BLOOD-GAS TENSIONS IN BRONCHIAL ASTHMA

644 Simon et al. 1965). In the year following this outbreak we found that 53 of 150 (35%) cultures of Str. pyogenes isolated by Dr. D. C. J. Bassett in Trinidad from sporadic " strains. In the cases of glomerulonephritis were " T-14 Baltimore investigation (Markowitz et al. 1965) there were 58 cases of streptococcal impetigo with 6 associated cases of acute glomerulonephritis. A sample of cultures from skin lesions included a number of " T-14 " strains, but from the cases of nothing is known about the streptococci " nephritis. All but 2 of the T-14 " strains isolated in connection with outbreaks of glomerulonephritis had the specific T-antigen of type 49, and 57 of the 100 cultures tested had the M-49 antigen. In the localised epidemics of nephritis, such as those in Holland and Czechoslovakia, and at Red Lake, Str. pY8genes type 49 was isolated from most of the cases. In Alabama and Trinidad, however, where infections were sporadic at the time of our investigation, and were drawn from relatively large populations, members of type 49 accounted for between a quarter and a third of all the cultures isolated. It is unlikely, therefore, that Str. pyogenes type 49 was the only nephritogenic strain endemic in these communities. The evidence that type-49 streptococci were indeed responsible for glomerulonephritis in Alabama and Trinidad is based on the observation that they were isolated more commonly from skin lesions in patients with nephritis than in those with uncomplicated pyoderma, and that they were found relatively seldom in the upper respiratory tract. This will be discussed further

BLOOD-GAS TENSIONS IN BRONCHIAL ASTHMA E. TAI M.B.

Sydney

RESEARCH FELLOW

JOHN READ M.D.

Sydney, F.R.A.C.P.

PROFESSOR OF MEDICINE

From the Department of Medicine, University of Sydney, and the Thoracic Unit, Royal Prince Alfred Hospital, Sydney

Arterial oxygen (Po2) and carbon-dioxide (Pco2) tensions were measured in 12 patients with clinically severe asthma (status asthmaticus) and 64 patients with clinically less severe asthma. Hypoxæmia, hypercapnia, and acidosis were common in patients in status asthmaticus. The greatest deviations from normal recorded were: Po2 39 mm. Hg, Pco2 200 mm. Hg, pH 6·81. Patients with clinically less severe asthma commonly showed disturbances of blood-gas tensions. Of 64 patients, arterial Po2 was less than 60 mm. Hg in 14, and arterial Pco2 greater than 45 mm. Hg in 9. Arterial Po2 values were as low as 50 mm. Hg without elevation of arterial Pco2. The demonstration of such disturbances of bloodgas tensions in patients whose asthma does not appear to be clinically severe provides a basis for sudden " unexpected " deterioration and death when airways obstruction increases further.

Summary

in subsequent publications (Dillon et al. 1967, Parker, Bassett, and Maxted 1967). When acute glomerulonephritis follows streptococcal pyoderma, it is usually not associated with Str. pyogenes type 12, but with other nephritogenic strains such as type 49, even though, as in Alabama, type-12 streptococci may be common in throat cultures collected in the same area (Dillon et al. 1967). Nevertheless, type-49 streptococci may

cause

acute

glomerulonephritis following

respiratory-tract infection. This suggests that the type-49 organism is one of those with a special ability to cause streptococcal pyoderma when hygienic conditions are more favourable to spread by the cutaneous than by the respiratory route. We thank the many colleagues who have sent us strains of streptococci, and in particular our collaborators Dr. Hugh Dillon (University of Alabama), Dr. D. C. J. Bassett (Trinidad Regional Virus Laboratory, University of the West Indies), and Prof. L. W. Wannamaker (University of Minnesota), for information and cultures; and Mi s. L. Ball, A.i.M.L.T., for excellent technical ’

assistance.

Requests for reprints should be addressed to M. T. P., Central Public Health Laboratory, Colindale Avenue, London N.W.9. REFERENCES

de Moor, C. E. (1960) Ber. Rijksdienst Inst. Volksgezondh. p. 129. (1962) ibid. p. 238. Dillon, H., Moody, M. D., Maxted, W. R., Parker, M. T. -

(1967)

Unpublished. Elliott, S. D., Dole, V.

