Lung function change and quantitative CT measurements associate with prospective frailty

Background Frailty, a state of reduced physiologic reserve, is associated with comorbid lung disease. Its relationship with lung function change over time and with lung computed tomography (CT) measurements is less clear. Methods COPDGene, a multicenter cohort study, enrolled adults aged 45–80 with a minimum 10 pack-year smoking history. This study included participants with normal baseline six-minute walk distance, spirometry at all three site visits, and frailty assessment. The primary exposures were baseline quantitative CT measurements (airway wall thickeningPi10, log 10 (% emphysema), pulmonary arteryPA enlargement, and relative volume in the small pulmonary vasculatureBV5/TBV) and spirometric decline over the 10-year study period. The primary outcomes were frailty and prefrailty at 10-year follow-up (defined using a modified Fried Frailty Phenotype). Secondary analyses evaluated associations between inflammatory markers and frailty and for mediation of these associations by spirometric decline. Results Among 2354 participants, 1200(51%) were prefrail and 297(13%) were frail at 10-year follow-up. Baseline Pi10, log 10 (% emphysema), and PA enlargement were significantly associated with increased odds of frailty (adjusted OR95% CI, respectively: 1.521.30–1.77, p<0.001; 1.381.14–1.67, p<0.001; 2.491.41–4.41, p=0.002), as was lower BV5/TBV, an indicator of pulmonary vascular pruning (OR 0.590.48–0.72, p<0.001). Forced expiratory volume in one second (FEV1) decline was associated with increased odds of frailty (OR 1.471.30–1.65, p<0.001 per 1%/year drop). White blood cell count and neutrophil:lymphocyte ratio were associated with frailty; this was partially mediated by spirometric decline. Conclusion In a population with a cigarette smoking history, lung function decline and CT measurements were associated with prospective frailty risk.