proceedings ofthethoracic societyproceedings of the thoracic society tions well below that producing...

Thorax (1976), 31, 238.

Proceedings of The Thoracic SocietyThe Spring Meeting of The Thoracic Society was held on 27 February 1976 at the Royal College ofPhysicians, London. Summaries of the papers follow:

Contaminated water from a factory machineproducing extrinsic allergic alveolitis

J. A. R. FRIEND, J. GADDIE, K. N. V. PALMER, C. A. C.PICKERING, and J. PEPYS Recently, there have beenreports of extrinsic allergic alveolitis arising fromcontamination of domestic air humidifiers with micro-organisms (Banaszak et al., 1970). Typical symptomsand signs of this illness developed in 24 employees ofa large modern stationery factory in Aberdeen. Anaerosol of water was induced by vacuum pumps anddistributed through the ventilation system to otherareas of the factory. Chest x-rays during attackswere normal, but pulmonary function tests showedsignificant reductions in vital capacity and singlebreath carbon monoxide diffusing capacity withhypoxaemia. All these employees, together with fiveapparently asymptomatic individuals, had abnormalserum precipitins to samples of water obtained froma recirculating cooling system serving air compressorsand vacuum pumps. Two of these employees werechallenged with an inhalation of extract of this water,and the symptoms and the functional changes of atypical attack developed after several hours. Althougha variety of microorganisms were cultured from thewater, no single specific organism could be associatedwith the precipitin reaction. Modifications have nowbeen made to the ventilation system and no furtherepisodes of the illness have occurred. In future factorydesign the possibility of dispersion of contaminatedwater into the air should be avoided.Banaszak, E. F., Thiede, W. H. and Fink, J. N. (1970). Hypersensitivity

pneumonitis due to contamination of an air conditioner. NewEngland Journal ofMedicine, 283, 271-276.

Influenza and parainfluenza virus titres in birdfanciers with acute allergic alveolitis

A. J. NEWMAN TAYLOR, P. TAYLOR, D. BRYANT, JOANLONGBOrTOM, and j. PEPYS Sera from pigeon fancierswith acute allergic alveolitis commonly have hightitre positive complement fixation tests (CFTs) toinfluenza A and B, and less commonly to influenzaC and Sendai virus (parainfluenza). In the absence ofavian exposure, a fourfold or greater fall in titre isobserved over a period of a few weeks, a findingwhich would generally be regarded as diagnostic of anacute viral infection. Sera from budgerigar fancierswith acute alveolitis commonly have negative CFTs tothese viruses but may occasionally have low titre posi-tive CFTs. The complement fixing activity in pigeon

fanciers is attributable to antibodies produced by thesesubjects which react with antigens of the chorio-allantoic membrane of chicken eggs in which influ-enza A and B are grown, and of the allantoic fluidfrom which influenza C and Sendai virus areharvested. Sera with positive CFTs to influenza A andB give positive CFTs to extracts of chorio-allantoicmembrane, and such sera have antibodies to chorio-allantoic membrane antigens demonstrable on im-munoelectrophoresis. These sera have negative CFTsto influenza A grown in monkey kidney cell culture,and also negative haemagglutination tests with tworecent strains of influenza A2.

It is uncommon for virology laboratories routinelyto include chorio-allantoic membrane extracts as acontrol for influenza A and B CFTs, and allantoicfluid as a control for influenza C and Sendai virus isnot generally available. Clinically and radiologicallyinfluenza pneumonia and acute allergic alveolitis mayhave similar features. Our findings indicate that adefinite diagnosis of influenza cannot be based in apigeon fancier on either a single elevated CFT titreor rapidly falling titres in paired specimens, in theabsence of appropriate serological controls.

