Clin[ Otolarynol[ 0888\ 24, 131135

Assessment of mucociliary transport in patients with chronicmucoid rhinitis

M[J[PRIOR\ K[SCHOFIELD\$ C[M[BOIVIN\$ P[ANDERSON$ +

A[B[DRAKE!LEEDepartments of Otolarynoloy and $Nuclear Medicine\ University Hospital Birminham\ Queen Elizabeth Medical Centre\Edbaston\ Birminham\ UK

Accepted for publication 00 February 0888

PRIOR M [ J [ \ SCHOFIELD K [ \ BOIVIN C [M [ \ ANDERSON P [ + DRAKES !LEE A [B ["0888# Clin[ Otolarynol[ 24, 131135

Assessment of mucociliary transport in patients with chronic mucoid rhinitis

Chronic rhinitis is the manifestation of a heterogeneous group of disease entities and often proves di.cultto manage successfully[ We present the investigations of the mucociliary system in 39 patients with mucoidrhinorrhoea as their principal symptom of whom 19 had pan respiratory disease[ The saccharin clearancetime "SCT# was measured and classi_ed as normal if it was below 19 min[ Objective measurement ofclearance was made using 88mTechnetium!labelled human serum albumin "88mTc!HSA#[ We havestandardized our method using a micrometer syringe driver to produce a droplet of consistent size "dropletsize\ 9[90 ml\ SD 9[9991 ml# that reduces the dose of radiation[ The movement of the droplet was measuredover 19 min "RLT#[ The mean\ maximum rate and percentage moved were calculated[ Patients weredivided into those who had chest disease "19# and those without and a x1!test was performed for the meanRLT time between the two groups[ There was a strong correlation between mean and maximum rates"r 9[80#[ One patient has a normal SCT and normal RLT[ Patients with chest disease had a signi_cantlylower mean RLT "P 9[90#[ Assuming that RLT is the standard investigation\ six patients were normalbut had an abnormal SCT\ this is a false positive error of 04)[ The false negative error was 3:39 "09)#[The association between sinus and chest disease with abnormal mucociliary clearance is stressed[

Keywords mucociliary transport chronic rhinitis Kartaener|s syndrome

Chronic rhinosinusitis is a heterogeneous group of diseases[0

The presenting symptoms may include some or all of thefollowing] rhinorrhoea\ nasal obstruction\ post nasaldischarge\ nasal itching and sneezing\ and anosmia[1 The mostcommon investigations\ skin tests and RAST tests\ are aimedat the diagnosis of allergic rhinitis[ Although this group com!prises only half the patients\1 it is the other 49) of patients\which present a signi_cant diagnostic challenge to the clin!ician[ The symptoms of chronic rhinitis are probably the _nalcommon pathway in a number of pathological states^ some arebetter understood than others are[ More di.cult conditionsto diagnose include minor immunological abnormalities andmucociliary dysfunction[

Temporary dysfunction of mucociliary transport occurs asresult of infection[ The immune response and other homeo!

Correspondence] A[B[ Drake!Lee\ Department of Otolaryngology\University Hospital Birmingham\ Queen Elizabeth Medical Centre\Edgbaston\ Birmingham B04 1TH\ UK[

131 0888 Blackwell Science Ltd

static mechanisms remedy the condition and the respiratoryepithelium returns to normal[ Profound immune de_cienciespresent early in life and are relatively easy to detect but thesubtle ones are more di.cult to diagnose and are frequentlymissed until chronic infection is present in both the upper andlower respiratory tract[ The chronic low!grade infection maythen give rise permanent mucociliary dysfunction[ Patientswith primary mucociliary abnormalities present similarly[

Assessment of mucociliary function is part of the work!upof patients with chronic respiratory tract symptoms and iswell!established[24 The saccharin clearance time "SCT# is sim!ple and it is cheap to perform[ The time is measured untilsaccharin is _rst tasted[ Although the SCT is a good screeningtest\ it does have a signi_cant false positive rate[ Even so\ it iswell correlated to more objective methods obtained by radiolabelled tracer methods[5 Radioisotope transit was developedin 0854 by Proctor and Wagner\6 and has since been adoptedclinically as the best investigation of mucociliary transportrate[ We report on the mucociliary function of 39 patients

