Provocative Dose of Methacholine Causing a 20% Drop in FEV1 Should Be Used to Interpret Methacholine Challenge Tests with Modern Nebulizers
Bibliographic record
Abstract
RATIONALE: The American Thoracic Society guidelines (1999) for methacholine challenge tests (MCTs) using the 2-minute tidal breathing protocol were developed for the now-obsolete English-Wright (EW) nebulizer. In addition, the guideline recommendation to use the provocative concentration of methacholine causing a 20% drop in FEV1 (PC20) rather than the provocative dose of methacholine causing a 20% drop in FEV1 (PD20) for determining the level of bronchial hyperresponsiveness has been challenged. OBJECTIVES: To determine if cumulative dose or concentration of methacholine delivered to the airways is the determinant for airway responsiveness and to validate use of the AeroEclipse* II BAN (Aero; Trudell Medical International, London, ON, Canada) nebulizer compared with use of the reference standard EW nebulizer. METHODS: Subjects with asthma (10-18 yr old) participated in randomized, controlled cross-over experiments comparing four MCT protocols using standard methacholine concentrations, but varying: (1) methacholine starting concentration (testing for cumulative effect); (2) nebulizer (EW versus Aero); and (3) inhalation time. PD20 was calculated using nebulizer output rate, inhalation time, and preceding doses delivered. ANOVA analyses were used to compare geometric means of PC20 and PD20 between protocols. RESULTS: A total of 32 subjects (17 male) participated. PC20 differed when starting concentration varied (0.46 vs. 0.80 mg/ml; P<0.0001), whereas PD20 did not (0.06 vs. 0.08 mg). PC20 differed with the EW versus the Aero nebulzer with 30-second inhalation (1.19 vs. 0.43 mg/ml; P=0.0006) and the EW versus the Aero nebulizer with 20-second inhalation (1.91 vs. 0.89 mg/ml; P=0.0027), whereas PD20 did not (0.07 vs. 0.06 mg and 0.11 vs. 0.09 mg, respectively). CONCLUSIONS: In MCTs, the cumulative dose (PD20), not the PC20, determines bronchial responsiveness. Modern nebulizers may be used for the test if clinical interpretation is based on PD20. Clinical trial registered with www.clinicaltrials.gov (NCT01288482).
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".