Occupational asthma in workers using epoxy resinsystems

I. W. FAWCETT and J. PEPYS Epoxy resins are widelyused in industry and are a well recognized cause ofcontact dermatitis. The addition of a hardening agentsuch as an amine or acid anhydride to the epoxy resineither at room temperature or in the presence of heatallows complete polymerization of the resin producinga high molecular weight and product. This process,particularly when it occurs at high temperatures,liberates fumes of the hardening agent into theatmosphere.Asthma in workers exposed to epoxy resins and

their hardeners has been reported but not previouslystudied in detail. The case histories and investigationsof three men working with these compounds are des-cribed. The epoxy resin systems were being used fordifferent purposes in each case-as an adhesive, as amoulding powder, and as an electrostatic paint spraycoating. Careful inhalation testing simulating theirexposure at work provoked asthmatic reactions, whichwere shown to be due to the amine or acid anhydrideconstituents of the system. In two of the three sub-jects, reactions occurred at atmospheric concentra-

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Proceedings of The Thoracic Society

tions well below that producing irritant effects in otherexposed workers, suggesting a hypersensitivity reac-tion; in the third subject asthma only followed pro-longed exposure.

In view of the widespread use of epoxy resinsystems in industrial processes and in various domesticproducts, it seems possible that these substances maybe responsible for many cases of asthma whose causeis as yet unrecognized.

Effect of prolonged asbestos exposure on regionallung function

N. N. STANLEY Regional distribution of ventilationwas studied in 14 pipe-laggers with more than 20 years'occupational exposure to asbestos dust and in eighthealthy control subjects. Chest radiographs showedearly evidence of pulmonary fibrosis in four andpleural fibrosis at the lung bases in six of the workers.Each subject was studied in the seated position. The

radioactivity in both lungs was recorded by a gammacamera during the washout of 1"Xe which had beenbreathed to equilibrium in a closed circuit. Activity-time plots were constructed using data obtained fromupper, middle, and lower lung zones. In healthy sub-jects the first 70% of washout was always fastest inthe lower zones. In two of the asbestos workers,though, the activity declined more slowly throughoutthe whole of washout in the lower compared with themiddle zones. In 10 others, the fall in activity wasinitially fastest in the lower zones but soon becameslower than in the middle zones, which caused a cross-over of the lower and middle zone curves beforewashout was 70% complete. No individual had a re-strictive or gas transfer defect. However, eight hadmild airways obstruction characterized by a reductionin maximum mid-expiratory flow rate and an increasein closing volume, although specific conductance wasusually normal. The abnormalities in regional andoverall ventilatory function occurred in smokers andnon-smokers alike.The findings are consistent with hypoventilation of

a proportion of lung units within the lower zones.Analysis of "'Xe washout may provide a sensitivemethod for the early detection of pulmonaryasbestosis.

Slow reacting substance as a preformed mediatorfrom human lung

A. B. KAY, D. G. JONES, and LESLEY S. TURNBULL SlOWreacting substance of anaphylaxis (SRS-A) is con-sidered a primary mediator in allergic (extrinsic)bronchial asthma since it is a potent constrictor ofbronchial smooth muscle and is released from IgE-sensitized lung fragments in vitro following challengewith specific antigen. It is thought that an antigen-antibody reaction on target cells is essential for theformation and release of SRS-A. We have found thatan agent with identical pharmacological and chemicalproperties to SRS-A can be extracted from human

lung tissue in a preformed state (pSRS). The patternof contraction on the guinea-pig ileum by pSRS wasindistinguishable from that of SRS-A. The activity ofpSRS could not be attributed to the presence of K,Na, Call, and Mg++ ions. As with SRS-A, pSRScould be absorbed onto Amberlite XAD-2 and silicicacid. Both were eluted from the former with 80%ethanol and from the latter with a mixture of n-propanol, ammonia, and water. Both pSRS and SRS-A were resistant to boiling in 0-05N NaOH whereasthese activities were destroyed by 005N HC1. Aryl-sulphatase IIB destroyed the activities of both pSRSand SRS-A. An antagonist of SRS-A, FPL 55712,inhibited the action of pSRS at concentrations com-parable to that of SRS-A. These studies suggest thatpSRS and SRS-A are identical and that, like hista-mine, SRS is preformed and can be released fromlung non-specifically as well as immunologically. Thenon-immunological release of slow reacting substancefrom human lung by mechanisms independent of IgEand other tissue sensitizing antibodies suggests thatSRS may participate in various forms of asthma in-cluding chronic (intrinsic) disease.

Comparison of aminophylline and salbutamolinfusion in the treatment of acute attacks of asthmaA. J. JOHNSON, J. PIDGEON, S. BATEMAN, S. G. SPIRO, andJ. W. PATERSON Salbutamol has recently becomeavailable in a formulation suitable for parenteral use.A study was designed to compare its efficacy withaminophylline when given as an infusion to patientswith acute attacks of asthma. In addition, the studyallowed an investigation of metabolic consequences ofasthma and its treatment, and the results are describedin a separate paper.

