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A sample of 147 men drawn from the workers in a pulp mill was compared with one of 124 men from a paper mill. The former included those exposed to chlorine and to sulphur dioxide. No significant differences were found in respiratory symptoms or in simple tests of ventilatory function in the two samples, but men working in chlorine had a somewhat poorer respiratory function and more shortness of breath than those working in sulphur dioxide. The working population of both mills together had a lower prevalence of respiratory disease than that of the male population of Berlin, N.H., previously studied, suggesting that working populations may not be representative of the general population. Further, a low prevalence of disease in a working population exposed to pollutants may not indicate their `safety9 in general populations.

The incidence of a variety of clinical and immunological features of an allergic state was studied at 7, 10, and 14 years of age in a group of children suffering from one of four grades of asthma, ranging from mild subclinical to severe unremitting, and compared with the incidence in a control group of non-asthmatic children. The incidence of all features of allergy was significantly higher in the asthmatics but no one feature unequivocally distinguished the asthmatics from the controls. Almost all the asthmatics showed several features of the allergic state at 14 years of age. A cluster of allergic features was a differentiating characteristic of the asthmatics, and the children with the most allergic manifestations were usually the children with the most severe and persistent asthma. The first appearance of and subsequent variation in some of the allergic manifestations often did not correspond to the clinical course of the asthma.Though many manifestations of asthma can be understood on an allergic basis the mechanism by which emotional disturbance, exercise, viral infections, and non-allergenic stimuli precipitate attacks of asthma and the relation of these factors to allergy are unknown.

1 The half-life of hydrocortisone (cortisol) has been measured in six patients before and after a three-week course of prednisone given for asthma. 2 There was considerable variation in peak plasma level of cortisol both within and between patients, but on both occasions the plasma half-lives were the same. 3 It was concluded that short courses of prednisone have no effect on the handling of hydrocortisone.

A sample of 315 asthmatic children, representative of the whole range of asthma in childhood, and a control group of 82 children were studied clinically and physiologically from 7 to 14 years of age. The asthmatic children were arbitrarily classified into four grades according to the relative frequency and persistence of their asthma to 14 years of age. Each of these grades could be more clearly defined on analysis of other clinical and physiological characteristics. The characteristics of severe persistent asthma were: onset usually in the first three years of life, a high frequency of attacks in the initial year, clinical and physiological evidence of persisting airways obstruction and pulmonary hyperinflation, chest deformity, and impairment of growth. By contrast, mild asthma usually began later in childhood, was episodic, and there was little or no evidence of airways obstruction between attacks. The attacks generally stopped before 10 years of age. In between these two extremes were two intermediate grades. The clinical and physiological characteristics of each grade of asthma at 14 years of age were usually evident by 10 years, and in the most severe grade by 7 years of age. These characteristics provide a sound basis for assessment, management, and prognosis.

Bronchilator is a triple-drug aerosol containing isoetharine, phenylephrine (a vasoconstrictor and mild bronchodilator), and thenyldiamine (an antihistamine). American workers (Spiel man, 1961 ; Siegel, 1962 ; Goldfarb and Romanoff, 1962) have reported the value of the triple aerosol in bronchial asthma, and its freedom from side-effects even in hypertensive patients. The aim of this work is to compare objectively the degree and duration of effect of Bronchilator1 with that of isoprenaline2 and a placebo aerosol3 in a double-blind controlled study.

Three randomly selected groups of 7-year-old schoolchildren in Melbourne with mild wheezy bronchitis, with moderate wheezy bronchitis, and with asthma were compared with a control group, and the patients followed up until 10 years of age. Comparison showed that if there was any significant difference between the study groups and the controls it was usually present in all these study groups. It was considered that children with wheezy bronchitis and asthma were from the same population with the same underlying basic disorder, and that there was a wide spectrum in various aspects of the natural history of the disorder.About 11% of all children aged 10 years had had some asthmatic episodes. Seventy per cent. of these children ceased having asthma before 10 years of age, while about 30% (3.7% of the whole community) continued to have episodes. There was a highly significant correlation between early age of onset, the frequency of episodes in the first year of symptoms, and the persistence of asthmatic episodes up to 10 years of age.Ten per cent. of all children with asthmatic episodes continued to have symptoms as severely at 10 years as at an earlier period. In this group the onset of symptoms was almost always before 3 years of age, there was a high frequency of episodes in the first year of symptoms, and boys and girls were affected in the ratio of 7:3.

