rinita.clearance

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Clin[ Otolaryn`ol[ 0887\ 23, 277Ð285 REVIEW Mucociliary transport and its assessment: a review A[M[LALE\ J[D[T[MASON + N[S[JONES$ Department of Otorhinolaryn`olo`y\ Addenbrookes| Hospital\ Cambrid`e\ Department of Otorhinolaryn`olo`y\ Royal Bolton Hospital\ Nottin`ham\ and $Department of Otorhinolaryn`olo`y\ University Hospital\ Nottin`ham\ UK Accepted for publication 03 April 0887 The clinical assessment of nasal mucociliary clearance The clinician should suspect a disorder of mucociliary clear! ance in a patient who has both rhinosinusitis and bronchi! ectasis\ an individual with purulent rhinosinusitis who repeat! edly fails to respond to medical treatment\ or if the nasal airway is _lled with tenaceous secretions[ This is a review of the various clinical tests which could be employed to assess mucociliary clearance Nasal mucociliary clearance is a fundamental function required to maintain the health and defence of the nose[ Muc! ociliary transport is disturbed in a variety of conditions which a}ect the activity of the cilia[ Twenty to forty ml of mucus are secreted from the normal {resting| nose each day from 059 cm 1 of nasal mucosa[ Nasal mucus provides a continuous blanket lining the nasal cavity onto which particles in the turbulent inhaled airstream can impact and stick^ 79) of particles larger than 01[4 mm are _ltered from the air before it reaches the pharynx[ The blanket of mucus can be moved by the co!ordinated waves of cilia from the front of the nose to the nasopharynx where it can be swallowed or expectorated[ The properties of mucus are geared to ful_ll these two roles] trapping and transporting airborne particles[ The periciliary ~uid is a lubricating layer in which the cilia beat\ 0 and is functionally distinct\ but structurally continuous\ from the viscous layer of mucus above[ Soluble material such as saccharin will dissolve and be transported through this layer\ and it has been suggested that transport through the periciliary layer is more e.cient than in the mucus layer[ 1Ð3 Cilia in isolation are sensitive to the e}ects of temperature\ working optimally at 24Ð39 >C\ and above and below these temperatures the natural beat frequency drops[ Mucociliary systems are very sensitive to drying but within the usual atmo! spheric conditions there is little alteration in nasal mucociliary transport rate\ 4 and this is due to the warming and humid! ifying functions of the nose[ Correspondence] N[S[Jones\ Department of Otorhinolaryngology\ University Hospital\ Nottingham NG6 1UH\ UK 277 Þ 0887 Blackwell Science Ltd Nasal mucociliary pathways In anaesthetised animals or in fresh cadaveric specimens the pathway of the mucus ~ow can be monitored by following particles or drops of blood on the surface of the mucus\ or bubbles and debris that are present in the mucus[ In the human nasal fossa the direction of the mucus ~ow is predominantly posteriorly towards the nasopharynx\ streaming above and below the tubal opening 5\6 and this is similar to other primates[ 7 Di}erences in mucociliary transport rates between di}erent sites in the nose depend on ciliary beat frequency\ density of the ciliary population\ length of the cilia and mucus quality[ 8 The rate of mucociliary transport is 0Ð1 mm:h just behind the anterior portion of the inferior turbinate\ and increases to 7Ð09 mm:h on the posterior portion of the inferior turbinate[ 09 In Quinlan et al[|s study on the human nose\ 00 radioactive particles placed on the septum travelled posteriorly to the soft palate\ either passing in a gentle slope to the inferior edge of the septum\ or travelling directly posteriorly and turning sharply down the inferior edge of the septum[ Those on the ~oor of the nose travel posteriorly\ but tend to deviate either laterally to the inferior meatus or medially towards the inferior edge of the nasal septum during their passage to the naso! pharynx[ Particles placed on the medial surface of the inferior turbinate pass laterally to the inferior meatus and then pos! teriorly^ they then pass above or below the tubal opening[ Where there is an obstruction to the normal path of muc! ociliary transport\ di}erent phenomena have been reported[ Where spurs on the septum or other mucosal irregularities present large obstructions\ or are associated with alterations in the epithelial surface such as squamous metaplasia\ the pathway is around these obstructions[ 00Ð03 If the bony spur is small and it has retained functioning ciliated epithelium on its surface\ and the mucus is of adequate viscosity to move up a slope\ then the mucus blanket will travel over this obstacle[ 01\02 If there is a defect in the mucosal surface\ and the cohesive properties of the mucus are preserved then the mucus carpet can move undisturbed from one edge of intact epithelium to the next[ 01\02 If there is a defect associated with pooling of the mucus\ 00 or with squamous metaplasia\ 04 normal mucociliary

