Bronchial Asthma. A Genetic, Population and Psychiatric Study

206 Pages·1967·5.191 MB·English

by  Denis Leigh and Edward Marley (Auth.)

BRONCHIAL
ASTHMA
A Genetic, Population and Psychiatric Study
by
DENIS LEIGH, B.Sc, M.D., F.R.C.P.
Physician, the Bethlem Royal
and Maudsley Hospitals, London
and
EDWARD MARLEY, M.A., M.D.,
F.R.C.P.E., D.P.M.
Senior lecturer, Institute of Psychiatry,
The University of London
with the assistance of
MISS DOROTHY BRAITHWAITE, M.A.
Psychiatric Social Worker
PERGAMON PRESS
OXFORD · LONDON · EDINBURGH · NEW YORK
TORONTO · SYDNEY · PARIS · BRAUNSCHWEIG
Pergamon Press Ltd., Headington Hill Hall, Oxford
4 & 5 Fitzroy Square, London W.l
Pergamon Press (Scotland) Ltd., 2 & 3 Teviot Place, Edinburgh 1
Pergamon Press Inc., 44-01 21st Street, Long Island City, New York 11101
Pergamon of Canada, Ltd., 6 Adelaide Street East, Toronto, Ontario
Pergamon Press (Aust.) Pty. Ltd., 20-22 Margaret Street,
Sydney, N.S.W.
Pergamon Press S.A.R.L., 24 rue des ficoles, Paris 5e
Vieweg & Sohn GmbH, Burgplatz 1, Braunschweig
Copyright © 1967
Pergamon Press Ltd.
First edition 1967
Library of Congress Catalog Card No. 67-14544
PRINTED IN GREAT BRITAIN BY A. WHEATON AND CO. LTD., EXETER
3100/67
PREFACE
THE field work on which this study is based was carried out by the
two authors, assisted by Miss Dorothy Braithwaite, during 1955-8.
A grant from the Research Fund of the Bethlem Royal and Maudsley
Hospitals made our work possible, and we are grateful for this. We
are particularly indebted to the general practitioners who, long before
it became fashionable, allowed us to carry out a research project
on their patients—Drs. John Fry, Raymond Gaze, George Gomez,
and the late Drs. N. Bodkin and Michael Howlett. To their patients
we are also grateful—they allowed us into their homes, answered a
great number of questions, and demanded little or nothing in return.
Professor C. D. Calnan helped us to decide on our classification of
the skin disorders. Dr. Eliot Slater has given us invaluable help—
without him, the final genetic work could not have been completed,
and he has cast a benevolent eye on the project from its inception.
Professor Sir Aubrey Lewis, Dr. R. S. Bruce Pearson, Dr. F. Kraupl
Taylor and Dr. J. K. Wing have read our manuscript and given us
the benefit of their advice and criticism. Whatever errors occur in the
following pages are solely our responsibility. The manuscript was
typed and retyped on innumerable occasions by Mrs. Louise Elsey,
Mrs. Evelyn Sparrowhawk and Mrs. Cynthia Sutton, to whom we
are very grateful.
vu
CHAPTER 1
INTRODUCTION
RICHET'S discovery of anaphylaxis in 1902, and the introduction of
the concept of allergy by von Pirquet in 1906, gave an entirely new
direction to the study of bronchial asthma. For centuries, indeed
since Hippocrates, bronchial asthma had been regarded as a "nervous
disorder". Both Major (1953) and Abramson (1951) have written
brief historical accounts of the condition. The position towards the
close of the nineteenth century was well described by Berkart (1889),
in his book on bronchial asthma. He pointed out that Laennec had
crystallized earlier views in concluding that "the chief and primary
cause of asthma could only be a sudden alteration of the nervous
influence". Laennec believed that although there were other
contributory causes, the dyspnoea was due principally to nervous
factors.
At the close of the nineteenth century there were four main
theories of the cause of asthma. These were (1) that attacks occurred
as a result of pathological changes in the heart, lungs or large
vessels; (2) that spasm and paralysis of the bronchi were produced by
nervous or humoral changes, or from bronchial exudation; (3) that
due to certain changes in the blood, spasm of the diaphragm and
other respiratory muscles occurred; and (4) that irritation from the
nasal organs produced reflex bronchial irritation.
