Phthalates trigger respiratory reflexes
Bibliographic record
Abstract
Epidemiological studies suggest that environmental exposure to Dibutyl phthalate (DBP), a commonly used plasticiser, found in flooring, cosmetics and food packaging, is linked with worsening or development of asthma (Bølling EXCLIJ:2013,12,733-59). DBP can accumulate in lung tissues and has been previously shown to activate some of the Transient Receptor Potential (TRP) family of ion channels expressed on airway sensory nerves (Shiba J Neuroimm:2009,66-74). Activation of these nerves can lead to respiratory reflexes which are exacerbated in asthma, such as cough and bronchospasm. The aim of this study was to investigate whether DBP can activate airway sensory nerves and identify possible mechanisms. Using a model of single afferent airway nerve firing in anaesthetised guinea-pigs, aerosolised administration of DBP caused firing of an Aδ fibre (conduction velocity 7.5 m/s) and calcium flux in airway terminating jugular and nodose neurons. DBP also caused concentration-dependent depolarisation of isolated vagal nerves from guinea-pigs and mice in an in vitro preparation. This depolarisation was inhibited 50% by a TRPV1 antagonist (JNJ-17203212 100µM: 0.12±0.014mV – 0.055±0.005mV), and confirmed in TRPV1 -/- mice (compared to wild type). Most of the remaining depolarisation was driven through TRPA1 via an oxidative stress mechanism (HC-030031 10µM: 0.12±0.011 – 0.06±0mV and NAC 1mM: 0.11±0.01mV – 0.055±0.01mV). Our data shows that DBP can activate airway sensory nerves through activation of TRPA1 and TRPV1, and can also trigger a non-reflex bronchoconstriction. These results also suggest a novel mechanism by which indoor air pollutants may act as an asthma trigger, which may contribute to non-allergic asthma phenotypes.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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 teacher head, 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".