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Eight asthmatic patients completed a 12-week, double-blind, placebo controlled study to assess the efficacy of ketotifen, 1 mg twice daily, in the inhibition of bronchoconstriction induced by isocapnic hyperventilation (IH). There was no significant difference in the degree of bronchoconstriction produced by IH after treatment with ketotifen or placebo. [ABSTRACT FROM AUTHOR]

A hospital self-admission service for asthmatic patients was started in December 1968. During a 15-year period, 195 asthmatic patients were responsible for 873 hospital self-admissions. During the last 3 years there were significantly more night admissions and shorter durations of asthma attacks prior to admission than during the first 3 years. Assisted ventilation was necessary on 36 occasions (4%), but one patient was responsible for 28 of these episodes. There were three hospital deaths. One patient died from a tension pneumothorax as mechanical ventilation was being started, and two patients were not actively resuscitated because of irreversible airways obstruction and ischaemic heart disease. There were six deaths outside hospital, one from myocardial infarction, four from asthma; one young female died on a holiday trip. The hospital death rate for patients admitted via this service is 0.34% (0.1% if the two patients who were electively not resuscitated are excluded). This low mortality rate suggests that this self-admission service saves lives. There are no costs and this service gives confidence to patients and general practitioners.

Forty-three previously untreated patients, all of whom had poor-prognosis small cell lung cancer and/or were greater than 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.

A 14-year-old previously fit schoolboy was admitted with staphylococcal pneumonia secondary to influenza A infection. His condition deteriorated as he developed adult respiratory distress syndrome (ARDS); during a stormy recovery exceptionally high doses of benzodiazepines and opiates were given in order to suppress voluntary breathing during a successful period of assisted ventilation. It is possible that benzodiazepine-opiate antagonism developed. Subsequent studies in laboratory mice indicate that the respiratory depressant effects of morphine can be antagonized by prior treatment with lorazepam.

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.

In a series of 65 patients with asthma with pulmonary eosinophilia 54 were adequately investigated for allergic aspergillosis and this was present in 32 (59%). Asthma with pulmonary eosinophilia was found to carry a relatively poor prognosis in terms of permanent symptoms, impairment of pulmonary function and residual radiographic abnormality. The prognosis was least favourable when allergic aspergillosis was associated with long-standing asthma. On the other hand there was a group of patients with asthma with pulmonary eosinophilia who had relatively little permanent disability. These were mainly women with asthma of recent onset, and in these evidence of allergy to Aspergillus fumigatus was less apparent. Those patients who received long-term daily corticosteroid therapy were less likely to develop further radiographic opacities than those given intermittent corticosteroid therapy. To prevent recurrent pulmonary infiltrates it is probably necessary to give prednisolone in a daily dosage of at least 10 mg for an indefinite period.

Peripheral blood mononuclear cells from asthmatic patients were cultured in soft agar with or without the synthetic glucocorticoid methylprednisolone (MP). The resulting colonies consisted mostly of T lymphocytes but included monocytes, often in a central position. Colony growth from patients whose asthma had responded satisfactorily to glucocorticoid medication was inhibited by MP in vitro at concentrations as low as 10(-9) M, and the ratio of helper to suppressor/cytotoxic T cells was reduced relative to untreated cultures. In contrast, patients shown to be resistant to the therapeutic effects of glucocorticoids yield colonies which differed little in number, size or constituent phenotype, whether untreated or exposed to MP at concentrations as high as 10(-8) M. Higher concentrations inhibited colony growth from both types of patient. Hybrid colonies were generated from partially purified cells from pairs of patients: monocytes from one member and lymphocytes from the other. The steroid sensitivity of these colonies was found to be dependent upon the source of the monocytes and not the lymphocytes. The results support the view that, in glucocorticoid resistant asthma, there is a defect in monocyte responsiveness to the hormone. This defect could explain the poor therapeutic effect of glucocorticoids in these patients. The results suggest that monocyte factors may be of importance in the pathogenesis of asthma in general.

