Deep inhalation bronchodilation and oral corticosteroids in asthma.

A irway smooth-muscle hyperresponsiveness is a characteristic feature of asthma.1 Airway hyperresponsiveness is most commonly identified in the laboratory by the leftward shift of bronchoconstrictor (eg, methacholine) dose-response curves. A reduction in methacholine concentration producing a 20% fall in FEV1 indicates increased ease of development of bronchoconstriction.1–2 Subjects with asthma also demonstrate an increased magnitude of bronchoconstriction, with progressive elevation of the level and eventual disappearance of the methacholine doseresponse plateau.2 Another feature of the hyperresponsive airway smooth muscle in asthma is the bronchoactive effect of maximal lung inflation. In subjects with asthmatic airflow obstruction in the midst of an exacerbation, maximal inflation has a bronchoconstrictor effect.3 By contrast, in normal nonasthmatic subjects and subjects with mild asthma, maximal lung inflation has a potent bronchodilator effect.4 While the mechanism(s) of airway hyperresponsiveness remain incompletely understood, there is little doubt that airway inflammation is linked to the hyperresponsiveness. Antiinflammatory therapy (eg, inhaled corticosteroid) can shift the methacholine dose-response curves to the right,5 can cause a reduction in the height of the dose-response plateau,6 and can restore or improve deep inhalation bronchodilation and bronchoprotection, at least at the mildly hyperresponsive end of the spectrum.7 In this issue of CHEST (see page 58), Slats and colleagues8 used their established deep inhalation bronchodilation model to evaluate the effect of oral prednisone in a group of subjects with asthma who were stable and at least reasonably well controlled with inhaled corticosteroids. The primary end point was deep inhalation bronchodilation assessed by measuring flow at 40% vital capacity (V̇40) from the maximal flow volume curve (M) compared to V̇40 from the partial flow volume curve (P) and expressed as a ratio (M/P); a greater M/P ratio indicates more deep inhalation-induced bronchodilation. Following methacholine in a provocative concentration that reduced V̇40 by 40% (PC40), prednisone improved the magnitude of deep inhalation bronchodilation. Other surrogate measures of antiinflammatory effect were also improved by prednisone either withingroup (airway responsiveness measured by FEV1), or between prednisone and placebo groups (airway responsiveness measured by P and exhaled nitric oxide levels). This investigation demonstrates that deep inhalation bronchodilation, at least following methacholine-induced bronchoconstriction at the level of PC40 flow volume curve, improves with more intensive antiinflammatory therapy and might be yet another surrogate measure to assess antiinflammatory efficacy. The important clinical message is that there is still room for improvement in subjects whose asthma is stable and acceptably controlled on inhaled corticosteroid. The clinical applicability, however, of these data are not clear. This ties in to the important and as yet unanswered question as to what is the ideal or preferred method for monitoring asthma control. Guidelines recommend primarily symptoms (including morbidity and exacerbations) and spirometry. However, investigations such as that by Slats et al suggest additional benefits might be achieved by using additional measurements such as deep inhalation bronchodilation, airway responsiveness,9 exhaled nitric oxide,10 and others that were not evaluated in this study, such as indirect airway responsiveness,11 exhaled breath condensate,12 and the “gold standard” for airway inflammation, sputum eosinophils.13 As is frequently the case, a novel article such as this often raises as many questions as it answers, and further studies in this important area are necessary.