Infections of the respiratory tract were studied in a group of families each containing a patient with chronic bronchitis or with asthma. A wide variety of infective agents may be associated with exacerbations in susceptible subjects, but the types of organism to which patients are most at risk differ according to the family structure. Exacerbations in the susceptible subject are more likely to be related to viral infections when the family contains children than when it does not.Two patients with asthma experienced frequent respiratory infections, many of which provoked attacks of asthma.

The influence on airway conductance of inhaled aerosols of prostaglandin F(2)alpha (PGF(2)alpha), histamine, and prostaglandin E(2) (PGE(2)) was studied in 10 patients with spirometrically reversible bronchial asthma and in 10 healthy subjects with no history of lung disorder. Both groups responded with bronchoconstriction after inhalation of PGF(2)alpha but the asthmatic patients were about 8,000 times more sensitive to the compound than were the healthy controls. In the patients, but not in the controls, PGF(2)alpha often caused a long-standing decrease in airway conductance with symptoms resembling allergen-provoked asthmatic attacks. On the other hand, the patients showed less than a 10-fold increase in sensitivity to histamine, and the ratio of histamine: PGF(2)alpha doses causing a 50% decrease of airway conductance was 2.6:1 and 2,400:1 in controls and patients respectively. Inhalation of PGE(2) while moderately but consistently increasing airway conductance in controls, had a variable-occasionally slight bronchoconstrictive-effect in patients. The decrease in airway conductance by a given dose of PGF(2)alpha was little modified by the simultaneous inhalation of a 100-times higher PGE(2) dose. It is suggested that endogenous, locally formed PGF(2)alpha may play an important part in the pathogenesis of bronchial asthma.

The bronchodilator and cardiac effects produced by aerosols of 0·5% isoprenaline and of 0·25, 0·5, and 1% salbutamol administered in 40% oxygen by intermittent positive-pressure ventilation were compared in 24 asthmatic patients. Isoprenaline and salbutamol in concentrations of 0·5% were equipotent in peak bronchodilator effect; salbutamol was superior in total bronchodilator effect and duration of average effect, but the peak bronchodilator effect occurred earlier after isoprenaline. Significantly greater tachycardia was produced by 0·5% isoprenaline than by the same concentration of salbutamol. The 0·25, 0·5, and 1% concentrations of salbutamol had about the same peak bronchodilator effect, but there was a stepwise increase in total effect and duration of average effect in relation to the concentration used. A similar stepwise increase in heart rate was also noted, but with all concentrations this was significantly less than with 0·5% isoprenaline. It was concluded that a 0·5% solution of salbutamol, which provided maximal bronchodilatation without important tachycardia, was therapeutically superior to the other three treatments.

Twenty-eight patients with asthma and house-dust allergy were investigated by five different challenge tests with mite extract ( Dermatophagoides pteronyssinus ). These tests were performed on the skin, bronchi, nasal mucosa, and leucocytes, and on normal human lung tissue passively sensitized by the patients9 serum. The results were compared with each other and with the clinical state of the patients. Of 21 patients on whom all five tests were carried out, positive reactions to every test were found in 14 (67%). Asthmatic attacks were readily induced by inhalation of the mite extract and occurred in 18 (86%). Nasal reactions were provoked in 18 (86%) and were not followed by asthmatic symptoms. A leucocyte test was positive in 19 (90%) and the serum test was positive in all (100%). Delayed asthmatic responses to bronchial challenge were seen in six patients, but there was no evidence that these were mediated by precipitins. Quantitatively there was no fixed pattern between the degrees of sensitivity of the different tissues in the same patient. The amount of mite antigen capable of causing an asthmatic reaction was extremely small—less than 1 μg. of mite material in several patients. In view of the prevalence of D. pteronyssinus in this country and its high allergenic potency, it is considered that this mite is an important factor in allergic asthma.