During the 10 year period 1972-81, 39 patients with neurological disorders referred to a respiratory unit required artificial ventilation, seven on two occasions. The decision to undertake ventilation was usually made on clinical grounds because of deteriorating respiratory effort, ineffective cough, or inability to swallow. Arterial blood gas studies were of limited value in assessing the need for ventilation. The most frequent complication was bronchopulmonary infection which occurred in almost every patient, Staphylococcus pyogenes, Pseudomonas pyocyanea, and coliforms being the organisms most commonly isolated. In contrast, serious complications of tracheostomy and pulmonary thromboembolism occurred infrequently. There were 10 deaths among the 39 patients ventilated on 46 occasions; six were directly attributable to the neurological disease itself but four resulted from complications of artificial ventilation.

Between 1971 and 1978, 140 cases of small cell anaplastic carcinoma of the bronchus were registered by a group of chest physicians in north Edinburgh. Sixty-five of these patients received specific treatment either with radiotherapy or cyclophosphamide and 75 patients were given treatment for symptoms only. Between 1979 and 1981 83 patients referred to the same physicians and pathologists were treated with combination chemotherapy (methotrexate, cyclophosphamide and CCNU) for 12 weeks. Overall median survival in the 1971 to 1978 group was two months with the actively-treated patients surviving for five months vs. less than one month for treatment of symptoms only. For the 83 patients treated with combination chemotherapy, median survival was nine months with 33 per cent alive at one year and 13 per cent at two years. Positive factors associated with prolonged survival included performance status at presentation and response to chemotherapy. This study demonstrates that the prognosis for the majority of patients with small cell carcinoma of the bronchus has improved significantly with the introduction of combination chemotherapy.

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.

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.

Thirty two patients with severe acute asthma, all of whom were hypoxaemic, entered a double blind comparative assessment of three doses of salbutamol (1.25, 2.5, and 5 mg) nebulised by an electrically operated air compressor. The study lasted for two hours, during which oxygen and corticosteroid treatment were withheld. All patients were observed in an intensive care area during this period. Four patients had to be withdrawn from the study. Two became distressed immediately after receiving salbutamol and were excluded from further analysis. Two other patients were withdrawn, one with persistent respiratory distress and an unchanged one second forced expiratory volume (FEV1) and the other because of the development of profound hypoxaemia and a deteriorating FEV1 within 60 minutes of treatment. No significant differences were observed between the three dosage groups. In the 28 patients completing the study there were only small increases in mean FEV1 (0.8 to 1.1 l) and forced vital capacity (FVC) (1.3 to 1.8 l) over the two hours. There was a fall in the mean pulse rate at 120 minutes of 15 beats per minute (117-102). No significant change in oxygen tension (PaO2) was observed at 15 or 60 minutes after administration of nebulised salbutamol in any of the three groups. Salbutamol nebulised in air, in a single dose of 5 mg, produces only slight relief of airflow obstruction and no worsening of hypoxaemia in severe acute asthma.

In a double-blind trial the effects on ventilatory function (FEV1), heart rate and blood pressure of oral pirbuterol and oral salbutamol in various single doses were studied in ten patients with chronic asthma. Pirbuterol (15 mg) and salbutamol (4 mg) produced equal peak levels of bronchodilatation. There was no significant difference in the mean rise in heart rates caused by the two drugs, and no other significant side-effects were noted.

In 78 patients with chronic asthma the increase in forced expiratory volume in one second (FEV-1) after the administration by intermittent positive-pressure ventilation (I.P.P.V.) of 10 mg of salbutamol was compared with that recorded after the inhalation of a conventional dose (200 mug) from a pressurized canister. The mean increase was significantly greater after I.P.P.V. administration, and the superiority of this method was greatest in patients with the lowest pretreatment FEV-1.

Severe reactions to oily propyliodone are rare. Side-effects are usually mild and self-limiting. Three cases are reported of early pulmonary reactions, the cause of which may be a chemical pneumonitis or possibly an allergic response to one of the components of the contrast medium. There was a good response to corticosteroid therapy in all three patients.

