Association of a Novel Index of Early-life Growth Conditions With Later-life Lung Structure and Function
Bibliographic record
Abstract
Abstract BACKGROUND: Early-life growth conditions are implicated in later-life lung health, but mechanisms remain uncertain. Standing height is determined in part by early-life growth conditions and by genetics, and the difference between attained height and genotype-predicted height (height-GaP) is associated with adverse early-life growth conditions. This study assessed the relationship of height-GaP with later-life lung structure and function at rest and at peak exercise. METHODS: CanCOLD is a multi-centre Canadian cohort of community-dwelling adults that underwent standardized thoracic computed tomography (CT), incremental cardiopulmonary exercise testing (CPET), full-body plethysmography, diffusing capacity for carbon monoxide (DLCO), and post-bronchodilator spirometry.Genotype-predicted height was calculated using a polygenic height score derived from individual genotype data.Total pulmonary vessel count (TVC), the percentage of emphysema-like lung (log-transformed low attenuation areas <-950 Hounsfield units [LAA-950]), airway-to-lung ratio, total airway count (TAC) and the percentage of high attenuation areas between -600 and -250 Hounsfield units (HAA-600-250) were quantified from CT. CPET was used to determine exertional dyspnea (Borg 0-10 category-ratio scale)/ventilation (V'E) and the peak rate of oxygen consumption (V'O2peak). Linear regression models adjusted for age, age2, sex and genotype-predicted height. RESULTS: Among 1,284 adults, the mean±SD age was 66±10 years and 43% were female. Compared with individuals in the lowest quintile of height-GaP deficit (Q1), those in the highest quintile of height-GaP deficit (Q5) had significantly fewer pulmonary vessels (adjusted mean difference: -1,275 [95%CI: -1764, -784]; p<0.001), lower DLCO (adjusted mean difference: -3.77 mL/min/mmHg [95%CI: -4.96, -2.58]; p<0.001), lower V'O2peak (adjusted mean difference -1.44 mL/kg/min [95%CI: -2.67, -0.20]; p=0.02), and greater dyspnea/V'E (adjusted mean difference: +0.01 Borg/L/min [95%CI: 0.001, 0.02]; p=0.03). There were no differences in post-bronchodilator ratio of forced expiratory volume in 1-second-to-forced vital capacity, LAA-950, visual emphysema, TAC, airway-to-lung ratio, HAA-600-250, or visual interstitial lung disease across quintiles of height-GaP (all p<0.13). Results remained consistent among non-smokers (n=207) and participants with spirometry-defined COPD (n=467). CONCLUSION: Using height-GaP as an index of adverse early-life growth conditions, we observed a pulmonary vascular phenotype among adults in the general population that was characterized by significantly fewer pulmonary blood vessels, lower DLCO, lower exercise capacity and greater exertional dyspnea, but no associations with airflow obstruction or CT-assessed obstructive or restrictive pathology. Future studies replicating and investigating the longitudinal significance of this potential pulmonary vascular phenotype seem warranted.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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".