Ventolin (salbutamol) and Medihaler-Duo (isoprenaline/phenylephrine combination) standard pressurized inhalers were used to administer doses of two or six "puffs" to 16 patients with known reversible airways obstruction. The doses were administered in random order over two days. Both the Ventolin and Medihaler-Duo inhalers substantially increased FEV(1), but in the doses used salbutamol was more effective than isoprenaline/phenylephrine (P0.01). There was no significant difference between two and six puffs of salbutamol, though there seemed to be an advantage of six puffs of isoprenaline/phenylephrine over two puffs (P0.05). Adrenaline (1/1,000) 0.5 ml and atropine 0.6 mg produced similar increases in FEV(1) to those produced by salbutamol.The Pao(2) fell more than 5 mm Hg in three patients after salbutamol and in three after isoprenaline/phenylephrine. There was no significant fall in mean Pao(2) in any of the treatment groups. It is concluded that the Ventolin inhalant, administered in the conventional dose of two puffs, is as effective a bronchodilator as subcutaneous adrenaline and atropine, is more effective than the Medihaler-Duo, and is without detectable side effects.

Ventilatory function after three types of exercise-running, cycling, and swimming-was studied in 10 control subjects and 40 asthmatic patients. All performed eight minutes of submaximal aerobic exercise during each of the programmes, which were conducted in a randomly selected order. Biotelemetric monitoring of heart rates was used to equate the intensity of the exertion undertaken during the three systems of exercise. No control subject showed any significant variation in ventilatory capacity after exercise, and the responses after the three forms of exercise did not differ.In asthmatics exercise-induced asthma was observed after 72.5% of running tests, 65% of cycling tests, and 35% of swimming tests. In addition, those patients who developed exercise-induced asthma after swimming were noted to have significantly smaller falls in FEV(1) levels than were recorded after running and cycling. These results were statistically significant (P

The most popular current method of inhalation bronchodilator therapy in asthma and bronchitis is by dry aerosol, stored in small cartridges under pressure and delivered in metered doses. There is evidence that this method is superior to conventional wet aerosol inhalation in delivering an effective dose with greater economy (Bouhuys, 1963 ; Feinmann and Newell, 1963). This paper reports a comparison of three proprietary dry aerosol bronchodilator products and a placebo of inert propellant. The active drugs were isoprenaline sulphate (Medihaler-iso-Forte) and two newer preparations?Bronchi lator and orciprenaline (Alupent). Bronchilator is a triple combination of two sympathomimetic amines (isoetharine and phenylephrine) and an antihistamine (thenyldiamine). The sympathomimetic amine isoetharine was found to be as effective as 1% isoprenaline without pro ducing systemic upsets (Herschfus et al., 1951). It is an effective antagonist of histamine-induced bronchoconstriction in the guinea-pig, an action that is enhanced by the addition of the antihistamine thenyldiamine hydrochloride (Lands et al., 1958). The triple aerosol has been shown to be of value in asthma and to be largely free of side-effects (Spielman, 1961 ; Goldfarb and Romanoff, 1962 ; Siegel, 1962). The British reports to date have confirmed the value of this preparation in both asthma and bronchitis (El-Shaboury, 1964 ; Jacobsen and Prime, 1964). Orciprenaline (Alupent), an analogue of isoprenaline, has been ?hown to be an effective bronchodilator when given by tablet, injection, or conventional wet aerosol (Zidek, 1961 ; G?nthner, 1961 ; Myers and Coltman, 1963 ; Kennedy and Jackson, 1963 ; Edwards, 1964). The above reports suggest that orciprenaline is superior to isoprenaline in being less toxic and in having a more prolonged action. There is little known, however, about the comparative effectiveness of orciprenaline given as the metered dry aerosol. In addition, this investigation was planned to compare two instruments commonly used for estimating airway resistance at the bedside and in the consulting-room. These are the peak-flow meter and the portable bellows spirometer.

