304P.full

Thorax 1990;45:304P-344PProceedings of the British Thoracic Society The 1989 winter meeting of the British Thoracic Society was held on 7 and Kensington Town Hall, London 8 December at C

Thorax 1990;45:304P-344P

Proceedings of the British Thoracic Society

The 1989 winter meeting of the British Thoracic Society was held on 7 and

Kensington Town Hall, London

8 December at

Computed tomographic scans of the

lung help distinguish Pneumocystis

carinii pneumonia from Kaposi's

sarcoma

RF MILLER, AB MILLAR, P SHAW, SJG SEMPLE

Departmentof Medicine, UCMSM,

Middle-sex Hospital, andDepartment of Radiology,

University College Hospital, London The

differentiation between Pneumocystis carinii

pneumonia (PCP)andKaposi'ssarcoma can

be difficult if an HIV positive patient

presents with alveolar consolidation and/or

interstitial shadowing on the chest

radio-graph (CXR).We havecomparedthe CXR

and thoracic computed tomographic (CT)

appearancesof 31HIVpositivemalesduring

acuterespiratoryepisodesin ordertoevaluate

the role of CT indistinguishingPCP from

Kaposi'ssarcoma.Ingroup 1sixteenpatients

had PCP Eleven patients in group 2 had

Kaposi'ssarcomaand ingroup3fourpatients

had both PCP and Kaposi's sarcoma.Both

CXR and CT were categorised as being

normal (N)orshowing one or more of the

followingabnormalities: interstitial

shadow-ing (INT); alveolar consolidation (ALV);

intrapulmonary nodules < 1 cm diameter

(NOD);mediastinaland/orhilar

lymphaden-opathy (LN); pleuraleffusions(EFF); cystic

air spaces (C); and on CT bronchial wall

thickening (BT) Results were as follows:

Interstitialshadowing,alveolar consolidation

and intrapulmonary nodules do not help

distinguish Kaposi'ssarcomafrom PCP The

presence of bronchial wall thickening and

cysticairspacessuggestadiagnosisof PCP

whereas pleural effusions and

lymphaden-opathy suggests Kaposi's sarcoma. These

abnormalities,whicharebetter demonstrated

by CT, helpdistinguishPCP from

intrapul-monaryKaposi'ssarcoma.

Pneumocystis carinii: attempted

isolation from induced sputum and

bronchoalveolar lavage specimens of

non-HIV infected individuals using

immunofluorescent stains

TR LEIGH, J WIGGINS, J MIDGELEY, N FRANCIS,

DC SHANSON, TW EVANS, JV COLLINS

Westminster and Brompton Hospitals, London

Pneumocystiscarinii(PC)maybea

Pediatrics 1978;61:35) and the clinical

sig-nificance of detecting PC in induced sputum(IS) andbronchoalveolar lavage fluid (BAL)

by highly sensitiveimmunofluorescent (IF)stains may be questionable (Leigh, BTS,summer 1989) We therefore attempted toisolate PC cysts in IS and BALspecimens ofnon-HIV infectedsubjects IS was obtainedfollowing inhalation of 30 mls ultrasonicallynebulised (Devilbissultraneb 99) hypertonic(3%)saline A standard BAL technique was

used All samples were promptly stainedusing a highly sensitive monoclonal IF stain(NorthumbriaBiologicals) Twelve IS (fromhealthy volunteers) and 12 BAL (frompatients investigated for possible bronchialcarcinoma) samples were studied; cytologyconfirmed that all specimens sampled the

lowerrespiratory tract PC was not detected

inany samples of IS or BAL This suggeststhat, while PC may be a commensal in non-HIVinfected individuals, it is not present insufficient numbers in IS and BAL to bedetected by IF PC detected by this technique

is likely to be of clinical significance andstudies of asymptomatic HIV individuals are

needed

Continuous positive airways pressureventilationas analternative to mechan-ical ventilation for respiratory failureassociated with Pneumocystis cariniipneumonia

RF MILLER, SJG SEMPLE Department ofMedicine, UCMSM, Middlesex Hospital,London Despite treatment up to 20% ofpatientswithPneumocystiscarinii pneumonia(PCP) will develop respiratory failure; in thisgroup ofpatients mortality is high despitetheuseof mechanicalventilation Wachter RM et

al.AmRevRespirDis1986;134:891.We haveused continuous positive airways pressure(CPAP) ventilation as an alternative tomechanical ventilationinpatientswith PCPwhodeveloped respiratory failure refractory

tosupplemental oxygenviafacemask.EightHIVpositive males with PCP received CPAP

via a tight fitting face mask using a flow

generator circuit Onadmissionpatientswere

treated with intravenous co-trimoxazole (7patients)orpentamidine(1 patient);admis-sionbloodgases breathingroom air werePao,

322-88-9 (mean 58-6) mmHg CPAP was

started 1-15(mean 7) days after admission

becauseofincreasing respiratory distressand

deteriorating blood gases (Pao2 35-2-78-5

(mean53-2)mmHgwhilereceiving oxygen

viaface mask atFio206).CPAPwasstarted

atFio20-6andPEEP5cmH2O(7patients)

and 10 cmH2O (1 patient) Sevenpatients

showed animprovementinarterial

oxygena-tion(Pao250-7-96-4(mean 78-4) mmHg) a

meanof four hours afterstartingCPAP One

patient died one hour after commencingCPAP with deteriorating oxygenation,

hypercapnia,andacuterightheartfailure;at

necropsy there was no evidence of thorax The sevenpatients made a completerecovery.CPAP was continued for 2-7 (mean4)days and theyweresubsequently weanedoff it No major complications (pneumo-thorax, heart failure) were seen; three patientsinitially found the CPAP mask claustro-phobic but persistedwith treatment Ventila-tion via mask CPAP has been foundtobeauseful means ofimproving oxygenation in

pneumo-patients with PCP who developrespiratoryfailureandmay obviatetheneed for intuba-tion and mechanical ventilation in such

patients

Aerosol pentamidine as prophylaxisagainst Pneumocystis canrniipneumonia for persons infected withhumanimmunodeficiency virusELC ONG, KR NEAL, EM DUNBAR, BK MANDALRegional Department ofInfectious Diseases andTropical Medicine, Monsall Hospital, NewtonHeath, Manchester Pneumocystis cariniipneumonia(PCP) develops in about 80% ofpatientswith theacquiredimmunodeficiencysyndrome (AIDS); in half of these patients

the infection recurs within 12 months

Thereforeprophylaxis using inhaled midineaerosol is onemethod of preventionagainst subsequent episodes (secondary pro-phylaxis) or initial episode (primary pro-phylaxis) foraHIVinfected personwhohas

penta-never had PCP We report our currentexperience of treating30malepatients withAIDS or symptomatic HIV infection(median age 36 range 25-56) with weeklynebulised pentamidine isthionate 600 mg

dissolved in 6 ml ofsterile waterusing an

AntibioticTee tube(System 22)andAcornnebuliserwith anOptimistfilter(Medic-aid)acting as a baffle delivered at 8I/min pressur-

isedoxygen.Thisgeneratedaerosoldroplets

witha massmedianaerodynamicdiameterof

1 2pm (GSD29)and89% were less than

3 9pm.On 31August1989 15patientswere

receiving pentamidine as secondary phylaxis Their mean duration of treatmentwas10-8months(range4-22).Tenpatientswhohave AIDS andfive symptomatic HIVpatientswhose CD4+ counts were < 200/

pro-mm3weretreated with this asprimary phylaxis.Their meandurationoftreatmentwas 9-6months(range4-16).Inbothgroups

pro-there were 22patientswho have been

receiv-ingtreatmentfor more thaneightmonths Nonew cases orrelapsesof PCP have occurred ineithergroup ofpatients There were three

otherpatientsthat had PCPpreviouslyandreceived pentamidine as secondary pro-phylaxisfor a meanduration of10 months

(range 9-12) and had since died of othercauses All patients were receiving

zidovudine in varying dosages No serious

drug related adverseeffects wereobserved.Our experience suggests that the dose and

Proceedings

frequency of inhaled pentamidine is a

sig-nificant factor in determining relapse and

initial rate of PCP among HIV infected

persons.

Clinical and radiological features of

recurrent Pneumocystis carinii

pneu-monia in patients with the acquired

immunodeficiency syndrome (AIDS)

TW EVANS, JV COLLINS Westminster and

Brompton Hospitals, London The classical

presentationof firstepisodesofPneumocystis

cariniipneumonia(PCP)is wellrecognised

However, atypicalfeaturesmay occur inup

to300Oofpatients (DeLorenzo-Chest 1987;

91:323) and the features of recurrent PCP

clinical and radiological presentation of

recurrent episodes (more than six months

apart) ofmicrobiologically proved PCP in

years) with AIDS All had cough and 8/9

presenting symptoms (sputum production,

300o ofpatients in each episode but were

inconsistentinan individual In firstepisodes

8 2(1-32)and2-4(1-8)weeksrespectively)

were longer whilst atypical chest radiology

(asymmetry, pneumothorax, honeycombing)

waslessfrequent (2of 9 and 5 of 9

respec-tively).AdmissionPao,(means (range) 11-3

(96-17)and 10 1(85-124)kParespectively)

radiological features of initial and second

episodes of PCP are not comparable in an

cannot be used for diagnosis and

microbiological confirmation is mandatory

whenrecurrentPCP issuspected

Pulsemegadosemethylprednisoloneas

adjuvant therapyfor the treatment of

Pneumocystis carinii pneumonia

RF MILLER, SJG SEMPLE Department of

Medicine, UCMSM, Middlesex Hospital,

London Initial reports suggested that

methylprednisolone in doses of160-240mg/

daywas useful adjunctive therapy in those

patients withPneumocystiscarinii pneumonia

(PCP) who developed respiratory failure

MacFadden DK et al Lancet 1987;i:1477

beenquestioned Clement Metal Am Rev

Respir Dis 1989;139:A250 Inan open

pros-pective study we have used mega dose

methylprednisolone in 26 HIV positivemales

with PCPwho became hypoxaemic despite

patients were treated with intravenous

co-trimoxazole, five nebulised pentamidine

(NP), and one intravenous pentamidine

326-96-8 (mean 65-3)mmHg

dyspnoea/radiographic appearances. One

gram of methylprednisolone was given by

intravenous infusionover onehouroncedaily

NPchanged tointravenous co-trimoxazole

Immediately before starting

methylpredn-isolonePao2 (room air)was29-4-66-9 (mean

452)mmHgand 24-36hours after the first

dose ofmethylprednisolone Pao2 (room air)

was 53 7-113 1 mmHg Twenty threepatients (880 ) responded and subsequentlyfullyrecovered; three patients died,oneafter

one dose ofmethylprednisolone despiteanimprovedPao2, thetwoothers died afterone

and two dosesofmethylprednisolonetively, withworseninghypoxaemia No sideeffectswere seenacutely (dyspepsia/gastro-

respec-intestinal bleeding/sepsis) but one patient

had areactivation of chronichepatitis B three

weeks after the methylprednisolone Pulse

megadosemethylprednisoloneappearstobe

auseful adjuvant therapy for patients withPCP who deteriorate and become hypox-

aemicdespite conventional therapy

BTS study of severe community

acquired pneumonia in the intensive

cover-adultsadmitted in 1987 to an intensive care

unit (ITU) with adiagnosis ofcommunity

acquired pneumonia wasundertaken Fiftynine patientswerestudied, ofwhom34(58%)weremale.Themean agewas54 years (range

19-76) with 38(64%) < 65 and 18 (34%)

<44 years Twenty three (39%) had

previously been fit Mediansymptomtion beforehospitaladmission was five days

dura-(range1-64) On hospital admission43(73%)had two or more ofrespiratory rate > 30,

diastolicblood pressure< 60and blood urea

> 7mmol/l Forty (64%)weretransferred totheITUwithin48hours ofhospital- admis-sion,buteightwereadmittedtothe ITU only

after a cardiorespiratory arrest-six (75%)

of these died A microbial aetiology was

identified in 35(59%). Pathogens included

Streptococcus pneumoniae (11), Legionellapneumophila (7), Haemophilus influenzae (7),

Mycoplasma pneumoniae (4) and influenzavirus(3); twoofwhich were complicated by

infection with Staphylococcus aureus Dualinfectionwas presentin 11(19%)cases.Fiftytwo (88%) received assisted ventilation(IPPV),1 (19%)receivinganFio,of1-0and

28 (48%)positive end expiratory pressure

Twelveof18(67%)still receiving IPPV at 14

dayssurvived Complicationswere recorded

in 43(730%),but 30 (51%)survived,

includ-ingallfourpatientswith Mpneumoniae andtwoof threewith influenza virus infection

The median duration of hospital stay in

survivors was one month Only 14 (24%)

madeacompleterecovery

Clinicalusefulness oftheantineutrophilcytoplasmicantibodytest

CMB HIGGS, MB SAMPSON Chest Unit andDepartment of Immunology, Royal UnitedHospital, Bath A recent editorial (Thorax

1989;44:369-70) states that a positive result

in the antineutrophil cytoplasmic antibody

test (ANCA) cannot replace the aggressive

pursuit of a tissue diagnosis in Wegener's

granulomatosis(WG) From a retrospectivereview of all 44 requests for ANCA in theBath Health District during March 1987-

September1988, we haveassessed the role of

ANCA indiagnosingorexcluding WGandtheincidence of falsenegative andpositive

results ApositiveANCA wasdefinedasthecharacteristic granular cytoplasmic fluores-cence pattern on ethanol fixed neutrophilcytospin preparations present at dilution1:80.There werenine positivecases:4M 5F,

age 30-81 years,time from onset todiagnosis

2-200 months All had clinical featuresentirely consistentwiththediagnosis of WG

Eight had a tissuebiopsy (4 nasal,2renal,2

lung);inonlyone (nasal)wasthe histologyregarded as diagnostic of WG, the others

being non-specific inflammationor

crescen-tic glomerulonephritis In three cases thecombination ofclinical features and histologyhadestablished thediagnosis, but in sixcasesthepositive ANCA established thediagnosisand often ledto achange intreatment.Ofthe

35negativecases,threehadpreviously nosed WG now in clinical remission, 32

diag-eventually had other confirmed diagnoses(Churg-Strauss 1, lymphomatoid gran-

ulomatosis 1,connective tissue disorders 6,

glomerulonephritis6,others21).Therewere

thereforenofalse positiveornegativeresults

in this study Therewere no cases of WG

(from diagnostic coding index) diagnosed

withoutANCA testing We suggestthat in

clinicalpractice, forthediagnosisofWG, the

ANCAtest, asdefined above, could replace

tissue biopsy and its reliability is so farexcellent

Progressive lungfibrosis 14 years after

childhood BCNU chemotherapy:

clin-icalandphysiologicalfeatures

BRO'DRISCOLL,HRGATTAMANENI, PMTAYLOR,

AA WOODCOCK Wythenshawe and ChristieHospitals and University of Manchester

BCNU (carmustine) is a cytotoxic drugwhichismostcommonly used to treat malig-nantgliomas Likebleomycin and methotrex-ate, it is a recognised cause of acute lung

fibrosis, whichmay appear up to two years

after the completion of therapy Thereportedincidence of this complication ranges from1% to20% (Weiss RBetal,Cancer Treat-mentReviews1981;8:1 11).Between1972 and1976,30children(age 2-16 years)with malig-

nantgliomasweretreatedwith surgery,

cran-ial irradiation and BCNU chemotherapy

Thirteenpatients died of their braintumour

andtwopatients died of lung fibrosiswithinthree yearsof completingtherapy A furtherfour patients have died of"delayed" lung

fibrosis 8-13 years after BCNU

chemo-therapy Of 11 long term survivors, eight

were available for investigation (mean 14years posttreatment, range13-17).Onlytwohad any respiratory symptoms (breathless-ness) and nonehad fingerclubbing or lung

crackles.However,allsurvivorsstudied had

arestrictive spirometric defect (mean FVC

52% ofpredicted,range21-81%).The TLCO

wasreduced (mean 58% of predicted, range

28-78%) but the Kco was well preserved

(mean1 17%ofpredicted,range 93-137%)

InonecasetheFVC had not changed over afive yearperiod,but in three other cases theFVC had declined by 0-1 to 0-8 litres over one

tosix years.We conclude that "delayed" lungfibrosis is a frequent (possibly universal)consequence of BCNU chemotherapy inchildhood This novel form of lung fibrosis

Hydrocortisone myopathy in acute

severeasthma

CD SHEE Chest Clinic, Medway Hospital,

Gillingham,Kent Inonehospitalover a15

month period, four out of nine patients

ventilated foracute severeasthmadeveloped

acute hydrocortisone myopathy All nine

patientshad beensedated,andparalysedwith

vecuronium All received intravenous

sal-butamol and aminophylline, nebulised

sal-butamol,and intravenoushydrocortisonein

doses under 1-0g/day Duration of

ventila-tionwas6-19daysinmyopathic patients(3F,

IM)and 2-9daysin the others(5F).Affected

patients hadseveregeneralised weaknesswith

normal reflexes and sensation Complete

recovery took 1-6 weeks Whenmyopathic

and non-myopathic ventilated asthmatics

were compared, there was no clearcut

dif-ferencewithrespect to age, sex, typesofdrug

used, serum potassiumlevels, total dose of

vecuroniumbromide,or meandailydosesof

hydrocortisone Duration of paralysis was

comparedto seeifneuromuscular blockade

might contribute to the development of

myopathy.Although myopathic patientshad

generally beenparalysed and ventilated for

longerthan the unaffectedsubjects,therewas

anoverlapbetween thetwo groups.Themain

difference between the groups was in total

doses ofhydrocortisone.Myopathic patients

all received > 5 0g hydrocortisone (range

5-4-10-2g) and the others <40g (range

09-3 5g) Hydrocortisone myopathy is

probably not an idiosyncratic reaction but

rather isdose related.Myopathycan occur on

< 10g/dayhydrocortisone,andevenwithas

littleas5-4ggivenoversixdays

Methotrexate in steroid dependent

asthma:aplacebocontrolled trial

RJ SHINER, AJ NUNN, F CHUNG, DM GEDDES

Brompton Hospital, London Sixty nine

steroid dependent asthmatics from 11

specialist centres participated in a

ran-domised, double blind, placebo controlled

trial All patients had been treated with a

minimum of 7-5mg, mean(SD)14-17(7-10),

ofprednisolone/day, for at least a year in

addition to inhaled steroids and

broncho-dilators Patients took 15mgmethotrexateor

placeboonce weeklyfor24weeks Patients

were seen atfourweeklyintervalsbythesame

physicianwho reduced thedaily prednisolone

dose by 2-5mg, depending on satisfactory

diarycardcriteria andspirometry.All other

treatment remained unchanged

Pred-nisolonedosagewascompared between the

two groups over twofourweekperiods,run

in, and 20-24 weeks of treatment.

Pred-nisolone dosewas reduced by 50% in the

methotrexate treatedgroup andby 14% in

theplacebogroupwhencomparedwith the

run in (p <0-005) Symptom assessment,

frequency of night waking, and peak flow

measurementsdidnotsignificantly changein

eithergroupduringthe trial Abnormalliver

functionwasnoted in12/38,whichimproved

orresolvedinsevendespitecontinuation of

therapy and persisted orworsened infive

Gastrointestinal side effects were severe in

twoof38 andmilder and self limitingin six.

Therewere nohaematologicalorpulmonary

complications of methotrexate therapy

Methotrexate mayhave a role in reducing

systemicsteroidrequirementin thisgroupof

patients

(Supported by a grant from the Asthma

ResearchCouncil.)

Management of recurrent malignant

pleural effusion: what are wedoing in

the UK?

LG MCALPINE, G HULKS, NC THOMSONDepartment of Respiratory Medicine,WesternInfirmary, Glasgow Malignant disease isestimatedto accountfor 25-50% ofcasesofpleural effusion These effusions are oftenlarge and recur after simple aspiration.

