Assessing bronchodilator response by changes in per cent predicted forced expiratory volume in one second

Abstract

In pulmonary function testing by spirometry, bronchodilator responsiveness (BDR) evaluates the degree of volume and airflow improvement in response to an inhaled short-acting bronchodilator (BD). The traditional, binary categorization (present vs absent BDR) has multiple pitfalls and limitations. To overcome these limitations, a novel classification that defines five categories (negative, minimal, mild, moderate and marked BDR), and based on % and absolute changes in forced expiratory volume in 1 s (FEV₁), has been recently developed and validated in patients with chronic obstructive pulmonary disease, and against multiple objective and subjective measurements. In this study, working on several large spirometry cohorts from two different institutions (n=31 598 tests), we redefined the novel BDR categories based on delta post-BD-pre-BD FEV₁ % predicted values. Our newly proposed BDR partition is based on several distinct intervals for delta post-BD-pre-BD % predicted FEV₁ using Global Lung Initiative predictive equations. In testing, training and validation cohorts, the model performed well in all BDR categories. In a validation set that included only normal baseline spirometries, the partition model had a higher rate of misclassification, possibly due to unrestricted BD use prior to baseline testing. A partition that uses delta % predicted FEV₁ with the following intervals ≤0%, 0%-2%, 2%-4%, 4%-8% and >8% may be a valid and easy-to-use tool for assessing BDR in spirometry. We confirmed in our cohorts that these thresholds are characterized by low variance and that they are generally gender-independent and race-independent. Future validation in other cohorts and in other populations is needed.

Keywords: chronic obstructive; pulmonary disease; respiration disorders; respiratory physiological phenomena; respiratory system.

Figure 1

Box-and-whisker plots representing delta post-BD–pre-BD % predicted FEV₁ (A), FVC (B) and FEV₁/FVC ratio (C) in the standard ATS/ERS BDR categories. Marker color coding was done based on the new BDR categories: green—negative, yellow—minimal, pink—mild, bright red—moderate and dark red—marked. ATS, American Thoracic Society; BD, bronchodilator; BDR, bronchodilator responsiveness; ERS, European Respiratory Society; FEV₁, forced expiratory volume in 1 s; FVC, forced vital capacity; GLI, Global Lung Initiative.

Figure 2

Box-and-whisker plots of delta post-BD–pre-BD % predicted FEV₁ (A), FVC (B) and FEV₁/FVC ratio (C) against the new BDR categories. Marker color coding was done based on the new BDR categories: green—negative, yellow—minimal, pink—mild, bright red—moderate and dark red—marked. BD, bronchodilator; BDR, bronchodilator responsiveness; FEV₁, forced expiratory volume in 1 s; FVC, forced vital capacity; GLI, global lung initiative.

Figure 3

(A) Partition by delta % predicted FEV₁ (training set), with random, internal cross-validation in 33% of the cohort (testing set): good partition model (high values for both generalized and entropy R²). (B) Partition by delta % predicted FEV₁ in validation set 1, from AVAHCS (preserved model performance). (C) Partition by delta % predicted FEV₁ in validation set 2, from Cleveland Clinic (a decrement in model performance is noted). AUROC, area under receiver operating characteristic curve; AVAHCS, Atlanta Veteran Affairs Healthcare System; BD, bronchodilator; BDR, bronchodilator responsiveness; FEV₁, forced expiratory volume in 1 s; Mean Abs Dev, mean absolute deviance; RASE, square root of the mean squared prediction error.