ClinicalAerosolInhalationCine-scintigraphyto ...jnm.snmjournals.org/content/36/8/1355.full.pdf ·...

abundant mucus in the airway. The mechanism of itspathogenesisremainsunknown.An abnormalityof the defense mechanism common to the upper and lower airwaysis suspected, since it is frequentlyaccompanied by chronicupper respiratory tract infection. The mucodiliaiy transport system is an importantdefense mechanism for theseairways. For diffuse panbronchiolitis, morphological orfunctional abnormality of ciliaiy motility has been documentedinJapan(Z3)butnotinanyothercountries.

Evaluation of the mucociliaiy transport system can beachieved by several methods. Aerosol inhalationcine-scintigraphy (AIcS), which was developed in 1981by Isawa etal. (4,5), permits noninvasive visual evaluation of the mucodiliaiy transport system under physiological conditionsbecause the movement of radiolabeled aerosol particlesinhaled into the lung and deposited on the respiratory tractis serially photographed and reproduced as dynamic images. We previously used this method to evaluate the mucociliaiy transportsystem in various pulmonarydiseases,including 16 cases of diffuse panbronchiolitis, and foundthat the mucociliany transport system was severely irnpaired in diffuse panbronchiolitis (6).

Formerly, diffuse panbronchiolitis was treated with antibiotics and steroids and produced a short-term beneficialeffect, but the prognosis remained poor because airwayinfectionusually recurred, resulting in respiratory failuredue to Pseudomonas aen@ginosainfection. In 1984, Kudoet al. (7) obtainedsuccessfultherapeuticresultstreatingpatients with diffuse panbronchiolitiswith low-dose, longterm erythromycin. Since then, many investigators haveexamined the effect of eiythromycin on diffuse panbronchiolitis (8—10).

Mikami et al. (11) studied neutrophil elastase activityand the physicalproperties of sputum from patients withchronic lower respiratory tract infection, including diffusepanbronchiolitis, who were undergoing eiythromycin therapy. They found that the diminished sputum viscosity observed in patients who responded to erythromycin therapycorresponded to a decrease in neutrophil counts and thatthe mucociliary transport system evaluated by the frog

This studyevaluatesthe mucoclllarytransportsystemin patientswithdiffusepanbronchiolitisusingaerosolinhalationdna-scmtigraphy(AICS).Methods:Forty-onesubjects,10healthycontrolsand31 patientswithdiffusepanbronchlolftls,werestudied.Inaddftion,themucodliaiytransportsystemwasevaluatedinIipatientswho had receivederythromycintherapyfor 3-8.3 yr.FollowingInhalationOf°°“‘Tc-humanserumalbuminaerosolfor3—Smmin a sfttingposition,the subjectswere @scedon theImagingtablein thesupinepositionandposteriorimageswereobtelneddynamicallyfor 20 seellrameover2 hrwitha gammacameralinkedto a digitalcomputer.The 360 20-secserialframeswereeditedintoa CinematographiCpresentationat 200-msecIntervals.Clinicalevaluationof the muco@y transportsystemwasbasedonthe bolusmovementOfradio@Iveaerosol from the mainbronchito the tracheaand the movementpatterns,whichweredMdedintofourtypesusingthemovementin the controlsas a standard@typeI): type I, rapidandsmoothmovement;type II, sbw movementtype III, stagnationat thecarina;andtype IV,completestasis.Results:M patientswithdiffusepanbronchiolitishadtypesIll andW,indicatingthatmucocillary transport system was severely Impaired. Of the 11patientsonerythromycintherapy,8 hedmovementpatterntypeIV and 3 had movementpatterntype Ill beforeerythromycmntherapy.In eightpatients(72.7%),movementpatternwas Im— totypeIorIIaftertherapy.Conclusion:Aerosolinhaletion dne-sclntlgraphyhelpsevaluatethe dinicalusefulnessOferythromycintherapyin diffusepanbronchiolitis.

