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Clin[ Otolaryn`ol[ 0888\ 24, 131135

Assessment of mucociliary transport in patients with chronic


mucoid rhinitis
M[J[PRIOR\ K[SCHOFIELD\$ C[M[BOIVIN\$ P[ANDERSON$ +
A[B[DRAKE!LEE
Departments of Otolaryn`olo`y and $Nuclear Medicine\ University Hospital Birmin`ham\ Queen Elizabeth Medical Centre\
Ed`baston\ Birmin`ham\ UK
Accepted for publication 00 February 0888

PRIOR M[J[\ SCHOF IELD K[\ BOIVIN C[M[\ ANDERSON P[ + DRAKES!LEE A[B[
"0888# Clin[ Otolaryn`ol[ 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.cult
to manage successfully[ We present the investigations of the mucociliary system in 39 patients with mucoid
rhinorrhoea as their principal symptom of whom 19 had pan respiratory disease[ The saccharin clearance
time "SCT# was measured and classi_ed as normal if it was below 19 min[ Objective measurement of
clearance was made using 88mTechnetium!labelled human serum albumin "88mTc!HSA#[ We have
standardized our method using a micrometer syringe driver to produce a droplet of consistent size "droplet
size\ 9[90 ml\ SD 9[9991 ml# that reduces the dose of radiation[ The movement of the droplet was measured
over 19 min "RLT#[ The mean\ maximum rate and percentage moved were calculated[ Patients were
divided into those who had chest disease "19# and those without and a x1!test was performed for the mean
RLT 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_cantly
lower mean RLT "P 9[90#[ Assuming that RLT is the standard investigation\ six patients were normal
but 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 Karta`ener|s syndrome

Chronic rhinosinusitis is a heterogeneous group of diseases[0


The presenting symptoms may include some or all of the
following] rhinorrhoea\ nasal obstruction\ post nasal
discharge\ nasal itching and sneezing\ and anosmia[1 The most
common investigations\ skin tests and RAST tests\ are aimed
at 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 _nal
common pathway in a number of pathological states^ some are
better understood than others are[ More di.cult conditions
to diagnose include minor immunological abnormalities and
mucociliary dysfunction[
Temporary dysfunction of mucociliary transport occurs as
result 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

static mechanisms remedy the condition and the respiratory


epithelium returns to normal[ Profound immune de_ciencies
present early in life and are relatively easy to detect but the
subtle ones are more di.cult to diagnose and are frequently
missed until chronic infection is present in both the upper and
lower respiratory tract[ The chronic low!grade infection may
then give rise permanent mucociliary dysfunction[ Patients
with primary mucociliary abnormalities present similarly[
Assessment of mucociliary function is part of the work!up
of patients with chronic respiratory tract symptoms and is
well!established[24 The saccharin clearance time "SCT# is sim!
ple and it is cheap to perform[ The time is measured until
saccharin is _rst tasted[ Although the SCT is a good screening
test\ it does have a signi_cant false positive rate[ Even so\ it is
well correlated to more objective methods obtained by radio
labelled tracer methods[5 Radioisotope transit was developed
in 0854 by Proctor and Wagner\6 and has since been adopted
clinically as the best investigation of mucociliary transport
rate[ We report on the mucociliary function of 39 patients
0888 Blackwell Science Ltd

Assessment of mucociliary transport 132

25

who had bilateral chronic anterior nasal discharge as their


main symptom[

20

Patients and methods


A total of 39 patients under a single consultant have been
included in this study\ all of whom were tertiary referrals
from other hospital consultants\ and who proved refractory
to 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[ Endoscopic
examination was performed and any abnormalities including
nasal polyps were noted[ All patients had skin prick tests to
detect allergy[ All had SCT and radio labelled transit "RLT#
measured[
MUCOCILIARY FUNCTION
Saccharin clearance time
A quarter of a saccharin tablet was placed 0[4 cm behind the
anterior end of the inferior turbinate as we have previously
described[7 The patient is asked not to sni}\ but to sit breath!
ing quietly through the nose[ The result of the test is the time
it takes for the patient to taste the saccharin[709 Patients with
a SCT 19 min had normal mucociliary function[ If the time
was over 19 min\ the patient sense of taste to saccharin was
tested and the SCT was repeated at the next appointment[
The same side "left# was tested on both occasions[ All the tests
were performed by AD!L[
Radiolabelled transit
Two radio!labelled markers are attached to the head with a
bandage\ one on the forehead and one on the occiput[ The
tracer\ 88mTechnetium!labelled microaggregated human serum
albumin "88mTc!HSA#\ is suspended in normal saline[ A drop
of tracer is placed inside one side of the nose and applied to
the ~oor of the nose\ 0 cm behind the muco!cutaneous junc!
tion[ We have modi_ed the existing method\ which uses a
syringe and canula by delivering the droplet with a micrometer
syringe driver "Figs 0\ 1#[ This gives a controlled volume of

15
No.

PATIENTS

10
5
0
0

10

Speed (mm/min)

