Influence of weight status in the response to Step-2 maintenance therapies in children with asthma
Why this work is in the frame
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Bibliographic record
Abstract
Introduction: Overweight children with asthma may display impaired response to inhaled corticosteroids (ICS), possibly due to non-eosinophilic inflammation or weight-related lung compression; these mechanisms may differentially affect response to ICS and leukotriene receptor antagonists (LTRAs). We assessed whether weight status modified the response to low-dose ICS and LTRA Step-2 monotherapy. Methods: A historical cohort study from clinical data linked to administrative databases was conducted among children aged 2-18 years with specialist-diagnosed asthma who were initiating or continuing a Step-2 monotherapy from 2000 to 2007 at the Montreal Children's Hospital Asthma Centre. The outcome was time-to-management failure defined as any step-up in therapy, acute care visit, hospitalisation or oral corticosteroids for asthma, whichever occurred first. The independent and joint effects of weight status (body mass index [BMI] percentile) and time-varying treatment on time-to-management failure were estimated with marginal structural Cox models. The likelihood ratio test (LRT) and relative excess risk due to interaction (RERI) were computed to assess treatment effect modification by weight status on the multiplicative and additive scales. Results: Of the 433 and 85 visits with a low-dose ICS and LTRA prescription, respectively, 388 management failures occurred over 14 529 visit-weeks of follow-up. Children using LTRA compared with low-dose ICS tended to have an overall higher risk of early management failure (HR 1.52; 95% CI 0.72 to 3.22). Irrespective of treatment, the hazard of management failure increased by 5% (HR 1.05; 95% CI 1.01 to 1.10) for every 10-unit increase in BMI percentile. An additional hazard reduction of 17% (HR 0.83; 95% CI 0.70 to 0.99) was observed for every 10-unit increase in BMI percentile among LTRA users, but not for ICS (HR 0.95; 95% CI 0.86 to 1.04). The LRT indicated a departure from exact multiplicativity (p<0.0001), and the RERIs for ICS and LTRA were -0.05 (95% CI -0.14 to 0.05) and -0.52 (95% CI -1.76 to 0.71). Conclusions: Weight status was associated with earlier time-to-management failure in children prescribed Step-2 therapy. This hypothesis-generating study suggests that LTRA response increases in children with higher BMI percentiles, although further research is warranted to confirm findings.
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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 | 0.008 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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 it