Exploring the Utility of Bronchodilator Response in Chronic Obstructive Pulmonary Disease Open Access
Russell, Stephen (Spring 2025)
Abstract
Background
Bronchodilator response (BDR) is a portion of spirometry which is frequently positive in patients with chronic obstructive pulmonary disease (COPD) but has unclear clinical significance. In 2021, the American Thoracic Society/European Respiratory Society (ATS/ERS) adopted a new BDR definition. BDR has intrapersonal variation over time, however it is not known if this is due to natural variation or clinical factors. We sought to compare the 2005 and 2021 BDR definitions, as well as year-to-year variation in BDR, and their association with symptoms, functional status, exacerbations, and mortality in patients with COPD.
Methods
We performed a secondary analysis of the Subpopulations and Intermediate Outcomes Measures in COPD (SPIROMICS) study. We included all enrolled patients with COPD. Spirometry, questionnaires, and 6-minute walk distance (6-MWD) were collected yearly for 3 years. We performed a cross-sectional analysis using both BDR definitions. We assessed each definition and its association with baseline 6-MWD, St. George’s Respiratory Questionnaire for COPD (SGRQ-C), future exacerbations, and mortality. We then assessed whether year-to-year variability in BDR was associated with 6-MWD, SGRQ-C, exacerbations, and mortality.
Results
Of the 1766 included subjects, 54.2% had positive BDR by the 2005 definition and 45.4% by the 2021 definition. The overall Kappa agreement between the definitions was 0.77. Between baseline and year 1, 442 (32.9%) subjects changed BDR status. There was no difference between BDR positive and BDR negative subjects for SGRQ-C, 6-MWD, or mortality using the 2021 BDR definition. Using the 2005 definition, subjects with positive BDR had higher SGRQ-C (39.2 vs. 35,3, p<0.001). Using both definitions, subjects with positive BDR were more likely to have an exacerbation during the study follow up (61.8% vs. 52.5%, p<0.001 for 2005 definition and 61.3% vs. 54.2%, p=0.003 for 2021 definition). BDR changes from baseline to year 1 were not associated with changes in SGRQ-C or 6-MWD.
Conclusion
The 2021 definition of BDR does not predict symptoms, function status, or mortality in patients with COPD but is associated with future exacerbations. Changes in BDR over time are not associated with changes in symptoms or functional status and more likely reflect natural variation of this test.
Table of Contents
Background……………………………………………………………………………………………………………………….1Table 1. Proposed Bronchodilator Response Thresholds………………………….…………………..………..1
Methods……………………………………………………………………………………………………………………………4
Study Design……………………………………………………………………………………………………………………..5
Table 2. Positive Bronchodilator Response Definition….………………………………………………..……..6
Table 3. Changes in BDR from baseline to year 1…………………………………………………….………….…7
Results……………………………………………………………………………………………………………………………..9
Discussion………………………………………………………………………………………………………..……………..12
Figure 1. Study Consort Diagram……………………..……………………………………………..…………………15
Table 4. Patient Characteristics for 2005 BDR…………………………..…………………………………..……16
Table 5: Patient Characteristics for 2021 BDR………………………………………………………………..……17
Table 6. Agreement between 2005 and 2021 Definition for Bronchodilator Response………..…..18
Table 7. Comparison of 2005 and 2021 BDR Definitions and Association with Patient Related outcomes……………………………………………………………………………………………………………………..….19
Table 8. Patients Characteristics for Four Strata formed based on pattern of BDR changes over 1 year………………………………………………………………………………………………………………………..………20
Table 9 Association between BDR Strata and Changes in SGRQ-C and 6MWD over 1 year……..21
Table 10. Association between BDR Strata and Exacerbations During SPIROMICS study follow up…………………………………………………………………………………………………………………………………..22
Appendix Figure 1. Investigating 2005 BDR Definition Component Distributions; volume and percentage for FEV1 and FVC……………………………………………………………………………………..……23
Appendix Figure 2. 2005 BDR, FVC Volume and Percentage Distributions………………………….23
Appendix Figure 3. 2021 BDR, FEV1 and FVC Distributions……………………………………………….24
Appendix Table 1. 2005 and 2021 definition, continuous FEV1 and FVC variables, means and medians………………………………………………………………………………………………………………………….24
Appendix Figure 4. Mortality, Kaplan Meier Curves, 2021 BDR…………………………………………..24
Appendix Figure 5. Kaplan Meier Curve of Mortality, Baseline 2021 BDR, 1000 days follow up…………………………………………………………………………………………………………………………………..25
Appendix Figure 6. Distribution of the difference between year 1 and baseline 6 MWD………….25
Appendix Figure 7. Distribution of the difference between year 1 and baseline SGRQ-C…………26
Appendix Figure 8. Distribution of SGRQ-C, Stratified by Strata of BDR Status at Baseline and Year 1……………………………………………………………………………………………………………………………..26
Appendix Table 2: Multivariate Analysis of BDR Strata and Any Exacerbation Required Healthcare Utilization……………………………………………………………………………………………………..27
Appendix Figure 9. Kaplan Meier Curve Survival Curve for Death During SPIROMICS study follow up, stratified by BDR Strata……………………………………………………………………………………27
References……………………………………………………………………………………………………………………..28
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