A Novel Index of Early-life Growth Conditions Moderates Susceptibility to Later-life Cigarette Smoking-associated Airflow Obstruction and Systemic Inflammation
Notice bibliographique
Résumé
Abstract Rationale: Early-life growth conditions and later-life cigarette smoking are major pathways to chronic obstructive pulmonary disease (COPD), but whether these factors interact is poorly understood. Attained height is determined in part by early-life growth conditions and by genetics, and the difference between attained and genotype-predicted height (height-GaP) is a prospectively validated index of early-life growth conditions. This study sought to investigate whether height-GaP moderates susceptibility to cigarette smoking-associated airflow obstruction and systemic inflammation. Methods: UKBiobank is cohort of community-dwelling adults 40-69 years old at enrolment. Participants completed standardised assessments of anthropometry, smoking behaviours, genotyping, spirometry and serum C-reactive protein concentration (CRP). Genotype-predicted height was calculated using a polygenic height score derived from individual genotype data. Airflow obstruction was defined using pre-bronchodilator FEV1/FVC <0.70. Regression models of airflow obstruction prevalence and CRP were fit with 10+ pack-years and current smoking status as the respective independent variables of interest. Moderation of these associations by height-GaP were assessed by including a height-GaP product term in each model and were additionally adjusted for age, age2, sex, principal components of genetic ancestry, and genotype-predicted height. Results: Among 293,018 adults with quality-verified spirometry, height, genotype and pack-year data (mean±SD age 56±8 years, 54.2% female, 27.4% smoked 10+ pack-years, 15.9% airflow obstruction prevalence), 10+ pack-years of cigarette smoking was associated with 10.3% excess airflow obstruction prevalence, but this association varied with height-GaP (p-interaction=4.35e-06). Smoking 10+ pack-years in the lowest height-GaP quintile (i.e., largest height deficit) was associated with 12.2% excess airflow obstruction prevalence compared to 8.7% excess airflow obstruction prevalence in the highest height-GaP quintile (Figure 1a) – a +40% relative excess of airflow obstruction prevalence. Among 461,108 adults with serum CRP, height, genotype and smoking status data (mean±SD age 56±8 years, 54.2% female, 10.5% current smokers, median (IQR) serum CRP 1.33 (0.66-2.76) mg/L), current smoking was associated with +0.84 mg/L higher CRP concentration, but this association varied with height-GaP (p-interaction=1.05e-12). Current smoking in the lowest height-GaP quintile (i.e., largest height deficit) was associated with +1.06 mg/L higher CRP concentration compared to +0.62 mg/L higher CRP in the highest quintile – a +70% relative increment in serum CRP concentration (Figure 1b). Conclusion: Early-life growth conditions, quantified as the difference between attained height and genotype-predicted height, appear to moderate susceptibility to cigarette smoking-associated airflow obstruction and systemic inflammation. These findings suggest that early-life conditions that affect growth may alter later-life susceptibility to pro-inflammatory stimuli and associated health outcomes.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,001 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».