Contractile Properties of Intrapulmonary Airway Smooth Muscle in Fatal Asthma
Bibliographic record
Abstract
Abstract Rationale: Asthma affects over 200 million people worldwide (WHO 2019). It is characterized by airway hyperresponsiveness (AHR), an excessive airway narrowing in response to benign stimuli. Evidence is accumulating that supports that asthmatic intrapulmonary airway smooth muscle (IP-ASM) is hypercontractile. IP-ASM has been shown to produce a greater stress (force/cross-sectional area) in asthmatic subjects and in the equine model of asthma compared to healthy controls. Maximum shortening velocity (Vmax) has also been shown to be increased in several human and animal models of asthma during acute exposure to inflammatory cells and mediators. The contractile properties of fatal asthmatics remain ill studied. Given that fatal asthma is considered more representative of poorly controlled asthma rather than severe asthma, we hypothesised that the contractile properties of fatal asthmatics would be comparable to those of mild to moderate asthmatics. To address this question, we compared the mechanics of control, mild asthmatic, and fatal asthmatic IP-ASM. Methods: Intrapulmonary airways 2-5mm in diameter from healthy control, mild asthmatic, and fatal asthmatic donor lungs (NDRI & IIAM) were dissected to yield small strips of ASM cleared of epithelium and cartilage. These strips were placed in an organ bath, and dose responses to methacholine (MCh) and isoproterenol (Iso) were performed. Vmax was also measured by the quick release technique during a MCh contraction. Data are from 25 ASM strips from 4 healthy control lungs, 50 strips from 5 mild asthmatic lungs, and 28 strips from 3 fatal asthmatic lungs. Results and Discussion: Relaxation of IP-ASM strips from fatal asthmatic lungs was significant less relative to healthy controls (32.1% ± 2.5 vs. 63.4% ± 5.7, P<0.0001) and mild asthmatic lungs (32.1% ± 2. 6 vs. 67.6% ± 1.6, P<0.0001). Interestingly, Vmax of fatal asthmatic was significantly lower compared to asthmatic IP-ASM (0.132 lengths/s ± 0.006 vs. 0.179 lengths/s ± 0.001, P=0.0017), with a similar trend when compared to control IP-ASM (0.132 lengths/s ± 0.006 vs. 0.166 lengths/s ± 0.010, P>0.05). The lower Vmax observed in the fatal asthmatics could be explained by their corticosteroids intake upon hospitalization, as there is evidence of their ability to decrease Vmax in equine asthma. However, it is interesting to see the refractiveness of the IP-ASM relaxation to these medications. Thus, our results suggest that future efforts should focus on the persistent lack of relaxation of IP-ASM in uncontrolled and fatal asthma.
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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) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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 | 0.001 |
| 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".