Proceedings of the Thoracic SocietyWWADDINGTON, A S BANNER, E V SUNDERRAJAN, MK AGARWAL, and J RODRIGUEZ The arterial and mixed venous (Pr,02) blood gases and haemodynamic state of

Thorax, 1979, 34, 414-429

Proceedings of the Thoracic SocietyA Meeting of the Thoracic Society was held in London on 1-2 February 1979. Summaries of

the papers follow:

Drug-induced oesophageal injuryH R MATTHEWS, F J COLLINS, S E BAKER, J STRAKOVAOesophageal injury from therapeutic agents has beenreported with increasing frequency and with an in-creasingly wide range of drugs since 1970. We reporta recent case of oesophagitis due to emeproniumbromide (Cetiprin) at the Queen Elizabeth Hospital,Birmingham, and review all the reported instances ofoesophageal damage caused by this and other drugs.A 15-year-old school girl developed severe pain and

difficulty on swallowing two months after startingemepronium for mild urinary incontinence. A bariumswallow was normal but endoscopy showed severeulcerative oesophagitis at the level of the aortic arch.There was no other oesophageal abnormality. Specialradiological and manometric studies established a con-nection between the drug and the oesophageal lesion,and complete healing occurred on withdrawal of thedrug.

Forty-one other cases of oesophageal damage due toeight different drugs have been reported, with ninedrug-related deaths. The clinical and pathologicalfeatures of these are reviewed in the hope of avoidingfurther instances of yet another iatrogenic disease.

Immediate and late consequences of heroin-inducedpulmonary oedemaW W ADDINGTON, A S BANNER, E V SUNDERRAJAN, M K

AGARWAL, and J RODRIGUEZ The arterial and mixedvenous (Pr,02) blood gases and haemodynamic stateof six patients with heroin induced pulmonary oedema(HIPO) were evaluated by Swan-Ganz catheterisationwithin three hours of admission to hospital. The F102was 1X0. The mean and range of the group as a wholeand the data of the two patients who died are shown:

pHPao2 (mmHg)Paco2 (mmHg)HCO3 (mEq/L)PvO2 (mmHg)BP (mmHg)RA (mmHg)PA (mmHg)PCW (mmHg)

Mean7-33

192402042123/70

5.327/109.5

Range6-89-7-47

34-34929-6513-2623-5960/40-150/1002-10

20/4-40/155-16

Died6-89, 7-02

34, 6529, 6513, 162360/40, 140/1005,10

25/4, 30/1510, 16

Hypoxaemia was due mainly to increased venousadmixture and the haemodynamic data are typical ofnon-cardiac pulmonary oedema. The two patients whodied were different from the survivors in having severemetabolic acidosis, a very low PVO2, and, in onepatient, systemic hypotension.

In a separate group of seven patients, referredbecause of productive cough and dyspnoea, broncho-grams were performed at least nine months after anepisode of HIPO. The chest radiographs were mini-mally abnormal and did not suggest significant air-way disease. In every patient extensive bronchiectasiswas recorded. Generalised bronchiectasis was foundin four patients while in the others findings were con-fined to the lower lobes. Abnormalities consisted ofvaricose or cylindrical bronchiectasis or both in allpatients and cystic changes in three. Pulmonary func-tion tests showed airflow obstruction, restriction, andimpaired co transfer.

In summary, the immediate consequences of HIPOare non-cardiac pulmonary oedema, severe hypox-aemia, metabolic acidosis, and death. A late conse-quence is bronchiectasis, which may be a commonfinding in symptomatic heroin addicts months to yearsafter recovery from HIPO.

Clinical, radiological, and pulmonary functionassessment in 13 long-term survivors of paraquatpoisoningG R FITZGERALD, G BARNIVILLE, R T N GIBNEY, and M X

FITZGERALD Death from ingesting the herbicideparaquat usually results from severe hypoxaemic respir-atory failure, secondary to characteristic diffuse intra-alveolar fibrosis. We studied 13 patients (11 adults andtwo children) who had survived a recorded episode ofparaquat poisoning for at least one year to determinethe prevalence of residual pulmonary disability. Of the11 adults, five (all non-smokers) had no clinical, radio-logical or functional evidence of pulmonary disease.A further four patients (all smokers) were considerednormal on clinical and radiological criteria but had amild deficit in pulmonary function, as evidenced byslight reduction in FEV/VC ratio and/or marginallyreduced arterial oxygen tensions in the resting re-cumbent position, the latter values improving onexercise. This physiological deficit could reasonably beattributed to the effects of cigarette smoking, but aparaquat effect could not be ruled out. The remainingtwo adult patients had pronounced arterial hypox-aemia. Both were known to have respiratory disabilityantedating paraquat poisoning, but one patient showednew and persistent pulmonary infiltrates that could beascribed to permanent paraquat lung damage. Finally,two young children had normal clinical, radiological,and simple pulmonary function indices. We concludethat most patients surviving an episode of paraquat

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poisoning have no clinically significant residual pul-monary damage. Based on serial radiological studiesbefore and after paraquat poisoning in one patient,there is some evidence to suggest that permanent lungdamage can occur occasionally.

Pulmonary vasoconstriction and oedema caused bytricyclic antidepressants in animalsG W GILL, GWENDA BARER, and D E SHIERS Fatalrespiratory changes resembling those of the respiratorydistress syndrome have occurred after amitriptylineoverdose (Lindstr6m et al, 1977). The tricyclic anti-depressant compounds are concentrated in the lungand only slowly removed. We have found in animalsthat amitriptyline, iprindole, and imipramine in largedoses cause pulmonary vasoconstriction, bronchocon-striction, and oedema.

Twenty-eight anaesthetised open-chested cats onartificial ventilation had one lobe of lung separatelyventilated and perfused at constant flow with blooddrawn from the right atrium. Lobar inflow and bron-chial and left atrial pressures were measured. Ami-triptyline (2-5 mg), iprindole (2-5 mg), and imipramine(1-6 mg) caused large often long-lasting rises in inflowpressure and smaller rises in bronchial pressure; leftatrial pressure hardly changed. The inflow pressurewas delayed until the fall in systemic pressure wasmaximal, suggesting that it might be secondary torelease of a vasoactive substance in the lung. We usedinhibitory drugs to investigate this possibility, but theexperiments were not entirely satisfactory since re-peated doses of tricyclics showed tachyphylaxis. Never-theless, pulmonary vasoconstriction and oedema stillfollowed doses of iprindole when an antihistamine, anca-adrenoreceptor blocker, a serotonin blocker, andprostaglandin synthetase inhibitors had been given(chlorpheniramine, phentolamine, methysergide, as-pirin, indomethacin, and flurbiprofen). The reaction isintrinsic to the lung as we observed pulmonary hyper-tension and oedema after all three tricyclic drugs inisolated rat lungs perfused with blood.The reaction is probably not due to platelet aggrega-

tion as an in vitro test showed that these drugs causeddeaggregation of platelets aggregated by ADP.

Investigation of these acute changes may help ex-plain the slow progressive changes after concentrationof the drugs in the lung in cases of poisoning, whichare increasing in number.REFERENCELindstrom, F D, Flodmark, 0, and Gustafsson, B (1977). Respiratory

distress syndrome and thrombotic non-bacterial endocarditis afteramitriptyline overdose. Acta Medica Scandinavica, 202, 203-212.

Occupational asthma, rhinitis, and urticaria in aresearch establishment breeding locustsP S BURGE, G EDGE, I M O'BRIEN, M G HARRIES, and J

PEPYS Locusts are now widely used in schools forteaching biology and in universities for research.Frankland (1953) described occupational asthma intwo scientists from each of two research establish-

ments. We describe a prevalence study in one of theseestablishments, where the two original cases were stillworking 24 years later. The study lasted six weeks. Arespiratory questionnaire was administered by one ofthree interviewers who also recorded FEV, and FVCbefore and after 200 jug salbutamol by inhalation.Workers were skin prick tested to six commonenvironmental antigens as well as antigens derivedfrom locusts, and blood was obtained for antibodyestimations.The workers were divided into four exposure groups

depending on their current job: (1) workers handlinginsects in the laboratory, (2) field workers, (3) otherlaboratory scientists, and (4) administrators, etc. Group2 workers were seen only if they were in Englandduring the survey. This included two thirds of group 2workers, and is likely to be an unbiased sample ofthem. All but one of groups 1, 3, and 4 workers wereseen.

Work-related respiratory disease was defined asbreathlessness, wheeze, or tightness in the chest thatimproved during a weekend away from work. It waslargely confined to group 1, where 28% were affected.Work-related rhinitis was more widespread, with 41%of group 1 workers affected. Clinical sensitisation waspresent in three workers before employment at thecentre; 16 of the remaining 20 workers were sensitisedwithin the first three years of employment. Atopy (oneor more positive skin prick tests to common environ-mental antigens) was found to predispose to respir-atory disease, particularly in group 1 workers, where47% of atopics and 18% of non-atopics were affected.FEV5 was reduced in those with work-related asthmacompared with the normal workers.

Specific antilocust antibodies correlated with expo-sure and disease. Positive skin prick tests were foundin 43% of group 1 workers and 27% of group 4workers. Of 100 consecutive patients in our allergyclinic 28% also had positive skin prick tests to locustantigens. There are probably cross-reacting antigensbetween insects and mites, which might lead to con-tinued symptoms in affected workers after occupationalexposure has ceased.REFERENCEFrankland, A W (1953). Locust sensitivity. Annals of Allergy, 1I,445-453.

Tuberculin-negative tuberculosis in children withpositive cultures for M tuberculosisP STEINER, M RAO, MINERVA S VICTORIA, H JABBAR, andM STEINER Results of repeated 5 TU PPD-S tuber-culin tests on 200 children with culture-proved Mtuberculosis infection showed that 28 initially werenegative reactors to the Mantoux test. Seventeen ofthem had extensive or overwhelming tuberculousdisease at the initial testing. Seven of these patientswere reactive to 250 TU PPD on admission, and allof the survivors (15) subsequently became positivereactors to 5 TU PPD-S after receiving antituberculo-sis treatment. Eleven patients who did not have life-threatening or serious forms of tuberculosis were

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negative reactors to 5 TU PPD, 250 TU PPD, and thenon-tuberculous mycobacterial antigens, PPD-A(Avium), PPD-B (Battey), PPD-G (Gause) on ad-mission and remained non-reactors to these antigens.These patients were retested monthly until dischargefrom hospital (three to six months).There was an explanation for the negative reactor

state of only two of these 11 children-one had leu-kaemia and the other sarcoidosis. There was no readyexplanation for the persistent negative reactor state inthe remaining nine children. It is concluded that a smallpercentage of children (4 5%) with non-threateningforms of tuberculosis may be negative tuberculinreactors despite no apparent cause. In such instancesother procedures must be used, such as lymphocytetransformation, biopsy, and culture, to establish thediagnosis of tuberculosis.

