Lung function change and quantitative computed tomography measurements are associated with prospective frailty.

Abstract

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 multicentre cohort study, enrolled adults aged 45-80 years with a smoking history of a minimum of 10 pack-years. This study included participants with normal baseline 6-min walk distance (6MWD), spirometry at all three site visits and frailty assessment. The primary exposures were baseline quantitative CT measurements (airway wall thickening (Pi10), log (% emphysema), pulmonary artery (PA) enlargement and the ratio of pulmonary blood volume in vessels with a cross-sectional area <5 mm² to the total blood vessel volume (BV5/TBV)) and spirometric decline over the 10-year study period. The primary outcomes were frailty and prefrailty at the 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: Of 2354 participants, 1200 (51%) were prefrail and 297 (13%) were frail at the 10-year follow-up. Baseline Pi10, log (% emphysema) and PA enlargement were significantly associated with increased odds of frailty (adjusted ORs, respectively: 1.52 (95% CI 1.30-1.77; p<0.001), 1.38 (95% CI 1.14-1.67; p<0.001) and 2.49 (95% CI 1.41-4.41; p=0.002)), as was lower BV5/TBV, an indicator of pulmonary vascular pruning (OR 0.59, 95% CI 0.48-0.72; p<0.001). Forced expiratory volume in 1 s (FEV₁) decline was associated with increased odds of frailty (OR 1.47 (95% CI 1.30-1.65; p<0.001) per 1%-per-year drop). White blood cell count (WBC) and neutrophil to lymphocyte (N:L) 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.