Mechanical effects of obesity on central and peripheral airway resistance in nonasthmatic early pubescent children

Abstract

Background:

In children, obesity typically reduces functional residual capacity (FRC), which reduces airway caliber and increases airway resistance. Whether these obesity-related changes in respiratory function can alter bronchodilator responsiveness is unknown.

Objective:

To investigate bronchodilator responsiveness in nonasthmatic children with and without obesity.

Methods:

70 nonasthmatic children, 8 – 12 years old, without (n=19) and with (n=51) obesity, completed spirometry, impulse oscillometry, and airway resistance measurements through plethysmography pre/post 360 μg of inhaled albuterol. FRC was assessed pre albuterol. A two-way ANOVA determined the effects of obesity (group) and inhaled albuterol (pre-post) on outcome measures.

Results:

FRC (%total lung capacity) was 16% lower in children with obesity compared with those without obesity. There was no significant group by pre-post albuterol interaction on any outcome variables. Albuterol inhalation reduced total, central and peripheral airway resistance and increased airway reactance (i.e., less negative) to a similar degree in children with and without obesity. In children with obesity, airway resistance was increased whether measured by impulse oscillometry or plethysmography. However, once airway resistance was adjusted for lung volumes (i.e., specific airway resistance or sR_aw), there were no differences between children with and without obesity. In addition, significant but moderate associations were detected between chest mass and FRC (r=−0.566;P<0.001), FRC and total airway resistance (i.e., R_aw; r=−0.445;P<0.001).

Conclusions:

In nonasthmatic early pubescent children, obesity increases total, central, and peripheral respiratory system resistance. However, the added respiratory system resistance and low lung volume breathing with obesity are not sufficient to reduce bronchodilator responsiveness.

Introduction

In children, obesity is associated with increased risk of asthma¹, but the specific mechanisms by which obesity produces asthma are largely unknown. One potential mechanism is that obesity exerts a mechanical effect on the chest wall leading to a reduction in functional residual capacity (FRC)^2,3, which increases airway resistance and airway hyperresponsiveness. To support this idea, experimentally lowering FRC through chest wall strapping has been linked with an increase in airway resistance and airway hyperresponsiveness in healthy nonasthmatic adults^4–6, presumably via a decrease in airway caliber and/or ventilation heterogeneity⁴ with reduced lung volumes. Also, within the context of a reduced airway caliber, the load that airway smooth muscles have to overcome during the process of contraction is also reduced, which makes bronchoconstriction easier⁵ and bronchodilation more difficult⁷. Asthmatic children with obesity show either no difference in bronchodilator responsiveness or reduced bronchodilator responsiveness when compared with their leaner counterparts but they also experience worse asthma control^8,9. Whether obesity itself, independent from asthma, can alter bronchodilator responsiveness is unknown and deserves to be studied because it could impact the approach to the management of respiratory symptoms in children with obesity who may or may not have asthma. Therefore, the first objective of this study was to investigate bronchodilator responsiveness in nonasthmatic children with and without obesity. We hypothesized that bronchodilator responsiveness would be reduced in nonasthmatic children with obesity, who will exhibit reduced lung volumes, when compared with nonasthmatic children without obesity.

Furthermore, most studies assessing the effect of obesity on pulmonary function use maximal expiratory flow maneuvers via traditional spirometry to elucidate potential obstructive patterns. However, the quality of these measures depends highly on effort. Measures of airway resistance demand access to a body plethysmograph, which can be expensive and inaccessible for most routine pediatric pulmonology practices. An easier and more sensitive method of detecting changes in airway function in children may be warranted¹⁰. One such method is impulse oscillometry, which is easier to perform than traditional spirometry (i.e., less effort dependent) and is also capable of distinguishing between central and peripheral airway resistance, with the caveat that impulse oscillometry does not adjust for lung volumes (i.e., FRC)¹¹. In the current study, we used three methods to assess bronchodilator responsiveness: spirometry for changes in forced expiratory volume in 1 second (FEV₁), plethysmography for changes in total airway resistance, and impulse oscillometry for changes in central and peripheral airway resistance. Our second objective was to investigate potential differences in central and peripheral airway function in response to bronchodilator administration. We hypothesized that central airways would retain their ability to bronchodilate more than peripheral airways that are more susceptible to obesity-related airway caliber reductions in children with obesity.

