EFL was present in 10 of the 22 subjects (45%), and the magnitude of EFL ranged from 11% to 58%, with an average of 37% ± 14%. All EFL values represent the maximum amount of EFL experienced by each subject; this occurred in the final work rate in all but one subject. Figure 2 depicts the MEFV curve along with resting and maximal exercise flow-volume loops in two representative subjects matched for height, body mass, and FVC. One subject did not show any EFL at any time during exercise (Fig. 2A), whereas the other subject was expiratory flow-limited for 41% of her tidal breath at maximal exercise (Fig. 2B). The primary differences between these subjects were their dysanapsis ratio and their expiratory flows throughout their MEFV curve. The larger dysanapsis ratio and higher maximal flows for any given lung volume indicate that the subject in Figure 2A had larger airways.
Expiratory flow rates.
Table 1 shows that the NEFL group had significantly higher peak expiratory flows (PEF) and flows at 75%, 50%, and 25% of FVC relative to the EFL group. However, when expressed as a percentage of PEF, the NEFL only had greater flows at 50% and 25% of FVC. Therefore, both groups had similar decreases in expiratory flow from PEF to 75% FVC, whereas the EFL group had a more dramatic drop in expiratory flow from 75% to 50% and from 50% to 25% FVC.
Operational lung volumes.
Figure 3 depicts changes in operational lung volumes from rest to maximal exercise between groups. There was no difference in EILV from rest to maximal exercise, with both groups increasing their EILV progressively from rest to maximal exercise. The NEFL group had a larger EELV at 20%, 60%, 80%, and 100% of maximal work rate. In addition, both groups decreased their EELV from rest and throughout the first part of their exercise bouts. At 60% and 80% of maximal work rate, the NEFL and EFL groups increased their EELV back toward resting levels, respectively. At their maximum work rates, neither group reached their resting EELV.
Figure 4 illustrates the ratio between FVC (to reflect lung size) and the dysanapsis ratio (to reflect airway size). Both groups demonstrated a downward trend in the dysanapsis ratio as FVC increased. However, the NEFL group had a larger average FVC and dysanapsis ratio than the EFL group (4.4 ± 0.4 vs 3.7 ± 0.4 L and 0.27 ± 0.06 vs 0.21 ± 0.04, respectively, P < 0.05). Moreover, throughout the range of FVC, the NEFL group had a larger dysanapsis ratio.
The purpose of this study was to determine potential mechanisms associated with EFL susceptibility during exercise in healthy women. The major findings of this study are threefold. First, EFL is more common in women with smaller lung volumes, expiratory flows, and a smaller dysanapsis ratio. Second, maximal aerobic capacity was not different between the flow-limited and non-flow-limited groups. Finally, EELV was higher in the women who did not experience EFL. Our findings indicate that the occurrence and severity of EFL is principally dependent upon differences in pulmonary anatomy rather than in aerobic fitness.
We found significant differences between the EFL and NEFL group with respect to their level of dysanapsis. The NEFL group demonstrated a larger dysanapsis ratio, which indicates a larger airway size (Fig. 4). This implies that, for a given lung volume, the NEFL group has larger airways than the EFL group. However, because the dysanapsis ratio is scaled to the specific lung volume, estimations of absolute airway size cannot be made between two different lung volumes. It is assumed that as lung volumes increase, the absolute airway size will show a gradual upward trend; however, the larger lung volumes will have a smaller dysanapsis ratio. The negative correlation between the dysanapsis ratio and lung volume we observed (Fig. 4; r = −0.61 and −0.69, P < 0.05; NEFL and EFL, respectively) agrees with the work of Mead (27), who used the same calculation to describe dysanapsis. The association is thought to be due to airway length being dependent upon lung volume, whereas airway diameter is independent of lung volume (16). Because larger lung volumes must have a longer airway length and not necessarily a larger airway radius, the relative expiratory flow will decrease as lung volume increases (16). Yet, as lung volume increases, the airways are thought to become relatively smaller to the lungs, when compared with smaller lung volumes.
