Robin M. Rudd

Is lung cancer associated with asbestos exposure when there are no small opacities on the chest radiograph

This study was designed to test the hypothesis that the risk of lung cancer from asbestos exposure is confined to persons with radiographic evidence of pulmonary fibrosis. Occupational and smoking histories were obtained from 271 patients with a confirmed diagnosis of primary lung cancer and 678 referents (279 with other respiratory disease and 399 with cardiac disease). Histories were reviewed blind to assess the timing, duration, and probability of exposure to asbestos. To allow for a lag between asbestos exposure and the development of lung cancer, subjects were classified by the time they had spent in an occupation entailing definite or probable exposure more than 15 years before diagnosis. The presence and extent of fibrosis was assessed blindly from chest radiographs by three readers and scored for small opacities with the ILO 1989 International Classification of Radiographs of the Pneumoconioses. 93 (34.3%) cases had worked in an occupation with definite or probable asbestos exposure compared with 176 (25.8%) referents (crude odds ratio for lung cancer 1.49, 95% CI 1.09-2.04). After adjustment for age, sex, smoking history, and area of referral, the odds ratio (95% CI) was 2.03 (1.00-4.13) in the subgroup of 211 with a median ILO score for small parenchymal opacities of 1/0 or more, and 1.56 (1.02-2.39) in the 738 with a score of 0/1 or less (ie, those without radiological evidence of pulmonary fibrosis). These results suggest that asbestos is associated with lung cancer even in the absence of radiologically apparent pulmonary fibrosis.

Covered expandable metal stent for recurrent tracheal obstruction

Rapidly recurrent symptoms of airways obstruction by tumour may require repeated radiotherapy or endoscopic laser treatment--but these procedures may themselves be distressing. Use of a novel coated metal stent may reduce the frequency with which such palliative intervention is required.

Reduced pulmonary microvascular permeability in severe chronic left heart failure

Pulmonary edema is a serious complication of heart failure, but often patients with chronic heart failure resist pulmonary edema despite elevated pulmonary venous pressures. This protection might be a result of decreased pulmonary microvascular permeability. Double-isotope scintigraphy with 113mindium-labeled transferrin and 99mtechnetium-labeled erythrocytes allows noninvasive estimation of pulmonary microvascular permeability; an index of transferrin accumulation is calculated that reflects microvascular permeability. Fourteen patients with severe chronic left ventricular dysfunction were compared with a control group of 15 patients with mild coronary artery disease. In the control group the transferrin accumulation index was 0.35 (range -0.3 to 1.0) x 10(-3)/min, and in patients with heart failure the index was 0.0 (range -1.0 to 0.7) x 10(-3)/min, which was significantly lower (p less than 0.01). The reduction in the transferrin accumulation index correlated weakly with the duration of heart failure (R = -0.5, p less than 0.02). These data indicate reduced protein efflux consistent with a decrease in pulmonary microvascular permeability in patients with severe chronic heart failure. Similar changes have been observed in severe mitral stenosis and may reflect a generalized adaptation to chronic pulmonary venous hypertension.

Inhibition of exercise-induced asthma by an orally absorbed mast cell stabilizer (M & B 22,948)

M&B 22,948 (2-o-propoxyphenyl-8-azapurin-6-one) is an orally absorbed mast cell stabilizer which is 30 times as potent as disodium cromoglycate in laboratory and animal studies. In a double-blind placebo-controlled cross-over trial we studied the protection afforded by a single oral dose of 10 mg of M&B 22,948 against asthma induced by histamine and exercise, each in 12 patients. Compared with placebo the drug had no significant effect on the response to inhaled histamine but significantly inhibited the fall in FEV1 induced by exercise on treadmill (P less than 0.005). The exercise-induced fall in FEV1 was less following M&B 22,948 than placebo in all patients and the fall was inhibited by more than 50% in five (42%) of 12 patients. The degree of inhibition was significantly correlated with the plasma drug concentration (r = 0.65, P less than 0.025). M&B 22,948 merits evaluation in the treatment of asthma.

Phase II study of Edatrexate in stage III and IV non-small-cell lung cancer

SummaryA total of 49 patients with advanced, previously untreated non-small-cell lung cancer (NSCLC) were treated with a new antifolate, Edatrexate (10-ethyl-10-deaza-aminopterin; 10-EdAM). Patients received 80 mg/m2 weekly for 12 weeks, and responders received a further 6 cycles at 2-week intervals. Dose reductions were carried out for haematological toxicity and mucositis. Response was assessed prior to each treatment according to WHO criteria. Among the 45 evaluable patients, 6 [13.3%; 95% confidence interval (CI), 6%–26%] achieved a partial response (PR) and 9 (20%; 95% CI, 11%–34%) showed a minor response (MR; 25%–50% reductions in the sum of 2 perpendicular tumour diameters). In those receiving four or more cycles of treatment, the PR and MR rates were 17.6% and 26.4%, respectively. The resultant toxicity mainly constituted skin rash, mucositis and myelosuppression. Edatrexate is active against NSCLC and produces toxicity profile similar to that of methotrexate.

