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      Area Under the Expiratory Flow–Volume Curve (AEX): Assessing Bronchodilator Responsiveness

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          Abstract

          Background

          Area under expiratory flow–volume curve (AEX) is a useful spirometric tool in stratifying respiratory impairment. The AEX approximations based on isovolumic flows can be used with reasonable accuracy when AEX is unavailable. We assessed here pre- to post-bronchodilator (BD) variability of AEX 4 as a functional assessment tool for lung disorders.

          Methods

          The BD response was assessed in 4330 subjects by changes in FEV 1, FVC, and AEX 4, which were derived from FVC, peak expiratory flow, and forced expiratory flow at 25%, 50%, and 75% FVC. Newly proposed BD response categories (negative, minimal, mild, moderate and marked) have been investigated in addition to standard criteria.

          Results

          Using standard BD criteria, 24% of subjects had a positive response. Using the new BD response categories, only 23% of subjects had a negative response; 45% minimal, 18% mild, 9% moderate, and 5% had a marked BD response. Mean percent change of the square root AEX 4 was 0.3% and 14.3% in the standard BD-negative and BD-positive response groups, respectively. In the new BD response categories of negative, minimal, mild, moderate, and marked, mean percent change of square root AEX 4 was − 8.2%, 2.9%, 9.2%, 15.0%, and 24.8%, respectively.

          Conclusions

          Mean pre- to post-BD variability of AEX 4 was < 6% and stratified well between newly proposed categories of BD response (negative, minimal, mild, moderate and marked). We suggest that AEX 4 (AEX) could become a useful measurement for stratifying dysfunction in obstructive lung disease and invite further investigation into indications for using bronchodilator agents or disease-modifying, anti-inflammatory therapies.

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          Most cited references33

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          Lung function testing: selection of reference values and interpretative strategies. American Thoracic Society.

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            Bronchodilator reversibility testing in chronic obstructive pulmonary disease.

            A limited or absent bronchodilator response is used to classify chronic obstructive pulmonary disease (COPD) and can determine the treatment offered. The reliability of the recommended response criteria and their relationship to disease progression has not been established. 660 patients meeting European Respiratory Society (ERS) diagnostic criteria for irreversible COPD were studied. Spirometric parameters were measured on three occasions before and after salbutamol and ipratropium bromide sequentially or in combination over 2 months. Responses were classified using the American Thoracic Society/GOLD (ATS) and ERS criteria. Patients were followed for 3 years with post-bronchodilator FEV(1) and exacerbation history recorded 3 monthly and health status 6 monthly. FEV(1) increased significantly with each bronchodilator, a response that was normally distributed. Mean post-bronchodilator FEV(1) was reproducible between visits (intraclass correlation 0.93). The absolute change in FEV(1) was independent of the pre-bronchodilator value but the percentage change correlated with pre-bronchodilator FEV(1) (r=-0.44; p<0.0001). Using ATS criteria, 52.1% of patients changed responder status between visits compared with 38.2% using ERS criteria. Smoking status, atopy, and withdrawing inhaled corticosteroids were unrelated to bronchodilator response, as was the rate of decline in FEV(1), decline in health status, and exacerbation rate. In moderate to severe COPD bronchodilator responsiveness is a continuous variable. Classifying patients as "responders" and "non-responders" can be misleading and does not predict disease progression.
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              Standardized single breath normal values for carbon monoxide diffusing capacity.

              Prediction equations for DLCO and diffusing capacity per unit of lung volume (DL/VA) were generated from 245 normal subjects (122 women and 123 men) using a standardized technique for measuring DLCO. Measurements were made at an altitude of 1,400 meters. Multiple linear regressions were made using standard and robust regression techniques. The resultant equations predicted values for DLCO and DL/VA that were higher than most previously reported values. The use of robust regressions did not add to the predictability of standard linear regressions.
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                Author and article information

                Contributors
                oioac@yahoo.com
                Stollej@ccf.org
                Journal
                Lung
                Lung
                Lung
                Springer US (New York )
                0341-2040
                1432-1750
                24 March 2020
                24 March 2020
                2020
                : 198
                : 3
                : 471-480
                Affiliations
                [1 ]GRID grid.189967.8, ISNI 0000 0001 0941 6502, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, School of Medicine, , Emory University, Atlanta VA Sleep Medicine Center, ; 250 N Arcadia Ave, Decatur, GA 30030 USA
                [2 ]GRID grid.239578.2, ISNI 0000 0001 0675 4725, Education Institute, , Cleveland Clinic, ; 9500 Euclid Ave, Cleveland, OH USA
                Article
                345
                10.1007/s00408-020-00345-2
                7242267
                32211978
                935f3033-b6f2-4c95-91a9-6b9fec7a94f4
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 7 January 2020
                : 11 March 2020
                Categories
                Respiratory Physiology
                Custom metadata
                © Springer Science+Business Media, LLC, part of Springer Nature 2020

                Respiratory medicine
                lung function,spirometry,lung volumes,area under flow–volume curve,bronchodilator response

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