-andright-handersaccordingtotheirnasalairflowpatterns. Category 1: Subjectswith definite changes in nasal airflowdominance thatweresustained,i.e.achangeinthedominanceofnasalairflowfromthelefttotherightnasalpassageorvice versa. Category 2: Subjects with little or no change in nasal airflow dominance, defined asconsecutive readings of dominance in one nasal passage throughout the measurement period.Category3:SubjectswithvariationsinthepatternsofnasalairflowdominancethatdidnotfitinwithCategory1orCategory2.
ComparisonwithSearlemanetal.(2005)
Theaboveanalysisusingthepercentageoftimeeachnasalpassagewasdominant
(calculatedfromthenumberofreadings)issimilartothatreportedbySearlemanet
al. (2005), the only published study to describe the possible relationship between
handpreferenceandnasalairflowinhealthysubjects(113).Theystate(p.117):
“During 24 trials of the 6-hour testing period, the left-handed males were
significantlymorelikelythanchance(50%)tohavetheirleftnostril,ratherthantheir
right, be the dominant one (59.3%, Z=2.73, p<.01). By an almost identical
percentage(59.5%),right-handersshowthereversepattern:therightnostril isthe
dominantoneinairflow(Z=3.09,p<.01).”(113)
0
2
4
6
8
10
12
Category 1 Category 2 Category 3
Num
ber o
f sub
ject
s
Nasal airflow paLerns
Le2-handers
Right-handers
86
Figures 25 and 26demonstrate the differences between the current data and the
resultspresentedbySearlemanetal. (2005) (113). There isanobviousdifference
between the current study results and thosepublishedby Searlemanet al. (2005)
(113). In Searleman et al.’s (2005) study, nasal airflowwas divided roughly 60:40
with overall nasal passage dominance positively correlating to hand preference
(113). This findingwasreportedtobesignificant,withapvalueof lessthan0.01,
howeverthestatisticalmethodsusedwerenotspecified. Inthecurrentstudy,the
divisionofnasalairflowwascloserto50:50,withnoclearcorrelationbetweennasal
passagedominanceandhandpreference.
Thereisasignificantissuewiththeabovedescriptionofthedataanalysis.Fromthe
informationprovidedinthearticle,whichisquitelimited,itappearsthatSearleman
et al. (2005) have used the average percentage of time one nasal passage was
dominanttocategorisesubjectsaseitherright-or left-nasalpassagedominantand
thenattemptedtocorrelatethiswithhandpreference(113).Theyhaveused50%as
thecutoffvalue,sothatleftnasalpassagedominanceisdefinedasgreaterairflow
throughtheleftnasalpassageformorethan50%ofthe24readingstakenovera6-
hourperiod,andviceversaforrightnasalpassagedominance(113).However,given
theknownvariabilityofnasalairflowpatternsandtherelativelyshortmeasurement
period of 6 hours on one day, it seems that having left or right nasal passage
dominanceforanaverageof50-60%ofthereadingscouldeasilyhappenbychance.
If themeasurementperiodweretobeextendedbyanhour,potentiallythis figure
and even the overall nasal passage dominance in one subject could change.
Therefore, a more robust method for determining nasal passage dominance was
usedforthisstudy,andthisisexplainedbelow.
87
Thisfigurehasbeenremovedbytheauthorforcopyrightreasons.
Figure25:GraphfromSearlemanetal.2005(113).Thegraphcomparesthepercentageoftimeeachnasalpassage(ornostril)wasdominantbasedonthemaximumairflowrate.
Figure 26: Graph using the data from this study formatted to reflect the format of the graphpublishedbySearlemanetal.(2005)(113).Thepercentageoftimeeachnasalpassagewasdominantinleft-handersandright-handersisshown.
48.3 46.4 51.8
44.9
0
10
20
30
40
50
60
70
Le2 nostril Right nostril
% o
f ?m
e no
stril
dom
inan
t
Le2 handers Right handers
88
Determiningnasalpassagedominance
Thesamplingdistributionofthedatacanbedescribedasbinomial,asithasafixed
numberofobservations(n=24),eachobservationis independent,eachobservation
represents one of two outcomes (nasal passage dominance or no difference
between the nasal passages) and the probability of success is the same for each
observation. The binomial distribution could therefore be used to determine the
numberofsuccesses i.e.dominantnasalpassagereadingsoccurringwithaspecific
probability (p). This isshown inTable11. Insomesubjects,someof thereadings
were“Equal”, inotherwords,adominantnasalpassagecouldnotbedetermined.
