Sulphasalazine and lung toxicity.

Sulphasalazine prescribing is on the increase. Pulmonary toxicity and blood dyscrasias are rare side-effects. Numerous case reports have been published implicating sulphasalazine in pulmonary toxicity. The authors searched the literature for cases of sulphasalazine induced lung toxicity and the 50 cases identified are discussed here. All published case reports/letters referring to sulphasalazine and lung toxicity were studied. The search terms "sulphasalazine" and "sulfasalazine" were combined with the terms "lung", "pulmonary disease", "pneumonitis" and "pleuritis" using Medline and PubMed databases. Typical presentation of sulphasalazine-induced lung disease was with new onset dyspnoea and infiltrates on chest radiography. Common symptoms were cough and fever. Crepitations on auscultation and peripheral eosinophilia were noted in half of the cases. Sputum production, allergy history, rash, chest pain and weight loss were inconsistent findings. Pulmonary pathology was variable, the commonest being eosinophilic pneumonia with peripheral eosinophilia and interstitial inflammation with or without fibrosis. Fatal reports were infrequent. Most patients were managed by drug withdrawal with 40% prescribed corticosteroids. In conclusion, sulphasalazine lung disease should be distinguished from interstitial lung disease due to underlying primary disease. Despite the increase in sulphasalazine prescribing, pulmonary toxicity remains rare. The majority of patients with suspected sulphasalazine-induced lung disease improved within weeks of drug withdrawal and the need for corticosteroids is debatable.

Occupational asthma due to porcine pancreatic amylase.

A case of occupational asthma in a 41 year old histopathology laboratory technician attributable to a powder preparation of the porcine pancreatic enzyme amylase is reported. The diagnosis was confirmed by a double blind, placebo controlled, inhalation challenge study which showed immediate and late asthmatic reactions associated with a significant increase in airway responsiveness to methacholine.

Wegener's granuloma. A series of 265 British cases seen between 1975 and 1985. A report by a sub-committee of the British Thoracic Society Research Committee.

In order to describe the British experience of Wegener's granulomatosis Hospital Activity Analysis was used to collect cases diagnosed in England, Wales and Scotland between 1975 and 1985. Where possible clinical details, histological material and chest radiographs were obtained. Two hundred and sixty five patients were considered to have Wegener's granulomatosis. In 109 a single pathologist confirmed the diagnosis by finding both granulomas and vasculitis in biopsy material. The diagnosis was made on clinical grounds or clinical grounds together with histological diagnosis in the local hospital in 156 patients. Wegener's granulomatosis was confined to the lung or upper respiratory tract in 22 per cent of patients and renal disease occurred in 58 per cent. Laboratory tests showed a pattern of mild anaemia, polymorph leucocytosis, eosinophilia and an elevated ESR and hypergammaglobulinaemia, with no specific pattern of changes. Histological confirmation was most frequently obtained by examination of nasal biopsy specimens, but multiple biopsies were often required. Renal biopsies showed focal proliferative glomerulonephritis but granulomatous glomerulonephritis was uncommon. Of available chest radiographs 61 per cent were abnormal, large opacities being most common. Small irregular opacities were found less often and other abnormalities were uncommon. Treatment varied widely and 10 per cent of patients received no drug therapy. This large series illustrates that even without specific treatment, patients with Wegener's granulomatosis can survive for several years and with modern treatment survival for more than a decade is possible. Conclusions about the effectiveness of the various therapies cannot be drawn from this retrospective study. Renal failure and disseminated vasculitis were the commonest causes of death; death was considered to result from complications of treatment with cytotoxic drugs or prednisolone in 6 per cent of patients.

A prospective randomized comparison of fine needle aspiration biopsy and fibreoptic bronchoscopy in the investigation of peripheral pulmonary opacities.

Twenty-nine patients, aged 66(+/- 7) years with a peripheral pulmonary opacity (mean diameter 3.6 +/- 1.8 cm) believed to be a tumor, were randomly allocated to initial investigation by either fibreoptic bronchoscopy or percutaneous fine needle aspiration biopsy, the latter performed under fluoroscopic control. The patients proceeded to the alternative investigation in the event of the first failing to achieve a diagnosis. Malignancy was confirmed by the initial procedure in 14/15 patients randomized to fine needle aspiration biopsy but only in 1/14 patients randomized to fibreoptic bronchoscopy (P less than 0.01). Overall, these figures were 25/28 fine needle aspiration biopsy and 2/15 fibreoptic bronchoscopy (P less than 0.01). These results confirm the clinical suspicion that fine needle aspiration biopsy is far more likely than fibreoptic bronchoscopy to establish the presence of malignancy in peripheral pulmonary opacities.

