Emphysema: past, present and future.
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Biomedical subjects
Publications and source records attributed to J Bignon.
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A study of the interaction of phospholipid model membranes and red blood cell membranes with UICC A chrysotile fibres using chemical analysis and photoelectron spectrometry showed that the interaction agreed with an adsorption of the membranes on to the chrysotile fibres. The photoelectron spectrometry analysis allowed the statement that phospholipid model membranes are adsorbed as bilayer. Chemical analysis showed that for each milligram of chrysotile the amount of phospholipids adsorbed was about 155 microgram and the available surface for phospholipids was about 38 m/g. It was established that entire membranes were adsorbed. A mechanism for the haemolytic capacity of chrysotile is suggested.
The authors review the different cellular types found in the airways, the alveoli and the pleura. They describe in detail the structure and the function of the bronchial mucociliary system and the immunological defense system of the airways. Also discussed, on an alveolar level, are the mechanisms of defense and filtering vis-à-vis air transported pollutants and the role of protease-antiprotease balance in the integrity of interstitial connective tissue.
Serum macromolecules such as albumin or type G immunoglobulins are found in the film lining the alveolus, by virtue of techniques of broncho-alveolar lavage as well as demonstration by immunocytochemistry. Passage of such molecules may be studied experimentally by the use of tracers. Two barriers are found: a first at the level of the vascular endothelium which is relatively permeable and a second which is relatively impermeable at the site of the alveolar epithelium. Rupture of this barrier during non-hemodynamic oedema is responsible for massive passage of serum proteins to the alveolus, in particular of fibrinogen.
Exposure to airborn fibres is an important health problem in man. Asbestos fibres (chrysotile, amphiboles) are the most frequently used; but, recently the same health problems were observed with other fibres (zeolite, glass fibres). The effects of inhaled fibres at the level of the respiratory system are related to the types of fibres and to the penetration and biological reactivity into the alveolar spaces. Two types of diseases can be observed: lung and pleural fibrosis and lung and pleural cancer. Actually, the size of fibres is a major point for these effects, the longest and thinnest fibres being the most dangerous. However, recent data with acid treated chrysotile indicate that the chemical composition must also intervene.
Understanding of the biological effects of fibres has been archievied due to a large number of in vitro (cytotoxicity on free cells) and experimental studies. However, the basic mechanisms are still unknown. Results showed that fibres act on various levels, nuclear, metabolic, immunologic or molecular.
The fibres used in this experiment were UICC asbestos fibres (chrysotile, amosite, crocidolite, either untreated or leached with oxalic acid), nemalite and glass fibres. Chrysotile was also treated with sulfur dioxide. Size distribution measurements by electron microscopic analysis, chemical analysis and measurement of specific surface area were performed. Haemolytic activity was studied in human red blood cells by kinetic analysis of the percentage of haemoglobin released; this generated information on the shape of the curve, the initial velocity of the haemolysis and the maximal haemolysis. The effect on rabbit alveolar macrophages was determined in vitro by the measurement of lactic dehydrogenase and beta-galactosidase released from alveolar macrophages cultured with the fibres. Amphiboles and chrysotile had opposite reactivities on red blood cells. Leaching did not change the shape of the curve with chrysotile whereas it modified that with amphiboles. The initial velocity decreased with leached chrysotile and increased with leached crocidolite or amosite. Maximal haemolysis was linearly dependent on the fibre concentration with amosite and crocidolite, but not with chrysotile or nemalite. The adsorption of sulfur dioxide onto chrysotile did not highly modify its haemolytic activity. In alveolar macrophages, chrysotile and leached amphiboles selectively released beta-galactosidase; and leached chrysotile and nemalite released both enzymes studied.
The definition and the classification of bullae are recalled and documented by some examples. Two types of bullae are opposed : bulla found in normal parenchyma and bulla associated with widespread emphysematous lesions. The biochemical and biological mechanisms of the emphysematous changes are briefly described, with a distinction of two different pathogenesis : on one hand, an inherited defect in connective tissue synthesis as in Marfan syndrome, and on the other hand, an unbalance between proteases and antiproteases. The pathologist's contribution to the classification of the surgical forms of emphysema is documented by an electron microscopic study of lung biopsy in some cases : two cases with bullae (a Marfan syndrome and an alpha 1 AT deficiency of the Pi Z phenotype) with diffuse panlobular emphysema; and 4 cases of bullae without radiological evidence of emphysema. The elastic fibres were modified only in the 2 first cases but were normal in the others. A follow up of such cases is needed.