Asthesereadingsareessentiallyunknowns,theyhadtobeexcludedinordertouse
the binomial distribution, and this was taken into account when calculating the
probabilityofsuccesses(seeTable11).
Inthiscase,thenullhypothesisisthatthereisnooverallnasalpassagedominance,
andthealternativehypothesisisthatasubjecthasadominantnasalpassage,which
iseitherthe leftortheright. Forapvalueof0.1,whenallofthe24readingsare
known values, 7 non-dominant readings were permitted to allow a subject to be
categorised as being nasal passage dominant. For example, if a subject had 18
readingsthatwereleftand6readingsthatwereright,theywerecategorisedasleft
nasal passage dominant. However if they had 16 readings that were right and 8
readingsthatwereleft,theywerecategorisedasunclear,meaningthattherewasno
clearoverallnasalpassagedominanceandthatthefindingsweremorelikelydueto
chance.Figures27and28arerepresentative(notactual)graphsofthedata,usedto
illustrate the differences between this method of determining nasal passage
dominanceand,fromtheinformationprovidedintheirarticle,whatwaspresumably
usedbySearlemanetal.(2005)(113).
89
Table11:Usingbinomialdistributiontodeterminehowtocategoriseeachsubjectaseither left-orright-nasalpassagedominant.
Numberofreadingswhereanasalpassageis
dominant
Numberofnon-dominantreadingsallowedinordertocategoriseasubjectasleft-orright-nasalpassagedominant
p=0.1 p=0.2 p=0.4
24 7 8 9
23 7 7 922 6 7 8
21 6 7 8
20 5 6 719 5 6 7
Figure27:Anormaldistributioncurveisrepresentedbytheverticallines.Thenullhypothesisisthatsubjects do not exhibit any nasal passage dominance, i.e. nasal airflow is divided roughly equallybetween the nasal passages. The alternative hypothesis is that subjects have a dominant nasalpassage,which is either left or right. At the extremes of both ends of the curve, subjects can becategorised as left (shown in red) or right (shown in blue) nasal passage dominant, i.e. the nullhypothesisisrejected.Thecut-offpointinthenumberofreadingsrequiredtocategoriseasubjectaseitherleftorrightnasalpassagedominantisdependentonthepvalueusedforthispurposeandthisisshownforpvaluesof0.05,0.1and0.2ateachextreme,whichwouldequateto0.1,0.2and0.4whenconsideringallofthereadings. The linesshowningreyrepresentthosewherenasalpassagedominancecannotbeassigned,i.e.thenullhypothesisisaccepted.
12#p#0.05# p#0.05#
p#0.1# p#0.1#
p#0.2# p#0.2#
Number#of#readings#
Le7#nasal#passage#dominant#
Right#nasal#passage#dominant#
90
Thepvaluesusedmayseemrelativelyhigh,howeverevenatapvalueof0.4, the
nullhypothesis isnotoutside theextremequartiles,asat this level20%wouldbe
left-nasalpassagedominant,20%wouldbe right-nasalpassagedominantand60%
wouldhavenooveralldominance.
Figure28: This figuredemonstrates themethodpossiblyusedby Searlemanet al. (2005) (113). Anormaldistributioncurveisrepresentedbytheverticallines.Acut-offof50%wasused,i.e.ifmorethan50%ofreadings(n=12)wereleftnasalpassagedominant,thesubjectwascategorisedasbeingleftnasalpassagedominant(showninred),andviceversafortherightnasalpassage(showninblue).