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  • Clin[ Otolarynol[ 0887\ 23, 277285

    REVIEW

    Mucociliary transport and its assessment: a review

    A[M[LALE\ J[D[T[MASON + N[S[JONES$Department of Otorhinolarynoloy\ Addenbrookes| Hospital\ Cambride\ Department of Otorhinolarynoloy\ Royal BoltonHospital\ Nottinham\ and $Department of Otorhinolarynoloy\ University Hospital\ Nottinham\ UK

    Accepted for publication 03 April 0887

    The clinical assessment of nasal mucociliaryclearance

    The clinician should suspect a disorder of mucociliary clear!ance in a patient who has both rhinosinusitis and bronchi!ectasis\ an individual with purulent rhinosinusitis who repeat!edly fails to respond to medical treatment\ or if the nasalairway is _lled with tenaceous secretions[ This is a review ofthe various clinical tests which could be employed to assessmucociliary clearance

    Nasal mucociliary clearance is a fundamental functionrequired to maintain the health and defence of the nose[ Muc!ociliary transport is disturbed in a variety of conditions whicha}ect the activity of the cilia[ Twenty to forty ml of mucusare secreted from the normal {resting| nose each day from 059cm1 of nasal mucosa[ Nasal mucus provides a continuousblanket lining the nasal cavity onto which particles in theturbulent inhaled airstream can impact and stick^ 79) ofparticles larger than 01[4 mm are _ltered from the air beforeit reaches the pharynx[ The blanket of mucus can be movedby the co!ordinated waves of cilia from the front of the noseto the nasopharynx where it can be swallowed or expectorated[The properties of mucus are geared to ful_ll these two roles]trapping and transporting airborne particles[

    The periciliary ~uid is a lubricating layer in which the ciliabeat\0 and is functionally distinct\ but structurally continuous\from the viscous layer of mucus above[ Soluble material suchas saccharin will dissolve and be transported through thislayer\ and it has been suggested that transport through thepericiliary layer is more e.cient than in the mucus layer[13

    Cilia in isolation are sensitive to the e}ects of temperature\working optimally at 2439 >C\ and above and below thesetemperatures the natural beat frequency drops[ Mucociliarysystems are very sensitive to drying but within the usual atmo!spheric conditions there is little alteration in nasal mucociliarytransport rate\4 and this is due to the warming and humid!ifying functions of the nose[

    Correspondence] N[S[Jones\ Department of Otorhinolaryngology\University Hospital\ Nottingham NG6 1UH\ UK

    277 0887 Blackwell Science Ltd

    Nasal mucociliary pathways

    In anaesthetised animals or in fresh cadaveric specimens thepathway of the mucus ~ow can be monitored by followingparticles or drops of blood on the surface of the mucus\ orbubbles and debris that are present in the mucus[ In the humannasal fossa the direction of the mucus ~ow is predominantlyposteriorly towards the nasopharynx\ streaming above andbelow the tubal opening5\6 and this is similar to otherprimates[7 Di}erences in mucociliary transport rates betweendi}erent sites in the nose depend on ciliary beat frequency\density of the ciliary population\ length of the cilia and mucusquality[8 The rate of mucociliary transport is 01 mm:h justbehind the anterior portion of the inferior turbinate\ andincreases to 709 mm:h on the posterior portion of the inferiorturbinate[09

