A New Bronchodilator Response Grading Strategy Identifies Distinct Patient Populations - PubMed (original) (raw)

Comparative Study

A New Bronchodilator Response Grading Strategy Identifies Distinct Patient Populations

James E Hansen et al. Ann Am Thorac Soc. 2019 Dec.

Abstract

Rationale: A positive bronchodilator response (BDR) according to American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines require both 200 ml and 12% increase in forced expiratory volume in 1 second (FEV1) or forced vital capacity (FVC) after bronchodilator inhalation. This dual criterion is insensitive in those with high or low FEV1.Objectives: To establish BDR criteria with volume or percentage FEV1 change.Methods: The largest FEV1 and FVC were identified from three pre- and three post-bronchodilator maneuvers in COPDGene (Genetic Epidemiology of COPD) participants. A total of 7,741 individuals with coefficient of variation less than 15% for both FEV1 and FVC formed bronchodilator categories of FEV1 response: negative (≤0.00% or ≤0.00 L), minimal (>0.00% to ≤9.00% or >0.00 L to ≤0.09 L), mild (>9.00% to ≤16.00% or >0.09 L to ≤0.16 L), moderate (>16.00% to ≤26.00% or >0.16 L to ≤0.26 L), and marked (>26.00% or >0.26 L). These response size categories are based on empirical limits considering average FEV1 increase of approximately 160 ml and the clinically important difference for FEV1. To compare flow and volume response characteristics, BDR-FEV1 category assignments were applied for the BDR-FVC response.Results: Twenty percent met mild and 31% met moderate or marked BDR-FEV1 criteria, whereas 12% met mild and 33% met moderate or marked BDR-FVC criteria. In contrast, only 20.6% met ATS/ERS positive criteria. Compared with the negative BDR-FEV1 category, the minimal, mild, moderate, and marked BDR-FEV1 categories were associated with greater 6-minute-walk distance and lower St. George's Respiratory Questionnaire and modified Medical Research Council dyspnea scale scores. Compared with negative BDR, moderate and marked BDR-FEV1 categories were associated with fewer exacerbations, and minimal BDR was associated with lower computed tomography airway wall thickness. Compared with the negative category, all BDR-FVC categories were associated with increasing emphysema percentage and gas trapping percentage. Moderate and marked BDR-FVC categories were associated with higher St. George's Respiratory Questionnaire scores but fewer exacerbations and lower dyspnea scores.Conclusions: BDR grading by FEV1 volume or percentage response identified subjects otherwise missed by ATS/ERS criteria. BDR grades were associated with functional exercise performance, quality of life, exacerbation frequency, dyspnea, and radiological airway measures. BDR grades in FEV1 and FVC indicate different clinical and radiological characteristics.

Keywords: airflow obstruction; bronchodilator responsiveness; forced expiratory volume in 1 second.

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Figures

Figure 1.

Figure 1.

Mean forced expiratory volume in 1 second (FEV1) bronchodilator response in volume (in L) and as a percentage by clusters of 100 individuals at each point as baseline FEV1 percent predicted value increases for the 6,107 participants with positive bronchodilator response. Changes in volume (left axis, ∆FEV1L) and percent predicted (right axis, ∆FEV1%) differ markedly. Although ∆FEV1L increases rapidly to approximately 0.16 L and stabilizes at that level (represented with the dashed line on the graph), ∆FEV1% fraction gradually declines in a hyperbolic fashion from 16% to 4%.

Figure 2.

Figure 2.

Restricted cubic spline models of bronchodilator response (BDR; as separate continuous variables change in forced expiratory volume in 1 second in liters [ΔFEV1 L], change in forced expiratory volume in 1 second percent predicted [ΔFEV1%], change in forced vital capacity in liters [ΔFVC L], and change in forced vital capacity percent predicted [ΔFVC%]), with 95% confidence intervals (in gray), for 6-minute-walk distance (6MWD), total St. George’s Respiratory Questionnaire (SGRQ) score, and quantitative computed tomography (CT) measures in the total study population. (A) The adjusted models of BDR (FEV1L and BDR − FEV1%) for 6MWD, SGRQ, wall area (WA) segmental percentage, and square root wall area of a 15-mm diameter airway (Pi15). (B) The adjusted models of BDR − FVCL and BDR − FVC% for SGRQ, emphysema percentage, and gas trapping percentage. ΔFEV1L, ΔFEV1%, ΔFVCL, and ΔFVC% were coded using a restricted cubic spline function with three knots, located at the 5th, 50th, and 95th percentiles. Models were adjusted for age, sex, race, smoking history, body mass index, baseline FEV1 or FVC, and CT scanner type (for CT measures).

Figure 3.

Figure 3.

Distribution of change in absolute volume for largest of three pre- to post-bronchodilator forced expiratory volume in 1 second (FEV1) differences (ΔFEV1L) and change in FEV1 percent predicted after bronchodilator in the whole study population (N = 7,741). Dashed vertical lines represent the limits of the new bronchodilator response (BDR) grading system (negative, ≤0.00% or ≤0.00 L; minimal [MIN], >0.00% to ≤9.00% or >0.00 L to ≤0.09 L; mild, >9.00% to ≤16.00% or >0.09 L to ≤0.16 L; moderate [MOD], >16.00% to ≤26.00% or >0.16 L to ≤0.26 L; and marked, >26.00% or >0.26 L). Percentages of participants in each BDR category are given between vertical lines that represent the limits of the BDR grading system. Curves were constructed as Gaussian fits on the histogram points consisting of 24 bins with equal distance of 0.0905 L spanning from −0.63 L to 1.45 L for ΔFEV1L and 6.46% wide bins from −31.8 to 116.8% for ΔFEV1% change. N.B.: To demonstrate the similarities and differences in distributions, only the segments from −0.4 L to 0.6 L and from −40% to 60% changes are shown.

Figure 4.

Figure 4.

Response trend of change in forced expiratory volume in 1 second (ΔFEV1) and change in forced vital capacity (ΔFVC) after bronchodilator in the total study population (N = 7,741). (A) Response trend of mean change in absolute volume of ΔFEV1L and ΔFVCL in 500 individuals at each point. (B) Response trend of mean change in ΔFEV1% and ΔFVC% in 500 individuals at each point. In both A and B, individuals are ordered by size of response.

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