Physiological parameters were recorded on admis-sion and, in line with the usual pratice of this hospital,the patients were treated with an aminophylline bolus(5 mg/kg) given slowly while the patient receivedoxygen, followed by two doses of salbutamol (5 mgeach) delivered from intermittent positive pressureapparatus (IPPB, Bird). Following each of these treat-ments the physiology recordings were repeated. At theend of the initial phase, if the clinician in charge de-cided an infusion of a bronchodilator drug was re-quired, aminophylline or salbutamol was given inrandom order to successive patients. Physiologicalparameters were recorded at regular intervals duringthe infusion, and four hours after cessation. Amino-phylline was given in a dose of 1 mg/min andsalbutamol at a rate of 10 ,ug/min, a dose chosen togive bronchodilatation without cardiovascular sideeffects (May et al., 1975). Blood samples were drawnfor the metabolism study on admission, on completionof the initial phase, one and four hours into the in-fusion. and in a fasting state during the convalescentperiod.To date 42 patients between the ages of 16 and

65 years without cardiovascular or renal disease have

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entered the study. Seventeen patients improved suffici-ently during the initial treatment phase not to requirean infusion. On admission these patients' attackswere only marginally less severe, as judged by peakexpiratory flow rates, than those of the 25 patientswho went on to an infusion, but they showed a greaterresponse to the initial treatment. Of the patients whoreceived an infusion the improvement in airflow ob-struction was significantly greater in the aminophyllinegroup. No patient required to be changed from amino-phylline, but in 10 patients the response to salbutamolwas insufficient and the infusion was changed toaminophylline. However, not all these patients im-proved on the second infusion. One patient developedmarked sy3temic hypotension which necessitated dis-continuation of salbutamol, but no serious side effectswere noted with aminophylline.At this stage in the study it would appear that

aminophylline is more effective than salbutamol in thedoses given, in acute asthma.May, C. S., Spiro, S. G., Johnson, A. J., and Paterson, J. W. (1975)

Thorax, 30, 236.

Lipid changes during acute attacks of severe bronchialasthma and following therapy

T. R. TICKNER, D. G. CRAMP, M. R. WILLS, J. PIDGEON,S. BATEMAN, A. J. JOHNSON, S. G. SPIRO, and s. w.CLARKE Salbutamol has been shown to produce amarked rise of plasma non-esterified fatty acids(NEFA) following its administration by intravenousinfusion (Goldberg et al., 1975; Leading article, 1975).In view of this finding it has been suggested that theadministration of salbutamol may endanger the myo-cardium, particularly if anoxia is also present.During a clinical trial of salbutamol and amino-

phvlline therapy the opportunity was taken to measureplasma NEFA, triglyceride, glucose, and insulin con-centrations during an acute asthmatic attack and itssubsequent treatment.A profound metabolic disturbance as assessed by

the measured variables was found to be present onadmission in nearly all the patients. Furthermore, nofurther enhancement of the disturbance was seenduring the drug administration. The initial gross ab-normalities did not persist after the acute phase of theattack had resolved.

These findings suggest that these metabolic distur-bances were likely to be due to the stress of theasthmatic attack. The findings also suggest that anycontribution to the metabolic disturbances from thedrug regimen per se. was unlikely. It seems, therefore,that neither salbutamol nor aminophylline producemetabolic disturbances greater than those of the con-dition for which they are used.Goldberg, R., van As, M., Joffe, B. L., Krut, L., Bersohn, T. and Seftel,H.C. (1975). Postgrad. med. J., 51, 53.

Leading article (1975). Brit. med. J., 4, 65.

