The Peak Index: Spirometry Metric for Airflow Obstruction Severity and Heterogeneity

Abstract

Rationale: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation. Spirometry loops are not smooth curves and have undulations and peaks that likely reflect heterogeneity of airflow.Objectives: To assess whether the Peak Index, the number of peaks adjusted for lung size, is associated with clinical outcomes.Methods: We analyzed spirometry data of 9,584 participants enrolled in the COPDGene study and counted the number of peaks in the descending part of the expiratory flow-volume curve from the peak expiratory flow to end-expiration. We adjusted the peaks count for the volume of the lungs from peak expiratory flow to end-expiration to derive the Peak Index. Multivariable regression analyses were performed to test associations between the Peak Index and lung function, respiratory morbidity, structural lung disease on computed tomography (CT), forced expiratory volume in 1 second (FEV1) decline, and mortality.Results: The Peak Index progressively increased from Global Initiative for Chronic Obstructive Lung Disease stage 0 through 4 (P < 0.001). On multivariable analysis, the Peak Index was significantly associated with CT emphysema (adjusted β = 0.906; 95% confidence interval [CI], 0.789 to 1.023; P < 0.001) and small airways disease (adjusted β = 1.367; 95% CI, 1.188 to 1.545; P < 0.001), St. George's Respiratory Questionnaire score (adjusted β = 1.075; 95% CI, 0.807 to 1.342; P < 0.001), 6-minute-walk distance (adjusted β = -1.993; 95% CI, -3.481 to -0.506; P < 0.001), and FEV1 change over time (adjusted β = -1.604; 95% CI, -2.691 to -0.516; P = 0.004), after adjustment for age, sex, race, body mass index, current smoking status, pack-years of smoking, and FEV1. The Peak Index was also associated with the BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity) index and mortality (P < 0.001).Conclusions: The Peak Index is a spirometry metric that is associated with CT measures of lung disease, respiratory morbidity, lung function decline, and mortality.Clinical trial registered with www.clinicaltrials.gov (NCT00608764).

Keywords: airflow obstruction; chronic obstructive pulmonary disease; heterogeneity; spirometry.

Figures

Figure 1.

Representative peaks analysis for participants across a range of disease severity. (A) A 51-year-old white man with forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) of 0.89 and FEV1% predicted of 84.5% has no peaks in the descending limb of the flow–volume loop. (B) A 70-year-old white woman with FEV1/FVC of 0.64 and FEV1% predicted of 69.6% has seven peaks. (C) A 54-year-old white man with FEV1/FVC of 0.31 and FEV1% predicted of 34.8% has 20 peaks. COPD = chronic obstructive pulmonary disease.

Figure 2.

Mean Peak Index in participants by Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage. Box plots show means and 95% confidence intervals.

Figure 3.

Kaplan-Meier survival curves for the four quartiles of Peak Index. After adjustment for age, sex, race, body mass index, current smoking status, and pack-years of smoking, compared with the lowest quartile (I), the higher quartiles were associated with greater risk of mortality (adjusted hazard ratio [HR], 1.10; 95% confidence interval [CI], 0.86–1.41; P = 0.441; adjusted HR, 1.50; 95% CI, 1.19–1.90; P = 0.001; and adjusted HR, 3.41; 95% CI, 2.75–4.23; P < 0.001, respectively).

Figure 4.

Schema showing choke points in airway segments in parallel and how these can potentially result in peaks on the expiratory limb of the flow–volume curve. Each segment is colored differently to show representative contribution from that airway segment to total airflow. The relative intrabronchial area occupied by a color represents the contribution to airflow from that airway segment. At the beginning of a forced exhalation maneuver, all segmental airways are open, and the colors are equally distributed. Initially, the intraalveolar pressures are very positive, and with exhalation this pressure gets progressively dissipated in the airways. With forced exhalation, the intrapleural pressure (Ppl) is initially high, and when the intrapleural pressure equals and exceeds the intrabronchial pressure in an airway branch, that airway collapses and there is a resultant decrease in the rate of decline of airflow. With progressive decrease in intrapleural pressure with exhalation, previously collapsed airway segments open up as their intrabronchial pressure rises above the intrapleural pressure.