Brit.J. Dis. Chest 0966) 6o, zoz.

A CLINICAL TRIAL OF A MUCOLYTIC AGENT-- ACETYLCYSTEINE--IN CHRONIC BRONCHITIS

BY GERALD ANDERSON

The Royal Free Hospital, London w.c.I

ACETYLCYSTEINE is a derivative of the amino-acid L-cysteine. Studies in vitro (Sheffner, 1963) have shown that it is able to break down mucus. In chronic bronchitis airway obstruction may be caused in part by viscid mucus, and acetylcysteine has been claimed to relieve breathlessness by dissolving mucus so that it can be more easily expectorated.

This study describes the effect of the drug on symptoms, sputum volume, and venfilatory function tests, in patients with chronic cough and expectoration due to chronic bronchitis.

Pat ients and Methods

Six men and two women patients, aged 28 to 75 years (mean 56 years), were studied. All had chronic bronchitis and had recovered from acute exacerbations of their bronchitis. All bronchodilator drugs were stopped on the day of the test and the preceding day.

The one-second forced expiratory volume (F.E.V.) was used as an index of the severity of airway obstruction: on each occasion two values were obtained and the higher selected. A basal value for the F.E.V. was obtained, and the patients were then given acetylcysteine by inhalation (2 ml. of 2o per cent. solution) as an Aerosol in air via an Agla inhaler at a flow rate of 6 litres per minute. The F.E.V. was then measured at the following times after giving the aerosol: immediately, 15 minutes, 3o minutes, t hour, t½ hours, and 2 hours. The procedure was performed in the early afternoon on each occasion to avoid fluctuations caused by the normal diurnal variations in the F.E.V. (Lewinsohn et al., 196o ).

The patients' opinion was obtained of the effect of the drug on their ability to cough up sputum. The volume of sputum expectorated during the 5 hours after giving acetylcysteine was measured and compared with that expectorated during the same time in the previous day when the drug had not been given.

Resul t s Fig. t shows that the drug had no effect on the F.E.V., and Fig. 2 shows

that acetylcysteine did not increase the volume of sputum expectorated (group mean on control day 37 ml., and on treatment day 34"5 ml.). Three of the eight patients were convinced that expectoration was assisted.

(Received for publication, November x 965)

1 0 2 A N D E R S O N

1900-

:~7oo. u.i

"1500-

1300.

1100 ,

900'

700,

500

J

j

i i i J i i

l u

._ -~ "~ =. y..~. .E ~ ~

~, e , a /

Time after taking drug

FiG. z . - -Effect of Acetylcysteine on the F.E.V. ( the thick line shows the m e a n value).

Side-effeas Vomiting occurred during administration of the Aerosol in one patient. In

another case the F.E.V. fell immediately from I75o ml. to zioo ml., but returned to the original reading in 3 ° minutes.

D i s c u s s i o n Acetylcysteine owes its in-vitro mucolytic properties to the presence of a

sulphydryl group which opens the disulphide bond in mucus. The viscosity of

100"

= 802

._.

~ /.0 X

~ 20

~ 0

I'-]before drug PT;lafter drug

1 Z 3 _ m

5 6 7 Patient

8

FxG. 2 . - -Effect of Acetylcysteine on spu tum volume.

A CLINICAL TRIAL OF A MUCOLYTIC AGENT--ACETYLCYSTEINE I0 3

TABLE I.--EFFECT OF ACETYLCYSTEINE ON EASE OF EXPECTORATION

Patient Effect

O O + O + O O +

o = no improvement; + = improvement

bronchial mucus is largely due to mucoprotein, which could be broken down by acetylcysteine. The drug is not inactivated by desoxyribose nucleic acid and is therefore active in the presence of pus. In vitro a I per cent. solution reduces the viscosity of human bronchial mucus and is more effective than detergents or trypsin (Le Maistre et al., 1963).

Reas (I963) reported that in a group of children with cystic fibrosis the drug caused an improvement in breathlessness and an increase in the forced vital capacity. These observations were made during a control period of six weeks followed by a period of ten to eighteen weeks with treatment by acetyl- cysteine inhalations. Unfortunately this treatment period was not interrupted, so that improvement may have been spontaneous or due to factors other than the drug. Favourable reports by Webb (I962) and Reggiani et al. (I963) were also uncontrolled.

The mucolytic action of acetylcysteine in vitro is very rapid (Sheffner et al., 1963; Reggiani et al., I963) and if the drug were clinically useful a rapid effect would be anticipated with a sharp increase in sputum volume and perhaps in F.E.V. No such effect was demonstrated, and the drug was not shown to be of any benefit.

ACKNOWLEDGEMENT The author wishes to thank Dr. David of British Drug Houses for supplies of acetylcysteine

(Airbron).

REFERENCES LE MAISTRE, C. A., SHAW, P. B., & HURST, G. A. Papers read at the Annual Meeting of the

American Thoracic Society, 2oth May, 1962 , and at the Scientific Assembly of the American Medical Association, Ohicago, 28thJune, 1962 , abstracted in Amer. Rev. resp. D/s. (I962), 86, i x5, and Med. Sci. (1962), 12, 509 .

LEWINSOHN, H. C., CAPEL, L. H., & SMART, J . (196o). Brit. reed. 07., x, 462. I~AS, H. W. (1964). 07. Pedlar., 65, 542- R~oGXAm, A., GALZlGNA, L., & GAFFURI, E. (1963). Minerva med., 54, 36oS- SHEFFNSR, A. L. (I963). Ann. N.Y. Acad. Sci., lO6, 298. WEEB, W. R. (x962). 07. thorac, cardiovasc. Surg., 44, 33 °.