Document Detail

The occurrence of refractoriness and mast cell mediator release following mannitol-induced bronchoconstriction.
MedLine Citation:
PMID:  21252215     Owner:  NLM     Status:  MEDLINE    
For several hours after exercise-induced bronchoconstriction, there is diminished responsiveness to repeated challenge. The mechanism causing this refractoriness is unclear. Inhalation of dry powder mannitol is a new bronchial provocation test that has been suggested as a surrogate for an exercise challenge. Refractoriness to repeated mannitol challenge has however not been established. Our objective was to investigate if repeated challenge with mannitol is associated with refractoriness and diminished release of mast cell mediators of bronchoconstriction. Sixteen subjects with asthma underwent repeated inhalation of mannitol 90 min apart. Lung function was assessed by forced expiratory volume in 1 s (FEV₁). The urinary excretion (ng/mmol creatinine) of the mediators 9α,11β-prostaglandin (PG) F₂ and leukotriene (LT) E₄ were measured. The group mean fall in FEV₁ after the second challenge was 48.5 ± 5.8% of the first (P < 0.001). The protection afforded by the initial challenge, however, varied considerably between subjects (range 88-0%). Furthermore, the urinary excretion of the two mediators was increased after both challenges. The average excretion of mediators after the challenges was significantly higher for the six most refractory subjects. This was observed both for LTE₄ (95.6 ± 5.2 vs. 58.0 ± 2.4 for the 6 least refractory) (P < 0.001) and for 9α,11β-PGF₂ (137.6 ± 6.7 vs. 50.1 ± 1.1 for the 6 least refractory) (P = 0.002). As occurs with exercise-induced bronchoconstriction, repeated inhalation of mannitol induced refractoriness. We propose that refractoriness is due to tachyphylaxis at the level of the airway smooth muscle responsiveness to mediators of bronchoconstriction rather than due to fatigue of their release from mast cells.
Johan Larsson; Clare P Perry; Sandra D Anderson; John D Brannan; Sven-Erik Dahlén; Barbro Dahlén
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-01-20
Journal Detail:
Title:  Journal of applied physiology (Bethesda, Md. : 1985)     Volume:  110     ISSN:  1522-1601     ISO Abbreviation:  J. Appl. Physiol.     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-04-13     Completed Date:  2011-08-15     Revised Date:  2013-09-26    
Medline Journal Info:
Nlm Unique ID:  8502536     Medline TA:  J Appl Physiol (1985)     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1029-35     Citation Subset:  IM    
The Unit for Experimental Asthma and Allergy Research, Division of Physiology, The National Institute of EnvironmentalMedicine, Sweden.
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MeSH Terms
Administration, Inhalation
Asthma / immunology,  physiopathology*,  urine
Bronchoconstriction / drug effects,  immunology*
Dinoprost / urine
Forced Expiratory Volume
Leukotriene E4 / urine
Mannitol / administration & dosage*
Mast Cells / drug effects,  immunology*
Reg. No./Substance:
551-11-1/Dinoprost; 69-65-8/Mannitol; 75715-89-8/Leukotriene E4

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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