A.R. Gellert

Effects of dihydrocodeine, alcohol, and caffeine on breathlessness and exercise tolerance in patients with chronic obstructive lung disease and normal blood gases.

We measured breathlessness and exercise tolerance in 12 patients with chronic airways obstruction, moderate or severe breathlessness, and low or normal arterial carbon dioxide tension, after the patients received dihydrocodeine, alcohol, caffeine, or placebo (through double-blind administration). Forty-five minutes after ingestion, dihydrocodeine had reduced breathlessness by 20 per cent and increased exercise tolerance by 18 per cent, with a reduction in ventilation and oxygen consumption at submaximal work loads but with no change in spirometric volumes. Oxygen also reduced breathlessness and provided additional benefit to that achieved with dihydrocodeine (at three hours after ingestion) when the two were given together: the reduction of breathlessness was 18 per cent with dihydrocodeine; 22 per cent with oxygen; and 32 per cent with dihydrocodeine plus oxygen. Alcohol increased forced vital capacity by 9 per cent, and exercise tolerance by 7 per cent. Caffeine had no deleterious effect on breathlessness or exercise tolerance, despite increasing ventilation during rest and exercise. We conclude that opiates may be valuable for the treatment of breathlessness in selected patients; further evaluation is needed, particularly of the long-term benefits and safety.

Fibreoptic bronchoscopy: effect of multiple bronchial biopsies on diagnostic yield in bronchial carcinoma.

The findings in bronchial biopsy specimens obtained at fibreoptic bronchoscopy in 271 patients with bronchial carcinoma were reviewed. Fifty-nine per cent of 703 specimens taken from the site of bronchoscopically visible tumours in 215 patients provided evidence of carcinoma. Unequivocal histological evidence of carcinoma was obtained in 78.6% of the 215 patients with visible tumours. When only one biopsy specimen was taken evidence of carcinoma was obtained in 65.2% of cases. At least five biopsy specimens were required to provide a greater than 90% probability of obtaining at least one positive sample. The anatomical site of the tumour had no significant effect on the proportion of biopsy specimens that were positive or the frequency of obtaining at least one positive sample. When extrinsic bronchial compression was the only visible abnormality evidence of carcinoma was obtained by bronchial biopsy in 26.8% of 56 cases.

Asbestosis: assessment by bronchoalveolar lavage and measurement of pulmonary epithelial permeability.

Thirty two patients with asbestosis were assessed by means of bronchoalveolar lavage (27 patients) and the half time clearance from lungs to blood (T1/2LB) of an inhaled aerosol of diethylenetriamine pentacetate (DTPA) labelled with technetium 99m (32 patients). T1/2LB was also measured in 20 non-smoking normal individuals and 17 smokers without a history of exposure to asbestos. Thirteen patients (46%) showed an increase in the percentage of neutrophils with or without an increase in the percentage of eosinophils and eight (29%) showed an increased percentage of lymphocytes. The number of neutrophils plus eosinophils expressed as a percentage of the total count was positively correlated with the length of the history of disease (r = 0.53, p less than 0.025) and greater percentages were associated with more severe impairment of lung function. Smokers had lower percentages of lymphocytes than non-smokers (p less than 0.002) and showed increased proportions of neutrophils and eosinophils more often than non-smokers (p less than 0.05). In 18 non-smokers with asbestosis the mean T1/2LB was 33.8 (range 10.0-62.0) minutes, significantly less than 57.2 (30.5-109) minutes in 20 non-smoking normal subjects (p less than 0.002). In non-smokers shorter T1/2LB correlated with a longer time since first exposure to asbestos (r = -0.65, p less than 0.005), longer duration of exposure (r = -0.70, p less than 0.001), and a shorter time since last exposure (r = 0.59, p less than 0.01). Shorter T1/2LB was also associated with increased inflammatory activity as shown by higher bronchoalveolar lavage cell counts (r = -0.53, p less than 0.025) and higher combined percentages of neutrophils, eosinophils, and lymphocytes (r = -0.47, p less than 0.05). The techniques of bronchoalveolar lavage and measurement of inhaled solute clearance may be useful in assessing inflammatory activity in asbestosis.

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.

Bronchoscopic and percutaneous aspiration biopsy in the diagnosis of bronchial carcinoma cell type.