Geographical distribution of mycobacteria other thanM tuberculosis in the eastern United StatesH GRUFT, J FALKINHAM, and B PARKER The epidemi-ology of Mycobacterium intracellulare infection isstill unknown. Because the frequency of skin sensi-tivity to PPD-B in the USA is higher in the south-eastern coastal region, it has been suggested by Gruft,Katz, and Blanchard that the micro-organism residesin the ocean and estuaries of the southeastern USAand is transmitted to man via wind-blown water drop-lets formed during wave formation and rain.To test this hypothesis we surveyed fresh, brackish,

and ocean waters in the eastern USA. Samples werecollected from lakes, inland rivers, brackish rivers,sounds, bays, and ocean waters off the Atlantic coastfrom Maine to Florida and along the Gulf of Mexicofrom Florida to Louisiana.To date about 90% of the 850 strains of acid-fast

bacilli isolated have been identified; the relation be-tween their distribution and several other variableshas been studied.The acid-fast bacilli isolated from Gulf coast and

southern Atlantic coast samples were predominantlymembers of the M avium-intracellulare-scrofulaceum(MAIS) complex (82% and 70% respectively). Non-MAIS mycobacteria were found in the waters ofFlorida and the northeastern USA in 76% and 89%of the samples, respectively. No bacilli from Runyon'sgroup I or IV were isolated from any samples.Although only 30% of ocean waters of high salinitywere positive for acid-fast bacilli, 40% of the positivescontained MAIS. MAIS also predominated in brackishwaters-especially those with 1 to 2% salinity whilethe other mycobacteria predominated in other waters.

Studies are currently under way in our laboratoryto examine the tolerance of these water isolates tosalt and to detect any characteristic that may reflectspecial preference for any ecological niche.REFERENCEGruft, H, Katz, J, and Blanchard, D C (1975). Postulated source ofMycobacterium intracellulare (Battey) infection. American Journal ofEpidemiology, 102, 311-318.

Beta-adrenergic responsiveness in asthmatic and atopicnon-asthmatic subjectsJ E HARVEY and A E TATTERSFIELD The developmentof diminished bronchial beta-adrenergic responsiveness,or resistance, from excessive bronchodilator aerosolusage, has been suggested as a possible cause for theincrease in asthma mortality in the 1960s (Connollyet al, 1971). Most clinical studies in asthma have notsupported this suggestion. The development of resist-ance to the bronchodilator effects of inhaled sal-butamol, however, has been clearly shown in normalsubjects taking large doses of regular beta-agonists(Holgate et al, 1977).Using a similar technique and dosage schedule to

Holgate et al (1977) we have now studied eight atopic,asthmatic subjects and six atopic subjects with noclinical or symptomatic evidence of asthma. Specificairway conductance was measured in the bodyplethysmograph, and dose-response curves to inhaledsalbutamol (10-600 Mg) were constructed. After base-line studies the subjects took regular, inhaled sal-butamol, increasing from 100 ug four times a dayduring the first week to 500 jig four times a day duringthe fourth week. Dose-response studies to inhaledsalbutamol were repeated after each week.

In contrast to the findings in normal subjects, wefound no reduction in the response to salbutamol afterthe month of salbutamol treatment, either in asthmaticor atopic subjects. We also studied the responses tohistamine inhalation and the protection afforded byinhaled salbutamol to histamine challenge during thecontrol period and again during the fourth week ofsalbutamol treatment. Neither group showed any sug-gestion of salbutamol resistance after four weeks'treatment.

Studies of diurnal peak expiratory flow rate patternsbefore and after four weeks on salbutamol showed nosignificant changes in either group. There was, how-ever, a consistent fall in baseline FEVY in the finalweek of the study, in both the asthmatic and theatopic group, though salbutamol responsiveness wasmaintained.These studies show no evidence of diminished beta-

adrenergic responsiveness in either asthmatic or atopicnon-asthmatic subjects after large doses of inhaledsalbutamol. The difference between these results andthose obtained in normal subjects suggests differencesin beta-receptor function.REFERENCESConnolly, M E, Davies, D S, Dollery, C T, George, C F (1971).

British Journal ofPharmacy, 43, 389-402.Holgate, S T, Baldwin, C J, Tattersfield, A E (1977). ,8-Adrenergic

agonist resistance in normal human airways. Lancet, 2, 375-377.

Effect of ipratropium bromide (Atrovent') andterbutaline (Bricanyl") on mucociliary clearance andpulmonary function in chronic obstructive bronchitisD PAVIA, J R M BATEMAN, N6IRIN F SHEAHAN, and s wCLARKE The effects of regular administration (twopuffs four times a day for seven days) of a syntheticanticholinergic ipratropium bromide (Atrovent"), and a

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beta2-adrenergic, terbutaline (BricanylR), on lungmucociliary clearance and as bronchodilators wereascertained in a controlled, double-blind, cross-overstudy in seven patients (six male, one female) withchronic obstructive bronchitis.The mean (+SD) age and height of the study group

were 62-9 (+8 9) years and 1-70 m (+0 08) respectively.Six were current cigarette smokers and one was anex-smoker with a mean (+SD) tobacco consumptionfor the group of 53 (+23) pack-years. The mean+SDpulmonary function indices for the group with thepercentage of predicted values in parentheses wereFEV1: 1-22+0-58 1 (44±15%); FVC: 2-56+0-52 1(73+20%); FEV1/FVC: 44+14%; and PEFR: 174±91 1 min-' (37+20%). The mean (+SD) increase inFEVI after the inhalation of two puffs (1 mg) ofisoprenaline administered from a metered dose inhalerwas 30 (+24)%.Two puffs from a metered dose inhaler of either

AtroventR_placebo (propellants only), AtroventR(40 gg), BricanylR-placebo (propellants only), orBricanyl? (500 jg) were administered four times a dayfor one week each, and mucociliary clearance wasmeasured by radioaerosol tracer (Pavia et al, 1978) aswell as pulmonary function at the end of each treat-ment period and after a control period (seven days) inwhich no treatment was given. On the mornings ofthe measurements, after the placebo and drug periods,one final dose of treatment was given about 135 minbefore the start of the test.Comparable improvements in pulmonary function

were noted for both bronchodilating agents, whichwere statistically significantly greater compared to therespective placebos. There was no statistically signifi-cant difference between the five mean mucociliaryclearance curves for the group; however, there was asignificantly (P<0-05) greater penetration towards theperiphery of the lung of the tracer radioaerosol (poly-styrene particles, diameter: 5±0-8 Mm) in the test afterthe ipratropium administration compared to the otherfour.We conclude that in chronic obstructive bronchitis

both AtroventR and BricanylR are equally effective inreversing bronchoconstriction and do not alter the rateof clearance of lung secretions. With Atrovent', how-ever, there was enhanced penetration of particles,suggesting the two drugs have a different site ofaction. Scrutiny of the maximum flow-volume curves,however, failed to differentiate this difference further.These results were confirmed when the total num-

ber of patients studied were increased to 12 for theAtroventR and nine for the BricanylE.REPERENCEPavia, D, Thomson, M L, and Clarke, SW (1978). Enhanced clearanceof secretions from the human lung after the administration ofhypertonic saline aerosol. American Review of Respiratory Disease117, 199-203.

How cardioselective are the new beta-blocking drugs?A D MACKAY, H R GRIBBIN, C J BALDWIN, and A ETAlTERSFIELD Many of the new beta-blocking drugsare claimed to be cardioselective and therefore

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relatively safe for patients with asthma. It has, how-ever, been difficult to assess cardioselectivity accuratelyin man since previous methods did not allow bronchialbeta-blockade to be measured quantitatively. Gribbinet al (1977) described a method for assessing bronchialbeta-blockade in man in a quantitative manner, and wenow describe the results with four new beta-blockingdrugs-atenolol, acebutolol, labetolol, and bevantolol.

Bronchial beta-blockade was assessed by carryingout salbutamol dose-response studies in six normalsubjects, measuring the change in specific airwayconductance (sGaw), after increasing doses of inhaledsalbutamol. These were then repeated after two dif-ferent doses of each beta-blocking drug and the shiftto the right of the dose response curve was used as ameasure of the amount of bronchial beta-blockade.To assess cardiac beta,-receptor blockade we carriedout steady state exercise at 70% of the previouslydetermined maximum work load in the same subjectsafter the same dose of each drug. All studies werecarried out at the same time of day and at least fourdays apart. The first studies on practolol and pro-pranolol were extended to include atenolol, 50 and100 mg, acebutolol, 100 and 200 mg, labetalol, 150and 300 mg, and bevantolol, 75 and 150 mg.

Our studies showed that all four drugs in bothdoses caused considerably less bronchial beta-blockadethan 40 mg of propranolol. Practolol, atenolol, andbevantolol produced a similar degree of bronchialbeta-blockade and less than acebutolol and labetalol.Atenolol and bevantolol also produced the greatestreduction in exercise heart rate.REFERENCEGribbin, H R, Baldwin, C J, and Tattersfield, A E (1977). A method of

assessing bronchial selectivity of beta-adrenoceptor antagonists inman. Thorax, 32, 643-652.

Response in asthmatic patients to ambient sulphateair pollutionANNE HERSEY COULSON, R DETELS, R G FREZIERES, andR KATZ The relationship between respiratory symp-toms, peak flow, and use of medicines in 34 individualswith atopic asthma diagnosed by a physician andchanges in levels of ambient air pollutants and pollenswas studied. Members of the asthma panel all livedwithin four miles of a monitoring station of theSouthern California Air Quality Management Districtin an area historically exposed to relatively high levelsof sulphate and particulate pollutants and relatively lowlevels of oxidant pollutants. Total particulates, sulphurdioxide, nitric oxide, nitrogen dioxide, oxides of nitro-gen, carbon monoxide, pollens, and moulds were con-tinuously measured. Levels of sulphates were measuredfive days a week during the study period. Climaticvariables including temperature, humidity, precipita-tion, barometric pressure, and wind direction andspeed were collected continuously.Panel members used portable Wright peak flow

meters three times each day and maintained a dailydiary of (lay and night symptoms, and use of medicinesfrom August 1977 to April 1978. Correlations ofsymptoms and medicines with peak flow were poor;

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between symptoms and use of medication, reasonable;and between day and night symptoms, good. The cor-relation of symptoms, changes in medication and peakflow with changes in level of each pollutant wereanalysed for each panelist. The mean symptom scoreof panel members on days falling in the highest andin the lowest tertile of sulphate levels were compared.Eleven of the 34 panelists responded to sulphates; fourreported symptoms only and seven reported symptomsplus peak flow and/or medication level changes thatcorrelated with levels of sulphate pollutants. All butone of these responded primarily to changes in sul-phates with few correlations to changes in otherpollutants. The results of this study suggest that atleast seven of the 34 asthmatic patients followed weresensitive to changes in levels of sulphates.