Key Words: mucociliarytransportsystem;diffusepanbronchioittis;aerosol inhalationdne-Sdritlgrsphy erythromyan

J NuciMed1995;36:1355-1362

iffusepanbronchiolitisis an intractabledisease indigenous to Japan, as reported by Homma et al. (1). Thischronic inflammatory disease of the respiratory bronchiolanregion is characterizedby dyspnea and the dischargeof

ReceivedMay2, 1994;revisiona@ceç@edJan. 3, 1995.For correspondenceor reprintscon@ TenMo Imi, MD,Depeftiient of

Oncoradiology,Na'sMed@Univeisity,840Sh@yo-cho,K@hlhaaCity,NanProie@ure,634,@

ClinicalEvaluationOfMucocsliaryTransportSystem•1mwat al. 1355

Clinical Aerosol Inhalation Cine-scintigraphy toEvaluate Mucociliary Transport System inDiffuse PanbronchiolitisTeruhiko Imai, Yoshiaki Sasaki, Hajime Ohishi, Hideo Uchida, Shinsaku Ito, Keiichi Mikasa,Masayoshi Sawaki and Nobuhiro Narita

DepwlmenLc ofOncoradio1o@ and RadiOlOgy, and 2nd Department oflnteinal M&JCÃœZe,Nara Medical Unive,@ity,Kashthani, Japan

Patientno.Age @yr)SexVC (%)FEV@ (%)\@ (%)Pa02 (tori)Sputum vdume(mi/day)DOE(H-J)118M83.576.230.369.8202248M56.954.012.560.01503356F39.166.017.069.7503458M50.561.28.3622503559M72.954.513.065.4703660M49.547.558.762.71203760M97.170.216.272.0802865M83.372.758.366.3703967F66.870.72.367.112031074F70.582.635.269.92021184M60.071.154.165.73021213M76.283.331.171.54021379M67.050.628.987.05031462M72.781.6119.279.51221573M54.578.155.678.61621628M98.855.916.864212031759M45.071.023.167.23021861F44.442.03.842.31104‘1924M41.366.76.163.65032056M65.752.015.268.313032119F67.860.812.277.329032241M47.045.37.970.06032338M44.534.72.759.34022468F72.457.312.263.55032572M84.546.37.168.03032614M66.384.731.089.35022747M78.529.85.369.56032867F64.071.017.071.03022955F54.659.815.664.46033059M85.452.725.566.47033131M81.265.617.376.3402Mean52.165.961

.824.568.668.32.6DOE

= dyspneaon exertion; H-J =Hugh-Jonesclassification. SasTable 1 forother abbreviations.

TABLE IPulmonaryFunctionTests OfHealthy Controls

chiolitis and to investigate the change in the mucodiliarytransportsystem in 11 patients with diffuse panbronchioli

Subjectno. Age(yr) Sex VC (%) FEV@(%)@ (%) t15who had received long-term erythromycin therapy andI 66 M 94 1 whose clinical course could be followed. Before starting2 26 M 1@@ 55.0 the study, patients were fully instructed about the nature of3 52 M 125.9 85.4 80.0 the study and informed consent was obtained from all of4 27 F 96.7 95.0 76.6 them.5 25 F 99.1 95.0 82.46 34 F 128.0 84.9 69.77 49 F 126.2 82.7 68.38 48 M 98.4 83.6 55.2 METHODS9 63 F 16.5 88.3 83.6

10 51 M 105.6 80.8 55.1 . . .A total of 41 subjectsparticipatedm the study, 10 healthyMean 44.1 99.1 86.0 68.3 control subjects (Table 1) and 31 patients with diffuse panbron

_______ chiolitisdiagnosedbytransbronchiallungbiopsyoropen-lungvc = vitalcapacity;FEy1= forcedexpiratoryvolumein1sec. biopsy(Table2).Alsoincludedintheevaluationwere11patients

withdiffusepanbronchiolitiswhohadreceivedeiythromycintherapy for more than 3 yr (range3-8.3 yr; mean 6.6yr) and whose

palate method (12) was thereby significantly improved in mucociliaiytransportsystemcouldbefollowedbyAICS(Table2,these patients. Patients1—11).For allpatientsexceptPatient5, who almostfailed

This study was designed to evaluate mucociliary trans- to respondto the therapy,the sputumvolumewas decreased,port system by AICS in 31 patients with diffuse panbron- dyspneawas relievedand Pa02 was improved(Table3).