In a survey of 400 consecutive patients with chronic asthma treated with beclomethasone dipropionate aerosol (up to 400 mug/day) the prevalence of oropharyngeal thrush was 4-5%. The prevalence of this complication was not significantly related to sex, age, duration of treatment with beclomethasone or concurrent treatment with prednisolone. Yeasts were isolated from throat swabs in about 60% of all patients and in 48% of normal controls. Thus, although a diagnosis of oropharyngeal thrush was recorded only when the presence of characteristic lesions in the pharynx was associated with a positive culture, there was a large number of patients and controls without thrush who harboured yeasts in the throat. One in 3 patients with thrush complained of sore throat or hoarseness, but 1 in 4 patients without thrush had similar symptoms. These findings suggest that, although treatment with beclomethasone dipoprionate aerosol undoubtedly can cause oropharyngeal thrush, this condition is not an inevitable result of colonization of the oropharynx by yeasts, nor is it necessarily associated with symptoms.

Three patients with chronic asthma developed pulmonary eosinophilia while oral prednisolone was being withdrawn after the introduction of treatment with beclomethasone dipropionate aerosol. These observations suggest that the development of pulmonary eosinophilia in patients with chronic asthma can be prevented by the systemic administration of corticosteroids, but not by a corticosteroid aerosol given by inhalation. It is considered that radiological examination of the chest should be carried out at frequent intervals during and for a few months after the substitution of corticosteroid aerosol therapy for oral corticosteroid therapy in order to ensure that those patients who are liable to develop pulmonary eosinophilia will be identified at an early stage. These precautions are even more essential when there is a previous history of pulmonary eosinophilia.

The hospital medical records of a patient with chronic lung disease and intractable social problems have been analysed. Multiple admissions resulted in the patient spending nearly three years out of seven and a quarter years in Edinburgh hospitals and in the performance of repeated and ofter unnecessary medical investigations. Such patients are a source of considerable uneconomic expense to the National Health Service, but at present it is difficult to see how their medical and social demands can be met in any other way.

A pilot study had suggested that bromocriptine (a dopamine agonist) might be of benefit in severe asthma, particularly in patients with marked diurnal variation in peak flow. Two studies are reported: (1) a longterm double-blind, controlled trial comparing bromocriptine (B) with placebo (P) in patients with severe asthma and, (2) a withdrawal study in patients who had received known bromocriptine, with apparent benefit, for at least one year. Of 27 patients (16B, 11P) admitted to the double-blind trial only eight (4B, 4P) completed 52 weeks on the trial drug as nine (6B, 3P) had been withdrawn for side-effects, eight (4B, 4P) for failure and two (2B) for both reasons. The results, based on changes in steroid dosage and other medication, daily symptom scores and PEF values, suggest that bromocriptine has little effect in asthma. In addition side-effects were frequent and troublesome. In the withdrawal study, ten patients who had been taking bromocriptine for a year or more were switched to an indistinguishable placebo if their asthma was considered to be stable. The results, of this second study, support the conclusion of the double-blind study, that bromocriptine has little beneficial effect in asthma.

This survey of acute asthma admissions points to a number of factors that may be relevant to the continuing asthma mortality at home and in hospital. 1. Complications in hospital occur with increasing frequency with increasing pulse rate, but mortality is low with intensive management. 2 Young patients tend to have the higher pulse rates and greater risk of complications. 3. Many patients with severe asthma do not receive adequate drug treatment, particularly corticosteroids, from their general practitioners before admission to hospital. 4. Many severe attacks of asthma come on quickly and these patients are particularly at risk.

Monocyte complement receptors (MCR) and enhancement of MCR by a monocyte chemotactic factor (casein) (CRE) were measured in corticosteroid-resistant and corticosteroid-responsive chronic asthmatics. In newly-diagnosed patients who subsequently responded to corticosteroids, the percentage of MCR and CRE was lower after taking oral prednisolone for 7 days and returned to pretreatment values when prednisolone was withdrawn. MCR and CRE in corticosteroid-responsive asthmatics receiving prednisolone were significantly lower than in corticosteroid-resistant asthmatics taking prednisolone. However, there was no significant difference in MCR and CRE between non-responders taking prednisolone and non-responders receiving other forms of therapy. These results suggest that one of the effects of systemic corticosteroids in asthmatics who respond to this form of treatment is a decrease in both MCR and the degree of CRE. Since these changes were not found in corticosteroid-resistant chronic asthmatics such patients may have a defect in the expression and mobilization of complement receptors on the monocyte cell membrane.