Tracheobronchial clearance in asthmaJ R M BATEMAN, D PAVIA, N6IRIN F SHEAHAN, J E AGNEW,and s W CLARKE Airway obstruction in asthma arisesfrom smooth muscle contraction, mucosal oedema,and mucus plugging (Dunnill, 1971). Little attention,however, has been focused on the role of mucociliaryclearance and mucus plugging in asthma. The presentstudy has been designed to assess tracheobronchialclearance of lung secretions, firstly, in patients in re-mission from asthma and, secondly, in patients withmild asthma.The method used the inhalation of uniform 5 ,um

polystyrene particles permanently labelled with theradionuclide 99"'Tc (half life 6 h) and subsequent wholelung counting at 30-minute intervals over an initialsix-hour period (Thomson and Short, 1969). A finalcount was made at 24 hours to determine alveolardeposition of the radioaerosol and thus enable calcula-tion of tracheobronchial clearance over the 24 hours.The data from five patients with asthma in remission(asymptomatic and requiring no treatment for oneto six months) and five patients with mild asthma(symptomatic and requiring regular treatment) havebeen non-parametrically compared with that frommatched normal control subjects.Pulmonary function was determined for each

asthmatic and control subject and only three indices(FEV1, PEFR, and MMFR2-75) expressed as a per-centage of predicted values were significantly reducedin the mild asthmatic group when compared with thecontrol group (P<0 01).

In the table the group mean clearance of depositedradioaerosol from the tracheobronchial tree is ex-pressed as a percentage of the total 24-hour clearancefor the asthma remission, the mild asthmatic, andrespective control groups for the first six hours afterradioaerosol inhalation. Clearance of radioaerosol wassignificantly less for the mild asthmatic group whencompared with the respective control group (P<0-05).Tracheobronchial clearance over the same period inthe asthma remission group was similar to therespective control group.We conclude that mucociliary clearance is impaired

in mild asthma but normal when patients are in com-


plete remission. This finding implies that mucociliaryslowing may be an important factor in the pathogenesisof asthma.REFERENCESDunnill, M S (1971). The pathology of asthma. In Identification ofAsthma, edited by R Porter and J Birch. Ciba Foundation StudyGroup No 38. Churchill Livingstone, Edinburgh and London.

Thomson, M L, and Short, M D (1969). Mucociliary function inhealth, chronic obstructive airway disease, and asbestosis. JourntalofApplied Physiology, 26, 535-539.

Tracheobronchial clearance of deposited radioaerosol over the initialsix-hour period expressed as a percentage of the total 24-hourclearance

Mean Range

Asthma remission 76 60-89Control group 72 55-91Asthma mild 56 49-64Control group 81 63-100

Physiological comparison of adult PiM and PiMZphenotype subjects from a random populationR J KNUDSON, M D LEBOWITZ, D J MCDONAGH, ands P NATHAN For plethysmographic studies of lungmechanics and pulmonary diffusing capacity, 62 sub-jects were drawn from a randomly selected populationsample. Data obtained from the 24 subjects of PiMZphenotype were compared by age group with datafrom 38 PiM subjects matched for sex, age, and smok-ing history. Comparison of mean values for lungvolumes, lung elastic recoil, maximum expiratoryflow, diffusing capacity, and the occurrence of fre-quency dependence of dynamic compliance showed nodifferences between phenotype groups.For comparison, previous data obtained from a

highly select group of normal subjects of the PiMphenotype have been included. A plot of the rate ofloss of recoil per year of age was obtained. From thisfigure it is apparent that the present subjects, viewedeither collectively or by phenotype, lose elastic recoilat a greater rate than those previous subjects studied.Despite the greater loss of elastic recoil in the presentsubjects there is no evidence of an accelerated effect ofage on the PiMZ subjects when compared to the PiMsubjects, nor was there evidence of an increased effectof smoking. From these data it appears that the PiMZphenotype per se is not a risk factor in developmentof emphysema.

Clinicopathological correlations in chronic corpulmonale complicating chronic bronchitis andemphysema after treatment with long-term domiciliaryoxygen therapyD LAMB, P M A CALVERLEY, R J E LEGGETT, R BULMER,and D C FLENLEY Clinicopathological relations are re-ported in 15 patients suffering from chronic hypox-aemia (PO2 breathing air 45-58 mmHg), with C02retention and pulmonary hypertension (mean pul-monary artery pressure 20-50 mmHg) along withsecondary polycythaemia (red cell mass 23-86 ml/kg).



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All suffered from irreversible airways obstructionand hyperinflation of the lungs due to chronic bron-chitis and emphysema, complicated by chronic corpulmonale, and 12 were treated with long-term domi-ciliary oxygen for three to 72 months beforedeath. Oxygen for 12-15 hours in the 24-hour day, ata flow rate of 2/lmin was provided to raise the daytime arterial oxygen tension to over 60 mmHg. Atnecropsy most of the patients had right ventricularhypertrophy, as shown by the ratio of the weight ofthe left ventricle plus septum to that of the rightventricle of between 1-0 and 2-7, and this hypertrophyappeared to persist despite partial reversal of pul-monary hypertension by the long-term oxygen treat-ment. Despite these homogenous abnormalities inclinical pattern and respiratory function, which wereallegedly typical of the "blue and bloated" types ofpatients, at necropsy there was considerable variabilityin the extent of bronchial gland hypertrophy (Reidindex 25-69%), and also in the extent of panlobularand centrilobular emphysema.There was no definite pathological evidence of

oxygen toxicity, and the alveolar to arterial oxygentension gradients were not increased during long-termoxygen treatment, suggesting that progressive pul-monary fibrosis from oxygen treatment is not a majorhazard in these patients undergoing this treatment overprolonged periods. The possibility of reversing thepulmonary vascular changes resulting from chronichypoxaemia in these patients will also be discussed.

Nature of chronic lung disease in highland Papua,New GuineaH R ANDERSON At Goroka, in the eastern highlands ofPapua, New Guinea, 46 men and 24 women withevidence of chronic lung disease underwent clinical,lung function, and other investigations. Forty-threepatients had an FEV1 of less than 50% predicted, and19 had cor pulmonale. All subjects were found to havechronic obstructive lung disease which closely re-sembled that seen in European populations. Comparedwith a series from London and Chicago, however, thehighland subjects were 10 years younger and had morenormal values for total lung function capacity andtransfer factor. Previous reports that highland chroniclung disease has a restrictive component due to pul-monary and pleural fibrosis were not confirmed.

Epidemiological studies have been unable to relatehighland chronic lung disease to tobacco smoking.Exposure to domestic wood smoke appears to be themost probable cause though the evidence for this andfor other possibilitites, such as acute respiratory in-fections, remains inadequate.

Corticosteroid trials in patients with chronic airflowobstructionJ WEBB, T J H CLARK, and CLAIR CHILVERS Patientswith chronic airflow obstruction inadequately con-trolled with bronchodilators are often given a courseof corticosteroids to reverse the airflow obstruction.

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These trials of corticosteroids vary in both durationand dose, since the time course and dose-responsecharacteristics of the response of airflow obstruction totreatment with corticosteroids is not well defined. Wehave performed a trial with 40 mg prednisolone a dayfor three weeks with an initial week on placebo in 19patients with chronic airflow obstruction in order tostudy the time course of response to corticosteroids.Each patient recorded the peak expiratory flow (PEF)twice daily for the four weeks, and in addition shorttetracosactrin tests were performed before and afterthe trial in eight patients, and the recovery of thebasal cortisol and ACTH levels were observed for fivedays after the last dose of prednisolone in a furtherseven patients.The PEF of the 19 patients were submitted to an

analysis of variance that showed a highly significantdifference in PEF over the four weeks (P<0-01) anda highly significant difference between morning andevening PEF. These morning and evening differencesin PEF remained constant throughout the four weeks.Individual response to prednisolone was assessed bycomparing the PEF during week 1 on placebo andthe PEF during weeks 3 and 4 while on prednisolone.Response or lack of response to prednisolone wasassessed in two ways: (1) using a 10% increase inPEF as a response criterion and (2) carrying out at test on the data with a significance level of 1%.The same 13 responders were identified using bothcriteria, and their mean response was 28%. The maxi-mum response occurred on the eighth day of treat-ment. The individual responses were assessed by eye,and in 12 patients the maximum response of PEFoccurred within eight days and in the remainingpatient 11 days. The morning and evening differencein PEF remained constant throughout the four weeksin the 13 responders.The basal cortisol and response to tetracosactrin

was normal before treatment (mean cortisol 381 nm/l,881 nm/l). The basal level and tetracosactrin responsewithin 24 hours of the last dose of prednisolone wereboth abnormal and highly significantly different fromthe pretreatment levels (75 6 nm/i P<0-01; 207 nm/lP<0-001). The basal cortisol and ACTH levels in afurther seven patients both rose simultaneously tonormal levels within four days.The following conclusions can be drawn: (1) 13

patients, considered as a group, reached a new im-proved level of PEF after eight days of treatment. Inindividual patients the time taken to reach the newlevel did not exceed 11 days. Six patients failed torespond to corticosteroid treatment; (2) basal cortisoland ACTH levels were depressed after three weekson 40 mg of prednisolone a day and rose to normallevels within four days; and (3) prednisolone did notsignificantly decrease the morning dip in PEF.

Factors contributing to the clinical grade ofbreathlessness in coalworkers with pneumoconiosisA W MUSK, CAROL BEVAN, M J CAMPBELL, and J E COTESFactors underlying the capacity for exercise have been



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investigated in 125 coalworkers with pneumoconiosis,first investigated in 1969 (mean age 52 years) andfollowed up in 1978. Investigations included the BMRCquestionnaire on respiratory symptoms, anthropometry,spirometry, measurements of transfer factor, lungmechanics, and the physiological response to exercise.

