Ian W B Grant

Substitution of Beclomethasone Aerosol for Oral Prednisolone in the Treatment of Chronic Asthma

In a double-blind study 10 patients with chronic asthma received beclomethasone dipropionate 400 μg 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 patients 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the mean maintenance dose of oral prednisolone was reduced by 5·6 mg/day but in only two cases could this drug be withdrawn completely.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 <0·01). Studies of pituitary-adrenal function showed that a normal adrenal response to tetracosactrin stimulation returned only in the two patients from whom prednisolone was withdrawn. Hence the addition of beclomethasone dipropionate by inhalation to systemic corticosteroid therapy allows useful reductions to be made in the oral maintenance doses of corticosteroid. Reductions must be made with caution since there is wide individual variation in response to beclomethasone and in only a minority of patients can oral treatment by completely withdrawn.

BECLOMETHASONE DIPROPIONATE BY INHALATION IN THE TREATMENT OF AIRWAYS OBSTRUCTION

Abstract In a controlled trial 7 patients with airways obstruction were treated with beclomethasone by inhalation (2 mg/day) and then with prednisolone by mouth (20 mg/day), each for a period of 7 days. In 4 patients the airways obstruction was partially relieved by beclomethasone, but further improvement was recorded in 3 of these patients after subsequent treatment with prednisolone. There was evidence of impairment of hypothalamo-pituitary-adrenal (HPA) function following the administration of beclomethasone by inhalation in 5 of the 7 patients and of complete suppression in all 7 after subsequent treatment with prednisolone by mouth. It was concluded that beclomethasone by inhalation in a dose of 2 mg/day had no real advantage over prednisolone by mouth (20 mg/day) in the treatment of airways obstruction, in terms either of increase in FEV 1 or of preservation of normal HPA function. Limited experience with a smaller dose of beclomethasone (0·4 mg/day) by inhalation in an earlier uncontrolled trial suggested that this dose did not impair HPA function but was insufficient in most cases to relieve airways obstruction.

Comparison of oral prednisolone and intramuscular depot triamcinolone in patients with severe chronic asthma.

In a double blind crossover study oral prednisolone was compared with intramuscular depot triamcinolone in the treatment of 20 patients with severe chronic asthma. A short term study comparing each treatment over four weeks showed only minor differences in therapeutic efficacy, but at the end of 24 week periods on each of the two treatments triamcinolone was significantly more effective than prednisolone in terms of forced expiratory volume in one second and forced vital capacity. Better control of asthma was accompanied by a significant fall in weight and some evidence of reduced adrenal suppression (improved cortisol response following a short tetracosactrin test). Side effects, including menstrual irregularities, muscle pain, and hirsuitism, were, however, more common during treatment with triamcinolone.

Cis-platinum and vindesine in combination in the treatment of non-small cell lung cancer

Sixty-three patients with advanced non-small cell carcinoma of the bronchus were treated with a combination of cis-platinum and vindesine. All patients had measurable disease and were of good performance status; none had received prior chemotherapy or radiotherapy. Thirty-three per cent of patients responded, with five patients achieving complete remission. Median duration of response was 4 months, with a median survival of 14 months in the responsers, compared with 6.5 months in the whole group and 4.8 months in the nonresponders. Severe toxicity was encountered, with alopecia, gastrointestinal toxicity and neurotoxicity common. Myelosuppression and renal toxicity were not dose-limiting. Thus the activity of this drug combination is confirmed, but severe toxicity precludes its widespread use in clinical practice.

Phase II trial of vindesine and VP16-213 in the palliation of poor-prognosis patients and elderly patients with small cell lung cancer

SummaryForty-three previously untreated patients, all of whom had poor-prognosis small cell lung cancer and/or were >65 years old, received treatment with vindesine and VP16-213. Thirteen patients had limited disease and 30 extensive disease. Response rates (CR+PR) of 86% (CR 29%) and 66% (CR 17%) were seen in patients with limited and extensive disease, respectively. Time to relapse was short in those responding (4–4.5 months), and most responders required additional treatments. The overall toxicity was minimal and patient compliance was high. This combination is useful for the palliative treatment of small cell lung cancer when aggressive chemotherapy is inappropriate.

Are corticosteroids necessary in the treatment of severe acute asthma

In clinical medicine, perhaps more than in any other area of scientific endeavour, we are prone to become prisoners of our traditional preconceptions. Gradually in most cases, but rapidly in a few, many of these preconceptions have been swept away. It took centuries for bed rest in the treatment of many serious diseases, such as pulmonary tuberculosis and coronary thrombosis, to be discredited, and decades for the barbarous practice of removing healthy tonsils from healthy children to be abandoned. In contrast, the discovery that high-concentration oxygen therapy in patients with ventilatory failure could cause coma and death had an immediate impact. In some of these instances, and in many others, therapeutic policy has turned full circle and forms of treatment once considered logical and beneficial have come to be regarded as irrational or even positively harmful. The iconoclast in medicine, although not always a popular figure in the profession, has often helped to open the way to major therapeutic advances. Yet it is important to realize that there can be false iconoclasts as well as false icons and that in their separate ways both can be dangerous. George Bernard Shaw, although not a doctor, was a powerful opponent of vaccination against smallpox, asserting in his well-publicized ignorance that the decline in the incidence of that disease was the result not of vaccination but of improved sanitation. He has now been proved completely wrong, but one of my most painful personal recollections is that of witnessing the death of an intelligent and well-read young soldier from haemorrhagic smallpox in India during the War after he had refused vaccination in the belief that the opinion of a man with the intellect of Shaw was more to be trusted than that of a Regimental Medical Officer. Although that is, of course, a bizarre example of the damage which can stem from a misinformed iconoclastic approach, it epitomizes the grave responsibility which doctors must accept when they publicize views which are diametrically opposed to those of the majority of their colleagues. No such crisis of conscience arises when a doctor, even perhaps quite wrongly, deems dangerous a drug which has been used uncritically for many years, but for which there is an adequate substitute. It is a different matter, however, to condemn a form of treatment which in certain circumstances may be life-saving, but, even if it is not, can do no harm if administered for short periods. The views expressed in Dr Luksza’s two articles, questioning the value of corticosteroids in the treatment of severe acute asthma, come into the second category. In purely scientific terms there is a lot to be said in his support. It has never been proved by a controlled clinical trial that corticosteroids in this condition actually save lives, and

