1 In six patients with chronic bronchitis, serial changes in both ventilatory function and plasma theophylline concentrations were measured simultaneously for 8 h following 500 mg aminophylline intravenously. 2 Using empirical mathematical models which can integrate this data, parameters were estimated which can express response as a linear function of steady state plasma theophylline levels. 3 Taking Forced Vital Capacity (FVC) as the target response, the mean (+/‐ s.d.) increase in FVC was 0.06 +/‐ 0.02 l/micrograms ml‐ 1, starting with pretreatment values in the range 1‐21. 4 This analytical approach could be used to determine whether or not a patient with chronic bronchitis could obtain a satisfactory response to theophylline at plasma levels normally encountered in clinical practice.

1 The effect of inhaled salbutamol following a maximally effective dose of theophylline given by intravenous infusion was determined in 12 patients with chronic bronchitis. 2 An initial single intravenous dose study was performed to estimate each patient's theophylline kinetics and to identify those patients who would respond to theophylline. 3 Pulmonary function was assessed at hourly intervals during four to five incremental steady state theophylline infusions over the concentration range 5‐25 mg/l. 4 Inhaled salbutamol (400 micrograms) was administered after the maximum effect from theophylline had been achieved or when theophylline concentrations reached 25 mg/l without maximum effect: pulmonary function was again assessed. 5 Ten patients achieved a further significant improvement in pulmonary function after salbutamol: in five, predicted values for FVC were exceeded. 6 Patients with chronic bronchitis may benefit from the combination of theophylline and salbutamol if steady state theophylline concentrations of 15‐20 mg/l are achieved.

Acquired immunodeficiency syndrome [Editorial]. Lancet 1983;i: 162-4. 2 Levy JA, Ziegler JL. Acquired immunodeficiency syndrome is an opportunistic infection and Kaposi's sarcoma results from secondary immune stimulation. Lancet 1983;ii:78-81. 3 Anonymous. Update on acquired immunodeficiency syndrome (AIDS)

This paper reports a study of the bronchodilator effects of doses of the beta 2 agonist fenoterol and the muscarinic blocker ipratropium suitable for administering in combination as a standard dose of two discharges from a single metered-dose pressurised aerosol. In 12 middle-aged bronchitics who had already been shown to respond to both types of drug the combination was almost always a little (6% on average) more effective than either drug singly. It is possible that an equal or better effect could have been obtained if fenoterol or perhaps ipratropium had been given alone in an individually determined maximally effective dose.

We have previously shown that inhaled salbutamol further increases the bronchodilator response after the maximum effect of theophylline has been obtained in patients with severe chronic bronchitis. We now report the results of adding maximally effective doses of theophylline to the maximum response obtainable from salbutamol in ten of these patients. We constructed dose response curves to ensure maximum possible effect from salbutamol. Response plateaus (in nine out of ten patients) were achieved with cumulative doses of between 200 micrograms and 3,000 micrograms salbutamol and there was a significant response (p less than 0.05) in every subject: the mean FVC response was 1.11 (ranging from 0.5 to 1.81) and the mean FEV1 response was 0.41 (ranging from 0.1 to 0.81). Theophylline, in their previously determined maximally effective doses, produced statistically significant (p less than 0.05) small further increases in both FVC (0.2 to 0.61) and FEV (0.1 to 0.61) in four patients only. The other six did not respond. In patients classified as chronic bronchitics there is clearly a wide variation in response to bronchodilators and a surprising degree of reversibility can be achieved. But because of this variation in response, conventional drug doses may be too small in some cases. Ideally, each bronchodilator should be prescribed after some form of individual dose response studies. Although this acute study shows little or no benefit in the height of the bronchodilator response the usefulness of this combination can only really be decided after similar studies including the duration of effect in long term administration.

3~measurements of lung function include the larynx as an in-series resistance to airflow it is important to know how the width of glottic chink varies in patients with lung disease. Patients undergoing fibre-optic bronchoscopy were studied; in each, lung function has been assessed by spirometry. From photographs of the vocal cords taken on inspiration and expiration via bronchoscopy, width of the glottic chink was assessed.Photographs were projected over a standard distance on to 1 mm-square graph paper and an area between the cords was obtained by counting squares. Area was divided by the anterwposterior diameter, a relatively invariant measurement, which provided a reference measurement, enabling correction for variations in photographic size due to differences in position of the bronchoscope and giving a measurement of width. A breathing trace obtained with a magnetometer and pneumotachograph was marked automatically for each photograph. Repeated photographs were taken during tidal breathing, panting and during a full exhalation.

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Forty-five patients with advanced non-small cell lung cancer (NSCLC), with progressive inoperable tumors were treated. Twenty-three patients were of "limited" stage. Six patients had received previous thoracic radiotherapy. Patients with central nervous system (CNS) metastases, Karnofsky scores of less than 30 or more than 70, and patients over 70 years of age were excluded from the study. Cyclophosphamide (2.5 g/m2) was infused intravenously over 3 hours with the same Mesna dose. At the midpoint of the infusion, 3.5 g/m2 infosfamide was delivered as a bolus. Additional Mesna was administered over the next 8 hours. A maximum of four courses were given at three weekly intervals. One-hundred-thirty-eight courses were administered and 53% of patients completed all four treatments. The response rate was 38%, with three (7%) complete responses. Seven additional patients (15%) with stable disease symptomatically improved by two steps or more on the Karnofsky scale at the end of treatment. Median survival for all 45 patients was 7 months, range less than 1 to 25 months. Sixteen courses were complicated by Grade 3 thrombocytopaenia and/or leukopenia (Grade 4 on six occasions, Grade 3 on seven occasions) on the blood count taken immediately before chemotherapy. Intravenous antibiotics were required on 14% of the total number of courses; and three patients died of probable treatment related causes. Two episodes of severe ifosfamide encephalopathy occurred but recovery was complete, and four episodes of frank hematuria also occurred. The Karnofsky score was more than 70 in 33% of patients one month after the end of chemotherapy compared with 0% before treatment. Unlike many chemotherapeutic regimens for NSCLC, double alkylating agent treatment with ifosfamide and cyclophosphamide improved the performance status without major toxicity in a selected patient population. The overall survival, however, remains short and further alkylating agent combinations need to be considered in the future.