These data were collected and analyzed as part of a larger ongoing study designed to examine the respiratory effects of obesity in children. Some of the data collected from the larger ongoing study have been published elsewhere^12–15.

Methods

Study participants

Participants were recruited for the study through local advertisements, emails to employees of Texas Health Presbyterian Hospital, a local weight management program for children (“Get Up and Go”, Children’s Health, Dallas, TX), and word of mouth among friends and family members. Study procedures were explained to the participants in detail. The parent or guardian provided written, informed consent, and all children provided written assent. This study was approved by the UT Southwestern Medical Center Institutional Review Board (approval #052012–076).

Participants were 8 – 12 years old with no history of significant medical issues (e.g., cardiovascular, metabolic, or respiratory disease). Body mass index (BMI, kg/m²) percentile was calculated for each participant using age and sex-specific BMI tables from the Centers for Disease Control and Prevention¹⁶. Children were classified as obese if BMI was ≥ 95^th percentile and nonobese if BMI was between the 16^th and 84^th percentile. A Tanner pubertal stage self-assessment questionnaire¹⁷ was given, and participants were included in the study if their Tanner score was ≤ 3. Children with or without obesity who had no previous history of bronchodilator responsiveness were enrolled in the study.

Study procedures

Participants were instructed not to eat a heavy meal or ingest caffeine for two hours before reporting to the laboratory. Study procedures were described to each participant in detail immediately before commencing each measurement. After consenting to participate in the study, participants performed a set of breathing maneuvers to determine measures of impulse oscillometry, spirometry, airway resistance (R_aw), specific airway resistance (sR_aw), and lung volumes while seated upright and breathing on a mouthpiece attached to a MicroGard II bacterial/viral filter (Vyaire Medical, Yorba Linda, CA, USA) with a noseclip. Impulse oscillometry parameters were measured using a Jaeger MasterScreen IOS system (Vyaire Medical, Yorba Linda, CA, USA), and all other lung function variables were recorded using standard pulmonary function equipment and software (model V62W body plethysmograph, Vmax, Vyaire, Yorba Linda, CA, USA).

To determine the airway response to albuterol, all measures except for lung volumes were repeated 15 minutes after inhaling from a spacer (OptiChamber Diamond, Phillips Respironics) four actuations of 90μg albuterol sulfate (Ventolin HFA; 360μg in total), each separated by one minute. Children without bronchodilator responsiveness (i.e., FEV₁ increase of < 12% and < 200 ml after inhaling 360μg albuterol), as defined by the American Thoracic Society (ATS)¹⁸, were included in the study.

On a separate day after pulmonary function testing, participants underwent dual-energy x-ray absorptiometry (DEXA) for the assessment of body composition (Lunar Prodigy Advance; GE Healthcare Lunar, Madison, WI).

Impulse oscillometry

Impulse oscillometry parameters were measured and reported in accordance with ATS guidelines on the forced oscillation technique¹⁹. Each participant was instructed to relax and breathe normally on the mouthpiece while firmly supporting their cheeks with both hands¹⁹. Each measurement lasted 30s. The procedure was repeated to obtain three trials with a coefficient of variation no larger than 10% and the mean value of those three trials was recorded for each variable.

The technique of impulse oscillometry consists of superimposing small-amplitude square-wave external pressure signals that propagate via movement of the air column in the conducting airways on normal tidal breathing¹¹. The consequent distension and recoil of the elastic components of the lung tissues create backpressure, which is continuously measured at multiple oscillation frequencies (e.g., 5 to 20 Hz), and mean values for resistance (in phase with airflow) and reactance (out of phase with airflow) are reported, each frequency representing a specific portion of the airway tree. For example, resistance measured at 5 Hz (R₅) indicates total airway resistance; resistance measured at 20 Hz (R₂₀) indicates central airway resistance; and the difference between R₅ and R₂₀ (R_5–20) indicates peripheral airway resistance. Likewise, reactance at 5 Hz (X₅) provides an index of total respiratory compliance and has been shown to correlate with peripheral airways obstruction²⁰. In addition, further insight into peripheral airways obstruction is provided by the area under the reactance curve (AX) as well as the frequency at which reactance is zero (i.e., resonant frequency, F_res)²¹.

