Abstract

The diagnosis of chronic obstructive pulmonary disease (COPD) relies on demonstration of airflow obstruction. Traditional spirometric indices miss a number of subjects with respiratory symptoms or structural lung disease on imaging. We hypothesized that utilizing all data points on the expiratory spirometry curves to assess their shape will improve detection of mild airflow obstruction and structural lung disease. We analyzed spirometry data of 8307 participants enrolled in the COPDGene study, and derived metrics of airflow obstruction based on the shape on the volume-time (Parameter D), and flow-volume curves (Transition Point and Transition Distance). We tested associations of these parameters with CT measures of lung disease, respiratory morbidity, and mortality using regression analyses. There were significant correlations between FEV1/FVC with Parameter D (r = −0.83; p < 0.001), Transition Point (r = 0.69; p < 0.001), and Transition Distance (r = 0.50; p < 0.001). All metrics had significant associations with emphysema, small airway disease, dyspnea, and respiratory-quality of life (p < 0.001). The highest quartile for Parameter D was independently associated with all-cause mortality (adjusted HR 3.22,95% CI 2.42–4.27; p < 0.001) but a substantial number of participants in the highest quartile were categorized as GOLD 0 and 1 by traditional criteria (1.8% and 33.7%). Parameter D identified an additional 9.5% of participants with mild or non-recognized disease as abnormal with greater burden of structural lung disease compared with controls. The data points on the flow-volume and volume-time curves can be used to derive indices of airflow obstruction that identify additional subjects with disease who are deemed to be normal by traditional criteria.

Highlights

  • The clinical diagnosis of chronic obstructive pulmonary disease (COPD) is based on the spirometric detection of airflow obstruction[1]

  • The cohort encompassed a range of severity of airflow obstruction with 49.5%, 9.1%, 21.9%, 13.0%, and 6.5% with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 0 through 4, respectively

  • Parameter D was progressively harder to calculate in more severe disease and could be calculated in 82%, 75%, 58%, 37% and 28%, respectively in participants with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 0 through 4

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Summary

Introduction

The clinical diagnosis of chronic obstructive pulmonary disease (COPD) is based on the spirometric detection of airflow obstruction[1]. One-half of subjects without airflow obstruction by traditional spirometric criteria have substantial respiratory impairment or have structural lung disease on computed tomography (CT)[2,3] These symptomatic smokers are at increased risk of greater lung function decline and developing overt airflow obstruction on follow-up[4]. A segment of the curve visually or through automated analyses[6,7,8,9,10,11,12,13], or by examining the change in the angle of flow during forced exhalation[14,15] These measures showed promising results, the results were limited by small sample sizes and lack of validation against structural lung disease.

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