Asbestosis. Bronchoalveolar lavage fluid proteins and their relationship to pulmonary epithelial permeability.

We measured levels of albumin and immunoglobulins in serum and bronchoalveolar lavage (BAL) fluid in 28 men with asbestosis and 11 control subjects. The half-time clearance of inhaled diethylene triamine pentacetate labelled with technetium-99m (99mTc-DTPA) from the lungs (t1/2LB) was measured in 26 patients with asbestosis and in 31 normal nonsmoking controls. In those individuals in whom immunoglobulins were detected in BAL fluid, the mean IgG:albumin ratio in BAL fluid was 0.30 (range, 0.11 to 0.97), significantly less than the ratio of 0.43 (0.28 to 0.66) in control subjects (p less than 0.05). There was no significant difference in IgA:albumin ratios between patients and control subjects. The mean BAL:serum albumin ratio in patients with asbestosis was 2.3 X 10(-3) (range, 0.2 to 9.5 X 10(-3), significantly greater than the ratio of 1.2 X 10(-3) (0.5 to 2.0 X 10(-3] in control subjects (p less than 0.02). The t1/2LB was significantly shorter in both smokers and nonsmokers with asbestosis, compared with 31 normal nonsmoking controls, but there were no relationships between t1/2LB and BAL:serum albumin ratio or any other BAL protein levels in either smokers or nonsmokers with asbestosis.

Bronchoalveolar lavage and 99mTc-DTPA clearance as prognostic factors in asbestos workers with and without asbestosis.

The aims of this study are to investigate the change-over time of lung function and chest radiographic findings in patients with asbestosis (AS) and asbestos workers without asbestosis (AW). Secondly, to correlate these changes with broncho-alveolar lavage (BAL) profiles and with lung epithelial permeability, as detected by half-time lung-to-blood (t1/2 LB) clearance of an inhaled aerosol of diethylene triamine pentacetate labelled with technetium 99 (99mTc-DTPA) obtained a mean period of 4.2 yr (range 2.3-5.8) previously. Thirty-three patients with asbestosis and 24 asbestos workers with substantial asbestos exposure were followed-up. Nineteen healthy smokers (HS) with no asbestos exposure who were followed up for a mean period of 3.9 yr were taken as a control group for spirometric changes. Compared with AW, FEV1, FVC and TLCO were lower in AS (P < 0.0001 in each case). Smoker AS and AW had lower numbers (P < 0.03) and percentages (P < 0.004) of BAL lymphocytes and higher numbers (P < 0.04) and percentages (P < 0.02) of BAL neutrophils plus eosinophils than ex- and non-smokers. Annual declines of FEV1 (dFEV1 yr-1) and FVC (dFVC yr-1) in AS and AW were significantly greater than in HS and predicted annual declines (P < 0.002 in each case). Annual declines of TLCO (dTLCO yr-1) and KCO (dKCO yr-1) in AS and AW were significantly greater than predicted annual declines (P < 0.002 in each case). No significant differences were noted between AS and AW in annual declines in any lung function measurement. dTLCO yr-1, dKCO yr-1 were significantly greater in smokers than in ex- and non-smokers, (P < 0.05 and P < 0.04 respectively). Annual decline did not relate to base line values for any lung function measurement. Numbers and proportions of BAL lymphocyte were higher (P < 0.008 and P < 0.02, respectively) and numbers and proportions of BAL neutrophils and eosinophils were lower (P < 0.02 and P < 0.03, respectively) in patients in whom dTLCO yr-1 was less than 0.3 mmol min-1 kPa-1 than in patients in whom dTLCO yr-1 was more than 0.3 mmol min-1 kPa-1. dTLCO yr-1 inversely correlated with t1/2 LB; r = 0.51; (P < 0.008). Patients in whom the radiograph remained unchanged had higher numbers (P < 0.002) and percentages (P < 0.001) of BAL lymphocytes than patients in whom the radiograph deteriorated.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevalence and management of asthma in a London inner city general practice.

A study was set up to examine the prevalence and management of asthma symptoms in a London inner city general practice. All case records were examined and evidence of past or currently active asthma or wheezing illness was identified in 1032 out of 11,148 records (9.3%). This gave a cumulative prevalence of asthma or wheezing illness of 7.2% among adults and 19.5% among children aged 15 years or under. These figures are consistent with previous estimates of prevalence in the UK published since the mid 1960s. In 92.5% of cases in which information was available, the initial diagnosis of asthma or decision to prescribe a bronchodilator was made in primary care. Only nine cases (0.9%) had evidence of recurrent wheezing without the benefit of bronchodilator therapy at any time. There was significant delay in diagnosis in children under five years compared with older children or adults. There was a significant association between a formal diagnosis of 'asthma' in the case notes and the inclination of general practitioners to monitor peak expiratory flow or offer inhaled bronchodilator or corticosteroid therapy. Of 111 asthmatics (83 adults and 28 children aged five to 15 years) with previously 'severe' disease who sought medical advice for their asthma over a 12 month period, 91.6% of adults and 92.9% of children received bronchodilator therapy; nevertheless, only 47.0% of adults and 14.3% of children received inhaled corticosteroids and only 12.0% of adults and 28.0% of children received inhaled cromoglycate. Only 59.0% of adults and 46.4% of children had at least one measurement of peak expiratory flow during the 12 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary epithelial permeability: vascular background effects on whole lung and regional half-time values.