Reported variables include R₅, R₂₀, R₅-R₂₀, X₅, AX, and F_res. Predicted values for R₅, R₂₀, X₅, and F_res were determined using reference sets provided by Nowowiejska et al. (2008)²². Reference values for R_5–20 and AX were not reported by Nowowiejska et al.²² and thus percent predicted values on those variables are not reported in the present study.

Spirometry

Spirometry was performed in accordance with ATS guidelines²³. Flow-volume curves were recorded to determine forced vital capacity (FVC), forced expired volume in one second (FEV₁), forced expiratory flow between 25% and 75% of FVC (FEF_25–75), and peak expiratory flow (PEF). The spirometer was calibrated before each test using a calibrated 3-liter syringe (Series 5530, Hans Rudolph Inc., Shawnee, KS, USA). Predicted values for spirometry were based on the norms from NHANES III²⁵.

Total Airway resistance and Lung Volumes

Airway resistance and resting lung volumes were measured as previously described^26–29, and lung volumes were accepted and variables reported based on ATS guidelines²⁷. While seated inside the plethysmograph with a stable resting breathing pattern, each participant performed “small gentle pants” at a respiratory rate of 60 breaths per minute while firmly supporting their cheeks with both hands. When a stable pattern of panting was seen on the computer monitor, airflow at the airway opening (V̇_ao) was plotted vs. pressure at the airway opening (P_ao) on four consecutive breaths, and a line connecting the points of maximum flow during inspiration and expiration was used to determine R_aw^26,29. Immediately after recording the last breath, and while panting at the same rate and effort, a shutter located along the breathing valve was closed to occlude V̇_ao, and plethysmographic lung volume vs. P_ao was recorded on four additional breaths to determine thoracic gas volume (V_tg) and thus FRC as previously described^27,28. Immediately after the acquisition of FRC, participants performed an inspiratory capacity (IC) maneuver, followed by a vital capacity (VC) maneuver (i.e., slow exhalation followed by an inhalation back to TLC).

If shutter closure occurred at a volume other than FRC, the volume difference between end-expiration during stable breathing and V_tg was corrected to determine FRC²⁷. The measure of sR_aw was calculated as the product of R_aw and V_tg²⁶, and the mean value of R_aw and sR_aw from three acceptable trials was reported. TLC was determined as the sum of FRC and IC. Expiratory reserve volume (ERV) was calculated as the difference between VC and IC. Predicted values for airway resistance and lung volumes were based on the norms from Dubois et al.³⁰ and from Polgar & Promadhat³¹, respectively.

Lastly, considering that R_aw is a primary component of total respiratory system resistance (i.e., R₅), the present study also sought to determine the level of agreement between impulse oscillometry (i.e., R₅) and plethysmographic airway resistance (i.e., R_aw).

DEXA

Whole body fat mass and fat-free mass were estimated using Prodigy encore software (GE Healthcare Lunar, Madison, WI). Custom region of interest analysis was completed for assessing chest mass and abdominal mass. The chest region of interest was selected from the sternal notch to the xiphoid process. The axillae were selected as the lateral boundary of the chest region to exclude the shoulders and arms. The abdomen region of interest was selected from the xiphoid process to the pubic symphysis. DEXA provides valid³² and reproducible³³ estimates of body composition in children.

Statistical analyses

All variables are displayed as mean ± SD. Independent samples t-tests were used to compare participant characteristics between children with and without obesity. A two-way mixed models ANOVA was used to detect differences in outcome parameters by group (i.e., with vs. without obesity) and bronchodilator (i.e., pre- vs. post-bronchodilator). Pearson correlations were used to examine associations between variables. The alpha level for statistical significance was set at P < 0.05. These analyses were assessed using SAS version 9.4 (SAS Institute Inc., Cary, NC, USA).

