Authors’ reply

We would like to thank Dr Strube for his interest in our recent paper¹ and his stimulating letter which is topical given that the new BTS guidelines on asthma management are currently in preparation.

Our study was an attempt to investigate the interrelationships between airway inflammation, airway structural change (remodelling), lung function, and bronchial hyperreactivity to methacholine in patients with mild to moderate symptomatic asthma. This included a longitudinal limb characterising the temporal effects of inhaled corticosteroid (ICS) treatment using a high proof of concept dosage (750 μg fluticasone propionate twice daily). The physiology, airway inflammation, and remodelling in asthma were found to be interrelated and improved by ICS, but the changes were not temporally concordant, with prolonged treatment necessary for maximal benefit in remodelling and bronchial hyperresponsiveness (BHR). We felt that the results support early and long term intervention with ICS, even in relatively mild asthmatics. This is a view shared by some and, arguably, provides a complementary pathophysiological and mechanistic context to recent clinical studies such as the OPTIMA trial.² This year long study found that ICS treatment, even in mild asthmatics who had not previously been treated with corticosteroids, was associated with a significant effect on clinical exacerbations.

In his letter Dr Strube states that “without anti-inflammatory treatment, symptoms resulting from bronchial hyperresponsiveness are never controlled and optimal lung function is never attained”. Our interpretation of the current BTS guidelines³ is that guidelines not only provide for—but also, indeed, indicate—regular ICS medication in such circumstances, with no prescriptive requirement to work linearly through the stages. This is because the outcome of the escalatory stepwise management is to attain control of symptoms and lung function: “The importance of gaining control of asthma is re-emphasised . . . by starting treatment at a level likely to achieve this”.³ It also seemed appropriate to consult the pre-publication draft of the 2002 update of the guidelines which have been available at the BTS website for comment.⁴ These state at step 2: “The threshold for introduction of inhaled steroids has never been firmly established” and that “patients with lower inhaler requirements (short acting β₂ agonist less than 2–3 times a day) may benefit”. Hence, the latest available guidelines further emphasise the importance of anti-inflammatory treatment with scope for early intervention based on clinical judgement. It would appear to us that Dr Strube‘s valid concerns about the potential of undertreatment in some asthmatics, also apparent in studies such as OPTIMA,² is also articulated in the BTS guidelines, but expressed slightly differently.

Our paper is supportive of a further point, adding to work from others,⁵ which we feel is potentially substantive, of possible importance to future guideline considerations, and perhaps relates to some of Dr Strube‘s concerns. The potential paradigm shift is that determining appropriate treatment only by reference to symptoms and lung function, as in current international and draft BTS guidelines, or even against indices of inflammation, may be oversimplistic, with prolonged treatment necessary to benefit airway remodelling reflected by improvement in BHR. It should be recognised that this remains a hypothesis and, pragmatically, it is of interest that the inclusion of BHR as an asthma management tool in the UK is not resourced and is not currently practicable.^6,7

We also realise that the demanding and detailed preparation of the BTS asthma guidelines has followed a due process, reliant on the available evidence base with “levels of evidence” leading to “grades of recommendation” and, in turn, to “recommended best practice”. If appropriate pathophysiological research relevant to the clinical questions does not exist, it cannot be included. We feel that longitudinal data that seek to integrate information on airway inflammation, airway remodelling, lung function, and bronchial hyperreactivity and the effects of treatment are required. Such work, though demanding, is possible and would require multidisciplinary cooperation, dialogue, and appropriate support.