Status asthnsaticus and death from asthmaRUTH M. CAYTON Since 1970 the number of deathsfrom asthma occurring annually in England and Wales

has not changed. Status asthmaticus is commonly be-lieved to precede death from asthma, but this may notnecessarily be true. A group of 61 asthmatic patientsadmitted to hospital during 76 attacks of statusasthmaticus has been studied. Patients who did notrespond to an initial injection of intravenous amino-phylline (250 mg) were treated with intravenous injec-tions of hydrocortisone (200 mg) at four-hourlyintervals until clinical improvement occurred. Clinicalsigns and measurements of respiratory function, in-cluding arterial blood gases, were documentedthroughout the acute illness and during convalescence.The initial assessment of the severity of the attack

gave no guide to those patients likely to respond to asingle injection of aminophylline or hydrocortisone orto those requiring repeated injections of hydrocorti-sone for several days. Two patterns of recoveryemerged, judged by symptoms, spirometr.c measure-ments of respiratory function, and arterial bloodgases. In one group of patients (aged 28 years) hydro-cortisone in dosages ranging from 200 to 1200 mgfor 18 hours was required to treat the acute attack.Rapid relief of symptems coincided with progressiveimprovement in the FEVo.7s and FVC for five days,not matched by improvement in the Pao2 which con-tinued for as long as four weeks. The second groupof 26 patients (aged 53 years) required dosages of 200to 8000 mg of hydrocortisone for 63 hours. Furthertreatment with oral prednisolone was required tomaintain the slow improvement which occurred insymptomatology, FEVo.75, FVC, and Pao2.

It is suggested that asthmatic patients are at riskfrom sudden death when gross disturbance in respira-tory function, especially Pao,, are not matched bycorresponding severe symptoms. This may occurfollowing the treatment of an acute attack of asthmaand is especially common to young people.

Pressure studies following high and lowoesophagogastrostomy

H. R. MATlsHEWS and D. WV. WARD Conventional oeso-phagogastrectomy involves an intrathoracic oesophago-gastrostomy below the aortic arch. This creates anhiatus hernia, and reflux with stricture often results.With anastomoses performed at cervical level, how-ever, these problems are less common. To investigatepossible reasons for this, transanastomotic pressureswere measured, using open-sided continuously per-fused catheters, in 14 patients.Group 1 comprised seven patients (aged 40-73

years) who were studied one to six years after athoracic ('low') anastomosis; all operations were forcarcinoma. No gradient was demonstrated across anyanastomosis. Group 2 comprised seven patients (aged55-74 years) who were studied eight months to twoyears after a cervical ('high') anastomosis; five opera-tions were for carcinoma, one for achalasia, and onefor peptic stricture.- All seven patients had a sphincterzone depicted within 3 5 cm of the anastomosis. Meanmaximum sphincter pressure was 29 mmHg (range

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9-53) and mean length 2-7 cm (range 1-5-3-5). Thiscompares with a mean pressure of 18 mmHg andmean length of 3 5 cm in seven unoperated subjects.Two principal conclusions are drawn: (1) that the

conventional 'low' anastomosis provides no sphinctericfunction whatsoever, and (2) that the 'high' anasto-mosis, rather than destroying the cricopharyngealsphincter, actually retains it as a functioning unit im-mediately adjacent to the anastomosis. The implica-tions of these findings with regard to the site ofelection for oesophagogastrostomy will be discussed.

Selective vagotomy of the oesophagus-a newpossibility for treatment of hiatal hernia

M. H. EDWARDS The view that hiatal hernia is aggra-vated by upward pull from the longitudinal muscle ofthe oesophagus has led to recent reports of transectionof the muscle as an adjunct to the usual repair(Davidson, 1972; Mullard, 1972). Transection of thevagal nerve supply cf the oesophagus along all orpart of its length would appear to be a logical alter-native to this possibly hazardous method of reducinglongitudinal muscle strength, especially if vagotomycould be selective, so preserving innervation of moredistal organs.

In a canine preparation, dissection of the wholeintrathoracic vagus from the oesophagus reducedlongitudinal muscle contraction by 88%. This was aneffect on striated muscle.

Since striated muscle in man is limited to theupper half of the oesophagus (Arey and Tremaine,1933), the effects of vagal dissections on this regionwere studied in the preparation. A highly significant(P<0 001) reduction of longitudinal contraction of thesuprahilar oescphagus was obtained by dissecting thevagus from the oesophagus between the hilum andthe upper border of the aorta. Lower oesophagealsphincter pressures and pyloric function wereunaffected.

Selective oesophageal vagotomy in this region inman may prove a useful adjunct to hiatal herniarepair.Arey, L. B. and Tremaine, M. J. (1933). The muscle content ofthe loweroesophagus of man. Anatomical Record, 56, 315.