Patients whoarereasonably wellmaybenefitfrom pleurodesis to prevent the need forfrequent thoracentesis.Several techniques ofpleurodesis have been described andmany

agents havebeen subjectedto trial yetthe

approach of practicing clinicians to thisproblemisnotknown.We aimed todeter-

mine the views of UK clinicians on their

approach to the management of recurrentmalignant pleural effusion and pleurodesisby

means of a postal questionnaire The 448

clinicians receiving questionnaires consisted

ofphysicians withaninterest inrespiratorymedicine (n = 150),generalphysicians with-out arespiratory interest (n = 173),thoracicsurgeons (n =48) and general surgeons(n =77) Therewas anoverallreskonse rate

of56%. Only 18 generalsurgeonswhosaw

> 2cases/year responded and44%of theseopted for repeated aspiration alone; furtheranalysis of this group was not performed

Most respiratory physicians (76%) wouldperform pleurodesis insuchpatientsbutonly

30%of generalphysicianswouldthemselves

do likewise,withafurther33%referring thepatient to a respiratory specialist andonly

15% managing such patients with repeatedaspiration alone Thoracicsurgeons under-

take pleurodesis (81%) and this is usuallyperformedundergeneralanaestheticbyboth

juniorandsenior staff.Sixty eightpercentof

respiratory physicians and 90% ofgeneralphysicians invariably delegate the task to

juniorstaff.Thoracicsurgeons use an

inter-costal tubedrain, usuallywithsuction, while

atube drainwasroutinely usedby only54%

and 32% ofrespiratory andgeneral

physi-ciansrespectively.Themajorityof drainsare

removedwithin 24 hours.Tetracycline wasthe agent selected for 2/3 cases ofmedical

pleurodesis while talc was the commonestsurgicalchoice.Local anaestheticwasadded

tothepleurodesisagentby52%and64%of

respiratory and general physicians tively The majority of respondents con-sidered the procedure to be moderately

respec-uncomfortable buteasilymanaged with

anal-gesiaandtobereasonablyeffective

(Supported by an award from the Chest,

Heart,andStrokeAssociation.)

Review of open lung biopsy in 431patientswith diffusepulmonarylesions

V TSANG, P GOLDSTRAW Brompton Hospital,London Patients with diffuse pulmonary

lesionscanpotentiallybenefitfromthetologicalinformationprovidedbyopenlungbiopsy (OLB), performed via a short

his-inframammaryincision(Venn etal Thorax1985;40:931) To re-evaluate thediagnostic

indicationsandbenefits,the entire seriesof

431 patients undergoing OLB between July

1979andAugust1989wasreviewed.Therewere256male and 175femalepatients,witha mean ageof 55years(range5 monthsto80

years) Twenty four patients (5 5%) were

immunocompromised (haematologicalmalignancies17;bonemarrowtransplants 6;

hypogammaglobulinaemia 1) One hundred

and twenty five patients (29%) were onsteroidtherapyatthe timeof operation OLB

provided diagnostichistological material in

409 of the 431 cases (95%), cryptogenic

fibrosing alveolitis and sarcoidosis beingthetwomostcommonfindings.Adiagnosis

was obtained in 20 of the 24 compromisedcases.Aninfectious agentwas

immuno-identified in four (17%) of the patients

(cytomegalovirus 1; Pneumocystis carinii 2;

Aspergillus fumigatus 1). Twelve patients

(2 7%) died following OLB, with three

(12-5%)intheimmunocompromised group.All thesepatientswereveryillpreoperatively,andonlyoneofthedeathswasdirectlyrelated

to the surgical procedure Twenty onepatients (5%)suffered complications related

tothe OLB (wound infection 11; thorax9;haemothorax 1), with no differencebetween the immunocompromised and the

pneumo-non-compromised groups OLB has beenshowntobeadefinitivemeansofestablishing

adiagnosisinchronic progressive pulmonary

diseases,withminimalrisk.Inthe

immuno-compromised patients OLB can be med safely with a significant therapeutic

of Edinburgh Mediastinal lymph node

involvement by tumour has an important

bearingonprognosisinlungcancer

(Moun-tain C.AnnThoracSurg 1977;24:365)

Imag-ingtechniqueswhich measuresize of tinallymph nodesareoften usedas a non-

medias-invasive method ofdeterminingmalignancy(eg Glazer GMetal AJR1984;147:1101-5)

We have therefore pathologically examinedmediastinal lymph nodes in patients withlungcancer aspart ofaprospective study ofthe value of mediastinal diagnosticimaging

in the detection of mediastinal lymph node

metastases.Fifty-six patients with potentiallyoperable histologically proven bronchogeniccarcinoma underwent thoracotomy All

accessible mediastinal lymph nodes (N2)

were removed at operation and fixed in

formalin The maximum node diameterwas

measured and each nodewas thenweighedandprocessed intotofor histologicalexamin-

ation In those which were malignant theproportion ofthenode replacedbytumourwasestimatedusingasimple pointcountingtechnique Forty-two percentof themalig-

nant mediastinal nodes (n = 31)measured

less than 15mm(maximumdiameter) while

43% ofbenign nodes measured 15 mm ormore.Only23%oflymph nodesmeasuring

15 mm or more weremalignant.Inthis seriesthere isnoevidence thatmalignantmedias-

tinal lymph nodes are larger than benignnodes These observations help explainthe

limitations of imaging techniques, whichmerely record lymph node size in"detecting"mediastinallymph node metastases

Survivalandprognosisfollowing

resec-tion for bronchogenic carcinoma

MA KADRI, JE DUSSEK Brook Hospital and

Guy's Hospital, London Between 1980and

1987495patients underwent lung resectionforprimary bronchogenic carcinoma underthecareof onesurgeonatGuy's Hospitaland

the BrookHospital, London Themeanage

of thepatientswas61-9 years and16-8% of

thepopulationwere overthe age of 70 Two

hundred andforty-three patients had stage 1

disease, 110patientsstage 2disease,and 142

patients stage 3 Lobectomywasperformed

in 290 patients, pneumonectomy in 197

patients,andwedge resection in 8 patients

Hospitalmortalitywas505% in all patients,

7-11% following pneumonectomy, 3 79%

after lobectomy; there was no mortality

followingwedge resection Overall actuarial

survivalat oneyearwas75-8%and38-6%at

five years Actuarial survival for stage 1

diseasewas88-5%atoneyear and55-6%at

five years; for stage 2 disease 77-3% and

34-4% and for stage 3 disease 57-9% and

15-4% With respect to histological type

squamous cell carcinoma had the best outlook

andoat cell carcinoma theworst Actuarial

survivalatfive yearswas45%for squamous

cell carcinoma, 36-3% for adenocarcinoma,

31-9% for dimorphic carcinoma and 21%

for undifferentiated carcinoma Oat cell

carcinoma hasa zerofour year survival

Pulmonary resection in children with

focal disease duetocystic fibrosis

P HELMS, SK JUSBASCHE, DJ MATTHEW

Respiratory Unit, Great Ormond Street

Hospitalfor SickChildren, London Overthe

period 1975 to 1989 nine cystic fibrosis

patients (age range 7 months to 11 years)

underwent surgical resection of localised

bronchiectasis, representingasmall

propor-tion (23%) of the 379regular clinic

atten-ders Indications included recurrent severe

respiratory exacerbations, failure to thrive

andunstablefocal disease whichwas

begin-ningto extendintoadjacentareas.Duringthe

14yearperiod attemptstoimprove associated

collapse/consolidationbybronchoscopyand

bronchiallavagewereabandonedas no

last-ing benefit was found Assessment of the

extentofthediseaseby bronchographywas

also replaced by radionuclide

ventilation-perfusion lung scans There were no

perioperative deathsorseriousmorbidity; the

longest period of air leak requiring pleural

drainagewas21days Allpatientsandortheir

parents described symptomatic

improve-mentsandduration ofhospital stay fell froma

mean of 36 days (range 1-78) in the year

beforeto3days (range 0-10)inthe year after

surgery Inthe fivepatients old enough to

perform reliable spirometry % predicted

FEV, and FVC didnotchange in the year

beforeandaftersurgery Lobar resection of

localised bronchiectasis can significantly

improve the quality of life in severely affected

patients withcystic fibrosis;it is a low risk

procedure and should beconsidered in the

presence of focal disease with important

symptoms

Diaphragmatic plicationforunilateral

diaphragmatic paralysis: experience

over10years andlong termfollowup

DR GRAHAM, D KAPLAN, CC EVANS, CRK HIND,

RJDONNELLY RegionalAdultCardiothoracic

Unit, Liverpool Unilateral paralysis ofthe

Some patients, however, experience

dysp-noeaandorthopnoea accompanied by tion inpulmonary function tests (J ThoracCardiovasc Surg 1985;90:195-8) We haveperformed unilateral diaphragmaticplication

reduc-on 17patientsoverthe last 10 years(16 male

and onefemale,meanage53(SD13-8)years,range28-74).Preoperativelyeachpatient was

showntohave paradoxicalmovementof theparalyseddiaphragm onsniffing andtohavea

reduction inFVC and lungvolumes.Thesereductions were greater when thepatientwas

supine All patients had moderate aemia(mean 9-45 (SD 1-45) kPa) Plication

hypox-wasperformed byimbricatingthediaphragm

in layers through a thoracotomy incision

After plication all patients showedimprovement (table).When sixpatientswerereassessed five or more yearsafterplication(range 5-10 years) all six showed that the

improvement which occurred immediately

afteroperationhad been maintained These

resultssuggestthatdiaphragmatic plication is

a safe and effective procedure for adult

patients with dyspnoea resulting fromunilateral diaphragmaticparalysis Further-more, the symptomatic and physiologicalimprovementsaremaintainedlong term

Evaluation of silastic endobronchial

stents for bronchial anastomotic

stenosis

VTSANG,MYACOUB, PGOLDSTRAW Brompton

Hospital, London Progressive bronchialanastomotic stenosis due toischaemic distal

bronchus after sleeve resection and singlelung transplantation (SLT) is a potentiallyseriouscomplication In an attempt to avoidtraumatic repeated bronchial dilatations andrisky rethoracotomy, silastic endobronchial

stentswere used There were two male and1femalepatients,witha meanage of 55 years(range 47-65 years) Their original diseases

were cryptogenic fibrosing alveolitis, chogenic carcinoma, and squamouspapilloma Theoperations were right SLT,sleeve resection of the right main bronchus,

bron-and theleft mainbronchus respectively The

suture material used for bronchial mosiswascontinuousnonabsorbable mono-filament intwo and continuous absorbablemonofilament in one Bronchial anastomotic

anasto-stricturesdeveloped within a mean periodof5-3weeks(range2-8weeks) after the opera-

tions with a bronchoscopic appearance of

denseflorid granulationtissue andconcentricfibrosis beneath the bronchialanastomosis

Progressively larger stents (10-14 mmdiameter) were inserted to maintain thepatencyofthe bronchialanastomosis Con-

tinuousstenting was maintained for a meanperiodof16-7months(range 12-20 months)

Asimple technique ofpreparation and

inser-tion of the stents was used There was no

complicationrelated to the technique. Theendobronchial stents were well tolerated,

withclearing ofchest infection

Re-expan-sion of the affectedlungswasdemonstrated

radiographically, associated with improved lung function.ThemeanFEV1/FVCbefore

stentingwas1-4/2-1 (range 0-5-2-0/1-0-2-8),

andsubsequent improvementwithoneyear

stenting producedameanFEV,/FVCof 26/

3-6 (range 1-83-1/2-4-4-9). Our mediumterm experience with theuseof thesilasticendobronchialstents as asimpleandeffective

treatment for early bronchial anastomotic

HR ANDERSON, EA MITCHELL, P FREELING,

PT WHITE St George's Hospital MedicalSchool, London, and School of Medicine,

University of Auckland New Zealand hashigher mortality and hospital admissionrates

for asthma than England and Wales Todetermine thereasonsforthis, available andspecialsurveydatafrom theAucklandRegion

ofNew Zealandwere compared withthosefrom the South West Thames Region ofEngland Asthma mortality in children ofEuropean descent aged5-14 years washigher

inAucklandthan in South West Thames by a

factor of2-5.Thereportedlifetime,12month

andonemonthprevalences ofwheeze were

alsohigher inAuckland(18-5%,32-1%and87-5% higher respectively) Unexpectedly,the hospital admission rate for asthma in

children ofEuropean descent aged5-14 years

was5%less inAuckland than inSouthWestThames.Comparativestudies ofhospital case

patientsimulations) found that inAuckland

theduration of illness beforeadmission wasgreater and that general practitionerswere

lesslikelytoadmit.The overallstandard ofgeneralpractitionercareinAuckland was, if

anything, higherthaninSouthWest Thames

but in both areas there was considerable

variation On balancewe conclude thatthe

higher mortality rate in New Zealand is

explainedby higherlevelsofmorbidity rather

thanrelativedeficiencies in care

Neverthe-less, the implications of the lower use of

hospital care for acute asthmaobserved in

Aucklandneedfurther consideration

Whyisthemortality oftuberculosis notimproving?

PDO DAVIES South Liverpool Chest Clinic,Liverpool Notification and mortality data

forall forms of tuberculosishavebeen

extrac-ted from therelevant Office of PopulationsCensuses andSurveysMonitors (MB2, DH5)fortheyears 1974-86 (the mostrecentyear

forwhich corrected data areavailable).The

Proceedingsratio of deaths due to tuberculosis (excluding

late effects) to notifications foreach year has

beenused as a measureof the mortality of

tuberculosis Over the 13 years studied there

has been remarkably little change in this

"mortality ratio," which has remained at

approximately7-5%of all notifications The

ratiosforthe 0-14and15-34agegroups have

improved from 1-5% to 0-7% for both

groups Theratio for the35-54age grouphas

also shownimprovement from6%to3%and

for the55-74age groupfrom 15%to 12%.

The ratiofor the75yearandoverage group

has remainedconstant atapproximately 35%o.

However, theproportion ofnotificationsin

the 75 + grouphad doubledoverthe13years

studied from 49% of all notifications to

1000%. As this group accounts for around

40%ofalldeaths fromtuberculosis, despite

the apparent improvement in mortality in

younger age groups, the overall mortality

for all age groups combined has shown

virtually no improvement From this and

data published elsewhere (I Sutherland,

VHSpringette.JEpidemiol Commun Health

1989;43:15-24)it isestimated that the

dis-continuation of routine BCG within thenext

twoyears may resultinone "preventable"

death from tuberculosis, in the 15-34 age

group, everytwoyears, fromabout1998, for

10-15 years The reason for the lack of

improvementintuberculosismortalityis the

increase in theproportion ofcasesin the very

old, wheremortalityrates arehighest.

Postal survey of asthma in the

community

RL LOVE, RM MURDOCH, SJ CAMPBELL,

WG MIDDLETON, JS MILLAR, CA SOUTAR

Institute of Occupational Medicine,

Edinburgh; Bangour GeneralHospital, West

Lothian; and Falkirk Royal Infirmary In

the context ofa proposed study of asthma

andoccupationwehavetested the response

to a postal self administered questionnaire

designed to investigate respiratory symptoms

compatible with a diagnosis of asthma

Thirteen hundred adults over the age of 16,

selectedby stratified random sampling, from

the electoral register of urban and rural

communities inEast CentralScotland, were

invitedtocompletea twopagequestionnaire,

basedonthatdescribedbyBurneyandChinn

(Chest 1987;91 (suppl):795) Non-responders

were sentreminders andafurther

question-naireduring the subsequenttwo monthsand

the responserate ateach stagewasrecorded

Intotal, 1026returnedcompleted

question-naires, corresponding to 79% of those

invited If those whohad diedorwho had

moved away were excluded from the total

number invited, this would have given a

response rate of 82% The prevalence of

symptomsduringthelast yearwasexamined

within strata, and theoverallfiguresaregiven

here.Twentytwopercentreportedwheezing

and 13% reported having woken up with

tightnessintheir chest.Ten percentreported

havinganattackof shortness of breath and

5%reportedbeing wokenatnightby suchan

attack Prevalence of these symptoms was

generally greaterin men than inwomen,and

menreportedshortness ofbreathincreasingly

more frequently with age Overall, 6%

reported ever having had asthma In

con-clusion,thispostalsurveyhasprovideddata

on respiratory symptoms, for use in an

epidemiological study,from more than three

quartersof thoseindividualstowhom

ques-tionnaireswere sent

(This work is supported by the AsthmaResearchCouncil.)

Comparison of self admitted smokinghabits and exhaled carbon monoxidemeasurements inindustrial employees

inthreeEuropean countries

WN TRETHOWAN, PS BURGE, I CALVERT,

JM HARRINGTON Institute of Occupational

Health, Birmingham University, and East

BirminghamHospital, Birmingham As part

of an evaluation of smoking history in a

respiratory morbidity survey amongst

employees in the European ceramic fibresindustry, measurements of exhaled carbon

monoxide (CO) were collected from 621

participants workingin sevenmanufacturingplants Overall participation was 87% and

included 268 inthe UK, 286 in France, and

67 in West Germany Participants were

classified into never smokers, ex-smokersandcurrent smokers, and current smokers byconsumption of cigarettes per day Compari-

sons weremade betweensmoking groupsin

each countryfor meanexhaled CO levelsand

proportions of participants withindividualmeasurements above 8 parts per million(ppm).Fromthequestionnaire response, theproportion ofparticipants in each country

whowere current smokers was 45% in the

UK,39% inFrance and 63% in Germany

Therelationship between exhaled breath COand numbers ofcigarettes smokedwassimilar

inthe three national groups, suggesting that

theirpatternsofsmoking were similar Theproportion of ex-smokers with CO levels

greater than 8 ppm, suggesting that theymightbelying about theircurrentsmoking,

was8%in theUK,6%inFrance,and9%inGermany.Thestudy showsthatsmokingis

prevalent inceramicfibremanufacturers, andthat national differences exist in smokinghabitsinthisindustry

Effect of alterations of dietary sodium

ontheseverity of asthma

OJ CAREY, CR LOCK, JB COOKSON Glenfield

GeneralHospital, Leicester Epidemiologicalandexperimentalevidence suggests that highlevelsof salt consumption are associated withincreased bronchial reactivity and asthmamortality(Burney PGJ Chest 1987;91:143S;

Burneyetal Thorax 1989;44:36).Totigate the effect of dietary sodium on theseverity of asthma, 27 asthmatic men (agerange12-67y)placedon alow salt (80 mmol)diet underwent arandomised double blind

inves-crossover trial to compare slow sodiumsupplements (SS) (200 mmol daily) withplacebo (P) Twentytwosubjects completed

thestudy Allparameters improved withP

compared with SS (for paired data, FEV,:

P 2-82 1 (SEM 0-27), SS 2 61 1 (0-26)(p <005);PD2.methacholineP0-38pimol

(0 75), SS0-13.mol(0 55) (p < 0-05); puffsperday of bronchodilator: P5-25(range 2-11), SS 6-54 (26-A15) (p <0-01); symptomscores on asixpointscale: P 1 47(0-01-3-4),

SS 2-03(0 5-3-6) (p <0-01).PEF data were

analysed as parallel groups for period 1because of atreatment/periodinteraction of

paired data.With P morning PEF rose by

277%andevening by 5% above thepretrialvalue,and fell with SSby 3-4% (p <0-05)

and 2-6% (p < 0-01) respectively Thedifference in urinary sodium excretion

between treatments was 188 mmol Thestudy shows that changes in salt consumptionalter theseverityof asthma inmen.Ahighsaltintake results in physiological deteriorationandincreasedmorbidity

Fenoterol and death from asthma in

New Zealand, 1977-1981: a new controldesign

case-N PEARCE, J GRAINGER, M ATKINSON, J CRANE,

C BURGESS, C CULLING, H WINDOM, R BEASLEYDepartments of Community Health and

Medicine, Wellington School of Medicine,Wellington, New Zealand A previous NewZealandcase-controlstudy of asthma deaths

in the 5-45 year age group during 1981-3found thatfenoterol bymetered dose inhaler