Assessment of variability of exercise tolerance limited by breathlessness.

A sequence of questions was designed to quantify the within subject variation of exercise tolerance limited by breathlessness, to serve as a guide to variation in airflow limitation for epidemiological purposes. The questions seek answers about breathlessness in relation to various levels of attempted activity when the subjects are at their best and at their worst. The difference between exercise tolerance at best and exercise tolerance at worst (variation in exercise tolerance) was expressed on a scale ranging from 0 (no variation) to 6 (greatest variation). The effectiveness of these questions has been assessed in 68 patients with airflow limitation attending a chest clinic, by comparing the results with variation in peak expiratory flow rate (PEF). Variation in PEF was expressed as the standard deviation of the first 24 PEF recordings from each patient (equivalent to four days' recordings). There was a highly significant relation between the measure of variation in exercise tolerance obtained from the questionnaire and PEF variation, though each point on the scale of variation in exercise tolerance covered a wide range of variation in PEF. The questions give some guide to the variation in airflow limitation and in combination with other questions may be helpful in epidemiological studies.

A single dose of sulfametopyrazine versus 7 days of ampicillin in acute on chronic bronchitis.

Forty-two patients with acute on chronic bronchitis received in double-blind fashion either a single dose of 2 g of sulfametopyrazine or ampicillin 250 mg thrice daily for 7 days. There were no significant differences between treatments in the number of patients achieving white sputum, the time to do so, or the incidence of pathogens at the end of treatment. Blood levels of sulfametopyrazine between 8 and 24 hours and on the seventh day were likely to result in sputum concentration adequate to kill Haemophilus influenzae.

A dose response study of oxitropium bromide in chronic bronchitis.

In a dose response study 12 patients with chronic bronchitis and airflow obstruction received inhaled placebo and incremental doses of oxitropium bromide. Significant improvements in peak expiratory flow rate, forced expiratory volume in one second, and forced vital capacity were recorded at all times up to 10 hours after all doses of oxitropium bromide. Oxitropium bromide is an effective bronchodilator in chronic bronchitis with an optimal dose of 400-600 micrograms.

A comparison of oxitropium bromide and ipratropium bromide in asthma.

Oxitropium bromide is a derivative of scopolamine and is an anticholinergic drug. Twenty asthmatics completed the study in which they received, in randomised double-blind fashion, placebo, ipratropium bromide 80 micrograms, and oxitropium bromide 200 micrograms. The patients recorded peak expiratory flow immediately before inhalation and up to 10 h afterwards. PEF were significantly higher than placebo between 10 min and 10 h, for both active treatments. There were no significant differences between values on oxitropium bromide and ipratropium bromide at any time points. Side effects were minimal and oxitropium bromide is an effective bronchodilator in asthma.

Sustained-release theophylline in chronic bronchitis.

Twenty-one patients with chronic bronchitis entered a double-blind, cross-over study in which they received sustained-release theophylline ('Nuelin'SA) 350 mg daily for 4 days followed by 700 mg daily for 4 days and matching placebo tablets for 8 days with one week separation. Seventeen patients completed the study. Three patients receiving higher doses for weight than the mean for the group were withdrawn because of side-effects. Mild side-effects only were reported in six other patients. Theophylline given twice daily produced a steady-state mean serum concentration of 13.9 micrograms/ml, 13 patients having concentrations inthe range of 10-20 micrograms/ml. There was no demonstrable improvement of symptoms but pulmonary function measurements in the clinic at the end of active treatment showed a statistically significant improvement in PEFR, 1-second forced expiratory volume and forced vital capacity.

Effects of long-term inhaled salbutamol therapy on the provocation of asthma by histamine.

Eight patients with asthma in remission were treated for 4 wk with a regular beta 2 stimulant. (salbutamol, 200 microgram) given 4 times/day by aerosol. Histamine provocation tests were performed at the beginning and at the end of the treatment period, and again 2 wk after cessation of treatment. Throughout the 6-wk period, the patients recorded peak expiratory flow (PEF) at home twice daily before and after inhaling 200 microgram of salbutamol. No significant differences were seen in the average PEF values or in the bronchodilator responses. There were no changes in the bronchial sensitivity to histamine during the study, and the protective effect of inhaled salbutamol against histamine provocation was preserved after the period of regular therapy. The results suggested that the regular use of a selective beta2 stimulant by inhalation in conventional therapeutic amounts in patients with asthma is unlikely to produce clinically important tolerance or increased susceptibility to an asthma-provoking stimulus.