Results

Participant characteristics are listed in Table 1. Children without obesity were slightly but significantly older than children with obesity (P = 0.044). There was no significant difference in height between children with and children without obesity (P = 0.806). Children with obesity were significantly heavier (P < 0.001) with a significantly greater BMI (P < 0.001) and body fat content (P < 0.001) as compared with the children without obesity. Six children were disqualified from the larger ongoing study for reasons unrelated to the outcome measures included in the present study. As a result, those children did not return to the laboratory for DEXA measures and therefore the present study includes DEXA data on 17 children without obesity and 47 children with obesity.

Table 1.

Participant Characteristics

Variables	Without Obesity (n = 19)	With Obesity (n = 51)	All Subjects (n = 70)
Age (years)	11.1 ± 1.0	10.4 ± 1.3*	10.6 ± 1.3
Sex (M / F)	9 M / 10 F	29 M / 22 F	38 M / 32 F
Height (cm)	148.3 ± 8.3	147.7 ± 8.3	147.9 ± 8.2
Body mass (kg)	38.9 ± 5.9	61.7 ± 14.7**	-
BMI (kg/m2)	17.61 ± 1.54	27.97 ± 4.44**	-
z-score	0.04 ± 0.66	2.18 ± 0.31**	-
% of 95 %-ile	74.7 ± 7.5	122.6 ± 17.2**	-
Total body fat (%)	26.1 ± 5.7	43.7 ± 4.1**	-
Fat free mass (kg)	29.33 ± 4.19	34.61 ± 7.92*	-
Chest mass (kg)	6.29 ± 0.92	10.90 ± 3.67**	-
Abdomen mass (kg)	9.80 ± 1.62	16.09 ± 5.08**	-

BMI, body mass index. All parameters are presented as mean ± SD. Body composition data (i.e., total body fat, fat free mass, chest mass, and abdomen mass) were included on 17 children without obesity and 46 children with obesity (see Results section for details).

^*Significant difference between groups (P < 0.05).

^**Significant difference between groups (P < 0.001).

Pre-bronchodilator spirometry variables were not significantly different between children without vs. those with obesity (Table 2). However, pre-bronchodilator FRC (in liters and percent TLC) and ERV (in liters and percent predicted) were significantly smaller with obesity.

Table 2.

Pre-bronchodilator pulmonary function

Variables	Without Obesity (n = 19)	With Obesity (n = 51)	P
FVC (L)	2.62 ± 0.49	2.74 ± 0.56	0.397
% predicted	103.1 ± 14.0	104.4 ± 10.6	0.660
FEV1 (L)	2.24 ± 0.39	2.27 ± 0.44	0.815
% predicted	101.1 ± 11.9	99.7 ± 11.1	0.664
FEV1/FVC (%)	85.8 ± 4.9	83.3 ± 5.5	0.078
FEF25–75 (L/s)	2.60 ± 0.67	2.50 ± 0.65	0.547
% predicted	98.9 ± 22.7	96.3 ± 23.5	0.680
FEF25–75/FVC (%)	100.6 ± 25.7	92.5 ± 22.1	0.194
PEF (L/s)	4.78 ± 0.67	4.60 ± 1.08	0.513
% predicted	97.7 ± 12.4	94.4 ± 17.3	0.454
TLC (L)	3.38 ± 0.61	3.51 ± 0.69	0.505
% predicted	97.7 ± 10.5	101.8 ± 11.0	0.173
FRC (L)	1.67 ± 0.36	1.45 ± 0.37	0.026
% TLC	49.3 ± 4.8	41.4 ± 7.0	< 0.001
ERV (L)	0.84 ± 0.20	0.64 ± 0.25	0.004
% predicted	100.7 ± 21.7	77.1 ± 27.5	0.001
IC (L)	1.69 ± 0.33	2.06 ± 0.49	0.003
% predicted	91.2 ± 12.4	111.9 ± 18.4	< 0.001
RV (L)	0.74 ± 0.21	0.71 ± 0.24	0.815
% predicted	93.0 ± 21.8	92.0 ± 28.1	0.891

FVC, forced vital capacity; FEV₁, forced expiratory volume in one second; FEF_25–75, forced expiratory flow between 25 and 75% of FVC; PEF, peak expiratory flow; TLC, total lung capacity; FRC, functional residual capacity; ERV, expiratory reserve volume; RV, residual volume; IC, inspiratory capacity. All parameters are presented as mean ± SD.