Figure 1[ Mean transport speeds[

the solution "7[3 ml 2 9[1 ml#\ representing a total radiation


dose of 7[3 MBq 9[1 MBq[ The patient is then sat beside a
gamma camera for 19 min\ with the activity recorded every
minute[ The results are given as an average transport rate over
19 min\ a maximum rate over 0 minute at any one time\ and
the percentage of the drop that moved within the 19!min
observation period[ We tested one side only and chose the left
side for all measurements[ All tests were conducted by AD!L
and the Department of Nuclear Medicine made the measure!
ments[
STATISTICS
A correlation was performed between the mean\ the maximum
and percentage of the droplet when the RLT was measured[
The patients were divided into two groups\ those with chest
disease "19# and those with nasal disease alone "19#[ Values of
the mean RLT below 2 mm:min were considered abnormal[
A x1!test was performed for the mean RLT time in these two
groups[

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

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


0888 Blackwell Science Ltd\ Clinical Otolaryn`olo`y\ 13\ 131135

133 M[J[Prior et al[

Table 0[ Results of radio!labelled mucociliary transport tests


Patient

Best STT
"min#

Mean speed
"mm:min#

Max speed
"mm:min#

) of drop
moved

Clinical diagnosis

0
1
2
3
4
5
6
7
8
09
00
01
02
03
04
05
06
07
08
19
10
11
12
13
14
15
16
17
18
29
20
21
22
23
24
25
26
27
28
39

19
19
19
19
19
19
19
19
19
19
19
19
19
19
19
19
19
08
19
19
19
19
19
19
7
19
19
3
19
07
19
19
19
19
19
04
19
19
19
19

0
4[1
9
0[6
2[2
9
8[2
9
9
9
9
3[7
1[1
5[6
9
9
9
9
9
9
9
9
9
9
0[4
9
1[3
1[5
0[5
4[4
0[0
0[3
9
9
9
9
0[7
3[4

9

4
7[2
9
1[1
3
9
05
9
9
9
9
09[5
4[2
6[3
9
9
9
9
9
9
9
9
9
9
4[2
9
4[2
5[7
2[7
07[7
1[4
1[4
9
9
9
9
4
09

9

78
50
9
099
04
9
34
9
9
9
9
49
26
83
9
9
9
9
9
9
9
9
9
9
16
9
25
65
27
70
19
43
9
9
9
9
26
47
61
9

Chronic sinusitis
Chronic sinusitis
Bronchiectasis\ nasal polyps
Chronic sinusitis
Nasal polyps
Chronic sinusitis
Asthma\ nasal polyps
Bronchiectasis\ chronic sinusitis\ chronic suppurative otitis media
Asthma
Chronic sinusitis
Bronchiectasis\ nasal polyps\ chronic sinusitis
Nasal polyps\ chronic sinusitis
Chronic sinusitis
Nasal polyps
Bronchitis\ chronic sinusitis
Bronchiectasis\ nasal polyps
Chronic sinusitis
Dextrocardia\ bronchitis
Bronchitis
Dextrocardia\ asthma
Chronic sinusitis
Dextrocardia\ bronchitis\ chronic sinusitis
Churg!Strauss syndrome\ asthma\ hypereosinophilic syndrome
Bronchitis
Nasal polyps\ ottis media with e}usion
Chronic sinusitis
Asthma\ nasal polyps
Asthma\ nasal polyps
Young|s syndrome
Chronic sinusitis
Chronic sinusitis
Asthma
Chronic sinusitis
Chronic sinusitis
Bronchiectasis\ chronic sinusitis
Chronic sinusitis
Bronchitis\ asthma
Chronic rhinitis
Bronchitis\ chronic sinusitis\ ottis media with e}usion
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#


Max[ speed "mm:min#
Percentage moved

98[2
910[1
9099

0[41[2
2[86[4
13[721[4

upper respiratory tract conditions with 19 patients having


chronic lower respiratory tract problems[
Mean RLT is shown in Fig[ 1[ There is a strong correlation

between mean and maximum RLT "r  9[80\ Fig[ 2#[ There is
a weaker correlation between percentage of the drop that
moved and the mean and maximum RLT "r  9[69 and 9[51\
respectively#[ Twenty!two patients had no tracer movement
in the 19!min observation period and of these\ two had SCT
less than 19 min "04 and 08 min#[ All the remaining 19 patients
had a SCT 19 min[ Six patients had normal RLT and had
a SCT 19 min[ One patient had a normal SCT and normal
RLT "subject 07\ SCT 07 min\ and mean RLT 4[4 mm:min#[
Eleven "49)# of patients who had a SCT 19 min and no
movement on RLT\ had serious chest disease[ Two of the three
patients with dextrocardia fell into this group[ The remaining
0888 Blackwell Science Ltd\ Clinical Otolaryn`olo`y\ 13\ 131135

Maximum speed (mm/min)

Assessment of mucociliary transport 134

20
18
16
14
12
10
8
6
4
2
0

E
E

E
E
E

E
E E EE
E

E
E EE

10

Mean speed (mm/min)


