Parameter D: New Measure of Airflow Obstruction

Abstract

Rationale: Currently used spirometry measures of airflow obstruction are influenced by demographics, predominantly by age, complicating selection of diagnostic thresholds for the presence of airflow obstruction. Objectives: To develop diagnostic thresholds for Parameter D, a new metric for detection of airflow obstruction, which quantifies the rate of rise of expiratory volume over time. Methods: We analyzed spirometry data of normal subjects enrolled in the 2007-2008, 2009-2010, and 2011-2012 NHANES (National Health and Nutrition Examination Survey) cohorts and calculated Parameter D using the expiratory volume-time curve. Relationships between demographics and lung function (forced expiratory volume in 1 second [FEV₁], FEV₁/forced vital capacity [FVC], and Parameter D) were tested using generalized linear models in NHANES and UK Biobank. The variation in lung function explained by demographics was estimated using R². A diagnostic threshold was developed for Parameter D using population-based percentiles. Based on concordance between the lower limit of normal (LLN) for FEV₁/FVC and the Parameter D threshold, four groups were identified: normal (no airflow obstruction by either criterion), D⁺chronic obstructive pulmonary disease (D⁺COPD; positive by Parameter D only), D^-COPD (positive by LLN only), and COPD (positive by both criteria), and associations with structural lung disease, exacerbations, and mortality were tested using multivariable analyses. Results: In contrast to FEV₁ and FEV₁/FVC, demographics cumulatively explained only 9% of the variance in Parameter D in NHANES (n = 4,945) and 3% in UK BioBank (n = 109,623). In COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease) (n = 9,542), a diagnostic threshold of -3.15 resulted in the identification of an additional 10.8% of participants with airflow obstruction. A total of 3.7% had FEV₁/FVC < LLN but were missed by the Parameter D threshold. Compared with subjects in the normal group, after adjustment for age, sex, race, body mass index, pack-years of smoking, and current smoking status, D⁺COPD was associated with worse structural lung disease (odds ratio [OR] for ⩾5% emphysema, 1.71; 95% confidence interval [CI], 1.37-2.12; OR for functional small airway disease ⩾ 15%, 2.1; 95% CI, 1.79-2.67) and significant symptoms (OR for modified Medical Research Council dyspnea score ⩾ 2, 1.25; 95% CI, 1.07-1.47; OR for St. George's respiratory questionnaire ⩾ 25, 1.31; 95% CI, 1.13-1.53), a greater frequency of exacerbations (incidence rate ratio, 1.26; 95% CI, 1.10-1.46), and higher mortality (hazard ratio, 1.32; 95% CI, 1.10-1.57). Over 5 years, 28% of the D⁺COPD group versus 8% of normal group progressed to COPD by traditional criteria. Conclusions: Parameter D is not affected by age, and a normal population-based diagnostic threshold results in the early identification of additional individuals with airflow obstruction with a substantial amount of structural lung disease and respiratory symptoms.

Keywords: Parameter D; airflow obstruction; chronic obstructive pulmonary disease; spirometry.

Figure 1.

Visual representation of Parameter D. A faster rate of rise of the volume–time curve results in a more negative Parameter D and reflects a less-severe degree of airflow obstruction. |D| represents the absolute value of Parameter D. Parameter D = a new metric for detection of airflow obstruction.

Figure 2.

Distribution of Parameter D in NHANES (National Health and Nutrition Examination Survey) and COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease). (A) Distribution of Parameter D in NHANES, with the 75th percentile (−3.15) depicted. (B) Distribution of the groups concordant and discordant for the presence of COPD when defined by Parameter D and lower limit of normal (LLN) thresholds. The plots show correlation between forced expiratory volume in 1 second and/or forced vital capacity (FEV₁/FVC) and the LLN for FEV₁/FVC. COPD = positive by both criteria; D⁺COPD = positive by Parameter D only; D⁻COPD = positive by LLN only; normal = no airflow obstruction by either criterion; Parameter D = a new metric for detection of airflow obstruction.

Figure 3.

Association between forced expiratory volume in 1 second (FEV₁), FEV₁/forced vital capacity (FVC), and Parameter D with demographics in NHANES (National Health and Nutrition Examination Survey). (A) Association between FEV₁ and age and height. (B) Association between FEV₁/FVC and age and height. (C) Association between Parameter D and age and height. Data points are displayed by sex in all panel. Parameter D = a new metric for detection of airflow obstruction.