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During pressure support ventilation, ventilator inspiration ends when inspiratory flow drops to a given percentage of the peak inspiratory flow cycling-off criteria. This study evaluated the effect of two different cycling-off criteria on breathing pattern, respiratory effort, and gas exchange in patients with chronic obstructive pulmonary disease.Clinical study.Thirteen mechanically ventilated patients with acute exacerbation of chronic obstructive pulmonary disease primarily due to pneumonia (Pao2/Fio2 291 ± 114 mm Hg, Paco2 53 ± 19 mm Hg).Two cycling-off criteria (5% and 40% of the peak inspiratory flow) at two levels of pressure support (5 and 15 cm H2O) with and without the application of an external positive end-expiratory pressure (6 and 0 cm H2O) were applied.Patient–ventilator time delay of cycling-off was computed as the difference between the end of inspiratory flow and the lowest value of inspiratory esophageal pressure. Inspiratory effort was estimated by computing the work of breathing, the pressure time product partitioned into the total pressure time product, and the pressure time product due to the dynamic intrinsic positive end-expiratory pressure.At 5 and 15 cm H2O of pressure support ventilation, the cycling-off criteria 40% significantly reduced the patient–ventilator time delay of cycling-off from 0.40 ± 0.20 secs to 0.29 ± 0.16 secs and from 0.93 ± 0.50 secs to 0.52 ± 0.25 secs, respectively; the dynamic intrinsic positive end-expiratory pressure from 3.9 ± 1.8 cm H2O to 3.1 ± 2.1 cm H2O and from 2.4 ± 2.0 cm H2O to 1.7 ± 1.4 cm H2O, respectively; and the pressure time product due to the dynamic intrinsic positive end-expiratory pressure.At 5 cm H2O of pressure support, the cycling-off criteria 40% significantly reduced the tidal volume and the inspiratory effort. The modification of cycling-off criteria did not affect the gas exchange.The modification of cycling-off criteria may have a beneficial effect on reducing the dynamic hyperinflation and inspiratory effort in chronic obstructive pulmonary disease patients, especially at low levels of pressure support.