Combined FEV1 and FVC Bronchodilator Response, Exacerbations, and Mortality in COPD

Article: Combined FEV1 and FVC Bronchodilator Response, Exacerbations, and Mortality in COPD

Authors: Spyridon Fortis, Alejandro Comellas, Barry J Make, Craig P Hersh, Sandeep Bodduluri, Dimitris Georgopoulos, Victor Kim, Gerard J Criner, Mark T Dransfield, and Surya P Bhatt

Journal: Ann Am Thorac Soc. 2019 Mar 25. doi: 10.1513/AnnalsATS.201809-601OC. [Epub ahead of print]

RATIONALE: The American Thoracic Society/European Respiratory Society defines a positive bronchodilator response (BDR) by a composite of BDR in either FEV1 and/or FVC ≥12% and 200ml (ATS-BDR). We hypothesized that ATS-BDR components would be differentially associated with important COPD outcomes.

OBJECTIVE: To examine whether ATS-BDR components are differentially associated with clinical, functional and radiographic features in COPD.

METHODS: We included subjects with COPD enrolled in the COPDGene study. In the main analysis, we excluded subjects with self-reported asthma. We categorized BDR into the following: (i) No-BDR: no BDR in either FEV1 or FVC, (ii) FEV1-BDR: BDR in FEV1 but no BDR in FVC, (iii) FVC-BDR: BDR in FVC but no BDR in FEV1, and (iv) Combined-BDR: BDR in both FEV1 and FVC. We constructed multivariable logistic, linear, zero-inflated negative binomial and cox-hazards models to examine the association of BDR categories with symptoms, computed tomography findings, change in FEV1 over time, respiratory exacerbations and mortality. We also created models using the ATS BDR definition (ATS-BDR) as the main independent variable.

RESULTS: Of 3,340 COPD subjects included in the analysis, 1,083 (32.43%) had ATS-BDR; 182 (5.45%) had FEV1-BDR; 522 (15.63%) had FVC-BDR and 379 (11.34%) had Combined-BDR. All BDR categories were associated with FEV1 decline compared to No-BDR. Compared to No-BDR, both ATS-BDR and Combined-BDR were associated with higher FRC %predicted, greater Pi10, and greater 6-minute walk distance. In contrast to ATS-BDR, Combined-BDR was independently associated with less emphysema (coef = -1.67, 95%CI= -2.68 to -0.65; p=0.001), more frequent respiratory exacerbations (Incidence Rate Ratio IRR 1.25, 95%CI= 1.03 to 1.50;p=0.02) and severe exacerbations (IRR=1.34, 95%CI=1.05 to 1.71; p=0.02) and lower mortality (adjusted hazards ratio HR =0.76, 95%CI=0.58 to 0.99; p=0.046). Sensitivity analysis that included subjects with self-reported history of asthma showed similar findings.

CONCLUSIONS: BDR in both FEV1 and FVC indicates a COPD phenotype with asthma-like characteristics, and provides clinically more meaningful information than current definitions of BDR.

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