I
Volume 69 February 1976
127
Section of Measurement in Medicine President C M Conway FFA RCS Meeting 17 March 1975 with the Breathing Club
Measurement of the Prevalence of Emphysema [Abridged] Professor Sir Charles Stuart-Harris (Faculty of Medicine, University of Sheffield, Sheffield, S10 2TN)
Introduction The basis of the scientific method is measurement and to effect this there must be understanding of the nature of that which is to be enumerated. In the Ciba meeting emphysema was defined as a condition of the lung characterized by increase beyond the normal in the size of air spaces distal to the terminal bronchiole either from dilatation or from destruction of their walls (Ciba Foundation 1959). Almost immediately controversy followed and since then general agreement seems to have been reached that the word 'dilatation' should be abandoned; the necessity for destructive changes of the alveolar walls is implied in the statement by the American Thoracic Society (1962). In turn this has raised the difficulty of defining methods of measurement of the process in life.
The second development over the past few years has followed the careful work of clinicians and physiologists who have correlated their findings with those obtained by pathologists at autopsy. 'Pure' cases of bronchitis or of emphysema have been described as the extreme ends of a spectrum of which mixtures of the two conditions form the middle majority. Controversy exists as to whether 'pure' cases are ever encountered and this is important when considering questions of etiology.
Finally, the subject of this meeting is measurement of the prevalence of emphysema and this is the goal towards which many workers have been striving over the past several years. Such a goal
cannot be reached until there is agreement both on definitions and on methods of measurement. REFERENCES American Thoracic Society (1962) American Review of Respiratory Diseases 85, 762 Ciba Foundation (1959) Thorax 14,286
Dr P D Oldham (MRCPneumoconiosis Unit, Llandough Hospital, Penarth, Glamorgan, CF6 I XW)
Problems of Definitions and Sampling Emphysema is a morbid-anatomical condition by definition but, when it exists in life, it may or may not reveal its presence through symptoms and signs of respiratory ill-health, through disturbances in the usual patterns of lung function test results, and through unusual appearances in the chest radiograph. How consistently it does this is unknown. The 'prevalence of emphysema' must mean numerical information about the proportions of persons in different demographic classes who, if examined by a pathologist, would be found to have the enlargement of air-spaces and destruction of tissue required by the Ciba Foundation definition. It follows that the prevalence of emphysema is, and must remain, unknown, because the population samples available to pathologists are in no sense representative samples. At all except the oldest ages the average man has no chance of inclusion in such samples, which contain only those attacked by a mortal illness, and in general these will be in life the ill and disabled, though the unlucky will be to some degree included.
128 Proc. roy.-Soc. Med. Volume 69 February 1976
2
In practice, studies in life must be based on clinical, physiological and radiological surveys, with the hope that at some time the appropriate manner of combining their results to give an index of the severity of emphysema may be discovered, based probably on the slow accumulation of cases measured in these ways, chosen originally as representative of the general population, whose eventual deaths can be attributed to chance, that is, to accident. The appropriate radiological and physiological studies of representative population samples have yet to be made. Meanwhile, the current practice of treating the results of clinical, physiological and radiological investigations as if they gave similar gradings of the severity of emphysema, or even similar measures of its prevalence, should be recognized as potentially misleading. The correspondence between these types of investigation, and between them and morbid-anatomical emphysema, is as yet unknown, and it would require great optimism to suppose it will in due course be found to be close.
of the disease associated in some instances with a-I -antitrypsin deficiency. Studies of the incidence of emphysema, mainly centrilobular emphysema, in necropsy material have confirmed the association of the disease with smoking. It was found that in smokers compared with nonsmokers there was a very significantly increased incidence of emphysema, including the volume of affected lung in relation to age (Ryder et al. 1971, Anderson et al. 1972). Thus a survey of the incidence of the disease in the necropsy population is not entirely.without use.