TABLE 2@1inicaIData of Patientswith DiffusePanbronchiolitis

1356 The Journal OfNuclear Medicine•Vol. 36 •No. 8 •August 1995

PatientD

raboc@EM

therapySputum

volume(mVday)

Pie- Post

DOE (H-J)Pa02(torr)Pre-

Post Pre- PostResponseno.(yr)therapytherapytherapy therapytherapytherapyscore16.320

102 169.899.2828.015003 160.080.9934.85003 269.774.0648.35003 162.276.1856.570

403 365.467.2266.0120303 162.782.0877.580102 172.073.8784.37033 166.378.7897.5120

303 267.168.96103.82002 269.971.64113.03052 165.772.67EM

= erythromydn;DOE=dyspneaonexertion;Age=before erythromycintherapyH-J= Hugh-Jones classification.

TABLE 3Follow-upOfPatientswith DiffusePanbronchiolftis(n = Ii)

AerosolInhalationC1n-ScintlgraphyRadioaerosols (particle size, approximate aerodynamic diame

ter 4—6 @m;airflow rate: 6 liter/mm) were generated from anebulizercontaining100mCi @“Fc-humanserumalbumin(HSA)in5 ml saline. In a sittingposition andwith theirnoses clipped, thesubjects inhaled for 3—5mm through the nebulizer mouthpieceuntil the total radioactivitywas over 300,000cpm (approximately2—3mCidepositedin the lungs)by normaltidalbreathing.Immediately after inhalation, the subjects were asked to rinse theirmouthswith waterto wash down the radioisotopesfromtheirmouths,oropharynxandesophagus.Theythenassumeda supineposition on the table, and posterior view images were obtaineddynamicallyat 20 sec/frame for over 2 hr with a low-energy,general-purposecollimatoranda largefieldof viewgammacameralinkedto a digitalcomputer.Afternine-pointsmoothing,the20-sec stored serial frames (360 frames) were edited into a cinematographicpresentationat 200 msec/frame.

ClinIcalEvaluationoftheMucocillaryTransportSystem

Thebolusmovementof radioactiveaerosol(BRAbolus)fromthe main bronchi to the tracheawas visually examined. The patternsof the BRAwereclassifiedintofourtypesusingthemovement in healthycontrol subjects (type I) as the standardtype (Fig.1). Types II—IVrepresent increasing degrees of impairedmucociliarytransport system function.

Type I represents smooth and rapid movement, in which the RIbolus ascends from the bilateralmain bronchi to the trachea in acontinuousflow immediatelyafter inhalationand upon reachingthe larynxis swallowed unconsciously(Fig. 2). Type II movementis slower and less smooth thantype I movement; the flow may beabnormal and disturbed, but the BRA ascends to the middletrachea in at least 2 hr. Type III represents stagnationof the RIbolus at the carina, althoughit ascends from the bilateralmainbronchi.TypeIVrepresentscompletestasisexceptby coughing.

Response ScoreTheclinicaleffectof erythromycintherapyin 11patientswas

assessedfromthedailysputumvolume,dyspneaon exertionand

Pa02.Theseparameterswerescored0to3, andimprovementwasjudgedfromthe totalscore(Table4).

RESULTS

Patterns of Radioactive Asrosol Bolus Movim.nt inHealthy Control Subjscts and Patients with DiffusePanbronchlolms

The BRA ascended smoothly and rapidlyfrom the mainbronchito the tracheain all healthy control subjects. Of the31 patients with diffuse panbronchiolitis, the RI bolusmovement was type IV in 29 (93.5%) and type III in theremaining 2. Thus, types Ill and N accounted for 100%ofthis group before therapy, indicating severe impairment oftheir mucociliary transport system function (Table 5).

