B102-08 Comparison Between Eupneic and Dyspneic People With Severe Airflow Limitation

Abstract Rationale In Chronic Obstructive Pulmonary Disease (COPD), as disease severity worsens, lung function declines and symptom burden increases. While symptom severity often parallels the degree of lung function impairment, the clinical significance of severe airflow limitation in those do not report dyspnea (eupneic) remains unclear. To characterize eupneic individuals (mMRC = 0) with severe airflow limitation (GOLD 3-4) and compare their structural and clinical outcomes to dyspneic individuals with similar or less severe respiratory function. Methods We analyzed data from 1,716 COPDGene participants with GOLD 3-4, categorized by mMRC dyspnea scores: 0 (eupneic), 1-2, and 3-4. Baseline assessments included spirometry, CT imaging, six minute walk, and symptom questionnaires. Longitudinal outcomes included FEV1 decline, exacerbation frequency, and mortality. A secondary analysis compared eupneic GOLD 3-4 participants to dyspneic GOLD 1 participants (mMRC 3-4). Results Among GOLD 3-4 participants, 8.2% were eupneic. Compared to those with mMRC 3-4, eupneic individuals had lower prevalence of chronic bronchitis, better exercise capacity, and less CT-detected emphysema, gas trapping, and PRMfSAD. Among 1,529 participants with follow-up data (median 6.3 years IQI: 3.4-11.3), those with mMRC 0 had significantly fewer total exacerbations (IRR = 0.54; 95% CI: 0.42-0.69; P 0.001) and severe exacerbations (IRR = 0.53; 95% CI: 0.38-0.73; P 0.001) compared to mMRC 3-4. During the median follow-up of 2,472 days (IQI 1,368 to 4,063), death occurred in 47.5% (67 of 141), 54.1% (235 of 434), and 67.2% (766 of 1,140) of participants with mMRC of 0, 1-2, and 3-4, respectively. Eupneic participants had significantly lower mortality (HR = 0.62; 95% CI: 0.48-0.80; P = 0.0003), as did those with mMRC 1-2 (HR = 0.64; 95% CI: 0.55-0.75; P 0.001), compared to mMRC 3-4. Conclusion A modest proportion of individuals with severe respiratory function impairment are eupneic and demonstrate better clinical outcomes and less structural lung damage than their dyspneic counterparts. Our findings support a multidimensional approach to COPD assessment that incorporates symptom burden alongside spirometry. This abstract is funded by: Award Number U01 HL089897, Award Number U01 HL089856, and by NIH contract 75N92023D00011 from the National Heart, Lung, and Blood Institute