Dr M S Dunnill
(Radcliffe Infirmary, Oxford, OX2 6HE) Post-mortem Studies The definition of emphysema quoted by Professor Stuart-Harris presupposes that the normal size of the air spaces is known. In fact although the average alveolar 'diameter' is 250 ,um there is considerable variation within the normal lung as alveoli at the base are smaller than those at the apex (Glazier et al. 1967). Most quantitative studies have taken lung air spaces of greater than 0.1 cm diameter as being the seat of emphysema (see Dunnill 1974). Data on the incidence of emphysema in a hospital necropsy population are likely to bear little relation to the incidence found by clinical methods in a live population. The reasons for this are: (1) the hospital necropsy population is highly selected; and (2) the definition of emphysema in terms of pathological anatomy leads to many cases of minor disease passing undetected on clinical examination. A further difficulty is that emphysema embraces at least two broad categories (Leopold & Gough 1957): centrilobular emphysema, characterized by dilatation and destruction of the respiratory bronchioles; and panacinar destructive emphysema, in which the architecture of the entire acinus is destroyed and all distinction between alveoli, alveolar ducts and respiratory bronchioles is lost. This is the form
REFERENCES Anderson J A, Dunnill M S & Ryder R C (1972) Thorax 27, 547 Dunnill M S (1974) American Journal of Medicine 57, 503-519 Glazier J B, Hughes J M, Maloney J E & West J B (1967) Journal of Applied Physiology 23, 694 Leopold J G & Gough J (1957) Thorax 12, 219 Ryder R C, Dunnill M S & Anderson J A (1971) Journal ofPathology 104, 59 DISCUSSION
Professor S J G Semple asked if the increased prevalence in smokers reflected an exaggeration of the ageing process. Dr Dunnili thought not. In answer to Dr D C S Hutchison, he found no correlation between the extent of emphysema and the volume of the bronchial mucous gland. Answering Dr J W Laws, Dr Dunnill said that amongst nonsmokers any severe emphysema was invariably panacinar, but it was uncommon. In smokers it was nearly always centrilobular. In answer to Professor Sir Charles Stuart-Harris, Dr Dunnill said that one-third of his cases were from accidents and suicides. Professor C M Fletcher said that a study confined to cases of sudden death had been published recently (Spain, Siegel & Bradess 1973, Journal of the American Medical Association 224, 322). Dr J C Gilson asked if amongst smokers there were differences in the amount of emphysema as between different parts of the country. An unidentified speaker thought, on the basis of studies in Oxford, London, South Wales and Durham, that there were not.
Dr J Bignon, Dr A Depierre, Dr J Andre-Bougaran and Dr B Hem
(Laboratoire d'Histologie et Cytologie Pulmonaire, Clinique de Pneumo-Phtisiologie, H6pital Laennec, 42 Rue de Sevres, 75007Paris, France)
Contribution of Morphometry, Bronchial Casts and Electron Microscopy to Study of Airway Obstruction in Chronic Obstructive Lung Disease The site and nature of the obstruction to air flow in chronic bronchitis, with or without associated emphysema, are still open to discussion.
Volume 69 February 1976
127
Section of Measurement in Medicine President C M Conway FFA RCS Meeting 17 March 1975 with the Breathing Club
Measurement of the Prevalence of Emphysema [Abridged] Professor Sir Charles Stuart-Harris (Faculty of Medicine, University of Sheffield, Sheffield, S10 2TN)
Introduction The basis of the scientific method is measurement and to effect this there must be understanding of the nature of that which is to be enumerated. In the Ciba meeting emphysema was defined as a condition of the lung characterized by increase beyond the normal in the size of air spaces distal to the terminal bronchiole either from dilatation or from destruction of their walls (Ciba Foundation 1959). Almost immediately controversy followed and since then general agreement seems to have been reached that the word 'dilatation' should be abandoned; the necessity for destructive changes of the alveolar walls is implied in the statement by the American Thoracic Society (1962). In turn this has raised the difficulty of defining methods of measurement of the process in life.
The second development over the past few years has followed the careful work of clinicians and physiologists who have correlated their findings with those obtained by pathologists at autopsy. 'Pure' cases of bronchitis or of emphysema have been described as the extreme ends of a spectrum of which mixtures of the two conditions form the middle majority. Controversy exists as to whether 'pure' cases are ever encountered and this is important when considering questions of etiology.
Finally, the subject of this meeting is measurement of the prevalence of emphysema and this is the goal towards which many workers have been striving over the past several years. Such a goal
cannot be reached until there is agreement both on definitions and on methods of measurement. REFERENCES American Thoracic Society (1962) American Review of Respiratory Diseases 85, 762 Ciba Foundation (1959) Thorax 14,286
Dr P D Oldham (MRCPneumoconiosis Unit, Llandough Hospital, Penarth, Glamorgan, CF6 I XW)
Problems of Definitions and Sampling Emphysema is a morbid-anatomical condition by definition but, when it exists in life, it may or may not reveal its presence through symptoms and signs of respiratory ill-health, through disturbances in the usual patterns of lung function test results, and through unusual appearances in the chest radiograph. How consistently it does this is unknown. The 'prevalence of emphysema' must mean numerical information about the proportions of persons in different demographic classes who, if examined by a pathologist, would be found to have the enlargement of air-spaces and destruction of tissue required by the Ciba Foundation definition. It follows that the prevalence of emphysema is, and must remain, unknown, because the population samples available to pathologists are in no sense representative samples. At all except the oldest ages the average man has no chance of inclusion in such samples, which contain only those attacked by a mortal illness, and in general these will be in life the ill and disabled, though the unlucky will be to some degree included.
