Objective measures and the diagnosis of asthma

We need a simple diagnostic test—but don't yet have one

Diseases represent extremes of continuously distributed characteristics, and defining exactly where and why in that distribution normality ends and disease begins may be difficult. The use of objective markers can be helpful, but these often force us to change our concept of a disease to accommodate the new information they provide—such as the identification of subclinical disease or adverse prognostic factors in otherwise healthy people. These conceptual changes are part of the natural evolution of disease definition and are justified if, in the long run, patients benefit.

Asthma has always been a clinical diagnosis, recognised on the basis of a characteristic history of variable wheezing, cough, and breathlessness and supported by objective, though non-standardised, evidence of variations in airflow. Many attempts have been made to define this diagnosis. Since 19581 all have highlighted the fundamental abnormality of variable airflow obstruction, and some have also invoked concepts such as airway hyperresponsiveness2 or airway pathology.3 None has yet provided objective criteria for the component parts of this process, and there remains no standardised definition of the type, frequency, or severity of symptoms or the degree of airflow variability necessary to diagnose asthma.

Nevertheless, measurements of peak flow variability and airway responsiveness have gained widespread use as markers of asthma, particularly in epidemiological studies, and a recent editorial in the BMJ suggested that where doubts linger after a careful history and spirometry a “positive” result from peak flow monitoring or methacholine challenge (a measure of airway responsiveness) is enough to diagnose asthma.4 Is this assertion justifiable, and what are its implications for our concept of asthma?

There are unresolved methodological issues arising from the need to provide standardised methods of measuring and expressing peak flow variability or airway responsiveness, not to mention the arbitrariness of current definitions of positivity for these tests. More important, however, is the fact that if we define asthma in terms of extreme values of these objective measures we would have to label as asthmatic many people who we do not now recognise as clinically asthmatic.

Individuals with hyperresponsiveness or increased peak flow variability include not only those with a diagnosis of asthma but also those who are simply atopic, smoke, are older, are female, have other diagnosed obstructive airways diseases, or indeed have normal but low lung function. 56 Some are completely normal, and many are asymptomatic. Even among people reporting symptoms, those with increased peak flow variability may be more likely to report current or relatively recent wheeze or cough, whereas those with hyperresponsiveness are likely to report longer term morbidity,7 which includes asthma but also the non-specific condition described by breathing that is “never quite right.”8

These observations, combined with the lack of specificity to clinical asthma and the poor concordance between the populations identified as abnormal by these different objective measures, 7910 show that populations defined by symptoms or either increased peak flow variability or hyperresponsiveness are different from, and generally embrace a much broader range of disorder than, our current concept of asthma, however ill defined. Have we reached a stage in our understanding of the pathogenesis, prognosis, or natural history of this disorder at which such a major change in the characteristics of the population we define as having asthma is justified?

There is no evidence that we have. Except for one study of newly presenting symptomatic asthma,which suggested that early intervention with inhaled steroids may preserve lung function in the longer term,11 there is no evidence that any therapeutic intervention in asthma does anything other than improve morbidity in people with symptoms. If we adopt an operational definition based on a response to treatment, therefore, there is no asthma without symptoms, no point in attempting to recognise asymptomatic disorder, and no justification for including asymptomatic individuals in our definition of disease.

If we are to adopt a prognostic definition based on these objective measures, we need to know the independent relation between hyperresponsiveness or increased peak flow variability and the long term risk of morbidity or mortality, over and above that provided by the characteristics used to make a clinical diagnosis. To date these relations are poorly defined. If we opt for a statistical definition, declaring that the highest 5% or 10% of the distributions of airway responsiveness or peak flow variability indicate asthma, we will have a definition that is attractively convenient but divorced from concepts of clinical abnormality without obvious justification. Thus, on present evidence, there seem to be few compelling reasons to abandon clinical criteria.

This is not to argue that attempts to refine the diagnosis of asthma should be abandoned. Peak flow variability does at least reflect the expression of the fundamental abnormality of asthma encompassed in the available definitions,^1–%3 and peak flow is an established means of monitoring asthma therapy. If the identification of early, asymptomatic, or just different disease by objective methods proves to have a practical application then our concept of disease should change to accommodate this. We have no such evidence, however, and the suggestion that decisions on long term management of people with equivocal symptoms should be based on the results of such tests4 is simply unjustified. We certainly need a simple objective diagnostic test for asthma, but we don't have one yet.