12#Number#of#readings#
Le3#nasal#passage#dominant#
Right#nasal#passage#dominant#
91
Table 12: Nasal passage dominance in each subject calculated using binomial distribution. Thenumberofknownvaluesindicatesthenumberofreadingsatwhichadominantnasalpassagecouldbeallocated,orthosewhereairflowwasnotclassifiedasbeing“Equal”betweenthenasalpassages.Thefourthcolumnunderoverallnasalpassagedominanceindicatesthenasalpassagedominanceifthecutoffused is50% i.e. ifmorethanhalfof thereadingswereeither rightor leftnasalpassagedominant.Subjectnumber
No.ofknownvalues
No.oftimesrightnasalpassagedominant
No.oftimesleftnasal
passagedominant
Overallnasalpassagedominance Handpreference
p=0.1 p=0.2 p=0.4 50%cutoff
002 21 10 11 Unclear Unclear Unclear Left Right
003 24 6 18 Left Left Left Left Left
004 24 14 10 Unclear Unclear Unclear Right Left
005 21 18 3 Right Right Right Right Left
006 19 14 5 Right Right Right Right Left
007 20 18 2 Right Right Right Right Left
008 22 3 19 Left Left Left Left Left
009 24 9 15 Unclear Unclear Left Left Left
010 24 0 24 Left Left Left Left Left
011 24 24 0 Right Right Right Right Left
012 24 12 12 Unclear Unclear Unclear Unclear Left
013 23 16 7 Right Right Right Right Right
015 21 17 4 Right Right Right Right Left
018 23 15 8 Unclear Unclear Right Right Right
019 23 11 12 Unclear Unclear Unclear Left Right
020 24 10 14 Unclear Unclear Unclear Left Right
022 24 12 12 Unclear Unclear Unclear Unclear Right
023 23 9 14 Unclear Unclear Left Left Right
024 24 23 1 Right Right Right Right Right
025 23 7 16 Left Left Left Left Right
027 22 7 15 Unclear Left Left Left Right
028 24 14 10 Unclear Unclear Unclear Right Right
030 24 8 16 Unclear Left Left Left Right
031 23 8 15 Unclear Unclear Left Left Right
032 24 12 12 Unclear Unclear Unclear Unclear Left
033 24 1 23 Left Left Left Left Right
034 24 11 13 Unclear Unclear Unclear Left Left
035 22 9 13 Unclear Unclear Unclear Left Left
036 24 0 24 Left Left Left Left Left
92
Table 13: Summary of the number of subjects categorised as unclear, right or left nasal passagedominantatdifferentprobabilitylevels.Nasalpassagedominance
Numberofsubjects
p=0.1 p=0.2 p=0.4 50%cutoff
Unclear 16 14 10 3Right 7 7 8 10
Left 6 8 11 16
Total 29 29 29 29
Table14:Nasalpassagedominanceasdeterminedusingbinomialdistributionintheleft-handedandright-handedgroups.
Nasalpassagedominanceatdifferentprobabilitylevels
Numberofsubjects
Right-handers Left-handers
p=0.1 Unclear 10 6Right 2 5
Left 2 4
p=0.2 Unclear 8 6Right 2 5
Left 4 4
p=0.4 Unclear 5 5
Right 3 5Left 6 5
50%cutoff Unclear 1 2Right 4 6
Left 9 7
JustfromlookingatthenumbersinTable14,theredoesnotseemtobeanobvious
correlationbetweenhandpreferenceandnasalairflowdominance.Evenusing50%
ofreadingsasthecut-offtodefineanasalpassageasdominant,moreright-handers
had left nasal passage dominance andmore left-handers had right nasal passage
dominance,althoughthenumberswereverysimilar.
93
Thedisadvantageofusingthebinomialdistributiontodeterminewhetherasubject
canbeclassifiedashavingadominantnasalpassageisthatof29subjectstested,the
finalnumberusedforanalysishasbeenreduced,assomesubjectsdidnotexhibita
dominantnasalpassage.Inanattempttocounteractthis,analysisofthedatawas
doneusingincreasingprobabilitylevelsinordertoincreasethenumberofincluded
subjects. However,evenatthehighestpvalueof0.4,10subjects(5right-handers
and5left-handers)couldnotbeclassifiedashavingadominantnasalpassageasthe
division of airflow between the right and left nasal passageswas not significantly
different.Searlemanetal.(2005)didnotstatethatnasalpassagedominancecould
notbeascertainedinanyoftheirsubjects(113).Converselyinthisstudy,3subjects
had 12 readings of left nasal passage dominance and 12 readings of right nasal
passagedominanceoutofatotalof24readings,meaningthatthedivisionofairflow
betweenthenasalpassageswasexactlyequalthroughoutthemeasurementperiod.
Determiningwhetheracorrelationbetweenhandpreferenceandnasalpassage
dominanceexists.