128 Proc. roy.-Soc. Med. Volume 69 February 1976
2
In practice, studies in life must be based on clinical, physiological and radiological surveys, with the hope that at some time the appropriate manner of combining their results to give an index of the severity of emphysema may be discovered, based probably on the slow accumulation of cases measured in these ways, chosen originally as representative of the general population, whose eventual deaths can be attributed to chance, that is, to accident. The appropriate radiological and physiological studies of representative population samples have yet to be made. Meanwhile, the current practice of treating the results of clinical, physiological and radiological investigations as if they gave similar gradings of the severity of emphysema, or even similar measures of its prevalence, should be recognized as potentially misleading. The correspondence between these types of investigation, and between them and morbid-anatomical emphysema, is as yet unknown, and it would require great optimism to suppose it will in due course be found to be close.
of the disease associated in some instances with a-I -antitrypsin deficiency. Studies of the incidence of emphysema, mainly centrilobular emphysema, in necropsy material have confirmed the association of the disease with smoking. It was found that in smokers compared with nonsmokers there was a very significantly increased incidence of emphysema, including the volume of affected lung in relation to age (Ryder et al. 1971, Anderson et al. 1972). Thus a survey of the incidence of the disease in the necropsy population is not entirely.without use.
Dr M S Dunnill
(Radcliffe Infirmary, Oxford, OX2 6HE) Post-mortem Studies The definition of emphysema quoted by Professor Stuart-Harris presupposes that the normal size of the air spaces is known. In fact although the average alveolar 'diameter' is 250 ,um there is considerable variation within the normal lung as alveoli at the base are smaller than those at the apex (Glazier et al. 1967). Most quantitative studies have taken lung air spaces of greater than 0.1 cm diameter as being the seat of emphysema (see Dunnill 1974). Data on the incidence of emphysema in a hospital necropsy population are likely to bear little relation to the incidence found by clinical methods in a live population. The reasons for this are: (1) the hospital necropsy population is highly selected; and (2) the definition of emphysema in terms of pathological anatomy leads to many cases of minor disease passing undetected on clinical examination. A further difficulty is that emphysema embraces at least two broad categories (Leopold & Gough 1957): centrilobular emphysema, characterized by dilatation and destruction of the respiratory bronchioles; and panacinar destructive emphysema, in which the architecture of the entire acinus is destroyed and all distinction between alveoli, alveolar ducts and respiratory bronchioles is lost. This is the form
REFERENCES Anderson J A, Dunnill M S & Ryder R C (1972) Thorax 27, 547 Dunnill M S (1974) American Journal of Medicine 57, 503-519 Glazier J B, Hughes J M, Maloney J E & West J B (1967) Journal of Applied Physiology 23, 694 Leopold J G & Gough J (1957) Thorax 12, 219 Ryder R C, Dunnill M S & Anderson J A (1971) Journal ofPathology 104, 59 DISCUSSION
Professor S J G Semple asked if the increased prevalence in smokers reflected an exaggeration of the ageing process. Dr Dunnili thought not. In answer to Dr D C S Hutchison, he found no correlation between the extent of emphysema and the volume of the bronchial mucous gland. Answering Dr J W Laws, Dr Dunnill said that amongst nonsmokers any severe emphysema was invariably panacinar, but it was uncommon. In smokers it was nearly always centrilobular. In answer to Professor Sir Charles Stuart-Harris, Dr Dunnill said that one-third of his cases were from accidents and suicides. Professor C M Fletcher said that a study confined to cases of sudden death had been published recently (Spain, Siegel & Bradess 1973, Journal of the American Medical Association 224, 322). Dr J C Gilson asked if amongst smokers there were differences in the amount of emphysema as between different parts of the country. An unidentified speaker thought, on the basis of studies in Oxford, London, South Wales and Durham, that there were not.
Dr J Bignon, Dr A Depierre, Dr J Andre-Bougaran and Dr B Hem
(Laboratoire d'Histologie et Cytologie Pulmonaire, Clinique de Pneumo-Phtisiologie, H6pital Laennec, 42 Rue de Sevres, 75007Paris, France)
Contribution of Morphometry, Bronchial Casts and Electron Microscopy to Study of Airway Obstruction in Chronic Obstructive Lung Disease The site and nature of the obstruction to air flow in chronic bronchitis, with or without associated emphysema, are still open to discussion.