    In Quinlan et al[|s study on the human nose\00 radioactiveparticles placed on the septum travelled posteriorly to the softpalate\ either passing in a gentle slope to the inferior edgeof the septum\ or travelling directly posteriorly and turningsharply down the inferior edge of the septum[ Those on the~oor of the nose travel posteriorly\ but tend to deviate eitherlaterally to the inferior meatus or medially towards the inferioredge of the nasal septum during their passage to the naso!pharynx[ Particles placed on the medial surface of the inferiorturbinate pass laterally to the inferior meatus and then pos!teriorly^ they then pass above or below the tubal opening[

    Where there is an obstruction to the normal path of muc!ociliary transport\ di}erent phenomena have been reported[Where spurs on the septum or other mucosal irregularitiespresent large obstructions\ or are associated with alterationsin the epithelial surface such as squamous metaplasia\ thepathway is around these obstructions[0003 If the bony spur issmall and it has retained functioning ciliated epithelium on itssurface\ and the mucus is of adequate viscosity to move up aslope\ then the mucus blanket will travel over this obstacle[01\02

    If there is a defect in the mucosal surface\ and the cohesiveproperties of the mucus are preserved then the mucus carpetcan move undisturbed from one edge of intact epithelium tothe next[01\02 If there is a defect associated with pooling of themucus\00 or with squamous metaplasia\04 normal mucociliary

  • Mucociliary transport and its assessment 278

    transport at this site will be lost[ Andersen demonstrated areasof the turbinate where clearance is slow and these showedintra!individual variation in position with time[05 Quinlan sug!gests that there is a speed gradient with the speed increasingtowards the oropharynx from the anterior parts of the nose[00

    Effect of airflow on nasal mucociliary function

    At a site of air~ow obstruction\ such as a septal de~ection\ oran enlarged anterior end of the inferior turbinate there aretissue changes\ such as hypertrophy of the subepithelialmucosa\ mucous glands or an increase in the thickness of themucoperiostium[ There is also atrophy of the epithelium withareas of metaplasia to squamous epithelium[06 In other mam!malian mucociliary systems the initial e}ect of drying is anch!oring of the mucus sheet to the epithelial surface\ the mucustending to remain plugged around its source of secretion andnot migrate to form a blanket above the periciliary ~uid andciliary tips[07\08

    Disruption of cilia by viruses and bacteria

    Haemophilus in~uenzae\ streptococcus pneumoniae\ staphy!lococcus aureus and pseudomonas produce speci_c toxins thatdisrupt epithelial cells with the loss of a con~uent ciliary _eld[Neutrophils which gather at the sites of purulent infectionproduce an elastase that is directly toxic to respiratoryepithelium[1913 Viruses responsible for the common cold dis!rupt the ciliated cell|s microtubules and there is an increase inmucus tethering at the sites of mucus glands making it di.cultfor the remaining cilia to transport mucus[

    Allergic rhinitis

    Changes in ciliary structure occur in patients with long!stand!ing allergic rhinitis and changes in secreted mucus occur attimes of acute allergen challenge[ The changes to mucus thatoccur during acute allergic nasal reactions are secondary to avariety of in~ammatory mediators[ There is likely to be animprovement in mucociliary transport due to alterations inthe rheological properties of the mucus and an increase inciliary beat frequency[ Damage to nasal cilia also occurs inpatients with allergic rhinitis with absence of dynein arms\and radial spokes\ ciliary membrane damage\ compound ciliaand disorientation of central tubules[1416 The results fromexperiments on the patients with allergic rhinitis are incon!clusive\ some suggesting there is an increase and some areduction in nasal mucociliary transport in response to aller!gen challenge[ In patients with positive skin tests and a positiveresponse to methacholine challenge saccharin clearance timesare prolonged[17 Ciliary abnormalities have been detected inpatients described as having perennial rhinitis\ but not allstudies have found this[18

