Static respiratory mechanics are unaltered in males and females with obesity

Abstract

We tested the hypothesis that independent of the obesity-related shift in lung volume subdivisions, obesity would not reduce the interrelationships of expiratory flow, lung volume, and static lung elastic recoil pressure in males and females. Simultaneous measurements of expiratory flow, volume, and transpulmonary pressure were continuously recorded while flow-volume loops of varying expiratory efforts were performed in a pressure-corrected, volume-displacement body plethysmograph in males and females with obesity. Static compliance curves were collected using the occlusion technique. Flow-volume, static pressure-volume, and static pressure-flow relationships were examined. Isovolume pressure-flow curves were constructed for the determination of the critical pressure for maximal flow. Data were compared with that collected in lean males and females. Individuals with obesity displayed a notable decrease in functional residual capacity. The interrelationships of flow, lung volume, static elastic recoil pressure, and the minimum pressure required for maximal expiratory flow in males and females with obesity were not different from that in lean males and females (all P > 0.05). Obesity does not alter the interrelationships of flow-volume-pressure of the lung in adult males and females (all P > 0.05). We further explored potential sex differences in static mechanics independent of obesity and observed that females have lower maximal expiratory flow due to a combination of smaller lungs and greater upstream flow resistance compared with males (all P ≤ 0.05).

NEW & NOTEWORTHY The potential influence of obesity on the interrelationships between maximal expiratory flow, lung volume, and static lung elastic recoil pressure is unclear. These data show that the presence of obesity does not alter the relationship of flow and pressure across the mid-expiratory range in males and females. In addition, independent of obesity, females have smaller lungs and greater upstream flow resistance, which contributes to reduced maximal flow, when compared with males.

INTRODUCTION

Obesity prevalence has reached epidemic status within the United States (1), and it is well established that obesity is related to numerous medical conditions, including an increased risk of cardiovascular disease (2, 3), diabetes (4), and some cancers (5, 6). The potential effects of obesity on the respiratory system receive considerably less attention (7), though the consequences are important. Obesity can decrease lung volume subdivisions, notably functional residual capacity (FRC) and expiratory reserve volume (ERV) (8), as well as total lung capacity (TLC) (9). However, expiratory flows and lung volumes are typically not influenced to the extent that they become less than the lower limit of normal in adults with obesity (9). Still, it is often uncertain whether alterations to resting pulmonary function, even when considered normal, and/or the symptom of exertional dyspnea (10) in adults with obesity are due to the obesity itself or perhaps are indicative of the beginning stages of underlying pulmonary dysfunction (11).

Maximal expiratory flow (MEF) is a hallmark measurement of the pulmonary function test. MEF is determined, in part, by static lung elastic recoil pressure (Pst), which itself is dependent upon lung volume. If TLC is altered due to obesity, this would be expected to contribute to a reduction of MEF. On the other hand, it has been shown that lung compliance decreases exponentially with increasing body mass index (BMI) and that the change is evident even in individuals with moderate obesity (12). Indeed, the accumulation of chest wall fat and increase in lung elastic recoil, or a decrease in lung compliance, in adults with obesity may serve to maintain or preserve MEF despite the reduction in lung volumes, as well as its relationship with pressure (13).

MEF is also determined by airway size and may be altered by airway narrowing or obstruction. Pelosi and colleagues (12) showed that total pulmonary resistance is increased in proportion to BMI, and the authors attributed this change to increased airway resistance. In addition, data from Auler et al. (14) are supportive of changes to airway resistance as a result of increasing obesity. If accurate, this would be expected to change the flow-pressure relationship, such that MEF would be reduced for a given Pst, perhaps due to changes in airway caliber (15). Yet, we recently demonstrated that a functional estimate of dysanapsis is unaffected by obesity in males and females (16). Importantly, this estimate provides only a snapshot of the relationship between MEF and Pst at a single lung volume (i.e., 50% forced vital capacity, FVC). The effect of obesity on the interrelationships among flow, volume, and pressure over the mid-expiratory volume range in healthy, young adults is unknown.