Achi-squaretestwasusedtolookforastatisticallysignificantcorrelationbetween
handpreferenceandnasalpassagedominance.Thiswasdoneforeachofthe
differentprobabilitylevelsusedtodeterminenasalpassagedominance(p=0.1,
p=0.2,p=0.4)andalsousingthe50%cutoff,andisshowninTables15–18.
Table15:Chi-squaretableusingpvalueof0.1tocategorisenasalpassagedominance.
Right-handers Left-handers Total
Rightnasalpassagedominant 2 5 7Leftnasalpassagedominant 2 4 6
Total 4 9 13
p=0.85
94
Table16:Chi-squaretableusingpvalueof0.2tocategorisenasalpassagedominance.
Right-handers Left-handers Total
Rightnasalpassagedominant 2 5 7Leftnasalpassagedominant 4 4 8
Total 6 9 15p=0.40
Table17:Chi-squaretableusingpvalueof0.4tocategorisenasalpassagedominance.
Right-handers Left-handers Total
Rightnasalpassagedominant 3 5 8Leftnasalpassagedominant 6 5 11
Total 9 10 19p=0.46
Table18:Chi-squaretableusing50%asthecutofftocategorisenasalpassagedominance.
Right-handers Left-handers Total
Rightnasalpassagedominant 4 6 10Leftnasalpassagedominant 9 7 16
Total 13 13 26p=0.42
Astatisticallysignificantcorrelationbetweenhandpreferenceandnasalairflowwas
notidentifiedinthisdataset.Thisisnotsurprisingasnotrendtowardsacorrelation
was seen earlier in the data analysis (see Figure 23). Unfortunately the subject
numbers in the data setwere reduced because in some subjects it was not clear
whether they had any overall nasal passage dominance, rather, it appeared that
nasalairflowwasdividedroughlyequallybetweenbothnasalpassages.Evenwhen
nasal passage dominancewas defined by having either right or left nasal passage
dominance for over 50% of themeasurement period, the p value remained non-
significant at 0.42 (see Table 18), however due to the variability in nasal airflow
patterns this method of defining nasal passage dominance should be considered
unreliable.
95
6.4:Discussion
ThefindingsofthisstudydirectlycontradictthosepublishedbySearlemanetal. in
2005(113). Someofthepotential issueswiththemethodsandfindingsdescribed
bySearlemanetal.(2005)havealreadybeenhighlighted,forexamplethemethods
used to measure nasal airflow, determine hand preference and analyse the data
(113).
Inordertolookfordisparitiesinthedataanalysis,thetheoreticalresultsneededto
produceasignificanceleveloflessthan0.01,asobtainedbySearlemanetal.(2005)
(113),wereascertained.Theirstudyhadatotalof20subjects,with9left-handers
and11right-handers.Thisinformationwasusedtopopulateachi-squaretablewith
thenumbersforleft-handed,left-nasalpassagedominantsubjectsandright-handed,
right-nasalpassagedominantsubjects.Thesenumberswerethenalteredtolookat
the different levels of significance that could be achieved. The total number of
subjectsinthenasalpassagedominancegroupswaschangedasthiswasunknown,
whereas the known values for the number of left-handers and right-handers was
kept the same. Unfortunately this is speculation, as although contacted several
times by email to request further detail about the data collected and its analysis,
therewasnoreplyfromtheleadauthor.Table19demonstratesthemostextreme
results that could have been found by Searleman et al. (2005) (113), that is all
(n=11/11) right-handers being right nasal passage dominant and all (n=9/9) left-
handers being left nasal passage dominant. In this case, thep valuewould have
been0.000007,inotherwordsahighlysignificantfinding.
96
Table19:Chi-squaretableusingthemostextremepossiblevaluesinSearlemanetal.’s(2005)(113)datai.e.alltheright-handerswererightnasalpassagedominantandalltheleft-handerswereleftnasalpassagedominant.
Right-handers Left-handers Total
Rightnasalpassagedominant 11 0 11
Leftnasalpassagedominant 0 9 9Total 11 9 20
pvalue=0.000007
Table20:Chi-squaretableusingtheleastextremevaluesrequiredtoproduceapvalueoflessthan0.01.
