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      Area under the forced expiratory flow-volume loop in spirometry indicates severe hyperinflation in COPD patients

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          Severe hyperinflation causes detrimental effects such as dyspnea and reduced exercise capacity and is an independent predictor of mortality in COPD patients. Static lung volumes are required to diagnose severe hyperinflation, which are not always accessible in primary care. Several studies have shown that the area under the forced expiratory flow-volume loop (AreaFE) is highly sensitive to bronchodilator response and is correlated with residual volume/total lung capacity (RV/TLC), a common index of air trapping. In this study, we investigate the role of AreaFE% (AreaFE expressed as a percentage of reference value) and conventional spirometry parameters in indicating severe hyperinflation.

          Materials and methods

          We used a cohort of 215 individuals with COPD. The presence of severe hyperinflation was defined as elevated air trapping (RV/TLC >60%) or reduced inspiratory fraction (inspiratory capacity [IC]/TLC <25%) measured using body plethysmography. AreaFE% was calculated by integrating the maximal expiratory flow-volume loop with the trapezoidal rule and expressing it as a percentage of the reference value estimated using predicted values of FVC, peak expiratory flow and forced expiratory flow at 25%, 50% and 75% of FVC. Receiver operating characteristics (ROC) curve analysis was used to identify cut-offs that were used to indicate severe hyperinflation, which were then validated in a separate group of 104 COPD subjects.


          ROC analysis identified cut-offs of 15% and 20% for AreaFE% in indicating RV/TLC >60% and IC/TLC <25%, respectively (N=215). On validation (N=104), these cut-offs consistently registered the highest accuracy (80% each), sensitivity (68% and 75%) and specificity (83% and 80%) among conventional parameters in both criteria of severe hyperinflation.


          AreaFE% consistently provides a superior estimation of severe hyperinflation using different indices, and may provide a convenient way to refer COPD patients for body plethysmography to address static lung volumes.

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          Most cited references 23

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          Improvement in resting inspiratory capacity and hyperinflation with tiotropium in COPD patients with increased static lung volumes.

          In patients with COPD, changes in inspiratory capacity (IC) have shown a higher correlation to patient-focused outcomes, such as dyspnea with exercise, than other standard spirometric measurements. Changes in IC reflect changes in hyperinflation. Tiotropium is a once-daily inhaled anticholinergic that has its effect through prolonged M3 muscarinic receptor antagonism and has demonstrated sustained improvements in spirometric and health outcomes. We sought to evaluate changes in resting IC and lung volumes after long-term administration of tiotropium. To evaluate the effect of tiotropium, 18 micro g/d, on IC, a 4-week, randomized, double-blind, placebo-controlled study was conducted in 81 patients with stable COPD. At each of the visits (weeks 0, 2, and 4) FEV(1), FVC, IC, slow vital capacity (SVC), and thoracic gas volume (TGV) were measured prior to study drug (- 60 and - 15 min) and after study drug (30 min, 60 min, 120 min, and 180 min). Mean age was 64 years; 62% were men. Mean baseline FEV(1) was 1.12 L (43% predicted). The mean differences (tiotropium - placebo) in FEV(1) trough (morning before drug), peak, and area under the curve over 3 h values (adjusted for baseline and center differences) at week 4 were 0.16 L, 0.22 L, and 0.22 L, respectively (p < 0.01 for all); differences in IC for these variables were 0.22 L, 0.35 L, and 0.30 L (p < 0.01 for all). Differences in TGV were - 0.54 L, - 0.60 L, and - 0.70 L, respectively (p < 0.01 for all). The percentage improvement in area under the curve above baseline with tiotropium was similar among FEV(1) and lung volumes (FEV(1), 18%; FVC, 20%; SVC, 16%; IC, 16%; TGV, 14%). Observed improvements in IC and reductions in TGV with once-daily tiotropium reflect improvements in hyperinflation that are maintained over 24 h.
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            Lung function in adults with stable but severe asthma: air trapping and incomplete reversal of obstruction with bronchodilation.

            Five to ten percent of asthma cases are poorly controlled chronically and refractory to treatment, and these severe cases account for disproportionate asthma-associated morbidity, mortality, and health care utilization. While persons with severe asthma tend to have more airway obstruction, it is not known whether they represent the severe tail of a unimodal asthma population, or a severe asthma phenotype. We hypothesized that severe asthma has a characteristic physiology of airway obstruction, and we evaluated spirometry, lung volumes, and reversibility during a stable interval in 287 severe and 382 nonsevere asthma subjects from the National Heart, Lung, and Blood Institute Severe Asthma Research Program. We partitioned airway obstruction into components of air trapping [indicated by forced vital capacity (FVC)] and airflow limitation [indicated by forced expiratory volume in 1 s (FEV(1))/FVC]. Severe asthma had prominent air trapping, evident as reduced FVC over the entire range of FEV(1)/FVC. This pattern was confirmed with measures of residual lung volume/total lung capacity (TLC) in a subgroup. In contrast, nonsevere asthma did not exhibit prominent air trapping, even at FEV(1)/FVC <75% predicted. Air trapping also was associated with increases in TLC and functional reserve capacity. After maximal bronchodilation, FEV(1) reversed similarly from baseline in severe and nonsevere asthma, but the severe asthma classification was an independent predictor of residual reduction in FEV(1) after maximal bronchodilation. An increase in FVC accounted for most of the reversal of FEV(1) when baseline FEV(1) was <60% predicted. We conclude that air trapping is a characteristic feature of the severe asthma population, suggesting that there is a pathological process associated with severe asthma that makes airways more vulnerable to this component.
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              Standardized lung function testing. Official statement of the European Respiratory Society.

               PHH Quajner (corresponding) (1993)

                Author and article information

                Int J Chron Obstruct Pulmon Dis
                Int J Chron Obstruct Pulmon Dis
                International Journal of COPD
                International Journal of Chronic Obstructive Pulmonary Disease
                Dove Medical Press
                14 February 2019
                : 14
                : 409-418
                [1 ]Laboratory of Respiratory Diseases, Department of Chronic Diseases, Metabolism and Ageing, Katholieke Universiteit Leuven, Leuven, Belgium, wim.janssens@
                [2 ]Division of Animal and Human Health Engineering, Department of Biosystems, Katholieke Universiteit Leuven, Leuven, Belgium
                Author notes
                Correspondence: Wim Janssens, Laboratory of Respiratory Diseases, Department of Chronic Diseases, Metabolism and Ageing, Katholieke Universiteit Leuven, O&N1, Herestraat 49, bus 706, Leuven 3000, Belgium, Tel +32 1637 7265, Fax +32 1634 6803, Email wim.janssens@
                © 2019 Das et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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