Inhalation of allergen and diesel exhaust increases urinary eicosanoids associated with impaired lung function and airway hyperresponsiveness: a randomized, double-blinded, human crossover study
Bibliographic record
Abstract
Background. Eicosanoids are potent regulators of homeostasis and inflammation that play an important role in asthma pathophysiology. In a controlled human exposure study, we showed that coexposure to an allergen and diesel exhaust (DE) led to eosinophilic inflammation, impaired airflow, and increased airway responsiveness. Eicosanoids may mediate the mechanism by which these exposures impair lung function. Methods. We conducted a randomized, double-blinded, four-arm crossover study. Fourteen allergen-sensitized participants were exposed to four conditions: filtered air and saline (FA-S; negative control); filtered air and allergen (FA-A; allergen alone); DE and allergen (DE-A; coexposure); and particle-depleted DE and allergen (PDDE-A; coexposure with minimal particles). Quantitative metabolic profiling of urinary eicosanoids was performed using LC-MS/MS. Results. Allergen inhalation increased urinary eicosanoids. The prostacyclin metabolite 2,3-dinor-6-keto-PGF 1α increased with DE-A, but particle depletion (PDDE-A) suppressed this pathway. Baseline airway hyperresponsiveness modified the allergen-induced increase in prostaglandin D 2 metabolites (tetranor PGDM and 2,3-dinor-11β-PGF 2α ) such that normally responsive individuals showed a greater allergen-induced increase of the two metabolites. Genetic risk scores (GRS) modified the effect of DE-A; those individuals with a high GRS demonstrated a greater increase in isoprostane metabolites following DE-A. Increased urinary leukotriene E 4 and tetranor PGDM correlated with increased airway responsiveness, while increased tetranor PGDM also correlated with decline in FEV 1 . Conclusions. Impaired airflow and increased airway responsiveness upon exposure to DE-A may be attributable to increased levels of leukotrienes and prostaglandins. Variants in genes known to mediate response to pollution appear to modulate these eicosanoid-mediated physiological responses known to contribute to asthma pathophysiology.
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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 | 0.006 | 0.003 |
| Meta-epidemiology (narrow) | 0.003 | 0.002 |
| Meta-epidemiology (broad) | 0.006 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.002 | 0.004 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.003 | 0.003 |
| Insufficient payload (model declined to judge) | 0.004 | 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".