(MDI)wasassociated withanincreased risk

of death in severeasthmatics(CraneJetal

Lancet 1989;ii:917-22) A new case-controldesign hasbeen used to evaluate the same

hypothesis during 1977-81 using the samesource for drug information for cases andcontrols This involved identifying allrelevant asthma deaths from nationalmortality records, and ascertaining thosepatientswho had been admitted to amajorhospital for asthma during the 12 month

period priortodeath For each of these casesfouragematched controlswerethenselectedfrom persons admitted tohospitalfor asthma

at the time ofthecase'sdeath who had alsohad apreviousadmission for asthma in the

past 12 months For the 58 cases and 227controls information on prescribed drugtherapywasthen collectedfrom thehospital

records relating to theprevious admission.Therelativeriskofasthmadeath inpatientsprescribedinhaled fenoterol was 1-99(95%

CI 1 12-3-55, p = 0-02) The inhaledfenoterol relative riskwas 3-91(95% CI1-79-

8-54, p < 0-01)inpatientswith aprevious

admission for asthma inthepast 12months,

and 5-83(95% CI 1-62-21-0, p = 0-01) inpatients prescribedoralcorticosteroids at the

time of admission In the group ofpatientswith themost severe asthma(defined by a

previous admission for asthma during the

past12months andprescribedoral steroids at time ofadmission) the inhaled

cortico-fenoterolrelativeriskwas 9-82(95% CI

2-23-434, p < 0-01) Thesefindings add furthersupport to the hypothesis that inhaledfenoterol increases the risk of death in

patientswith severeasthma

Potassiumchannel activationinhumanairway smooth muscle in vitro

PJ BARNES, CL ARMOUR, L ALOUAN, P JOHNSON,

JLBLACK Departmentof ThoracicMedicine,NationalHeartandLungInstitute, London,

andDepartment ofPharmacology, University

of Sydney, Sydney, Australia Potassium

(K +) channels are involved inrecovery of

excitable cells after depolarisation Drugswhich block these channels causeanincrease

in excitability, whereas activation of K +channels should reduceexcitability.There is

a great diversityof K + channels and thismakes selectivity ofdrug action a realisticpossibility.We haveinvestigatedthe effect of

aK+ channelactivating drug,BRL 38227

(L-enantiomer of cromakalim), on humanbronchial smooth muscle in vitro Subseg-mental bronchiobtained atlung surgerywere

suspendedinorganbathscontaining

Krebs-Henseleit solution at 37'C and changes in

isometrictensionwererecorded BRL 38227

caused a dose related relaxation ofairways

precontractedwithhistamine,themean

con-centration causing half maximal relaxation

(EC50) being 0-21 pM (95% confidence

intervals0-11-0-38,n =8).BRLwasequally

effectiveagainstsimilar contraction induced

by carbachol and neurokinin A with ECu0

valuesof 0 55 and 0-41 pMrespectively,and

gave relaxation responses which were

70-90%of the maximalresponse toisoprenaline

(1 mM) Therelaxant effect of BRL 38227

was blocked by glibenclamide in a

com-petitive manner, suggesting that an ATP

sensitive K+ channel was involved The

calcium channel blocker verapamil, at a

maximally effective dose (10 pM), caused

40%ofisoprenalinerelaxationincomparison

to 77% relaxation with BRL 38227 in the

sametissues(n= 3).Thissuggeststhat K+

channel activation may not only reverse

Ca++ entryviavoltagedependent Ca++

channels but may also produce additional

relaxation,whichmayrelatetosequestration

or extrusion of intracellular Ca++ K +

channel activatorsappear tobe useful

func-tionalantagonistsin human bronchi in vitro

and may be effective bronchodilators in

asthmatherapy

Phorbol myristate acetate (PMA)

potentiates responses to cholinergic

nervestimulation in rabbitairway

KG CRABB, JC MCGRATH, NC THOMSON

Department of Respiratory Medicine,

Western Infirmary, Glasgow,and Autonomic

Physiology Unit, University of Glasgow

Receptor operated stimulation ofdifferent

cell types causes hydrolysis ofmembrane

phospholipids to produce inositol

triphos-phate and diacylglycerol Diacylglycerol

activates protein kinase C, which may be

involved in theregulationofairwaytone.To

examine the role ofproteinkinase C inairway

smooth muscle contractionwehaveexamined

the effects of thephorbolesterPMA,which

activates protein kinase C, on cholinergic

stimulation of isolated rabbitairway rings

Bronchial rings were suspended in baths

containing oxygenatedKrebs-Henseleit

solu-tion.Electrical fieldstimulation(50 V,16Hz,

0-1msfor10s)wasappliedandchangesin

tensionweremeasured isometrically PMA

(10-6-10` M)didnot causecontraction of

airwaysmooth muscle but itpotentiatedthe

contractile response to electrical field

stimulation, reaching a plateau at

approxi-mately60min.At this timepointPMA(10-,

10- 10-6 M) produced a mean (SEM)

maximum contraction frombaseline values of

235(50))%, 178(27)%and 124(8)%

respec-tively.Theseresponses weresignificantly (p

< 005) greater than the respective time

control values: 93 (5)%, 74 (10)% and 77

(9)O%.Atropine (10-'M)abolished the

elec-trical field stimulation response and no

potentiation was shown by PMA These

resultsindicate that the phorbolesterPMA

potentiates responses to cholinergic nerve

stimulation in rabbitairwaysmoothmuscle

InvolvementofaG protein in

pharma-comechanical coupling in bovine

tra-chealsmooth muscle

IP HALL, S HARDING, SJ HILL, AE TATTERSFIELD

Departmentof PhysiologyandPharmacology,

Queen's Medical Centre, and Respiratory

Medicine Unit, City Hospital, NottinghamAgents such as histamine are thought to

initiate a contractile response in airway

smooth muscleby stimulatingthehydrolysis

ofphosphatidylinositol 4,5-bisphosphate byphosphoinositidaseCtoyieldinositol1,4,5-trisphosphateanddiacylglycerol.Theformer

is abletorelease calcium from intracellular

stores,and the lattertoactivateproteinkinase

C Activation of phosphoinositidase C inmany tissues is dependent on a G proteintermed GP. In thisstudywehave examined

the involvement of GP in

pharmaco-mechanical coupling in bovine trachealsmooth muscle (BTSM) by utilising the

abilityof fluoroaluminate(AIF4-)toactivate

GP.At concentrationsreportedtoactivateGP

in othertissues (>1 mM), AlF4- produced

concentration related contraction ofstripsofBTSM (n = 6) The maximal contractileresponse seen withA1F4- accounted for 59(SEM7)%of theresponse to 10 pM carba-

chol This contractileresponse toAIF4-wasmaintained in calcium free medium, andreversedby isoprenaline (50 nM,n = 4).Inaddition, AlF4- produced dose related

formation of ('H]-inositol phosphates at

concentrations above 1 mM The inositol

AIF4-accounted for 38(7)% of the maximal ponse to carbachol (1 mM, n = 9) Aspreviously reported,theresponse to20 mM

res-AlF4, was inhibited by the beta2 agonist

salbutamol(IC500-08pM;Hall and Hill.BrJPharmacol(in press)).Our data demonstratethat AlF4- can induce both a contractileresponseandaninositolphosphateresponse

in BTSM, and that these responses areboth subjecttoregulation bybeta-agonists

pharmacomechanical couplinginBTSM

Wearegratefulfor financialsupportfrom the

Asthma Research Council

Immunolocalisation of glutathione transferases in normallung

of Pathology, Edinburgh Glutathione

S-transferases(GST)maybeimportantin the

regulation oflunginjurycaused by

inflam-matory processesinvolvingleukotrienes(Int

J Biochem 1988;20:661) and by cigarettesmoking (Carcinogenesis 1986;7:751)

Individuals nulled for GST mu have anincreased susceptibility to lung cancer.

Previousstudies havemainly reliedonchemicalassessmentoflungtissue.This fails

bio-todistinguish between the three functional

compartments oflung: air conducting, gas

exchange,and vascular We haveinvestigated

thedistribution ofGSTisoenzymesinlung

byimmunohistochemistry Lungblockswereobtained froman uninvolved love ofpneu-

monectomy specimensremoved for oma. Allpatientsweresmokers Antibodiesagainst pi classGST stained bronchial and

carcin-bronchiolar epithelium strongly Alveolar

liningcellsand alveolar macrophages insome cases also contained GST pi Staining for

GST alpha was restricted to bronchial and

bronchiolar epithelium GSTmu was

dis-tributedsimilarlytoGSTpi but theintensity

ofstainingwasless andtherewas intercase

andintracase variation Somecasesexpressed

no detectable GST mu. Microsomal GSTwas present in alveolar lining cells butwas

heterogeneous within single and

between cases. Some cases had strong

endothelialstaining Overall fivecaseswerestrongly stained for microsomal GST, twocases wereweakly stained, and threecaseshad

nodetectablestaining.Thesefindings formthe basis for further studyof therole of GST

in thepathogenesisoflungdiseasessuchasemphysema

Histamine release inisolated large

air-way segmentsof normal and asthmatic

subjects in vivo

DL MAXWELL, BA ATKINSON, M BARROS, TH LEEDepartment ofAllergyandAllied RespiratoryDisorders, Guy's Hospital, LondonAsthmaticairwaysarehyperresponsiveto a

number ofnon-specificstimulisuchas

exer-ciseanddry airhyperventilation.Itis

sugges-ted that thecommonpathway isanincrease intheosmolarity offluid lining the bronchial

epithelium Challenge with these stimuli

causes mediator release into the peripheral

circulation, butlittle is known aboutmediatorrelease withinthe airways inman.Adaptinga

technique of Smith et al (Eur Respir J1988;1:792) we have obtained lavage fluidfrom isolated segments of large airwaysbefore, duringandfollowing challenge withhypertonicsaline insix normal and five mild

asthmatics with exercise induced asthma

Under bronchoscopic guidance a

multi-channel cathetertipped with aballoon wasinserted into the left main bronchus Theballoon was then inflated just above thebifurcation of thebronchus Six aliquots of

normal saline (PRE) were instilled and

aspiratedfrom above theballoon (dwell time

of45-60s) Thiswasfollowedby six aliquots

of3 M saline andthen sixmoreofN saline

Pooledsamples fromeachofpre,hyper and

post were assayed for histamine immunoassay) and geometric mean values

(radio-(nM) givenin the table

Baseline and stimulated concentrations ofhistaminewerehigherintheasthmatics thanthose of normals (p < 0025) One of sixnormaland four of five asthmatics showedsignificant increases in lavage histamineduring and following hyperosmolarchallenge Two of five asthmatics developedmild bronchoconstriction following theprocedure, which was otherwise welltolerated.These data show that the fluid fromlarge airways of asthmatics contain greaterconcentrations of histamine than that of

normals andthat asthmatic epithelium pondstohyperosmolar stimuli with increased

res-secretion ofhistamine

Assessment of the bronchial mucosalbioelectric responses with a modifiedUssing chamber

V TSANG, EWFW ALTON, ME HODSON, MYACOUB Brompton Hospital, LondonMeasurements of bronchial mucosal bio-electricproperties and responses to different

mediators can provide useful information,particularly inpatients with cystic fibrosis,

(CF) before and after heart-lung

transplanta-tion(HLT) Thismaydemonstrate whether

thetypical CF biochemicaldefectrecursin

the transplanted lungs after HLT A

pre-liminary in vivoreportsuggestedthismay not

be thecase(Altonetal Lancet1987;i: 1026)

We have assessedthepossibilityof invitro

measurementsof the basal properties(SCC,

short circuit current; PD, potential

dif-ference; R, tissue resistance) and the

phar-macological responses of the bronchial

mucosal biopsy specimensobtained from the

transplanted lungs A pilot study involved

CF and non-CF bronchial mucosal sheets

with sizesranging from 2to4mmdiameter,

and bronchial mucosalbiopsy specimens (2

mmdiameter) using a rigid bronchoscopic

biopsy forceps, obtained fromtheexplanted

lungsatthe time ofHLT.Theywere

moun-ted in a modified Ussing chamber (tissue

diameter of2 or4mm),and the bioelectric

propertieswere assessed (Tayloretal, Gut

1988;29:957-962)-see table In non-CF

biopsy specimens,amiloride(10 pM)caused

a mean decrease in SCC of62%, and

sub-sequent stimulation with isoprenaline (10

pM)produced a mean increase of60% In

contrast, CF biopsy specimens produced a

slightly greater fall in SCC of66.5%, but

with no response from isoprenaline The

typical pharmacological responses of the

(Knowles et -al J Clin Invest 1983;

71:1410) Despitealowered tissue resistance

in the 2mm diameterUssingchamber,the

other basalpropertiesof both CF and

non-CF bronchialmucosalbiopsy specimensdid

chamber, whichsuggestedthefeasibility of

this method

pul-monaryemboli

AG FENNERTY, HG SHETTY, G ROBERTS,

IA CAMPBELL, PA ROUTLEDGE Llandough

Hospital, Penarth, S Glamorgan Patients

withacarcinomaare at anincreased riskof

developing thrombo embolic disease, but

whether patients presenting with thrombo

underlying malignancy is controversial To

establish if there is an increased risk of

carcinomadeveloping in patients presenting

withpulmonaryembolus (PE) 100

consecu-tivepatients with PE confirmed by a high

probability lungscan(meanage56+14yrs,

47 female) were compared with 100

con-secutivecontrolsubjects with low probability

scans(meanage51(SD 16)y,61female) ina

prospective study At the time of presentation

sevenPEand11controlpatientswereknown

86controls fora meanof 39 (16)months, with

oneandthreepatients losttofollowupinthe

two groups.TwentyonePEpatients and 18

PE patients and four controls developedcarcinomaduring followup.The calculatedincidence of newly diagnosed carcinoma ineachgroup,taken from figures published inthe OPCS cancerregistry for 1984was 2-3and 2-01respectively, givingarelative risk of1-3for PE patients and 2-0 for controls (NS)

While this studycannot exclude thebility that patients with PE haveanincreasedrisk of developing a malignancy, the

possi-incidence of carcinoma in these patientsappears tobe low (0-86per100patient years)

and no higher than in patients with low

probability scans. We conclude that tigation to detect occult carcinoma is not

inves-indicated in patients with high probabilitylungscans.

Low dose rate endobronchial therapy using caesium-137

radio-PJM GEORGE, BS MANTELL, RM RUDD LondonChestHospital andLondonHospital,London

Endobronchialradiotherapy has considerablepotentialas apalliativetreatmentin advanced

tracheobronchial malignancy Treatment

withhigh activity iridium has been shownto

be safe and effective inrelievingupperairwayobstruction; however, it requires costlyequipment which is not widely availablewithinthe NHS We have developedatech-nique using caesium-137, which employsstandardafterloading equipment(Curietron)used to treat gynaecological malignancy

Treatments have been combined with

endo-scopic laser therapy with the intention of

prolonging the palliative response. After

completion of laser therapy under generalanaesthesia,aflexiblepolythenecatheterwaspassed into the trachea through a mini-

tracheostomy incision The catheter wasguidedinto the affectedairwaywithaflexible

bronchoscope and, when correctly tioned, clampedto aplasticmountwhichwastapedto the neck.After recovery from the

posi-anaesthetic, a caesium source of the

appropriate length was loaded by remote

control into the catheter Treatment timeswerevaried from5-7-5 hourstodeliver doses

rangingfrom2000-3000cGyat0-5cmfromthe source. This technique has been per-

lungcancer. Six derived immediatebenefit,although one died after twoweeks from a

sevenand 10 weeks andrequiredrepeatlaser treatments; one of these patients has sub-

sequentlybeen retreatedwith caesiumusingahigher radiation dose Theremainingthree

patientswhoresponded have remained well

did not respond, has not been retreated.

Although treatment with caesium-137 is

high activity iridium,it has theadvantagesof

being morewidely availableand much less

expensive We believe that the combination

therapy providedurablepalliation

Does pulmonary inflammation fluence benign lymph node size inpatients withbronchogenic carcinoma?

in-KM KERR, CG WATHEN, WS WALKER, EW

Edinburgh Lymph node size is often sidered importantwhen using imagingtech-niques to detect mediastinal lymph node

con-metastases in patients with bronchogenic

carcinoma who are being considered forsurgery We wished to examine whetherinflammatory changes in the lungs ofsuch

patients produced benignlymphadenopathy.Forty four patients with operable bron-chogenic carcinoma and no other causefor

benign adenopathy (forexample,sarcoidosis

oranthracosis) hadpulmonary resectionandremoval ofallaccessible mediastinal lymph

nodes Two pathologists scored, in a

semiquantitative manner, the degree of

inflammatorychange in fixed lung slices and

inrepresentative histological sections Each

lymph nodewasmeasured and processedin

toto No correlation was found between

benign lymph node size and chronic

inflam-matory changes in the lung, includingendogenous lipoid pneumonia However,maximum node size was greater in the 14patients with significant acute inflammatory

changes in the lung than in those without

for both hilar (p=0 02) and mediastinal

(p = 0-01)lymphnodes Allofthosepatientswith a positive score for acute pulmonaryinflammation had at least one mediastinal

lymphnode of maximum diameter 15 mm ormore Acute inflammation distal to lungcancersis associated withsignificant reactivelymph node enlargement in both hilar and

mediastinal nodes

Initial staging of non-small cell lung

radioisotopebone scanning

F MICHEL, M SOLER, E IMHOF, AP PERRUCHOUD

Division of Respiratory Diseases, University

Hospital, Basel, Switzerland The skeletalsystem is a preferred location for distantmetastasesinprimary lungcancer It is stilla

the initial staging of NSCLC radioisotope

bone scans should beperformedroutinely or

only when there is clinical suspicion of

skeletalmetastases(SM) Thepurposeof thisstudy was to compare the sensitivity ofclinical indicators of SM (bonepain inhistory

calcium, increasedalkalinephosphatase)with

routine bonescanning We studied110secutive patients referred for preoperative

con-staging ofNSCLC during 1983-5 Ninety

fiveper centof these patients werefollowed

up for up to five years Routine staging

included history, physical examination,laboratorytests, CT of the thorax and upperabdomen and bonescanning In patients with

positive bone scans additionalradiography,conventional andcomputed tomography,or

biopsywasperformedtoconfirm or exclude

SM Oninitialstaging37of110bone scans

(34%)showed areas of increaseduptake,onlynine of which (8%) wereconfirmed to bemetastases At least one clinical indicator for

SMwaspresentin 54(49%)ofthepatients,including all patients with proved SM

Comparedwith bonescanningthesensitivity

of these clinical indicatorswas 100%with a

specificityof54%.Follow up data on 96 out

of101patients(95%) with no initial SM wereavailable to validate our skeletal staging

Proceedings

Withinone yearthree of 27patients with

non-confirmed positivebonescanshad SM Two

initiallyincreaseduptake Allthree patients

had signs of SM and all had inoperable,

advancedcarcinoma Four of 69patientswith

initially negative bone scan developed SM

withinone yearafterstaging(negative

concludethat inNSCLC bone scanning is

necessary only in patients with clinical

indicatorsofSM.Thisapproach reducesthe

number of bone scans and consecutive

examinationswithout lossof sensitivity

Bronchoscopic cryotherapy for

advanced lungcancer

DA WALSH, OM MAIWAND, AR NATH,

P LOCKWOOD, M SAAB Harefield Hospital,

Harefield, Middlesex Bronchialobstruction

andhaemorrhagefromintraluminaltumours

cause significant morbidity in advanced

carcinoma of the lung Radiotherapy is

limitedby maximumpermitteddoses and the

insensitivity of some histological types.