Different lung function tests have been studied in a group of 39 spray workers, with exposure of a few months to 20 years, in order to determine early impairments in ventilatory or gaseous exchange parameters. Lung function was assessed by conventional spirometric tests, plethysmographic measurement of lung volume, determination of arterial oxygen tension at rest and on exercise and measurement of single-breath diffusion of carbon monoxide. Asbestos exposure was assessed using a standardized questionnaire administered by an interviewer to determine length of exposure, and light microscopic examination to ascertain the number of ferruginous bodies in one sputum sample or in lung washing fluid. The results of the functional tests are expressed with respect either to duration of working exposure or to the number of ferruginous bodies. Restrictive ventilatory impairment with decrease in diffusion of carbon monoxide and increase in the oxygen alveolar-arterial difference on exercise was observed both in the group with 1-50 ferruginous bodies and in workers exposed for more than five years. The decrease in lung volume was approximately 10% when the length of asbestos exposure varied from 0-5 to 10-15 years, and 15% between those with no ferruginous bodies and those with more than 50. No obstructive profile was observed, even in heavy smokers. All function tests were altered equally. Plethysmography therefore appears to be a suitable technique for the follow-up of asbestos workers.
The relationship was studied between the presence in X-rays of one or several regions of straightness on the diaphragm, which interrupt or replace its normal curve, and the intensity, length and latency of asbestos exposure. Subjects were four groups in whom intensity of exposure, assessed by questionnaire and by ferruginous body counts, increased progressively. Diaphragmatic straightness increased with increasing intensity but not with length or latency of asbestos exposure.
Two different methods have been tested for assessing retrospectively occupational exposure to asbestos dust in 80 cases with suspected asbestos-related thoracic diseases: 1) Occupational history was recorded by an interviewer using a standardized questionnaire. The patients were divided into three groups: those obviously exposed (E), those obviously not exposed (NE) and those with an inconclusive questionnaire (IQ). 2) Ferruginous bodies were isolated from lung washing fluid and counted under the light microscope. In the questionnaire groups, the proportions positive for ferruginous bodies in lung washing fluid were as follows: E, 29/33; NE, 1/7; IQ, 17/40. In cases positive for ferruginous bodies in lung washing fluid, the median numbers of bodies per ml of fluid were: E, 11.7 (range, 0.05-31,250); NE, 0.06; IQ, 1.1 (range, 0.06-350) Since the data provided by the two methods were in good agreement (P less than 0.001) for the E and NE questionnaire groups, the presence of ferruginous bodies in lung washing fluid is considered to be a good indicator of past exposure. In the IQ group, the monitoring of ferruginous bodies in lung washing fluid demonstrated exposure to asbestos in 43% of cases.
The French mesothelioma register has three objectives. The first, collection of morbidity data could not be achieved since the data collected are not exhaustive. The second, the collection of histological material for establishing diagnostic criteria, has provided interesting data; and the third, etiological research, may constitute the basis for well-defined studies.
Three groups of people working in buildings with insufficient protection against sources of asbestos (ceilings, lagging, cupboards, etc.) have been compared by clinical and radiological examinations. The first group, G1 (n = 160), comprised people working in direct contact with sources of asbestos; the second one, G2 (n = 277), comprised people who had worked for at least 10 years in buildings with little protection; and the third one, G3 (n = 157), may be considered a control group, since the only period of exposure was while the buildings were being constructed. The prevalence of lung abnormalities (clinical, functional and radiological) was higher in G1 than in G3; G2 was closer to G1 for some signs, but closer to G3 for most. These differences are no explained by obvious possible confounding factors (such as age, sex or tobacco consumption). They were analysed taking the number of years of presence in the buildings into account.