Thus, the purpose of this study was to investigate the interrelationships of MEF, lung volume, and pressures in males and females with obesity. We examined MEF, lung volume, and pressures, as well as their relationships in males and females with obesity compared with their lean counterparts. It was hypothesized that despite the potential obesity-related reduction in lung volume subdivisions, obesity would not influence the interrelationships of MEF, lung volume, and pressures. This is a retrospective analysis of previously collected data (17, 18), but the relationships between MEF, lung volume, and pressures in males and females with obesity are new to this report.

MATERIALS AND METHODS

Subjects, Body Composition, and Pulmonary Function

Males and females (n = 36) were recruited from the local community through posted advertisements. All subjects were asymptomatic, had no history of asthma, respiratory disease, or overt cardiovascular disease, and were nonsmokers. Subjects were classified as lean or obese based on BMI. Lean subjects had BMI values <25 kg·m⁻² and subjects with obesity had BMI values ≥30 kg·m⁻² but <45 kg·m⁻². Percent body fat was measured by underwater weighing and pulmonary function was measured in accordance with the ATS/ERS guidelines (19, 20). All details of the study were discussed and written and informed consent was obtained in accordance with the local Institutional Review Board (UT Southwestern IRB 0195 00100).

Static Respiratory Mechanics

Maximal flow-volume and pressure-volume relationships were measured in a pressure-corrected, volume-displacement body plethysmograph to eliminate gas compression artifact. Expiratory flow rates were measured using a pneumotachograph located distally to the mouthpiece. Transpulmonary pressure (Ptp) was estimated as the difference between airway opening and esophageal pressures with the placement of an esophageal balloon (21). Data were subsequently analyzed using a software program specifically developed for these purposes (22). Resting seated Pst versus lung volume curves were obtained by having the subject inspire to TLC, relax, inspire to TLC again, and relax against an occluded airway. Subjects exhaled passively during which occlusion of the airway was removed intermittently. These maneuvers were performed approximately 6–10 times. A line of best fit was drawn through the plot of lung volume versus Ptp measured during occlusion. From the line, Pst was determined at specific lung volumes. In addition, Pst was recorded at 90% and 100% TLC in each subject. Isovolume-pressure flow curves were constructed by having subjects perform multiple vital capacity maneuvers at varying efforts (22, 23). From these plots, critical pressures (Pcrit) at corresponding lung volumes were obtained. Pcrit was estimated as the minimum Ptp required for maximal flow at a given lung volume (23). MEF, Pst, and Pcrit were assessed at lung volumes corresponding to 25%, 50%, and 75% FVC. Lines of best fit were applied to the individual data points for MEF, Pst, and Pcrit at lung volumes of 25%, 50%, and 75% FVC, and the slopes were recorded to further examine the relationships between flow, volume, and pressure.

Statistical Analysis

Data were checked for normality using the Shapiro–Wilk test. Data that were not normally distributed were rank-transformed before analysis (24). Statistical analysis was performed using a two-way analysis of variance test (SAS, Cary, NC). If there was a significant group by sex interaction, Scheffe’s post hoc test was performed (25). Statistical significance was set at P < 0.05 for all comparisons. Data are reported as means ± SD.

RESULTS

Subject Characteristics, Body Composition, and Pulmonary Function

Subject characteristics are presented in Table 1. Individuals with obesity were similar to the lean subjects regarding age and height. As expected, males and females with obesity were heavier and had greater percent body fat than the lean males and females. Pulmonary function measurements are presented in Table 2. No differences for FVC, or peak expiratory flow measured at the mouth were observed between the lean adults versus adults with obesity. Forced expiratory volume in 1 s (FEV₁) as a percent of predicted was lower among adults with obesity compared with their lean counterparts. In addition, males and females with obesity exhibited significantly reduced lung volume subdivisions. Specifically, FRC and ERV expressed as absolute lung volumes were smaller in males and females with obesity compared with their lean counterparts. Residual volume as a percent of predicted was smaller in females with obesity compared with lean females (P < 0.05), while these differences were not observed between the lean males and males with obesity. Respiratory muscle strength, assessed at FRC and TLC, was unaffected by obesity in both males and females. The diffusing capacity of carbon monoxide (DL_CO) as a percent of predicted, but not absolute, was reduced in adults with obesity. When DL_CO was expressed relative to the volume of alveolar gas, adults with obesity had higher diffusion capacity compared with lean.

Table 1.