    0887 Blackwell Science Ltd\ Clinical Otolarynoloy\ 12\ 277285

    Chronic rhinosinusitis

    In patients with chronic rhinosinusitis areas of ciliary denude!ment have been demonstrated\ but in areas where cilia werepreserved ciliary motility appeared normal[ Prolonged sac!charin clearance in patients with maxillary sinusitis has beenattributed to abnormalities of the mucus[ The mucosa of pat!ients with chronic sinusitis shows changes including oedema\shedding of epithelial cells and squamous metaplasia[ Ciliaryabnormalities have been reported including compound ciliaand deviation from the usual {81| _lament arrangement[2939

    Nasal polyps

    Nasal polyps are oedematous swellings of the nasal mucosa[Their ciliated surface can undergo squamous metaplasia[Where the mucociliary blanket is preserved the mucus ismoved in a normal fashion\ but due to the pedunculatedswelling of the mucosa the direction of the mucus ~ow maybe changed[ Patients with nasal polyposis have disturbed muc!ociliary function as measured by saccharin clearance andgamma scintigraphy[3034

    Effect of commonly used intranasal preparationson nasal mucociliary transport

    The commonly used intranasal preparations which have ster!oids or antihistamines as active agents have not been shownto be detrimental to nasal mucociliary function in humans\35\36

    despite reports that isolated cilia beat less e}ectively whenperfused with these drugs or the preservatives that are addedto these drugs[3742

    Congenital anomalies which affect nasal muc-ociliary function

    Five to ten per cent of the cilia show abnormalities in childrenand adults who have no apparent nasal disease[ In Kar!tagener|s syndrome there is absence of the dynein arms of thenine peripheral microtubules[ These individuals have only39) of their ciliated cells working and they also lack co!ordination or metachronicity[43\44 In primary ciliary dyskinesiaimpaired mucociliary clearance has been shown to be due tostructural defects of the ciliary axoneme[4548

    In Young|s syndrome "obstructive azoospermia with recur!rent sinobronchial disease# there is a disorganisation of ciliaryorientation\ which is more pronounced at the cilial tip\ butthe other features of the cilia are normal[59

    Nasal acilia "RothmundThomson# syndrome is an isolatedabsence of cilia in the nasal mucosa[50\51 The condition presentswith chronic rhinitis[

    Immunode_ciency is associated with deranged mucociliarytransport[ Patients with common variable immunode_ciency

  • 289 A[M[Lale\ J[D[T[Mason + N[S[Jones

    have slower nasal mucociliary transport and more extensivemucosal damage than those with selective IgA de_ciency[52

    In cystic _brosis the primary abnormality is not with thecilia\ but with the production of abnormal mucus\ possiblysecondary to defective chloride transport[5355

    Measurement of mucociliary function

    This can be separated into three types of studies] "0# measure!ment of ciliary form and motion^ "1# measurement of mucusproduction and its chemical and physical properties^ and "2#measurement of the e.ciency of the combined e}ects of themucus and ciliary systems[

    MEASUREMENT OF CILIARY FORM AND MOTION

    Ciliary activity has attracted a lot of interest because cilia arerelatively easy to harvest and their function is relatively easyto measure[ Isolated\ mucus!free\ ciliary activity has beenmonitored on unicellular organisms\56 and from the res!piratory and reproductive tracts of many mammals[ Whenmucociliary systems such as nasal mucosa demonstrate chan!ges in response to a stimulus\ it is di.cult to be certain whetherthe change represents alteration in ciliary activity or in theproduction and properties of mucus[ Studies of mucus!freeisolated cilia permit the study of direct e}ects on cilia[ Nasalcilia are easy to harvest] familiarity with simple anterior rhi!noscopy allows ready access to the inferior turbinate\ the ~oorof the nose and the anterior third of the nasal septum[ All ofthese sites have been described as sources of ciliated cells bynasal brushing with a 1!mm nylon brush[5760 A larger numberof cells that are in contact with the basal membrane can beobtained with a curette or forceps[ It has been suggestedthat a group of cells in contact with the basement membraneshould be used for ciliary beat measurements\ and that forcepsare preferable to curettes[61

