Airway and Parenchymal Disease in Chronic Obstructive Pulmonary Disease Are Distinct Phenotypes
Bibliographic record
Abstract
The relative importance of genetic factors and tobacco smoking intensity in the pathogenesis of the airway disease and emphysematous components of chronic obstructive pulmonary disease (COPD) is unknown. We addressed this question in a family-based study that recruited probands (FEV1 5 pack-year smoking history) and their current/ex-smoking siblings. The family-based design allowed us to test the relationship between COPD phenotype (emphysema or small airway disease) in a proband and his or her siblings. Subjects completed a questionnaire and underwent spirometry, and a subset of participants underwent chest computed tomography (CT) scans. Results: The number of pack-years was only weakly correlated with FEV1 in 634 individuals with emphysema, as assessed by radiologist scoring of chest CT scans (r = −0.09, p = 0.02). The amount of emphysema on CT scan was inversely related to FEV1 (p < 0.001), but there was no relationship between pack-years and amount of emphysema. Emphysema was more prevalent in the siblings of probands with emphysema (41.7%) than in siblings of nonemphysema probands (23.6%, p < 0.001); this was independent of pack-years smoked (adjusted odds ratio, 2.12; p = 0.03). In 482 individuals without emphysema, FEV1 was correlated with pack-years smoked (r = −0.38, p < 0.0001). The correlation between pack-years and FEV1 was particularly strong (r = −0.58, p < 0.0001) in 48 siblings who were from families in which the proband had predominantly small airway disease. These data suggest that emphysema and airway-related COPD are distinct phenotypes and have different relationships with smoking. Moreover, differences in amount of emphysema are not explained by cumulative smoking, suggesting a complex gene–environment interaction.
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How this classification was reachedexpand
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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.002 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".