Multiple regression and discriminant functiontechniques were used to describe the clinical grade ofbreathlessness and the symptom limited maximaloxygen uptake in 1978 and the change in clinicalgrade of breathlessness between 1969 and 1978 interms of the other variables. About 40% of thevariance in the symptoms limited maximum oxygen

uptake and in the clinical grade of breathlessnesscould be described by the anthropometric, spirometric,and gas transfer variables. Measurements of pul-monary compliance, conductance, and recoil pressures

did not add significantly to the predictive value of thepulmonary function tests. A deterioration in breath-lessness in previously healthy subjects was presagedby a relatively low symptom limited maximum oxygen

uptake, high exercise ventilation, low FEV1 andrelative to the FEV a high airways conductance, thelatter combination possibly reflecting narrowing ofthe small lung airways. An increase in breathlessnesswas associated with a gain in body mass and increasein the questionnaire score for bronchitis. The pro-gressors were then heavier, had a lower Kco andFVC, and a higher V-isoV but similar specific con-ductance, closing volume, and bronchitis score com-pared with those whose breathlessness remained thesame or was reduced. These findings may be ofuse in designing means of reducing the progressionof exercise-related symptoms in coalminers withpneumoconiosis.

Ventilatory control in the obesity-hypoventilationsyndromeM LOPATA, R A FREILICH, E ONAL, J PEARLE, and R VLOURENCO We investigated the causes of impairedventilatory control in six patients with the obesity-hypoventilation syndrome (OHS) by assessing theresponse to co2 rebreathing of the three major comn-ponents of the respiratory control system: (1) neWal-drive, assessed by moving average diaphragmatic EMG(EMGdi); (2) muscle output, assessed as pressure de-veloped at the mouth 150 msec after airway occlusion(Po.,s); and (3) minute ventilation (VI). The linear re-

gression of EMGdi, Po.15, and VI, vs end tidal Co2

(PAco2) in the OHS patients were compared withthose from patients who had recovered from OHS,and from obese, as well as non-obese controls. In theOHS patients the mean VI vs PAco2 response was lessthan that in the obese and former OHS subjects. TheEMGdI response to co2 in the OHS patients did notdiffer from the other groups, while in only three wasthe PO015 response reduced. The coupling of neural tomuscular and muscular to ventilatory events was

assessed as the ratio of the slopes of EMGd, to Po.15and Po.15 to VI, respectively. Three OHS patients had


impaired neural-muscular coupling with normalmuscular-ventilatory transfer. Monitoring of thoraco-abdominal motion by respiratory magnetometersshowed that abdominal end tidal position was displacedoutward during co2 rebreathing in these three patients.Normal neural-muscular coupling with impairedmuscular-ventilatory transfer was present in the otherthree OHS patients, in whom end tidal abdomenposition moved inward during rebreathing. We con-clude that the impaired ventilatory response to Co2seen in patients with OHS is secondary to mechanicallimitations to breathing, due either to impaired dia-phragm efficiency or abnormal lung and/or chestwall mechanics.

Influence of hyperinflation and inspiratory musclestrength on mouth occlusion pressure in chronicairflow obstructionH R GRIBBIN, G J HEINZ III, I GARDINER, and N B PRIDEMeasurements of mouth occlusion pressure (MOP) atthe start of inspiration reflect changes in pleural pres-sure and have been used as an index of respiratorycentre output which is independent of the mechanicalproperties of the lung. The measurements used havebeen either Po., (pressure at 01 s after start ofoccluded inspiration) or dP/dt/max (maximum rateof rise of mouth pressure at the start of occludedinspiration). In chronic airflow obstruction, however,the chest wall is hyperinflated and the inspiratorymuscles are at a potential mechanical disadvantage sothat a given amount of neuronal activity may produceless change in MOP than in a normal subject. Thiswas recognised in the original description of themethod (Whitelaw et al, 1975).We have studied 12 patients with chronic airflow

obstruction of similar severity (FEV1: range 0-7-1-0 1,mean 0-9+01 1) but with varying degrees of hyper-inflation (TLC as % predicted; range 103%-161%,mean 128±16%) all of whom were eucapnic. ThePo., responses expressed as Po.1 (60) (Po.1 value at aPco2 of 60 mmHg) and the slope of the P0., response,APo.i/ ALPCO2 were compared with TLC as % pre-dicted and diaphragm contour. A weak negative cor-relation existed between APo.i/APco2 and TLC as %predicted (r=-0 49, P=0-1). Maximum inspiratorymouth pressures at lung volumes from RV to TLCwere obtained in six of the patients and were reducedcompared with normals (max insp mouth pressureat FRC=-36110 cmH20). No relationship betweenmaximum inspiratory mouth pressure and Po., re-sponses emerged.

In spite of hyperinflation considerable adaptationof inspiratory muscle function is present, althoughmaximum pressures are reduced. This does not appearto influence Po.1 responses but it is still not clearwhether ventilation is similarly unaffected.REFRENCEWhitelaw, W A, Derenne, J-P, Milic-Emili, J (1975). Occlusion

pressure as a measure of respiratory center output in consciousman. Respiration Physiology, 23, 181-199.



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Thoracoabdominal motion and pressures duringcoughingA J R MORRIS, N SIAFAKAS, and M GREEN We havestudied chest wall configuration during voluntarycoughs in seven normal subjects. We measured antero-posterior diameters of the rib cage (RCA-P) andabdomen (ABDA-P) and lateral diameters of the ribcage at high (RCEL) and low (RCLL) levels usinglinearised magnetometers, with simultaneous recordingsof oesophageal (Poe) and gastric pressures (Pg) andvolume (V) and flow (V) at the mouth. During thoracicgas compression preceding the cough Poe and Pg roseabruptly and continued for 80-120 ms after openingof the glottis. During the cough Poe fell as flow dimin-ished, but Pg remained slightly raised for longer.Transdiaphragmatic pressure (Pg-Poe) was raised,indicating activity of the diaphragm during this ex-piratory manoeuvre.The chest wall diameters decreased abruptly during

compression, except RCA-P which enlarged due todistortion of the rib cage. When the glottis opened,RCA-P and RCHL diminished, but RCLL and ABDA-Pheld their positions constant in three subjects andactually began to enlarge in four subjects, despitecontinued expiration.The two adjacent lateral diameters (RCHL and

RCLL) therefore moved in opposite directions relativeto each other during the early part of expiration. Thisdistortion of the lower region of the rib cage may bedue to outward abdominal pressure. Positive ab-dominal pressure tends to expand the lower rib cageat low lung volumes when there is a substantial area ofapposition of the diaphragm on the rib cage. We con-clude that this distortion and paradoxical movementmay be the mechanism of cough fractures. This is con-sistent with the observation that cough fractures arepeculiarly common in pregnant women (Savage, 1956)and relatively uncommon in emphysema (Pearson,1957).REFERENCESSavage, D (1956). Stress fractures of the ribs in pregnancy. Lancet, 1,

420-421.Pearson, J E G (1957). Cough fracture of the ribs. British Journal of

Tuberculosis and Diseases ofthe Chest, 51, 251-254.

Added respiratory load detection in normal subjectsand patients with restrictive and obstructiveventilatory defectsN K BURKI The sensation generated by added inspiratoryloads has been examined in several studies in healthysubjects and in patients with increased airways resistance.It has been shown, both in normal subjects (Wiley andZechman, 1966), and in asthmatics (Burki et al, 1978) thatthe difference threshold for added resistive loads is afunction of the initial, intrinsic load (Weber-Fechnerrelationship). Similar studies have not been performed inpatients with increased pulmonary elastance (that is, withrestrictive lung disease), nor has the correlation betweenelastic (E) and resistive (R) load detection in the samesubject been studied.

Six patients with chronic airways obstruction (CAO),six patients with restrictive lung disease (RLD), and 15

normal subjects were studied. Spirometry, body plethys-mography, pulmonary resistance by the interruptermethod (Rint) and total thoracic elastance (Etot) weremeasured in all patients and subjects. The differencethresholds for detection of resistive and elastic loads(expressed as the load detected 50% of the time, AR50and AE50, respectively) were measured on at least twoseparate occasions. Mean AR50 was higher in both theCAO and the RLD groups than in the normal subjects;the Weber fraction AR5O/Ro (where Ro=Rint+minimalresistance of apparatus) was very similar in the normaland CAO groups (0-19 and 0-18 respectively) but washigher (0 26) in the RLD group. Mean AE50 was signifi-cantly greater in both patient groups compared with thenormal group, as was the Weber fraction for elastic loads,AE50/Eo, where Eo is equal to Etot. The correlation ofdifference thresholds in the individual subjects andpatients, that is, the correlation coefficient between /\R50and AE50 was good in the normal subjects (r=+0-71,P<0-005), but not significant in the CAO group (r=+0 52, P> 0 1) and poor in the RLD group (r=-0 07).These results indicate that the increased intrinsic elastic

load in RLD patients alters the difference threshold valuefor externally applied resistance loads and similarly theincrease in lung elastance alters the elastic load differencethreshold. The significant difference in the Weber fractionfor elastic load difference thresholds for both CAO andRLD patients compared with the normal group mayreflect the possibility that the change in thoracic elastancedoes not reflect the magnitude of change in lung elastance,hence underestimating the denominator in the Weberfraction. The poor correlation between AR50 and AE50in the patient groups probably reflects differences in therelative intrinsic resistive and elastic loads in these patients.REFERENCESBurki. N K, Mitchell, K, Chaudhary, B A, and Zechman, F W

(1968). The ability of asthmatics to detect added resistive loads.American Review ofRespiratory Disease, 117, 71-75.

Wiley, R L, and Zechman, F W, jun (1966). Perception of addedairflow resistance in humans. Respiration Physiology, 2, 73-78.

Dynamic collapse of large airways in chronicobstructive lung diseaseK PROWSE and S BRADBURY A study of maximal flow-volume loops was carried out in 124 patients withchronic obstructive lung disease. All patients hadspirometric evidence of airflow obstruction, as shownby an FEV, less than 70% predicted normal and anFEV,/vital capacity ratio less than 60%.The shape of the flow-volume loop was indicative of

dynamic airway collapse (DAC) during expiration in46 patients (37%). The expiratory curve showed arapid fall from peak expiratory flow to a much reducedrate of flow over a small part of the vital capacity(VC), and the flow rate then remained fairly constantfor the remainder of expiration. The shape of theflow-volume loop was abnormal in a further 48patients (39%) but did not show evidence of DAC.

In the patients with DAC the ratio of forced expir-atory to forced inspiratory flow at the midpoint ofVC (FMEF/FMIF) was 0-31+0-15, significantly lowerthan in those without DAC (0 53+0132; P<0-001).

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The subjects with DAC also showed significantly lowervalues for FEV,, VC, and transfer factor (TL) andsignificantly higher values for TLC and RV. Twenty-six patients with DAC (57%) had radiological evidenceof emphysema compared to 16 (20%) of those withoutDAC.

