Effect of low-dose theophylline on airway inflammation in COPD.
OBJECTIVE
Recent studies have shown that theophylline may exert anti-inflammatory effects on neutrophils. We undertook to assess the effect of theophylline on airway inflammation in COPD.


METHODS
We performed a 4-week randomized double-blind, placebo-controlled study in 11 theophylline-naive patients with mild to moderate COPD. After a 1-week run-in period, six subjects were administered 400 mg/day theophylline (Theodur; Nikken Chemicals Co. Ltd, Tokyo, Japan) for 4 weeks, while five subjects were administered a placebo. Induced sputum was obtained before and after the run-in period and then after 2 and 4 weeks of treatment. Cell differential count and levels of interleukin-8, matrix metalloproteinase-9, neutrophil elastase (NE), myeloperoxidase (MPO), alpha1-antitrypsin (alpha1-AT), leukotriene B4 and tissue inhibitor of metalloproteinases-1 (TIMP-1) were assessed.


RESULTS
No variable was significantly different during the run-in period or with placebo treatment. In contrast, theophylline treatment significantly decreased NE and MPO levels at 4 weeks, although the cell differential count did not change appreciably as a result of treatment.


CONCLUSIONS
These results suggest that 4 weeks of theophylline treatment attenuates neutrophil-associated inflammation in the airways of mild to moderate COPD patients. However, the clinical benefits remain to be determined.
Kobayashi
Motoko
M
First Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
Nasuhara
Yasuyuki
Y
Betsuyaku
Tomoko
T
Shibuya
Eiji
E
Tanino
Yoshinori
Y
Tanino
Mishie
M
Takamura
Kei
K
Nagai
Katsura
K
Hosokawa
Takeshi
T
Nishimura
Masaharu
M
D000368:Aged; D000369:Aged, 80 and over; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D019272:Leukocyte Elastase / Q000032:analysis; D008297:Male; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D012129:Respiratory Function Tests; D013183:Sputum / Q000166:cytology / Q000187:drug effects*; D013806:Theophylline / Q000008:administration & dosage*
D001993:Bronchodilator Agents; D013806:Theophylline; D019272:Leukocyte Elastase