Flow can be considered laminar, turbulent, or transitional. Laminar flow typically occurs in small diameter airways, which have a large total cross-sectional area, whereas turbulent flow occurs in the larger diameter airways (39). The majority of airway resistance arises in the larger conducting airways, whereas the smaller (<2 mm) distal airways contribute little; the major reasons for this are the difference in total cross-sectional area and the different forms of flow present in the various airways (39). Laminar flow is bound by the properties of flow through a tube as described by the Poiseuille law. Because the viscosity and the density of exhaled air are similar between individuals breathing room air, intersubject differences in resistance are principally due to differences in airway radius and length. In contrast, turbulent and transitional flows are governed by a nonlinear equation that is dependent on airway radius and a friction factor dependent on the Reynolds number. Completely turbulent flow probably occurs only in the trachea and the first few airway generations, where the radius is large and the airflow velocities are high, or in areas where there are multiple branches (39). EFL occurs over the middle part of the MEFV curve where flow is determined by intrinsic factors such as airway size and static recoil rather than driving pressure (28). To our knowledge, this is the first study that has measured EFL during exercise and used an index of dysanapsis in a group of healthy subjects. We (12,36) and others (26) have suggested that relatively smaller airways and therefore dysanapsis will influence the occurrence and severity of EFL. Consequently, because of their smaller airways, the EFL group may reduce expiratory flows from more turbulent flow and thus increase resistance. As such, there may be a threshold effect with respect to the dysanapsis ratio and EFL. As seen in Figure 4, the two groups exist discretely and have a distinctive area separating them. Such an area could represent a critical point in airway size where flow in the smaller airways becomes less laminar and possibly turbulent from the increased resistance, whereby flow is decreased and EFL can arise. However, we make the suggestion of a threshold cautiously because several factors are assumed and the number of subjects in the present study is relatively small (n = 22). Furthermore, we do not know where dysanapsis is present in the airway tree, and we are not able to determine the pattern of airflow in the airways. Nevertheless, we believe this finding warrants further investigation with a large sample size and a broad range of fitness levels and body sizes, where airway diameter and airway resistance are measured.
We found that our NEFL group had an absolute FVC that was significantly larger than that of the EFL group (4.4 vs 3.7 L, respectively), and when expressed as a percent predicted value, they were marginally different (110% vs 103%, P = 0.052, respectively). The larger lung volumes of the NEFL group seem to provide a protective benefit from developing EFL. Furthermore, the absolute expiratory flows of our NEFL group were significantly higher throughout the MEFV curve. The higher expired flows would be the results of both larger lung volumes and possibly the larger airway size, as discussed above. However, when we expressed the flows as a percentage of the PEF, the NEFL group was only different at forced expired flow at 50% of FVC (FEF50) and at 25% of FVC (FEF25). This indicates that both groups had similar decreases from PEF to forced expired flow at 75% FVC (FEF75), but the EFL group had a larger decrease from FEF75 to FEF50 and from FEF50 to FEF25 (Table 1). This finding is noteworthy because EFL occurs over the center part of the MEFV curve, generally from FEF25 to FEF75 (17). The relatively larger drop from FEF25 to FEF75 could be due to the relatively smaller airways and the equal pressure point that governs expiratory flow over the effort independent part of the MEFV curve. The EFL groups, having a smaller dysanapsis ratio and therefore more resistance, could have their equal pressure point develop earlier and occur at a larger percentage of the lung volume (28). Consequently, the higher expiratory flows, particularly in the FEF75 to FEF25 region of the MEFV curve, along with the larger FVC, give the NEFL group a larger overall MEFV curve. The larger MEFV curve serves to increase the capacity to generate minute ventilation before any EFL occurs.
We did not find a difference between the groups with respect to aerobic fitness, nor did we show a strong relationship between EFL and aerobic fitness (r = 0.13, P = 0.22). The NEFL and EFL groups were similar with respect to aerobic fitness levels (50.8 vs 46.7 mL·kg−1·min−1, respectively, P = 0.264). In addition, subjects were split into more fit (V˙O2max >48 mL·kg−1·min−1) and less fit (V˙O2max <48 mL·kg−1·min−1) groups, as previously done (25), with no difference in EFL (12% vs 23%, respectively, P = 0.20). Indeed, our subjects with the highest and lowest levels of aerobic fitness both showed 0% EFL. This finding differs from other studies that have looked at EFL and varying fitness levels in young women (25). In this study, McClaran et al. (25) found that aerobically fit young women showed more EFL during exercise than their less fit counterparts. We believe there are several reasons for the contrasting results between the present study and the work of McClaran et al. (25). First, our study used a bicycle ergometer, whereas their study (25) used a treadmill. The use of a treadmill will normally result in a higher maximal oxygen consumption; thus, a larger minute ventilation will be needed to meet the increased metabolic demands (8,34). Both groups in the aforementioned study had larger maximal minute ventilations compared with our groups (104 