Subject characteristics

Subjects	n	Age, yr	Height, cm	Weight, kg	BMI, kg·m−2	Body Fat, %
Males
Lean	8	31 ± 8	176.8 ± 6.3	72.9 ± 6.4	22.9 ± 2.8	18 ± 4
Obesity	12	34 ± 7	179.8 ± 3.4	113.0 ± 9.5	35.0 ± 3.5	37 ± 5
Females
Lean	7	35 ± 9	162.9 ± 5.6	58.4 ± 6.0	22.0 ± 2.5	19 ± 3
Obesity	9	35 ± 7	168.2 ± 7.9	97.9 ± 15.6	34.3 ± 4.3	41 ± 6
P group × sex		0.475	1.000	1.000	1.000	0.155
P group		0.530	0.028	<0.001	<0.001	<0.001
P sex		0.351	<0.001	0.293	<0.001	0.181

Values are means ± SD. BMI, body mass index.

Table 2.

Pulmonary function

	Males		Females
	Lean	Obesity	Lean	Obesity	Group × Sex, P [η2]#	Group, P [η2]	Sex, P [η2]
FVC, L	5.36 ± 0.49	5.39 ± 0.61	3.96 ± 0.54	3.95 ± 0.55	1.000	0.710	<0.001 [0.64]
% predicted	106 ± 10	101 ± 9	115 ± 13	107 ± 13	1.000	0.088	0.049 [0.11]
FEV1, L	4.29 ± 0.35	4.23 ± 0.50	3.23 ± 0.43	3.14 ± 0.37	0.646	0.826	<0.001 [0.64]
% Predicted	100 ± 5	95 ± 8	110 ± 9	101 ± 9	0.840	0.016 [0.14]	0.005 [0.19]
FEV1/FVC, %	80 ± 6	79 ± 6	82 ± 8	80 ± 4	1.000	0.347	0.473
% predicted	95 ± 6	94 ± 6	98 ± 8	95 ± 3	0.613	0.384	0.431
PEF, L·s−1	10.21 ± 1.20	10.24 ± 1.63	7.70 ± 0.78	7.63 ± 0.96	1.000	0.849	<0.001 [0.54]
% predicted	108 ± 11	105 ± 14	120 ± 15	115 ± 12	1.000	0.326	0.021 [0.15]
TLC, L	6.70 ± 0.74	6.90 ± 0.77	5.32 ± 0.56	5.07 ± 0.70	0.376	0.818	<0.001 [0.59]
% predicted	96 ± 8	95 ± 9	105 ± 12	92 ± 9	0.055	0.078	0.612
IC, L	3.27 ± 0.33	4.48 ± 0.96	2.25 ± 0.48	2.65 ± 0.69	0.116	0.002 [0.15]	<0.001 [0.45]
FRC, L	3.22 ± 0.56	2.50 ± 0.39	2.85 ± 0.31	2.28 ± 0.46	0.637	<0.001 [0.35]	0.067
FRC/TLC, %	48 ± 6	36 ± 4	54 ± 5	45 ± 10	0.544	<0.001 [0.32]	0.002 [0.18]
ERV, L	1.79 ± 0.41	1.07 ± 0.44	1.46 ± 0.23	1.17 ± 0.27	0.099	<0.001 [0.35]	0.578
RV, L	1.33 ± 0.31	1.44 ± 0.40	1.39 ± 0.20	1.11 ± 0.28	0.100	0.608	0.120
% predicted	72 ± 10	72 ± 17	86 ± 20	61 ± 9*	0.019 [0.15]	0.048 [0.10]	0.876
RV/TLC, %	20 ± 3	21 ± 5	26 ± 4	22 ± 4	0.081	0.378	0.034 [0.12]
MVV, L·min−1	172 ± 19	169 ± 22	122 ± 15	115 ± 8	0.450	0.679	<0.001 [0.71]
% predicted	98 ± 9	95 ± 10	110 ± 11	103 ± 8	0.862	0.150	0.003 [0.23]
MIP, cmH2O	128 ± 16	143 ± 30	90 ± 29	107 ± 26	1.000	0.063	<0.001 [0.34]
% predicted	110 ± 12	97 ± 22	110 ± 36	99 ± 20	1.000	0.123	0.841
MEP, cmH2O	208 ± 33**	239 ± 41***	159 ± 45	136 ± 26	0.042 [0.06]	0.420	<0.001 [0.53]
% predicted	88 ± 16	100 ± 17	99 ± 29	94 ± 16	0.622	0.347	0.711
DLCO, mL·min−1 ·mmHg−1	30.5 ± 3.9	32.1 ± 3.8	21.3 ± 2.9	22.3 ± 3.0	1.000	0.160	<0.001 [0.67]
% predicted	106 ± 9	93 ± 12	99 ± 11	79 ± 8	0.129	<0.001 [0.31]	0.004 [0.15]
DLCO/VA, mL·min−1 ·mmHg−1·L−1	4.98 ± 0.61	5.35 ± 0.61	4.30 ± 0.32	5.01 ± 0.73	0.657	0.010 [0.16]	0.015 [0.14]
% Predicted	110 ± 10	120 ± 13	97 ± 7	113 ± 14	1.000	0.003 [0.22]	0.018 [0.13]

