Comparison of methacholine and mannitol challenges: importance of method of methacholine inhalation
Bibliographic record
Abstract
BACKGROUND: Direct inhalation challenges (e.g. methacholine) are stated to be more sensitive and less specific for a diagnosis of asthma than are indirect challenges (e.g. exercise, non-isotonic aerosols, mannitol, etc.). However, data surrounding comparative sensitivity and specificity for methacholine compared to mannitol challenges are conflicting. When methacholine is inhaled by deep total lung capacity (TLC) inhalations, deep inhalation inhibition of bronchoconstriction leads to a marked loss of diagnostic sensitivity when compared to tidal breathing (TB) inhalation methods. We hypothesized that deep inhalation methacholine methods with resulting bronchoprotection may be the explanation for conflicting sensitivity/specificity data. METHODS: We reviewed 27 studies in which methacholine and mannitol challenges were performed in largely the same individuals. Methacholine was inhaled by dosimeter TLC methods in 13 studies and by tidal breathing in 14 studies. We compared the rates of positive methacholine (stratified by inhalation method) and mannitol challenges in both asthmatics and non-asthmatics. RESULTS: When methacholine was inhaled by TLC inhalations the prevalence of positive tests in asthmatics, 60.2% (548/910), was similar to mannitol, 58.9% (537/912). By contrast, when methacholine was inhaled by tidal breathing the prevalence of positive tests in asthmatics 83.1% (343/413) was more than double that of mannitol, 41.5% (146/351). In non-asthmatics, the two methacholine methods resulted in positive tests in 18.8% (142/756) and 16.2% (27/166) by TLC and TB inhalations respectively. This compares to an overall 8.3% (n = 76) positive rate for mannitol in 913 non-asthmatics. CONCLUSION: These data support the hypothesis that the conflicting data comparing methacholine and mannitol sensitivity and specificity are due to the method of methacholine inhalation. Tidal breathing methacholine methods have a substantially greater sensitivity for a diagnosis of asthma than either TLC dosimeter methacholine challenge methods or mannitol challenge. Methacholine challenges should be performed by tidal breathing as per recent guideline recommendations. Methacholine (more sensitive) and mannitol (more specific) will thus have complementary diagnostic features.
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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 | 0.043 | 0.096 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.004 | 0.003 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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".