Some clay minerals occur naturally in a fibrous or lath-like crystal state as attapulgite and sepiolite. Because of their sorptive and colloidal properties, attapulgite and sepiolite have numerous industrial applications, mainly as additives in oil-drilling muds, in chemical fertilizers, pesticides, paints, adhesive products, bleaching agents, cosmetic compounds and phytosanitary products. World consumption of each is over one million tons annually. Acid-treated attapulgite is used in the composition of certain drugs used for the treatment of gastrointestinal diseases. Such drugs available commercially in France were analysed for their mineral content by transmission electron microscopy and found to contain attapulgite fibres [mean length: 0.9 micrometers (0.1-3.6); mean diameter: 0.05 micrometers (0.01-0.5)]. The haemolytic activities of a Spanish attapulgite sample and of three samples of drugs sold in France were greater or similar to that of UICC chrysotile asbestos. Attapulgite fibres were encountered in large quantities in the lung washing fluid of a patient suffering from lung fibrosis who had been exposed recently for three years during the processing of attapulgite material. Attapulgite fibres were also found in a urine sample from a patient who had ingested 6-9 g/day of an attapulgite drug for six months.
Asbestos fibres in respiratory tissues from 29 cases diversely exposed to asbestos dusts have been characterized, sized and counted using a transmission electron microscope. Comparison of data obtained by measurement of fibres in lung parenchyma and in parietal pleura samples showed the following: -- In each case, the proportion of chrysotile fibres (as opposed to amphiboles) was higher in parietal pleura than in lung parenchyma. (The proportion of chrysotile in pleura was greater than 90% in 30 of the 40 samples.) -- Fibres encountered in parietal pleura were shorter than those in the parenchyma. -- There was no evident correlation between numerical concentrations of fibres in lung parenchyma and those in parietal pleura. This study has shown that characteristics of asbestos retention in parietal pleura cannot be derived from measurements in lung parenchyma. On the basis of the cases analysed here, who were exposed to mixed types of asbestos dust, chrysotile seems to be the asbestos type retained almost exclusively in parietal pleural tissues. These findings might be taken into account when assessing the risk of pleural diseases (especially mesothelioma) attributable to each type of asbestos fibre.
Intrapleural injections of 20 mg of various mineral fibres were made to rats. Three types of fibres (chrysotile, crocidolite and glass fibres) were untreated; other chrysotile fibres were leached to different degrees. The results show that chrysotile is the most toxic of the three: animals died sooner and presented mesotheliomas earlier. With increased leaching, toxicity and carcinogenic effect decreased. Crocidolite is less toxic than untreated chrysotile but later produces as many mesotheliomas; with glass fibres, some mesotheliomas are observed. Small groups of animals were exposed to two types of irradiation before intrapleural injection of 2 mg of chrysotile. Whole-body irradiation was delivered to a third group of animals which were given asbestos-contaminated food. The paper analyses the synergistic action of these two insults.
Evidence for a no-threshold concentration-effect relationship for many environmental carcinogens, and especially for asbestos fibres, has been substantiated. Thus, the risk for humans of low concentrations of fibres in the diet could be predicted if the absorption of fibres through the gut could be measured. In this study, the behaviour of ingested fibres (asbestos and attapulgite) has been investigated by the collection of lymph, as described by Bollman et al. (1948). Fibres were found to cross the gut wall and to circulate in the abdominal lymph at 2-24 hours after feeding. The kinetics of the fibre passage could be measured: 50% of the total load absorbed was found in the lymph within the first six hours. The greatest fibre passage was observed with long asbestos fibres, which reached 2.1 X 10(-4) of the ingested load. Selection of the longest fibres was observed when size distributions were compared in the lymph and in the diet. negative results were obtained consistently in controls and in some of the treated animals. Lymph collection was found to be the most appropriate method for detecting intestinal absorption.
A culture system of rat pleural mesothelial cells has been developed for short-term experiments and long-term maintenance. In short-term experiments, endocytosis of chrysotile fibres (100 microgram/ml) has been demonstrated by electron microscopy of the pleura in situ. Structural modifications, mainly cytoplasmic vacuolization, were observed when the cells were cultured with sublethal doses of chrysotile (0.5, 1, 2 and 10 micrograms/ml). Untreated cells had a mean population doubling time of 37 hours. When the cells were treated with 2 or 10 micrograms/ml, the mean population doubling time was slightly increased.