Exercise-induced asthma (defined as a fall in PEF of at least 25% of the pre-exercise value) was studied in adult patients with uncomplicated asthma. This was found to occur in 22 out of 52 patients. Pre-exercise inhalation of disodium cromoglycate reduced the mean fall in PEF after maximal exercise from 50% of the pre-exercise value to 23% (open assessment in 11 cases). After submaximal exercise for eight minutes the reduction was from 18% to 10% (double-blind crossover study in 28 cases). It is concluded that disodium cromoglycate partly inhibits the increase of airways resistance after exercise in asthmatic patients.

In 13 patients with allergic asthma disodium cromoglycate protected fully only two from an allergen-induced asthmatic attack. Inhalation of disodium cromoglycate did not improve lung function in five patients with long-standing chronic asthma. Previous clinical trials do not show convincing evidence that this drug improves bronchial asthma in a high percentage of cases, but it seems to help a small minority of patients.

A double-blind clinical trial of hyposensitization with aqueous extracts of Dermatophagoides pteronyssinus (the house-dust mite) and human skin scales showed a substantial improvement in symptoms in 11 asthmatics allergic to house dust treated with the D. pteronyssinus extract and a reduction in their need for other therapy. Five patients were well for a year but six relapsed. These results contrasted with the generally unfavourable course of the patients treated with the extract of human skin scales. Asthma due to house-dust allergy may be substantially improved by hyposensitization with D. pteronyssinus extract.

The synthetic polypeptide depot-tetracosactrin (Synacthen-Depot) was given to nine steroid-treated asthmatic patients hypersensitive to animal corticotrophin. Eight had a satisfactory increase in plasma and urinary 17-hydroxycorticosteroids (17-OHCS). The remaining patient had been shown previously to have adrenal suppression. None of the patients developed allergic reactions to depot-tetracosactrin, and seven have been receiving regular injections of the polypeptide twice weekly for the past eight months. In 13 normal subjects intramuscular injections of 1 mg. and 0.5 mg. of depot-tetracosactrin and 40 units of corticotrophin-gel were equally potent in raising the plasma 17-OHCS, but depot-tetracosactrin had a significantly longer action than corticotrophin-gel.

Twenty chronic asthmatic subjects were treated with disodium cromoglycate in open trial. Although in the group as a whole spirometric findings improved, some patients showed a significant increase in arterial oxygen tension or a significant fall in functional residual capacity without any appreciable changes in spirometry. These changes may partly explain the clinical efficacy of this drug.

A survey of the respiratory disorders in schoolchildren from rural areas showed no significant differences between the United Kingdom and Australia and New Zealand in loss of time from school owing to chest illness. Contrary to expectations the warmer the region the greater the prevalence of bronchitis, asthma, and hay fever. These results should encourage a critical appraisal of the respiratory benefits of warmer climates, and also suggest that the English climate should prove to be no more than a minor barrier to any future reduction of respiratory mortality in the U.K.

Tests in three patients with asthma occurring only on exertion showed that F.E.V.(1) fell progressively on exercise, to reach a minimum after 10 minutes. All patients showed a striking metabolic acidosis, with an accumulation of the products of anaerobic metabolism.

The relationship between the F.E.V.(1) as an index of airways obstruction and Pco(2) as an index of hypoventilation was investigated in 13 patients with chronic obstructive airways disease. Patients who had a normal Pco(2) despite severe airways obstruction retained relatively normal sensitivity to CO(2) as assessed by their "inspiratory mechanical work rate" response to CO(2). Others showed a raised Pco(2) in the presence of lesser degrees of airways obstruction and had reduced sensitivity to CO(2).

Ten normal and five asthmatic subjects were given intravenous injections of 10 ml. of 0.9% saline with and without 10 mg. of propranolol, and specific airway conductance was followed in a whole-body plethysmograph. Saline alone had no significant effect on conducatance in either group of subjects. Propranolol had no significant effect on conductance in normal subjects, but caused a mean fall of 34.9% in the asthmatics.