In 19 patients with DAC fibreoptic bronchoscopyconfirmed the presence of pronounced tracheal nar-rowing during expiration, and tracheal tomographyshowed variable tracheal narrowing in a further 10patients.The development of the low-flow plateau occurred

after expiration of 225±7% VC and probably indi-cates that the tracheal lumen has reached minimal size.Although loss of airway distending forces may

account for airflow obstruction under static conditionsin subjects with emphysema, dynamic factors may beimportant during forced expiration (Leaver et al,1974). Regrouping of our patients into "emphysema,""bronchial," and "indeterminate" subgroups accordingto the criteria of Burrows et al (1966) showed that 33out of 49 patients in the emphysema subgroup hadevidence of DAC, whereas only seven out of 40 inthe bronchial and six out of 35 in the indeterminatesubgroups showed DAC.We conclude that dynamic collapse of large airways

is relatively common in emphysema and suggest thatit may be a more important cause of disability thanhas hitherto been accepted.REFERENCESLeaver, D G, Tattersfield, A E, and Pride, N B (1974). Bronchial and

extrabronchial factors in chronic airflow obstruction. Thorax, 29,394-399.

Burrows, B, Fletcher, C M, Heard, B E, Jones, N L, and Wootliff, J S(1966). The emphysematous and bronchial types of chronic airwaysobstruction. Lancet, 1, 830-835.

Relationships between radiographic progression, lungfunction decline, and asbestos exposure levelH WEILL, J E DIEM, R N JONES, J C GILSON, and HGLINDMEYER Previous studies from this unit haveshown that radiographic and physiological evidence ofasbestosis and excess lung cancer mortality are doserelated in asbestos cement manufacturing workers(Weill et al, 1975; Hughes et al, 1978). In a cohort(n=204) of this population followed longitudinally(six years) average length of exposure was 22 years,and individual exposure dose was reconstructed usingduration and average levels of dust exposure. Tworeaders (JCG and RNJ) independently assessed pro-gression on a four-point scale using paired films ofknown sequence. Progression was assumed in 17 indi-viduals where one or both readers classified the filmpair in one of the two upper categories (probable ordefinite progression).Average and cumulative exposure at time of study

entry correlated significantly with progression ofsmall irregular opacities (logistic regression analysis,P<0001), but not with small rounded opacities orpleural thickening. Progression of pleural thickeningand calcification depend only on length of exposure.Smoking did not correlate with progression of small

irregular opacities. Annual decline of forced vitalcapacity and forced expiratory volume in one secondcorrelated significantly with level of past dust exposure(P<0-04) beyond a significant smoking effect (P=001).Radiographic progression was strongly associated withlarger annual decline in FEV, and FVC (P<0 001).Progression of small irregular opacities appears to bemore specifically related to asbestos dust effect than isdecline in lung function.REFERENCESWeill, H, Ziskind, M M, Waggenspack, C, and Rossiter, C E (1975).Lung function consequences of dust exposure in asbestos cementmanufacturing plants. Archives ofEnvironmental Health, 30, 88-97.

Hughes, J Waggenspack, C, and Weill, H (1978). Mortality study ofworkers engaged in manufacture of asbestos cement products.American Review of Respiratory Disease, 117, 292.

A proposed diagnostic classification for asbestosisG R EPLER, J M SAMET, B ROSNER, and E A GAENSLERGuidelines for diagnosis of asbestosis are essential forclinicians, compensation boards, and industrial en-vironmental control officers. We undertook this studyto determine if a classification based on clinical andradiographic criteria could be developed to defineasbestosis. Altogether 852 employees of asbestos andshipbuilding industries were studied. Data includedMRC questionnaire, forced vital capacity (FVC),forced expired volume in one second (FEV,), andsingle breath diffusing capacity (Dsb). Chest radio-graphs were coded by the ILO U/C internationalclassification for the pneumoconioses.We classified workers into three groups. The first

was "definite asbestosis," which comprised allworkers with (a) radiographic profusion (severity) ofat least 2/1 or (b) a film of 1/0-1/2 plus two of threecriteria: bilateral fine crackles, FVC or Dsb of lessthan 80% of the predicted value. The second groupwas designated as "possible asbestosis" and includedall workers with (a) film of at least 1/0 or (b) two ofthree criteria, if the film was normal. All remainingworkers were classified as "unlikely."The 852 workers were further divided into those

exposed or not exposed to asbestos. Among 433 withexposure, 61 or 14% were classified as "definite" and91 or 21% as "possible," while among the 419 non-exposed, less than 1% were classified as "definite"and 11% were in the "possible" group. In the "defi-nite" group 51% had bilateral crackles, the meanFVC was 74%, and the mean Dsb was 70%, while inthe "possible" group, 14% had crackles, the meanFVC was 91%, and the mean Dsb was 95%.There were 567 employees with sufficient follow-up

studies to determine yearly change of FVC, FEVj,and Dsb values. The yearly decrease of the FVC was110 ml, 70 ml, and 49 ml for the exposed workers inthe "definite," "possible," and "unlikely" group re-spectively. Several exposed workers in the "possible"group progressed to "definite" on subsequent tests.

Finally, lung biopsy results were available fromseveral of the workers and other asbestos exposedpatients. Using our diagnostic classification for these46 confirmed cases of asbestosis, 74% were classified

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as "definite" and the histological grade of severitywas significantly higher than the 15% who wereclassified as "possible."

Spectral and wave-form analysis of cracklesM MORI, K KINOSHITA, H MORINARI, T SHIRAISHI, S

KOIKE, and s MURAO We performed waveform andspectral analysis of crackles recorded from six patients,four with tuberculosis and two with chronic bronchitis.Lung sounds were recorded by placing an air-coupleddynamic-type microphone firmly on the chest wallwhere crackles were heard by auscultation. We useda memory (TDK 8810), which has a capacity of 1 kilo-words, for the sampling and time expansion. Weexpanded the time scale 1600 times for the waveformanalysis, and for the spectral analysis we set thesampling frequency at 64 KHz and the time windowat 31-25 msec.By waveform analysis we could separate a waveform

of a single crackle into two portions, initial highpitched portion (HP) and the subsequent low pitchedportion (LP). We measured amplitudes and half-periods of the wave components in the low pitchedportion out of 286 crackles recorded from six patientsand found that the attenuation of the amplitude was

almost exponential and that in 92% the half-periodsbecame longer with the development of the wave-

forms. In crackles with high amplitudes we noticed as

in shock waves triangular distortions at the top of thewaveforms. The spectrum of a single crackle had a

peak near 200 Hz and a notching between 250 and350 Hz. Since this notching is caused by an interactionof the two waveforms, initial high pitched portion andsubsequent low pitched portion, we can calculateusing basic characteristics of Fourier transform thetime interval between the two (HP and LP) from theinverse of the notch frequency. We found this timeinterval about 3 msec (2-843-91 msec). On the basesof these observations we speculate crackles are shockwaves similar to a sonic boom.

Pulmonary hypertension accompanying combinedventricular septal defect and patent ductus arteriosus.Management in infancy and early childhoodJ M REID, E N COLEMAN, and J G STEVENSON The com-

bination of patent ductus arteriosus (PDA) and ventri-cular septal defect (VSD) is relatively uncommon,Keith et al (1978) recording a VSD in only 5% of PDApatients. During 1959-78 41 children were encounteredwith this combination. The age at presentation rangedfrom 1 month to 11 years (mean 19,7 months), and24 were under the age of 1 year. These 24 presentedwithin the first three months of life. After treatmentof the failure, cardiac catheterisation was performed.Haemodynamic data obtained included presence orotherwise of pulmonary hypertension (present in 32 ofthe 41), the pulmonary: systemic blood flow ratio(Qp: Qs), pulmonary vascular resistance (PVR), the

pulmonary to systemic pressure (Pp: Ps), and the pul-monary to systemic resistance (Rp: Rs).Four patients had no surgical treatment, but 37

underwent various surgical procedures that will bediscussed fully. Thirteen patients had pulmonary vas-cular disease (Rp: Rs>024) (Kirklin, 1965). Of the41 patients, six died, two of whom had pulmonaryvascular disease.From an analysis of the data obtained in our

patients, a policy of management is advocated. All whohave cardiac failure require treatment of this followedquickly by catheterisation. The finding of serious pul-monary hypertension or failure to thrive are indica-tions for early surgical treatment. Ligation of the PDAis performed first; only if the pulmonary artery pres-sure does not fall significantly is repair of the VSDconsidered necessary. In all patients in whom eithersurgery is deferred or PDA ligation alone is performed,repeat catheterisation is mandatory at 1 year to assesswhether pulmonary vascular disease is developing; ifso early operation is necessary.REFERENCESKeith, J D, Rowe, R D, and Vlad, P (1978). Heart Disease in Infancyand Childhood, 3rd edn, p 321. Macmillan, New York.

Kirklin, J (1965). Ventricular septal defect with pulmonary vasculardisease. New Zealand Medical Journal, 34 (cardiac supplement), 64.

Total and differential counts in smokers and somepulmonary disordersP L HASLAM One significant smoking-related featurehas been identified from total and differential lungwash cell counting in 86 Brompton Hospital patients.Heavy "pigmentation" of variable numbers of macro-phages was observed in 43 smokers (P<0-001) and20 ex-smokers (P<0-01) contrasting with their extremerarity in non-smokers.Trends distinct from any influence of smoking were

identified in differential lung wash cell counts fromsmokers with cryptoegnic fibrosing alveolitis (CFA).Macrophage percentages tended to be lower insmokers with "lone" CFA (P<0-01) and in smokerswith CFA associated with other connective tissue dis-orders (P=0-01) than in 13 smoking control patientswithout peripheral lung disease. These decreases re-flected increases in percentages of eosinophils (P<0-001for lone CFA; P<0025 for CFA with associated dis-orders), neutrophils (P<005 for CFA with associateddisorders) and lymphocytes (P<0-025 for lone CFA).Total cell yields in smokers with CFA did not, how-ever, differ from those in the smoker controls. Theseobservations generally confirm findings for patientswith CFA reported by Reynolds et al, 1977, andWeinberger et al, 1978. We also confirmed their find-ings of striking increases in percentages of lympho-cytes-predominantly T-lymphocytes-in patients withhypersensitivity pneumonitis in one of our ownpatients with symptomatic budgerigar fancier's lung.We were unable, however, to confirm lymphocyte in-creases in four of our patients with clinically "active"sarcoidosis. (Statistical comparisons were made usingthe Mann-Whitney U test.)