    The measurement of ciliary beat frequency started in 0733with Martius who used a stroboscope to estimate frequency[This is unreliable at frequencies around 519 Hz\62\63 becauseof the phase di}erence between groups of cells and met!achronous movement[ Nearly a century later\ in the 0829s\the investigation of ciliary movement began in earnest withProetz[64

    Direct observation of ciliary function can only detect thedi}erence between active and paralysed cilia[65 It is importantthat methods of measurement are consistent between readings[There is great variability in beat frequency between di}erentcells in the same tissue sample[ Some reports only considerthe beat frequency of only the most vigorous cilia\10\66 whileother researchers suggest that beat frequency should be mea!sured at random sites and the variability of beat frequencywithin the sample should be considered[67 Diurnal rhythmsmay in~uence the measurements of beat frequency\ and the

    0887 Blackwell Science Ltd\ Clinical Otolarynoloy\ 12\ 277285

    time of day should be considered[68 Intracellular calcium andc!AMP are so in~uential in the ciliary beating that it may beworth stating these at the same time as the beat frequencymeasurements[79

    Measurement of ciliary beat frequency using a photo!sensitive cell that converts the re~ections of light from beatingcilia into an electric current and then an oscilloscope displayvia an ampli_er was described in 0851\70 and this is the mostwidely applied method[7173 Re~ected light from the cilia isnot the only altering light intensity that can be transduced toan electrical signal[ Video images of beating cilia from a moni!tor with the altering light intensities of individual pixels orpixel groups\67\74\75 or interruptions of a light source76 or scat!tering of a laser beam by the cilia can be utilised[77\78 Allthese can be transduced to an electrical signal which can beampli_ed\ _ltered\ and then digitised[ A computer using fastFourier transformation can then be used to calculate\ anddisplay the ciliary beat frequency results\ and include somestatistical analysis[89

    When studying preparations with beating cilia it is impor!tant they are maintained at constant temperature\ and the pHand the osmolality are maintained in a physiological range[61

    Ciliary beat frequency shows consistent readings in the tem!perature range 2139 >C[ Between 08 >C and 21 >C it increasesin a linear fashion\ and above 39 >C it declines[80 This is con!sistent with studies into the temperature range of nasal tissuein vivo[81\82 When interpreting the results of ciliary beatmeasurements or the structure of cilia in a clinical setting ifabnormalities are detected they are usually secondary to otherabnormalities[ Also\ it has been shown that abnormalities ofthe cilia are reversible when cultured in tissue medium[54 Ciliaobtained with a nylon brush can be examined under the elec!tron microscope[83\84 The following features can be looked forand measured quantitatively from electron micrographs oftransversely sectioned cilia] the incidence of compound cilia\the incidence of central and peripheral microtubule defects\the numbers of inner and outer dynein arms per cilium\ andciliary orientation[59 The ciliary beat axis is perpendicular to aline drawn through the centres of the two central microtubules"Figure 0#[ In a group of cilia sectioned axially and displayedon an electromicrograph\ the angle subtended by each ciliacan be measured and the mean ciliary angle can be calculated[From this the ciliary deviation can be calculated\ that is theSD of the ciliary angle for the cilia sectioned can be determined[In normal patients the ciliary angle is 03 >\ and at the tip theciliary deviation is 3 >[ In cilia that show disorganisation thismay be more marked at the tip than at the base\ as has beendemonstrated in Young|s syndrome[59

    The biopsy of nasal cilia is straightforward\ but the equip!ment required to measure ciliary beat frequency and measureciliary angles is complex and expensive and will only be avail!able in a few centres[ The axial section of nasal cilia is not easy\and it requires patience to section cilia cleanly and parallel tothe surface of the cell[

  • Mucociliary transport and its assessment 280

    Figure 0[ The ciliary beat axis\ mean ciliary angle and the ciliarydeviation[ The ciliary axis is perpendicular to a line drawn throughthe centres of the two central microtubules[ The angle subtended bythis line to an arbitrary reference point is averaged to determine themean ciliary angle\ and the SD gives the ciliary deviation[