In a double-blind trial of the effect of inhaling three different beta-adrenergic stimulants (isoprenaline sulphate 1,000 mug., orciprenaline sulphate 1,500 mug., and salbutamol 200 mug.) and a placebo on ventilatory function in 24 patients with chronic asthma salbutamol was found to have a much longer action than isoprenaline, and it produced a slightly more intense and prolonged effect than orciprenaline. In a double-blind subjective assessment 13 of the 24 patients selected salbutamol as the most effective preparation, while only five preferred isoprenaline and three orciprenaline. Hence salbutamol, given by inhalation, may prove to be the most effective drug at present available for the short-term relief of asthmatic symptoms.

A study has been made of the personality of 44 patients with chronic airways obstruction (using the Eysenck Personality Inventory), this being related to the difference between their observed Pvco(2) and that predicted from their F.E.V.(1). This was designed to test the hypothesis that those patients with a lower Pvco(2) than predicted were the more extravert.The results showed a significant correlation between extraversion and the departure of Pvco(2) from predicted Those patients having a lower Pvco(2) than predicted were more extravert than those with a Pvco(2) higher than predicted. There was no correlation between neuroticism and the Pvco(2).These results support the hypothesis that the personality of a patient may play an important part in determining the alveolar ventilation found in patients with chronic airways obstruction. Patients known as "pink puffers" could more appropriately be named "pugnacious pink puffers."

An indication of obstruction to the upper airways (trachea and larynx) may be obtained by calculating the ratio of the forced expired volume in one second to the peak expiratory flow rate (FEV(1)/PEFR). This index was found to be usually less than 10 in normal subjects (mean 7.3), and in patients with asthma (mean 6.9), chronic bronchitis (mean 7.7), or interstitial lung disease (mean 6.3). A study of simulated upper airways obstruction showed that this index rises as the obstruction becomes more severe. All of 18 patients with proved upper airways obstruction had FEV(1)/PEFR indices greater than 10 (mean 14.0). This test can be carried out with forced expiratory manoeuvres only, and it does not require the use of complicated equipment. An FEV(1)/PEFR ratio greater than 10, when upper airways obstruction is suspected, indicates that significant obstruction may be present. High values suggest that the obstruction may be severe, and that further investigations are indicated.

A new drug, AH 7725, with properties similar to those of disodium cromoglycate (Intal) has the additional feature of being effective when taken by mouth. Six patients with allergic asthma were studied by bronchial challenge tests with antigen. In every one the drug was found to inhibit (either partially or completely) the immediate-type asthmatic response. Late responses were not influenced. The results were significant at the 0·5% level. These findings suggest that AH 7725 given by mouth may be able to inhibit naturally occurring asthmatic attacks in allergic patients. In this case its particular advantage as a prophylactic drug would lie in the treatment of very young asthmatic children and other patients who cannot take drugs by inhalation.

This study was undertaken to examine the possibility that IgE is not the only immunoglobulin responsible for immediate allergic reactions. A group of asthmatics were investigated in whom immediate allergic reactivity of the bronchi to common inhalant allergens had been confirmed by provocation tests. Their sera were fractionated and the reaginic activity of the immunoglobulin classes was studied by passive cutaneous anaphylaxis testing in monkeys. The results showed that the immediate allergic reactions were due to IgE antibodies in most patients, but there was a group with reactions due to short-term anaphylactic IgG antibodies. It was not possible to inhibit the IgG-mediated responses with disodium cromoglycate. As these two groups had clearly different serum IgE levels the estimation of IgE provided an important guide to the management of these patients.

In a double-blind study 10 patients with chronic asthma received beclomethasone dipropionate 400 mug daily in a Freon propellant from a pressurized dispenser, and 10 patients received the Freon propellant alone. At the start of the trial each patient was receiving long-term maintenance treatment with oral prednisolone in a dose of 7.5 to 15 mg daily. The daily dose of prednisolone was reduced by 1 mg every four weeks and the patient's progress followed by regular clinical assessment and studies of pituitary-adrenal function. The trial was continued until the dose of prednisolone was reduced to zero or until asthmatic symptoms increased to an unacceptable level.In the 10 patients who received beclomethasone the mean maintenance dose of oral prednisolone was reduced by 5.6 mg/day but in only two cases could this drug be withdrawn completely. In the placebo group the mean reduction in dose was only 1.3 mg, thus there was a significant difference between the two groups (P