Davidson, J. S. (1972). Circumferential oesophageal myotomy. BritishJournal ofSurgery, 59, 938.

Mullard, K. S. (1972). The surgical treatment of diaphragmaticoesophageal hiatal hernia. Annals of the Royal College of SurgeonsofEngland, 50, 73.

Diagnosis of recent viral infection from single serumsamples

J. V. COLLINS, Y. BUCHNER, J. R. PATTISON, and R. B.HEATH Conventional methods for identifying a recentviral infection require the isolation of the virus fromthe patient or the demonstration of a rise in titre ofantibodies in consecutive serum samples taken atintervals after the onset of illness. Both methods aredependent upon the presentation of the patient soonafter the onset of the illness which is uncommon in

hospital practice. If it were possible to identify recentinfection from a single serum sample this would haveobvious practical advantages. The presence in theserum of high titres of complement-fixing antibodiesagainst soluble influenza antigens is suggestive ofrecent infection but methods for their detection areunreliable.We have developed a method of sucrose-density

gradient ultracentrifugation for fractionating serawhich separates immunoglobulins of the IgM and IgGclasses. We have been able to detect specific IgM andIgG antibodies in the sera of patients recovering frominfection with influenza viruses. Our results show thatin more than 90% of patients specific IgM and IgGantibodies are detectable in the serum by about 14days from the onset of symptoms, and IgM classantibodies persist for a further 20-70 days. Con-versely, in patients with no recent history of influenzainfection or in whom infection is known to haveoccurred more than 100 days previously, antibodiesare exclusively of the IgG class, and no specific IgMantibodies are detectable.From our results we conclude that the demonstra-

tion in the serum of specific IgM antibodies againstinfluenza viruses is a suitable method for identifyingrecent infection using single serum samples. The use-fulness of this technique in identifying the role ofinfluenza infections in precipitating various respiratoryillness is illustrated.

A study of methods and results of treatment ofpulmonary tuberculosis in Scotland

JOAN F. HEFFERNAN, A. J. NUNN, J. PETO, and w. FOX Asurvey of a 50% random sample of all patients newlynotified as having pulmonary tuberculosis in Scotlandin 1968 was undertaken to study methods of treatmentand management in the routine services; resultsachieved up to two years are reported. The estimatednotification rates were higher in the males, rising to90 per 100 000 at 55 or more (Heffernan et al., 1975).After exclusions, 770 patients were eligible for follow-up. The deaths are based on 795 patients, including 20diagnosed post mortem and five other inadequaterecords. There were 106 (13-3%) deaths, 34 (4 3%)from tuberculosis, the rest from non-tuberculouscauses. Bacteriological failures totalled 4 5 % and non-bacteriological failures (eg, regimen changed for drugtoxicity, long-term defaulters) 11-4%.For the stuidy of methods of treatment and manage-

ment patients have been classified as initially bacterio-logically positive (372) or negative (309). Of these,87% positive and 65% negative were admitted tohospital for an average of 18-0 and 10-7 weeks re-spectively; in 80% and 57% the initial chemotherapywas streptomycin/PAS/isoniazid, and the total dura-tion of chemotherapy averaged 22-2 and 191 months.An analysis of time off work showed that 4% positiveand 24% negative patients never stopped work, 41°%and 19 % were off work for more than six months, and18 % and 8 % never returned. An analysis of four

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groups of patients classified according to pretreatmentbacteriological status and radiological classification atan independent assessment showed that the proportionof patients admitted to hospital was higher, strepto-mycin was more frequently used and for longer,and total duration of chemotherapy was longest inthe bacteriologically positive/radiographically activegroup. Nevertheless, at the other extreme, the bac-teriologically negative/radiographically inactive groupreceived substantial therapy.The survey provides a useful basis for evaluating

tuberculosis programmes.Heffernan, J. F., Nunn, A. J., Peto, J., and Fox, W. (1975). Pulmonary

tuberculosis in Scotland-a national survey and follow-up. Thecharacteristics of the cases notified in 1968. Tubercle, Lond., in press.