There was no significant group (i.e., without vs. with obesity) by pre-post bronchodilator interaction detected on any outcome parameter (Table 3). However, there was a significant main effect of bronchodilator on all outcome parameters as evidenced by a reduced airway resistance. There was a significant main effect of group on R₅, R₂₀, R_5–20, AX, and F_res (Table 3). No significant difference between children with and without obesity was detected on reactance (i.e., X₅) (Table 3). Although R_aw was significantly higher in children with obesity, once the measure was adjusted for low lung volume breathing (i.e., sR_aw), there was no difference in airway resistance between children with and without obesity.

Table 3.

Impulse oscillometry and plethysmographic measures of airway resistance

Variables	Without Obesity		With Obesity		P
	Pre-BD	Post-BD	Pre-BD	Post-BD	Int	Grp	Pre-Post
R5 (cmH2O/L/s)	5.96 ± 1.11	5.01 ± 0.76	7.38 ± 1.44	6.06 ± 1.14	0.133	< 0.001	< 0.001
% predicted	116 ± 24	98 ± 18	142 ± 24	116 ± 18	0.134	< 0.001	< 0.001
R20 (cmH2O/L/s)	4.17 ± 0.72	3.57 ± 0.42	4.79 ± 1.08	3.99 ± 0.75	0.261	0.016	< 0.001
% predicted	109 ± 21	93 ± 15	123 ± 23	103 ± 17	0.285	0.015	< 0.001
R5–20 (cmH2O/L/s)	1.79 ± 0.63	1.45 ± 0.52	2.59 ± 0.72	2.07 ± 0.62	0.339	< 0.001	< 0.001
X5 (cmH2O/L/s)	−1.36 ± 0.38	−0.97 ± 0.29	−1.19 ± 0.67	−0.98 ± 0.55	0.229	0.539	< 0.001
% predicted	81 ± 28	58 ± 20	67 ± 36	55 ± 31	0.167	0.256	< 0.001
AX (cmH2O/L)	4.26 ± 2.37	2.60 ± 1.27	5.87 ± 4.45	4.07 ± 2.91	0.889	0.047	< 0.001
Fres (Hz)	11.53 ± 3.02	9.77 ± 1.31	13.31 ± 2.91	11.90 ± 2.75	0.625	0.003	< 0.001
% predicted	82 ± 21	70 ± 11	94 ± 21	84 ± 19	0.634	0.006	< 0.001
Raw (cmH2O/L/s)	3.71 ± 0.83	2.85 ± 1.08	4.50 ± 0.95	3.20 ± 1.03	0.077	0.017	< 0.001
% predicted	114 ± 26	87 ± 33	138 ± 28	97 ± 27	0.077	0.011	< 0.001
sRaw (cmH2O/L/s)	7.66 ± 1.93	6.07 ± 1.63	8.66 ± 2.03	6.25 ± 1.91	0.084	0.207	< 0.001
% predicted	138 ± 34	111 ± 31	156 ± 36	113 ± 35	0.073	0.228	< 0.001

R₅, resistance at 5 Hz; R₂₀, resistance at 20 Hz; R_5–20, difference between R₅ and R₂₀; X₅, reactance at 5 Hz; AX, area under the reactance curve; F_res, resonant frequency; R_aw, airway resistance; sR_aw, specific airway resistance. All parameters are presented as mean ± SD.

Higher chest mass was moderately associated with reduced FRC as a percent of TLC (r = −0.566; P < 0.001). In addition, a lower FRC was associated with increased airway resistance and peripheral airway resistance (Figure 1). Higher percent body fat and percent of the 95^th BMI percentile were associated with increased peripheral airway resistance (i.e., R_5–20) (Figure 2A and 2B).

Figure 1:

Individual values for total airway resistance (R_aw) (panel A), total respiratory system resistance (R₅) (panel B), central airway resistance (R₂₀) (panel C), and peripheral airway resistance (R_5–20) with functional residual capacity (FRC) displayed as percent of total lung capacity (TLC). The dashed line represents the line of best fit for the total cohort of children.

Figure 2:

Individual values for peripheral airway resistance (R_5–20) with percent body fat (panel A) and percent of the 95^th percentile for age and sex (panel B). The dashed line represents the line of best fit for the total cohort of children.