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REFERENCESReynolds, H Y, Fulmer, J D, Kazmierowski, J A, Roberts, W C,

Frank, M M, and Crystal, R G (1977). Analysis of cellular andprotein content of broncho-alveolar lavage fluid from patients withidiopathic pulmonary fibrosis and chronic hypersensitivity pneu-

monitis. Journal of Clinical Investigation, 59, 165-175.Weinberger, S E, Kelman, J A, Elson, N A, Young, R C, Reynolds,H Y, Fulmer. J D, and Crystal, R G (1978). Broncho-alveolar lavagein interstitial lung disease. Annals ofInternal Medicine, 89, 459-466.

Clinical correlations with bronchoalveolar lavage incryptogenic fibrosing alveolitisC W G TURTON, P HASLAM, B HEARD, and M TURNER-

WARWICK The inflammatory cell exudate in patientswith cryptogenic fibrosing alveolitis (CFA) has beeninvestigated by differential cell counts in broncho-alveolar lavage fluid. Twenty-four patients were

lavaged, and 17 had open lung biopsy. Lavage differ-ential cell counts were compared with histology assessedsemiquantitatively and with differential cell counts ofcells extracted from lung tissue in vitro. Correlationswere made with response to treatment with cortico-steroids, and with "disease progression" assessed retro-spectively. Histology always showed a mixed picturewith intra-alveolar cell exudate and alveolar wall

fibrosis, and did not predict response to treatment. Cor-relations between lavage and histology were weaklypositive and not significant statistically, but lavage maybe more representative because of wider sampling. Cor-relations between lavage and cell extraction weremore positive, and significant for neutrophils (r.=0 63,P=0-02) suggesting that lavage is sampling much more

than airways. There was a trend for the percentage oflavaged lymphocytes to be greater in treatment re-sponders and this was significant for cells extractedfrom tissue (P<0-01). Macrophages were increased in"rapid progressors" (P<0-05), but the parallel de-creases in other cells were not significant. Broncho-alveolar lavage is relatively non-invasive and maysometimes help in managing CFA.

Alveolar macrophage enzymes and C3b receptors inCFAR DU BOIS The alveolar macrophage has been shownto contain and secrete a wide variety of biochemicallyand immunologically active substances. Animal modelsof chronic inflammation suggest that the secretion oflysosomal acid hydrolases may be important in patho-genesis, and we present evidence that this may be truein cryptogenic fibrosing alveolitis (CFA).

Alveolar macrophages were obtained by lavagefrom 13 patients with CFA and 12 with no inter-stitial lung disease. Enzyme levels of the acid hydro-lase N-acetyl-B-D-glucosaminidase were found to belower in the CFA macrophages and higher levels were

found in the lavage fluid from these patients, sug-gesting in-vivo release. Using a rosetting technique, itwas shown that CFA macrophages possess fewer C3breceptors than the control group. This could be ex-

plained if C3b, generated in vivo, had already occu-

pied macrophage receptor sites, thereby stimulatingacid hydrolase secretion.

A further functional difference between the groupswas illustrated by the increased spreading on glass ofCFA monolayer cultures of macrophages.

In conclusion, alveolar macrophages from patientswith CFA appear to be functionally different fromthose from patients with no interstitial lung disease,and may play an active role in the perpetuation ofthe chronic inflammatory response.

Technique of bronchoalveolar lavage at fibreopticbronchoscopyJ V COLLINS Routine fibreoptic bronchoscopy wasperformed via the nose with the patient semi-recumbent. Biopsy specimens were obtained whereindicated, and lavage was carried out in the otherlung. The tip of the bronchoscope was normally im-pacted in inspiration in a segmental or more per-ipheral bronchus in the lateral or posterior segmentof the lower lobe and held in place by an assistant.Using a hand-held syringe, 60 ml of sterile 0 9%sodium chloride solution (corrected to pH 7 0) at 37°Cwas injected while the patient inhaled very slowly tototal lung capacity and then quietly exhaled to func-tional residual capacity. Further quantities of thesolution were injected until 120-180 ml had been in-serted. The tip of the bronchoscope was withdrawnby 1-2 cm, and the fluid was aspirated as the patientbreathed quietly within the tidal range. The procedurewas repeated until about 100-150 ml of fluid had beenrecovered, this usually entailed the injection of 300-500 ml of solution.

Contraindications to the procedure include severeventilatory defect (FEV,<1 litre), hypoxaemia at rest(Pao2<9 kPa) and cardiac disease. Because significanthypoxaemia developed with lavage in six patients'studies (mean Pao2 fell from 11-2 to 8-2 kPa) it isrecommended that oxygen be given during and afterthe procedure. The other common sequelae of slightfever and radiographic shadowing occurred most oftenin patients with a history of recurrent chest infectionsbut did not require specific treatment.

Alveolar washings in recurrent respiratory infectionsincluding cystic fibrosis: detecting defects inmacrophage functionPETER COLE Phagocytosis and killing of Staphy-lococcus pyogenes by alveolar macrophages (AM)from 73 patients with frequent acute respiratory in-fections, 14 patients with bronchiectasis, and sevenpatients with cystic fibrosis have been tested usingglass-adherent cells harvested from bronchoalveolarwashings and characterised as AMs by electron micro-scopy. Normal ranges for these assays was establishedusing seven healthy and 14 non-infective respiratorydisease control subjects.

Phagocytic function was assessed after a 30-minuteinfection period using a multiplicity of infection of50 bacteria to one phagocyte and was found to benormal in all 14 bronchietatic patients. In all sevencystic fibrosis patients, however, and in 11 of the 73

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patients with recurrent-acute infections phagocytosiswas subnormal (P<001), and this defect was serum-dependent. Five patients in the latter group were IgAdeficient.

Bacterial killing was measured over a 60-minuteperiod and bronchiectatic patients' AMs killed morethan 70% of the phagocytosed inoculum that com-posed the lower limit of the normal range. All sevencystic fibrosis patients were subnormal in bacterialkilling, and this appeared to be serum-dependent. Thebacterial killing of AMs from 15 out of 73 patientswith frequent acute infections was subnormal(P<0 01), not improved by incubation in normalserum but improved by incubation in levamisole5 gg/ml.Although the results could be interpreted as being

secondary to infection, patients with recurrent-acuteinfections were studied between episodes. It is con-cluded that there is a serum opsonin defect for AMfunction in some patients with cystic fibrosis and withfrequent acute infections, and that the AMs them-selves appear to be defective in killing Staphylococcusin a small number of the latter group.

Serum lysozyme in farmer's lungC W G TURTON, G FIRTH, B G RIDGEN, and M TURNER-WARWICK Serum lysozyme (LYS) may be raised insome granulomatous inflammatory disorders includingtuberculosis and sarcoidosis. LYS has been measuredin 60 asymptomatic Devon farmers previously diag-nosed as having farmer's lung (FL) and in 51 healthyfarming controls. Criteria for the diagnosis of FLwere a typical history, chest radiographic abnormality,and circulating precipitins to Micropolyspora aeni.LYS was assayed by spectrophotometric measurementof the rate of lysis of Micrococcus lysodeiktious usinga standard human lysozyme from urine of patients withmonocytic leukaemia. LYS in 31 FL subjects assessedin the water was higher than 36 winter controlfarmers (P<001), and higher than 18 FL subjectsassessed in summer (P<0 01). In summer there was nodifference between FL and controls. LYS tended tobe lower in FL in those working on large farms, thosewith full time assistance, and those using silage, butnot significantly so. The results suggest that there maybe active inflammation in FL in the absence of acutesymptoms.

Monitoring provocation tests in the investigation ofallergic alveolitisD J HENDRICK, R MARSHALL, and JENNIFER FAUX Inha-lation provocation tests were carried out on 31 subjectsusing four- and five-fold sequential increments in anti-genic exposure (interspersed with indistinguishablecontrol challenges) until either characteristic "al-veolar" reactions were obtained or the arbitrarilychosen maximum dose had produced no response.Subjects and observers alike were convinced of thepositive or negative nature of the result from the en-suing symptoms and signs in all but 15 of the 144 tests.

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To assess the potential diagnostic usefulness of severalmonitoring parameters, the distributions of thechanges noted in association with the 23 positive testswere compared with those associated with the 82obligatory negative tests (all control tests plus allactive tests in the 13 non-reactors). Diagnostic end-points were chosen to produce specificities of about95%. The subjective parameters-symptoms of a"flu"-like illness, undue breathlessness on exertion,signs of an unwell appearance, increased respiratoryeffort on exercise-were the most discriminatory, butthese largely determined the initial result category. Theobjective parameters monitoring the systemic responses-body temperatures exceeding 37 2°C, circulatingneutrophil increases of at least 2,5X109/1, circulatinglymphocyte decreases of at least 0-5Xl0'/l to levels ofabsolute lymphopenia-had sensitivities of 78%, 68%,and 50% respectively. Those monitoring the pul-monary responses-increases in minute ventilation andrespiratory frequency during exercise of at least 15%and 25%, decreases in vital capacity of at least 15%-had sensitivities of 85%, 64%, and 48% respectively.These ten parameters allowed eight of the 15"equivocal" tests to be reclassified retrospectively as"positive." Auscultation, chest radiography, andmeasurement of diffusing capacity or lung volumesubdivisions apart from the vital capacity, proved to beso insensitive as to be worthless, though changes didoccur in association with the stronger reactions. It isconcluded that responses that do provoke significantchanges in these less sensitive monitoring parametersare unnecessarily distressing and, presumably,hazardous.

Abrogation of bronchial, cardiovascular, andcutaneous sensitivity in a canine model of IgEmediated hypersensitivityW KEPRON, A H SEHON, and K S TSE We have inducedspecific IgE antibody to dinitrophenol (DNP) andovalbumen (OA) by administering a conjugate ofDNP and OA (DNP2-OA). Inhalation challenge ofsensitised dogs with either 5 mg of aerosolised OA ora polyvalent conjugate of DNP with bovine IgG(DNP,,-BGG) produced a five-fold increase in airwayresistance as measured by the forced oscillation tech-nique (Kepron et al, 1977). Abrogation of specific IgEanti-DNP antibody in sensitised dogs was producedby administering the tolerogenic conjugates of DNPwith either canine IgG (DNP9-CGG) or the copolymerof D-glutamic acid-d-lysine (DNP1eDGL) (Tse et al,1978). Inhalation challenge of dogs after IgE anti-DNPantibody had been abrogated failed to show airwayresistance changes to DNP9-BGG aerosolisation. Pro-found falls in systemic blood pressure in sensitiseddogs were recorded after intravenous administrationof 25 mg of either DNP,,-BGG or OA. After abro-gation of IgE anti-DNP antibody, intravenouschallenge with DNP,,-BGG did not produce anychange in blood pressure. Similarly, sensitised animalswere recorded as having direct skin test reactivity tointracutaneous injection of 1 vng of DNP,5-BGG. This



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skin reactivity was completely abolished after abro-gation of IgE anti-DNP antibody, and skin testingwith up to a 106 increasel concentration of DNP,5-BGG was entirely negative. Sensitivity to OA afterabrogation of IgE anti-DNP antibody remained un-affected, and IgE anti-OA antibody production andbronchial, cardiovascular, and skin reactivity to appro-priate challenge with OA remained unaltered frompretolerogen administration levels. These results indi-cate that specific abrogation of the serum IgE anti-body response of sensitised dogs by appropriatetolerogenic conjugates was associated with a cor-responding loss of systemic allergic sensitivity.REFERENCESKepron, W, Sehon, A H, and Tse, K S (1977). A canine model for

reaginic hypersensitivity and allergic bronchoconstriction. JournalofAllergy and Clinical Immunology, 59, 64.

