Clinical control and histopathologic outcome of asthma when using airway hyperresponsiveness as an additional guide to long-term treatment

According to international guidelines, the level and adjustment of antiinfl ammatory treatment for asthma are based solely on symptoms and lung functio n. We investigated whether a treatment strategy aimed at reducing airway hy perresponsiveness (AHR strategy) in addition to the recommendations in the existing guidelines (reference strategy) led to: (1) more effective control of asthma; and (2) greater improvement of chronic airways inflammation. To accomplish this, we conducted a randomized, prospective, parallel trial in volving 75 adults with mild to moderate asthma who visited a clinic every 3 mo for 2 yr. At each visit, FEV1 and AHR to methacholine were assessed, an d subjects kept diaries of symptoms, beta(2)-agonist use, and peak expirato ry flow (PEF). Medication with corticosteroids (four levels) was adjusted a ccording to a stepwise approach (reference strategy), to which four severit y classes of AHR were added (AHR strategy). At entry and after 2 yr, bronch ial biopsies were obtained by fiberoptic bronchoscopy. Patients treated acc ording to the AHR strategy had a 1.8-fold lower rate of mild exacerbations than did patients in the reference strategy group (0.23 and 0.43 exacerbati on/yr/patient, respectively). FEV1 also improved to a significantly greater extent in the AHR strategy group (p less than or equal to 0.05). In bronch ial biopsies this was accompanied by a greater reduction in thickness of th e subepithelial reticular layer in the AHR strategy group than in the refer ence strategy group (mean difference [95% confidence interval (CI): 1.7 mu m (0.2 to 3.1) mu m]). The changes in AHR in both strategy groups were corr elated with eosinophil counts in the biopsies (r = -0.48, p = 0.003). We co nclude that reducing AHR in conjunction with optimizing symptoms and lung f unction leads to more effective control of asthma while alleviating chronic airways inflammation. This implies a role for the monitoring of AHR or oth er surrogate markers of inflammation in the long-term management of asthma.