Values are means ± SD. FVC, forced vital capacity; FEV₁, forced expiratory volume in 1 s; PEF, peak expiratory flow; TLC, total lung capacity; IC, inspiratory capacity; FRC, functional residual capacity; ERV, expiratory reserve volume; RV, residual volume; MVV, maximal voluntary ventilation; MIP, maximal inspiratory pressure; MEP, maximal expiratory pressure; DL_CO, diffusing capacity of the lung for carbon monoxide; V_A, alveolar gas volume. #P values reported for all variables and semi-partial eta square (η²) reported in parentheses for variables with significant differences. *Females with obesity significantly lower than lean. **Lean males significantly different from males and females with obesity. ***Males with obesity significantly higher than lean females and females with obesity.

Static Respiratory Mechanics with Obesity

Pst measured at 90% (Lean: 12.5 ± 1.6 cmH₂O; Obesity: 12.4 ± 2.9 cmH₂O; P = 0.88) and 100% of TLC (Lean: 37.0 ± 6.4 cmH₂O; Obesity: 32.1 ± 7.8 cmH₂O; P = 0.28) were not different between lean males and males with obesity. Similarly, Pst at 90 (Lean: 10.8 ± 2.8 cmH₂O; Obesity: 11.3 ± 1.2 cmH₂O; P = 0.65) and 100% TLC (Lean: 32.0 ± 6.6 cmH₂O; Obesity: 33.6 ± 5.1 cmH₂O; P = 0.60) in lean females and females with obesity did not differ. MEF–lung volume (Fig. 1A), Pst–lung volume (Fig. 1B), and MEF–Pst relationships over the mid-expiratory range (Fig. 2) are presented separately for males and females. Lung volume is expressed as a percent of FVC to minimize the potential effect of height. Obesity did not alter the ability to produce maximal flow or the driving pressure, as similar MEF and Pst measurements at each lung volume examined were observed (all P > 0.05). Characteristics of the relationships of MEF, lung volume (expressed as absolute values for lung volumes corresponding with 25%, 50%, and 75% of FVC), and Pst are displayed in Table 3. No differences in the slopes and intercepts between the lean individuals and individuals with obesity were noted.

Figure 1.

Expiratory flow (A) and static elastic recoil pressure of the lung (Pst; B) in males (left) and females (right) at 25%, 50%, and 75% of forced vital capacity (FVC). Numbers in parentheses indicate a change in the number of subjects. No differences were detected in expiratory flow and Pst due to obesity. All data are presented as means ± SD.

Figure 2.

Maximal expiratory flow vs. static elastic recoil pressure of the lung (Pst) in males (left) and females (right) at 25%, 50%, and 75% of forced vital capacity (FVC). Dashed lines represent data from Mead et al. (26). All data are presented as means ± SD.

Table 3.