Assessment of mucociliary transport 132

who had bilateral chronic anterior nasal discharge as theirmain symptom[

Patients and methods

PATIENTS

A total of 39 patients under a single consultant have beenincluded in this study\ all of whom were tertiary referralsfrom other hospital consultants\ and who proved refractoryto conventional therapy[ The patients were referred over a 2!year period[ All these patients had chronic rhinitis with bilat!eral anterior rhinorrhoea as the main symptom[ Endoscopicexamination was performed and any abnormalities includingnasal polyps were noted[ All patients had skin prick tests todetect allergy[ All had SCT and radio labelled transit "RLT#measured[

MUCOCILIARY FUNCTION

Saccharin clearance timeA quarter of a saccharin tablet was placed 0[4 cm behind theanterior end of the inferior turbinate as we have previouslydescribed[7 The patient is asked not to sni}\ but to sit breath!ing quietly through the nose[ The result of the test is the timeit takes for the patient to taste the saccharin[709 Patients witha SCT 19 min had normal mucociliary function[ If the timewas over 19 min\ the patient sense of taste to saccharin wastested and the SCT was repeated at the next appointment[The same side "left# was tested on both occasions[ All the testswere performed by AD!L[

Radiolabelled transitTwo radio!labelled markers are attached to the head with abandage\ one on the forehead and one on the occiput[ Thetracer\ 88mTechnetium!labelled microaggregated human serumalbumin "88mTc!HSA#\ is suspended in normal saline[ A dropof tracer is placed inside one side of the nose and applied tothe ~oor of the nose\ 0 cm behind the muco!cutaneous junc!tion[ We have modi_ed the existing method\ which uses asyringe and canula by delivering the droplet with a micrometersyringe driver "Figs 0\ 1#[ This gives a controlled volume of

Figure 0[ Micrometer syringe driver used to give a measured dose of 88mTc!HAS[

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No.

25

20

15

10

5

00 1 2 3 4 5 6 7 8 9 10

Speed (mm/min)Figure 1[ Mean transport speeds[

the solution "7[3 ml 2 9[1 ml#\ representing a total radiationdose of 7[3 MBq 9[1 MBq[ The patient is then sat beside agamma camera for 19 min\ with the activity recorded everyminute[ The results are given as an average transport rate over19 min\ a maximum rate over 0 minute at any one time\ andthe percentage of the drop that moved within the 19!minobservation period[ We tested one side only and chose the leftside for all measurements[ All tests were conducted by AD!Land the Department of Nuclear Medicine made the measure!ments[

STATISTICS

A correlation was performed between the mean\ the maximumand percentage of the droplet when the RLT was measured[The patients were divided into two groups\ those with chestdisease "19# and those with nasal disease alone "19#[ Values ofthe mean RLT below 2 mm:min were considered abnormal[A x1!test was performed for the mean RLT time in these twogroups[

Results

The clinical details and results of the patients are given inTable 0[ The patients represent a heterogeneous group of

133 M[J[Prior et al[

Table 0[ Results of radio!labelled mucociliary transport tests

Patient Best STT Mean speed Max speed ) of drop Clinical diagnosis"min# "mm:min# "mm:min# moved