Right-handers Left-handers Total
Rightnasalpassagedominant 8 1 9Leftnasalpassagedominant 3 8 11
Total 11 9 20pvalue=0.006
Table21:Chi-squaretableusinganotherpossiblecombinationoftheleastextremevaluesrequiredtoproduceapvalueoflessthan0.01.
Right-handers Left-handers TotalRightnasalpassagedominant 9 2 11
Leftnasalpassagedominant 2 7 9Total 11 9 20
pvalue=0.008
Tables20and21showtwodifferentcombinationsofvaluesthatwouldbetheleast
extremevaluesrequiredtoproduceapvalueoflessthan0.01.Thesevaluesshould
stillbeconsideredasextremeandthecorrelationisimmediatelyobvioussince73–
82%ofright-handerswouldhavebeenright-nasalpassagedominantand78%ofleft-
handerswouldhavebeenleft-nasalpassagedominant.Tables22and23showtwo
differentcombinationsofvaluesthatwouldbethemostextremevaluesresultingin
a p value of greater than 0.01. Again, although the p value is higher than that
reportedbySearlemanetal. (2005) (113), the results required toproduce thesep
values are still extreme, with high percentages of subjects having positively
correlated hand preference and nasal passage dominance. If any of the above
97
resultsorsimilaroneswereactuallyobtained,surelytheywouldhavebeenclearly
reportedinthisfashionbySearlemanetal.(2005)(113),insteadofthepercentage
oftimevaluesthatwerepublished.
Table22:Chi-squaretabledemonstratestheresultsrequiredtoproduceapvalueofover0.01,thesignificancelevelfoundbySearlemanetal.(2005)(113).
Right-handers Left-handers Total
Rightnasalpassagedominant 8 2 10Leftnasalpassagedominant 3 7 10
Total 11 9 20
pvalue=0.02
Table23:Chi-squaretableusinganotherpossiblecombinationtheresultsrequiredtoproduceapvalueofover0.01.
Right-handers Left-handers TotalRightnasalpassagedominant 9 3 12
Leftnasalpassagedominant 2 6 8
Total 11 9 20pvalue=0.03
Considering the results that were published by Searleman et al. (2005) (113),
specificallythatleft-handershadleftnasalpassagedominanceforalmost60%ofthe
timeandvice versa for right-handers, a chi-square testwas thenperformedusing
60% to determine the number of right-handed, right-nasal passage dominant
subjectsand thenumberof left-handed, left-nasalpassagedominant subjects (see
Table24). Using thesenumbers, thep valuewas0.4. This is interestingas thep
value obtained in this study was 0.4 to 0.86 depending on the categorisation of
subjects’nasalpassagedominance.
98
Table24:Chi-squaretableusing60%tocalculatethepresumptivevalueforright-handed,right-nasalpassagedominantsubjectsandleft-handed,left-nasalpassagedominantsubjects.
Right-handers Left-handers Total
Rightnasalpassagedominant 7 4 11
Leftnasalpassagedominant 4 5 9Total 11 9 20
pvalue=0.4
99
Chapter7:FinalDiscussionandConclusions
Theaimsofthisstudywere:
1. To summarise the literature concerning nasal airflow and brain activity,
focusing on a possible correlation between cerebral asymmetries and
asymmetriesinnasalairflowpatterns.
2. To look specifically for a correlation between hand preference and nasal
airflowinhumansubjectsbymeasuringnasalairflowpatternsoveraperiod
ofhours,andcomparethesefindingstotheavailableliterature.
7.1:Nasalairflowasymmetryandcerebralasymmetry
Correlations between nasal airflow and cerebral asymmetry have been suggested,
however unfortunately the literature base concerning this topic is hugely varied
making itdifficult toconstruct firmconclusions. Theasymmetry innasalairflow is
controlled by asymmetrical sympathetic output from collections of sympathetic
neurons in thebrainstem (38). The roleofhigher cortical centres in thispathway
however is not clear, and the potential influences of handedness (113), ultradian
rhythms in cerebral activity (128) and disease (70, 108) have all been suggested.
Conversely, there isalsosomeevidencetosuggest thatasymmetricalnasalairflow
can affect the brain. In patients with certain types of epilepsy, nasal
hyperventilationhasbeenshowntoactivateepilepticfociinthebrain(140).Further
tothis,someresearchershavepostulatedthatunilateralforcednostrilbreathingcan
affectbrainactivityandcognitivefunctions(142,156),althoughtheevidenceforthis
isweakandhasbeencontestedbyotherstudies(136,158).
