Expression of COX-1, COX-2, 5-LOX and $$\hbox {CysLT}_2$$ in nasal polyps and bronchial tissue of patients with aspirin exacerbated airway disease
Bibliographic record
Abstract
Abstract Background Aspirin exacerbated respiratory disease (AERD) is a disease of the upper and lower airways. It is characterized by severe asthma, chronic sinusitis with nasal polyps (CRSwNP) and intolerance towards nonsteroidal analgesics (NSAR). Arachidonic acid (AA) metabolites play an important role in the pathogenesis of AERD. It is still unknown, whether metabolism of AA is comparable between the upper and lower airways as well as between patients with and without NSAR intolerance. Objective We sought to analyze differences in the expression of cyclooxygenases type 1 and 2 (COX-1, COX-2), arachidonate 5-lipoxygenase (5-LOX) and cysteinyl leukotriene receptor type 2 ( $$\hbox {CysLT}_2$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mtext>CysLT</mml:mtext><mml:mn>2</mml:mn></mml:msub></mml:math> ) in nasal polyps and the bronchial mucosa of patients with aspirin intolerant asthma (AIA, $$n=23$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi>n</mml:mi><mml:mo>=</mml:mo><mml:mn>23</mml:mn></mml:mrow></mml:math> ) as compared to patients with aspirin tolerant asthma (ATA, $$n=17$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi>n</mml:mi><mml:mo>=</mml:mo><mml:mn>17</mml:mn></mml:mrow></mml:math> ) and a control group with nasal polyps, but without asthma (NPwA, $$n=15$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi>n</mml:mi><mml:mo>=</mml:mo><mml:mn>15</mml:mn></mml:mrow></mml:math> ). Methods Tissue biopsies from nasal polyps and bronchial mucosa were obtained during surgical treatment of nasal polyps by endonasal functional endoscopic sinus surgery (FESS) under general anesthesia from intubated patients. Immunohistochemistry was used to analyze the expression of COX-1, COX-2, 5-LOX and $$\hbox {CysLT}_2$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mtext>CysLT</mml:mtext><mml:mn>2</mml:mn></mml:msub></mml:math> in nasal and bronchial mucosa. Categorization into the different patient groups was performed according to the patient history, clinical and laboratory data, pulmonary function and provocation tests, as well as allergy testing. Results We observed a stronger expression of 5-LOX and $$\hbox {CysLT}_2$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mtext>CysLT</mml:mtext><mml:mn>2</mml:mn></mml:msub></mml:math> in submucosal glands of nasal and bronchial tissue compared to epithelial expression. The expression of COX-1 and COX-2 was stronger in epithelia compared to submucosal glands. There was a similar expression of the enzymes and $$\hbox {CysLT}_2$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mtext>CysLT</mml:mtext><mml:mn>2</mml:mn></mml:msub></mml:math> between upper and lower airways in all patient groups. We did not detect any significant differences between the patient groups. Conclusions The AA-metabolizing enzymes and the $$\hbox {CysLT}_2$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mtext>CysLT</mml:mtext><mml:mn>2</mml:mn></mml:msub></mml:math> were expressed in a very similar way in different microscopic structures in samples of the upper and lower airways of individual patients. We did not detect differences between the patient groups indicating the pathogenetic role of AA metabolism in these disorders is independent of the presence of NSAR-intolerance.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 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".