Response to mannitol in asymptomatic subjects with airway hyper-responsiveness to methacholine.
BACKGROUND
Bronchial provocation using methacholine, a cholinergic agonist, causes airway narrowing directly by contraction of bronchial smooth muscle. While methacholine has a high sensitivity for identifying airway hyper-responsiveness (AHR), it does not have a high specificity to diagnose asthma and false-positive responses may be observed in non-asthmatics. Mannitol is an osmotic stimulus that acts indirectly to cause airway narrowing by release of endogenous bronchoconstricting mediators.


OBJECTIVE
We tested the hypothesis that subjects with asymptomatic AHR to methacholine would not have AHR to mannitol.


METHODS
Sixteen subjects with a methacholine PD(20) <8 micro mol were challenged with mannitol. A positive response to mannitol was defined as a 15% decline in forced expiratory volume in 1 s (FEV(1)) after <635 mg (PD(15)). Expired nitric oxide (eNO) and blood eosinophils were also measured.


RESULTS
The GM PD(20) for methacholine was 2.25 micro mol [95% confidence interval (CI): 2.19-5.29], the mean eNO was 14.7 p.p.b. (CI: 10.1-19.4) and the eosinophil count was 0.20 x 10(-9)/L (CI: 0.14-0.27 x 10(-9)/L). Only one subject (a smoker, 10 pack-years, FEV(1) 76% pred, non-allergic rhinitis, normal eNO and eosinophil count) also had a mild positive response to mannitol (PD(15): 451 mg).


CONCLUSIONS
The response to mannitol was within the normal range in asymptomatic subjects with AHR to methacholine. Further evidence on the responsiveness to mannitol compared with methacholine in a random population sample is required to elucidate whether mannitol is a more specific test for diagnosing asthma.
Porsbjerg
C
C
Respiratory Research Unit, Bispebjerg Hospital University of Copenhagen, Copenhagen NV, Denmark. porsbjerg@dadlnet.dk
Rasmussen
L
L
Thomsen
S F
SF
Brannan
J D
JD
Anderson
S D
SD
Backer
V
V
D000328:Adult; D001249:Asthma / Q000175:diagnosis*; D001944:Breath Tests; D016535:Bronchial Hyperreactivity / Q000139:chemically induced*; D001985:Bronchial Provocation Tests; D016085:Bronchoconstrictor Agents; D004234:Diuretics, Osmotic; D004305:Dose-Response Relationship, Drug; D004802:Eosinophilia; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008297:Male; D008353:Mannitol; D016210:Methacholine Chloride; D008875:Middle Aged; D009569:Nitric Oxide / Q000032:analysis; D012680:Sensitivity and Specificity; D012907:Smoking
D016085:Bronchoconstrictor Agents; D004234:Diuretics, Osmotic; D016210:Methacholine Chloride; D009569:Nitric Oxide; D008353:Mannitol