100
7.2:Handpreferenceandnasalpassagedominance
This study did not identify a relationship between hand preference and nasal
passagedominance,andinfactinarelativelyhighproportionofsubjectsadominant
nasalpassage couldnotbeascertained (although theexact figuredependson the
methodofclassifyingnasalpassagedominance–seesection6.3).
The following are the possible reasons for not identifying an association between
handpreferenceandnasalairflow:
1. Lack of statistical power. It remains possible that there is a relationship
betweennasalairflowandhandpreferencehowevertheeffectwastoosmall
tobedetectedinthissample.Conductingthesameanalysisinamuchlarger
sample couldpossiblydetectaneffect. It shouldbenotedhowever thata
smallersamplesizewasusedinthestudybySearlemanetal.(2005),inwhich
statisticalsignificancewasreported(113).
2. The measurement period was too short. Alternation of nasal passage
dominance,sometimesreferredtoas thenasalcycle,hasbeenreportedto
occurupto8-hourly(8).Therefore,withameasurementperiodof6hours,it
ispossiblethatinsomesubjectsthealternationofnasalpassagedominance
wasmissed.Inthreesubjects,onenasalpassageremaineddominantforthe
entire measurement period, and it is possible that they will have had
alternation innasalpassagedominancethateitheroccurred justbeforethe
first measurement or after the last one. Also, in subjects who did
demonstratealternationsinnasalpassagedominance,somecouldhavebeen
missed by the 6-hourmeasurement period,which could have affected the
results. For example, if the next few readings after the 6-hour period had
demonstratedanotherswitchinnasalpassagedominance,thepercentageof
time each nasal passage was dominant would have changed, which could
have altered the classification of the subject as left- or right-nasal passage
dominant.
101
3. Thereisnorelationshipbetweenhandpreferenceandnasalairflowandthe
resultsreportedbySearlemanetal.(2005)(113)occurredbychance.
Itistheopinionofthisauthorthatthe3rdoptionisthemostlikely.Therearethree
reasons for reaching this conclusion. First, the physiological reasoning underlying
thisrelationshipisimplausible.Handednesshasbeenshowntocorrelatewithother
behavioural lateralpreferences, forexampleeyepreference,handclaspingand leg
crossing,howeverthecorrelationsaresmallandthesemeasurescannotbereliably
usedtodeterminehandedness(118). Nasalairflowiscontrolledbytheautonomic
nervous system and is dissimilar to behavioural lateral preferences such as hand
clasping and leg crossing. Since there isn’t a consistent relationship between
handedness and these behaviours, it doesn’t seem logical to have a consistent
relationshipbetweenhandednessandnasalairflow.
Althoughnotfullyunderstood, it is likelythatthepurposeofhavingfluctuationsin
nasalpassagedominanceisrelatedtotheair-conditioning(26)andimmunedefence
functions of the nose (18). Therefore, equal or roughly equal division of labour
betweenthetwonasalpassageswouldberequired.Thedivisionoflabourmaynot
occurhourlyorevendaily,whichiswhyitcouldbemissedinsomestudies.Infact,
studies have shown that nasal airflow patterns vary whenmeasured in the same
individualondifferentdays(11). Bearingthis inmind, itwouldbepossibleforthe
findingsbySearlemanetal. (2005) (113) tohaveoccurredbychance,andhadthe
experimentbeen repeatedon a different day, theopposite relationshipmayhave
beendiscovered.
In addition, there is no obvious reason why the air-conditioning and immune
functionsof thenosewouldbe related tocerebralorganisation. Handpreference
mayberelatedtospeechdevelopmentwhichusuallyoccursinthelefthemisphere
(121), and the lateralisation of speech may confer advantages for speech
development (125). Whena complexactionoriginates in thebrain, theremaybe
102
advantagestohavingitariseinonlyonehemisphere(119).Theconductanceofair
through the nasal passages is not a complex action such as speech or hand
movements and therefore having a dominant nasal passage would not be
advantageousinthisrespect.
