Controlled-release theophylline inhibits early morning airway obstruction and hyperresponsiveness in asthmatic subjects.
BACKGROUND
Nocturnal asthma reflects the severity of the disease, and thus its pharmacologic prevention represents one on the main goals of asthma management.


METHODS
To determine whether controlled-release theophylline inhibits the development of airway obstruction and/or airway hyperresponsiveness early in the morning, we examined 18 subjects reporting recurrent nocturnal asthma. In each subject, after five days' treatment with an 8 PM increasing dose of oral controlled-release theophylline, up to 10 +/- 1 mg/kg or placebo the night before the study day, we measured serum theophylline, FEV1 and PC20FEV1 at 6 AM, 2 PM and 10 PM.


RESULTS
At 6 AM, both FEV1 and PC20FEV1 were significantly higher on theophylline than on placebo (3.52 +/- 0.22 versus 3.17 +/- 0.25 L; P < .005 and 2.76 divided by 3.61 versus 1.55 divided by 3.73 mg/mL; P < .05, respectively). At 2 PM and 10 PM FEV1, but not PC20FEV1, was higher on theophylline than on placebo (3.73 +/- 0.21 versus 3.54 +/- 0.25 L; P < .05 and 3.40 +/- 0.22 versus 3.24 +/- 0.24 L; P < .05). Serum theophylline was 12.8 +/- 1.1 micrograms/ml, 8.9 +/- 0.77 and 9.5 +/- 0.85 at 6 AM, 2 PM and 10 PM, respectively.


CONCLUSIONS
We conclude that an evening dose of controlled-release theophyl line inhibits early morning airway obstruction and hyperresponsiveness, and that it may be helpful in the prevention of nocturnal asthma.
Crescioli
S
S
Institute of Occupational Medicine, St. Antonio Hospital, University of Padua, Italy.
Dal Carobbo
A
A
Maestrelli
P
P
Boschetto
P
P
Santagada
T
T
Steinijans
V W
VW
Hurst
T S
TS
Parise
G
G
Fabbri
L M
LM
D000280:Administration, Inhalation; D000284:Administration, Oral; D000328:Adult; D000402:Airway Obstruction / Q000150:complications / Q000517:prevention & control*; D001249:Asthma / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D002940:Circadian Rhythm; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume; D006261:Headache / Q000139:chemically induced; D006801:Humans; D008297:Male; D016210:Methacholine Chloride / Q000008:administration & dosage / Q000494:pharmacology; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D013806:Theophylline / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D014202:Tremor / Q000139:chemically induced
D003692:Delayed-Action Preparations; D016210:Methacholine Chloride; D013806:Theophylline