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

被引:685
作者
Sont, JK
Willems, LNA
Bel, EH
van Krieken, JHJM
Vandenbroucke, JP
Sterk, PJ
机构
[1] Leiden Univ, Med Ctr, Dept Pulmonol, Lung Funct Lab, NL-2300 RC Leiden, Netherlands
[2] St Antoniushove Hosp, Leidschendam, Netherlands
[3] Langeland Hosp, Zoetermeer, Netherlands
[4] Diaconessenhuis Hosp, Leiden, Netherlands
[5] Leiden Univ, Med Ctr, Dept Clin Epidemiol, NL-2300 RC Leiden, Netherlands
[6] Leiden Univ, Med Ctr, Dept Pathol, NL-2300 RC Leiden, Netherlands
[7] Leiden Univ, Med Ctr, Dept Hematol, NL-2300 RC Leiden, Netherlands
关键词
D O I
10.1164/ajrccm.159.4.9806052
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
According to international guidelines, the level and adjustment of antiinflammatory treatment for asthma are based solely on symptoms and lung function. We investigated whether a treatment strategy aimed at reducing airway hyperresponsiveness (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 involving 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, and subjects kept diaries of symptoms, beta(2)-agonist use, and peak expiratory flow (PEF). Medication with corticosteroids (four levels) was adjusted according to a stepwise approach (reference strategy), to which four severity classes of AHR were added (AHR strategy). At entry and after 2 yr, bronchial biopsies were obtained by fiberoptic bronchoscopy. Patients treated according 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 exacerbation/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 bronchial biopsies this was accompanied by a greater reduction in thickness of the subepithelial reticular layer in the AHR strategy group than in the reference 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 correlated with eosinophil counts in the biopsies (r = -0.48, p = 0.003). We conclude that reducing AHR in conjunction with optimizing symptoms and lung function leads to more effective control of asthma while alleviating chronic airways inflammation. This implies a role for the monitoring of AHR or other surrogate markers of inflammation in the long-term management of asthma.
引用
收藏
页码:1043 / 1051
页数:9
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