Flow, volume, and pressure relationships

	MEF–Lung Volume			Pst–Lung Volume			MEF–Pst
Subjects	Slope	Intercept	R 2	Slope	Intercept	R 2	Slope	Intercept	R 2
Males
Lean	2.75 ± 0.34	−5.80 ± 2.12	0.98 ± 0.03	3.14 ± 0.69	−7.10 ± 2.21	0.98 ± 0.03	0.92 ± 0.22	0.53 ± 1.40	0.98 ± 0.03
Obesity	2.82 ± 0.54	−5.94 ± 2.42	0.99 ± 0.03	2.84 ± 0.98	−5.99 ± 1.87	0.98 ± 0.01	1.11 ± 0.36	0.15 ± 1.71	0.98 ± 0.03
Females
Lean	3.08 ± 0.46	−5.77 ± 1.50	0.98 ± 0.03	3.52 ± 1.06	−7.57 ± 2.96	0.99 ± 0.00	0.85 ± 0.34	1.25 ± 1.61	0.96 ± 0.06
Obesity	2.99 ± 0.29	−5.26 ± 1.77	0.99 ± 0.02	4.11 ± 1.13	−8.32 ± 3.47	0.99 ± 0.01	0.78 ± 0.27	0.84 ± 1.34	0.98 ± 0.03
P group × sex	0.678	0.658	0.847	0.196	0.302	0.364	0.301	1.000	0.368
P group	0.936	0.860	0.039	0.809	0.663	0.631	0.443	0.431	0.926
P sex	0.140	0.589	1.000	0.010	0.170	0.072	0.051	0.141	0.391

Values are means ± SD. Lung volume measurements used in these analyses are the absolute values recorded at lung volumes corresponding with 25%, 50%, and 75% of forced vital capacity. MEF, maximal expiratory flow; Pst, static lung elastic recoil pressure.

No differences in Pcrit at 25%, 50%, and 75% FVC were detected between adults with obesity compared with lean (P = 0.33, P = 0.05, and P = 0.44, respectively, for the main group effect; interaction P > 0.20 for all three) (Fig. 3A). Furthermore, the Pcrit–lung volume (absolute) slopes were similar for all groups (Lean males: 13.58 ± 5.54 cmH₂O·L⁻¹; Obese males: 12.29 ± 3.19 cmH₂O·L⁻¹; Lean females: 11.79 ± 3.92 cmH₂O·L⁻¹; Obese females: 12.29 ± 10.15 cmH₂O·L⁻¹; P interaction = 0.57, P group = 0.68, P sex = 0.25). Pcrit as a function of Pst also was not altered due to obesity or sex (P interaction = 0.61, P group = 0.75, P sex = 0.09) (Fig. 3B). In addition, the relationships of MEF to Pcrit did not differ by group or sex (P interaction = 0.65, P group = 0.98, P sex = 0.10) (Fig. 4).

Figure 3.

Relationships of critical pressure (Pcrit) with lung volume as a percentage of forced vital capacity (FVC; A) and with static elastic recoil pressure (Pst; B) in males (left) and females (right). All data are presented as means ± SD.

Figure 4.

Maximal expiratory flow against critical pressure (Pcrit) in males (left) and females (right). All data are presented as means ± SD.

Sex Differences in Static Respiratory Mechanics

As an exploratory analysis, we also examined the potential effect of sex, independent of weight classification, on the interrelationships of flow, lung volume, and pressure. Thus, data from lean males and males with obesity were pooled and compared with the pooled data of lean females and females with obesity. When the absolute values for lung volumes corresponding with 25%, 50%, and 75% of FVC were used, the relationships between MEF and lung volume were not different between males and females (Table 3). In addition, the Pcrit–lung volume relationships were similar (Males: 12.8 ± 4.1 cmH₂O·L⁻¹, Females: 12.1 ± 7.6 cmH₂O·L⁻¹; P = 0.25). However, the relationships between Pst and lung volume were significantly different, as females (3.86 ± 1.10 cmH₂O·L⁻¹) demonstrated a greater slope than males (2.96 ± 0.87 cmH₂O·L⁻¹; Table 3). The MEF–Pst relationship and Pcrit–Pst slopes were similar between males and females. Pcrit at 25%, 50%, and 75% FVC was higher in males compared with females (P = 0.04, P < 0.01, and P < 0.01, respectively; Fig. 3A).

DISCUSSION

We observed that obesity does not modify the interrelationships of flow, lung volume, and pressures over the mid-expiratory range (25%, 50%, and 75% of FVC). Thus, these data demonstrate that individuals with obesity may have altered lung volume subdivisions, but the flow-volume-pressure interrelationships are unchanged. This indicates that factors governing MEF are preserved in otherwise healthy adults with obesity. Overall, these findings are clinically relevant because they suggest that patients with obesity who present with reduced MEF, unrelated to a reduction in TLC, may need further evaluation for the presence of underlying respiratory disease. Therefore, clinicians should consider the potential effects of obesity on these parameters when evaluating patients for potential underlying respiratory abnormalities.