Tse, K S, Kepron, W, and Sehon, A H (1978). Effects of tolerogenicconjugates in a canine model for reaginic hypersensitivity. I.Suppression of hapten-specific IgE antibody response. Journal ofAllergy and Clinical Immunology, 61, 303.

Epithelial cell adherence as a determinant ofrespiratory tract colonisationJ H HIGUCHI and w G JOHANSON, jun Nosocomialpneumonia due to Gram-negative bacilli (GNB) is aserious threat among ill patients. Colonisation of theupper respiratory tract with GNB usually precedes thedevelopment of pneumonia. In the present study weinvestigated the adherence of Pseudomonas aeruginosa(PA) to respiratory epithelial cells (buccal cells) invitro to determine whether changes in the cell-bindingcharacteristics could explain the occurrence of col-onisation with GNB. In groups of rats subjected to0%, 50%, 75%, and 100% nephrectomies (N) buccalcell adherence was studied in vitro using washedbuccal cells that were incubated with PA for twohours; attachment results were assayed by both quan-titative cultures and visual counting and expressed asnumber of PA per cell. To correlate buccal cell ad-herence in vitro with susceptibility to colonisation invivo, each animal was inoculated once (day 1) intra-orally with a gentamicin-resistant strain of PA; col-onisation was defined as the persistence of this organismin the oropharynx, using gentamicin-containing select-ive media. Results are shown in the table.Attachment of PA was similar for all groups pre-

operatively and was unchanged subsequently in shams;

Buccal cell adherence of Ps aeruginosa in vitro and colonisation byPs aeruginosa in vivo

Group No Preop Day I Day 2 Day 4

Sham (18) 4-9+17* 5-6+1-3 5-31-3 -

Colonised - 1/18t 1/18 1/1850%N (6) 4-1+0-8 17-2+1 7 5 9+0 6 -

Colonised - 6/6 4/6 0/675%YN (6) 5-8+2-6 17-2+2-0 25-8+6-7 -

Colonised - 6/6 6/6 6/6100%N (6) 4-2+1-2 28 0+3-4 46-2+10-1 -Colonised - 6-6 2-2

*Ps aeruginosa/cell (mean i SD).tNo animals colonised/No animals inoculated.

1 of 18 became colonised. Fifty per cent N was followedby a transiently increased attachment in vitro andcolonisation tended to persist. Among 75% N, attach-ment in vitro postoperatively increased and colonis-ation in vivo persisted. One hundred per cent N causeddeath in 36-56 hours; attachment in vitro was greatlyincreased and all were colonised.These data show a significant relation between

epithelial cell binding of PA in vitro and susceptibilityto colonisation by GNB in vivo. The nature of thechange in cell properties is not known.REFERENCESEllen, R P, and Gibbons, R J (1974). Parameters affecting the ad-

herence and tissue tropisms of Streptococcus pyogens. InfectiousImmunology, 9, 85-91.

Gibbons, R J, and van Houte, J (1971). Selective bacterial adherenceto oral epithelial surfaces and its role as an ecological determinant.Infectious Immunology, 3, 567-573.

Gibbons, R J, and van Houte, J (1975). Bacterial adherence in oralmicrobial ecology. Annual Review ofMicrobiology, 29, 19-44.

Gibbons, R J, Spinell, D M, and Skobe, Z (1976). Selective adherenceas a determinant of the host tropisms of certain indigenous andpathogenic bacteria. Infectious Immunology, 13, 238-246.

Higuchi, J H, Chaudhuri, T, and Johanson, W G, jun (1978). Deter-minants of postoperative colonization with Gram-negative bacilli.American Review ofRespiratory Disease, 117, 274 (abstract).

Johanson, W G, jun, Pierce, A K, and Sanford, J P (1969). Changingpharyngeal bacterial flora of hospitalized patients: emergence ofGram-negative bacilli. New England Journal of Medicine 281,1137-1140.

Johanson, W G, jun, Pierce, A K, Sanford, J P, and Thomas, G D(1970). Nosocomial respiratory infections with Gram-negativebacilli: the significance of colonization of the respiratory tract.Annals ofInternal Medicine, 77, 701-706.

Redman, L R, and Lockey, E (1967). Colonisation of the upperrespiratory tract with Gram-negative bacilli after operation,endotracheal intubation, and prophylactic antibiotic therapy.Anaesthesia, 22, 220-227.

Role of digitalis treatment in cor pulmonaleMILENA L LEWIS and LYNN C CHRISTIANSON Digitalisapparently enhances the inotropic state of the rightventricle, when administered acutely (Ferrer et al,1950; Jezek and Schrijen, 1973), but its role in themanagement of chronic cor pulmonale remains am-biguous (Green and Smith, 1977). This ambiguity ispartly due to lack of adequate definition of the typeand severity of respiratory illness in many case studies.Therefore, we have matched two groups of patientswith chronic pulmonary disease, in stable clinicalcondition, for severity of lung disease, as indicated byventilatory parameters and compared their haemo-dynamic function. Group 1 had been on chronic digi-talis, whereas group 2 had not. Average values for theparameters of respiratory disease were:

N Age Pao, Paco, FVC, FEV,/ MVV,% pred FVC, % % pred

Group 1 15 56 53 49 55 51 41

Group 2 15 54 54 49 51 53 41

None of the differences between the two groups are statisticallysignificant.

Values of cardiac index (CI), stroke index (SI),right ventricular ejection fraction (EfR), right ventricu-lar diastolic volume (VDVR), as determined from pre-

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cordially detected isotope dilution curves (Lewis et al,1970) and lesser circulation pressures were comparedin the two groups.

CI HR SI EfR VD VR, PRA PPA PLAml/M'2

Group 1 3-3 89 37 0 40 101 4 37 8Group 2 3-6 85 43 0-44 105 6 30 8

Differences ofmean values of haemodynamic parameters between thetwo groups were not statistically significant, although pulmonaryartery pressure tended to be higher in the group on digitalis.

Differences between mean values of haemodynamicparameters were not statistically significant. Obviousabnormalities include raised pulmonary artery pressureand reduction of ventricular ejection fraction. Theventricular ejection fraction is an indicator of myo-cardial contractility. In the presence of increasedafterload, however, a reduced Efa does not necessarilyimply right ventricular dysfunction. In fact, fromnormal ventricular pressure-volume loops, the heartin these patients may be shown to exhibit increasedcontractility.

In the normal heart, the role of digitalis is prob-lematical. An analogy can be drawn between presentobservations and those published regarding thenegligible effects of digitalisation on cardiac perform-ance in patients with mitral stenosis, without heartfailure (Beiser et al, 1968). The trend to greater pul-monary hypertension in patients with cor pulmonaleon digitalis may represent a direct vasoconstrictoreffect of the drug on the pulmonary vasculature, andwould be detrimental. The data presented cast doubton the value of maintenance digitalis treatment incor pulmonale in the absence of a low cardiac output.REFERENCESBeiser, G D, Epstein, S E, Stampfer, M, Robinson, B, and Braunwald,E (1968). Studies on digitalis. XVII. Effects of ouabain on thehemodynamic response to exercise in patients with mitral stenosis innormal sinus rhythm. New EnglandJournalofMcdicine, 278,131-137.

Ferrer, M 1, Harvey, R M, Cathcart, R T, Webster, C A, Richards,D W, jun, and Cournand, A (1950). Some effects of digoxin uponthe heart and circulation in man. Circulation, 1, 161-186.

Green, L H, and Smith, T W (1977). The use of digitalis in patientswith pulmonary disease. Annals ofInternal Medicine, 187, 459-465.

Oat cell carcinoma of the bronchus-is there a placefor surgery?M J DRAKELEY, H R MATTHEWS, and DEIDRE WATSONUncertainty exists regarding the proper treatment ofoat cell carcinoma of the bronchus. Chemotherapy iseffective only in the short term and, particularly afterthe Medical Research Council's study comparing sur-gical treatment with radiotherapy, many clinicians nowconsider that surgery is no longer indicated in treatingthis tumour. We have reviewed 494 patients with oatcell carcinoma of the bronchus who were treated bysurgery alone during the 20 years from January 1951to December 1970 at the Liverpool Regional Cardio-thoracic Surgical Unit. Altogether 366 tumours provedsuitable for resection, and 52 patients survived formore than five years, of whom 19 patients lived

for more than 15 years, three of them still being alivemore than 23 years after surgery. After a review ofthe histological slides, two patients were excluded.Seventeen patients had positive preoperative broncho-scopic biopsies, the other 33 having peripheral tu-mours. Fifteen of the 50 survivors had lymph nodesaffected by tumour, and tumour cells were found inthe resection line in three others. Twenty patientshave since died, and of the 19 for whom informationis available, only 7 died with recurrent disease.

Similar five-year survival figures can be extractedfrom other published surgical series which, althoughnot high, are better than those for patients treatedwith cytotoxic drugs or radiotherapy. Our concern isthat with the advent of the fibreoptic bronchoscopemore peripheral tumours will be diagnosed beforesurgery, and the patient denied a potentially curableoperation. As the results of immunotherapy will beenhanced by the removal of the tumour, we are certainthat surgery still has a place in the treatment of oatcell carcinoma of the bronchus.

Regional lung function in patients with inoperablebronchogenic carcinoma studied before and afterpalliative radiotherapyF FAZIO, T A PRATT, C G MCKENZIE, and R E STEINERVentilation/perfusion (V/0) scans, a clinical assess-ment of breathlessness, routine chest radiographs and(in most cases) tests of overall lung function were ob-tained in 45 patients with inoperable carcinoma ofthe bronchus. Thirty-five patients were then reinvesti-gated after palliative radiotherapy. Seventeen of themhad one or more further follow-up studies up to 490days from the end of radiotherapy.