Hazards of bronchoscopy

not found the presence of these tender areas to be ofhelp in predicting the outcome oftranscutaneous electrical nerve stimulation. Some of the patients who responded to the treatment did not have these sensitive areas, while others in whom they were present were not helped. We thank Dr Homer for the chance to explain ourresults further. Transcutaneous electrical nerve stimulation requires a cutaneous sensation for it to work. This means that the construction ofa double blind trial is difficult. For this reason we decided to perform an open trial without a control group for comparison. The data we obtained from the study were discussed with a statistician, who advised that the use of mathematics to show a small p value would not increase the studys validity. Furthermore, as the data at three and six months were incomplete because 14 of the subjects had discontinued treatment (eight because no help, four insufficient benefit to warrant cost, two could not afford machine) the application of the statistical tests suggested by Dr Homer would have necessitated several unwarranted assumptions. We therefore decided that the results should be described in terms of the number of the subjects responding and not responding to the treatment, as has been done by others.3 Dr Homer states that the benefit of transcutaneous electrical nerve stimulation at three and six months may be a placebo response. In our paper we draw attention to this point but suggested that factors responsible for the placebo effect in the irritable bowel rarely last more than two months.4 Our main concem was to draw attention to the use of transcutaneous electrical nerve stimulation as a possible treatment for unexplained abdominal pain, a condition in which new treatments are always desired. We agree that further studies to prove its effectiveness are required. As with all forms of treatment of chronic pain the message with transcutaneous electrical nerve stimulation in functional abdominal pain is to try it and see. Our policy is to lend a machine to the patient for one to two months to see if it is of benefit. Patients who find it to be helpful are usually more than happy to buy a machine for themselves, possibly the best indicator of its benefit. GARRY KENDALL KAREN SYLVESTER J E LENNARD-JONES St Marks Hospital, London EC1V 2PS

Rigid bronchoscopy under intravenous general anaesthesia with oxygen Venturi ventilation.

In a study of 100 patients undergoing rigid bronchoscopy under intravenous general anaesthesia with oxygen Venturi ventilation no major complications were observed. Minor complications included one adverse reaction to alphaxalone-alphadolone acetate (Althesin), one prolonged episode of laryngeal spasm after removal of the bronchoscope, and subsequent muscle pain attributed to suxamethonium in 36 patients. The last complication occurred significantly less frequently (p less than 0 . 025) in those patients who were pretreated with a small dose of a non-depolarising neuromuscular blocking agent. Serial arterial blood gas sampling in 10 patients showed adequate ventilation during bronchoscopy, but carbon dioxide retention developed in nine cases immediately after the bronchoscope was withdrawn. With adequate precautions, however, the procedure is safe and well tolerated, even in patients with severe impairment of respiratory function.

Salbutamol by intermittent positive pressure ventilation in status asthmaticus.

A wet aerosol of 0.5 per cent salbutamol was administered for 3 minutes via a Bennett intermittent positive pressure ventilator driven by compressed air to 8 patients considered to be in status asthmaticus. Arterial blood gas analysis performed before and after salbutamol administration showed marked individual rises and falls in the partial pressure of oxygen with no predictable pattern of response. No dysrhythmia was observed on the E.C.G. but small changes of a non-specific nature occurred in the level of S-T segments and in the height of T-waves. It was concluded that in the dosage employed a salbutamol aerosol administered by I.P.P.V. produced no significant disturbance of myocardial function.

A comparative study of two doses of salbutamol nebulized at 4 and 8 litres per minute in patients with chronic asthma

A comparative study of the clinical response to salbutamol nebulized by an Inspiron Mini-Neb using flow rates of 4 and 8 litres/min is described. Forty patients with chronic asthma were given doses of approximately 1 mg and 5 mg of salbutamol using flow rates of either 4 or 8 litres/min. The two flow rates and the two dosages produced similar increases in FEV1 and FVC and similar changes in pulse rate. These results demonstrate that flow rates of 4 litres/min, such as can be produced by a domestic oxygen cylinder, and doses of 1 mg salbutamol are effective in the treatment of patients with chronic reversible airflow obstruction. While we do not advocate the general use of oxygen cylinders to drive nebulizers, our study shows that this form of administration produces a bronchodilator response similar to that using a flow rate of 8 litres/min.