Endobronchial laser therapy may produce

bronchial clearance butisassociatedwitha

significant morbidity and mortality We

report aprospectiveassessmentofsubjective

and objective palliation with 81

broncho-scopic cryotherapysessions in 37 consecutive

patients Twenty three patients (70%)

reported overall subjective improvement

improved in37% and670, ofpatients

res-pectively Stridor was relieved in four of

sevenpatients (560o).Radiographicevidence

of collapse resolved in two of 29 patients

(70o) and improved in a further five

(170/O). Nineteen patients (58%) showed

improvement in at least one objective

measure of lung function Seven patients

(2400)showedanimprovementofmorethan

score(r =036,p < 002) Twenty (770o)of

26 patients reviewed by bronchoscopy

showed some clearance of endobronchial

were attributable to cryotherapy and there

was no treatment related mortality

Bron-choscopic cryotherapy provides a safe and

haemoptysis in advanced endobronchial

malignancy

Malignant mesothelioma in the south

experienceof245cases

DH YATES, K O'DWYER, FG WARD Medical

orproved mesothelioma in the South East

Region were examined by the London

presentation and necropsy were obtained,

cases good information was available,

inlife, hospital records, andverification of

occupationaldetailsby correspondence with

formeremployers A retrospective studywasperformedon245casesof mesotheliomafor

theyearofdeath 1987 Maletofemaleratiowas 14:1 Necropsies were performed in

9844% Occupational exposure to asbestoswas documented in 78.5%, with definiteabsence ofexposurein 9% andneighbour-hood exposure in 16% Pleural mesothe-liomawas farcommoner than peritoneal orpericardial, being present in 95.5% The

commonestmode ofpresentationwaslessness and chest pain with accompanyingpleural effusion; but pneumothorax, throm-bocytosis and a chest wall mass were alsoobserved The previously reported pre-dominance of right pleuralmesotheliomawasagain observed (ratio right: left 14:1)

breath-Asbestosis was commoner in peritonealmesothelioma, and overall was found in

7.3%.Asbestos bodieswere present onlightmicroscopyin54.4%,with plaques in326%0

Average time from onset of symptoms todiagnosiswas5l/2 months, and diagnosiswasconfirmed most commonly byopen biopsy

In1500 ofcasesthe diagnosiswas notmade in

life Spread through the chest wall wasdocumented at necropsy in 24% Distant

metastases were presentin57%,aproportionlower thanreported insomeother studies buthigher than has been previously assumed

Industrialdisablementbenefitwasclaimed inless than half of the cases, despite written

apply

Comparison of dosimeter and tidalbreathing methods for measuringnon-specific bronchial responsiveness(NSBR)

JR BEACH, SC STENTON, CL YOUNG, EH WALTERS,

DJ HENDRICK Chest Unit,Newcastle GeneralHospital, University ofNewcastle upon Tyne

or compare results from the dosimeter and

two pairs ofmeasurements ofNSBR in20

subjects using (1) a locally designed meter which generates 50 p1 of aerosol perdose,and(2)aWrightnebuliser from which

dosecomprises theamountinhaledfromtwo

minutes of tidal breathing (Clin Allergy

1977;7:235)-seetable.NSBR isexpressedas

provokes a 200,, decrement in FEV, (PD20,PC,0) Forour ownmethod, FEV, is takenas

from six made 210-300 seconds afterchallengeonset.This isgreatly influenced by

the bronchodilation which occurs after the

method, FEV, is takenas thelower of only

two measurements-at150and210seconds

PC20) by both methods in this particularstudy, one measurement was made at 150

*Expcoefficient of repeatability.

seconds.Thepairedmethacholinetests werecarriedoutby differentinvestigators,blindto

anyprevious results CRprovidesa measure

ofprecisionforeachmethod and defines the

9500 confidence interval forthe second ofa

further pair of readings (first/CR-first xCR) Weconclude(1)that the greatest pre-cisionwasachievedbythedosimetercoupled

with the "best three of six" measurement

method forFEV,the lattermakingthelarger

contribution; (2) that FEV, measured as

"best threeofsix"comparedwith the "lower

of 2" approximately doubled the PD20 and

PC20; and (3) that a PC20 of 1 mg/ml was

equivalentto aPD20of the order 40-50 pg

Assessmentofbronchodilatorresponse

by spirometric and impedance

methods:acomparison

P MCLOUGHLIN, JS PRICHARD Department

of Medicine, Trinity College, Dublin

Spirometry is a common method of

deter-mining air flow obstruction and responsetobronchodilators Recently, another simple

method-change in airway impedance

(measured by forced oscillation)-hasbecomeavailable Itrequires little coopera-tion and is an attractive alternative tospirometry We have compared the twoapproaches Spirometrywasperformedusing

aVitalograph and impedance was assessed bytheSiregnost(Siemens)system In 40normalsubjects (ages24-60,22male, 18 female) twomeasurementseachofFEV,and respiratory

impedance (Z) were made separated by 20min In each casethe difference between thefirst and the second wasdetermined(AFEV,, AZ) and the mean and SD for the groupcalculated Values were AFEV, = -5 ml(125); AZ = -0-008kPa/l/s (0 397).Thirty

patients with obstructive airways disease

(aged 26-75, 17 M, 13 F) were examined

similarlyandAFEV, = 15 ml (139); AZ =

0 023kPa/l/s(0-492) Each method was found

tobeequallyreproducible in normal subjectsandpatients(F= 08, p> 005; F=15, p>

005) The distribution of AFEV, and AZallowed a means of assessing response tobronchodilators If thechange inAFEV,or

AZ before and after a bronchodilatorexceeded the 950 confidence level thepatientwasconsidered to show asignificantresponse Thus in 50 patients with obstruc-tive airways disease, when assessment ofreversibility by impedance was comparedwithspirometry,theformer had a sensitivity

of 5000 a specificity of 72%, a negativepredictive value of690%and apositive predic-tive value of50%.However, if the conven-tional spirometric method(15% increase in

FEV,) is applied assessment by impedance

change showssensitivity of65%0 specificity

of 8300, positive predictive value 72%,

negative predictivevalue78%.Thisison in turn raises questions about the defini-tion ofsignificantbronchodilator response

compar-Effect ofairway calibre on the tivity of the human cough reflex

sensi-NB CHOUDRY, RW FULLER, ST MARY'S BSc

Pharmacology, Royal Postgraduate MedicalSchool, and St Mary's Hospital (Praed

Street) London Thesensitivityof thecough

reflex is thoughttobedetermined inpartby

airway tone. Studies have shown that

artificially induced coughmaybe modifiedby

agentswhichrelaxairwayssuchas#agonists

and antimuscarinic agents. There is also

evidence of coughing during

bronchocon-striction duringattacksofasthma We have

investigated the effects of altering airway

calibre in normal volunteers by using the

spasmogenmethacholine andbronchodilator

salbutamol Baseline FEV, and capsaicin

coughchallenge using singlebreaths of saline

or 04-50 nmol capsaicin to determine the

dose causing two or more coughs was

and methacholine(dosewhich causeda40%

increase in airwaysresistance)weregivenina

randomised doubleblindmanner.FEV,and

treatment.The resultsareshown in the table

Significant increasesordecreasesin airway

tone innormal volunteers doesnot cause a

change insensitivityof thecoughreflex This

suggeststhatchangesofairwaytonewithin

insensitivity of thecoughreflex inpatients

withcough

Wewouldlike toacknowledgethehelp given

Mary's Hospital: D Barron, D Gillen, M

Harbord,LSeal,NSpittle,and A Stears

Recovery from voluntary

hyperventila-tioninnormaland asthmaticsubjects

SG CHURCH, WN GARDNER Department of

Physiology, King's College, London

Hyper-ventilation(HV) with alow end tidalPco,

(PETCo2)isarecognised complication of mild

asthma butthecauseisuncertain.During the

recovery from voluntary hyperventilation

(VHV) in hyperoxia in normalman,there isa

influence of "feedforward" mechanisms We

studied therecovery from threeminutesof

VHVto aPETCO2of20mmHgin four normal

subjects andfouryoungmild asthmatics in

ranges, but they were hyperresponsive to

humidified, hyperoxic gasmixture from an

and mouthpiece PETCO2 was measured by

mass spectrometer. Respiratory drive and

timingvariableswereaveragedbycomputer

recovery. The pattern of recovery in the

(Gardner et al Am Rev Respir Dis 1987;

135(suppl 4):A372)withanexponentialrise

ofPETCO2 to a plateau andlong expiratory

chemoreceptor threshold In the asthmaticgroup,FEV, and PEF remained unchangedduring VHVrecovery.TherecoveryofPET-

co2 wasfasteroverthe first few minutes and

time to recovery back to nofnal PETCO2.

During resting breathing before VHV, piratory time was slightly longer andexpiratorytimeslightly shorter than inthe

exaggerated during therecoveryfrom VHVand thelong end expiratorypauses seen innormalsubjectswereabsent ThesechangeswereheightenedinbothgroupswhenVHVwasimmediately preceded by inhalation of

methacholineat adose of 50% ofPc2,forfive

unmaskabnormalities ofrespiratory

normalbreathing and lungfunction These

chemical drive

Ventilatory responses to exercise in

patientswithchronic cardiac failure

JS ELBORN, M RILEY, CF STANFORD, DP NICHOLLS Royal VictoriaHospital, BelfastPatients with chronic cardiac failure (CCF)are commonly limited by dyspnoea during

re-sponses to exercise are abnormal in such

patients is unclear We have studied

ven-tilatory responses toprogressiveandsteady

stateexercise in 45patientswith CCF and 23

restingpulmonary functiontests.Ventilatoryresponses to progressive treadmill exercisewere compared betweennormals and CCF

patients Subsequently comparisons weremadeduringa20 minutesteadystateexercise

test at50% ofpeakoxygen uptake(PIVo,).

production (VCO2), Vo2 and end tidal Co2

(PETCO2) weremeasured onlinethroughout

comparedat the same percentage ofPVo,2patientswithCCF hadasignificantly higherVE/VO2andVE/NCO2, whichwasprogressive

with increasing severity of CCF Duringsteadystateexercise absoluteVE was similar

inthetwo groups:controls408(80) ml/min/

kg andpatients 352(85) ml/min/kg

Differ-ences inVE/VO2, VE/VCO2 and dead space/

VE/VCO stronglycorrelated withVD/VT (r=

0-87, p 0-0001) Weconclude that patientswithCCF have abnormalventilatoryrespon-

andVg/Vo,and the relation to therelativelyhigh VD/VT suggests inequalityofventilation

and perfusion These abnormalities may

contribute to the sensation ofbreathlessness

inCCF

Familial aspects of peripheral sensitivity and/or central respiratory

chemo-drive in the determination ofarterial

Po,inchronic obstructive lung disease(COPD)

Respiratory Medicine, City Hospital, burgh The inheritedintensity of the carotid

Edin-bodymediatedhypoxic ventilatory responsemay partly determine the Pao, ofpatients

with COPD We haverelated thePao,(stable,

onair) of 24 patients with COPD (FEV,

12-430") pred;Pao251-9-5 kPa; Paco24-9-8-7kPa) to the ventilatory responses to bothtransient(threebreathsN2) and rapid onset,three minute isocapnic step change (Fio,20.9-150,, and20o9-12%)hypoxia measuredduring moderate exerciseVO211-9(SEM 1-8)

mlmin-' kg-') in their offspring (20M, 15F,

age 18-47 y; FEV, 77-112% pred).Measurements were also made in 24 controlswho were age and sex matched with theoffspring, but whose parents did not haveCOPD The patients' Pao2 correlated withVE/Sao2 relationship in response to stepchange (r = -0 48, p < 001) but nottransienthypoxia in theoffspring The dyn-amicventilatory response to the twohypoxicstimuli was analysedby means of a mathe-maticalmodel consisting of two differentialequations in parallel (1 and 2) with gains GIand G2.Equation 1 describes therapid onsetresponse (time constant <3s, possiblyreflecting peripheral drive) and equation 2the sustained response (possibly reflecting

peripheral and central mechanisms) Thepatients'Pao2wasbest described(p < 002)

by themultiple regression equation:

Pao2(patient) =(035) (0-14))G2 +(030)

(0-15)) G1 +(6 08)(035))

Therewas nosignificant difference betweentheoffspring(0)and theage andsexmatchedcontrols (C) for the VtE/Sao2relationship tostep changehypoxia(0, 0 37to -1-75; C,-0-08 to -159, 1 min-' %-'), GI (0,

-145to417; C, 0 24to394,1min'%%),or

G2 (0, -1-83 to 385; C -2-27 to 309

1 minm'O1') The Pao2 in COPD seems to

dependon ageneticallydetermined variation

in the normalpopulationof bothperipheral

hypoxic sensitivity and central respiratorycontrol mechanisms

Isthe carbon dioxideresponserelevant

to ventilation and sensation duringexercise in normal man?

JE CLAGUE, MG PEARSON, PMA CALVERLEY

Regional ThoracicUnit,Fazakerley Hospital,

Liverpool Previous studies have shown thattheventilatoryresponse tohypercapnia(VE/

Pco,) correlateswiththe rate of increase ofventilation withCo,production during exer-cise(VEVco2)(Rebucketal Clin Sci 1972)but neither relates to perceived breathless-

nessinCOPDpatients(Robinson et al AmRevRespirDis 1987).Wehave investigatedtheserelationshipsin 11normal subjects (10

M).Eachperformed duplicateCo2rebreathesandcycle exercise tests both free breathing

(FB) and with a 10cm H20/l/s inspiratory

resistive load (IRL) We recorded VE,

PETCO2, mouthocclusionpressure(Po 1) and

inspiratory effort sensation (IES) using a

Borg scale During rebreathing IRL

depres-sed the ventilatoryresponseVE/PcO,by 25%

while theIES/Pco2slope increased by 57%

Duringexercise IRL depressedVE/VCO2by

only 9% yet increased IES/Vco2 by 95%

Neither the FBnorthe IRLventilatory (VE/

Pco2) or effort sensation responses (IES/

Pco2) during rebreathingwererelatedtoVE/

Vco2during exercise Thus the hypercapnic

ventilatory response does not predict the

ventilatory response to isocapnic exercise

During both rebreathing and exercise IRL

hadnoinfluenceonthe slope of the IES/Po.1

response.Differencesinindividualbreathing

pattern responses toIRLduring exercise and

hypercapnic rebreathingmayexplain the lack

of association between the ventilatory

re-sponsesandperceived effort(IES)

Inspira-toryeffortsensation during both exercise and

hypercapnia remained relatedtorespiratory

centre output asreflected by Po 1

Relative effectsofinspiratory sensation

andrespiratory drive onpeak exercise

ventilation

JE CLAGUE, MG PEARSON, PMA CALVERLEY

Regional- Thoracic Unit, Fazakerley Hospital,

Liverpool Exercise performance is often

in patients with chronic obstructive lung

performance of normal subjects is limited by

theonsetofinspiratory muscle fatigue (Baiet

limited by breathlessness We have

inves-tigated 11 normal subjects (10 M) who

progres-sivecycle exercisetestsboth freebreathing

(FB) and witha 10cm H20/l/s inspiratory

resistive load(IRL) Werecorded VE,

inspiratory effort sensation (IES) using a

Borg scale VEmax, Po.Imaxand peak heart

rate (HR) were reproducible between

duplicateexercise testswithacoefficient of

respec-tively During exercise IRL significantly

depressedVEmax(532 FBto31-71/min IRL)

andVco2max (1882 FBto 1243 1/min IRL)

while IESmax (4-6 FB to 6-5 IRL) arnJ

increased (allp < 001)) Peak values were

notpredicted by the VE/PCO2, IES/Pco2or

Po.1/Pco2 responses during hypercapnia

However, the "total inspiratory effort per

minute" (IESmax x VEmax) wasthesame

during FBand IRLexercise (242 FBv251

IRL) Similarly the "total inspiratory drive

"productvalues"varied betweenindividuals

(161to394forIESmax x VEmax) butwere

reproducible for the four exercisetests(CV

27%) Thepeak respiratoryperformance is

dependent onchanges in both IES and VE

assess-ing the respiratory disability ofpatients

tophysical traininginasthma

CJ CLARK, LM COCHRANE Department of

Respiratory Medicine, Hairmyres Hospital,

Glasgow Innormalsubjects physical

train-ing produces metabolic adaptations that

reduce the ventilatory demands ofexercise

In asthma, however,there may be

impair-ment of a variety of metabolic responses

(Haas etal Am Rev Respir Dis 1988), and

beta2 selectiveagonistsalsoproduce changes

in lactatemetabolism(Holgateetal Clin Sci

1981) It is thereforenotclear what impact

venti-latoryadaptationstophysical training.This

studyreportstheeffects ofphysical training

on36asthmaticsubjects (14 male,22female)randomisedintotrainingandcontrolgroups.

progressive incremental exercise weremeasured at 0 and three months At work

rates corresponding to 20% and 40% of

initialVo2maxnosignificant changein blood

lactate, carbon dioxide output (Vco2) orminute ventilation(VE)occurred At60%of

Vo2maxtherewas asignificantfall inVco2 (p

<001) and VE(p < 0-01).At80%and95%

of initialVo2maxtherewas asignificantfall(p

< 0001) of all three indices Nosignificantchangeswere seen at anyof theseworkrates

inthe controlgroupaftertraining This study

metabolic adaptations in asthmatic patients

response toexerciseathighworkloads,the

magnitudeofwhichmaybeadvantageousfor

endurance exercisein the asthmaticpatient

patternsduringprogressive

incremen-talexercisetesting

LM COCHRANE, CJ CLARK Department ofRespiratory Medicine, Hairmyres Hospital,Glasgow A recent study (Cochrane et al

BTS Proceedings, Thorax 1989;44:885P)showedmorebreathlessnessduringprogres-sive incremental exercise with bicycle

ergometrythanwith treadmillwalking Thisstudy investigates breathing patterns

produced by thetwomodesof exercise.Fortyfive healthy subjects (25 male, 20 female)performedthe two progressive incremental

days.Fromaquadratic analysisof therelation

plateau height(peak tidal volume); (2)

turn-ing point (minute ventilation at peak tidalvolume); and (3) slope (of ascending curve)

Resultsaregiveninthetable At equivalent

breathingweredemonstrated duringbicycle

reachedatlowerminute ventilation and theslopeof tidal volume relatedtominuteven-

part explain our previous observation that

progressive incremental exercise

Use ofalowintensity submaximalcycle

patients with poor exercise tolerancethrough an exercise training pro-

gramme

R TIPSON, D DUGMORE, AHARDMAN,MF BONE

Department of Thoracic Medicine, RussellsHall Hospital, Dudley, West Midlands, and

DepartmentofPE andSportsScience, borough University, Loughborough Exercise

Lough-trainingmay improveexercise tolerance in

patientswithawiderangeof chronicdisease,notablyischaemic heart disease and obstruc-

tiveairwaysdisease(COAD) Optimal

train-ing dependson an assessmentoffunctional

fitnesscapacityand achievement of60-70%

workrates.Previouslyestimation of maximaloxygen uptake from extrapolation of sub-

maximalheart rate datahas been used butresponses in apatient populationare fickle

steady state cycle ergometer test with low

exercisework loads ofapproximately 25, 50,

75, 100 watts in monitoring such patients

withlow exercisetolerance inamixed

train-ingprogramme of 12 weeks' durationusingindividualisedwork intensities of60-70oo for

30 minutes three timesweekly During the

exercise stress testheart rate (HR), minute

ventilation (VE), oxygen uptake (Vo,) and

HR(94 (4)v110(6) b.min-',p < 001); VE

298(18)v37-8(26) l.min-',p < 001);and

(0 16)mmol.l ',p <0 01were seen at stage4

patients In patient groups such a low

employedas anindex of fitness

inchildren and adults

H DAVIES, P HELMS, I GORDON Hospital for

SickChildren, London Daviesetal(Davies

etal.Regional ventilation in infancy: reversal

1626)havedemonstrated that ventilation ispreferentially distributed in infantsto upper-

most lung regions, the opposite pattem tothatseeninadults Groups of older children,

todetermineatwhatagethispatternchanges

Supine, right and left lateralkrypton 81m

ventilationlungscans wereperformedon43

Hospital for Sick Children, and 16 adult

volunteers (mean age 30 7) The childrenwere divided into three subgroups on the

interpretation of theirchest radiograph

(nor-mal, unilateral or bilateral lung disease)

