Airway inflammation and hyperresponsiveness in subjects with respiratory symptoms and normal spirometry
Bibliographic record
Abstract
Background Subjects without a previous history of asthma, presenting with unexplained respiratory symptoms and normal spirometry, may exhibit airway hyperresponsiveness (AHR) in association with underlying eosinophilic (type 2 (T2)) inflammation, consistent with undiagnosed asthma. However, the prevalence of undiagnosed asthma in these subjects is unknown. Methods In this observational study, inhaled corticosteroid-naïve adults without previously diagnosed lung disease reporting current respiratory symptoms and showing normal pre- and post-bronchodilator spirometry underwent fractional exhaled nitric oxide (FENO) measurement, methacholine challenge testing and induced sputum analysis. AHR was defined as a provocative concentration of methacholine causing a 20% fall in forced expiratory volume in 1 s (PC20) <16 mg·mL−1and T2 inflammation was defined as sputum eosinophils >2% and/orFENO>25 ppb. Results Out of 132 subjects (mean±sdage 57.6±14.2 years, 52% female), 47 (36% (95% CI 28–44%)) showed AHR: 20/132 (15% (95% CI 9–21%)) with PC20<4 mg·mL−1and 27/132 (21% (95% CI 14–28%)) with PC204–15.9 mg·mL−1. Of 130 participants for whom sputum eosinophils,FENOor both results were obtained, 45 (35% (95% CI 27–43%)) had T2 inflammation. 14 participants (11% (95% CI 6–16%)) had sputum eosinophils >2% and PC20≥16 mg·mL−1, suggesting eosinophilic bronchitis. The prevalence of T2 inflammation was significantly higher in subjects with PC20<4 mg·mL−1(12/20 (60%)) than in those with PC204–15.9 mg·mL−1(8/27 (30%)) or ≥16 mg·mL−1(25/85 (29%)) (p=0.01). Conclusions Asthma, underlying T2 airway inflammation and eosinophilic bronchitis may remain undiagnosed in a high proportion of symptomatic subjects in the community who have normal pre- and post-bronchodilator spirometry.
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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 | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".