and 113 vs 98 and 86 L·min−1, respectively) (25). Furthermore, we used a different variable to divide our groups, compared with the previous study (25). Our groups were separated on the basis of the occurrence of EFL, and they had notable differences in pulmonary anatomical features (FVC, expiratory flows, dysanapsis ratio). Conversely, McClaran et al. (25) partitioned their groups on the basis of aerobic fitness, with no differences in features related to pulmonary anatomy (vital capacity and expiratory flows). To illustrate the possible difference in EFL, we use several theoretical situations. First, if two women were matched for aerobic fitness and presumable maximal minute ventilations but not anatomical features, we would expect the individual with larger anatomical features to be less flow limited than the individual with smaller anatomical features. If we matched two women for anatomical features but not aerobic fitness, we would expect the fitter individual to show more EFL because she is more likely to achieve a higher minute ventilation. However, if we matched two women who have larger-than-predicted anatomical features, similar to that of a like-sized male, different aerobic fitness levels may not change the occurrence of EFL. Men generally require much higher levels of aerobic fitness before EFL is present. Achieving such a high level of fitness may be unattainable by all but a few women. This is consistent with the "demand versus capacity" concept, whereby the capacity to generate flow and therefore ventilate is bound by the mechanical limits of the respiratory system, whereas demand is a function of fitness (6). An individual's capacity to ventilate is generally believed to be fixed and not altered by habitual training (21,24,25,32); demand, however, can vary immensely and is easily trainable. Because of the lower minute ventilation, some of our fitter subjects may not have approached their capacity to ventilate and therefore may not have come close to experiencing EFL. In contrast, most of McClaran et al.'s (25) fitter subjects approached their ventilatory capacity and had to alter their breathing patterns to continue exercise, which may explain the increased EFL. Our less fit subjects would have reached their ventilatory capacity because of constraints to their MEFV curve (see above discussion). Ours and the aforementioned study (25) both argue that the smaller anatomical features of women contribute to their increased prevalence and severity of EFL; however, because of the above reasons, we were unable to show the secondary fitness effect.
Operational lung volumes.
Both groups showed the expected drop in EELV as exercise intensity increased (14,21,29,35,40). This decrease, from the recruitment of expiratory musculature, allows the diaphragm length to be optimized and the tidal volume to increase without excessive increases in EILV. However, we found that the NEFL group breathed at higher EELV at 20%, 60%, 80%, and 100% of maximal work rates (Fig. 3). When breathing at a higher EELV, an individual can take advantage of the higher expiratory flows available at larger lung volumes and thereby increase their capacity to ventilate (9). At maximal work rates, the NEFL subjects may have increased their EELV to avoid EFL. Similarly, Mota et al. (29) demonstrated increases in EELV in the absence of EFL. They (29) speculate that the increase in EELV is due to individuals approaching their mechanical limits to generate expiratory flow, and EELV must therefore be increased to avoid any dynamic compression of the airways and thus avoid EFL. Dynamic compression of the airways has been implicated as a trigger to a reflex that can cause the premature cessation of expiration, possibly leading to dynamic hyperinflation (31). A similar change in EELV was demonstrated in our EFL group but not to the same degree as the NEFL group. Therefore, we speculate that because of their lower minute ventilation, the EFL group may not have approached their mechanical limit to ventilate until near maximal exercise, when their ventilation increased. Upon approaching their mechanical limit thereby experiencing EFL, the flow-limited group may have increased their EELV to minimize the flow limitation. However, because neither group increased their EELV above resting levels, they probably did not incur significant energetic consequences because they were not breathing above resting levels (i.e., dynamically hyperinflating). There was no difference in EILV, with both groups increasing consistently from rest to maximal work rates.
The specific mechanisms underlying the perception of breathlessness remains obscure but dyspnea is associated with increased central respiratory neural drive, altered afferent feedback from respiratory sensors, and the dissociation between efferent output and afferent sensory inputs. The list of peripheral receptors that respond to stimuli that are potentially dyspnogenic is long and has been reviewed elsewhere (23). EFL is associated with an increased work of breathing and presumably greater sensory input arising from the respiratory muscles. However, we found no difference between the NEFL and EFL groups with respect to their RPE for breathlessness at maximal exercise. Several studies have shown that externally imposed EFL can lead to an increase in the sensation of dyspnea when compared with an identical exercise protocol without EFL (19). The present study was not designed to specifically assess the mechanisms of dyspnea; however, it is possible that the similar dyspnea levels observed in our study were due to an absence of significant dynamic hyperinflation. Dynamic hyperinflation has been associated with the increase in dyspnea with EFL (19). It is also possible that sensory input that was unrelated to EFL may have masked any between-group differences during exercise.