PeakTV VEat peak TV Slope

MALES

(Mean (SEM)) Bicycle 2-84 (0-55) 99-5 (34) 0-003 (0-000)

Treadmill 2-78 (0-49) 116-8 (30) 0-002 (0-000)

(NS) (p< 0004) (p< 0-018) FEMALES

Pulmonary functiontests wereperformedin

those children ableto cooperate. Inchildren

aged 2-10 years distribution of the

radio-nuclidetothe right lung (VfR) supinewas

depen-dent VfRfellto36 00o (12800),risingwhen

uppermost to56-10 (990). Both changes

were significant (p < 0 0005) In children

aged 10-18 years VfR (supine) was 5720,)

(730o), fallingto480o (820o0)when

depen-dent andrisingto6290,(7 9°0) when

upper-most. These changes were also significant

(p < 00005) A different pattern was

observed in adults VfR (supine)was52 40o

(15O0)), rising when dependent to 53*40o

(490,)andfalling whenuppermost to4890°o

(7.70,). The change in ventilation from

supineto uppermostand from dependentto

uppermostreached significance (p < 005),

although the change from supineto

depen-dent did not. Neither chest radiograph

appearances nor pulmonary function test

results altered thispattern.The physiology of

these differences and clinical consequences

willbediscussed

resis-tanceinthesupinepostureinasthmatic

subjects

CJ DUGGAN, A WATSON, SB PHAGOO, NB

PRIDE Department of Medicine, RPMS,

Hammersmith Hospital, London Subjects

with asthmafrequently have nasalsymptoms

andcomplainoforthopnoea,evenwhenthey

areawake However almost allassessmentsof

airways resistance inasthmatic subjects are

made in the sitting posture. We have

resis-tance (Rrs) and midtidal lung volume

(MTLV) when breathing via thenose orvia

the mouth inthe sitting and supineposturein

10subjects with both asthma and nasal

symp-toms(6 males,mean age62 8years: range

38-80 years) mean FEV, 00 predicted 54 60o,

andmeanFEVI/VC640,.Rrswasmeasured

at6 Hzusing the pseudorandom noise

oscilla-tion technique of Landser (J Appl Physiol

1976;43:101) and values were obtained

breathingvia thenose ormouthpieceinthe

erectandsupine posture. Inboth postures

each subject had ahigher Rrs via thenose

comparedtothemouth,and Rrswashigher

route.In theerect postureresistance

breathing via a mouthpiece In the supine

posturenasalbreathingwasagainmorethan

posture. Normal subjectsalso have rises in

the increase in resistance both in absolute and

percentage terms waslargerinourasthmatic

subjects Thus,inthesepatientswith chronic

breathingin thesupineposturereachedhigh

arelikelytobeevenhigher

Supported bythe AsthmaResearch Council

andaRoyalNorth ShoreHospital Centenary

A AAAA-t 20

JH DENNIS, SC STENTON, EH WALTERS, DJ

HENDRICK Chest Unit, Newcastle GeneralHospital, and Division of Environmentaland Occupational Medicine, University ofNewcastle upon Tyne Anumber ofrecent reportsdescribe increasing jet nebuliserout- put with increasing temperature of thereservoirsolution,outputbeing measured bythe total weight lost during nebulisation

Bradley and Durham further suggest that

temperature exerts an importanting effect when nonspecific bronchial res-ponsiveness (NSBR) is measured using aWright nebuliser and the tidal breathingmethod (BTS proceedings, Thorax1989;44:864P) This has stimulatedus to use

confound-a newtechnique (impaction of aerosolonto

glass fibre filters coupled with assay of afluoride chemical tracer) for assessing the

+vapour) from bothaWrightnebuliser and

at anairflowrateof 7 1pmfor theTurbo and

thermocouplewithin the nebuliser reservoir

monitored temperature changes over therange 2-40'C.Weight loss increased mark-

edlywithtemperaturefor both Turbo(3 fold)

and Wright (6 fold) nebulisers, but the

(Turbo96-12 7mg/2s,Wright41-82mg/

(10-20'C) this effect on aerosol output-is

inconsequential Since dosimeters nebulise

only tiny proportionsof the nebuliser

solu-tions, vapour loss will not produce any

appreciable change in concentration and measurementof NSBR shouldnotbe affected

bytemperaturechange.With tidalbreathing,however,aconsiderableconcentratingeffect

may occur and this would be exaggerated

temperature-thereby influencing the measurement of

NSBR

Temperature profile of a maximal

I MADAN, J LLOYD, AC PINCOCK, MR MILLERUniversity of Birmingham, Department ofMedicine,GoodHope Hospital,Sutton Cold-

field, West Midlands The temperature

profile during a maximal forced expiratorymanoeuvreisnotknown and itmayinfluencetheperformance of flow measuring devices

(5 pm diameter) placed 10 mm from the

mouth end ofa 28 mm i.d mouthpiece to

record air temperature on expiration Thetimeconstantof thethermocouplewas7ms

onimmersionincoldwater,260msinanair

flow of 0-51/s and 60msinaflow of1021/s

In 12 normalsubjects,whoperformedarapidinhalation through the mouth followed byimmediate exhalation, the temperature at

PEFwas33-4 (0 9) 'C (mean (SD))andwasalso 334(1 1)'CatFVC At25%, 50o%and75% of FVC the temperature was signifi-cantly higher (p < 005, Mann-Whitney),withapeak of 34-4 (0-4)'Cat75%of FVC In

10 patients with chronic airflow limitation

(mean FEV, 10 (0 5) 1) the temperature

profile was not significantly different from

that of the normalsubjects, being33-0(1-7)

When the normal subjects inhaledambient

airslowly throughthenoseall the tures, exceptthatatFVC,weresignificantlyhigher than before, with the maximum

inhala-tionofairat6'Cthroughthe mouth followed

theexpiredairtemperaturevariesbyup to

inspired air temperature.

Distribution of changes in tracheal

blood flow in dogs during isocapnichyperventilation and PEEP

DJ GODDEN, EM BAILE, PD PARE UBC

Pul-monaryResearch Laboratory, StPaul's

Hosp-ital, Vancouver We examined the effectsontrachealblood flow of (a) isocapnic hyperven-

positive end expiratory pressure (PEEP) in

dogs Five mixed breed dogswere

anaesthe-tised, paralysed, and ventilated through a

tracheostomy Tracheal blood flow was

reference flow technique (Baile et al JAP1982;53:1044) Measurements ofaorticbloodpressure, cardiacoutputand trachealblood

minutes'isocapnic hyperventilation(rate40/min, VT25ml/kg) and 20 minutes' ventilationduring which 15 cm H,O of PEEP wasapplied (rate15/min, VT 20 ml/kg) The dogswerethenkilledbyanoverdose ofanaesth-

etic,and thetracheawasexcised anddivided

andlower).Tissueswereprocessedtoallow

portion,andthe adventitia ineach sectionto

be separately determined Under baselineconditions,theratio of bloodflow expressedperunitmassoftissue,in mucosa:cartilage:

warm dry air increased blood flow to the

mucosa(mean (SEM) increase frombaseline

165(32)%)butcausednosignificant overallchangeinblood flow cartilage and adven-

Proceedings

titia PEEPmarkedlyreduced blood flowto

all levels of the airway wall,the reduction

58 (5) %in thecartilage,and36(9) %inthe

adventitia.The resultssuggest that, during

hyperventilation, vasomotion occurs in the

mucosalvesselsindependentofthe vesselsin

theunderlyingwall.DuringPEEP

substan-tial fallsin blood flowoccurthroughthefull

significance of this degree of ischaemia

requiresfurtherinvestigation

DGwassupported bythe WellcomeTrust

Endobronchial pH

P MCLOUGHLIN, P BYRNE, A STUART, J

PRIS-CHARD Departments ofMedicine and

Sur-gery, Trinity College, Dublin We have

measured endotracheal and endobronchial

disease, with chronic obstructive airways

disease and with pneumonia We used a

monocrystant, unipolar antimony electrode

(Synectics Ltd, Sweden, 2-1 mm tip

diameter) This was inserted through the

channelofanOlympus BF3 fibrescopeanda

Ag/AgCl reference electrodewasplacedon

the shoulder The possibility that such a

system might mislead by measuring

trans-epithelial potentialswaschecked So results

com-paredwithsimultaneousmeasurementsfrom

a bipolar glass microelectrode (Radiometer

EK2802C diameter4mm) positioned under

visualcontrol,sothatthetwoelectrodeswere

adjacentontheairwaysurface Nosignificant

difference was observed (A pH

(glass-antimony) + 0-15 ± 0-24(6),p > 01) In

lignocaineinstillationinto thelarynxnorby

equip-ment.We found that theendobronchialand

pH 5 71 (SEM029), right mainbronchus

5 62 (0-18), left main bronchus 5-60(0 25)

Theseresultswere notsignificantly different

lobar bronchi In 21 patients with COAD

airways) were found: tracheal 5-76 (0 33),

RMB 5-65 (050), LMB 5-60 (0 32) In

patientswithpneumonianodifference could

of peripheral airways by "wedging" the

antimony microelectrode Results were

sig-nificantly less acid than the central airways

(for example,leftlower lobe bronchus5-34

(0 11) (5), LLLwedge 6-87(0 27)(5), right

wedge6 89(0 64)(13)

Slowing of sternomastoid twitch

inspi-ratoryloadedbreathing

VHF MAK, SG SPIRO RayneInstitute,

Univer-sity College Hospital, London We have

previously reported slowing of the

rate (TMRR) with fatigue induced by

proceedings, Thorax 1989;44:887P)

How-ever, the role of stemomastoid fatigue in

respiratoryfailure isunclear,so we set out to

is subjectedto aheavy work load Five normalsubjects (mean age 24-6) were tested Thetechniques usedto measureTMRRwere asdescribed previously Fresh state twitchesweremeasured and then the subjectswere sat

up to perform maximal inspiratory effortsagainstafixedinspiratory resistance Expira-tionwasunloadedand theinspiratory effortwas measured on a Bourdon type vacuum gauge. The subjects had several practice

attempts before their maximal inspiratorypressure (Pimax) was determined Thesubjectswere thenasked to make maximal

inspiratoryeffortssustained fortwosecondseveryfourtofive seconds untiltheycouldnot

achieve70% oftheir initial Pimaxonthree

successive attempts (inspiratory loadedbreathing, ILB) ThestemomastoidTMRRwasthen determinedat oneminute intervals

following ILB for 10 minutes The meanfreshstateTMRRwas8-47%forceloss/10

ms (range 7 27-986) and the meanPimaxwas 118cmH2O (range 90-150).Themeandurationof ILBwas8-33min (range6-125)

ILBwas672%of freshstate(SD9 4)andthemaximum fall occurred at two minutes

(6622%SD 73).At five minutes the TMRR

minutes to87-2% (SD 13-4) Weconclude

that the sternomastoid TMRR can detect

fatigue induced by heavy respiratory loads

and thereforemaybe usedtodetectfatigue oftheaccessorymuscles in breathlesspatients

Association for financialsupport.

Aerosol delivery during mechanical

ventilation:nebuliserornebuhaler?

AK SIMONDS, SP NEWMAN, D COX, SW

CLARKE Department of Thoracic MedicineandIntensive CareUnit, RoyalFreeHospital,

ventilation ispoorly standardised and often

usedcommonly inventilatedpatientsand it

metered dose inhaler (MDI) via a spacerdeviceissuperiorto wetnebulisationduringmechanical ventilation (Crit Care Med1989;17:S153) UsingaServo900B ventilator(MV 10 litres, R 15/min, I:E ratio 1:2)

tube(ETT)to amodellungsystem, wehavecompared efficiency of delivery ofbroncho-dilatorfromastandard nebuliser andMDI/

be-tween the ventilator circuit and catheter

mount. Five milligrams of salbutamollabelled with Tc99m in 4 ml saline was

CR-60 compressor (Medic-Aid) For thespacer comparison four puffs of Tc99mlabelled salbutamol were inserted into aNebuhaler whichwasplaced in the ventilator

theperiodofincorporationofthe nebuhaler

to20 litresto compensateforincreased dead

space.Radiolabelleddrugwascollectedon a

PallUltiporfiltersituated between the ETTand model lung and counts corrected forbackground activity Mean (SD) deliveryas a

% of initial dosewas 11-04(0 93) from thenebuliser and 1-77 (0 29) from the MDI/

Nebuhaler.Despite the advantages of

reduc-ingprecipitation and duration oftreatment,

theMDI/Nebuhaler system is less efficient

tem-porarily increases the deadspaceand

com-pressiblegasvolume of the ventilatorcircuit,whichmaybe detrimental

Transbronchial lung biopsy (TBB)appearancesbefore and aftertreatment

foracutelung rejection (AR) in lung transplants (HLT)

heart-CA CLELLAND, S STEWART, TW HIGENBOTTAM,

JP SCOTT, J WALLWORK Heart-Lung

Trans-plant Research Unit, Papworth Hospital,Cambridge TBBisincreasingly beingused

todifferentiate ARfrom pulmonary infection

in HLTsasothermethodsareless sensitive

and less specific The characteristic logical feature of AR is dense perivascularlymphocytic infiltration SomeHLTpatients

important to be ableto distinguish treatedrejection (TR) from AR To aid the inter-pretation ofserial TBBswehave documented

the histological features of 28 biopsyspecimenstakenduringAR beforeinstitution

of treatment and their subsequent paired

augmented immunosuppression (meanintervalbetween initial andfollow-up biop-

sieswas23-5days, SD 13-4 days).Infectionwasstrictly excludedby histology and culture

ofbronchoalveolarlavage andsputum.Thefrequencyofperivascular infiltrates andthepresence of lymphocytes, plasma cells,neutrophils and eosinophils in the inflam-

matory infiltrateswereassessed titativelyas washaemosiderindeposition (-,

semi-quan-+, or + + allocated for each cell type)

Lymphocytes beforetreatment were ally large and blast like and were more numerous than in the follow up biopsieswhere morphologically there was a change

The frequency and size of infiltrates also

4-8)cellthickness in AR and 3-8 (3 5) aftertreatment) The lack of plasma cells pointstowards a cell mediated response in AR

Neutrophils and eosinophils were lessnumerous aftertreatment buthaemosiderindeposition was increased The changes in

morphological changes in follow up TBBspecimens offers some assistance in deter-mining the efficacy oftreatment.Inaddition,

two episodes of infection were diagnosed

Survival and quality of life following

heart-lung transplantation in

Eisen-menger's syndrome

G CREMONA, JP SCOTT, N CAINE, L SHARPLES, AT

DINH XUAN,TW HIGENBOTTAM, J WALLWORK

Papworth Hospital, Cambridge Patients

withend stageEisenmenger's syndrome (ES)

represent the largest disease group

under-going combined heart and lung

transplanta-tion (HLT) at Papworth Hospital (2985%).

Although HLT represents the only

poten-tially curative therapy forES,the selection

andtiming of ES patientsisoften difficultas

thepatients haveusuallybeenchronicallyill

foralong time and withrecentdeterioration

overseveral years.BetweenMarch 1982 and

July1989,42patients,meanage29-8(range

9-50) y,wereassessed andaccepted for HLT

Twenty ofthem,meanage29(range14-43)

y, underwent HLT All the transplanted

patients hadseverelongstanding pulmonary

hypertension (mean PAP 79 70 mm Hg)

secondary to congenital heart defects and

severe functional limitation (classes III/IV;

mixed venousoxygen saturation: 73%). At

the time of last follow up 15 patients have

survived Onepatient diedofcerebrovascular

accident 12 days post operation (PO); two

patients diedofCMVinfectionat46and 85

days PO Onepatient died of infectionat9

days PO Onlyone patientdied of chronic

rejection (416daysPO) Twopatientshave

obliterative bronchiolitis The actuarial

probability ofsurvivalat oneyear is78-95%

(SEM 935) Mean rejection rate is 132

episodes perpatient per year.The

Notting-ham Health Profilewas appliedtoeight of

thesepatientsto assess qualityoflife before

and after HLT A significant (p < 005)

improvementwasfound in allareasexplored

by theprofileexceptforsleep.Theseresults

indicate that HLT is a suitabletreatment for

end stage ES and offers a very significant

improvementinquality of life

Pulmonary function as a predictor of

pneumonitis in bonemarrowtransplant

recipients

HJMILBURN, HG PRENTICE, RM DUBOis Royal

FreeHospital, London If thehighmortality

associated withpneumonitisfollowing bone

marrow transplantation (BMT) is to be

reduced,adiagnosismustbe madeearly.In

the initial stages ofpneumonitis,thepatient

may have noabnormal clinical signs and a

normal chest radiographleadingto a

reluc-tance to investigate at this stage We have

measuredpulmonary function(PF) in BMT

recipients to attempt to (1) identify those

patients at risk ofdeveloping pneumonitis,

and(2) determine whetherchangesinPFare

good earlyindicators ofpneumonitis.PFwas

measuredbefore andatintervalsafter BMT

in 39patients.Fifteen of these laterdeveloped

pneumonitis and PF was measured when

symptomsfirstdeveloped.Before BMT there

was nodifferenceinPFbetweenpatientswho

later developedpneumonitisand those who

did not Six weeks post BMT the carbon

monoxidegas transfer(TLCO)was71(SEM

11)%ofthepretransplantvalue in those who

%inpatientswhodidnot(p< 0-01).These

measurements threemonths after BMTwere

77(7) % and 96(26) % respectively (p <

005) Therewas nodifference between the

twogroups ofpatients for FEV,, FVC, or

lung volumes six weeks and three months

after BMT Inpatients developing

pneumo-nitis, all parameters fell a further25-32%

predicted at the onset ofsymptoms, even in

those withno abnormal signs andanormalradiograph These results suggest that (1)pulmonaryfunction measurements aregoodindicators of developing pneumonitis afterBMT, and (2) a significant fall in TLCOsixweeksand/or three months after BMTcom-

pared with pretransplant levels predicts thosepatients at risk of developing pneumonitis

This further suggests that pneumonitisdevelops ona background oflung damagepresumably sustained at or shortly aftertransplantation

Value ofpulmonary function testing inthe diagnosisof lung rejectionorinfec-

tionfollowing lung transplantation

P NEILL, AD GASCOIGNE, TN STONE, JH DARK,

GJ GIBSON, PA CORRIS Departments of

Respiratory Medicine and CardiothoracicSurgery, Freeman Hospital, Newcastle upon

Tyne Themostimportant clinicalproblemsfollowing successful single lungorheartlungtransplantation lie in the promptrecognition

ofopportunisticpneumonia and pulmonaryrejection Symptoms and signs, ifany, are

non-specific and the chestradiograph

com-monly showsnoabnormality Penkethetal(Thorax 1988;43:762) suggested that

spirometric measurements were helpful inthis situation buttheyreportedonlyincon-sistent changes in gas transfer We haveevaluatedretrospectivelythepredictivevalue

ofchanges in FEV, and carbon monoxide

transfer factor(TLCO)performed priorto82

transbronchial lung biopsy and lavageproceduresin18lungorheartlung transplantrecipients at Freeman Hospital On 63

occasions the patients were investigated

because of clinical deterioration and in the

remaining 19 instances the only indicationwas asustained decline inlung function In

theformer grouprejectionorinfection was

provedon 51of63occasions.In the

predic-tionof thesechangesafall inFEV, > 10%

below theprevious baseline showed a

sen-sitivityof80% and specificityof75%; the

correspondingsensitivity andspecificityofa

fall in TLCO > 10% were 86% and 66%

respectively.When theindication forbiopsy

was a decline in function alone, a positivebiopsyand/or lavagewasobtainedon12 of 19

occasions.In thesecasesthepositive

predic-tive value of a10% decline in function was72% for FEV, and 69% for TLCO We

concludethatdeteriorationsinFEV,orTLCOare equally usefulasguides toinfectionorrejectionoftransplanted lungs