Changes in the mucociliaiy transport system were exarninedin the 11 patientswho had undergone3 to 8.3 yr oferythromycin therapy. On average, they had been given800-1200mgorallyover 6.6yr. Beforeerythromycintherapy, 8 of the 11 had type N BRA pattern and 3 had typeIII. After erythromycintherapy, improvementto type I orII was obtained in eight patients (72.7%) and, thus, the

FiGUREI. ClassificationofBRAfromthemainbronchitothefrachaa

rapidand slow stagnation completesmooth movement at the stasismovement carina

1357Clinical EvalUatiOnOfMucoalsaryTransport System •1mwat al.

Parametera Score

SubjectsNumberPatterns

ofbolusmovementType

I TypeII TypeIllTypeIVHeaIthyCOntrOIS1010DPB31229HC

= healthycontrol;DPB= diffuse panbronchiolitls.

FiGURE2. Aerosolinhalationdne-sdntlgraphyin a healthycontrolsubject(typeI).Sinceitwasimpossibletoshow360framesinthis report,16 frameswere presented,I forevery24. The BRA ascendedsmoothlyandrapidlyinacontlnuousflowfrombilateralmainbronchito the trachea After reachingthe larynx, ftwas swallowedintothe stomsch.

mucodiliaiytransport system was significantlyimproved(Fig. 3).

eiythromycintherapy, and an 18-yr-oldboy who was theyoungest patient in the series.

Case ReportChest Radiograph and AICS before and after &ythro

mycin [email protected] 8 had obstructive ventilatory disturbance, with a daily sputum volume of 70 ml and respiratorydysfunction (VC = 83.3%, FEV1 = 72.7%).Arterialblood gas analysis revealed hypoxemia with a Pa02 of 66.3torr. The patient also had dyspnea on exertion. Chest radiographs showed overinfiation of both lungs due to astructure caused by edematous hypertrophy of the respiratory bronchiolarregion. Diffuse granularshadows dominated the middle to lower lung fields caused by centrolobular inflammation. Aerosol inhalation cinc-scintigraphyrevealed a highly irregulardistributionof aerosol and the

3 formation of multiple hot spots in both lungs immediately2 after inhalation. Diffuse obstructive ventilatory disorder inI both lungswas confinned.

3 TABLE 52 Patterns Of Radioactive Bolus Movement in Healthy ControlsI and Patients with Diffuse Panbronchiolltis

RelationshIpbatweenResponseScoreandRadioactive Aerosol Bolus Movement

The improvement in the mucociliaiy transport systemafter eiythromycin therapywas correlatedto the responsescore (Fig. 4). Mucociliary transport system impairment,however, persisted in two patients despite high responsescores: an 84-yr-old man who had the shortest history of

TABLE 4ResponseScore*

0

DalyvolumeofsputumImprovedmarkedly(almostnosputum)Improved(volumedecreasedby1i@3ormore)Improvedslightly(decreasedslightly)Nochange

Dyspneaonexertion(Hugh-JonesclassificatIon)ImprovedmaIICedIy(almostnodyspnea)Improved(decreasedmorethan1 grede)ImprovedslightlyNochange 0

Pa02Improvedmarkedly(increasedmorethan20torr) 3Improved 2Improvedslightly INochange 0

*Responsescore:assessedbyt@aiscoreofthreeparameters.

1358 TheJournalOfNudearMedians•Vol.36•No.8 •August1995

O@

.@ @..

0

1 2 3 4 5 6 7 8 9 10Durationof EM administration (ye&5)

0

Type of BolusMovement

Ill

lV@

:.@-‘@@

@fQ,.@@@@@@

DISCUSSION

Measurement of tha Mucocillary Transport SystemIn vivo observation of the mucociliaiy transportsystem

in the airway can be achieved by an invasive or noninvasive method. Invasively, a markersuch as a Teflon disc isplaced on the airway under bronchofiberscopic guidance,and its movement is observed by a bronchofiberscope (13)or a fluoroscopic image intensifier(14). In the noninvasivemethod, radioactive aerosol is introduced into the lung,and its movement (15) or clearance (16) is observed atregular time intervals. Many investigators have studiedmucocilialy transport system noninvasively, since it permits observation under physiologic conditions.