The bronchodilator and cardiac effects produced by aerosols of 0.5% salbutamol and 0.5% and 1% rimiterol administered for three minutes in 40% oxygen by intermittent positive-pressure ventilation (I.P.P.V.) were compared in 15 asthmatic patients. Salbutamol and both the concentrations of rimiterol were equipotent in peak bronchodilator effect, but salbutamol had a significantly longer duration of bronchodilator action. There was significantly less increase in heart rate after rimiterol than after salbutamol. Aerosols of 0.5% rimiterol, 0.5% salbutamol, and saline were administered by I.P.P.V. to 10 normal volunteers. There was no difference between the mean heart rates after 0.5% rimiterol and saline but a highly significant increase in mean heart rate was observed after 0.5% salbutamol. It was concluded that 0.5% rimiterol was an effective short-acting bronchodilator drug with little or no cardiac beta(1)-adrenergic activity when administered for three minutes by I.P.P.V. in 40% oxygen.

Behavioural disturbances in the child, the mother-child and family relationships, and the family social structure were studied in a representative sample of the whole range of asthmatic children and compared with a control group of normal children. Behavioural disturbances occurred more often and at a statistically significant level only in the small group of children with severe and continuing asthma. These children were those with severe chronic airways obstruction as assessed physiologically and also with the most severe allergic manifestations.Predominant in the mother-child relations was an over-concern to protect the child's health in those children with continuing asthma at 14 years of age. The families of the very severely affected group of children showed evidence of more stress than other families. Socioeconomic conditions were not significantly different in any group of asthmatic children compared with the control group.

The finding by several workers that biochemical responses to catecholamines are diminished in asthmatic patients during periods of active asthma as compared to normal subjects has led to the recognition of the beta-adrenergic blockade phenomenon, a common accompaniment of extrinsic bronchial asthma. Using an intact cell method to measure leucocyte adenyl cyclase activity, we have been able to show that there is a noticeably reduced responsiveness of this enzyme system (which is now identified with beta-receptor function) to isoprenaline in the leucocytes of patients suffering from acute bronchial asthma, but that asthmatic patients in remission could not be distinguished from normal persons in this respect. Evidently the defective beta-receptor function may be associated with overactivity of the alpha-receptors in acute bronchial asthma, since the responsiveness to isoprenaline stimulation could be restored towards normal by concomitant treatment of the leucocytes of these patients with alpha-receptor blocking drugs such as phentolamine or thymoxamine. Ouabain, though somewhat less potent, also enhanced responsiveness to isoprenaline stimulation. The relation of these results to the clinical observation of adrenaline resistance in active asthma suggests that alpha-receptor blocking drugs may be of value in restoring the sensitivity of beta-receptors to sympathomimetic amines.

Betamethasone valerate aerosol is a new compound for the treatment of asthma. Its clinical effectiveness was established in a double-blind cross-over trial in non-steroid-dependent asthmatic patients. At a dosage of 400 to 800 mug/day for three months there was no evidence of suppression of hypothalamic-pituitary-adrenal function, as assessed by tetracosactrin and insulin stress tests.A 12-month follow-up study of 120 patients using steroid aerosols (betamethasone valerate or beclomethasone dipropionate) indicated that tolerance does not develop and that a daily maintenance dose of 200 mug/day was adequate in most patients. Temporary lack of response was observed during episodes of sputum production or of heavy exposure to antigen.There were no observed side effects other than fungal infections of the respiratory tract. However, the incidence of candidiasis of the pharynx (13%) and particularly of the larynx (5%) in apparently immunologically normal patients was disturbing. These infections were not seen in patients taking 200 mug/day. Though there is yet no evidence that fungal infections associated with steroid aerosols may penetrate the trachea and bronchi the possibility of this indicates that caution should be exercised in their use, particularly in long-term high dosage.