Heart-lungtransplantation for children

withcystic fibrosis

B WHITEHEAD, P HELMS, M GOODWIN,

IMARTIN, JPSCOTT,RLSMYTH, TW TAM,J WALLWORK,M ELLIOTT, M DE LEVALHospitals for Sick Children, Great Ormond

HIGENBOT-Street,London,andPapworthHospital,

Pap-worth Everard, Cambridge Children with

cysticfibrosis(CF)remain thelargest group

ofpatients(67%)referredtotheHospitalforSick Children forheart-lungtransplantation(HLT).Between March 1988 andSeptember

1989, 24 have been assessed, of whom 17

(70%)wereacceptedon to anactiveplant list Eight have received transplants(age range5-14years)while five havediedawaitingsuitableorgans.Donor andrecipient

trans-werematchedbyABObloodgroup,lungsizeandcytomegalovirus antibodystatus Initial

quadruple immunosuppression (cyclosporin

A, Azathioprine, methylprednisolone, andantithymocyte globulin) was used reducing

to dual or triple therapy There were sixsurvivors (8-440 days) The two deathsoccurred respectively at 36 hours from donororgan failure and 69 days from severe pul-monary infection Surveillance and grading

of rejection was made histologically fromtransbronchial biopsy specimens obtainedthrough a rigid or fibreoptic bronchoscope.There was a mean incidence of four episodes

of rejection in the first six post-operativemonths Other complications included: pul-monary infection (total number= 18) ofwhich Pseudomonas aeruginosa was the mostcommonpathogen; diabetes mellitus (n = 3);meconium ileus equivalent (n=3)and pan-creatitis (n= 1) All survivors experiencedsustained improvement in quality of life and

in dynamic lung function Postoperative

mean FEV, was 68% of predicted normal,compared with a mean of210% before trans-plantation

Vasodilatory properties of prostacyclinaidlung preservation

ofColorado Health Sciences Centre,Denver,Colorado, USA Using an isolated rat lungmodel, we have investigated preservationsolutions used in clinical heart-lung trans-

plantation.Prior to theremoval ofheart andlungs from anaesthetised rats, the lungs wereflushed with 50mlsolutions at4'C and thenkept incold saline for 6 hours They werethenreperfused with blood at 37C for 30

minutes Weight gain and wet to dry lungweight ratios were used as indices of lunginjury We foundthat an extracellular solu-

tioncontaining blood, albumin, mannitol andprostacyclin (Wallwork's solution: Trans-plantation 1987;44:654) gave significantlybetterprotection (p < 0-05,ANOVA) than

an intracellular solution, an extracellularsolution with lowpotassium plus dextran,or

a no flush technique We then compared

standard Wallwork'ssolution(WS)towork's solution without prostacyclin(WS - PG12) and Wallwork's solutionwithoutprostacyclinbutwith5mg and 10 mg

Wall-of glyceryl trinitrate (WS + 5GTN and

WS + lOGTN) Results (mean(SD))were

compared with ANOVA (* =p < 0 05

com-pared with WS - PG12) These resultssuggest that therat model isa simple and

efficient method for screeningpreservationsolutions, that Wallwork's solution has

advantagesoverothersinlungpreservation,

and that theaddition of prostacyclin confersbenefit but that a conventional vasodilatormayworkjustaswell

Role of viral culture in thediagnosisof

pneumonia afterheart-lung

transplan-tation

JP SCOTT, TW HIGENBOTTAM, G FRADET, RL

Heart-lung Transplant Research Unit,Papworth Hospital, Cambridge Opportunist

viralpneumonia has longbeen amajorcause

ofmorbidityandmortality after

tion (Dummer et al J Infect Dis

1987;155:202) In heart-lung transplant

(HLT) recipientsmost cases haveinvolved

infections with cytomegalovirus (CMV) or

herpes simplex virus (HSV). We have

previously reported the value of

transbron-chialbiopsies both in infection and rejection

inthesepatients(Higenbottametal

Transp-lantation 1988;46:532) We have taken

serially lung biopsy and bronchoalveolar

lavage material for viral culture and

trans-bronchial biopsytissueforhistologyon126

occasions on 42 HLT recipients since

November 1988 CMV was cultured from

lavage and/or biopsy specimens on 28

occasionsin 16 seropositive patients Lavage

specimens more commonly gave positive

results,lungbiopsy having65%ofthe

sen-sitivityoflavage specimens, butbothwere

required.Ofthe 14 cases ofhistology

confir-med CMV reactivation, in onlyfive (36%)

was viral culture positive whereas it was

positive in31%ofthecaseshistology

confir-med lung rejection Of the CMV positive

lung cultures only three out of 27 have

preceded, within six months, a need for

clinical treatment withganciclovir.By

com-parisonwith fivepositive culturesforHSV,

four(80%)werefollowed withintwoweeks

bytreatmentwithintravenous acyclovirfor

HSVpneumonitis In contrastto

transbron-chial biopsy histology, we conclude that

CMVlungandlavageculture is oflittlevalue,

whereas positive culture ofHSV isfrequently

so.Thismayreflect thechronic CMV

infec-tion ofourpatients

Which predicted values for

transplan-tedlungs?

Papworth Hospital, Cambridge Following

lung transplantation pulmonary function

tests are commonly expressed as per cent

predicted based on therecipient

characteris-tics.Although convenient,noscientific proof

has been advanced to support the use of

recipient characteristics in preference tothe

donor's Thetransplanted lung retains

nor-mal elasticproperties(Glanville et al Am Rev

Respir Dis 1988;137:308) but the host

thoracic cagedetermines the ultimate size of

thelungs (Otulana et al Transplantation(in

press)) We have studiedFEV,,FVC, PEF,

TLCO,Kco, RV, and TLC in 17 (11males),

meanage28-1 y,longestsurviving recipients

ofheart-lungtransplantation (HLT) Donors

were selected on the basis of radiological

matching as previously described (Hakimet

al J Thorac Cardiovasc Surg 1988;95:474).

ThePFTmeasurements were taken before

transplantation and then at one, two, and six

months and thereafter every three months,

periods of lungrejection and infection and

patients withobliterative bronchiolitis being

excluded Multipleregression analyses were

carried out with the time related

both the predicted recipient andpredicted

donor valuesasindependentvariables(table).

Acloserelationshipisshownbyahighand

significant (p < 0-05) regressioncoefficient

FVC(and PEF)relatesmore totherecipient predictedvaluesbeforetransplantation,and

againfrom nine months aftertransplantationonwards(the FEV,didnotassumerecipient

characteristics until one year). TLCO (and Kco)didnotshowaconsistently significant relationship with either predicted value

TLC (and RV) progressively assumes

recipient characteristics from immediately

after transplantation. These preliminary findings may providea basis for referencevaluesinlungtransplantpatients.

Bronchoalveolar lavage cell counts

during acute rejection and infection

following lung transplantation

HSR HOSKER, P MCARDLE, B SHENTON,JKIRBY,

JH DARK, PA comiRs Departments of

Res-piratoryMedicine andHaematology,Freeman

Hospital,Newcastle upon Tyne,and

Depart-mentof Surgery, University ofNewcastle upon

Tyne Wehaveperformedbronchoalveolar lavage (BAL)on40occasions in 12patients following singlelungorheart-lungtransplan-

tation as part of a study of lymphocyte

activation inrejection. BAL andchiallung biopsywereperformedin response

transbron-to aclinicaldeterioration suggestingrejection

orinfection on31 occasions andas partofroutinesurveillanceonnineoccasions BALwasperformedinasubsegmentoftheright

middle lobeorlingulausing 180 ml bufferedsaline.Differential cellcountsweremadeon

300 cells using May-Grunwald-Giemsa

stained cytospin preparations Bacterial or

fungal infection wasconfirmed on-41- viralinfectiononseven, andacuterejectionon13occasions No evidence ofinfectionorrejec-

tion was seen on nine occasions No

sig-nificant differenceswere seenbetween viralinfection andacuterejection but the propor-tion oflymphocyteswassignificantlyhigher

inboth of these than in normal (p < 0-001)orbacterial infection specimens (p < 0-001).

Bacterial infection was characterised by a

significantly higherneutrophilcountthan inanyothersituation We conclude that BAL %

lymphocytecountsrise in both acute tion and viralinfection following lungtrans-plantation and do not help to distinguishbetweenthese twoclinical events

Detection ofmalignantcells inpleuralfluidusingtheAgNOR stainingmethod

DBOLDY, JG AYRES,DROWLANDS,JCROCKER,J

YOUNG Departments of RespiratoryMedicineandHistopathology, EastBirmingham Hosp-

ital, Birmingham, andDepartment of ology, University of Birmingham A simplesilver staining method to demonstratenucleolarorganiser regions (NORs)showedhigh AgNORcounts in tumour cells com-

Path-pared to normal tissue (for instance,

squamouscell carcinoma of thebronchusvcolumnar epithelium, mesothelioma vmesothelial cells). In cell imprint prepara-

tions, higher AgNORcounts werefound inwhole cells than in3 gmsections(Boldyetal

JPathol1989;157:75).Theclarityofstaining suggested that the technique might beusefully appliedto cytological preparations

egpleuralfluid.Nineteenpleuralfluidswereexamined and slidespreparedfrom each OneslidewasstainedbythePapanicolaoumethod

in a routinelaboratory and reported byanindependent pathologist aseithermalignant

ornegative. The second slidewasstainedbythe AgNOR method and was classified as

probably malignant (many cells withnumerous AgNOR dots, without clum-ping=++), possibly malignant (few cellswithnumerousAgNOR dots, noclumping

=+)andnegative (no cells withnumerous

AgNOR dots=0). The case notes were

examined subsequently to determine if thepleuraleffusionwasassociated withamalig-

nant course. Good agreement was notedbetween a positive cytological report andeffusion associated witha malignantcourse(p=00048)andbetween theAgNORresultand clinical diagnosis (p=00048). TheAgNOR method identified two of threecytology negative, clinically positive cases,butalso hadthree falsepositiveresults(two

postpneumonic). A prospective study isrequiredtoexaminemorecloselywhether theAgNORmethodmay be useful in thediag-nosis ofmalignant pleuraleffusion

This work was supported by the Chest,

Heart,andStrokeAssociation

AgNOR

- 3 2 7

TheAgNOR stainingmethod and

prog-nosis in squamous cellcarcinoma of thebronchus

DBOLDY, JGAYRES,DROWLANDS,JCROCKER,

MGILTHORPE,JWATERHOUSE Departments of

Respiratory Medicine and Histopathology,

East Birmingham Hospital, and WestMidlands Regional Cancer Registry,

Birmingham Recent work using a silverstaining method (AgNOR) to demonstrate

nucleolar organiser regions (NORs) hasshownthatAgNORcountsrelatetotumour

differentiationinsquamouscellcarcinoma ofthebronchus (SqCCB) andnon-Hodgkin's lymphoma. To investigate whether theAgNORmethodmightbeusefulas aprog-nostic indicator, we studied retrospectively

138patientswhounderwentsurgical

resec-tion fora SqCCB at the EastBirmingham Hospitalin1977 Pathological T,N and M

status were determined by examination of

the notes, operation and

pathologyreportsandtumours,staged

accor-ding to the recent IUCC classification

Details of age, sex, site and type of operation,

completeness of resection, length of survival

and cause of death were also collected A

representative block of tumour tissue was

classified histologically and AgNOR

count-ing and DNA flowcytometrywereperformed

with the same paraffin block Full clinical

data were available for all 138 patients

Overall survival, age adjusted, excluding

postoperative deaths, was27-3%atfive years

and 20 7% at 10 years Thefive year survival

by T status was T1 360%;T2270%;T3 27%;

T410%;by NstatusNO40%;N121%;N2

8%;by stageofdisease I40%;II22%;IIIa

20%; IIlb 10%; IV0%. Completeness of

resection and operation performed both

affected prognosis Age, DNA ploidy and

AgNORscores were notrelated tosurvival,

even allowing for stage.of disease Thus,

although theAgNOR countingmethod may

behelpful in the diagnosis of malignancy, it

doesnotappear tobeanimportant prognostic

indicatorin squamous cell carcinomaofthe

bronchus

Thisworkwassupported byagrantfrom the

Chest, Heart, and StrokeAssociation

DNAploidy isaprognostic

discrimin-atorin early stage, surgically treated,

smallcelllungcancer

FA CAREY, S PRASAD, D LAMB, CC BIRD

Department of Pathology, University of

Edinburgh, and Department of Thoracic

Surgery, City Hospital, Edinburgh Fifty

three surgically resected small cell

carcin-omasoflung receivedinEdinburgh

Univer-sityPathologyDepartment in theyears

1982-7 were analysed for DNA content byflow

cytometry.DNAaneuploidywasdetected in

4155%ofthecaseswhile58-5%oftumours

were either diploid or tetraploid. The

relationship of bothploidyandTNMstatus

patients with diploid/tetraploid tumours,

7422% survived fortwoyearsormorewhile

only410%of the DNAaneuploidgroupwere

aliveat twoyears Nodalstatusis, however,a

betterpredictor ofsurvival, 72% ofNo/Nl

butonly2855%ofN2patients livingfortwo

years.Whenanalysisisconfinedtoearlystage

(No/Nl)tumours(39cases) 20/24 (8333%)of

diploid/tetraploid cases but only 8/15

(53.3%)of DNAaneuploidcases wereamong

thesurvivors This difference isstatistically

significant (p < 0-05). It is concludedthat,

whilenodalstatusis the bestoverallpredictor

ofprognosis insurgicallytreated small cell

lung cancer, DNA ploidy allows for finer

prognostic discrimination in early stage

tumours

Stereoisomers of verapamil in drug

resistant tumour cell lines

R MILROY, J PLUMB, S BANHAM, S KAYE

Departmentof RespiratoryMedicine, Glasgow

RoyalInfirmary,and Cancer Research

Cam-paign, Department of Medical Oncology,

University of Glasgow Verapamil (V), a

racemicmixtureofthe DandL isomers(DV

andLV)has beenused in clinical studies in

small cell lungcancer to tryandovercome

drug resistance (Milroy etal Lung Cancer

1988;4(suppl):A101). Theplasma

concentra-tionof V achievable in the clinic is limitedby

cardiovasculartoxicity. DV is aless potent

calcium channel blocker and may be less

cardiotoxic than LV(Echizen et al Am Heart

J 1985;109:210) Wehavestudied the

resis-tance modifying activity of both V and theindividual isomers, on the chemosensitivity

of the drug resistant tumour cell lines2780AD, MCF7/AdrR and H69LX10 to

doxorubicin (DOX) Neither V, nor theindividual isomers had any effect on the drugsensitivity of the parental cell lines (A2780,

MCF7, NCI-H69) V increased the

sen-sitivity ofall three DOX resistant cell lines

This activity was concentration dependent

Theincrease in sensitivity to DOX was only2-3 fold at 2 pM, the maximum plasmaconcentration achievable in patients This

activitywasmaximalat6-7uM,resultingina10-12fold increase in sensitivity for all threecelllines BothDV and LV were aseffective

as Vin terms of resistancemodifyingactivity

DV demonstrated the same concentrationdependentactivityasV Totalcellular DOXaccumulation inboth 2780AD andMCF7/

AdrR wasincreased2fold in the presence of

V (6-6 pM). Both DVand LV produced asimilar increase indrug accumulation Use of

DV alone in patients could i9crease the

maximum toleratedplasmaconcentration ofverapamil.ThusDV may be a more effectiveresistance modifier inlung cancerpatients

Clinical studiesusing DV are nowunderway

Lungcancerclassification: problems of

classification based on biopsy andcytological material

workingparty set upunder the auspices of the

UKCCR Subcommitteefor the Management

of Lung Cancer and presented on their

behalf) Departmentof Pathology, University

of Edinburgh Medical School, EdinburghThe WHO classification of Lung Cancer

or to cytological material Small cell

car-cinoma is one ofthe most straightforward

diagnoses butevensoaccuracyis probably nobetter than 95% While it is possible to

diagnose the better differentiatedsquamous

andadenocarcinomas, itmayonlybepossible

tostate that the tumour is not of small celltype Suchneoplasms are best described as

showing no discernible differentiation butnot small cell carcinoma This descriptionmay apply to halfthe non-small cell car-

cinomas Webelieve that correlation between

cytologyandhistology wouldbeimprovedifthe following categories were used: (1)

Squamous cell carcinoma; (2)

adenocar-cinoma; (3) small cell caradenocar-cinoma; (4) otherspecified tumours; (5) no discernible dif-ferentiation butnotsmall cell carcinomna; (6)

no discernible differentiation unclassifiedcarcinoma; (7) not typable for technical

attempttodescribe criteria for thediagnosis

andclassification oflungcancersuitable forsmall biopsies and cytological preparationsandaudit suchaclassification with the inten-tion ofintroducingsuchaclassificationon a

national basis

Prospective comparison ofdisposableand reusable bronchoscopic cytology

brushes

WJM KINNEAR, MJWILKINSON,PDJAMES,IDA

JOHNSTON University Hospital, Nottingham

We have undertaken a prospective

com-parisonof the twomain typesof

broncho-scopiccytology brushes,reusablebristleand

disposable rake, since our impression was

that the formeryielded superiorspecimens

Fiftypatients undergoing bronchoscopy forsuspected malignancy were studied.Samples

were taken from each patient withboth types

of brush in random order The pathologists'

gradingof the quality of the specimens (readblind) was similar for both types of brush Apositive diagnosis of malignancy was made in

31 patients with the disposable brush and in

28 patients with the reusable brush (p >

005) In six patients the disposable brushgave a positive diagnosis of malignancy butnotthe reusable bristle, and in three patients

thereusable brush was positive but the

dis-posable was negative The reusable brushgave apositive diagnosis of malignancy in 12

of 25 patients in which it was used first and in

16of25patients in which it was used second

(p > 0-05) Prior to this study our usualpractice was to use the reusable bristle brush

atthe end of the bronchoscopy, withdrawing

the bronchoscope with the brush stillprotruding Of the 25 patients in this study in

whichthis procedure was followed, a positive

diagnosis of malignancy was obtained withthereusable brush in 16 patients, whereas the

disposablebrush specimens taken from thesamepatients were positive in 19 patients (p

> 0-05) We conclude that the quality of

specimens and diagnostic yield from the

disposable rake andreusable bristle cytology

brushes are similar The time needed for

cleansing thereusable brushes and the risk of

transmitting infection may make the

dis-posable rake type the cytology brush ofchoice, despite the greater cost

Prevalence ofobstructive lung disease

in Norwegian communities and the riskassociated withoccupationaltitles

Thoracic Medicine and Sectionfor Medical

InformaticsandStatistics, University ofgen,Norway In a twophased cross sectionalsurvey the prevalence of obstructive lung

Ber-disease(OLD)wasexamined in thegeneral

population aged 18-73 years ofHordalandcounty,Norway, in 1988 Thefirstphase was

aquestionnairesurveyof 4992subjectsponse rate 900o) In the second phase a

(res-stratifiedsample(n=1512) of thoseingin thefirstphasewasinvitedtoaclinical,spirometric,and chestradiographicexamina-tion and an occupational history interviewcoveringall jobs held since leavingschool.The attendance rate was84%. The disease

twophased populationsurveyin Oslo county

in1974,including 1268subjectsaged20-69

years,usingthe samediagnosticcriteriaasthepresent study The overall prevalence ofOLDwas 5-50O in Oslo 1974and 7-7% inHordaland 1988(p < 0-05) ThemeanFEV,

of those withOLDwas78% ofpredictedinOslo and7400inHordaland(p > 0-05).Therole ofoccupational title as a predictor ofOLDwasexamined inacase-controldesign

where thesubjectswith OLD(n= 103) of theHordaland study werecomparedwith con-

trols (n=453) from a population tative subsample of those attending thesecondphaseof the Hordalandstudy.Hold-

represen-ing a job with high degree or airborneexposure (OT++) increased the odds forOLD with64(950/ CI23-184)comparedwithholdingajobwithnoairborneexposure