Clearance from the lung involves both mucodiliary andalveolar clearance. Aerosol particles deposited on cilia inthe respiratory tract are completely excreted within 24 hr.For strict calculation of mucodiliaryclearance, it is necessal.), to subtract the amount of alveolar deposition of partides at 24 hr from total clearance from the lung. Since thealveolar deposition of particles should be measured repeatedly at 24 hr, this method is too complicated. In addition,coughing is an interfering factor that may disturb clearancequantification. Furthermore, in severe chronic obstructivepulmonary diseases such as diffuse panbronchiolitis, intrapulmonary deposition of radioactive aerosol particlesimmediately after inhalation may be distributed diffuselyand irregularly in both lungs, or may form numerous hotspots. This has been estimated to have a non-negligibleeffect on the quantification of mucociliary clearance (17).

. :ImprovdCa..0 :SligMtyknprovd

no improved cui

FIGURE3. ChangesinBRA.

After 4.3 yr of eiythromycin therapy, sputum almostdisappeared. Respiratory function was improved (VC =124.3%, FEV1 = 78.3%). Pa02 was 78.7 torr in arterialblood gas analysis. Dyspnea on exertion was remitted.Chest radiographs confirmed the disappearance of thegranular shadows. Pulmonary overinfiation was also improved. Upon AICS evaluation, the previously seen hotspots were no longer observed and aerosol was evenlydistributed in peripheral parts of the airway (Fig. 5).

AICS before and after E,ythmmycin Thenipy. Beforeerythromycintherapy, the RI bolus ascended slightly fromthe main bronchi to the carina but ceased to move anyfurther (type III) (Fig. 6A), indicating that the mucociliaiytransport function was severely impaired. After eiythromycin therapy, immediately after inhalation, the BRA rapidly ascended from the bilateral main bronchi to the trachea and was unconsciously swallowed when it reachedthe larynx (type I) (Fig. 6B). Mucociliaiy transportsystemfunction was thus restored to normal.

FIGURE5. chestradiographandaerosolinhalationcine-ScIntigrambeforeandaftererythromycmntherapyin Patient8, a 65-yr-oldmanwitha responsescoreof 9. inhomogeneouspulmonarydistilbutionof redlosctiveaerosolsequalized,hotspotsdisappearedandchestradiOgraphicfindingsimproved.

ResponseScore 9-

..

6

3-.

0-@ I I IIv III II

Type of BolusMovement( post EM therapy)

FIGURE4. RelatIonbetweenresponsescoreandBRA.

ain@al EValUatiOnOfMucocilsaryTransport System •1mwat al. 1359

“.,@.@)O@6.@-

O:@5

FiGURE6@Aerosolinhalationclne-sdntigraphyinPatient8.(A)Beforeerythromycm therapy, the RI bolts ascended onlyslightlyfromthemainbronchitothecarinabutceasedto moveanyfurther,suggestingadvancedimpairmentofthemucociliaiytransportsystem(typeill)(B)Altertherapy,immediatelyafter inhalationthe RI bolusrapidlyascendedfromthebilateralmainbronchito thetrachea(typeI).

The rate of BRA in the airway can be measured by themethod of Yeates et al. (15). In our previous study of 116patientswith various pulmonarydiseases (6), the measurement of RI bolus was frequently precluded due to a diversity of abnormalmovement patterns such as spiral movement, regurgitationand stasis, while the ratewas relativelystable (3.2—10.9mm/rn;mean 8.0 mm/m)in healthy control

subjects. In this study, we therefore decided to classify theBRAfromthe mainbronchi to the trachea into four majorpatterns, as observed by several nuclear medicine specialists. We allowed a full 2 hr for such observation. We sawno reason to shorten the observation time since we basically adopted the method of Isawa et al. (4,5) and becausethe BRA thatmightnot be visualized duringthe firsthalfof

1360 The Journal OfNuclear Medicine•Vol. 36 •No. 8 •August 1995

B£2?@0£2@[email protected]@@3Q3@6£@c@

observation was expected to appear during the latter half.During the observation period, the patients assumed a supine position on the table and the chest was immobilized.We have performedM@S without any problems on morethan 200 patients. The patients were requested to refrainfrom coughing, but even if they did, any RI bolus movement induced by coughing could be easily distinguishedwhen carefully observed in cine-scintigraphy.