    MEASUREMENT OF MUCUS PRODUCTION AND ITS RHEO !LOGICAL PROPERTIES

    Measurement of the rheological properties of mucus is a well!established _eld[85\86 The rheological properties of nasal mucusare carefully matched to its biological function[ In the cat theaverage tracheal mucus viscosity is 1372095 poises at a shearrate of 0 s0 and recoverable shear strain 2[020[0 units at 099dynes cm1[87 It has been suggested that these are optimumparameters of viscosity and elasticity for mucociliary trans!port\ but the normal levels for human nasal mucus areunknown[ The quoted parameters for viscoelastic propertiesdo not have a directly comparable physiological function\ thusit remains uncertain what changes in {spinnability|\ {shearstrain|\ {elastothixotropy|\ {pseudoplasticity|\ {creep|\ and{adhesiveness| would have on mucociliary transport[ It is likelythat interaction of the cilia with mucus alters the dynamicrheological properties of nasal mucus\ and thus mucus at thecilial tips may have di}erent viscoelastic properties to thatwhich is carrying the mucus load[88\099

    Machines have been built to measure certain properties ofmucus] the magnetic microrheometer\ the controlled stresstechnique\ capillary viscometer\ the coaxial cylinder sensorsystem[ From these machines\ di}erent properties of mucusare measured\ but none correspond precisely to a de_nitephysiological function[ The harvesting of mucus samples andtheir subsequent storage may well lead to alteration of theirchemical and rheological properties[ The measurement of the

    0887 Blackwell Science Ltd\ Clinical Otolarynoloy\ 12\ 277285

    rheological properties of human nasal mucus has potentialvalue\ but a reliable test with a de_nite clinical application isyet to be found[

    MEASUREMENT OF THE COMBINED EFFECTS OF THE

    MUCUS AND CILIARY SYSTEMS

    It is important to distinguish between mucociliary transportwhich is the movement of particles in an anatomically de_nedlocation and mucociliary clearance which is the measure ofelimination of inhaled or insu/ated aerosols[

    Saccharin testThis involves placing a particle or solution of saccharin onthe anterior end of the inferior turbinate or nasal septum\behind the area of slow anterior clearance[05 The method ofthe test most commonly used is that described by Rutlandand Cole which is a modi_cation of Andersen|s originaldescription of the test[ A 0 mm diameter or quarter fragmentof a saccharin tablet is placed just behind the anterior end ofthe inferior turbinate\ and the patient is asked to sit quietlywith their head forward\ not to sni}\ sneeze\ eat or drink[ Thetime taken to the _rst perception of the sweet taste is thesaccharin clearance time[54

    The saccharin dissolves in the mucus layer and presumablythe periciliary ~uid layer\ and is transported to the naso!pharynx and the base of the tongue[ This is a useful screeningtest\090 those with times greater than 59 min having sig!ni_cantly disturbed mucociliary transport[ In these patients itis necessary to con_rm their ability to taste saccharin[ Theaverage saccharin clearance time for an adult free from nasaldisease would be 604 min "see Table 0#[17\18\090094 In 31 pat!ients who were starved and waiting to go to the theatre forvarious non!nasal procedures and were free of any nasal dis!ease the mean SCT was 02[2 min "range 4[221[4 min#[ Fromthis data it is likely that patients who have a saccharin clear!ance time greater than 19 min have disturbed nasal muc!ociliary transport[

    It has been shown that saccharin clearance times show a

    Table 0[ Saccharin clearance times for normal subjects

    No[ Mean SCTAuthor subjects "min# Range

    Corbo "0878#17 87 7 013Coromina "0889#093 19 01 "SD\ 5# *Yergin "0867#094 09 09[7 "SD\ 2[1# 4[506[0Stanley "0873#090 24 03[9 "SD\ 9[8# *Stanley "0874#18 16 00[6 "SD\ 2[7# *Moriarty "0880#092 5 * 600Lale et al[ "0887#$ 31 02[2 "SD\ 4[4# *

