Decreased Sputum Type-2 Gene Expression in COPD Current Smokers
Bibliographic record
Abstract
Thomas Southworth,1,2 Andrew Higham,1 Augusta Beech,1,2 Jian Li,1 Sophie Wolosianka,2 Dave Singh1,2 1Division of Immunology, Immunity to Infection and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester and Manchester University NHS Foundation Trust, Manchester, UK; 2Medicines Evaluation Unit, Manchester, UKCorrespondence: Thomas Southworth, Medicines Evaluation Unit, The Langley Building, Southmoor Road, Manchester, M23 9QZ, United Kingdom, Tel +44 161 946 4066, Email tsouthworth@meu.org.ukBackground: Higher blood eosinophil counts in COPD patients are associated with a greater response to inhaled corticosteroid (ICS) treatment, with type 2 (T2) inflammation being the target for ICS in COPD. Current smokers have reduced responses to ICS treatment. We have investigated whether current smoking modulates the levels of T2 mediators in the airways, thereby influencing ICS responsiveness.Methods: Induced sputum samples were collected from 73 COPD patients, including 41 ex-smokers. Twenty-six patients donated a second sputum sample, approximately 6 months after the initial sample. Sputum cell gene expressions of IL13, CLCA1, CCL26 and CST1 were assessed by quantitative RT-PCR. Differential cell counts were performed.Results: Expression levels of all four genes significantly correlated with sputum eosinophil percentages. IL13 and CCL26 gene expression levels were significantly lower in COPD current versus ex-smokers (IL13 p< 0.0001; CCL26 p=0.005); there were no differences for CLCA1 or CST1. In repeat samples, IL13, CCL26 and CST1 expression showed good or very good consistency, while CLCA1 levels were more variable.Conclusion: Sputum gene expression of IL13 and CCL26 is affected by the smoking status of COPD patients and have stable expression over time. These findings implicate IL-13 and CCL26 as key components of T2 inflammation in COPD but also suggest that current smoking skews the immune response away from a T2 profile.Keywords: COPD, sputum, type 2 inflammation, smoking
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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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 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".