{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T07:36:12Z","timestamp":1770968172623,"version":"3.50.1"},"reference-count":38,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2001,12,24]],"date-time":"2001-12-24T00:00:00Z","timestamp":1009152000000},"content-version":"vor","delay-in-days":510,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Experimental Allergy"],"published-print":{"date-parts":[[2000,8]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The precise mechanism of action of theophylline in asthma is not fully understood but recent data have drawn attention to its potential anti\u2010inflammatory effect.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>The purpose of this study was to assess the effect of theophylline on sputum eosinophilia and sputum eosinophil chemotactic activity in steroid\u2010naive asthmatics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>We performed a 4\u2010week randomized double\u2010blind, placebo\u2010controlled, parallel group study in 21 mild to moderate steroid\u2010naive asthmatics whose sputum eosinophilia was found twice &gt;\u20035% during the run in period. Eleven subjects received 600\u2003mg\/24\u2003h theophylline for the first 2 weeks and 900\u2003mg\/24\u2003h for the last 2 weeks while 10 subjects took a placebo for 4 weeks. Sputum was induced after 2 and 4 weeks of treatment and 1 week after stopping the treatment. The sputum samples were compared for their cell counts, eosinophil cationic protein (ECP) levels and eosinophil chemotactic activity using micro\u2010Boyden chambers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Serum theophylline concentrations reached 7 and 11\u2003\u03bcg\/mL at V3 and V4, respectively. Intragroup comparisons showed that theophylline, but not placebo, caused a significant reduction in sputum eosinophil counts at V3 (62\u2003\u00b1\u200310% from baseline, <jats:italic>P<\/jats:italic>\u2003&lt;\u20030.01) and a strong trend at V4 (67\u2003\u00b1\u200316% from baseline, <jats:italic>P<\/jats:italic>\u2003=\u20030.07) when compared to baseline. The intergroup difference obtained after comparing the area under the curve over the 4 week treatment period only approached the statistical significance (<jats:italic>P<\/jats:italic>\u2003=\u20030.08). At baseline the fluid phase of the sputum contained a significant eosinophil chemotactic activity which was inhibited after a 4\u2010week treatment by theophylline (<jats:italic>P<\/jats:italic>\u2003&lt;\u20030.01) but not by placebo. The mean sputum theophylline levels after 4 weeks of treament (1.7\u2003\u03bcg\/mL) was lower than that required to cause significant inhibition of eosinophil chemotaxis <jats:italic>in vitro<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Theophylline decreases the natural sputum eosinophil chemotactic activity present in asthmatics. However, when using a small sample size, the 35% reduction in sputum eosinophilia achieved by theophylline failed to reach statistical significance when compared to that seen after placebo.<\/jats:p><\/jats:sec>","DOI":"10.1046\/j.1365-2222.2000.00867.x","type":"journal-article","created":{"date-parts":[[2003,3,11]],"date-time":"2003-03-11T09:44:07Z","timestamp":1047375847000},"page":"1151-1160","source":"Crossref","is-referenced-by-count":15,"title":["Effect of a 4\u2010week treatment with theophylline on sputum eosinophilia and sputum eosinophil chemotactic activity in steroid\u2010naive asthmatics"],"prefix":"10.1111","volume":"30","author":[{"family":"Louis","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"family":"Bettiol","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"family":"Cataldo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"family":"Sele","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"family":"Henquet","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"family":"Radermecker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2001,12,24]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199605233342107"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197506052922305"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198107303050503"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.94.07030579"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm\/142.2.434"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0091-6749(90)90151-S"},{"key":"e_1_2_6_8_2","first-page":"36","article-title":"Drug Trials","volume":"11","author":"Adelroth E","year":"1998","journal-title":"Eur Respir J"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0091-6749(85)90779-1"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm\/136.6.1403"},{"key":"e_1_2_6_11_2","first-page":"245","article-title":"Theophylline inhibits early and late asthmatic reactions induced by allergens in asthmatic subjects","volume":"66","author":"Crescioli S","year":"1991","journal-title":"Ann Allergy"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.96.09030456"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(94)90127-9"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.151.6.7767539"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.96.09081672"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1136\/thx.47.1.25"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm\/147.5.1126"},{"issue":"26","key":"e_1_2_6_18_2","first-page":"9","article-title":"Methods for sputum induction and analysis of induced sputum: a method for assessing airway inflammation in asthma","volume":"11","author":"Kips J","year":"1998","journal-title":"Eur Respir J"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.155.2.9032180"},{"key":"e_1_2_6_20_2","first-page":"1575","article-title":"Fluoresence polarization immunoassay (FPIA) for theophylline; 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