Sputum Cellularity and Immune Biomarkers During Acute Exacerbations of Asthma
Bibliographic record
Abstract
Abstract Rationale: Acute asthma exacerbations are frequently triggered by viral infections and the airway epithelium is the principal target. Various pro-inflammatory molecules are released including the alarmins (interleukin (IL)-33, thymic stromal lymphopoietin and IL-25). The sputum is frequently used to phenotype asthma but is subject to contamination from the upper airways. The aim of the present study was to assess the markers of innate immune responses during an acute exacerbation of asthma by the analysis of sputum and to relate the levels of pro-inflammatory molecules to the quality of the sputum as reflected in the percentage of squamous cells.Methods: We studied asthmatic subjects (n= 45) presenting to the Montreal Chest Institute with a physician diagnosed asthma exacerbation. Clinical data, spirometry, Asthma Control Questionnaires (ACQ), complete blood counts and expectorated sputum were acquired on admission to the study (day 1) and on days 10 and 28. Sputum was processed for differential cell counts and sputum supernatants from a subset of subjects (n=25) were analysed by Bioplex for 25 inflammatory markers. Cysteinyl leukotrienes (CysLTs) in the sputum supernatants were analyzed by enzyme immunoassay. Results: On day 1, subjects had an ACQ score of 3.56 ± 0.84 and an FEV1 was 69.1 ± 21.4 (% predicted). Blood eosinophil counts >150/µl were present in 26/45. Expectorated sputum had squamous cell counts that ranged from 0 to 90%, with a median value of 16.81%. Mediator levels (interleukin (IL)-4, IL-5, IL-8, and TNF-α) were significantly lower in samples for which squamous cells exceeded 16 (%). Similarly, CysLTs were significantly higher in sputum squamous cell counts < 16% (median 697 pg/ml) than when sputum squamous cells were > 16% (median 364 pg/ml; p=0.006). Alarmins were an exception to this finding and levels of IL-33 were 5.29 ± 1.12pg/ml for samples below 16% squamous cells and 8.13 ±2.74 pg/ml for samples above 16%. Similarly, TSLP levels were not statistically significantly different for sputum with < 16% squamous cells to > 16% squamous cells (1.39pg ± 0.43/ml vs 2.15 ± 2.23 pg/ml) and for IL-25 (4.16 ± 2.87 pg/ml and 6.19 ± 1.17 pg/ml, respectively). Alarmin levels were not significantly different between subjects with peripheral blood eosinophils above and below 150/µl.Conclusions: Selected cytokines/chemokines and CysLTs in expectorated sputum are likely under-estimated in sputum samples in which squamous cells are elevated. Alarmin levels are not affected by the squamous cell counts, suggesting a significant contribution to these mediators from the oropharynx.
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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 | 0.001 |
| 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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".