Investigating the Effect of Stretch and Environmental Exposures on Airway Epithelium-derived Extracellular ATP
Bibliographic record
Abstract
Abstract Rationale: Chronic cough is a common condition in which patients experience frequent exaggerated coughing bouts, placing a significant burden on quality of life. Adenosine triphosphate (ATP) is a neurotransmitter that can activate vagal sensory nerves via P2X3 ion channels, inducing a cough reflex. Patients with refractory chronic cough (RCC) demonstrate an exaggerated cough response to ATP inhalation, suggesting ATP in the airways plays a role in cough sensitization. We hypothesized that mechanical stimulation and exposure to cigarette smoke or nitrogen dioxide (NO2) may induce ATP release from the airway epithelium. Methods: Calu-3 bronchial epithelial cells and primary normal human bronchial epithelial cells (HBECs) were cultured under submerged conditions in stretchable silicone chambers or under air-liquid interface (ALI) conditions in Transwell™ inserts. The ATPlite™ Luminescence ATP Detection Assay System (Revvity) was used to measure ATP from syringe-filtered cell culture media or apical wash samples. A programmable stretching device was used to apply cyclic uniaxial stretch with varied strain and frequency to submerged cell cultures, followed by ATP measurement. Primary HBEC cultures differentiated at ALI were directly exposed to 10 ppm NO2 for varying durations, whole smoke from 0.375 g of combusted 3R4F research cigarettes, or room air control exposures. Results: Time-dependent differences in ATP release, irrespective of cyclic stretching, were measured in submerged monolayer cultures of Calu-3 and primary HBECs. No statistically significant differences in ATP were observed from Calu-3 or primary HBECs with cyclic stretch compared to pre-stretched measurements. With tobacco smoke and NO2 exposure, increasing trends in ATP release were observed from the apical compartment of primary HBEC ALI culture, whereas the basal compartment did not reveal these trends. The present work includes data from seven healthy control primary HBEC donors. These responses will be compared with RCC primary HBEC donors enrolled in the study. Apyrase eliminated ATP signal, supporting the specificity of the assay used. Conclusions: These data provide insight on ATP release dynamics in Calu-3 cells and healthy HBECs with cyclic stretch and environmental exposures. Ongoing directions for this work involve combining data with experiments using primary HBEC from individuals with refractory chronic cough.
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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 | 0.000 | 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 | 0.000 | 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) | 0.002 | 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".