The cell type of bronchial carcinoma predicted from the results of bronchial biopsy at fibreoptic or rigid bronchoscopy or of percutaneous aspiration lung biopsy was compared with the type determined by histological examination of specimens obtained by thoracotomy, biopsy of an extrapulmonary metastasis, or necropsy in 180 cases. The rates of agreement with the final diagnosis were 95.7% for bronchial biopsy through the fibreoptic bronchoscope and 86.5% through the rigid bronchoscope. For percutaneous biopsy, which was usually carried out on tumours inaccessible to the bronchoscope, the rate of agreement was 61%, significantly lower than by the other methods (p less than 0.001). The diagnosis of oat-cell carcinoma by any technique was very reliable. Bronchial biopsy was more reliable than was percutaneous biopsy in diagnosing squamous-cell carcinoma. With any technique the commonest error was the incorrect diagnosis of squamous-cell carcinoma or adenocarcinoma as large-cell undifferentiated carcinoma.

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.

Regional distribution of pulmonary epithelial permeability in normal subjects and patients with asbestosis.

The overall and regional clearance of an inhaled isotope labelled solute from the lungs was examined on the basis of a 15 minute period of data collection, for which a technique was developed that does not require intravenous injection to correct for blood-tissue background activity. The technique was applied to 52 normal subjects (31 non-smokers and 21 smokers) and to 37 patients with asbestosis (21 non-smokers and 16 smokers). In normal smokers solute clearance was faster in the upper and middle zones, with a mean ratio of T1/2 LB (half time solute clearance from lungs to blood) in the upper two thirds to the lower one third of the lungs of 0.66 (0.28-1.33), compared with 1.24 (0.43-2.77) in normal non-smokers (p less than 0.002). In patients with asbestosis solute clearance was accelerated throughout the lungs even though radiographic abnormalities were limited to lower or lower to middle zones. Regional distribution of clearance was not affected by posture in normal subjects. Overall solute clearance was significantly faster in normal current smokers and in patients with asbestosis than in normal non-smokers (p less than 0.001 respectively). Among patients with asbestosis, smokers had faster overall clearance than non-smokers (p less than 0.01). Among normal non-smokers T1/2 LB was not significantly different between those who had never smoked and ex-smokers. Regional abnormalities in pulmonary epithelial permeability may offer insight into the pathogenesis of interstitial lung diseases and smoking related disorders.

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

CLEARANCE OF 99m-TECHNETIUM- LABELLED DTPA IN ASBESTOS-EXPOSED SUBJECTS WITHOUT CLINICAL OR RADIOLOGICAL EVIDENCE OF INTERSTITIAL LUNG DISEASE

The half-time clearance of an inhaled aerosol of 99m-technetium-labelled diethylene triamine pentacetate from lung to blood (T1/2LB) was measured using a gamma camera in 20 non-smoking subjects (mean age 54, range 40-69 years) with previous occupational asbestos exposure, but no clinical or radiological evidence of asbestosis, and 20 non-smoking normal subjects (mean age 54, range 40-62). Mean T1/2LB was 44.7 minutes (range 12-102) in exposed subjects, significantly less than 57.2 minutes (range 30.5-109) in normal subjects (P less than 0.05). There was no correlation between age and T1/2LB in either group. In exposed subjects T1/2LB showed a weak rank correlation with the membrane component of DLco (Dm) (r = 0.40, P less than 0.05) but no significant correlation with FVC, TLC, DLco, Kco, resting Pao2 or change in Pao2 on exercise. In six exposed subjects T1/2LB was shorter than in any of the normal subjects. These six did not differ from the other 14 exposed subjects in any physiological variables. T1/2LB is abnormal in some asbestos-exposed subjects without clinical, radiological or physiological evidence of asbestosis. Follow-up will show whether it is an early indicator of development of interstitial lung disease.

Pleural mesothelioma: Diagnosis by trephine biopsy

Abstract Fourteen patients submitted to trephine biopsy of the pleura at the London Chest Hospital for suspected mesothelioma were reviewed. A diagnosis was made in twelve patients including nine with mesothelioma. In seven of these patients other percutaneous aspiration techniques had been unsuccessful. No complications were encountered, and no instance of needle track spread was recorded.