Whilst granting that attacks might occur in all these ways,
Berkart held that asthma was a "nervous disorder". He considered
that
. .. this so-called nervous asthma develops itself upon an endogenous
neuropathic basis. The individuals whose somatic conditions have just been
referred to exhibit from early infancy unmistakable signs of a functional
disease of the central nervous system which is generally inherited, most
frequently on the mother's side. They have a reduced resistance to all irrita­
tions, whether peripheral or visceral, and with it an increased tendency to
reflexes, which are readily transferred to centrifugal sensory, motor and
vasomotor nerve tracts. There is also a marked hypersensitiveness to all
1
2 BRONCHIAL ASTHMA
kinds of stimuli, the effects of which are in the healthy hardly or not at all
perceived, but which are here attended by the most distressing sensations.
They suffer from a variety of most pronounced nervous symptoms, which if
these occur before the onset of the dyspnoea are commonly described as the
prodromata of the asthma. In every case there is a history of a long childhood
respiratory illness with often incomplete recovery. Under the anxious care
of a nervous mother and during the persistence of recurrence of the more
striking bronchitis symptoms the word "asthma" is frequently mentioned;
and although the children do not understand its meaning, it becomes im­
portant by sheer repetition.
The child lives and is brought up in an atmosphere of "asthma". The
"traumatic" insult which the disease originally produced is converted into a
"psychic trauma", and every functional disturbance, however slight, ad­
versely affects respiration. Although the neuropathic disposition, the root of
nervous asthma, is always endogenous and most frequently inherited, there
is yet a reasonable prospect that it may be favourably modified if appropriate
measures are instituted early in life.
Richet's discovery altered all this. The "nervous factor" fell out of
fashion, and was replaced by anaphylaxis, and a little later, by
allergy. Wolff-Eisener (1906, 1907) suggested that hay fever and
urticaria were anaphylactic phenomena. De Besehe (1909), an
asthmatic, described the near-fatal effect of injecting himself with
tetanus antitoxin, after which he developed severe asthma and
vasomotor rhinitis. He commented wryly on the similarity of his
symptoms to those of anaphylaxis in the guinea-pig. Biedl and Kraus
(1910), and 2 months later Meltzer (1910), suggested that asthma
might be an anaphylactic manifestation. Soon, other conditions
began to be classified as "allergic", such as migraine, eczema and
psoriasis, certain gastro-intestinal illnesses, arthritis, epilepsy, and
reactions to drugs or chemicals, until the list of possible allergic
disorders became alarming in its comprehensiveness. Over the years
bronchial asthma became even more firmly established as one of the
most important allergic disorders. However, in 1952 Michael
Schwartz reviewed the historical development of anaphylaxis and
allergy, and was forced to conclude that it was not possible to "set-up
any well-defined syndrome, the allergic diseases". As a result, he
decided to reinvestigate the relationships between bronchial asthma
and a variety of conditions commonly regarded as allergic in nature.
These were hay fever, vasomotor rhinitis, Besnier's prurigo, eczema,
urticaria, Quincke's oedema, migraine, gastro-intestinal allergy,
epilepsy, ichthyosis and psoriasis. He used the Weinberg genealogical
proband method, whereby the family incidence of a particular dis­
order is established, taking his data from an unselected group of
INTRODUCTION 3
probands suffering from the disorder and their families, and compar­
ing the findings with those from a group of matched "normal"
probands and their families. Schwartz found that asthma, vasomotor
rhinitis, hay fever and Besnier's prurigo occurred with a far higher
incidence in relatives of Asthma probands than in the relatives of the
Controls. There was no significant difference in the incidence of
migraine, gastro-intestinal allergy, ichthyosis, epilepsy or psoriasis.
He concluded that asthma is an inherited disease, and that a genetic
relation exists between it and vasomotor rhinitis, hay fever and
Besnier's prurigo. The allergic and non-allergic sub-groups of
Asthma probands were identical in so many respects "that
asthma must be presumed to be a genetic entity". Schwartz found
the inheritance "probably dominant with failing manifestation".
The manifestation of the "asthma gene", which comprises asthma,
vasomotor rhinitis, hay fever and Besnier's prurigo was about
40 per cent.