MucociliaryTransportSystemInDiffusePanbronchlolitis

Because diffuse panbronchiolitis is a disease indigenousto Japan, diffuse panbronchiolitisin the mucociiary transport system has not been documented in other countries.Our earlier study using AICS (6) showed that the mucociiaiy transport system in chronic lower respiratory diseases such as bronchiectasis, chronic bronchitis and diffuse panbronchiolitisis impairedby various abnormalitiesand that the mucociliary transportsystem is most severelyimpairedin diffuse panbronchiolitis. In this study, the mucodiiary transport system before erythromycintherapy inthe 31 patients with diffuse panbronchiolitiswas extremelyimpaired (type IV in 29/31 [93.5%] and type III in 2). Indiffuse panbronchiolitis, the concentration or activity ofneutrophil elastase in the airway has been found to beelevated because of persistent infectionof the lower airway(18). Elastase has a strong proteolytic action and is knownto induce airwayepithelial injury(19), to inhibitcilia movement (18,20) and to increase airway mucus discharge. Abnormality of both mucus and cilia results in mucociiarytransportsystem impairment.

Efficacyof ErythromyclnTherapyInDiffusePanbronchiolitis

Comparedto other lower respiratorytract diseases, diifuse panbronchiolitis had been considered an intractabledisease with poor prognosis leading to respiratoryfailurewith a largeamountof sputum in the airway. Recently, theeffectiveness of low-dose, long-termerythromycintherapyhas been established, and the prognosis has been dramatically improved. Earlierstudies have suggested that erythromycin augments the host's defense by suppressing thedevelopment of infection through inhibition of bacterialattachment,by inhibitingelastase andprotease production,by elevating the activity of naturalkillercells or by increasing the production of various cytokines (21—23).

In all patients except Patient 2, the clinical symptoms(sputum volume, dyspnea on exertion and Pa02) and mu

codiiary transport system functionwere improvedand, insome patients, recovery to a normal condition was obtamed. In one of the two patientswhose mucociliarytransport system remained impaired despite improved clinicalconditions, the history of erythromycin therapywas short(3 yr), but the symptoms were expected to improve withcontinuation of this therapy; many patients have responded to the therapy after receiving it for 3 yr. For theother patient, erythromycin therapy was administeredfor6.3 yr. Although the total response score in this patientwas

8, whichis highenoughto be interpretedasmarkedlyresponsive, the mucociiary transport system impairmentremained unimproved. Both mucus and cilia are mutuallyinvolved in the mucociiary transport system. As the patient is only 18 yr old, this is a case of early onset ofmucociiary transportfunctionaldisorder. Therefore, morphological or functional abnormality of the ciiary motilityitself is suspected. Electron-microscopic evaluation or examinationof diary function would be requiredif the current condition persists.

The clinical effect of erythromycintherapy is characterized by the improvementof both subjective symptoms andobjective symptoms. In patients highly responsive toerythromycin therapy, mucociiary transport function hasbeen estimated to reach a plateau in approximately 6 mo.In patients with progressive pulmonarydisease, the symptoms have been estimated to improve 1 or 2 yr after erythromycin therapy. Even after 17 mo of treatment, the mucociiary transport system was only slightly restored inthese patients despite considerable improvement of theclinical symptoms (24). Of the present series of patientswho had undergoneerythromycintherapy for more than 3yr, however, clinical symptoms and mucociiaiy transportfunction were simultaneously improved in those who responded well to the therapy. Interestingly, in some of thepatients, mucociliary transport system impairment persisted while clinical symptoms improved;yet, mucociiarytransport function did eventually improve, although in adelayed manner, with continued erythromycin therapy.This fact demonstrates that mucociiary transport systemevaluation by AICS is important as a subjective assessment of the effect of erythromycintherapy on mucociliarytransport system in diffuse panbronchiolitis. It also suggests that mucociiary transport system evaluation byAICS may help in determining the time of eiythromycintherapywithdrawalor the posttherapeutic course.

