Epigenetic Age as Both Effect and Modifier of Response to Nasal Corticosteroid Under Diesel Exhaust and Allergen Exposure in Adults With Allergic Rhinitis
Bibliographic record
Abstract
Abstract Rationale: Allergic rhinitis (AR) is a nasal inflammatory disease triggered by exposure to aeroallergens. Exposure to air pollution, including diesel exhaust (DE; a model of traffic-related air pollution) can drive allergic rhinitis (AR) and may alter airway DNA methylation. Nasal corticosteroids (NCS) are anti-inflammatory agents used as first-line treatment for AR, and in vitro studies have also shown budesonide to modulate DNA methylation. The effect of budesonide treatment, in combination with exposures to DE and allergens, on DNA methylation-based biomarkers of age in AR has not been previously studied. Methods: In a double-blinded crossover trial, twenty healthy non-smokers (aged 18-65) with AR used a once-daily budesonide or placebo nasal spray treatment for four weeks each in a randomized order. Allergen and DE exposures were completed twice over two-day periods separated by a ≥2-week washout, starting with allergen two weeks after the start of each treatment arm. A ≥4-week washout was completed between treatment arms. Nasal brushings were collected at the start of each treatment period, as well as before and at 24h and 48h after the initial allergen or DE exposure in each treatment arm. Re-exposures occurred 24h after each initial exposure. Allergen challenges were titrated for each participant, while 2h DE exposures were standardized to 300μg/m3 of PM2.5. DNA methylation was quantified using Illumina EPIC arrays and epigenetic age measurements were computed by the Clock Foundation. Data analysis was completed using linear mixed effects models. Results: The effects of budesonide treatment on various measures of epigenetic age at each timepoint are given in Table 1. Allergen increased Horvath1 age acceleration (AA) following initial (2.58 years [0.29, 4.86], p=0.03) and re-exposure (3.35 years [1.03, 5.56], p=0.006), while decreasing Grim AA (-2.10 years [-3.36, -0.85], p≤0.001) following re-exposure. Re-exposure to DE also decreased Grim AA (-1.33 years [-2.48, -0.19], p=0.02). Grim AA scores moderated budesonide's effect on IL-1β (β=1.20-fold [1.09, 1.32], p=0.02) and VEGF-A (β=1.07-fold [1.03, 1.12], p=0.03) relative to placebo at the DE baseline, as well as an increase in DE's effect upon GM-CSF (β=1.12-fold [1.04, 1.21], p=0.03) and IL-16 (β=1.15-fold [1.06, 1.26], p=0.03) 24h after re-exposure to DE. Conclusions: Budesonide and exposure to allergen and DE significantly affected epigenetic age acceleration. Epigenetic age may moderate cytokine responses to budesonide treatment and common environmental exposures.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| 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".