Schwartz's method of selection, and the constitution of his control
material are open to criticism. He writes "it is a factor of decisive
significance that the control material should conform as far as
possible to the proband material—only the persons who make up
the control material must not suffer or have suffered from the
diseases embraced by the study". To reject, as did Schwartz, those
subjects with hay fever, vasomotor rhinitis, eczema, urticaria,
ichthyosis, epilepsy, etc., is tantamount to assuming that these
diseases are genetically or constitutionally linked to asthma.
From the Control material should be excluded only those persons
who were suffering or had suffered from bronchial asthma. Schwartz
found that "while it was not difficult to collect a suitable number of
probands with asthma, it proved—as in previous studies of this
nature—to be connected with much greater difficulties to procure a
sufficient number of applicable controls". Control families certainly
may have less motivation for co-operating in such an investigation,
but the random selection of Control material from the same popula­
tion as those of the asthmatics has no intrinsic difficulty. Schwartz's
Control material, however, was derived from various sources. It
included 200 probands, comprising 101 persons who attended for
ambulatory treatment at the Clinic of the National Poliomyelitis
Society, 50 in-patients from the Copenhagen Municipal Hospital,
5 from the Surgical Department, 27 from the Surgical Out-patient
Department of the University Hospital, 20 medical students and 2
4 BRONCHIAL ASTHMA
masseuses. While these probands lived in Copenhagen or its suburbs
and were matched against the Asthma probands for economic status,
sex and age, they are obviously not a random sample, but rather an
unusually selected group. This factor, together with the proviso that
no one of the Control probands should have suffered from any of the
diseases specified, makes it unlikely that they could be a normally
distributed Control population.
Ratner and Silberman (1953) have also criticized the composition
of Schwartz's material, and considered also that Schwartz's findings
did not reveal an inherited capacity for sensitization. What was in­
herited was a respiratory tract which responded to a variety of
stimuli by producing attacks of asthma or rhinitis. They also
maintained that a condition cannot be called allergic unless an
antigen-antibody reaction can be demonstrated. Consequently,
Schwartz's data did not show that the capacity for sensitization is
genetically determined. In the same issue of the Journal of Allergy
(1953) the editor pointed out that the definition of allergy is con­
troversial, and that the merit of Schwartz's method was that it
avoided this.
In view of the methodological shortcomings in the selection of
patients for Schwartz's study and the fact that he had confined
himself to a study of the so-called allergic disorders, it was decided
to enlarge the inquiry so that besides asthma and allergic ailments,
psychiatric illness and certain psychosomatic disorders such as
peptic ulcer, migraine and rheumatoid arthritis would be included.
The population to be studied would not depend on referral to
hospital, as had that of Schwartz. Instead, it would consist of
asthmatics and their families belonging to practices in south London
and visited and interviewed in their own homes. Many of the Asthma
probands and asthmatic relatives would never have been to hospital.
The Control population would be obtained from the same districts
as the Asthma group, the only stipulation being that the Control
probands had not suffered from asthma.
By selecting the material in this way, it would be possible to
compare the prevalence of the various diseases in the Asthma and
the Control populations. The relation between asthma and other
chest illness, particularly chronic bronchitis, would also be examined,
a point omitted by Schwartz. Finally, the relation, if any, between
bronchial asthma, psychiatric illness and certain psychosomatic dis­
orders would be clarified.
INTRODUCTION 5
REFERENCES
ABRAMSON, H. A. (Ed.) (1951) Somatic and Psychiatric Treatment of Asthma,
Williams & Wilkins, Baltimore.
BERKART, J. B. (1889) On Bronchial Asthma: its pathology and treatment,
Churchill, London, 2nd edn, vii, 220.
BESCHE, A. DE. (1909) Et tilf. ab abnorm, reaktion for diphteriserum, Norsk mag.
f. laege vidensk., 70, 569.
BIEDL, A. and KRAUS, R. (1910) Experimentelle Studien über Anaphylaxie,
Wien Klin. Wchnschr., 23, 385.
EDITORIAL (1953) Hereditary factors in allergy, /. Allergy, 24, 379.
MAJOR, R. H. (1953) A Note on the History of Asthma, In Science, Medicine, and
History, Ed. E. A. Underwood, Oxford University Press, Oxford, p. 518.
