Clinical control and histopathologic outcome of asthma when using airway hyperresponsiveness as an additional guide to long-term treatment. The AMPUL Study Group.
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, beta2-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 </= 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 micrometers (0.2 to 3.1) micrometers]). 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.
Sont
J K
JK
Departments of Pulmonology, Clinical Epidemiology, and Pathology, Leiden University Medical Center; and Asthma Management Project University Leiden (AMPUL) Study Group, Leiden, The Netherlands.
Willems
L N
LN
Bel
E H
EH
van Krieken
J H
JH
Vandenbroucke
J P
JP
Sterk
P J
PJ
D000280:Administration, Inhalation; D000287:Administration, Topical; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D001249:Asthma / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D001706:Biopsy; D001980:Bronchi / Q000473:pathology*; D016535:Bronchial Hyperreactivity / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D001993:Bronchodilator Agents / Q000008:administration & dosage; D005260:Female; D005541:Forced Expiratory Volume; D005938:Glucocorticoids; D006801:Humans; D007249:Inflammation; D008297:Male; D016210:Methacholine Chloride; D010366:Peak Expiratory Flow Rate; D017410:Practice Guidelines as Topic; D011446:Prospective Studies; D016037:Single-Blind Method; D013256:Steroids
D000893:Anti-Inflammatory Agents; D001993:Bronchodilator Agents; D005938:Glucocorticoids; D013256:Steroids; D016210:Methacholine Chloride