0 19 0 4 78 Chronic sinusitis1 19 4[1 7[2 50 Chronic sinusitis2 19 9 9 9 Bronchiectasis\ nasal polyps3 19 0[6 1[1 099 Chronic sinusitis4 19 2[2 3 04 Nasal polyps5 19 9 9 9 Chronic sinusitis6 19 8[2 05 34 Asthma\ nasal polyps7 19 9 9 9 Bronchiectasis\ chronic sinusitis\ chronic suppurative otitis media8 19 9 9 9 Asthma09 19 9 9 9 Chronic sinusitis00 19 9 9 9 Bronchiectasis\ nasal polyps\ chronic sinusitis01 19 3[7 09[5 49 Nasal polyps\ chronic sinusitis02 19 1[1 4[2 26 Chronic sinusitis03 19 5[6 6[3 83 Nasal polyps04 19 9 9 9 Bronchitis\ chronic sinusitis05 19 9 9 9 Bronchiectasis\ nasal polyps06 19 9 9 9 Chronic sinusitis07 08 9 9 9 Dextrocardia\ bronchitis08 19 9 9 9 Bronchitis19 19 9 9 9 Dextrocardia\ asthma10 19 9 9 9 Chronic sinusitis11 19 9 9 9 Dextrocardia\ bronchitis\ chronic sinusitis12 19 9 9 9 Churg!Strauss syndrome\ asthma\ hypereosinophilic syndrome13 19 9 9 9 Bronchitis14 7 0[4 4[2 16 Nasal polyps\ ottis media with e}usion15 19 9 9 9 Chronic sinusitis16 19 1[3 4[2 25 Asthma\ nasal polyps17 3 1[5 5[7 65 Asthma\ nasal polyps18 19 0[5 2[7 27 Young|s syndrome29 07 4[4 07[7 70 Chronic sinusitis20 19 0[0 1[4 19 Chronic sinusitis21 19 0[3 1[4 43 Asthma22 19 9 9 9 Chronic sinusitis23 19 9 9 9 Chronic sinusitis24 19 9 9 9 Bronchiectasis\ chronic sinusitis25 04 9 9 9 Chronic sinusitis26 19 0[7 4 26 Bronchitis\ asthma27 19 3[4 09 47 Chronic rhinitis28 19 61 Bronchitis\ chronic sinusitis\ ottis media with e}usion39 19 9 9 9 Bronchitis\ chronic sinusitis

Patient sni}ed and 29) of the droplet moved into the post!nasal space within 1 min[

Table 1[ Summary of analytical statistics

Variable Range Mean SD

Mean speed "mm:min# 98[2 0[41[2Max[ speed "mm:min# 910[1 2[86[4Percentage moved 9099 13[721[4

upper respiratory tract conditions with 19 patients havingchronic lower respiratory tract problems[

Mean RLT is shown in Fig[ 1[ There is a strong correlation

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between mean and maximum RLT "r 9[80\ Fig[ 2#[ There isa weaker correlation between percentage of the drop thatmoved and the mean and maximum RLT "r 9[69 and 9[51\respectively#[ Twenty!two patients had no tracer movementin the 19!min observation period and of these\ two had SCTless than 19 min "04 and 08 min#[ All the remaining 19 patientshad a SCT 19 min[ Six patients had normal RLT and hada SCT 19 min[ One patient had a normal SCT and normalRLT "subject 07\ SCT 07 min\ and mean RLT 4[4 mm:min#[Eleven "49)# of patients who had a SCT 19 min and nomovement on RLT\ had serious chest disease[ Two of the threepatients with dextrocardia fell into this group[ The remaining

Assessment of mucociliary transport 134

Mean speed (mm/min)

Max

imum

spe

ed (m

m/mi

n)

20181614121086420

0 2 4 6 8 10

E

E

E

E

EE

E

E

EEEEE

EEE

Figure 2[ Correlation mean and maximum transport speeds[

patient with dextrocardia had a SCT of 08 but no movementon RLT[ Patients with chest disease had a signi_cantly lowermean RLT "P 9[90# compared with those who just hadnasal disease[

Discussion

Since patients with chronic mucociliary dysfunction are rare\careful selection of patients is necessary to investigate thevalidity of di}erent tests[ We used the symptom of bilateralchronic anterior nasal discharge to investigate possible muc!ociliary transport abnormality to improve the yield[ Clinicalproblems include chronic obstructive pulmonary disease\infertility\ glue ear and chronic sinusitis[ Inherent de_cits ofmucociliary transport a}ect the upper and lower respiratorytract\ the middle ear and the genital tract to a variable extent[A high index of suspicion of mucociliary dysfunction shouldbe given to patients with symptoms that a}ects the nose andsinuses and lower respiratory tract[

Primary ciliary dyskinesia shows this complex of symptomsand signs[ The syndrome _rst described by Kartagenerincludes situs invs[ but the incidence of dextrocardia is 49)[00

