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Both the prognosis of childhood asthma and the incidence of asthma in early adulthood are strongly influenced by bronchial hyperreactivity, a measurement few of us make routinely.
One of the most neglected aspects of the epidemiology of asthma is the period of transition from childhood to adulthood, perhaps because paediatricians feel insecure about trespassing on adult territory and adult physicians do not have access to paediatric cohorts. Adolescence is, in fact, an important period for asthmatic patients, not only because the condition itself may be difficult to manage, but because this is a time when asthma sometimes remits1–,3 and when the male preponderance of childhood gradually gives way to the female preponderance of adulthood.4,5
Numerous cross sectional studies have spanned this period. Secondary schools provide a captive population of adolescents and have been widely used in the ISAAC studies,6 and college students7,8 and army recruits9,10 provide ready sources of young adults for study. However, although such cross sectional studies demonstrate very clearly that adolescence is a time when significant changes occur in the asthmatic population, they cannot examine the factors that might influence the prognosis of individual children.
There have, of course, been longitudinal studies—notably those from Melbourne,11,12 Groningen,13 and Copenhagen14—all of which have emphasised the importance of childhood bronchial hyperreactivity in determining the persistence of asthmatic symptoms into adult life. However, most of these studies have been incomplete to varying degrees, different studies focusing on asthmatic symptoms, family history, pulmonary function, bronchial hyperreactivity to a variety of stimuli, and allergic phenomena including IgE levels and the results of skin tests. What has been lacking is a study in which children have been subject to comprehensive evaluation of what is sometimes described as the “asthma phenotype” at regular intervals during childhood, through adolescence, and into adulthood.
Some years ago the late Ann Woolcock posed the question: “Is there a specific phenotype for asthma?”15 Of course there isn't, but rather there is a group of clinical features that are seen with varying frequencies in children in whom a diagnosis of asthma has been made. Virtually all will have had recurrent wheeze, with the exception of those rare children with cough variant asthma, and virtually all will have evidence of reversible airways obstruction if seen during an attack. Many (but not all) will show evidence of allergy, with associated eczema or hay fever, positive skin tests, or raised total or specific IgE levels. The more severely affected will show bronchial hyperreactivity in response to challenges such as cold air, exercise, or nebulised water, saline, histamine, methacholine, or allergen. There will be direct or indirect evidence of bronchial inflammation, although such measurements have not yet been simplified sufficiently for use in epidemiological studies. And, of course, many will have a family history of asthma or allergy.
The interactions between these various components of the asthma phenotype are complex. Thus, bronchial hyperreactivity appears to be inherited independently of atopy,16 yet it is not only closely associated with the severity of asthmatic symptoms17 but also correlates with the number of positive skin tests.18
In an attempt to evaluate the relative importance of these asthmatic features in determining the long term course of childhood asthma, a paper by Professor Woolcock and her colleagues in this issue of Thorax reports on data collected from a series of studies performed in Belmont, New South Wales.19 The subjects in this study have been investigated extensively on a maximum of seven occasions and were included in the present analysis if studied on a minimum of three occasions.
The results make fascinating reading. More than one third of the subjects had had recent wheeze in at least one of the studies and, although remission did occur, the rate of remission was less than the incidence of new cases—so much for asthma disappearing at puberty! Atopy also tended to accumulate with a higher incidence than remission rates. In contrast, bronchial hyperreactivity did remit, and did so at a substantially faster rate than the incidence of new cases.
However, the real fascination of this paper is in the examination of risk factors for persistence of wheeze and for late onset wheeze. There is no need to repeat the contents of the paper here; suffice it to say that we now have information that will be potentially useful to practising clinicians whose patients ask those awkward and hitherto unanswerable questions about their future. Unfortunately, these prognostications depend, to a large extent, on the assessment of bronchial hyperreactivity, a time consuming procedure using materials that are not even licensed for the purpose and which few of us have the resources to include in the routine assessment of asthmatic patients.
The greatest value of this study will therefore be to research workers. Numerous interesting questions are raised. Why, for instance, is being female a risk factor for late onset bronchial hyperreactivity, but being male a risk factor for late onset atopy? The sex difference for childhood asthma is narrowing20 and these unexplained gender differences may shed some light on the current “epidemic” of asthma and why it has apparently peaked,21 if indeed it has.22 And why should early onset atopy be a greater risk factor for subsequent wheeze than late onset atopy? It is clear that the genes have a lot to answer for; other things being equal, a positive family history of asthma continues to be an independent risk factor well into adult life.
This paper will provoke much discussion and will undoubtedly stimulate further research. It is enormously sad that the senior author did not survive to see it published.
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