Lastly, the agreement between R₅ and R_aw is displayed in Figure 3. There was a statistically significant relationship between R₅ and R_aw (Figure 3A), and measures of R₅ were slightly greater than R_aw, with a bias towards R₅ overestimating airway resistance at higher levels of resistance (Figure 3B).

Figure 3:

Individual resistance at 5 Hz (R₅) with plethysmographic airway resistance (R_aw) (panel A), and level of agreement between the two methods as represented by a Bland-Altman plot (panel B), in children without and with obesity.

Discussion

The findings of this study indicate that although airway caliber is reduced and consequently central and peripheral resistance are increased in children with obesity, there is no difference in bronchodilator responsiveness between children with and without obesity. These findings contrast with our original hypothesis that reduced airway caliber would reduce bronchodilator responsiveness in children with obesity who would need to overcome a greater load to increase airway diameter in response to bronchodilation. Since reactance (X₅) did not differ between children with and without obesity, it could be that the physical properties of the lung parenchyma and chest wall are not substantially altered in children with obesity, thus allowing the central and peripheral airways to bronchodilate to a similar extent as that in children with obesity. Lastly, as shown previously^34,35 there was a moderate correlation between total respiratory system resistance as assessed via impulse oscillometry (i.e., R₅) and total airway resistance as assessed by plethysmography (i.e., R_aw), indicating agreement between the two measures.

The finding that total respiratory system resistance (R₅), assessed via impulse oscillometry, is greater in children with obesity has been reported by a few previous studies^36–38. Assumpcao et al. reported in a group of children between the ages of 6 and 14 years old a higher R₅ in children with obesity (5.83 ± 1.43 vs. 7.02 ± 1.94 cmH₂O/L/s, respectively)³⁶. Contrary to our findings, Assumpcao et al. reported no statistically significant difference in the central component of respiratory system resistance (i.e., R₂₀) between children without and those with obesity (4.82 ± 1.02 vs. 4.92 ± 1.02 cmH₂O/L/s, respectively), although the reported values are similar in magnitude to those reported in the present study (see Table 3). In addition, similar to the findings of Assumpcao et al., we also report no difference in X₅ between children without and those with obesity, but there was a significant difference in AX and F_res between groups, indicating that while reactance at low frequencies (i.e., X₅) is not different between groups, total respiratory system reactance (reflected by AX and F_res), is increased with obesity in children, likely reflecting an increase in peripheral airway obstruction³⁹. Assumpcao et al. also included overweight children in their analyses and reported a significant increase in total respiratory system resistance (i.e., R₅) in that group as compared with normal weight children, suggesting that increases in resistance may begin to occur at a BMI below the cutoff for obesity.

Our study results also seem to agree with the findings of Ekstrom et al.³⁷, who reported a significant correlation between BMI and peripheral airways resistance (i.e., R_5–20) in a group of nonasthmatic 16-yr-old adolescents. Lauhkonen et al. reported in children between the ages of five to seven years, who were admitted for bronchiolitis before the age of six months, significant correlations between age-adjusted BMI z-score and impulse oscillometry parameters, although R_5–20 as an indicator of peripheral airways obstruction was not reported in that study⁴⁰. In summary, our data agree with the literature reporting higher levels of peripheral airway resistance in children with obesity.

In addition to group differences, we also detected a significant correlation between percent body fat and R_5–20. The underlying mechanism describing the increase in peripheral airway resistance with an increase in percent body fat is difficult to elucidate. For example, in agreement with the present study, previous studies also report reductions in FRC in children (including adolescents)^2,3 and adults³⁵ with obesity. In adults, a reduction in FRC results in an increase in airway resistance due to the reduction in transpulmonary pressure transmitted across the bronchial airway wall, which reduces airway radius⁴¹. Therefore, in adults, a reduction in FRC with added chest mass would result in an increase in R_aw⁴². In the present study however, there was a moderate relationship between FRC (percent TLC) and R_aw, but only a weak relationship between FRC (percent TLC) and peripheral airway resistance (i.e., ‘R_5–20’). It is important to consider that R_5–20 is not exclusively a peripheral airway measure, whereas R_aw is an overall airway resistance measure⁴³, and therefore it is not surprising that there is only a weak correlation between FRC and R_5–20. Considering that, by definition, sR_aw corrects for differences in resting lung volume⁴⁴, our finding that sR_aw was similar between groups provides evidence of FRC as the source of variance in airway resistance among children without and with obesity. However, based on the weak association between FRC and IOS parameters, the added respiratory system resistance with obesity may be due to factors other than reduced FRC. It is also important to consider that in the presence of a main effect of obesity, the correlations presented in Figures 2A and 2B may be spurious. In the children with obesity (n = 51), we noted a weak correlation between percent of the 95^th BMI percentile and R_5–20 (r = 0.273, P = 0.053) but no relationship between percent body fat and R_5–20 (r = 0.158, P = 0.290). The inclusion of participants in the overweight category (i.e., those with a BMI between the 85^th and 95^th percentile) could offer important insights on the role of body composition on R_5–20.