Young|s syndrome is due to hyper!viscous mucous and is ofuncertain aetiology[01 One patient here had been previouslydiagnosed with Young|s syndrome and three with Kar!tagener|s syndrome[ A further 05 patients had disease a}ectingthe lower respiratory tract and in 09\ it was either bronchi!ectasis or bronchitis^ the remaining six patients had asthmaand in one it was associated with Churg!Strauss vasculitis[ Itis not the purpose of this article to deliberate on the meaningof {asthma|[ Other diseases may present with similar symp!toms such as cystic _brosis where the secreted mucus is tooviscid to allow e}ective ciliary transport[02

The aim of management is to investigate the pathologicalprocess underlying their symptoms\ so that treatment can betargeted more rationally[ Saccharin is a simple\ cheap ande}ective way to screen patients and its role is widelyaccepted[09 The rate may be slow or absent when the patients

0888 Blackwell Science Ltd\ Clinical Otolarynoloy\ 13\ 131135

have normal mucociliary transport due to technical error[09

One of the commonest errors is placing saccharin or traceronto the squamous epithelium\ this is one of the reasons thatthe saccharin test is repeated[ This error should be avoidablewith training[ When we looked at 33 patients with upperrespiratory tract symptoms but excluded chronic infectivesinusitis\ one patient had absent transit but failed to re!attendfor repeat testing[ The same person "AD!L# performed all thetests in both studies[8

There was good correlation between both sides of the nosewhen 11 controls were tested 1 weeks apart with no statisticaldi}erence between the two readings[09 There is debate aboutthe length of time required to measure the SCT\ and on thebasis of previous results obtained by us\ we have reduced thetime from 14 min to 19 min[8 The patients in the study reportedpreviously by us had upper respiratory tract disease[ Theirmean SCT was 01 min "range\ 514 min\ SD 4# and the controlgroup was 7 min "range\ 600 min\ SD 1#[ Stanley and col!leagues09 noted a similar _nding but some of their patientshad conditions of the lower respiratory tract as well whichwill a}ect the results as this study con_rms[

RLT allows objective measurements to be made[ If themean time is over 2 mm:min then transport is considerednormal[03 Assuming that RLT is the standard investigation\ 5patients were normal but had an abnormal SCT\ this is a falsepositive error of 04)[ The false negative error was 3:39 "09)#[The slow or absent transport might be due to temporaryderangement due to an upper respiratory tract infection whichis also why the test is repeated[ Even if patients are instructednot to sni}\ the habit may be di.cult to control\ as was thecase in patient 28[ She sni}ed before 0 min had passed and29) of the tracer disappeared then[ Further sni}s reducedthe dose further but the main droplet did not appear to moveotherwise[ It was not included in the statistical results for thisreason[

There are variations in the method used to measureRLT[3\04\05 The tracer may be put into both sides of the noseand recorded both together averaging the results or di}erenttracers can be placed onto the ~oor of the nose on di}erentsides] the resulting energy di}erences analysed by the gcamera[ We have modi_ed the RLT and only record one sidesince we got similar times from the _rst six patients when wemeasured both sides consecutively[ Patients found the longerprocedure unacceptable and since previous work with sac!charin found little di}erence\09 we believe that this is accept!able[ We chose the left side since all the saccharin tests wereconducted on this side[ The radiation dose is reduced conse!quently[ We have standardized the drop size by using amicrometer syringe driver[ This produces a very similar drop!let with less than 2) variation in size[ Any similar gradeddevice could be used[ Overall\ eight patients had normal muc!ociliary transport measured by RLT "mean\ 4[5 mm:min^range\ 2[28[2 mm:min#[ Eight patients had a slower transit"mean\ 0[6 mm:min^ range\ 0[01[5 mm:min#[ The remaining

135 M[J[Prior et al[

13 patients "59)# had no measurable mucociliary transport[Proctor and Andersen reported that 19) of normal patientshad slow or absent transport03 but this study looked at anumber of di}erent papers using di}erent techniques[

In conclusion\ saccharin clearance time is a simple a}ectiveway to measure mucociliary transport\ but when patients havea delayed transit or symptoms suggestive of mucociliary prob!lems\ then radio labelled transit should be contemplated[ Thepresence of disease in the lower respiratory tract makes thelikely hood of an abnormality more likely[

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0888 Blackwell Science Ltd\ Clinical Otolarynoloy\ 13\ 131135

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