Three patients with sensitivity to an intravenous anaesthetic—thiopentone, propanidid, and Althesin (alphadolone and alphaxalone)—are described. In the cases of thiopentone and Althesin the reaction was characterized by cardiovascular collapse, while bronchospasm also occurred with thiopentone. The reaction to propanidid was a direct skin sensitivity. All patients had a personal or family history of asthma and all had been previously exposed to the offending drug. A leucocyte challenge test showed an allergic response to thiopentone and Althesin in two patients but gave a negative result in the patient with the skin reaction. Allergic reactions can occur to all types of intravenous anaesthetics in a few patients.

The conventional method of lung scanning detects defects of pulmonary artery perfusion. False positive results occur because regions of hypoventilation, such as are present in obstructive airways disease, also cause defects of perfusion. The converse is not true, however, as defects of perfusion continue to be ventilated. Thus in pulmonary embolism ventilation-perfusion discrepancy (normal ventilation and impaired perfusion) occurs.We have assessed the clinical value of this discrepancy. Out of 18 patients with ventilation-perfusion discrepancy 14 had a final diagnosis of pulmonary emboli, whereas in none of the 34 patients without the discrepancy was this final diagnosis made. We conclude that combined ventilation-perfusion lung scanning distinguishes pulmonary emboli from other lung conditions such as asthma and bronchitis which cause impaired pulmonary perfusion. The false positive rate was only 4% overall and 7.7% in patients with perfusion defects.

Indoramin, an alpha-adrenoceptor blocking drug, has been found to prevent the occurrence of exercise-induced bronchoconstriction. Evidence is provided in two cases that this was not due to the antihistamine properties of indoramin.

A total of 117 asthmatic patients were studied in a double-blind, cross-over trial with half-periods of three weeks in which disodium cromoglycate (D.S.C.G.) was compared with an inactive preparation. D.S.C.G. improved spirometric measurements, at a very high level of statistical significance, more than did placebo. The mean advantage of D.S.C.G. was less than 10% after three weeks. Symptomatic improvement by D.S.C.G. was small though significant; it was not correlated with spirometric improvement. A history of chronic cough was the only clinical characteristic associated with a better-than-average spirometric response to D.S.C.G.

anterior position. The more experienced practitioner may wish to extend the range of his intervention, but this should be limited to institutional conditions. There are many general practitioners in this country, including several of our former house-surgeons, who are using the instrument successfully. Further extension of this trend would help to reduce the dan gers of forceps in unpractised hands and lead to improved figures for infant survival in the home, as we believe it has in the hospital.

Terbutaline, a new bronchodilator acting on beta-adrenergic receptors, was given to 10 asthmatic patients, who received on separate days 5 mg orally, 10 mg orally, and 0.25 mg subcutaneously. The ventilatory response was assessed by measurement of the FEV(1) before and at intervals after administration. The cardiovascular response was assessed by measurement of the heart rate and blood pressure and by electrocardiography at the same times as spirometry was performed.The ventilatory response to all three doses and by both routes was satisfactory. The maximal increase in FEV(1) after 5 mg orally was only slightly less than that after 10 mg. The maximal increase in heart rate after 5 mg orally was about half that which occurred after 10 mg. It is concluded that 5 mg orally and 0.25 mg subcutaneously are suitable doses.In general a modest fall in blood pressure affected the diastolic more than the systolic. On E.C.G. the T wave was often depressed, and in one patient, it was inverted. A trough-like depression of the QRS baseline occurred several times. The significance of the E.C.G. changes is uncertain.

Since Barger and Dale (1910) described the chemical struc ture and sympathomimetic action of adrenaline-like amines, adrenaline and adrenergic drugs have been extensively used for the treatment of asthma. Adrenaline itself is active only when it is given parenterally or by inhalation, whereas the more recently introduced isoprenaline is more stable and can be given by inhalation or as a sublingual tablet, though it is not suitable for parenteral use. Over the past two decades the number of inhalants that have been available for the treatment of asthma has increased enormously. They consist basically of adrenaline or isoprenaline ; many proprietary brands also contain other ingredients?for example, atropine sulphate, atropine methonitrate, benzocaine, papaverine, posterior pituitary extract, stramonium, as well as other trace ingredients.