Figure 2[ Correlation mean and maximum transport speeds[

patient with dextrocardia had a SCT of 08 but no movement


on RLT[ Patients with chest disease had a signi_cantly lower
mean RLT "P 9[90# compared with those who just had
nasal disease[

Discussion
Since patients with chronic mucociliary dysfunction are rare\
careful selection of patients is necessary to investigate the
validity of di}erent tests[ We used the symptom of bilateral
chronic anterior nasal discharge to investigate possible muc!
ociliary transport abnormality to improve the yield[ Clinical
problems include chronic obstructive pulmonary disease\
infertility\ glue ear and chronic sinusitis[ Inherent de_cits of
mucociliary transport a}ect the upper and lower respiratory
tract\ the middle ear and the genital tract to a variable extent[
A high index of suspicion of mucociliary dysfunction should
be given to patients with symptoms that a}ects the nose and
sinuses and lower respiratory tract[
Primary ciliary dyskinesia shows this complex of symptoms
and signs[ The syndrome _rst described by Kartagener
includes situs invs[ but the incidence of dextrocardia is 49)[00
Young|s syndrome is due to hyper!viscous mucous and is of
uncertain aetiology[01 One patient here had been previously
diagnosed with Young|s syndrome and three with Kar!
tagener|s syndrome[ A further 05 patients had disease a}ecting
the lower respiratory tract and in 09\ it was either bronchi!
ectasis or bronchitis^ the remaining six patients had asthma
and in one it was associated with Churg!Strauss vasculitis[ It
is not the purpose of this article to deliberate on the meaning
of {asthma|[ Other diseases may present with similar symp!
toms such as cystic _brosis where the secreted mucus is too
viscid to allow e}ective ciliary transport[02
The aim of management is to investigate the pathological
process underlying their symptoms\ so that treatment can be
targeted more rationally[ Saccharin is a simple\ cheap and
e}ective way to screen patients and its role is widely
accepted[09 The rate may be slow or absent when the patients
0888 Blackwell Science Ltd\ Clinical Otolaryn`olo`y\ 13\ 131135

have normal mucociliary transport due to technical error[09


One of the commonest errors is placing saccharin or tracer
onto the squamous epithelium\ this is one of the reasons that
the saccharin test is repeated[ This error should be avoidable
with training[ When we looked at 33 patients with upper
respiratory tract symptoms but excluded chronic infective
sinusitis\ one patient had absent transit but failed to re!attend
for repeat testing[ The same person "AD!L# performed all the
tests in both studies[8
There was good correlation between both sides of the nose
when 11 controls were tested 1 weeks apart with no statistical
di}erence between the two readings[09 There is debate about
the length of time required to measure the SCT\ and on the
basis of previous results obtained by us\ we have reduced the
time from 14 min to 19 min[8 The patients in the study reported
previously by us had upper respiratory tract disease[ Their
mean SCT was 01 min "range\ 514 min\ SD 4# and the control
group was 7 min "range\ 600 min\ SD 1#[ Stanley and col!
leagues09 noted a similar _nding but some of their patients
had conditions of the lower respiratory tract as well which
will a}ect the results as this study con_rms[
RLT allows objective measurements to be made[ If the
mean time is over 2 mm:min then transport is considered
normal[03 Assuming that RLT is the standard investigation\ 5
patients were normal but had an abnormal SCT\ this is a false
positive error of 04)[ The false negative error was 3:39 "09)#[
The slow or absent transport might be due to temporary
derangement due to an upper respiratory tract infection which
is also why the test is repeated[ Even if patients are instructed
not to sni}\ the habit may be di.cult to control\ as was the
case in patient 28[ She sni}ed before 0 min had passed and
29) of the tracer disappeared then[ Further sni}s reduced
the dose further but the main droplet did not appear to move
otherwise[ It was not included in the statistical results for this
reason[
There are variations in the method used to measure
RLT[3\04\05 The tracer may be put into both sides of the nose
and recorded both together averaging the results or di}erent
tracers can be placed onto the ~oor of the nose on di}erent
sides] the resulting energy di}erences analysed by the g
camera[ We have modi_ed the RLT and only record one side
since we got similar times from the _rst six patients when we
measured both sides consecutively[ Patients found the longer
procedure 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 were
conducted on this side[ The radiation dose is reduced conse!
quently[ We have standardized the drop size by using a
micrometer syringe driver[ This produces a very similar drop!
let with less than 2) variation in size[ Any similar graded
device 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 patients
had slow or absent transport03 but this study looked at a
number of di}erent papers using di}erent techniques[
In conclusion\ saccharin clearance time is a simple a}ective
way to measure mucociliary transport\ but when patients have
a delayed transit or symptoms suggestive of mucociliary prob!
lems\ then radio labelled transit should be contemplated[ The
presence of disease in the lower respiratory tract makes the
likely hood of an abnormality more likely[

6
7

8
09

00

References
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0888 Blackwell Science Ltd\ Clinical Otolaryn`olo`y\ 13\ 131135

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