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Response to mannitol in asymptomatic subjects with airway hyper-responsiveness to methacholine


Celeste Porsbjerg, Respiratory Research Unit, Bispebjerg Hospital University of Copenhagen, Bispebjerg Bakke 23, 2400 Copenhagen NV, Denmark.


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.

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

Methods Sixteen subjects with a methacholine PD20 <8 μmol were challenged with mannitol. A positive response to mannitol was defined as a 15% decline in forced expiratory volume in 1 s (FEV1) after <635 mg (PD15). Expired nitric oxide (eNO) and blood eosinophils were also measured.

Results The GM PD20 for methacholine was 2.25 μmol [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 × 10−9/L (CI: 0.14–0.27 × 10−9/L). Only one subject (a smoker, 10 pack-years, FEV1 76% pred, non-allergic rhinitis, normal eNO and eosinophil count) also had a mild positive response to mannitol (PD15: 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.