Sarcoidosis of the upper respiratory tract (SURT)and its relationship to lupus pernio

E. NEVILLE, R. G. S. MILL.S, D. JASH, D. MCKINNON, andD. GERAINT JAMES Sarcoidosis of the upper respira-tory tract (SURT) is an uncommon but disablingmanifestation involving the nose, nasopharyngealmucosa, and larynx. Involvement of the nose mayalso include the nasal bone and cartilage and over-lying skin. Long-term follow-up suggests that SURTsometimes progresses inexorably to lupus pernio withwhich it is closely linked. We report a series of 32patients with clinical and histological evidence ofmultisystem sarcoidosis comprising seven patients withSURT alone, another eight with the transition stageof SUJRT and lupus pernio, and 17 patients withirreversible lupus pernio. The series has a femalepreponderance of 7: 1, and one-quarter of the patientswere negro. Patients with mucosal disease presentedin the third decade and patients with lupus pernio inthe fourth and fifth decades. SURT and lupus pernioare chronic fibrotic manifestations of sarcoidosis andare frequently accompanied by similar fibroticlesions, including bone cysts, chronic uveitis, andlymphadenopathy. SURT was accompanied bylaryngeal sarcoidosis in five instances so it should besought by examination of the larynx at bronchoscopy.SURT frequently presents to the nose and throat

surgeon who may perform submucous resection toovercome the symptom of longstanding nasal stuffi-ness. This may have disastrous consequences, such asnasal septal perforation, so it is important torecognize SURT early and treat it without surgicalintervention.

Aerosolized lignocaine and irritab!e airwaysP. HOWARD, S. R. BRENNAN, P. B. ANDERSON, and RUTH M.CAYTON Intrapulmonary afferent receptors may beconcerned with the control of breathing and with thesensation of breathlessness. The sensation of breath-lessness in patients with obstructive airways disease isnot closely related to mechanical limitation of air flowjudged by simple spirometric tests. It is possible thatairways disease increases the sensitivity of afferent

terminals, giving rise to inappropriate reflex stimula-tion of higher nervous centres. Lignocaine in doses of150-400 mg was instilled into the airways of 15 patientswith obstructive airways disease. Eleven patientsderived no benefit but four patients improved, largelydue to the prolonged supression of a persistent irritat-ing cough. Compared with saline, aerosols of ligno-caine often increased airways resistance, but, despitethis, the cough was suppressed for many days orweeks beyond the time when all local anaestheticeffects on taste or numbness had disappeared. Onepatient has returned to work as a miner after twoyears' absence but continues to attend for lignocaineaerosolization every six weeks. An increased sensi-tivity of tracheal cough receptors is suggested as themechanization for the persistent irritating cough andwill be discussed.

Airway responses to inhaled bronchodilators inpatients with reversible airflow obstruction

0. M. P. JOLOBE, J. S. PRICHARD, and D. J. LANE Air-way responses to inhaled atropine methonitrate 0-2%followed after 60 minutes by an inhaled 8-adrenergicagonist (isoprenaline or salbutamol) have beenfollowed in patients with reversible airflow obstruction(Altounyan, 1964).

Tests were performed on subjects who had not re-ceived bronchodilator drugs for at least 12 hours.Results were expressed as an index giving the per-centage response to atropine seen in relation to thetotal response to both agents. Using conventionalspirometric indices, 200 patients were tested.The results showed a bimodal distribution of the

index with one peak at 20-30% and a second peakat 90-100%. These two peaks corresponded in clinicalterms to patients who could be classified as asthmaticsand bronchitics respectively.

In 30 patients, additional measurements were madeof airways resistance and specific conductance using awhole body constant volume plethysmograph, and flowvolume curves were recorded breathing air and ahelium/oxygen mixture. In general, the changes inspirometric flow volume and plethysmographic indiceswere similar in magnitude and direction, but in sixinstances FEVy and SGAW changed in opposite direc-tions following administration of the 8-agonist.

Particular attention will be drawn to a group ofbronchitic subjects who, following maximal broncho-dilatation with atropine, showed deterioration in air-ways function, by whatever index that was assessed,with a ,8-agonist.Altounyan, R. E. C. (1964). Variation ofdrug action on airway obstruc-

tion in man. Thorax, 19, 406-15.

