Asthma and lower airway disease
Airway hyperresponsiveness to mannitol and methacholine and exhaled nitric oxide: A random-sample population study

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Background

Studies of selected patient groups have shown that airway hyperresponsiveness (AHR) to mannitol is more specific than methacholine for the diagnosis of asthma, as well as more closely associated with markers of airway inflammation in asthma.

Objective

We sought to compare AHR to mannitol and methacholine and exhaled nitric oxide (eNO) levels in a nonselected population sample.

Methods

In 238 young adults randomly drawn from the nationwide civil registration list in Copenhagen, Denmark, AHR to mannitol and methacholine, as well as levels of eNO, were determined, and the association with asthma was analyzed.

Results

In diagnosing asthma the specificity of methacholine and mannitol was 80.2% (95% CI, 77.1% to 82.9%) and 98.4% (95% CI, 96.2% to 99.4%), respectively, with a positive predictive value of 48.6% versus 90.4%, whereas the sensitivity was 68.6% (95% CI, 57.1% to 78.4%) and 58.8% (95% CI, 50.7% to 62.6%), respectively. In asthmatic subjects AHR to mannitol was associated with increased eNO levels (positive AHR to mannitol: median, 47 ppb [interquartile range, 35-68 ppb]; negative AHR to mannitol: median, 19 ppb [interquartile range, 13-30 ppb]; P = .001), whereas this was not the case for AHR to methacholine (median of 37 ppb [interquartile range, 26-51 ppb] vs 24 ppb [interquartile range, 15-39 ppb], P = .13).

Conclusion

In this random population sample, AHR to mannitol was less sensitive but more specific than methacholine in the diagnosis of asthma. Furthermore, AHR to mannitol was more closely associated with ongoing airway inflammation in terms of increased eNO levels.

Section snippets

Study design

The study is a cross-sectional population study performed at the Respiratory Research Unit, Copenhagen University Hospital Bispebjerg, Denmark. The same data were used in the recently published characterization of the diagnostic properties of inhaled mannitol in asthmatic subjects.8 A sample of 1000 young adults between the ages of 14 and 24 years was randomly drawn from the civil registration list. All subjects received a validated self-administered asthma and rhinitis screening questionnaire

Population characteristics

Population characteristics are shown in Table I. Most asthmatic subjects had normal or near-normal lung function in terms of FEV1 and FEV1/forced vital capacity ratio, although the percent predicted FEV1 was slightly lower compared with that seen in nonasthmatic subjects. Most were nonsmokers, and the prevalence of smoking was comparable between asthmatic and nonasthmatic subjects. Atopy was observed in 77% of asthmatic subjects compared with 32% of nonasthmatic subjects.

Current asthma was

Discussion

This study compares the diagnostic properties of inhaled mannitol and methacholine in a random population sample and the correlation with the inflammatory marker eNO. We found that mannitol was significantly more specific in the diagnosis of asthma than methacholine because 98% of the subjects without asthma had a negative mannitol test response compared with 80% when using methacholine, and the respective PPVs were 91% for mannitol compared with 49% for methacholine. As expected based on

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    The Danish Agency for Science, Technology and Innovation, an institution under the Danish Ministry of Science, Technology and Innovation, supported the study with a 1-year scholarship. Pharmaxis provided the research team with an unrestricted grant, with which one of the research assistants was employed. Moreover, mannitol test kits were provided by Pharmaxis Ltd (Frenchs Forest, NSW, Australia).

    Disclosure of potential conflict of interest: C. Porsbjerg receives honoraria from Pharmaxis and receives research funding for the Danish Agency of Science and Technology. The rest of the authors have declared that they have no conflict of interest.

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