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Published on: April 13, 2010
Airway refractoriness to inhaled mannitol after repeated challenge
Dong In Suh1, Ju Kyung Lee, Jin-Tack Kim
1Department of Pediatrics, Seoul National University Hospital, Seoul, Korea.
Pediatric Pulmonology
|April 27, 2011
Summary
Repeatedly inhaling mannitol causes airway refractoriness in children with asthma, similar to exercise. This suggests a shared mechanism for bronchoconstriction that can be overcome with repeated exposure.
Area of Science:
- Pulmonary Medicine
- Pediatric Respiratory Research
- Asthma Pathophysiology
Background:
- Exercise and inhaled mannitol are known to induce bronchoconstriction in asthma.
- Exercise-induced bronchoconstriction exhibits refractoriness after repeated challenges.
- The mechanism of mannitol-induced bronchoconstriction is thought to be similar to exercise-induced bronchoconstriction.
Purpose of the Study:
- To investigate if repeated inhaled mannitol challenges induce airway refractoriness in children with asthma.
- To compare the bronchoconstrictive response to repeated mannitol challenges.
- To explore potential mechanisms underlying mannitol-induced refractoriness.
Main Methods:
- Forty-one children with asthma underwent two consecutive inhaled mannitol dose-response challenges.
- Bronchoconstriction was measured by the provocative dose causing a 15% fall in FEV1 (PD15) and the response-dose ratio (RDR).
- A subset of subjects underwent methacholine challenges to assess non-specific effects.
Main Results:
- Repeated mannitol challenges resulted in significantly higher PD15 values and lower RDR, indicating reduced bronchoconstriction.
- The geometric mean PD15 increased from 66 mg in the first challenge to 163 mg in the second challenge (P < 0.001).
- The geometric mean RDR decreased from 0.083%/mg to 0.029%/mg (P < 0.001) in the second challenge.
Conclusions:
- Repeated inhaled mannitol challenges induce airway refractoriness in children with asthma.
- This refractoriness to mannitol is analogous to exercise-induced refractoriness.
- The findings suggest a common mechanism for refractoriness to both stimuli, not explained by functional unresponsiveness or non-specific effects.
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