Validation of a method to assess emphysema severity by spirometry in the COPDGene study

Abstract

Background Standard spirometry cannot identify the predominant mechanism underlying airflow obstruction in COPD, namely emphysema or airway disease. We aimed at validating a previously developed methodology to detect emphysema by mathematical analysis of the maximal expiratory flow-volume (MEFV) curve in standard spirometry. Methods From the COPDGene population we selected those 5930 subjects with MEFV curve and inspiratory-expiratory CT obtained on the same day. The MEFV curve descending limb was fit real-time using forced vital capacity (FVC), peak expiratory flow, and forced expiratory flows at 25, 50 and 75% of FVC to derive an emphysema severity index (ESI), expressed as a continuous positive numeric parameter ranging from 0 to 10. According to inspiratory CT percent lung attenuation area below − 950 HU we defined three emphysema severity subgroups (%LAA-950insp < 6, 6–14, ≥14). By co-registration of inspiratory-expiratory CT we quantified persistent (%pLDA) and functional (%fLDA) low-density areas as CT metrics of emphysema and airway disease, respectively. Results ESI differentiated CT emphysema severity subgroups increasing in parallel with GOLD stages (p < .001), but with high variability within each stage. ESI had significantly higher correlations (p < .001) with emphysema than with airway disease CT metrics, explaining 67% of %pLDA variability. Conversely, standard spirometric variables (FEV1, FEV1/FVC) had significantly lower correlations than ESI with emphysema CT metrics and did not differentiate between emphysema and airways CT metrics. Conclusions ESI adds to standard spirometry the power to discriminate whether emphysema is the predominant mechanism of airway obstruction. ESI methodology has been validated in the large multiethnic population of smokers of the COPDGene study and therefore it could be applied for clinical and research purposes in the general population of smokers, using a readily available online website.

Standard spirometry to assess emphysema in patients with chronic obstructive pulmonary disease: the Emphysema Severity Index (ESI)

“…Second, as in all large trials, CT densitometry was not available in the CLIMA study, and we assumed that ESI represents parenchymal destruction without reference standard measurements. However, the accuracy of ESI in mirroring accurately the occurrence of emphysema damage by comparison with CT densitometry had already been previously validated in a very large population of smokers and COPD patients [ 23 ].…”

“…The computation assumes that at a given time the pressure drop of a fluid flowing in a cylindrical duct resembling the airways is directly related to the specific friction factor, to the density and the velocity of the fluid, and inversely related to the diameter of the duct. Details of the theoretical and biomechanical background are reported in previous publications [ 22 , 23 ].…”

“…It approximated very well the scores obtained by means of CT in COPD and proved suitable enough for both clinical and research application [ 22 ]. The ability of ESI to identify the emphysema component and to assess its severity has been further validated by comparison with the CT-quantified emphysema in a very large multiethnic population of smokers of the COPDgene study [ 23 ].…”

Clinical and Radiological Features of COPD Patients Living at ≥3000 m Above Sea Level in the Tibet Plateau

“…According to the LAA%, the severity of emphysema was classified as no emphysema (LAA% <6%), moderate emphysema (LAA% ≥6% and <14%), and severe emphysema (LAA% ≥14%), as described previously. 15 , 16 …”

Correlation of the Radiological Emphysema Score of Chronic Obstructive Pulmonary Disease Patients with Clinic Parameters

“…3 Structural lung alterations such as emphysematous parenchymal destructions and conductive airway narrowing can be one of the explanations of heterogeneity of the disease. 4 In the literature, there are some controversial opinions regarding the emphysema level in patients with COPD. While some state that the severity of emphysema varies widely even in patients at the same stage of COPD, 5 others suggest that the amount of emphysema increases with COPD severity.…”