Mitomycin, ifosfamide and cisplatin in non-small-cell lung cancer

SummaryChemotherapy with mitomycin C, ifosfamide and cisplatin (MIC) is reported to produce responses of 56% and 69% in inoperable non-small-cell lung cancer (NSCLC) [1,2]. We evaluated the regimen in 45 similar patients who received up to six courses of 6 mg/m2 mitomycin C, 3 g/m2 ifosfamide, and 50 mg/m2 cisplatin every 3 weeks. In all, 18 patients had limited disease (LD) and 27 had extensive disease (ED). A total of 18 patients responded (40%), 9/18 with LD and 9/27 with ED; there were 4 complete responders. The median duration of response was 25 weeks, and median survival was 32 weeks (range, 2–96 weeks). Toxicity was moderate. Nausea and vomiting were controlled with i.v. dexamethasone and high-dose metoclopramide. Other toxicities included myelosuppression and alopecia. This study confirms that MIC is one of the most active regimens for treatment of NSCLC, with acceptable toxicity.

Changes in pulmonary microvascular permeability accompanying re-expansion oedema: evidence from dual isotope scintigraphy.

The pathophysiological mechanism of pulmonary oedema following rapid re-expansion of a collapsed lung is poorly understood. It has been suggested that the period of collapse or subsequent reinflation produces an increase in pulmonary microvascular permeability. To investigate this, the pulmonary accumulation of the plasma protein transferrin was measured by radiolabelling it in vivo with indium-113m. Plasma protein accumulation was calculated after correcting the accumulation of transferrin for changes in intrathoracic blood distribution by simultaneously monitoring technetium-99m labelled red blood cells. Functional images of plasma protein accumulation were constructed for the lung fields on a pixel by pixel basis. Investigations were performed on 14 subjects after drainage of a pleural effusion (n = 9) or evacuation of a pneumothorax (n = 5), and on 11 control subjects. Plasma protein accumulation was greater over the regions of lung re-expansion (-0.1-9.6, mean 2.9 x 10(-3)/min) than over the corresponding region of the contralateral lung (-1.2-0.8, mean 0.01 x 10(-3)/min; p less than 0.001). Patients who had undergone re-expansion procedures also had significantly greater plasma protein accumulation than normal controls. Nine of the 14 patients in the re-expansion group had clearly identifiable areas of increased plasma protein accumulation that corresponded to the part of the lung that had been re-expanded; no regional abnormalities were recorded in the control group. These results suggest that the reinflated lung displays abnormal microvascular permeability.

Bronchoalveolar lavage and clearance of 99m-Tc-DTPA in asbestos workers without evidence of asbestosis.

We performed BAL and measured the clearance of 99m-Tc-DTPA in 20 non-smoking subjects (mean age 50, range 36-68 years) occupationally exposed to asbestos (mean duration 14, range 3-30 years). All had normal lung function and none had clinical or radiological evidence of asbestosis. The mean BAL results were: total cells per ml 737 X 10(3) (360-1210), percentage macrophages 79 (49-96), percentage lymphocytes 13 (1-42), percentage neutrophils 8 (1-40), percentage eosinophils 0 (0-3), asbestos bodies per ml 83 (0-550). Eight subjects showed increased percentage of lymphocytes and four others showed increased percentages of neutrophils when compared with normal ranges in our laboratory. Higher percentages of neutrophils correlated with longer duration of exposure to asbestos (r = 0.54, P less than 0.025), and shorter time since last exposure to asbestos (r = -0.54, P less than 0.025). Four subjects showed faster clearance of 99m-Tc-DTPA than was observed in 31 normal non-smoking control subjects. There was a tendency for faster solute clearance to be associated with greater numbers of BAL macrophages (r = -0.39, P less than 0.10) but there were no significant relationships between solute clearance and other BAL variables. BAL profiles in asbestos workers may be abnormal in the absence of clinical or radiological evidence of asbestosis.

The effects of theophylline and salbutamol on right and left ventricular function in chronic bronchitis and emphysema

We have compared the effects of oral theophylline and salbutamol on right and left ventricular function in twelve patients with chronic bronchitis and emphysema. Right and left ventricular ejection fraction (RVEF and LVEF) were measured using multiple gated radionuclide ventriculography. Theophylline 600 mg and salbutamol 4 mg both produced increases in RVEF and LVEF. There were no significant changes in blood gases after either drug. The clinical significance of the effects of oral bronchodilators on cardiac function in patients with chronic bronchitis and emphysema has yet to be determined.

Fibreoptic bronchoscopy: Effect of experience of operator on diagnostic yield of bronchial biopsy in bronchial carcinoma

Abstract The results of biopsies of tumour seen during 144 fibreoptic bronchoscopies, performed by five operators, were reviewed to investigate the effect of experience with the procedure on diagnostic yield. 60.4% of a total of 490 biopsies showed carcinoma. At least one positive biopsy was obtained in 77.1% of cases. The modal number of biopsies taken per case by each operator was three. The diagnostic yield increased with the previous bronchoscopic experience of the operator ( P