    This is the median value for the SCT\ mean not quoted[$ Present paper[

  • 281 A[M[Lale\ J[D[T[Mason + N[S[Jones

    diurnal variation\ being at their lowest between 96[99 and02[99\ and being longest at 93[99[095 When the saccharin testwas compared with tracking times of a 149 mm anion resinparticle labelled with 88mTc there was a signi_cant negativecorrelation\096 and this correlation was maintained with theday to day variation in saccharin clearance times[

    If the times for saccharin clearance are normal there isprobably no correlation with ciliary beat frequency\ thoughthe log value has been reported to correlate with frequency ofciliary beat[097

    Modi_cation of the saccharin clearance test has beendescribed where inert tracers such as ion exchange resin par!ticles are coated with saccharin[ The authors argue that thiswould measure the movement of the particle on the mucuslayer only[098 It would seem likely that some of the saccharinwill dissolve into the mucus and the periciliary ~uid and betransported by di}usion in this layer\ but this would not befaster than active movement of the periciliary layer towardsthe tongue[

    A study compared saccharin "soluble substance# clearancetimes with the time for charcoal powder "insoluble# to appearin the nasopharynx in subjects free from nasal disease[ Thecharcoal powder was reported as the most reproduciblemethod of assessing nasal mucociliary clearance[009 In anotherstudy comparing saccharin with other insoluble substances\the insoluble substances are transported more rapidly throughthe nose] saccharin\ 06[3 min^ charcoal powder\ 7[2 min[000

    This suggests that the mucus layer is the most e}ectivelytransported layer[

    When using the saccharin clearance test it must be taken inconjunction with the patient|s symptoms and proper exam!ination of the nasal mucosa[ If the test is prolonged beyond59 min then there is a likelihood that there is a signi_cantdefect in cilia or mucus[ If the test is prolonged beyond 19min and there is treatable nasal disease then there is a possi!bility that this could be improved by the adequate treatmentof the nasal disease[

    DyePlacing a dye such as indigo carmine097 on the anterior nasalmucosa and measuring the time taken to appear in the oro!pharynx\ provides a measure similar to that provided by thesaccharin clearance time[5\001\002 This is time!consuming for theinvestigator who has to watch the oropharynx and requiresthe subject to keep his mouth open for up to 19 min[

    Stained vegetable charcoal powder has been studied in chil!dren "age 201 years#\ this gave a mean time of 8[86 min\ andthere was no di}erence between the sexes or between lyingand standing[

    Trackin of intranasal radioisotopic particlesProctor003 describes injecting a saline solution of mic!roaggregated albumin labelled with iodine "I020# behind theanterior end of the inferior turbinate and onto the ~oor of the

    0887 Blackwell Science Ltd\ Clinical Otolarynoloy\ 12\ 277285

    nose[ The radioactivity is tracked using parallel slit colli!mators[ Using this apparatus the mean mucociliary transportrate was estimated as 5 mm:min\ and he showed that a childwith cystic _brosis had de_cient mucociliary transport[

    Studies have utilized radiolabelled single non!dispersibleparticles such as 9[4!mm resin particles labelled with 2 mCitechnetium!88m placed on the superior surface of the inferiorturbinate or the nasal ~oor or the nasal septum[ The courseof these particles can be tracked through the nose using aseries of collimators and a scinticounter\ or a pinhole Angercamera[00\05\004006

    Gamma scintiraphyThis provides the most physiological information about thedeposition\ dispersion and clearance of particles in the nose[It follows the movement of many particles once they havebeen deposited in the nasal cavity\ rather than the movementof individual particles or the passage of a substance in solutionsuch as saccharin[ A gamma camera is able to track the move!ment of particles that are inhaled\ sprayed or insu/ated intothe nose[ The radiolabelling is generally achieved by the incor!poration of 88mTc or 000I into a particle of known size[ Thispermits the study of the e}ects of particle size and the methodof delivery to the nose on the deposition and clearance of theparticle by the nasal mucosa[ The equipment and a radiationprotected room are not freely available to every clinical rhi!nologist\ and this remains a research method for the study ofintranasal drug delivery[007