Pulmonary artery pressure in severe thoracicdeformity

J. M. SHNEERSON For many years it has been knownthat patients with severe thoracic deformities fre-quently die in middle age with right ventricular failure

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due to pulmonary hypertension. The cause of thelatter is, however, still uncertain. Studies on 32patients, mainly young adults, have helped to resolvethis question.A Bradley microcatheter was passed into the pul-

monary artery, and pressure readings were obtainedat rest and during and after a progressive exercise teston a bicycle ergometer.The results show that the resting pressure is in-

versely proportional to the resting Pao2 and that therate of rise of pressure during exercise is closely re-lated to the VC, FRC, and TLC. Breathing pureoxygen at rest led to a fall in pressure which was pro-portional to the degree of pre-existing hypoxaemia.However, breathing oxygen during exercise had noeffect on the rate of rise of pressure.

A rat model for long-term oxygen therapyE. LEACH, P. HOWARD, and G. BARER Chronicallyhypoxic rats were subjected to different recoveryregimes in an attempt to mimic long-term oxygentherapy in chronic bronchitis.

Rats kept for three weeks in a 10%.0 chamber('hypoxic rats') developed muscularization of pulmon-ary arterioles, right ventricular hypertrophy (RVH),and polycythaemia (Hunter et al., 1974). Some'hypoxic rats' were compared immediately with litter-mate controls, others were allowed to recover in airfor six weeks ('recovery rats') while still others spent8 or 16 hours daily in air and the rest of the day in10% 02 for six weeks ('intermittent-normoxic rats').During 'intermittent-normo*ia' Pao2 is higher thanin bronchitic patients on oxygen therapy.

Right ventricle/left ventricle weight ratio in 'hy-poxic', control, 'recovery', 8 and 16-hour 'intermittent-normoxic' rats was, respectively, 0-61+0-02 (SEM),0133±0-02, 0-36+0-01, 0 50±0 02, 0,48+0,02. The ratioin 'hypoxic rats' was significantly different from thatin controls and in 16-hour 'intermittent-normoxic' rats(P<0 001) but the latter was still significantly differentfrom controls. The ratio was similar in control and'recovery' rats. In eight-hour 'intermittent-normoxicrats' it was reduced compared with 'hypoxic rats' butnot significantly. Thus 16-hour 'intermittent-normoxia' was required to reduce RVH but did notallow complete resolution.

Muscularization of vessels, assessed by counting theproportion of peripheral vessels with thick walls, re-solved even more slowly. The percentage of thesevessels in 'hypoxic', control, 'recovery', and 8-hour'intermittent-normoxic' rats was, respectively, 23+0-9(SEM), 12+1-1, 18±1-1, 20-7±2-3. Thus vessels werestill thickened after six weeks' recovery in air andwere not changed by the 'intermittent-normoxic'regime. The vessel changes compared qualitatively andquantitatively with those in patients with chronic ob-structive lung disease.The haematocrit was 64±15 (SEM) in 'hypoxic'

and 43+0L9% in control rats. Recovery was completein air and non-existent after 'intermittent-normoxia'.

The rat model indicates some problems facing long-term oxygen therapy.Hunter, C., Barer, G. R., Shaw, J. W. and E. J. Clegg (1974). Growthofthe heart and lungs in hypoxic rodents; a model ofhuman hypoxicdisease. Clinical Science and Molecular Medicine, 46, 375-391.

Pattern of stimulated breathing in patients withchronic airflow obstruction

C. S. GARRARD and D. J. LANE We have previouslyshown that in normal subjects the pattern of breathingduring CO2 stimulation can be adversely influenced bythe introduction of an expiratory non-elastic resistanceat the mouth (Garrard and Lane, 1975). Tidal volumeresponse was diminished compared with the unloadedstate and there was a progressive rise in functionalresidual capacity (FRC).

In this communication we report an analysis of thepattern of breathing during CO2 stimulation in 12patients with chronic airflow obstruction. The patternwas expressed in terms of a plot of tidal volumeagainst breath duration. At all levels of CO:, breathduration was shorter than would be anticipated, andtidal volume response was small.

Intermittent estimations of thoracic gas obtainedapproximately every tenth breath using a whole bodyconstant volume plethysmograph showed a progressiverise in FRC during CO2 stimulation in 10 of the 12subjects. Maximum tidal volumes attained approachedand in some instances exceeded the inspiratorycapacity of the subject (taking into consideration theincrease in FRC).