Lean individuals and individuals with obesity in the current study were of similar height, weight, BMI, and percent body fat to those in our previous studies using otherwise healthy males and females with obesity (27–29). Lung volume subdivisions were affected due to obesity, which is consistent with our previous reports in obese adults (10, 29). Spirometric measurements were not different between the lean individuals and individuals with obesity and were within normal limits. However, there were differences in lung volume subdivisions between lean individuals and individuals with obesity. These differences were expected based on previous study findings (8) and all values were still considered normal. Also expected were the differences in DL_CO (17). Thus, we are confident the subjects included in the current investigation represent otherwise healthy young males and females with obesity who are free of respiratory disease.

MEF at each quartile of FVC was unaltered due to obesity in both males and females (Fig. 1A). Because we were able to account for the potential effects of gas compression on MEF and Pst by conducting testing within a body plethysmograph, we are confident that the flow and pressure values reported correspond to the appropriate lung volume. There are no current standards in which to compare MEF measured in relation to absolute lung volume by body plethysmography. We did not observe an effect of obesity on FVC, which is in contrast to some studies (30, 31) but in agreement with others (32). When the similarities in lung volume are combined with the lack of differences for MEF, it is clear that the relationship of MEF to lung volume is maintained in adults with obesity.

Individuals with obesity included in the current study displayed lung elastance (i.e., pressure-volume slope) that was similar to lean adults over the mid-expiratory range. Though some investigations report that obesity decreases lung compliance (i.e., increased elastance) when compared with normal-weight patients (33, 34), this may only be true in more extreme cases of obesity and/or influenced by the use of anesthesia (33) during measurement. Within the cohort tested in the present study, the Pst versus lung volume curve follows closely the relationship observed in normal individuals (35–37). Pst values at TLC were approximately 98% and 97%predicted in males and females, respectively, confirming the ability of our participants to fully inspire. This also suggests, in combination with a near-predicted TLC, that obesity does not impair inspiratory muscle function.

That we did not observe any differences in the absolute values of MEF and Pst, nor the relationships between MEF and Pst between lean individuals and individuals with obesity, emphasizes that the driving pressure of flow at various lung volumes is maintained in otherwise healthy, adults with obesity. Additionally, these findings indicate that the upstream resistance of the airways, estimated as the ratio of Pst over MEF at each lung volume, is similar between lean adults and adults with obesity. This is in contrast to the data of Auler et al. (14) but can be explained by the fact that the individuals included in their study were classified as having morbid obesity.

Although the relationships between flow, volume, and pressure were not different between the lean individuals and individuals with obesity, it would appear that individuals in the current study had slightly reduced Pst values and/or were capable of achieving greater MEF for a given Pst (i.e., curve shifted leftward; Fig. 2) when compared with previous studies (26). Additionally, compared with data reported by Turner et al., (35), our Pst values at 90% TLC are approximately 75% and 66% of those reported in males and females, respectively. We believe these slight differences in pressure may be partly attributed to differences in balloon volume (21) and measurement technique. Regardless of the potential effect of balloon volume, we believe that the pressures recorded in all participants would be affected equally and not be biased toward any one group. Furthermore, differences in balloon volumes between studies would not be expected to significantly alter the relationships of flow, volume, and pressure examined in the current study. These differences could also be due to a slightly decreased TLC in individuals with obesity, such that these individuals may not have been able to displace the extra mass on the thorax enough to reach TLC. Thus, while we acknowledge the slightly lower Pst values, we do not believe this diminishes the current study findings.

We demonstrated that lean adults and adults with obesity exhibit similar Pcrit over the mid-expiratory range, and this has not been previously reported. According to the equal pressure point theory, the difference between the pressure within the airway and the intrapleural space (i.e., transmural pressure) decreases as air moves downstream from the alveoli toward the “choke point.” When transmural pressure reaches zero, expiratory flow becomes fixed, or what is commonly referred to as expiratory flow limitation. Expanding upon the concept of Pcrit, the resistance to flow in the downstream airway segment from the point where transmural pressure is zero to the airway opening can be approximated (26, 38). Because we did not observe differences between lean and individuals with obesity for Pcrit and MEF, the flow resistance through the segment between the “choke point” and airway opening also is likely similar. We acknowledge that the equal pressure point is an over-simplification of the determinants of MEF, as wave-speed theory has shown that flow does not become limited only when transmural pressure is equal to zero (39). However, modeling has repeatedly demonstrated that the point at which flow becomes limited is close to the point where transmural pressure equals zero. Therefore, we believe our approach is valid and shows that airway characteristics primarily involved in MEF are unaffected in the presence of mild-to-moderate obesity.