Secondly,arelationshipbetweennasalairflowandhandpreferenceisnotsupported
by the other literature concerning nasal airflow. In the wealth of observational
studiesperformedoverthelastcenturylookingatnasalairflowpatternsinhealthy
individuals,nonehave reportedan incidental findingofoverall rightnasalpassage
dominance. IfSearlemanetal.’s (2005) (113) findingswerecorrect, thiswouldbe
extremely surprising given the overwhelming majority of right-handers in the
generalpopulation.Inastudycomparingnasalairflowpatternsofschizophrenicvs.
healthyindividuals,53.1%ofthehealthycohorthadnooveralllateralisationofnasal
airflow,meaning that the left and rightnasalpassagesweredominant for roughly
equal amountsof time (108). The rateof left nasal passagedominancewas25%,
andtherateof rightnasalpassagedominancewas21.9%(108). Thiswasa larger
studywith64healthycontrolsubjectswhowereallright-handed,conductedovera
longerperiodof12hours(108). Thisfinding isconducivewiththetheoriesonthe
functionofthealternationsinnasalpassagedominance,asexplainedabove.
Thirdly,reproductionofSearlemanetal.’s2005studyusingsimilarmethodsfailedto
identify a relationshipbetweenhandpreferenceandnasal airflow (113). In recent
years, there have been concerns amongst the scientific community that many
publishedstudyfindingsarenotreproducible.Inhis2005paper,Ioannidisstates:
“Itcanbeproventhatmostclaimedresearchfindingsarefalse”(176).
Colquhoun(2014)describedthemisuseandmisinterpretationofpvaluesasamajor
contributortothis,asthereisalackofunderstandingwhenitcomestosignificance
testing (177). It is generally accepted that a p value of less than 0.05 confers
statisticalsignificance,howeverthisiscommonlymisinterpretedastheerrorrate.In
fact, a p value of less than 0.05 suggests that the test sample provides enough
evidencetorejectthenullhypothesis,howeveritdoesnotprovethatthealternative
103
hypothesisistrue.Withapvalueof0.05,thereisa5%chancethatthealternative
hypothesis has occurred by chance alone. Colquhoun (2014) argues that a 5%
chance is actuallyquitehigh in itself, butdue to themisinterpretationand lackof
powerinmanypublishedstudies,thisfigureisactuallyalothigher(177).Theerror
rate,or falsediscovery rate, isequivalent to the falsepositive rate, i.e. incorrectly
accepting the alternativehypothesis (177). Sellke et al. (2001) estimated that the
errorrateforapvalueof0.05wasover29%,andforapvalueof0.01wastypically
closeto15%(178).
Searlemanetal.(2005)statedthattheyobtainedapvalueoflessthan0.01fortheir
results, although the statistical methods used to calculate this have not been
described (113). This equates to a less than 1% chance that the alternative
hypothesis (in this case a positive correlation between nasal airflow and hand
preference)hasoccurredbychancealone,howeverhowmuch lessthan1%this is
cannotbeknown.Theerrorrateorfalsediscoveryrate,ontheotherhand,islikely
tobemuchhigher (seeSellkeet al. 2001 (178)andColquhoun2014 (177)). This
maybecompoundedbythefactthatthesamplesizewassmallmeaningthestudy
was probably underpowered, and there was a risk of bias, for example as
participantswerenotrandomisedandtherewasnoblinding.Ithasbeensuggested
thatevenawell-poweredepidemiologicalstudymayonlyhaveaoneinfivechance
of being true (176). Colquhoun (2014) suggests that ap value of less than 0.001
shouldberequiredtodemonstrateapositivefinding.
Anothermajorissueisthegeneralreluctancetoreportnegativefindings(177).Itis
thereforeimpossibletoknowwhetherotherresearchgroupshaveconductedsimilar
studiesonhandpreferenceandnasalairflow,butnotreportedtheirfindingsifthey
were not positive or significant. As discussed previously, Searleman et al.’s 2005
study is theonlypublishedreportofacorrelationbetweennasalairflowandhand
preference (113), and so presumably the scientific community has accepted this
finding. It has in fact been cited on 12 occasions. Accepting and re-iterating the
104
resultsobtainedbyasingleresearchteam,eveniftheywerestatisticallysignificant,
canbemisleading(176). This isparticularlytrueforsmallstudieswithsmalleffect
sizeswheretheremaybedifferencesindefinitions,studydesign,methodologyand
outcomes(176).Intherelativelysmallfieldofnasalairflowresearch,thereisahigh
degreeofvariability in themethodsandoutcomemeasuresused (seesections1.2
and 1.7 on the nasal cycle and methods of measuring nasal airflow), and many
studies have small numbers of participants. One could argue that accepting the
findingsofSearlemanetal.(2005)(113)astrueisnotadisaster,asit isunlikelyto
haveaffectedclinicalpracticeorpatientsafety.However,understandingphysiology
isthebasisforunderstandingpathology,andcurrentlythephysiologicalfactorsthat
influencenasalairflowandthenasalcyclearenotfullyunderstood.
