Archives of Disease in Childhood, 1989, 64, 546-550
`
`Measurement of nasal mucociliary clearance
`G M CORBO,* A FORESI,* P BONFITIO,t A MUGNANO,* N AGABITIt AND P J COLET
`*Centro Auxologico Italiano, Divisione di Pneumologia Pediatrica, Milan, tIstituto di Clinica Medica,
`Servizio di Fisiopatologia Respiratoria, Universita Cattolica del S Cuore, Rome, Italy, and *Host Defence
`Unit, Cardiothoracic Institute, Brompton Hospital, London
`
`SUMMARY The saccharin test was carried out in a randomly selected sample of schoolchildren
`(142 boys and 153 girls, age range 11-14 years) to determine the variability and reproducibility of
`the test and to assess whether it could be used as a screening test for nasal mucociliary clearance.
`Nasal mucociliary clearance times were analysed according to clinical history (asthma, rhinitis,
`asthma with rhinitis, and acute upper respiratory tract infections), laboratory findings (positive
`skin test responses and bronchial hyper-reactivity assessed by methacholine challenge), and
`parental smoking. Nasal mucociliary clearance times showed a narrow coefficient of repeatibility
`(six minutes) in 50 subjects and there was substantial agreement between the two tests. Nasal
`mucociliary clearance times were less than 40 minutes in all the children. Normal children had
`nasal mucociliary clearance times of less than 24 minutes while significantly impaired nasal
`mucociliary clearance was detected in those with positive skin reactions and a positive response to
`methacholine challenge. We were unable to show that passive smoking had any consistent effect
`on nasal mucociliary clearance.
`We suggest that a time response between 30-60 minutes should be checked again at least two
`weeks later, and that children in whom repeated saccharin tests show a nasal mucociliary
`clearance of greater than 30 minutes should have ciliary beat frequency estimated.
`
`Mucociliary clearance is a key defence mechanism in
`human upper and lower airways, and its impair-
`ment, both acquired' and genetically determined,2 3
`predisposes to chronic infection of the nose, para-
`nasal sinuses, and respiratory tree. The age of onset
`of clinical symptoms is usually early but diagnosis is
`often late, because symptoms are not specific (for
`example, cough and sputum) and techniques for
`measurement of mucociliary clearance are time
`consuming and too expensive for routine screening.
`There is, however, evidence that mucociliary clear-
`ance occurs in the trachea and main bronchi at a
`similar rate as in the nose and so several simple
`methods have been developed to measure the nasal
`mucociliary clearance.4
`The saccharin test is inexpensive and simple to
`perform, and its results are similar to those obtained
`using a radioactively labelled particle.5 Recently it
`has been proposed as a screening test to detect
`abnormal mucociliary clearance.6 We have used the
`test to measure nasal mucociliary clearance in a
`random sample of schoolchildren. The purpose of
`the present study was to establish the normal range
`of results and reproducibility of the test in children,
`546
`
`and to determine whether acute upper respiratory
`tract infection (common cold), allergic diseases
`such as bronchial asthma and rhinitis,
`clinical
`bronchial hyper-reactivity and atopy, and exposure
`to passive smoking, prolonged the nasal mucociliary
`clearance.
`
`Subjects and methods
`
`SUBJECTS
`The study was conducted in Verbania in northern
`Italy. Two hundred and ninety five schoolchildren,
`142 boys and 153 girls, age range 11-14 years, were
`studied. The group was a 20% sample stratified for
`age and sex and randomly selected from secondary
`school records.
`Information about respiratory diseases such as
`asthma and rhinitis was obtained from a question-
`naire that was completed by the parents. The
`smoking habits of mothers and fathers were also
`the
`incorporated
`recorded. The questionnaire
`American Thoracic Society children's questionnaire9
`expanded to include more detailed questions on
`allergic diseases. A diary card to complete daily was
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`Measurement of nasal mucociliary clearance
`547
`Comparisons were made between each of the first
`seven groups and the normal group separately using
`the Mann-Whitney U test. Lastly, to assess the
`effect of parental smoking, the children were
`grouped by the number of parents who currently
`smoked. Children whose parents had never smoked
`were compared separately with those who had one
`parent or both parents who were currently smokers,
`also using the Mann-Whitney U test.
`Reproducibility was assessed by calculating the
`difference
`nasal mucociliary clearance time
`in
`between the tests on successive days in each subject
`and then the mean and standard deviation (SD) of
`the differences in the overall sample. The 95%
`coefficient of reproducibility is given as two SD.12
`The interclass correlation coefficient (Ri) was also
`computed. 13
`
`Results
`
`In 36 subjects the test was not carried out either
`because of rhinorrhoea (n= 12) or because the child
`was unwilling (n=24). The median nasal mucociliary
`clearance as measured by the saccharin test in the
`remaining 259 children was eight minutes (range
`1-40)
`(fig
`1).
`the
`The difference
`between
`measurements on successive days with respect to
`the mean in each subject is shown in fig 2. The mean
`value of the differences (-0-26) was not significantly
`different from zero.
`The computed coeffficient of reproducibility was
`
`110.