It is suggestedw that the changes in FRC may be animportant component in the genesis of dyspnoea dur-ing stimulated breathing in these patients.Garrard, C. S. and Lane, D. J. (1975). The pattern of stimulated

breathing in man during non-elastic expiratory loading. Journal ofPhysiology, 251, 4041.

Pulmonary mechanics in respiratory muscle weaknessG. J. GIBSON, N. B. PRIDE, and J. NEWSOM DAVIS Iffull expansion of the lungs of normal subjects islimited by strapping the chest wall, secondary changesin the elastic properties of the lungs occur (Caro etal., 1960). Weakness of the respiratory musclessimilarly restricts lung expansion, but information onthe lung distensibility of such patients is limited tomeasurements of dynamic compliance which are diffi-cult to interpret. We have investigated the staticpressure volume characteristics of the lungs in a seriesof patients with respiratory muscle weakness due tovarious neuromuscular diseases. The results weresimilar to those obtained acutely in strapping experi-ments, with a low value of lung recoil pressure atfull inflation but also a reduction in the slope of thepressure volume curve, indicating that secondarychanges in lung distensibility occur. These might bedue to diffuse microatelectasis or to a generalizedalteration in alveolar elastic properties. The implica-tions of these findings are:

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1. The restricted vital capacity of these patientsmay be due not only directly to the loss of dis-tending pressure but also to secondary changesin the lungs themselves.

2. A single measurement of pulmonary com-pliance (static or dynamic) may not differentiatebetween primary intrapulmonary disease andchanges secondary to extrapulmonary restric-tion.

3. Reduced distensibility of the lungs may berelevant to the breathing pattern of suchpatients.

Caro, C. G., Butler J. and Du Bois, A. B. (1960). Some effects of restric-tion of chest cage expansion on pulmonary function in man. Anexperimental study. Journal of Cli. ical Investigation, 39, 573-583.

Use of radioactive N2 in demonstrating localizeddisease in children believed to have asthma

S. GODFREY, G. HAMILTON, N. FREEDMAN, and P.WINLOVE We have recently developed the techniqueof radioisotope scanning to measure total andregional lung function in children of all ages(Ronchetti et al., 1975; Godfrey et al., 1975) and nowpresent the use of the method to help make thecorrect diagnosis in children erroneously thought tohave bronchial asthma.The technique consists of administering a bolus of

3N by inhalation and perfusion while the child liesover a gamma camera linked to a computer systemwhich processes the data. For the inhalation study

the gas is given through a nasal catheter at end ex-piration and for the perfusion study it is dissolved insaline and injected intravenously. The technique re-quires no active co-operation from the child, and it ispainless apart from the injection and carries a negli-gible radiation hazard. The computer system enablesthe investigator to divide the lung fields into regionsand provides a record of the arrival and washout of'3N for each region from which information aboutventilation and perfusion is obtained.Wheezing is extremely common in infancy and

childhood and, while the commonest cause of severeand persistent wheezing is bronchial asthma, it isrecognized that other lesions may mimic asthma.Over a relatively short period several children havebeen referred to the asthma clinic with apparentlyintractable asthma which had failed to respond totreatment including steroids in some cases. Certainatypical features suggested that the diagnosis mightbe incorrect and '3N gamma scans were carried out.In each case the scan revealed disease confined to onelung, the other being entirely normal, the character-istic change in the scan being diminished ventilationand perfusion of the affected lung with gas trapping.Illustrative cases will be discussed and the value of thenew technique will be considered.Godfrey. S., Ronchetti, R., Stocks, J. and Hallidie-Smith. K. (1975).

Generalised pulmonary hyperinflation and Fallot's tetralogy in aneonate investigated by pulmonary physiological and radioisotopicmethods. Thorax, 30,456-460.

Ronchetti, R., Stocks, J., Freedman, N., Glass, H. and Godfrey, S.(1975). The clinical application of regional lung function studies ininfants and small children using 13N. Archives ofDisease in Childhood,50, 595-603.

CORRECTION

In the October 1975 issue of Thorax on p. 594, line 8of the right-hand column should read as follows:R. C. GODFREY Epidemiological evidence suggests

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