Document Detail

Different response to doubling and fourfold dose increases in methacholine provocation tests in healthy subjects.
MedLine Citation:
PMID:  11083688     Owner:  NLM     Status:  MEDLINE    
RATIONALE: In a modified methacholine provocation test that was used to study changes in airway responsiveness to occupational irritants or sensitizers in healthy subjects, two protocols were used: a long protocol (doubling methacholine concentrations between dose steps) or a short protocol (fourfold increases in concentration). This modified methacholine provocation allows measurements of the provocative dose causing 20% decrease in FEV(1) (PD(20)) in a high proportion of a normal population. METHODS: The distribution of PD(20) was investigated in healthy nonatopic men without history of allergy or asthma symptoms using the long protocol (n = 101) or the short protocol (n = 309). In addition, 30 healthy subjects underwent methacholine provocation tests using both protocols. RESULTS: PD(20) was defined in 79% of subjects with the long protocol and in 48% of subjects with the short protocol. The provocative concentration of methacholine causing a 20% decline in FEV(1) (PC(20)) and PD(20) were significantly lower using the long protocol: long-protocol PC(20) (median [25th to 75th percentile]), 19.9 mg/mL (3.9 to > 32 mg/mL) compared with short-protocol PC(20), > 32 mg/mL (8.7 to >32 mg/mL; p < 0.0001); long-protocol PD(20), 4.2 mg (1.6 to 20 mg) compared with short-protocol PD(20), > 13.7 (2.6 to > 13.7 mg; p = 0. 006). The differences in PD(20) using short and long protocols were confirmed in a randomized trial of 30 healthy subjects tested with both protocols. CONCLUSION: Using doubling concentrations, PC(20) and PD(20) could be defined in a higher proportion of healthy subjects than a protocol using fourfold dose increases. Furthermore, the doubling protocol results in a PD(20) estimate that is less than half the value obtained when using a protocol with fourfold concentrations between dose steps. The difference remains, whether the methacholine effect is regarded as cumulative or noncumulative. The explanation for the difference between the protocols is unclear.
B M Sundblad; P Malmberg; K Larsson
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Publication Detail:
Type:  Clinical Trial; Comparative Study; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Chest     Volume:  118     ISSN:  0012-3692     ISO Abbreviation:  Chest     Publication Date:  2000 Nov 
Date Detail:
Created Date:  2000-11-29     Completed Date:  2000-12-14     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0231335     Medline TA:  Chest     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1371-7     Citation Subset:  AIM; IM    
Programme for Respiratory Health and Climate, National Institute for Working Life, Stockholm, Sweden.
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MeSH Terms
Allergens / adverse effects
Bronchial Hyperreactivity / physiopathology
Bronchial Provocation Tests / methods*
Bronchoconstrictor Agents / administration & dosage,  diagnostic use*
Chi-Square Distribution
Dose-Response Relationship, Drug
Forced Expiratory Volume / drug effects
Irritants / adverse effects
Methacholine Chloride / administration & dosage,  diagnostic use*
Middle Aged
Occupational Exposure
Statistics, Nonparametric
Time Factors
Reg. No./Substance:
0/Allergens; 0/Bronchoconstrictor Agents; 0/Irritants; 62-51-1/Methacholine Chloride

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

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