    The radioactivity at the tip of the nose can be measuredafter placing the particle behind the anterior end of the inferiorturbinate\ the fall in detected radioactivity is proportional tothe square of the distance from the nasal tip to the movingparticle\ using this method a speed of 4[2 mm:min "range 2[27[1 mm:min# has been calculated[008

    The type of tracer used can make a di}erence to the speedof transport in the nose\ seroalbumin labelled with Tc88 wastransported at 7 mm:min but pertechnetate labelled with Tc88

    was transported at a speed of 4 mm:min[000 Tracking thepassage of radiolabelled particles through the nose providesuseful information regarding the handling of individualparticles\ but the equipment is expensive\ the patient has toremain in a room suitable for radioactive materials\ and thesubject is exposed to radiation[

    Radioraphic methodMovement of radiopaque 0!mm diameter discs of Te~onmixed with bismuth trioxide can be followed with a ~uo!roscopic image intensi_er[094 The discs were 9[97 mm thickand had an average weight of 0[65 mg[ This is a modi_cationof a technique described for the trachea and bronchi[019 Themovement of the discs was displayed on a monitor\ and thedistance travelled was determined from a radiopaque scaleplaced on the cheek[ This provides information about the

  • Mucociliary transport and its assessment 282

    direction of travel of these particles\ but the subject is exposedto radiation[

    The method is reproducible at 04 min intervals\ and therewas no signi_cant variation over a 01 h period[094 The resultsobtained were similar to those by the radioisotopic method\05

    there were no variations with sex or age\ and no correlationwith saccharin clearance times[094

    Mucociliary transport on isolated human nasalmucosa

    Mason010 has described using video image analysis to measureparticle movement on the surface of isolated human inferiorturbinates[ This allows the direct measurement of the muc!ociliary transport rate and direction of graphite particles onthe surface of isolated mucosa[ This is largely a research tool\and has no clinical application as yet[

    Figure 1[ Flow chart for the management of patients with a suspecteddisorder of mucociliary transport[

    0887 Blackwell Science Ltd\ Clinical Otolarynoloy\ 12\ 277285

    Summary of the clinical assessment of patientswith suspected defective mucociliary transportrate

    In patients with symptoms and signs suggestive of defectivenasal mucociliary function\ the saccharin clearance testremains the most straightforward method of assessing nasalclearance[ Gamma scintigraphy is the most physiological testof mucociliary clearance but the equipment is con_ned toresearch units only[ If the measured time is less than twentyminutes then the nasal mucociliary clearance can be assumedto be normal[ Should the time be above 39 min\ then biopsyshould be performed to study the structure and orientation ofthe cilia\ and the immune status of the patient investigated[Tests should include levels of IgG\ and total immunoglobulin[Should the time be between 19 and 39 min then any conditionsthat appear treatable should be tackled either medically orsurgically and the test repeated[ If the clearance time is below19 min then no further assessment is required[ Should theclearance time be prolonged beyond 19 min despite adequatemedical or surgical treatment then the patient should be inves!tigated for abnormal cilia and immune de_ciencies[

    A su.ciently sensitive and reproducible way of measuringthe rheological properties of mucus has yet to be devised[ "seeFigure 1#[

    References

    0 SILBERBERG A[ "0878# On mucociliary transport[ Biorheoloy 16\184296

    1 LUCAS A[M[ + DOUGLAS L[C[ "0823# Principles underlyingactivity in the respiratory tract[ II] A comparison of nasal clear!ance in man\ monkeys and other animals[ Arch[ Otolarynol[ 19\407430

    2 SAKAKURA Y[\ UKAI K[\ MAJIMA Y[ et al[ "0872# Nasal muc!ociliary clearance under various conditions[ Acta Otolarynol[85\ 056062

    3 TAKEUCHI K[\ SAKAKURA Y[\ MURAI S[ et al[ "0878# Nasal muc!ociliary clearance in Sjogren|s syndrome[ Acta Otolarynol[ 097\015018

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