(OT-) after adjustment for sex, age and

smokinghabits Theadjustedodds ofOLD

in thosewho had OT + +jobsand OT +jobs

in 1970was83 (95% CI 20-344)and 1-6

(950%CI1-1-2-4) respectively comparedwith

indicatethattheprevalenceof OLD ishigher

in Hordaland county in 1988 than inOslo

countyin1974,and thatoccupationaltitle isa

predictor of OLD

Protective effectof neonatal BCGmay

CP BREDIN, M GODFREY St Finbarr's and

Regional Hospitals, and University College,

Cork, Ireland An episode of tuberculosis

occurredina604pupil girlssuburban

case was a 14 yearold student with smear

positive pulmonarytuberculosis(PTB).Five

other activecases weredetected(two PTB,

one pleural, one uterine, one meningitis)

Seventy five Heaf positive, radiographic

negativepupilswerealso identified Routine

December 1972 The BCG pupils(n=442,

majorityage >14years)showednostatistical

difference inattackrate (0o94%)versusthe

(attack rate 109%, n=182) In teenage

A comparison of the prevalence of

asthma, non-specific bronchial

hyper-responsiveness andatopyinTokelauan

J CRANE, TV O'DONNELL, D WAITE, I PRIOR

Departments of Medicine and Community

Health, Wellington School of Medicine,

Wellington, New Zealand We have

com-pared the prevalence of asthma symptoms,

non-specific bronchial hyperresponsiveness

(BHR),andatopyin5-15yearold children of

Pacific atolls that comprise the Tokelau

group. Among the younger children (aged

5-9 years) theprevalence of asthma

(NZ 300o,Tokelau 5%). Among the older

were moreprevalentin NZ thanTokelau(NZ

similarly more frequent in New Zealand

p =0-03) and was more severe (NZmean

Atopywasthree timesmore commoninNZ

These differences indicate that older but not

youngerTokelauanchildren in NewZealand

severityofabnormalairway responsiveness

Vacuum cleaningcarpetsandairbornelevels ofDermatophagoides pteronys-sinus

S OWEN, L WALLWORK, R MILLER, J HEPWORTH,

R NIVEN, D FISHWICK, S KALRA, A WOODCOCK

Wythenshawe Hospital, Manchester Housedust mite sensitive asthmatics frequentlybecome symptomatic aftervacuumcleaning

carpets.This ispresumedtobesecondaryto

increased airbome levels ofDermatophagoidespteronyssinus antigen (Derpl) contained inmitefaeces (10-40pmindiameter).Wehave

compared a conventional vacuum cleaner

(Hoover Junior) with a newhigh filtration

cleaner (Medivac), which filters 99.99% ofparticles down to0-3 gm We sampled air

in 16 domestic rooms (Rothero-MitchellSampler; Whatman GFFfilter;60 litresper

minute for fivehours) On the following dayrooms wererandomisedtobe vacuumedwith

either Medivac or Hoover Junior Duringvacuuming, and for thenextfivehours,roomairwassampled Sampleswerethencoded,weighed and analysed blind for Der pl(ELISA) Airborne Derpl levels increased

significantly followingvacuumcleaning withstandardcleaner(control mean(SEM) 179(0-19)ng;after Hoover 7 19 (6 75)ng; p <

0-01) There was no significant change in

(0 65); afterMedivac 1-88(0 79) ng).Therewas no change in airborne dust weight

prevents the increase in airborne Der p1

cleaning

AS ROBERTSON, PS BURGE Institute ofOccupational Health, University ofBirmingham, and East Birmingham Hospital,Birmingham Four boileroperatorsandone

from a Birmingham engineering company werereferredtooutpatientswithwork related

symptoms. All workerscomplainedofacute

Respiratory symptoms consisted of chesttightness, wheeze, coughandbreathlessness

runny nosewithpain,crusting and bleeding

involvedoperatingandoccasionally cleaning

employed, one having left one yearpreviously They had been employed fora mean of 10-6 (range 5-19) years. All had

previously been well while workingasboiler

operators elsewhere (mean 13-8 y) In

systematically unwell in association with

symptoms of asthma and profound nasal

Subsequenttothisexposureallworkers had

symptoms.One workergave a pasthistoryof

mucosaeandonehadanasalperforation Themeanlung function of those currently work-

(SD 18%), FVC 88% (SD 11%) Chestradiographswerenormal in allfive Onlyone

had positive skinprick test to

commonallergen Serial peak flow recordings

in thoseengaged in routineboileroperationsshowed occupational asthma in one, smallconsistentdeclines inmeanpeak flow intwo,

andanormal record in theremainingworker.Although the acute irritant effects of thevanadium contained within oil fired boilerdust is well recognised, the recurrentnasaland respiratory symptoms associated withlowlevel exposure describedhere havenotpreviouslybeen described

Establishing threshold values for lateasthmatic reactions (LARs) to occu-pationalagents

SC STENTON, JH DENNIS, EH WALTERS,

DJ HENDRICK ChestUnit, Newcastle GeneralHospital, University of Newcastleupon TyneInhalation challenge tests are frequentlyperformed in the investigation ofoccupational asthma but therehas been little

attempt toestablish dose responseships or threshold levels for the ensuingLARs.Theuseofastandardised protocol for

relation-testswiththree differentagentshas allowed

us todetermine thethresholdsatwhich LARs

deter-gentingredient iso-nonanoyl oxybenzene phonate (SINOS) (Thorax 1988;43:501), thedetergentenzymesubtilisin and theantibiotic ceftazidime Test subjects wereexposed workers with symptoms suggestive

sul-ofoccupational asthma Allwerechallengedwith the appropriate agent dissolved innormal saline using a locally designeddosimeterwhich delivers 50plofaerosolper

measurementsintheworkplace The initial

dosewaschosentobeapproximately 1/100th

of the calculated low average cumulativeexposureexperiencedover anormalworking

used, thechallengesequencefinishing when

anunequivocal LARoccurredorwhenthepredetermined maximum dose had beenadministered-generally10 x thecalculatedmaximumcumulativeexposure over awork-ing shift Saline challengeswereinterspersed

ventilatory function andastatistical analysis(Thorax 1988;43:866P) was used todetermine whenLARshad occurred (table)

2

3 4 5

The extraordinarilywide range encompassed

by these thresholds, particularly those for

SINOS, indicatesthe great difficulties whichwould be encountered in establishing work-

placeexposure limitsoncesensitisation hasoccurred

Respiratory symptoms in

pharma-ceuticalworkers manufacturing opiates

RM AGIUS Institute of Occupational

Medi-cine, Edinburgh Following diagnosis ofoccupational asthma and rhinitis in a process

workerexposed to dust from morphine andother opiates (Agius RM Br Med J1989;298:323), a cross sectional survey of

other employees was carried out using a

questionnaire administered by interview

opportunistically over a 13 month period

The workers were classified into six

occupational groups on the basis of a

qualitative assessment of current exposure

to opiates All 112 full time workers who

presented responded to the questionnaire

They comprised 69% of the full time work

force at the start of the study There were no

statistically significant differences between

the exposure groups in the prevalence of

symptoms including the following (overall

prevalence in brackets): persistent cough

(140%),wheeze ordyspnoea(17%), persistent

itchy nose with sneezing andstuffiness (21%)

andsneezing not broughtonby acold (56%).

Analysis of the unprompted attribution of

symptoms to a particular place,

supplement-edby temporal relations betweensymptoms

and exposure, showed that 19workers had

one or moreoftheirsymptomsinassociation

with opiate exposure These comprised

cough, wheeze or dyspnoea (four), rhinitic

symptoms(eight), sneeze (14) Twenty eight

reported symptoms, predominantly of

sneez-ing (19) with other occupational exposures

knowntobe associated withsuchsymptoms

(thecommonest wascapsaicin infive) Thirty

six reported symptoms in relation to

non-occupational exposures Analysis ofthepast

history identified commoner or worse

previous respiratory symptoms in 43

employees since commencement of this

employment In 18 of them this had been

associated with opiate exposure although

only seven of them hadcurrent symptoms

with opiate exposures Occupational

exposure may beassociated with symptoms of

rhinitis and/or asthma Further health

surveillance and environmental monitoring

oftheseworkers is warranted

Atmospheric air sampling and

implica-tionforestimation of antigen exposure

inpigeon breeders

K ANDERSON,RAMEWING, G BOYD, G MORRIS

Department of Respiratory Medicine, Glasgow

Royal Infirmary,andDepartmentof

Environ-mental Health, Strathclyde University,

Glasgow Previous reports of factors

influen-cing the development of pigeon breeder's

disease have used a calculated estimate of

antigen exposure based onthe variables of

pigeon number and duration of exposure to

pigeons with inconsistent conclusions (Fink

et al Chest 1972;62:266; Anderson et al

Thorax 1988;42:798), but no studies have

directlymeasured dustconcentrationswithin

loftsto confirm these assumptions

Respir-able and non-respirable airbome dust was

measured in21pigeon lofts, usingfree

stand-ing open face, cyclone, and lapel mounted

personalsamplers, for comparison with the

number ofpigeonsintheloft and fivesubjects

with pigeon breeder's disease within the

group.The number ofpigeons (median40,

range20-100)correlated with totalinhalable

dustcollectedovereighthoursbytheopen

face sampler (mean0-51 mg/m3, SEM0-1)

when theloftwasundisturbed(R = 0-481,

p=0-041) As expected, dust levels rose

after cleaningtheloft, doubling onaverage

overtheeighthourperiod Personalsamples

demonstrated peaks of exposure to higher

levelsof dust(respirable:mean3-59mg/m3,

SEM0-67 non-respirable: mean 15-25 mg/

mi3, SEM483), whichwereindependentof

thenumber ofpigeons (R -0-129 and

-0-168 respectively; NAS,). No significantdifferences in the dust measurements werefound between the subjects with and withoutpigeon breeder's disease These resultsexplain observed discrepancies betweenassumed degree of exposure based on thenumber ofpigeons kept and the presence ofsymptoms reported by others Dust exposure

is not related topigeon number, which at bestrelates only to the undisturbed loft, and doesnot reflect short term peaks of antigenexposure

Occupational asthma: a surveillancescheme

PFG GANNON, PS BURGE for the Midland

Thoracic Society Solihull Hospital,Solihull, West Midlands InJanuary 1989a

surveillance scheme ofoccupational asthmastarted in theWest Midlandsregion Chestphysicians and occupational physicians,together with the Health and Safety andMedical Boarding Centre (Pneumoconiosis

Panel) doctors,are circulatedmonthly. For

thefirst year it islookingatbothnewand oldcases,todate 164caseshave beenreported

Specificcauses ofoccupationalasthma were

foundin28%ofcases.Thetop10agents thatworkerswereexposedtoincludeisocyanates

(24%), colophony (11%), flour (10%), oilmists(7%), epoxy resins(7%), wood dusts

(70o), chrome (6%), hard metal (4%),

humidifiers (40%), and zinc (3%). In ourown unit (129cases) the diagnosis is made

on a history of holiday improvement ofrespiratory symptoms (88%), weekendimprovement of symptoms(78%),serialpeakflow measurement (72%), specific IgEantibodies(44%)and bronchial provocationtests(85%).Atthe MedicalBoarding Centre(22 cases) the figures are holidayimprovement (86%), weekendimprovement

(95%),serialpeakflowmeasurement(50%),specific IgE antibody (0%) and bronchialprovocationtests(5%) Chestphysicians (12

cases) make the diagnosis on holiday

improvement (100%), weekend ment(92%),serialpeak flow(61%), specific

improve-IgE antibody (0%) andbronchial

provoca-tion tests (80%) Only one case has been

reported from the Health and Safety

Executive Theoutcomeofdiagnosiswasasfollows:32% werestillexposedtothesameagent, 27% were unemployed, 16% had

changedto a newemployer, 11% had beenmoved within the same employer to avoidexposure,70%wereoffsick,and6%hadtakenearly retirement; but in only 2% had theagentbeenactually removed fromthework-

place to prevent further exposure to theindividual or their colleagues. Thissurveillance schemeshowsthat thediagnosis

ofoccupational asthmaisoften basedonsoftdata, specific immunology or bronchialchallenge testing being used infrequently

despitethe seriousconsequences of thenosisonthe worker'semployment.

diag-Correlation betweencottondust levelsand the prevalence of byssinosis inLancashire cotton mills

R NIVEN, D FISHWICK, CAC PICKERING,

A FLETCHER Department of ThoracicMedicine,WythenshaweHospital,ManchesterNinehundredandfifty-sixworkers and407manmade fibre workerswerestudied witharespiratory questionnaire to assess the

prevalence of byssinosis (4-1% in cotton)

Dust levels in the personal breathing zone

(PBZ) were estimated for 744 cotton workers

using standard(IOM) personal cotton plers Current legislation is based on themeasurement of work area dust concentra-

sam-tions (WAC) and these were measured in allworkrooms A retrospective dust loading(RDL) was ascribed to each of the 1363

operativesusing previous known dust levels

overa ten year period for each mill These

three dust parameters (PBZ, WAC, and

RDL)were correlated with the percentage ofoperatives with byssinosis A significant

positivecorrelation was found with each dustparameter Pearson's correlation coefficientswere: PBZ 0 54, WAC 0-60 and RDL 0-88

Multiple regression analysis was used tocompareRDL with time in the cotton indus-try,smoking and age This revealed that only

the additionoftime in the cotton industry tothe equation significantly increased the R'

value This study suggests that cumulative

dust loading is the most important factor

associated with the development ofbyssinosis

Respiratory symptoms and dust levels

in Lancashireweaving mills

SN RAZA, CAC PICKERING, D FISHWICK,

AFLETCHER, RNIVEN Department of Thoracic

Medicine,Wythenshawe Hospital,Manchester

Acrosssectional study of 1295 weavers was

performed in 15 cotton mills (1202operatives)andone manmade fibre mill(93)

Aquestionnaire was administered toassess

respiratory, nasal and eye symptoms Dust

levels were measured in thepersonal ingzone The meanagewas38years,57%were white and 43% Asian The following

breath-work related symptom prevalences werefound in the cotton mills (manmade fibremill): Byssinosis 0 33% (0%), productivecough 3% (3%), persistent non-productivecough 4% (1%), wheeze5% (6%),rhinitis

18% (8%)andeye irritation 13%(6%) Onlynasalandeyesymptomsdifferedsignificantly

between cotton and manmnadefibre In thecotton weaving mills the mean (SD) dust

concentration lessflywas1-63(1-32)mg/m3

and in manmade fibre 0-32 (024) mg/m3.

This difference was highly significant(p <0-001) The four operatives with

byssinosishad a meanageof43.The mean

dust level in this group was significantlyhigherat5-51(5-16)mg/m3(p < 0-001) Thisstudy documents the low prevalence ofbyssinosisin cottonweavingandrecognises

theproblemofpersistentwork related nasalandeyeirritation

Occupational asthma dueto lene shrinkwrapping

polyethy-PFG GANNON, GFA BENFIELD, PS BURGESolihull Hospital, Solihull, West Midlands

Meat Wrappers asthma due to polyvinyl

chloride (PVC) has been described (Sokal

WN et al JAMA 1973;226:639) It believed to be caused by acid anhydrides(from label adhesives) and from pyrolysis

is-productsofsoybeanoilincorporatedinto the

PVCwrapping (Pauli Getal ClinAllergy1980;10:263) Occupational asthma due topolyethylenehas beendescribed (Skerfving

S Lancet 1980;i:21 1) butnotconfirmed by

bronchial provocation testing. We havedocumented occupational asthma in an 18

year old packer with some pre-existing

asthma who worked on a shrink-wrap

machine,whichbrieflyheatsgoodssealedin

purepolyethylene packagingto760 Cwhen

the wrapping partially shrinks Twoweeks

afterstartingto usethis machine hebeganto

getasthmatic attackssixto sevenhoursafter

startingwork He had severalperiodsoffsick

and on the last occasion required hospital

admission after 30 minutes at work The

diagnosis was confirmed with serial

measurements of peak flow at home and

work, and by specific bronchial challenge

testing which showedalate asthmatic

reac-tionfollowing an eightminute exposure to

polyethylene heated to 76 degrees celsius

Following diagnosis he has been removed

fromexposure to theshrink-wrap machine

has confirmedpolyethyleneas a new causeof

occupationalasthmatobe addedtotheever

expandinglist ofcauses of thispreventable

condition.

Investigation of the effects of oral

p carotene on the chemiluminescence

responses and the frequency of sister

leucocytesfromcigarettesmokers

R ANDERSON, GA RICHARDS, AJ THERON,

CEJVAN RENSBURG MedicalResearch Council

Unitfor the Study of Phagocyte Function,

Division of Immunology, Department of

MedicalMicrobiology,Institutefor Pathology,

University of Pretoria, South Africa Sixty

asymptomatic cigarette smokers were

randomly allocated into three treatment

groups.Smokers ingroup1received 900IU

mgof carotene(BC) dailywasadministered

Individuals ingroup 3 were treated with a

counts, sister chromatid exchanges (SCEs)

and the luminol enhanced

chemilumines-cence(LECL)responsesof bloodphagocytes

(PMA) and FMLP with cytochalasin B

(FMLP/CB) were measured prior to the

SCEs and leucocyte counts remained

unchanged throughout the trial in all three

treatment groups.Administration of vitamin

(p <0-005) activated LECL responses.

However,with PMAasstimulant the

recovery observed after six weeks despite

progressive inhibition of both

appearedtoinhibitthegenerationofoxidants

H,0,/halidesystem.

Proteolytic activity and chemotaxis inperipheral blood and pulmonaryexudate neutrophils

GM BROWN, DM BROWN, S LANNAN, W MACNEE,

K DONALDSON Institute of OccupationalMedicine, and Department of Respiratory

Medicine,City Hospital, Edinburgh During

pulmonary inflammation neutrophils(PMN)exudate from the vascular space into t.e

tissue Activation of PMN during thisprocessis thoughtto causeincreasedsecre-

tion of proteinases with potential to cause

epithelial and connectivetissuedamage.We

therefore measured "'I fibronectin

proteolysis, epithelialinjuryandchemotaxins

inratperipheral blood PMN (BPMN) andexudated PMN(EPMN)obtained from the

bronchoalveolar space of experimentallyinflamed rat lungs Both populations were

oftheEPMN (5798 (58)), expressedas mean(SEM) cpm degraded "'I fibronectinreleased,wassignificantlygreaterthanthat ofthe BPMN (3758 (79); p < 0001) At aneffector:targetcell ratio of 1:1injurytocells

ofanepithelium like line (A549) caused byEPMN (8014 (398) cpm "Cr labelleddetachedcells)wassignificantlygreaterthanBPMN (5607 (239); p <0005) Both thechemotactic and chemokinetic activities ofthe EPMN were also significantly greater

thanthose ofthe BPMN:chemotaxissedas mean(SD) migrated cells/highpowerfield) EPMN92-1 (17-2), BPMN 35-3 (9-0);

(expres-chemokinesisEPMN71-8(17-8), BPMN 4-8(1-8); p <0001 Neutrophils in inflamedlungs have enhanced mobility and increasedcapacity to damage cellular septal andconnective tissue compared with peripheralbloodneutrophils

Human neutrophil mediated injury to

alveolarepithelialcells invitro

K DONALDSON, GM BROWN, DM BROWN, W

MACNEE InstituteofOccupationalMedicine,

Edinburgh, and Department of Respiratory

Medicine, UniversityofEdinburgh

Recruit-mentofneutrophilstothealveolar region of

the lung is found in emphysema and in a range of diseases which lead to fibrosis

Injurytothealveolarsepta mayresultfrom

thepresenceofthese neutrophils andmaybemediatedby neutrophilprotease oroxidant

Neutrophilswereisolatedfromthe blood of

labelled alveolar epithelial cells; both lysis

and detachment injury were then assessed

However, the neutrophils didcause ment injury to the epithelial cells withoutPMA (epithelialdetachment injury inmean

at5:13808(978)) On addition of PMA therewas a considerable increase in detachmentinjury (detachment injurytoepithelial cells

expressedasabove:noneutrophils + PMA

3661 (330), neutrophils at 5:1 3808 (978),

neutrophilsat5:1 + PMA8546(415)) The

detachment injury could be abolished byincluding antiprotease in the coculturesdetachmentinjury expressed asabove: epi-

thelial cells + neutrophils + PMA 1081

(859), epithelialcells+neutrophils + PMA

+a, proteaseinhibitor 41(70);antioxidantshad no effect ondetachmentinjury.Suitablytriggeredininflamedlung, neutrophils may

have thepotentialtoinjurealveolarepithelial

cells

ResearchfundedbytheColt Foundation

How-mightsmokeaffectneutrophilsinthepulmonarymicrocirculation?

