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However, in a more detailed study, minor impairment of function in type MZ individuals was observed (Cooper et al. 1974). In conclusion, there appears to be no firm evidence that heterozygotes of types MZ or MS have a predisposition to develop severe emphysema, though there may be a tendency to develop minor lung function abnormalities.

of the peripheral pulmonary arteries, with a paucity of branches and a reduction in background filling of the lung, best recognized in areas of lung projected free of overlying ribs. Tomography is useful in demonstrating the areas of affected lung and in locating bullous changes. If the vascular bed in one area is destroyed, there is often a compensating increase in bloodflow through other parts of the lung resulting in a comparative increase in the size of the peripheral vessels in the relatively normal areas. In severe cases the radiographic changes give topographical information about pulmonary bloodflow similar to that obtained from xenon-133 scans of the lung. Some patients with chronic obstructive lung disease have increased rather than attenuated lung vascularity. Instead of areas devoid of vascularity, the periphery of the lungs appears plethoric, especially in the lower zones. There is usually enlargement of the right ventricle and main pulmonary arteries. Such patients are most unlikely to have panlobular emphysema, although some have centrilobular emphysema. Unfortunately the correlation is poor and at autopsy a few have no emphysema at all, while centrilobular emphysema of similar severity may be found in patients with normal chest films and no pulmonary symptoms.

REFERENCES Cole R B, Nevin N C & Blundell G (1974) Clinical Science and Molecular Medicine 47, 26P Cook P J L (1974) Postgraduate Medical Journal 50, 362 Cooper D M, Hoeppner V, Cox D, Zamel N, Bryan A C & Levison H (1974) American Review of Respiratory Diseases 110, 708 Eriksson S (1965) Acta Medica Scandinavica Suppl. 432 Hutchison D C S, Cook P J L, Barter C E, Harris H & Hugh-Jones P (1971) British Medical Journal i, 689 Jones M C & Thomas G 0 (1971) Thorax 26, 652 Kellerman G & Walter H (1970) Human Genetics 10, 145 Kueppers F, Briscoe W A & Bearn A G (1964) Science (New York) 146, 1678 Kueppers F & Donhardt A (1974) Annals of Internal Medicine 80, 209 Kueppers F, Fallat R & Larson R K (1969) Science (New York) 165, 899 Lieberman J, Mittman C & Schneider A S (1969) Journal of the American Medical Association 210, 2055 Talamo R C, Allen J D, Kahan M G & Austen K F (1968) New England Journal of Medicine 278, 345 Webb D R, Hyde R W, Schwartz R H, Hall W J, Condemi J J & Townes P L (1973) American Review of Respiratory Diseases 108,918 DISCUSSION

Dr Bignon reported evidence from France that amongst adults with cirrhosis of the liver the incidence of abnormal phenotypes resembled that of the control group (Morin et al. 1975, Lancet i, 250). Dr R B Cole confirmed this from his series in Belfast. From a limited study of 7 cases he could find no conspicuous evidence that individuals of Sz or ZO phenotypes had an increased liability to emphysema. He asked what was the likelihood of patients with the ZZ phenotype getting the disease. Dr Hutchison answered that among antitrypsindeficient smokers the incidence of emphysema was very high; nonsmokers had a chance of escaping the disease but often the onset of emphysema was merely postponed. He thought that there were also other forms of hereditary emphysema for which the biochemical basis was not yet known.

Dr J W Laws

(King's College Hospital, London SE5 9RS) Prevalence of Emphysema: Radiographic Features The chest film is a simple but insensitive method of demonstrating the extent and severity of emphysema. Correlation of radiology and pathology has shown that the most reliable sign of panlobular emphysema is destruction of lung tissue and, in particular, of the vascular bed of the lung. This gives rise to a premature narrowing

DISCUSSION

Professor C M Fletcher commented on the large observer differences between radiologists interpreting the extent of emphysema from chest radiographs; in one series Dr R G Fraser and Dr G Simon agreed in only 8 out of 100 cases. Dr Laws replied that Dr Frazer had abandoned his view that increased lung markings were associated with centrilobular emphysema so the disagreement might now be less. H4owever, recognition of patterns was difficult. He thought that computer analysis of relevant variables might help; this was being done at Northwick Park. In relation to airways obstruction the use of an ultrafine focus X-ray tube with 50 ,tm anode spot might provide better structural detail by magnification, radiographs. Whien combined with localized bronchography this could reveal airways stenosis of the sort mentioned earlier. Another useful technique for demonstrating localized air trapping was to take a chest film at the end of one second of forced expiration. Dr B E Heard commented that Dr B M Wright and others at Northwick Park had improved the technique for fume fixation of the lung; this simplified the comparison of the radiographic and structural features of the lung. Dr D C Flenley suggested that it might be useful to compare a lateral tomogram slice obtained in life with a whole section in a similar lateral plane of the fixed inflated post-mortem specimen. Dr Laws, in answer to Dr P D Oldham, agreed that a lateral chest radiograph often showed localized

