Sodium cromoglycate alone and in combination with montelukast on the airway response to mannitol in asthmatic subjects.
BACKGROUND
Mannitol, inhaled as a dry powder, is used for bronchial provocation to identify bronchial hyperresponsiveness. Bronchoconstriction is associated with an increase in urinary excretion of the metabolites of prostaglandin D(2) and leukotriene E(4). Sodium cromoglycate provides about 60% protection against the fall in forced expiratory volume in one second (FEV(1)) provoked by inhaled mannitol and appears to do so by inhibiting the release of prostaglandin D(2) but not leukotriene E(4).The leukotriene receptor antagonist montelukast does not alter sensitivity to mannitol, as measured by the provoking dose to cause a 15% fall in FEV(1) to mannitol, but it significantly enhances recovery from the bronchoconstriction provoked by mannitol.


OBJECTIVE
The authors proposed that the combination of these two drugs would be superior to sodium cromoglycate alone and result in greater protection from the bronchoconstriction provoked by mannitol.


METHODS
The % fall in FEV(1) from baseline and the area under the 30-min FEV(1) time curve and time to recover to 95% baseline FEV(1) were used to express protection from 40 mg sodium cromoglycate alone, and in combination with 10 mg montelukast, in subjects with asthma. Mannitol was inhaled in the dose that caused a 20% fall in FEV(1) on the screening day. The prechallenge medications were randomised on the 3 treatment days and were (1) placebo sodium cromoglycate and placebo montelukast; (2) sodium cromoglycate and placebo montelukast; and (3) sodium cromoglycate and montelukast.


RESULTS
The protection by sodium cromoglycate alone on the % fall in FEV(1) was 64.4% +/- 21.0% versus 65.8% +/- 62.8% (p = NS) on the combination. The protection on the area under the 30-min FEV(1) time curve for sodium cromoglycate was 81.8% +/- 14.0% (p <.04) and 89.3% +/- 9.8% for the combination (p <.001) compared with placebo. Recovery to 95% baseline FEV(1) by 5/10 min occurred in 58%/66% of subjects on sodium cromoglycate and 66%/83% on the combination compared with 0%/0% on placebo.


CONCLUSIONS
The addition of montelukast to sodium cromoglycate provided only a small additional benefit against the airway response to mannitol.
Anderson
Sandra D
SD
Department of Respiratory and Sleep Medicine, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia. sandya@med.usyd.edu.au
Brannan
John D
JD
Perry
Clare P
CP
Caillaud
Corinne
C
Seale
J Paul
JP
D000085:Acetates / Q000008:administration & dosage / Q000627:therapeutic use*; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects; D004205:Cromolyn Sodium / Q000008:administration & dosage / Q000627:therapeutic use*; D003521:Cyclopropanes; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D008353:Mannitol; D011804:Quinolines / Q000008:administration & dosage / Q000627:therapeutic use*; D013440:Sulfides
D000085:Acetates; D018927:Anti-Asthmatic Agents; D003521:Cyclopropanes; D004338:Drug Combinations; D011804:Quinolines; D013440:Sulfides; D008353:Mannitol; C093875:montelukast; D004205:Cromolyn Sodium