Semiquantitative assessment of regional V and ?showed that both were, at the initial evaluation, alwaysreduced to the lung affected by the tumour, 2 beinggenerally more impaired than V. These abnormalitieswere either undetected or underestimated by an evalu-ation of regional perfusion derived from the standardchest radiograph. After radiotherapy, a significantimprovement of regional V and 0 (probably due toshrinkage of the tumour) was observed, which wasassociated to a corresponding amelioration of breath-lessness. Slow but progressive deterioration of bothregional lung function and breathlessness was subse-quently observed in the follow-up. This was oftenassociated to the development of radiation fibrosis. Onthe contrary, tests of overall lung function (VC, FEV,),which were moderately impaired at the initial assess-ment, did not show significant changes after radio-therapy or in the follow-up, thus confirming previousindependent findings (Saunders et al, 1978).We conclude that (a) impairment of overall pul-

monary function tests in patients with carcinoma ofthe bronchus is likely to be due to coexisting mild ormoderate chronic airways obstruction, rather than toa direct effect of the tumour on the airways; and (b)isotope studies of regional lung function (V/a) beingmore sensitive and more specific than tests of overalllung function, can be a valuable adjunct to chest

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radiographs for the assessment, guidance to effective-ness of treatment, and follow-up of patients with in-operable carcinoma of the bronchus.REFERENCESaunders, K B, Rudolf, M, Banks, R A, and Riordan, J F (1978).

Central airways obstruction in carcinoma of the bronchus treatedby radiotherapy: a study of pulmonary function. British JournalofRadiology, 51, 286-290.

Transthoracic needle lung biopsy after denitrogenationwith 100% oxygen

Y CORMIER, M LAVIOLETrE, and A TARDIF Trans-thoracic needle lung biopsy is an effective and wide-spread diagnostic procedure. One drawback of thisuseful technique is its frequently resulting pneumo-

thorax (Sinner, 1975; Herman and Hessel, 1976; Lalliet al, 1977). The objective of this study was to evalu-ate the effect of breathing 100% oxygen during theprocedure. Since oxygen, in a closed collapsible cavity,reabsorbs faster than nitrogen (Dale and Rahn, 1952),it was expected that this substitution would enhancepneumothorax's reabsorption and thus decrease theassociated morbidity. Fifty consecutive biopsies on 46hospital patients were randomised and performed on

subjects breathing either 100% oxygen or compressedair. The selected gas was given for five minutes beforethe biopsy and continued until 30 minutes after.Twenty-six procedures were done on air (group 1)and 24 on 100% 02 (group 2). Four subjects in group 2were eliminated because they were unable to sustainthe required oxygen breathing. Results showed fewerpneumothorax with subjects breathing 100% 02 (fourout of 20) than with those breathing air (11 out of 26).Three patients in group 1 but none in group 2 requiredchest tube drainage for symptoms of dyspnoea. Thepeak area of gas accumulation for each pneumothorax,calculated by the method described by Northfield(1971), was smaller in group 2, with a mean surfacearea of 27-1 cm2 (range 96-63 8), than in group 1(mean of 68-1 cm2 (range 6-4172-4)). These resultswere statistically significant (P<0-05). Neither thepatients' characteristics nor the biopsy procedure couldaccount for these observed differences. We concludethat 100% 02 breathing during transthoracic needlebiopsy decreases the number and size of pneumothoraxand therefore may help avoid the need for chest tubedrainage. We propose this simple technique to de-crease the morbidity of transthoracic needle lungbiopsy.REFERENCESDale, W A, and Rahn, H (1952). Rate of gas absorption during

atelectasis. American Journal ofPhysiology, 170, 606-615.Herman, P G, and Hessel, S J (1976). The diagnostic accuracy and

complications of closed lung biopsies. Radiology, 125, 11-14.Lalli, A F, McCormack, L J, Zelch, M, Reich, N E, and Belovich, D

(1977). Aspiration biopsies of chest lesions. Radiology, 127, 35-40.Northfield, T C (1971). Oxygen therapy for spontaneous pneu-mothorax. British Medical Journal, 4, 86-88.

Sinner, W N (1975). Complications of percutaneous transthoracicneedle aspiration biopsy. Acta Radiologica Diagnosis, 17, 813-827.

Comparison of techniques for diagnosis of corpulmonale in cystic fibrosisC J L NEWTH, I MITCHELL, K BLOOM, R FOWLER, and D

GILDAY Cor pulmonale is a major cause of death in


cystic fibrosis (CF). The diagnosis is often difficult tomake in CF because classic clinical signs are oftenabsent or misleading (Goldring et al, 1964), radiologicalsigns occur late, and the electrocardiogram is insensi-tive (Lamarre et al, 1972).Because of these difficulties, we performed thallium

201 myocardial perfusion scan, a vectorcardiograph,and M-mode echocardiograph assessments of theright ventricle in 36 patients with CF, on the sameday. We used the echocardiogram as the standard testfor cor pulmonale arbitrarily, on the basis of publisheddata showing good correlation between angiographic(Liebman et al, 1976) and necropsy (Gewitz et al,1977) measurements of right ventricular anterior wallthickness and those made by echocardiography. Wealso found good correlation between our echocardi-ographic and post-mortem assessments of cor pul-monale in the four patients in this study who diedand had a necropsy performed.Each of the echocardiograms, thallium scans, and

vectorcardiograms were read by the same specialist ineach field and the right ventricle graded as normalor hypertrophied (cor pulmonale). In two cases theechocardiograms were technically inadequate becauseof severe pulmonary hyperinflation between the heartand sternum, and in another case the vectorcardio-gram could not be interpreted because of dextrocardia.The thallium scans in these cases were readily obtainedand predicted right ventricular hypertrophy. Of theremaining 33 cases (19 boys, 14 girls), 21 (64%) hadcor pulmonale by echocardiogram. Similarly, 16 (48%)patients had cor pulmonale by vectorcardiogram,whereas only 10 of 33 (30%) had positive thalliumscans.

In nine of the patients all three tests were positive-in five patients, all three were negative. Thus in 14of 33 patients we had complete agreement as to thestate of the right ventricle by all three techniques. Ina further five subjects there was agreement betweenecho- and vector-cardiograms.

In this study vectorcardiography was an unreliableindex of cor pulmonale in agreement with previousreports (Siassi et al, 1971). Thallium myocardial per-fusion scans were much less reliable in children withCF contrary to previously published data (Cohen et al,1976) on adults with pulmonary disease.

REFERENCESCohen, H A, Baird, M G, Rouleau, J R, et al (1976). Thallium 201

myocardial imaging in patients with pulmonary hypertension.Circulation, 54, 790-795.

Gewitz, M et al (1977). Echocardiography in cystic fibrosis. AmericanJournal of Diseases of Children, 131, 275-280.

Goldring, R M et al (1964). Pulmonary hypertension and cor pul-monale in cystic fibrosis of the pancreas. Journal of Pediatrics, 65,501-524.

Lamarre, A et al (1972). Early detection of pulmonary functionabnormalities in cystic fibrosis. Pediatrics, 50, 291-298.

Liebman, J et al (1976). Cor pulmonale and related cardiovasculareffects of cystic fibrosis. In International Conference on CysticFibrosis, edited by R C Talamo. New York, Stratton Inter-continental Medical Book Conference.

Moss, A J et al (1965). Cor pulmonale in cystic fibrosis ofthe pancreas.Journal ofPediatrics, 67, 797-807.

Siassi, B, Moss, A J, and Dooley, R R (1971). Clinical recognition ofcor pulmonale in cystic fibrosis. Journal ofPediatrics, 78, 794-805.



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Mucosal droplet spread of Pseudomonas aeruginosafrom cough of patients with cystic fibrosis

J BLESSING-MOORE, B MAYBURY, N LEWISTON, and AYEAGER Pseudomonas aeruginosa is ubiquitous in theenvironment, colonises the GI tract and saliva of6-24% of normal individuals (Young, 1977), and is amajor pathogen in the immunologically compromised.The major portals of human entry include wounds,blood, respiratory tract, and urinary tract (Franklinand Franklin, 1971). In the mucous droplets it maysurvive for long periods and with evaporation thedroplet nucleus becomes a potential airborne sourceof infection (Wistreich, 1976).For hospital patients certain acquired serotypes may

be more pathogenic (Moody, 1977), and the acquisitionof an aminoglycoside resistant strain is a major threat.Family studies in which one or more children havecystic fibrosis (CF) have failed to show significant(nasal) carriage of the organism in non-CF members.Other CF members, however, may carry the sameserotype (Lourdes et al, 1976).We placed EMB culture plates at varying distances

from 25 CF patients during an hour of chest physio-therapy (PVD) and within four feet of 15 patientsduring a four-hour period which included PVD. Allplates were evaluated for growth of Ps aeruginosa.The data are presented as the percentage of plateswhich grew Pseudomonas.

In an attempt to find a reservoir for nosocomial in-fections we obtained throat, nasal, and rectal swabsfrom 25 professional personnel who had daily contact

Location No ofplates % withPseudomonaslhour

"Cough plates"-1 ft 42 19%Bed during PVD-3-4 ft 11 9%Room during PVD-1-9 ft 14 -

Breakfast tray after PVD 3-4 ft 5

with CF patients. None of these cultures grew Psaeruginosa.

Significant growth of Ps aeruginosa was noted onplates held at less than 1 ft from the mouth during thecough phases of the treatment. This may be importantin determining hospital "isolation" policies for youngCF patients. In the older patient with severe pul-monary disease the incidence of mucus bacterial spreadwas higher. Pseudomonas was not cultured from nor-mal individuals caring for the patients. Nevertheless,cultures of the room showed organisms of the samesensitivities as the patient occupying the room-apotential reservoir for Pseudomonas.REFERENCESFranklin, M, and Franklin, M (1971). A Profile ofPseudomonas, p 18.Beecham Pharmaceuticals.

Lourdes, R, Laraya-Cuasay, Cundy, K, and Huang, N (1976).Pseudomonas carrier rates ofpatients with CF and members of theirfamilies. Journal ofPediatrics, 89, 23-26.

Moody, Marcia (1977). In Pseudomonas aeruginosa: Effect of Acquisi-tion on the Incidence of Psa in Hospitalized Patients edited byViola Mae Young. Raven Press, New York.

Wistreich, G and Lechtman, Max (1976). Microbiology and HumanDisease, p 577. Glencoe Press.

Young, Viola Mae (1977). In Pseudomonas aeruginosa: Effect ofAcquisition on the Incidence of Psa in Hospitalized Patients. RavenPress, New York.

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Documents

Proceedings of the Thoracic SocietyWWADDINGTON, A S BANNER, E V SUNDERRAJAN, MK AGARWAL, and J RODRIGUEZ The arterial and mixed venous (Pr,02) blood gases and haemodynamic state of