E DROST, C SELBY, C LANNAN,

W MACNEE Department of RespiratoryMedicine, Rayne Laboratory City Hospital,Edinburgh (During cigarette smoking,neutrophils are delayed in the pulmonarycirculation(MacNeeetal NEnglJMed(inpress)) This delay may occur within the

pulmonary capillaries fromasmokeinduced

decrease in cell deformability This can bemeasured as an increasein theplateau pres-

sure developed by these cells, after smokeexposureinvitro, when passedat aconstant

flow across a micropore filter whose sizemimics theaveragedimensions of thehuman

pulmonary capillarysegments(MacNeeetal

AmRev Respir Dis 1989:A298) Inordertoinvestigate the mechanism of this smokeinduced decrease in neutrophil defor-mability,wecomparedthe plateau filtration

pressureproduced by smoke exposed

neutro-phils from normal subjects with that of

neutrophils activatedwithphorbol myristate

acetate(PMA) Although the increase in the

plateau filtrationpressurewassimilar in cellsexposed for four minutes to vapour phasecigarette smoke (control4 17(SEM205) cmH20;smoked 15 02 (7 03) cmH20,n = 10;

p <0-01) when compared with PMA

activatedcells(control 5 04 (1-64) cmH20;

PMA9 55(243)cmH20,n = 7; p < 0-01),

both the spontaneous (Sp) and PMA (P)stimulated release ofH202 was lowerfrom

smoke exposed cells (Sp 14(0 69), P 7-38

(185), n = 5) compared with control cells

(Sp 4 25 (2 15); P 21-67 (6 38), n = 5;

p <005 and <0 01 respectively)

Further-more, disruption ofthe cytoskeleton ofthe

neutrophilby theadditionofcytochalasinB

(10 5 M) reduced the plateau filtration

pressureof smokeexposedcellsfrom 16 16

oxidant These datasuggestthat thedecrease

in neutrophil deformability induced by

cigarette smoke doesnotresult incell tion,but may be aneffect of smokeonthe

activa-cytoskeletonas a result of oxidant inducedcell injury

Supported bytheChest, Heart,andStroke

AssociationandSHERT

Effects of phospholipase C in the

isolated rat lung: injury, eicosanoidproduction,and vonWillebrandfactor

(PLC) isabacterial exotoxinwhichmaybe

involved in the pathophysiology of acute

pulmonary infections 1 unit of PLC (or

control) was injected into isolated

salt-perfusedratlungs Measurementsweremade

of increase in pulmonary artery pressure

(A PAP)and lungwetweighttobody weight

ratios(wet/body wt)asindices of lunginjury;

vonWillebrand factor antigen (vW:Ag)as an

indexofendothelial cell damage; and

perfu-satelevels of6-keto-PGF,,,(PGF,,),

aspotential mediators A combination ofa

cyclo-oxygenase inhibitor anda

lipo-oxygen-aseinhibitorwasadministered priortoPLC

inafurther experiment.Resultsaregiven in

thetableas mean(SEM); differences between

means were significant at p <0-05 with

ANOVA

These results show that PLC is capable of

injuring the pulmonary endothelium directly

and thatblockade ofeicosanoid production

onlypartially ameliorates the lung injury

Relation between bronchoalveolar

lavage (BAL) cell profiles and airway

reactivity to histamine after smoke

J KINSELLA, R CARTER, CG GEMMELL, WH REID,

CJ CLARK Departments of Respiratory

Medicine, Hairmyres Hospital and Royal

Infirmary, Glasgow In a study of the

airways reactivity (Kelly et al Thorax

1988;43:684acorrelationwas found between

reactivityand bothneutrophilnumbers and

macrophage activity.Acutesmokeinhalation

is veryfrequentlyassociated with increased

airways reactivity (Kinsella et al BTS

proceedings, Thorax 1989;44:362P) This

study investigates the relationship between

in a group of 13 patients following acute

within24 hours ofinjuryandlungfunction

assessmentwithinone week Onepatienthad

ml), eight had mildly increased reactivity

(histamine PC20 1-8 mg/ml) and four had

moderately increased reactivity (histamine

negativecorrelation of histamine PC20 with

percentage neutrophil count (r = 0-65,

p <0-01) There were no other significant

counts, chemiluminescence of neutrophils

(leucigenin enhanced) or macrophage

(luminol enhanced) with increased airways

reactivity Thisstudy suggests that

pathogenesisofincreasedairways reactivity

Effect ofdexamethasone onneutrophilfunction in vitro and in vivo

DA LOMAS, A CHAMBA, RA STOCKLEY Lung

Immunobiochemical Research Laboratory,General Hospital, Birmingham Cortico-steroidsare potentanti-inflammatory drugsandare widelyused in the managementofpulmonary disease Their precise mode ofactionis unclear but theymay exert someoftheir effects by modulation of neutrophil

function In this studywehave demonstrated

that dexamethasone causes a significant(p <0025) dose related fall in neutrophilchemotaxisin vitrofrom53-7(SEM 9 6) to

247(8 9) cellsperhighpowerfield (cpf)at

10- mol/l However,dexamethasone hadno

invitro Sixhealthyvolunteers then took 12

mg ofdexamethasone daily for three secutive days and neutrophil function wasmeasured for two days prior to therapy,during therapy andoneweek aftertreatment.

con-Dexamethasonelevelsweremeasured duringoraltherapy for comparison withneutrophilfunction The serum concentrations were1-26(028) x 10-7'mol/londay1,1-44(0-15)

X 10-7mol/londay 2 and 1-31 (0-13) x 10-7

mol/l on day 3 Fibronectin digestion fell

from4 3 (0 12) to3 24 (0-2) ugfibronectin/

105 cellsduring therapy (p <0-001), butroseagainwithinoneweekofcessation of therapy

to3-96 (0 12).A330 changewasobservedat

a plasmaconcentration 1 44 x 10 mol/l,

Sci 1989;77:35) The average chemotacticresponse to 10 8 MFMLPwas29 5 (1-55)

(1 8) cpfwithintwohoursoftakingthe first

but roseagainto 25 75 (2 4) cpfoneweek

plasmadexamethasone levels of 1 26 x 10-7

mol/l in vivo compared witha similar fall(460o) occurringat 10-'mol/lin vitro Therewas nochangeinsuperoxideproduction (613

(0 91) nmol/10' cells/hour prior to therapy

treat-ment), confirmingthefindingsof the in vitro

experiment

flax dust on human respiratory

A MOGHADDAM, P NICHOLLS, C FELDMAN,

RC READ, L-Y HAN, A RUTMAN, H TODD, PJ COLE,

R WILSON HostDefence Unit,Department of

Institute, London, and Welsh School ofPharmacy, University of Wales, CardiffByssinosisoccurs among workersexposedto

occur acutelywhile chronic bronchitis may

may be plant derived, or a product of Gram

negative bacterial contamination (forexample, lipopolysaccharide) We haveexamined the effects of aqueous extracts ofplant dusts on normal human respiratoryepithelium over six hours by measuring

ciliary beatfrequency (CBF) and examiningepithelial structure by light and transmissionelectron microscopy The lipopolysaccharidecontentof the dusts was: cotton 684ng/mg,

flax 240 ng/mg and hemp 179 ng/mg Allthree extracts (5 mg/ml) slowed CBF

(p < 0-001) andcaused epithelial disruption

in a dose dependent manner Cotton dust,however, caused onlysmall changes in CBF

(2050°o ciliary slowing) and minor epithelialdisruption, while hemp and flax were muchmorepotent(89-4%and53-6%respectively).Progressive ciliary slowing occurred before

epithelialdisruption, but dyskinesia was notseen.The activityof hemp extract was heatstable (70°C, 30 minutes) and most was

removedby dialysis Although gel filtration

yieldedsomeactivity in the high molecularweight fraction, the majority was in thefraction below 10 kDa We conclude thatalthough the clinical syndrome produced bythe three dusts is similar their effects onrespiratory epithelium differ Hemp activitywas mainly due to a low molecular weight

factor(s),which could be of plant or bacterialorigin

Effect of recombinant cytokines on a,

antitrypsinproductionby monocytes

CA OWEN, RA STOCKLEY Lung

Immuno-biochemical Research Laboratory, General

Hospital, Birmingham Monocytes and

macrophages may be an important source oflunga,antitrypsin(a, AT) We have shown

that only 20% ofmonocytes from normalsubjects are spontaneously adherent (Clin Sci1988;75 (suppl 19):45P) We have comparedthe effects of recombinantcytokinesandLPSpurified from Haemophilus influenzae (LPSHI) on a, ATproduction by adherent and

non-adherent monocytes Monocytes wereisolated from six normal subjects, the

adherent and non adherent subpopulationswereseparated and cultured for 24 hours with

and withoutinterferongamma(IF, 1000U/

ml),tumournecrosis factor (TNF, 1000U/

ml), granulocyte macrophage colony

stimulating factor(GMCSF,50U/ml), andLPS HI (1 ug/ml). The average baseline

cellular contentof the non adherent cytes (81 (SEM 16) ng/million cells) wasgreater(p <0-025)than thatoftheadherentmonocytes (22 9 (2 8); p < 0025) The con-

mono-trol adherent cellssynthesiseda,ATover 24hours in culture, increasing to 79 7 (157)

(p < 0025)butincreasedmorewhentreatedwith all of the cytokines tested (IF 108 6(17 3); LPS HI98-9(17 3) (p <0025) andTNF 962 (14 6) (p <005) The controlnon-adherent monocytes alsosynthesised a,

AT in culture, increasing to 149-2 (21-5)(p <0025) but this production was not

increasedbyIF,TNForLPS HI.GMCSFwasthe onlycytokinewhich increased a, ATproduction by both the adherent (control 69 1(148) and GMCSF96-9 (173); p <0025)and non-adherent monocytes (control 206 5

(51-3)andGMCSF228-8(507); p <0-05).The results indicate thatupregulationofai,

ATproduction by avariety ofcytokines is

generallyafeature ofasubsetofmonocytesfrom normalsubjects

Endothelin (ET), a potent

vasocon-strictor, is also a growth factor and

chemoattractantfor fibroblasts(FB)

PEACOCK AJ, SHOCK A, GRAY AJ, REEVES JT,

LAURENT JG Medicine 1, Southampton

General Hospital, and Biochemistry Unit,

Department of Thoracic Medicine, National

Heart and Lung Institute, London

Pulmonary hypertension (PHT) from

whatevercauseis accompanied by pulmonary

vascularremodellingandhypertrophyof the

pulmonary arteries This involves deposition

of both contractile and connective tissue

elements in media and adventitia

respec-tively, but the mechanism ofthehypertrophy

is unknown We hypothesised that thesame

mediator mightcauseboththe

vasoconstric-tion and the hypertrophy ET is a novel

peptidesecretedbyvascular endothelial cells

which is knownto bea vasoconstrictor in

both the systemic and pulmonary

circula-tions We tested the effect of ET on the

chemotaxis and growth of rat skin FB

Chemotaxis: FB were placed in the upper

wells of modified Boyden chambers,

separated byfilters fromlower wells

hours theFBthatpassedthrough the filter

were counted ET stimulated chemotaxis

occurredover a rangeofconcentrations but

1 1) cells/fieldv 4 0 (1-6) field for control;

p < 0-001) Growth: FBwere grown in96

wellplatesinthepresenceof ETatvarying

werecounted by measuringlightabsorbarxce

after staining with methylene blue ET

M(121% (9%) stimulation relativeto

con-trol;p < 001).We conclude that ETcauses

chemotaxisandgrowthofFBbut thatgrowth

requireshigherconcentrations of thepeptide

These data support the hypothesis that a

single endothelialcellproductmayplaya part

subsequent hypertrophy which occurs in

PHT

Pyocyanin and 1-hydroxyphenazine

neutrophilsinvitro

GJ RAS, R ANDERSON, GW TAYLOR, R WILSON, PJ

University of Pretoria, South Africa;

Post-graduate Medical School, London; and Host

DefenceUnit,National HeartandLung

Ins-titute, London The effects of the

Pseudomonas aeruginosa derived pigments

pyocyanin and 1-hydroxyphenazine (1-hp)

on thespontaneous and stimulusactivated,

responses and on the release of lysosomal

enzymes by human neutrophilswere

inves-tigated in vitro Pyocyanin but not 1-hp

zymosan, calcium ionophore and

phorbol-myristate-acetate) generation ofsuperoxide

by neutrophils (p < 005), with maximal

the pigment Pyocyanin also increased the

agents, but especially 1-hp, increased the

myeloperoxidase (MPO)mediated iodinating

activityofneutrophils (p < 005) which, in

the of1-hp, due stimulation of the

release ofMPObyactivatedneutrophils (p <

0 05) In comparison with 1-hp, pyocyanincausedonly slight enhancement of the release

of MPO andlysozyme by stimulated

neutro-phils, butwasfoundtobemorepotentwith

respect tothe releaseof thespecific granulemarker, vitaminB-12binding protein Thesedata demonstrate diverse, proinflammatoryinteractions of pyocyanin and 1-hp withhuman phagocytes, which may intensifyneutrophilmediated tissuedamageduring Paeruginosa infections

In vitroneutrophil "filterability"

deter-mines in vivoneutrophil retention in thelungsinman

C SELBY, E DROST, PK WRAITH, GDO LOWE, W MACNEE Departments of RespiratoryMedicine, City Hospital, Edinburgh, and

Medicine, Royal Infirmary, Glasgow In a gamma camera computer system tofollowthe

reinjection of indium-l neutrophils(PMN) and technetium-99m erythrocytes(RBC),11 -3(SEM322%)ofinjectedPMNin

passage through the pulmonary circulation

(FPR)relativetothepassageofRBC

Sub-sequently, PMN washout from the lungsexponentially.We have shown in bothyoung

andelderlynormal individuals thatregional

PMNlung sequestration10minafter

reinjec-tion(1O'S)correlates with local bloodvelocitymeasured as RBC lung transit time (TT)(MacNeeetal NEnglJ Med(in press); Selby

etal Thorax1989;44:874P.Thisrelationship

(r=0-82, p < 0001), suggesting that

haemodynamic factors are important in

influencing this sequestration However,

(r= 009;p =07)orwith PMN 1O'S (r=033;

p =02).Inan attempt tomodel thepassageofPMN (diam 7 pm) through the lungcapillaries (diam5 pm),wehave measuredthe

plateau pressure that develops when 10'PMN ml-' pass at constant flow through amicroporefilter(porediam5 m) Aliquotsof

measurements oflung kinetics, were taken

just priortoradiolabelling Immediatelyafter

reinjection of the radiolabelled cells, the

aliquot was filtered The plateau pressure

developed by these cells in vitro correlated

significantly with their in vivo lung FPR

(r=0-89; p=0003) but not with 10'S

(r=047;p =02),nor to rateof washout fromthelungs (r=0-5; p=02) Clearly, neutro-

phil "filterability" which reflects cell

deformability,determines the firstpass

negotiatethelungmicrocirculation.By

con-trast, five to 10 minutes after reinjection,haemodynamic factors are important in

neutrophil sequestration, whichmayreflectcellmarginationwithinthelargerpulmonary

vessels

N-Acetyl cysteine partially prevents

S SHAHZEIDI, B SARSTRANDT, PK JEFFERY, RJ MCANULTY, GJ LAURENT Biochemistry Unit,Department of Thoracic Medicine, National

acetylated derivative ofL-cystein, which is

severalinvestigatorsinmodels of lung injury

butmostlywithhistological techniquesanditsability to prevent lung fibrosis remainscontroversial In thisstudywe assessed the

ability of L-NAC to prevent excessive

collagendeposition in mice given bleomycin.Mice (B6D, F,)were given L-NAC in thedrinkingwater(10% solution)for sevendays

prior to intratracheal administration ofbleomycin (150 ug per animal) L-NACadministration was continued and animalswerekilled after35days Collagen levelswere

assessed basedonhydroxyprolinetions following acid hydrolysis Total lungcollagencontentoftheanimals receivingL-NAC withbleomycinwere2-9(SD 0 3)mg

determina-compared with3-8(0 5)mgin those receivingbleomycinalone.Lung collagenincreasedby

41-0% (233%) above control in animalsreceiving L-NAC compared withanincrease

of 8400% (4.7%) for animals receivingbleomycin alone The collagencontentofthegroup given bleomycin alone were signifi-cantlyhigherthanfor animals treatedbyL-NAC(p <0 01) These datasuggestthatL-

NACispartially effective intheprevention of

the collagen deposition which followsbleomycin inducedlunginjury in mice

Effect of inhaled beclomethasone

dipropionate on peripheral neutrophil

function in vivo

DC WEIR, S JONES, A CHAMBA, PS BURGE, RA

STOCKLEY East Birmingham Hospital and

Lung Immunobiochemical Research tory, General Hospital, BirminghamIncreasedactivationandrecruitment of peri-

Labora-pheral neutrophils(PMN) are thought to play

amajor role in the pathogenesis of many lung

diseases including chronic bronchitis and

emphysema Previous studieshave suggested

that corticosteroids may reduce PMNchemotaxis and degranulation We havetherefore investigated the effect of inhaled

beclomethasone(750 or 1500pgtwice daily)

inpatients withchronic airflow obstructionand PMNfunction.Twentypatients (seven

female) aged 56-77yearswerestudied(mean(SEM) FEV,=1-07 (010)) Inhaled

beclomethasone increasedmean(SEM) peak

223(18)andplacebo value of 225 (19) (p <

0-05) The chemotactic activity of sputum

wasassessed ineight patients using

neutro-phils from healthy control subjects Theaveragenumber of cellsrecruited/highpower

field by the sputum diluted 1:5 was 90-8

(SEM65) beforetreatmentand 103-1 (13-4)

withplacebo, butwas lower 72-2 (6 6) with

inhaled steroids (p < 005) Spontaneous

degranulation of PMN (as measured by

fibronectin degradation)wasassessed in 10 ofthe patients The mean (SEM) baseline

values for thepatientsPMNbefore treatment

was 1 41 (0-38)pg/5x105cells/3 hours and1-39(0 19) on placebo There was significant

reduction during steroid therapy to 0 73

(0-17) (p < 0-05) Finally, the chemotacticresponseof the patients cells to 10' molarFMLP was reduced during therapy from a

baselinevalue of 67-0 (6-1) cells/high power

field to 48-1 (6-8) (p < 001) The resultsconfirm that inhaledcorticosteroids have asmall beneficial effect on lung function in

patients with chronic airflow obstruction

However, the treatment also reduces the

chemotactic activity of sputum and the

activation of peripheral PMN These latter

effects may beneficially influence theprogression of their lung disease