We previously used AICS to evaluate the effects ofdrugs on mucociliary transport system (25). More extensive M@S applicationto clinical research is expected, suchas assessing mucociiary transport system impairment byradiotherapy and analyzing the pathology of pulmonaryatypical mycobacteriosis, which may be related to mucociiary transportsystem impairment.

CONCLUSIONThe mucociiary transportsystem in 10 healthy control

subjects and 31 patients with diffuse panbronchiolitiswasevaluated using AICS. In addition, mucociiary transportsystem was evaluated in 11 patients who had receivederythromycin therapy before participating in this study.The mucociliary transport system, severely impaired inpatients with diffuse panbronchiolitisbefore therapy, wasimproved significantly after therapy. AICS is a usefulmethod for evaluatingthe clinical effectiveness of erythromycin therapy in patients with diffuse panbronchiolitis.

ClinicalEvaluationof MucocdiaiyTransportSystem•Imaiet ai. 1361

14. Friedman M, Scott FD, Poole DO, et al. A new roentgenographic methodfor estimating mucus velocity in airways. Am Rev RespirDis 1977;115:67-74.

15. Yeates DB, Aspin N, Levison H, Jones MT. et al. Mucociliaiy trachealtransport rates in man.JAppi Physiol 1975;39:487-495.

16. Morrow PE, Gibb FR, Gazioglu KM. A studyofparticulate clearance fromthe human lungs. Am Rev RespfrDis 1967;96:1209—1221.

17. Wanner A. Clinical aspects of mucociliaiy transport. Am Rev Respir DLc1977;116:73—125.

18. Ninomiya H, Ichikawa Y, Koga H, et al. Elastase activity in bronchoalveolarlavage fluidfrom patientswithdiffuse panbronchiolitis. KansenshogalasZ.ass!zi1991;65:672—680.

19. Tegner H, Ohisson K, Toremaim NO, et al. Effect of human leukocyteenzymeon tracheal mucosa and its mucociliaryactivity.Rhinology1979;17:199—206.

20. Smallmann LA, Hill SL, Stockley RA, et al. Reduction of ciliaiy beatfrequencyin vitro by sputum from patients with bronchiectasis:a serineproteinaseeffect. Thorax1984;39:663-667.

21. Kits E, Sawaki M, Oku D, et al. Suppression of virulence factors ofPseudomonasae,vgznosaby erythromycin.IAntimicmb Chemother1991;27:273-284.

22. MikasaK, Kits E, SawakiM, et al. The anti-inflammatoryeffectof erythromycinin @yn@c@[email protected] mice.I AntimiCrabChemother1992;30:339—348.

23. Tanakadate A, Sasaki K, Nemoto H, et al. Effectoflong.term, low doses ofeiythromycin on diffuse pan-bronchiolitis(DPB).I Med Soc TohoJpn1991;38:211—220.

24. Imai T, Ohishi H, Katada H, et al. Bronchoscopic findings and aerosolinhalationcine-scintigraphyin cases with diffusepanbronchiolitistreatedeffectivelyby erythromycin.IIpn Soc Broschology1990;12:382-390.

25. Ohnuki M, Ito S, Imai T, et al. The immediate effect of terubutaline salphate, a @-adrenoreceptor stimulating agent, on the mucociliaiy transportsystem.Jpn I ChestDi@1990;49:536-541.

Scatter(Continuedfrom page 5A)

Happily, Thomas' foreboding evoked by Mahier's Ninth Symphony hasnot been sustained by events since the publication ofthat essay. In seekinginspiration in music, I prefer the message ofBeethoven's Ninth Symphonyin which the promise ofthe first movement, darkened by the brooding ofthe second, is ultimately fulfilled in the fourth. The exhilaration andoptimism are explicitly expressed in the words of Schiller which becomethe text for the final movement. This renaissance ofhope occupies mythoughts as I recall the dark days of5O years ago and the progress sincethen in using atomic energy.

Stanley J. Goldsmith, MD, Editor-in-ChiefTheJournal ofNuclear Medicine

August 1995

1362

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The Journal OfNuclear Medicine•Vol. 36 •No. 8 •August 1995