MELTZER, S. J. (1910) Bronchial asthma as a phenomenon of anaphylaxis,
/. Amer. Med. Ass., 55, 1021.
PIRQUET, C. VON. (1906) Allergie, Münch. Med. Wchnschr., 53, 1457.
PORTIER, P. and RICHET, L. (1902) De Faction anaphylactique de certains venins,
Comp. rend. Soc. Biol, Paris, 54, 170.
RATNER, B. and SILBERMAN, D. E. (1953) Critical analysis of the hereditary
concept of allergy, /. Allergy, 1A,?>1\.
SCHWARTZ, M. (1952) Heredity in Bronchial Asthma, Munksgaard, Copenhagen.
WOLFF-EISENER, A. (1906) Das Heufieber, München.
WOLFF-EISENER, A. (1907) Über die Urticaria von Standpunkt der neueren
Erfahrungen, Dermat. Zentr., 10, 164.
CHAPTER 2
METHODS
THE Weinberg genealogical proband method was employed, the
principle of which is as follows. Among an unselected representative
group of probands suffering from the disease to be studied, the
familial incidence is determined. The incidence of the disease among
the general population is determined from a Control series of normal
probands. If it can be demonstrated that the disease is significantly
more common among the relatives of the probands than among the
general population, then there is every likelihood of its being due to
inherited factors in the absence of exogenous differences between the
Proband and Control series.
The information obtained about the family pedigree included data
relating (1) to the proband, (2) to the first-degree relatives, i.e. the
proband's parents, siblings and children, and (3) to the second-
degree relatives, i.e. parent's siblings, and grandparents. The diseases
under scrutiny included bronchial asthma and other chest ailments,
hay fever, vasomotor rhinitis, urticaria and Quincke's oedema,
eczema, peptic ulcer, psoriasis, rheumatoid arthritis, herpes zoster,
epilepsy, migraine and psychiatric illness. Neurotic traits were also
inquired about. In several of these diseases, an allergic basis would
appear unlikely, but as some workers have endeavoured to relate
one or other of them to allergy, this type of study should provide
evidence for or against such a view.
SELECTION OF PROBANDS
The prevalence of the major allergic disorders in the general
population has been variously estimated as from 7 to 10 per cent.
One of these disorders, bronchial asthma, occurs in some 1-2 per
cent of the population. With common conditions such as these, it is
essential, for any genetic inquiry, to obtain an unselected group of
patients suffering from the condition. Factors of selection so much
enter into hospital referral that hospital groups are unsuitable for
6
METHODS 7
such a study. The investigator must, therefore, seek out his material
in the field, which, in Great Britain, for practical purposes means
within the ambit of general practice.
The National Health Service, financed via compulsory National
Health Insurance, provides a free medical service for every man,
woman and child in the British Isles. Practically every individual is
registered with a general practitioner, who assumes responsibility
for his or her medical care. Each patient has a National Health
Insurance number, and a card on which details of age, sex, address,
and clinical facts are noted, and which is filed in the doctor's office.
It is thus possible, in well-organized practices, to obtain information
about, or access to, that sector of the general population in a
district who are registered with one particular practice. Practices
may vary from one-man to four-men practices, and the number of
patients from 1000 or less, to 14,000 or more.
Owing to the relation built up over several years between one of us
and a number of general practitioners in London, it was possible to
carry out a study of bronchial asthma in these practices, and so
avoid the selective factor operating in hospital populations. And
most important, the hitherto untested possibility of obtaining a
carefully matched control group was most likely to meet with success.
The incentives motivating sick people and their families to co­
operate in a psychosomatic and genetic study were postulated to be
stronger than those motivating "normals" and their families. The
personal nature of psychiatric inquiry, and the reluctance to reveal
details of mental illness in the family led us to expect some difficulties
in both groups. The very nature of the investigation, entailing
personal interviews with as many members of the family as possible,
and the obtaining of information from each member about their
relatives might prove to be a delicate matter in the light of the
prejudices relating to psychiatric inquiry. That the investigation was
successfully completed, involving as it did information about 1741
persons, is a tribute both to the relations in the two practices between
the doctors and their patients, and to the good sense and kindness
of the Londoners who helped us so much.
THE TWO PRACTICES
The vast population of London is so heterogeneous as immedi­
ately to present difficulties in a study such as this. It was therefore