132 Proc. roy. Soc. Med. Volume 69 February 1976

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bulli and depression of the diaphragm better than the

usefulness of this test compared with the so-called more sensitive tests. The results might be different if only those within 90% of the predicted FEV1 were used for study. Professor Milic-Emili replied that his conclusions were unaffected by raising the cut-off point to 85% but the numbers of subjects were smaller. Mrs M McDermott said that data for people living on Bornholm (Olsen & Gilson, 1960, British Medical Journal i, 450-456, McDermott et al., 1975, Bulletin de Physio-Pathologie Respiratoire 11, 41P-45P) showed the closing volume to be greater in cigarette smokers than in cigar and pipe smokers. However, the closing volume bore no relation to respiratory symptoms at the 'time of the study or to subsequent prognosis. The FEV was a better test in these respects. Dr M Sudlow commented that the iso-volume test performed using three breaths of helium exhibited an up to 70% variation; this was greatly reduced by the subjects breathing helium for ten minutes before the test. The difference reflected the extent of washout of nitrogen from the lung. Dr Sudlow suggested this might be the mechanism underlying Professor MilicEmili's findings, and not airways narrowing associated with loss of elastic recoil pressure. Dr T J H Clark had evidence for asthmatics that the three-breath and the ten-minute helium results were similar. Dr Sudlow agreed that they were similar in the absence of airways obstruction. In the presence of obstruction the variability was reduced by taking the best flowvolume curve after three breaths instead of taking the mean of them. Professor C M Fletcher questioned if the closing volume test which yielded abnormal results in 60% of smokers could be a valid predictor of disability, since only a small proportion of smokers were likely to develop airways obstruction. In answer to Mrs McDermott, there was no information on for how long after smoking a cigarette the helium flow volume test was influenced by the acute effects of smoking. Professor Milic-Emili found it disturbing that many new tests were used before they were fully developed.

P-A films. In answer to Dr G Cumming, he had no evidence on the interpretation to be placed oIn a large retrocardiac space. Dr T J H Clark emphasized the need for grading the emphysema; this was an essential step in determining the prevalence.

Professor J Milic-Emili (Department ofPhysiology, McGill University, PO Box 6170, Station A, Montreal, Canada, H3C3GI) Prevalence of Emphysema: Physiological Features Recently several new tests have been described which can detect abnormalities in lung function in patients in whom the conventional lung function measurements are within normal limits. They include (a) regional lung function using radioactive xenon, (b) frequency dependence of lung compliance, (c) frequency dependence of N2 washout, (d) flow dependence of the intrapulmonary distribution of inspired boluses of '33Xe, (e) closing volume and closing capacity, (f) analysis of the alveolar plateau, (g) analysis of flow-volume curves during helium breathing. The last three are sensitive as well as relatively simple and rapid, and appear potentially suitable for epidemiological studies (see McCarthy et al. 1972, Buist & Ross 1973, Buist et al. 1973, Dosman et al. 1975). Although their precision and reliability has not been as yet fully defined, most of these tests appear sufficiently reproducible for epidemiological studies. However, they lack specificity, in that they reflect abnormalities in both small airways and lung parenchyma and their validity has still to be determined. Future longitudinal epidemiological studies are needed to establish if these new lung function tests are of any prognostic value. Additional fundamental information will also be gained by comparing the results of these tests with findings at autopsy. REFERENCES Buist A S & Ross B B (1973) American Review of Respiratory Diseases 108, 1078 Buist A S, Van Fleet D L & Ross B B (1973) American Review of Respiratory Diseases 107, 735 Dosman J, Bode F, Urbanetti J, Martin R & Macklem P T (1975) Journal of Clinical Investigation 55, 1090 McCarthy D S, Spencer R, Greene R & Milic-Emili J (1972) American Journal of Medicine 52, 747 DISCUSSION

Dr T J H Clark said that the FEV,0 had a smaller intra-subject variability than the other tests. On this account the practice of selecting subjects from amongst those whose FEV lay within 75% of the predicted value could lead to under-estimation of the

Dr R B Cole, Dr N C Nevin, Dr B L Bradley, Dr G Blundell, Dr J D Merrett and Dr J R McDonald

(Departments of Medicine and Medical Statistics, Queen's University of Belfast, and Department of Clinical Chemistry, Belfast City Hospital)' Effect of Variation in Alpha-1-antritrypsin Phenotype upon Incidence of Respiratory Illness in an Unselected Working Population In a population sample of 1995 people of both sexes between 30 and 70 years of age living in Northern Ireland, the percentage frequencies of 'Correspondence may be addressed to: Dr R B Cole, Respiratory Physiology Department, North Staffs Hospital Centre, Stoke-on-Trent

Prevalence of emphysema: radiographic features.

131 5 Section of Measurement in Medicine However, in a more detailed study, minor impairment of function in type MZ individuals was observed (Coope...
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