`
`90-
`
`70-
`
`50-
`
`30-
`
`10-
`
`a'
`
`0*s
`
`m
`
`0 z
`
`4
`
`8
`
`m
`16
`20 24
`12
`32
`28
`36
`Nasal mucociliary clearance time
`Nasal mucociliary clearance time measured by
`Fig 1
`the saccharin test in 259 children.
`
`-
`
`40
`
`given to the parents two weeks before the examina-
`tion, and children who had a common cold during
`the seven days before the test were defined as
`having an acute upper respiratory tract infection.
`
`SACCHARIN TEST
`The saccharin test was carried out by the method
`first described by Andersen et a17 and modified by
`Rutland and Cole.8 A particle 1 mm in diameter was
`placed under direct vision on the inferior nasal
`turbinate 1 cm from its anterior end. The child was
`instructed not to sniff, sneeze, or cough during the
`test and to report a taste as soon as it was noted.
`Subjects who had severe watery rhinorrhoea were
`excluded. The time to the initial perception of a
`sweet taste was recorded in minutes. If no taste was
`apparent after 60 minutes the test was stopped and
`the ability of the subject to taste saccharin placed
`directly on the tongue was verified. In 50 children
`(25 boys and 25 girls) the test was repeated in the
`same nostril the following day to assess its repro-
`ducibility.
`
`ATOPIC STATE AND BRONCHIAL RESPONSIVENESS
`Atopic state was assessed by performing skin tests
`(grass,
`using five commonly inhaled
`allergens
`mugwort, birch, and parietaria, and house dust
`mite). The details of the skin test technique and the
`allergen extracts have previously been published.10
`Wheal reactions were measured by a planimeter and
`a wheal area of 3 mm2 or greater was recorded as a
`positive response. Bronchial responsiveness was
`evaluated by the methacholine test using a standard
`method." Twelve concentrations (from 0-03 mg/ml
`up to 64 mg/ml) were given through a DeVilbiss 646
`nebuliser attached to a dosimeter (Mefar). A
`reduction in forced expiratory volume in one second
`(FEVy) of 20% or more was selected to categorise
`subjects into responders (in whom the provocative
`concentration of methacholine needed to reduce the
`FEV1 by 20% was less than 64 mg/ml), and
`non-responders (in whom a dose of 64 mg/ml of
`methacholine failed to reduce the FEV, by 20%).
`STATISTICAL ANALYSIS
`Having assessed data from the questionnaires, diary
`cards,
`reactions,
`skin
`and the
`bronchial
`test
`response to methacholine we divided the sample
`into eight groups: patients with asthma alone;
`patients with rhinitis alone; those with asthma and
`rhinitis; those who had an acute upper respiratory
`tract infection within the last week; those who had
`positive reactions to skin tests alone; those who had
`a positive response to the methacholine challenge
`alone; those who had positive reactions to both the
`skin tests and the methacholine challenge; and
`normal subjects.
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`548
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`03 c 4
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`(Uu
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`c _
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`v.
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`8-
`12-
`
`16-
`
`10
`15
`Mean time of two tests (minutes)
`Fig 2 Mean nasal mucociliary clearance time of two
`tests plotted against the difference in time between the
`two tests. Horizontal lines indicate mean and two standard
`deviations above and below.
`
`Corbo, Foresi, Bonfitto, Mugnano, Agabiti, and Cole
`16-
`1
`rhinitis, those with positive skin test reactions, those
`who responded to the methacholine challenge or
`children with acute upper respiratory infections.
`Children with colds had longer nasal mucociliary
`clearance times than normal children though the
`difference was not significant (p=009). A signi-
`ficant reduction in nasal mucociliary clearance was,
`however, found in those with positive reactions to
`skin tests and a positive response to the methacholine
`challenge (z=2.404, p=0 01469).
`Ninety eight subjects (38%) had one parent
`currently smoking, 51 (20%) had both parents
`currently smoking, and 110 (47%) had parents who
`had never smoked. There was no significant differ-
`ence between children whose parents never smoked
`and children whose parents currently smoked.
`
`I
`
`0
`
`I
`
`5
`
`I
`
`I
`
`I
`
`20
`
`I
`
`25
`
`----I
`30
`
`six minutes (2SD).'3 The agreement between the
`two tests was substantial (Ri=0-80) according to
`the guidelines of Landis and Kock.14 When the data
`from the questionnaire were analysed six children
`were reported to have asthma without rhinitis, 25
`had rhinitis alone, and 10 had both asthma and
`rhinitis. Forty children had positive reactions to skin
`tests and did not respond to the methacholine
`challenge. A reduction in FEV, of more than 20%
`after the methacholine challenge was detected in 20
`subjects who did not react to the skin tests, and both
`positive
`reactions
`skin
`tests and bronchial
`to
`responses to the methacholine challenge were found
`in 20 children (table).
`Normal subjects had nasal mucociliary clearance
`times of less than 24 minutes, while longer times
`were detected in some subjects in other groups.
