Diagnostic comparison of methacholine and mannitol bronchial challenge tests for identifying bronchial hyperresponsiveness in asthma: a systematic review and meta-analysis

Abstract

Objective

Bronchial hyperresponsiveness (BHR) is a representative feature of asthma. Although methacholine and mannitol are commonly used for bronchial challenge tests, the optimal roles of the two agents for assessing BHR remain unclear. We compared the diagnostic performance of methacholine and mannitol in bronchial challenge tests.

Methods

A systematic literature search was performed using MEDLINE, EMBASE, and the Cochrane Central Register. The sensitivity, specificity, diagnostic odds ratio (DOR), and a hierarchical summary of the receiver-operating characteristic curve (HSROC) of the two agents for detecting BHR in asthma were pooled using meta-analysis. A meta-regression analysis was used to identify potential sources of heterogeneity within the selected studies.

Results

We identified six studies comprising 565 patients. The pooled sensitivity, specificity, and DOR of methacholine were 0.61 (95%CI, 0.44-0.76), 0.93 (95%CI, 0.70–0.99), and 23.47 (95% CI, 2.51–219.89), respectively. The pooled sensitivity, specificity, and diagnostic odds ratio of mannitol were 0.50 (95%CI, 0.28–0.73), 0.97 (95% CI, 0.94–0.99), and 35.22 (95% CI, 8.82–140.62), respectively. The area under the HSROC for mannitol was higher than that for methacholine (0.97 vs. 0.81, p < 0.01). Considerable between-study heterogeneity was present for sensitivity and specificity in studies of both index tests. Univariate meta-regression analysis revealed that age and sex of the study participants were probable sources of heterogeneity for specificity in studies of methacholine.

Conclusion

Although mannitol showed better diagnostic performance than methacholine for identifying BHR in asthma, substantial between-study heterogeneity necessitates caution when interpreting the data.

Keywords:

• Asthma
• bronchial hyperreactivity
• bronchial provocation tests
• methacholine chloride
• mannitol

Acknowledgments

The authors would like to thank Sung Ryul Shim for assistance with statistical analysis.

Conflicts of interests

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Notes on contributors

J-U.S contributed to data acquisition, data interpretation, and statistical analysis and drafted the manuscript. J.L. contributed to the study design, data acquisition, data interpretation, statistical analysis, writing of the manuscript, and critical revision of the manuscript.

Additional information

Funding

This work was supported by a research grant from the Jeju National University Hospital Research Fund of Jeju National University in 2019.