AsdiscussedintheChapter2,conflictingtheorieshavebeensuggestedforcortical
influenceonnasalairflow. Nasalblockage isacommonpresentation toEar,Nose
andThroatsurgeons,andat timesthere isnopathologydetected. In thesecases,
theremay be a physiological explanation for the patient’s symptoms. The results
presentedhere,alongwithevidence fromother studies,donot suggest thathand
preferenceisafactor.
105
7.3:Limitationsofthisstudy
The sample size of 29 subjectsmay have been too small to detect a relationship
betweennasalairflowandhandpreference.UnfortunatelythestudybySearleman
et al. (2005) did not provide enough information for power calculations to be
performed (113), and therefore this was a pilot study. Measuring nasal airflow
patterns and how they alter over time is, by definition, time consuming, and
therefore many studies that have looked at nasal airflow have involved small
numbersofparticipants.Itisalsopossiblethatthemeasurementperiodof6hours
wastooshort,howeverthiswaschosentoreflectthemethodsusedbySearlemanet
al.(2005)(113).
ThemethodchosentomeasurenasalairflowwasthemodifiedGM,whichdoesnot
providequantitativevalues.Instead,theinvestigatormadeajudgementastowhich
nasalpassagewasdominantateachtimepointbylookingatthecondensationareas
producedbyeachnasalpassage.Therefore,itispossiblethathumanerrorandbias
mayhaveoccurred.Theinvestigatorwasblindedtohandpreferencewherepossible
inanattempttominimisetheriskofbias.
106
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Appendix1:InclusionandExclusionCriteriaInclusioncriteria:
1. Aged18orover
2. Havegivenwritteninformedconsent
Exclusioncriteria:
1. Anyhistoryofchronicnasalconditions
2. Activenasaldiseasee.g.currentupperrespiratorytractinfection
3. Anyhistoryoftrauma(includingsurgery)tonose,sinusesorcentralnervoussystem
4. Anysignificantseptalabnormality
5. Anydiseaseormedical or surgical history that the investigator deemsmayaffect nasal physiology and influence the results of the study e.g. chronicrespiratorydiseaseor intakeofmedicinesknowntoaffectthenosesuchastopicalcorticosteroidsordecongestants
6. Knownallergytoaluminium
7. Memberofstudystafforpartnerorrelativeofstudystaff
8. Intakeofmore than 4 units of alcoholwithin 12hours ofmeasurement ofnasalairflow
9. Performance of vigorous exercise within 3 hours ofmeasurement of nasalairflow
10. Currentsmoker,definedbyadailyuseofanytobaccoproduct
11. Pregnantorlactatingwomen
12. Mixedorunclearhandedness
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Appendix2:ParticipantInformationSheetThissectionhasbeenremovedbytheauthorforcopyrightreasons.
118
Appendix3:ConsentFormThissectionhasbeenremovedbytheauthorforcopyrightreasons.
119
Appendix 4: Edinburgh Handedness Inventory – Short Form. Adapted
fromVeale(2014)(172).
Please indicate your preferences in the use of hands in the following activities orobjects: Always
right
Usuallyright
Bothequally
Usuallyleft
Alwaysleft
Writing
Throwing
Toothbrush
Spoon
ScoringForeachitem:Alwaysright=100;Usuallyright=50;Bothequally=0;Usuallyleft=-50;Alwaysleft=-100TocalculatetheLateralityQuotientaddthescoresthendividebyfour:
Writingscore
Throwingscore
Toothbrushscore
Spoonscore
Total
Lateralquotientscore(total/4)
Classification LateralityQuotientScoreLefthanders -100to-61Mixedhanders -60to60Righthanders 61-100