P. (1947) J. exp. Med. 85, 305. Kleinman, H. (1954) Minn. Med. 37, 479. Köhler, W. (1963) Z. ImmunForsch. 125, 145. Lancefield, R. C. (1957) J. exp. Med. 106, 525. (1962) J. Immun. 89, 307. Perlmann, G. E. (1952) J. exp. Med. 96, 71. McLean, S. J. (1953) J. gen. Microbiol. 9, 110. Markowitz, M., Bruton, D., Kuttner, A. G., Cluff, L. E. (1965) Pediatrics, Springfield, 35, 393. Pakula, R. (1951) J. gen. Microbiol. 5, 640. Parker, M. T., Bassett, D. C. J., Maxted, W. R. (1967) Unpublished. Poon-King, T., Mohammed, I., Cox, R. (1965) W. Indian med. J. 14, 139. Rammelkamp, C. H., Weaver, R. S., Dingle, J. H. (1952) Trans. Ass. Am. Physns, 65, 168. —

—

Subcommittee on Streptococci and Pneumococci (1967) Int. J. syst. Bact. (in the press). Simon, N. S., Potter, E. V., Siegel, A. C., McAninch, J., Poon-King, T., Humair, L., Earle, D. P. (1965) J. Lab. clin. Med. 66, 1022. Šramek, J. (1967) Personal communication. Vendl, L., Kliment, J., Panocha, M. (1964) Zentbl. Bakt. ParasitKde. Abt. I (ref.) 196, 56. Updyke, E. L., Moore, S., Conroy, E. (1955) Science, N.Y. 121, 171. Wannamaker, L. W. (1967) Personal communication. Pierce, H. C. (1961) Jl-Lancet, 81, 561. Wiley, G. G. (1960) Fedn Proc. Fedn Am. Socs exp. Biol. 19, 204. Williams, R. E. O. (1958) Bull. Wld Hlth Org. 19, 153. Maxted, W. R. (1953) Int. Congr. Microhiol. 1, 46. —

—

645 levels of vital capacity (v.c.) and forced expiratory volume in one second (F.E.V.1) after recovery were recorded, indicating that asthma rather than permanent lung disease was the major cause of their disability. 64 patients had less severe asthma at the time of study. They consisted of outpatients, patients admitted electively to hospital for investigation and control of chronic asthma, and patients who had partly recovered from more serious episodes of asthma, during which blood-gas tensions had not been measured. At the time of study all were " wheezy ", but none appeared very ill. It was judged that none would have obtained admission to hospital via the casualty department on clinical

grounds. In the 12 patients regarded on clinical grounds as being in asthmaticus a polyethylene catheter was inserted into the brachial artery by the Seldinger technique and left in place for six to forty-eight hours to allow serial measurements of bloodgas tensions. In the 64 less ill patients, a single sample of arterial blood was withdrawn by percutaneous brachial-artery puncture. Arterial oxygen tension (Po2) was measured with a polarographic electrode, and arterial carbon-dioxide tension (Pco2) with a Severinghaus electrode. Arterial blood pH was status

ARTERIAL

BLOOD-GAS

TENSIONS

AND

r’TTMTF’ATTV <:t!VT!F

pH

IN

12

PATIENTS

WITH

A.QTT-TMA

Fig. 1-Arterial oxygen tension (Po.) in mm. Hg, compared with forced expiratory volume in I second (F.E.V.1) in litres, in 64 patients with asthma who were not judged to be seriously ill on clinical grounds.

Figs. 1 and 2 show arterial P02 and PC02 levels, compared with F.E.v.i, in the 64 patients with clinically mild to moderate asthma. Arterial Pco2 was greater than 45 mm. Hg in 9 patients; of these, 4 showed arterial P02 levels less than 60 mm. Hg. Arterial P02 was less than 60 mm. Hg in 14 patients, including the 4 in whom arterial PC02 was greater than 45 mm. Hg. Arterial oxygen saturation derived from P02 and PC02 values in the 14 patients with an arterial P02 of less than 60 mm. Hg ranged from 81 to 91%. Discussion The present data demonstrate that many patients with asthma of only moderate clinical severity show a considerable reduction of arterial oxygen tension. Even when this reduced oxygen tension is, of itself, not sufficient to produce a dangerous degree of hypoxsemia, it renders the patient very vulnerable to any further increase of airways