We initially hypothesized a reduced bronchodilator response in children with obesity. However, we report no differences in changes in central, peripheral or total airway resistance after albuterol between children with and without obesity. We have previously reported no difference in FEV₁ and FEF_25–75 responses to inhaled albuterol between children with and without obesity¹⁴. Similarly, in non-asthmatic adults, Nicolacakis et al. reported no differences in FEV₁ responses to inhaled albuterol between individuals with and without obesity. We expected that measures of resistance via impulse oscillometry may be more sensitive to changes in airway caliber in response to albuterol, particularly among the peripheral airways. However, lack of differences by obesity status suggest that although there is an increase in central and peripheral airway resistance secondary to differences in transpulmonary pressure with a reduced FRC in nonasthmatic children with obesity, the capacity to bronchodilate in response to albuterol is well-preserved likely due to similar reactance (X₅) or elasticity of the lung between the two groups. In addition, considering that healthy airway smooth muscle likely has a limited capacity to relax and thus result in bronchodilation, repeating the study in asthmatic children with and without obesity may be warranted.

In the present study, we estimated respiratory system resistance using impulse oscillometry because it is easier to perform than traditional spirometry and offers much greater sensitivity to detect peripheral airway obstruction than spirometry and plethysmographic measures of airway resistance. While plethysmography is used solely to measure airway resistance, impulse oscillometry evaluates the resistive and elastic properties of the respiratory system, including the airways, lung parenchyma, and chest wall tissue²¹. Considering the significantly greater chest wall mass in children with obesity, it is conceivable that the agreeability between impulse oscillometry and plethysmography may differ between normal weight and obesity in children, whether due to differences in chest wall mass or differences in resting lung volume. We found that the agreement between the two measures is relatively high and seems to agree with previous studies. For example, Tomalak et al. retrospectively analyzed the results of these two tests in 337 children (165 girls) aged 5 – 18 years, including 197 children with asthma and other allergic diseases and reported an agreement between R₅ and R_aw of r = 0.64. Zerah et al. also tested the agreeability between R₅ and R_aw in 46 healthy nonasthmatic subjects with a wide range of BMI (25 to >40 kg/m²), aged 16 – 63 years and reported an agreement of r = 0.82 (p < 0.001). It is important to note that, while the agreement between R₅ and R_aw in the present study cohort is similar to those reported by previous studies, there may be a bias toward R₅ at resistances exceeding approximately 7 cmH₂O/L/s in children with obesity (see Figure 3B). While we did not investigate the cause of this finding, our data suggest that increases in chest mass beyond a certain point could disproportionately contribute to a greater R₅ but not R_aw. Further research is warranted to investigate this question.

Conclusion

This study has shown that obesity by itself is not sufficient to alter bronchodilator responsiveness in non-asthmatic children. Furthermore, lack of differences in X₅ between children with and without obesity combined with a similar increase in X₅ (i.e., less negative) after inhaled albuterol suggests that the simple mechanical effects of obesity in childhood do not alter respiratory system compliance to the point of altering physiological airway dilatation. Impulse oscillometry may offer important insights into respiratory system resistance and reactance beyond traditional measures from spirometry and plethysmography. However, the technique is limited because it does not allow for adjustments to be made based on where the child is breathing (i.e., FRC).

Data Availability

Data are available upon request from the authors.