We explored potential biological sex differences in the relationships between flow, volume, and pressure. We observed that the relationships between MEF and absolute lung volume were similar between males and females. Thus, for a given change in absolute lung volume, males and females achieved similar changes in maximal flow over the mid-expiratory range. The data further demonstrate that differences in MEF between males and females are, in part, attributed to differences in lung size. Yet, the relationships between Pst and lung volume were different between males and females when lung volume was expressed in absolute terms but were similar when expressed as a percent of FVC (data not shown). This demonstrates that Pst is scaled to relative lung size (i.e., %FVC or %TLC) over the mid-expiratory range, which is in agreement with previous reports (40, 41). In the current study, females exhibited less of a change in flow for a given change in recoil pressure (i.e., a smaller MEF–Pst slope). In other words, flow increased to a lesser extent for the same change in driving pressure in females than in men. This suggests that females have a greater increase in flow resistance upstream of the flow-limiting segment over the mid-expiratory range compared with men. By extension, these results reinforce the fact that females are more likely than males to experience expiratory flow limitation as high flow rates are required to achieve ventilation, such as during exercise (42). The larger change to upstream flow resistance may be attributed to relatively smaller conducting (or central) airways in females, even when matched with males for lung size (43, 44), or potentially to sex-related differences in the locus of the equal pressure point within the lung (45). Interestingly, that the relationships between Pcrit and lung volume, as well as between MEF and Pcrit, were similar between males and females suggests that the change in flow resistance downstream of the flow limiting segment at maximal flow over the mid-expiratory range is scaled to lung volume and independent of sex. Taken together, these results suggest that females display reduced MEF compared with males due to the combination of smaller lungs and greater airway resistance upstream of the flow-limiting segment.

We are aware the sample sizes in the current study are small, which could limit the generalizability of our findings. However, the study of static and dynamic respiratory mechanics is particularly complex and requires substantial detail. Further, we believe that despite the low sample size, our findings accurately reflect the interrelationships between MEF, Pst, Pcrit, and lung volume in healthy males and females with and without obesity.

Conclusions

The findings of the present study demonstrate that obesity does not alter the interrelationships of MEF, lung volume, and Pst despite the changes to lung volume subdivisions. Additionally, the pressure required to achieve MEF is maintained in the presence of obesity, and airway characteristics do not appear to be altered. Taken together, the lung and airway characteristics responsible for MEF are maintained in males and females with obesity. Therefore, alterations in the parameters responsible for MEF likely are indicative of pulmonary disease (or dysfunction) but are not directly due to the obesity itself. Furthermore, that MEF is lower in females than in men, independent of obesity, can be attributed to the combination of smaller lungs and greater airway resistance upstream of the flow limiting segment at maximal flow.

DATA AVAILABILITY

Data will be made available upon reasonable request.

GRANTS

This work was supported in part by American Lung Association (ALA) Career Investigator Award, American Heart Association (AHA) Grant-in-Aid, NIH Grants HL096782 and NIH K99HL164957, King Charitable Foundation, Atwell Gift for Pulmonary Research, Cain Foundation, and Texas Health Presbyterian Hospital Dallas.

DISCLOSURES

No conflicts of interest, financial or otherwise, are declared by the authors.

AUTHOR CONTRIBUTIONS

T.G.B. conceived and designed research; J.L.S. and T.G.B. performed experiments; J.L.S., D.M.B., and T.G.B. analyzed data; J.L.S., D.M.B., B.N.B., and T.G.B. interpreted results of experiments; J.L.S., D.M.B., and B.N.B. prepared figures; J.L.S., D.M.B., B.N.B., and T.G.B. drafted manuscript; J.L.S., D.M.B., B.N.B., and T.G.B. edited and revised manuscript; J.L.S., D.M.B., B.N.B., and T.G.B. approved final version of manuscript.