`There were no significant differences between nor-
`mal children compared with children with asthma,
`children with rhinitis, children with both asthma and
`
`Discussion
`
`The results of our study confirm those of Stanley et
`a16 that the saccharin test is an useful screening
`technique for measuring nasal mucociliary clearance
`as it is inexpensive, simple to do, and reproducible,
`and we have extended their results in adults to
`children. The nasal mucociliary clearance times
`found in normal children did not differ from those
`found by Andersen and Proctor4 who considered
`that any time in excess of 30 minutes was abnormal;
`we did not find any result in excess of 24 minutes.
`The test showed a rather narrow coefficient of
`reproducibility (six minutes, figure) and the mean
`value of the differences (-0.26) was not significantly
`different from zero, which means that the first
`measurement is not affecting the second and the
`difference does not vary in any systematic way over
`the range of measurements. The agreement between
`the two tests was substantial (Ri=0.80).
`Nasal mucociliary clearance depends on two
`principal components, the physiochemical qualities
`and quantity of the mucus, and the properties of the
`
`Table
`
`Nasal mucociliary clearance times in each group measured by the saccharin test
`
`Clinical group
`
`Normal subjects
`Patients with asthma alone
`Patients with rhinitis alone
`Patients with asthma and rhinitis
`Patients with upper respiratory tract infections
`Patients with positive skin responses alone
`Patients with positive response to methacholine challenge alone
`Paticnts with positive skin responses and positivc
`response to methacholine challenge
`
`Total
`No
`
`98
`6
`25
`10
`40
`40
`20
`
`20
`
`Median (ranige)
`clearance tiine
`(ninutes)
`
`8 (1-24)
`9 (3-36)
`8 (2-36)
`9 (3-32)
`9 (1-40)
`8 (2-35)
`7 (2-36)
`
`10 (3-40)
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`cilia that propel it (for example, beat frequency and
`coordination); these are affected by disease. We
`did, however, find a significantly impaired nasal
`mucociliary clearance only in children with both
`positive skin reactions, and a positive response to
`the methacholine challenge. At present data on
`mucociliary clearance in allergic diseases are contro-
`versial.'5 16 Abnormal mucociliary clearance was
`patients with bronchial asthma,'7 and
`seen in
`abnormal cilia were found in subjects with perennial
`rhinitis.18 Impairment of mucociliary clearance in
`patients with asthma seems to be the result of
`qualitative'9 2(0 and quantitative21
`alterations
`in
`respiratory secretions rather than differences in
`ciliary beating.22 As these changes are transient, the
`saccharin test may fail to show impairment of nasal
`mucociliary clearance depending on the time that
`has elapsed since the exposure to the allergen. We
`found a prolonged nasal mucociliary clearance time
`only in subjects with both skin reactivity to allergen
`extracts and increased bronchial response to metha-
`choline.
`Acute upper respiratory tract infections may
`reduce the nasal mucociliary clearance by direct
`damage to the cilia and change in the rheological
`properties of the nasal secretions.2325
`Tobacco smoke has a ciliostatic effect26 and
`changes the viscoelastic properties of mucus.27 28
`Recently
`mucociliary
`nasal
`clearance
`time
`in
`smokers has been found to be longer than in non-
`smokers.29 In the same study the route of exhalation
`was shown to be crucial, as smokers who regularly
`exhaled through their noses had a longer mean nasal
`mucociliary clearance time than smokers who did
`not regularly exhale by this route. We have not
`shown any consistent effect of passive smoking on
`nasal mucociliary clearance, however, probably
`because the effect is cumulative,29 and depends on
`the degree and the duration of exposure (that is, the
`current amount of parental smoking of cigarettes,
`number of parental smokers during the child's
`lifetime, and the duration of parental smoking
`during child's lifetime).
`In conclusion, we have shown that the saccharin
`test can be used on a large sample to study nasal
`mucociliary clearance in childhood because it
`is
`simple to carry out and the results have a good
`coefficient of repeatability. We have confirmed that
`30 minutes is the cut off point that discriminates
`normal subjects from subjects with impaired nasal
`mucociliary
`clearance.
`Patients
`with
`positive
`responses to skin tests and increased bronchial
`reactivity showed a significantly prolonged nasal
`mucociliary clearance time. We failed to show any
`differences between the normal group and the other
`groups, because the range in the results in the
`
`Measurement of nasal mucociliary clearance
`549
`various groups was so wide that it was difficult to
`pick up small differences.
`Nevertheless, a time response of more than 30
`minutes should be checked again at least two weeks
`later in case it is due to an acute upper respiratory
`infection. Lastly, children who have repeated sac-
`charin tests in which they take longer than 30
`minutes to respond when they do not have an acute
`infection need further investigation.
`
`We thank I Annesi and F Kauffmann for their comments and
`suggestions, and M Lebowitz for his advice.
`
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`Corbo, Foresi, Bonfitto, Mugnano, Agabiti, and Cole
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`Correspondence and requests for reprints to Dr G M Corbo,
`Divisione di Pneumologia Pediatrica, Centio Auxologico Italiano,
`28044 Verbania-Intra(No), Italy.
`
`Accepted 11 October 1988
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