Many of the arterial P02 levels illustrated in fig. correspond to a point at the " knee " of the haemoglobin-oxygen dissociation curve, where any further reduction of P02 may lead to an abrupt and dangerous fall of arterial oxygen saturation. It is, then, not surprising that dangerous levels of hypoxaemia may develop rapidly

obstruction. 1

*

oxygen via face-mask from respirator. oxygen via cuffed endotracheal tube. t Patient breathing 40% oxygen via cuffed endotracheal tube. § Patient breathing oxygen at flow-rate of 4 litres per minute via mask

Patient

breathing 100 %

t Patient breathing 100%

OJ

intranasal catheter.

measured with electrometer.

a

glass electrode and

E.I.L.’Vibron’

when an exacerbation of asthma occurs. The data shown in the table illustrate the profound disturbances of blood-

Results

The accompanying table shows arterial blood-gas tensions and pH soon after admission to hospital in 12 patients in status asthmaticus. 7 patients were receiving oxygen therapy in various forms at the time the measurernents were made; and we did not, at the time, feel justified in interrupting this therapy in order to obtain arterial blood samples during air breathing. 5 patients breathing air showed Po2 values ranging from 39 to 62 mm. Hg; and 3 patients receiving 100% oxygen showed P02 values from 80 to 265 mm. Hg. 8 patients showed PC02 levels greater than 50 mm. Hg; in 2 of these patients (1 and 2), arterial PC02 levels exceeded 100 mm. Hg. In 7

patients, arterial blood pH was less than 7-30 and, in patients 1 and 2, it was less than 7-00. At the time of withdrawal of the intra-arterial catheter, six

hours after admission to hospital, all had shown distinct clinical improvement. Arterial patients levels P02 were, however, still less than 65 mm. Hg in 10 patients; and arterial PC02 remained greater than 50 mm. Hg in 2 patients (see table). to

forty-eight

Fig. 2-Arterial carbon-dioxide tension (PC02) in mm. Hg, compared with forced expiratory volume in 1 second (F.E.V.1) in litres, in 64 patients with asthma who were not judged to be seriously ill on clinical grounds.

646 gas tensions and the degree of acidosis which may occur during such exacerbations of asthma. The degree of hypercapnia and of acidosis in patients 1 and 2 (see table) is quite remarkable. In neither instance is the accuracy of the measurements in doubt. Adequate calibration procedures were applied, the measurements

or the previous conditioning of the doctor must commonly fail to alert the physician to the seriousness of the situation. The present data indicate the serious blood-gas disturbances present in many patients with asthma of only moderate clinical severity, and the extreme disturbances which may arise in status asthmaticus.

made by a skilled and experienced observer, and step-wise return to a more normal state was observed over a regular series of observations in each case. Patient 1 had been injudiciously given 100 mg. pethidine intramuscularly in a small hospital because of restlessness and confusion before transfer to the Royal Prince Alfred Hospital, and both patients had received oxygen freely. Both were unconscious at the time of admission, but were conscious and cooperative after sixteen hours and eight hours respectively. The most likely mechanism of the hypoxaemia found in the 64 less severely ill subjects is maldistribution of ventilation/blood-flow ratios in the lungs. In 39 of these patients, physiological dead-space/tidal-volume (VD/VT)

This work was supported by a grant-in-aid and research fellowship (E. T.) from the Asthma Foundation of New South Wales. We thank Mr. Peter Donnelly for technical assistance; and Dr. M. R. Joseph, Dr. H. P. B. Harvey, Dr. E. J. Halliday, and the general physicians and assistant physicians of Royal Prince Alfred Hospital for permission to study patients under their clinical care. Requests for reprints should be addressed to J. R., Department of Medicine, University of Sydney, Sydney, N.S.W., Australia.

