{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T02:34:48Z","timestamp":1791254088311,"version":"4.1.0"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[1999,4,1]],"date-time":"1999-04-01T00:00:00Z","timestamp":922924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1999,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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, \u03b22-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 \u2264 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 \u03bc m (0.2 to 3.1) \u03bc m]). The changes in AHR in both strategy groups were correlated with eosinophil counts in the biopsies (r = \u2212 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.<\/jats:p>","DOI":"10.1164\/ajrccm.159.4.9806052","type":"journal-article","created":{"date-parts":[[2013,4,4]],"date-time":"2013-04-04T13:53:06Z","timestamp":1365083586000},"page":"1043-1051","source":"Crossref","is-referenced-by-count":682,"title":["Clinical Control and Histopathologic Outcome of Asthma when Using Airway Hyperresponsiveness as an Additional Guide to Long-Term Treatment"],"prefix":"10.1093","volume":"159","author":[{"given":"JACOB K.","family":"SONT","sequence":"first","affiliation":[{"name":"Departments of Pulmonology, Clinical Epidemiology, and Pathology, Leiden University Medical Center; and Asthma Management Project University Leiden (AMPUL) Study Group, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"LUUK N. A.","family":"WILLEMS","sequence":"additional","affiliation":[{"name":"Departments of Pulmonology, Clinical Epidemiology, and Pathology, Leiden University Medical Center; and Asthma Management Project University Leiden (AMPUL) Study Group, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ELISABETH H.","family":"BEL","sequence":"additional","affiliation":[{"name":"Departments of Pulmonology, Clinical Epidemiology, and Pathology, Leiden University Medical Center; and Asthma Management Project University Leiden (AMPUL) Study Group, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.HAN J. M.","family":"van KRIEKEN","sequence":"additional","affiliation":[{"name":"Departments of Pulmonology, Clinical Epidemiology, and Pathology, Leiden University Medical Center; and Asthma Management Project University Leiden (AMPUL) Study Group, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JAN P.","family":"VANDENBROUCKE","sequence":"additional","affiliation":[{"name":"Departments of Pulmonology, Clinical Epidemiology, and Pathology, Leiden University Medical Center; and Asthma Management Project University Leiden (AMPUL) Study Group, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"PETER J.","family":"STERK","sequence":"additional","affiliation":[{"name":"Departments of Pulmonology, Clinical Epidemiology, and Pathology, Leiden University Medical Center; and Asthma Management Project University Leiden (AMPUL) Study Group, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[1999,4,1]]},"reference":[{"key":"2026032708532896200_B1"},{"key":"2026032708532896200_B2","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1164\/ajrccm\/142.2.434","article-title":"Mucosal inflammation in asthma [State of the art].","volume":"142","author":"Djukanovi\u0107","year":"1990","journal-title":"Am. 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