The accurate assessment of EFL is dependent on both the MEFV curve and the correct placement of the tidal breaths within this curve. The approach used in this study addresses previous concerns over this method because we have accounted for both thoracic gas compression and bronchodilation in generating the MEFV curve (11). However, this technique does not account for differences in volume and time history that precede tidal expirations and forced expiratory maneuvers (5,29). We instructed the subjects to rapidly inhale to total lung capacity and then expire without an inspiratory pause, allowing elastic recoil of the lungs and chest wall to be at its greatest (5). The placement of tidal breaths within the MEFV curve depends on the subject's ability to fully inspire to total lung capacity with each IC maneuver. We took several precautions to ensure that subjects correctly performed this maneuver. All subjects had extensive practice with and without visual feedback, and no data were collected until each subject could consistently perform the maneuver without visual cues. Moreover, the experimenter had continuous online feedback to ensure the maneuver was performed accurately throughout exercise. IC maneuvers have consistently been shown to be an accurate and reproducible measurement that has been extensively used in healthy and clinical populations (14,20,21,29,40).
Values for Pst(l)50 were obtained using a prediction equation from a previously published work (37). The subjects in the aforementioned study varied in age and were primarily male (37). However, sex-based differences with respect to Pst(l) are unlikely, because the lungs and chest walls of men and women have the same intrinsic elasticity (4). Any variation between the sexes is due to men generally having larger lung volumes and, therefore, larger distending forces (4). We chose to estimate Pst(l)50 on the basis of the method of Mead (27) because directly measured Pst(l)50 involves a difficult procedure for subjects to perform and the increased invasiveness of an esophageal catheter (39). To accurately measure Pst(l)50, subjects must inhale to total lung capacity and expire passively. At 50% of total lung capacity, the tubing that leads to the spirometer (or another device measuring volume) is occluded, stopping all expired flow. With the tube occluded, the subject must completely relax their respiratory muscles while their glottis remains open. The procedure must be repeated several times because any muscular effort can easily alter the results. To date, few studies have measured Pst(l)50 with a similarly large sample size across varying ages, as did Turner et al. (37). Therefore, the variability and reliability of the estimate is unknown. However, to ensure a Pst(l)50 prediction equation would be appropriate for use in the dysanapsis ratio, we reanalyzed our data by applying a random ±15% error to the Pst(l)50 values. The new Pst(l)50 values, along with the unaltered values for the dysanapsis ratio, were graphed and analyzed using the same statistical approach. Although the values shifted, the discrete NEFL and EFL groups that were statistically different remained, suggesting that our estimation of Pst(l)50 did not affect our primary outcome.
Sex differences and future directions.
As most women have smaller lungs and airways, compared with similar-sized men (1,27), they tend to develop EFL more often than men (12). Indeed, the increased occurrence of pulmonary system limitations in women may not be trivial because studies have shown women may be more prone to exercise-induced arterial hypoxemia (13,33). In women, when the mechanical constraint to ventilation is partially removed (by inspiring a heliox gas mixture), ventilation can increase but not to the extent needed to fully offset the hypoxemia (25). However, this sex difference with respect to hypoxemia is not a universal finding, with evidence indicating that the prevalence is similar between the sexes (15). To date, there has not been a conclusive study to address the discrepancy. Several unknowns remain with respect to our findings. Specifically, does the relationship between the dysanapsis ratio and EFL extend toward men or a group including both sexes? Second, does a threshold in the dysanapsis ratio exist, and if so, what change occurs when the threshold is met or exceeded? Third, what are the mechanisms underlying the appearance of EFL with a smaller dysanapsis ratio, a change in flow characteristics or simply a reduction in flow due to radius changes? Finally, how are between-subject differences with respect to dysanapsis manifested in women with reduced exercise ventilatory capacity such as healthy aging or cardiorespiratory disease?
We found that the occurrence of EFL is primarily related to differences in respiratory anatomy rather than in aerobic fitness levels. Specifically, individuals with larger airways relative to their lungs' volumes (i.e., larger dysanapsis ratio), larger absolute lung volumes, and larger expiratory flows seem less susceptible to EFL during dynamic exercise. Secondary to anatomical differences, individuals who are more aerobically fit may develop more severe EFL at maximal work rates because of their higher metabolic and therefore ventilatory demands.
This study was supported by the Natural Science and Engineering Research Council of Canada (NSERC) and the British Columbia Lung Association. J.A. Guenette was supported by graduate scholarships from the NSERC, the Michael Smith Foundation for Health Research, and the Sir James Lougheed Award of Distinction and is currently supported by a postdoctoral fellowship from the NSERC and the John Alexander Stewart Fellowship. S.S. Wilkie was supported by a Canadian Graduate Scholarship graduate award from the NSERC. G.E. Foster was supported by a postdoctoral fellowship from the NSERC. A.W. Sheel was supported by a New Investigator award from the Canadian Institutes for Health Research.
The authors thank their subjects for their enthusiastic participation.
The results of the present study do not constitute endorsement by the American College of Sports Medicine.
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Keywords:©2011The American College of Sports Medicine
DYSANAPSIS; EXPIRATORY FLOW LIMITATION; GENDER; LUNG MECHANICS