were a

measured at the time of arterial puncture. The value of VD/VT ratio was 0-40 (range 0-20-0-59). This is significantly above normal levels in our laboratory, and indicates the presence of considerable maldistribution of ventilation/blood-flow ratios. This situation was doubtless exaggerated in the 12 patients with severe asthma, but no VD/VT ratio measurements were possible. Among the severely ill patients, an additional right-to-left shunt effect was evident at least in patients 1, 2, and 3, in whom arterial POll failed to reach expected levels whilst they were breathing 100% oxygen. This shunt probably depends on continued blood-flow through completely unventilated regions of the lung. There was a general correlation between the degree of reduction of F.E,V’l and the extent of disturbance of blood-gas tensions in the 64 patients with clinically less severe asthma (figs. 1 and 2). F.E,V’l levels of less than 1 litre were particularly associated with significant reduction of arterial POll’ At the same time, the correlation was not so close as to make an F.E.v.i level greater than 1 litre a reliable indicator of a fairly normal arterial Po2. Similarly, only 4 of the 14 patients with an arterial Po2 level of less than 60 mm. Hg showed arterial PC02 levels greater than 45 mm. Hg. A normal level of arterial Pco2, readily determined by say the re-breathing technique (Campbell and Howell 1960), offers no guarantee, based on the present data, that the patient’s arterial Po2 is not as low as 50 mm. Hg. We have been unable to find reports of measurements of arterial oxygen tensions in any large group of patients with asthma. The two largest series in which any blood-gas measurements have been reported are those of Herschfus et al. (1953) and Williams and Zohman (1960). Each of these reported measurements of arterial oxygen saturation in 15 patients with asthma of various degrees of severity; and in each group some patients showed a reduction of arterial oxygen saturation. There appears to be a widespread (and quite unjustified) belief that asthma is not a serious disorder. It used to be taught that death from asthma was very uncommon. In fact, Jacoby (1966) has drawn attention to the significant mortality from asthma even among young people in Great Britain, and several hundred deaths are certified as due to asthma in Australia each year. Yet any individual death from asthma is often described as " unexpected ". This implies that the clinical features presented by the patient ratio

REFERENCES

V., Christie, (1964) Respiratory Function in Disease; Bates, p. 144. Philadelphia. Campbell, E. J. M., Howell, J. B. (1960) Br. med. J. i, 458. Herschfus, J. A., Bresnick, E., Segal, M. S. (1953) Am. J. Med. 14, 23. Jacoby, N. M. (1966) Lancet, ii, 1354. Williams, M. H., Zohman, L. R. (1960) Am. Rev. resp. Dis. 81, 173. R. V.

D.

was

mean

MULTIPLE SEROTYPES OF VIBRIO CHOLERÆ ISOLATED FROM A CASE OF CHOLERA Evidence Suggesting In-vivo Mutation E. J. GANGAROSA M.D. Rochester UNIT, EPIDEMIOLOGY PROGRAM, NATIONAL COMMUNICABLE DISEASE CENTER, BUREAU OF DISEASE PREVENTION AND ENVIRONMENTAL CONTROL, P.H.S., ATLANTA, GEORGIA, U.S.A.

CHIEF,

ENTERIC DISEASES

A. SANATI

H. SAGHARI

M.D. Teheran

M.D. Teheran

OF THE INSTITUTE OF PUBLIC HEALTH

Ph.D.

RESEARCH, TEHERAN, IRAN

J. C. FEELEY California, Los Angeles.

OF THE DIVISION OF BIOLOGICS

STANDARDS, NATIONAL HEALTH, BETHESDA, MARYLAND, U.S.A.

INSTITUTES OF

Three serotypes—Ogawa, Inaba, and Hikojima—were isolated on 3 different days from a patient with cholera gravis. Ogawa was initially isolated from her stool: Inaba appeared the day before clinical relapse. Evidence suggests that the appearance of Inaba and Hikojima types was due to in-vivo mutation.

Summary

Introduction

JAPANESE workers (Kabeshima 1918, Nobechi 1923) defined three cholera serotypes-Inaba, Ogawa, and Hikojima-all of which share group-specific 0 antigens and differ in minor type-specific 0 antigens. Ogawa and Inaba are usually designated by the antigenic symbols AB and AC, and Hikojima forms an intermediate type ABC. This is a report of the isolation of these three serotypes on 3 different days from a patient with cholera. Case-report The patient, a seamstress-teacher by trade, aged 55 years, was admitted to a cholera treatment centre in Iran at 2.30 A.M. on Oct. 14, 1965. She gave a history of voluminous, painless, and frequent diarrhoea, followed by vomiting for about 26 hours. She had received an antiemetic the evening before admission and had taken no other drugs. About 15 days before admission, one of her students had had similar symptoms but had recovered without being sent to hospital. The patient herself had received no cholera vaccination. The patient was a moribund, moderately obese woman in obvious cardiovascular collapse. The pulse was absent at the