Journal of Applied Physiology
Vol. 82, No. 3, pp. 721-722, March 1997

Invited Editorial on "Detection of expiratory flow limitation during exercise in COPD patients"

Joe R. Rodarte

Pulmonary and Critical Care Section, Department of Medicine, Baylor College of Medicine, Houston, Texas 77030-2720

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IN HUMANS, EXPIRATION during quiet breathing is usually considered passive, since expiratory muscles are not active. Expiration is driven by elastic energy stored in the respiratory system at end inspiration. Inspiratory muscles relax gradually, reducing flow in the early part of expiration so that lung volume does not reach functional residual capacity (FRC) before time to initiate the next breath (12). In humans at rest, FRC is the elastic equilibrium volume between the recoils of the lung and chest wall. Dogs and most other animals utilize active expiration while awake (4) so that FRC is lower than the relaxation volume of the respiratory system. During exercise, normal humans increase ventilation in part by recruitment of expiratory muscles (7). Tidal volume increases initially as much by reduction of FRC as increase of end-inspiratory volume (1, 15). Both tidal volume and frequency increase, although over most of the exercise range increased ventilation is produced predominantly by increases in tidal volume. The reduction in FRC can exceed 50% of the expiratory reserve volume (1, 15). In individuals who never reach maximal expiratory flow, the decrease in FRC presumably is limited by nonlinearities of the chest wall pressure-volume relationship.

Recent data support the following scenario of the effects of reduction of maximal flow on ventilation during exercise. With aging, there is a reduction in maximal expiratory flow so that increasing ventilation with FRC below the resting volume soon produces maximal flows (2, 6, 8, 15). Once this occurs, further increases in ventilation are produced by preserving the normal relationship between mean inspiratory and expiratory flow rates and increasing FRC rather than increasing expiratory effort to utilize maximal flows throughout expiration. Extremely fit elderly individuals may return to or exceed resting FRC at maximal exercise (8). When end inspiration approaches total lung capacity (TLC), end-inspiratory volume does not increase further.

If respiratory timing (inspiratory-to-total time) is preserved, increased ventilation requires an increased mean expiratory flow rate. When expiratory flow is maximal, mean lung volume must be increased to increase mean expiratory flow. Once end-inspiratory volume approaches TLC, mean lung volume can only be increased by increasing FRC. Therefore, at high levels of ventilation, tidal volume plateaus and then decreases (6). Ventilation increases only by increased frequency. Although the mechanisms of this response are not known, it appears that the respiratory controller is programed to maintain normal timing if possible and that achievement of maximal flow is a powerful stimulus to terminate expiration and initiate the next breath (10).

With airway obstruction, more inspiratory muscle activation is required during inspiration to overcome the increased airway resistance, but less inspiratory muscle braking is required to retard expiratory flow. Peak expiratory flow occurs earlier during expiration, and the tidal flow-volume loop resembles a miniature of the maximal flow-volume curve. Expiration may be slowed to the point that the relaxation point is not reached before the next inspiration, and FRC becomes dynamically rather than statically determined (14). With more severe obstruction, elastic recoil of the respiratory system may be sufficient to generate maximal flow without expiratory effort. Whether or not the subjects use maximal expiratory flow at rest, maximal flow below FRC is so low that patients cannot reduce FRC with exercise, and both FRC and end-inspiratory volume increase with increasing ventilation. This reduces the ability of subjects to increase tidal volume and thus limits maximal exercise ventilation (2, 14). When end inspiration is near TLC, each inspiration requires a near-maximal inspiratory effort (11).

These findings suggest that lung mechanics may be a much more important determinant of exercise capacity than has previously been appreciated. There is considerable variability in these general relationships. Some subjects use maximal flow over most of the tidal volume and others only at FRC. Maximal inspiratory volume occurs at different fractions of TLC. These differences may contribute to the variability of the relationship between maximal exercise capacity and forced expiratory volume in 1 s (FEV₁) in patients in whom lung mechanics may be an important determinant of maximal oxygen uptake (O_{2 max}). Reaching maximal expiratory flow over even part of the tidal volume range appears to play an important role in both the mechanics and neural control of respiration, which have not been studied adequately.

The paper by Koulouris et al. (9) in this issue of the Journal of Applied Physiology describes a useful technique for determining when subjects are utilizing maximal flow. The classic description by Fry and Hyatt (5) that for lung volume <20% vital capacity expired maximal flow is constant and independent expiratory effort remains a valid foundation for pulmonary mechanics. However, this relationship is influenced to a significant degree by volume and time history and by measurement artifacts discussed by Kourlouris et al. (9). There is a significant body of literature on the difference of flow between maximal expiratory forced vital capacity curves and "partial" flow-volume curves, typically begun from a volume of 60-70% of vital capacity above residual volume (3, 13). Maximal flow can be very sensitive to end-inspiratory volume, and subjects who may be flow limited during tidal breathing may not appear to be so on a partial flow-volume curve initiated from a volume higher than the spontaneous end inspiration. Although most subjects can, on command, make a brief increased expiratory effort over the tidal volume range, some find this quite difficult. Furthermore, if subjects are flow limited and there is not an esophageal balloon in place, the investigator cannot confirm whether the subject has, indeed, increased expiratory effort on command. By definition, demonstration of expiratory flow limitation requires demonstration of an increase in transpulmonary pressure with no increase in expiratory flow. The technique for an abrupt decrease in airway opening pressure in the absence of an increase in expiratory flow fills this criterion, without requiring patient cooperation and with changes in pressure, which, although perceptible, are certainly not disconcerting. This technique provides a very useful tool for further dissecting the ventilatory responses of patients with airway disease.

In addition to demonstrating a method for detecting flow limitation, Koulouris and associates (9) present interesting data in normal subjects and in chronic obstructive pulmonary disease (COPD) patients, illustrating uses of this technique. There was a highly significant relationship between percent predicted FEV₁ and O_{2 max}, as would be expected given a range of FEV₁ from 30 to 115% predicted. However, there is considerable residual variability even among those subjects with significant COPD (FEV₁ <60% predicted). Mean FEV₁ was progressively lower in subjects who were flow limited at one-third maximum work output and at rest, compared with those flow limited at only two-thirds maximum work or not at all, but there was considerable overlap between the three groups. The tidal volume response to exercise and the lung volumes over which breathing occurred were different, depending on at which workload flow limitation developed. Maximum tidal volume was a better predictor of O_{2 max} than was FEV₁. However, this result may be due, in part, to the fact that the normal subjects were younger and taller and the tidal volume data were not normalized for age or size. These data confirm that the presence of flow limitation affects the ventilatory response to exercise and maximum exercise capacity. It remains to be demonstrated how much this contributes to the variability in O_{2 max} for an FEV₁ low enough that O_{2 max} should be determined by lung disease.

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