Pulmonary epithelial permeability was first measured by Jones et al. We have adapted their technique for use with a gamma camera. Both regional half-time values and background correction factors vary from apex to base in the lung. Examination of two methods of background correction show: that inter-segmental half-time comparison is possible without applying individual correction factors to regions. the use of a region of interest with similar vascular supply to that of the lung eliminates the need for a background correction technique that relies upon an intravenous injection of radioisotope. The inter-renal area provides such a vascular area.

Comparison of Mantoux, tine, and 'Imotest' tuberculin tests.

In a study designed to compare the Mantoux with the tine and 'Imotest' multiple-puncture tuberculin tests 200 subjects underwent a Mantoux test (10 IU PPD-Weybridge) and, simultaneously, either a tine test or an imotest. All tests were read after 72 h by two observers independently. The false-negative rate for the Mantoux was estimated by immediate repetition of the Mantoux in subjects with an initially negative Mantoux but positive multiple-puncture test. When the criterion for a positive reaction was at least 5 mm of induration for the Mantoux and at least 2 mm of induration for the multiple-puncture tests, the false-negative rate of 27% for the imotest was significantly higher than the 4% for the tine and 5% for the Mantoux (p less than 0.001 in each case). Positive multiple-puncture tests were always associated with a Mantoux test that was positive on either the first or second application. Observers agreed in their interpretation of 98% of all tests, and there were no significant differences between testers in frequency of false-negative results for any test. The tine test, when carefully applied and correctly interpreted, gives results which correlate well with those given by the standard Mantoux test. The imotest is less reliable and has no advantages over the tine test.

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.

Lymphocyte subpopulations in bronchoalveolar lavage fluid in asbestos workers.

We examined peripheral blood and bronchoalveolar lavage (BAL) fluid lymphocyte subpopulations in 29 asbestos workers, 10 with and 19 without clinical or radiologic evidence of asbestosis. Peripheral blood lymphocyte subpopulations were also measured in 13 control subjects. The mean OKT4:OKT8 (T-helper/inducer:T-suppressor/cytotoxic lymphocyte) ratio in BAL fluid in the 29 asbestos workers was 0.96 (range, not detected to 3.33), significantly less than 1.76 (1.33 to 2.67) in peripheral blood (p less than 0.001). There were no significant differences in OKT4:OKT8 ratios in peripheral blood between the 10 patients with asbestosis, the 19 asbestos workers without asbestosis, and the 13 normal control subjects or in the OKT4:OKT8 ratios in BAL fluid between patients with asbestosis and asbestos workers without asbestosis. In the group as a whole, 83% of those who had suffered more than 5 yr of exposure to asbestos showed OKT4:OKT8 ratios less than 1.2, whereas in those who had suffered fewer than 5 yr of exposure, 80% showed ratios greater than 1.2 (p less than 0.02). No other relationships between OKT4:OKT8 ratios and clinical, radiographic, or physiologic variables were observed.

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.

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.

Asbestos fibres in bronchoalveolar lavage fluid from asbestos workers: examination by electron microscopy.

The uncoated and coated fibre load in bronchoalveolar lavage (BAL) fluid was assessed using light microscopy, scanning electron microscopy, and x ray microanalysis in 15 subjects with previous, unprotected exposure to asbestos, including three with clinical and radiological evidence of asbestosis, and in 13 urban dwelling control subjects with no known occupational exposure to asbestos. The mean ferruginous body count per ml BAL fluid in asbestos exposed subjects as determined by light microscopy was 52 (range 0-333). No ferruginous bodies were detected in control subjects. The mean fibre count per ml BAL fluid in asbestos exposed subjects as determined by electron microscopy was 793 (133-3700), significantly greater than 239 (44-544) in controls (p less than 0.05). Electron microscopic counts correlated with duration of previous exposure to asbestos (r = 0.47, p less than 0.05) and with percentage neutrophil counts (r = 0.53, p less than 0.025). There was no relation between electron microscopic fibre counts and light microscopic ferruginous body counts. In 11 asbestos exposed cases x ray microanalysis confirmed the presence of asbestos and in six the asbestos fibre type was clearly identified. Of five subjects showing no asbestos bodies by light microscopy, all showed fibres by electron microscopy, and in three cases the presence of asbestos was confirmed by microanalysis. Among control subjects, fibres were either large organic fibres or smaller particles which microanalysis showed were not asbestos. In only one control case were a few fibres identified which were confirmed as asbestos fibres on microanalysis. Electron microscopic examination of BAL fluid may confirm past exposure to asbestos and probably gives a crude quantitative estimate of asbestos load.

Bronchoalveolar lavage in the diagnosis of diffuse pulmonary shadowing.

Bronchoalveolar lavage (BAL) was performed during fibreoptic bronchoscopy in 79 patients with undiagnosed diffuse radiographic pulmonary shadowing and in 20 control subjects undergoing investigation for respiratory symptoms not associated with diffuse radiographic shadowing. The highest percentages of cells other than macrophages found in BAL fluid from the controls were 11% for lymphocytes and a total of 10% for neutrophils and eosinophils. 72 (91%) of the patients with diffuse shadowing had higher percentages of one or more of these inflammatory cell types than were found in any of the controls. Patients with increased lymphocytes differed in their eventual diagnosis from those without increase lymphocytes but with increases in other inflammatory cells (P less than 0.001). The use of BAL cell profiles as an aid to diagnosis in certain situations is illustrated by calculation of predictive values using Bayes' theorem. BAL has diagnostic value in the investigation of diffuse pulmonary shadowing if the cell profile is considered in conjunction with other information.

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.

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.

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.

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.