Chest wall strapping increases expiratory airflow and detectable airway segments in computer tomographic scans of normal and obstructed lungs

Abstract

Chest wall strapping (CWS) induces breathing at low lung volumes but also increases parenchymal elastic recoil. In this study, we tested the hypothesis that CWS dilates airways via airway-parenchymal interdependence. In 11 subjects (6 healthy and 5 with mild to moderate COPD), pulmonary function tests and lung volumes were obtained in control (baseline) and the CWS state. Control and CWS-CT scans were obtained at 50% of control (baseline) total lung-capacity (TLC). CT lung volumes were analyzed by CT volumetry. If control and CWS-CT volumetry did not differ by more than 25%, airway dimensions were analyzed via automated airway segmentation. CWS-TLC was reduced on average to 71% of control-TLC in normal subjects and 79% of control-TLC in subjects with COPD. CWS increased expiratory airflow at 50% of control-TLC by 41% (3.50 ± 1.6 vs. 4.93 ± 1.9 l/s, P = 0.04) in normals and 316% in COPD(0.25 ± 0.05 vs 0.79 ± 0.39 l/s, P = 0.04). In 10 subjects (5 normals and 5 COPD), control and CWS-CT scans at 50% control-TLC did not differ more than 25% on CT volumetry and were included in the airway structure analysis. CWS increased the mean number of detectable airways with a diameter of ≤2 mm by 32.5% (65 ± 10 vs. 86 ± 124, P = 0.01) in normal subjects and by 79% (59 ± 19 vs. 104 ± 16, P = 0.01) in subjects with COPD. There was no difference in the number of detectable airways with diameters 2–4 mm and >4 mm in normal or in COPD subjects. In conclusion, CWS enhances the detection of small airways via automated CT airway segmentation and increases expiratory airflow in normal subjects as well as in subjects with mild to moderate COPD.

NEW & NOTEWORTHY In normal and COPD subjects, chest wall strapping(CWS) increased the number of detectable small airways using automated CT airway segmentation. The concept of dysanapsis expresses the physiological variation in the geometry of the tracheobronchial tree and lung parenchyma based on development. We propose a dynamic concept to dysanapsis in which CWS leads to breathing at lower lung volumes with a corresponding increase in the size of small airways, a potentially novel, nonpharmacological treatment for COPD.

INTRODUCTION

Chest wall strapping (CWS) is a technique that was first described in 1960 by Butler et al. (7) and Caro et al. (8) as an experimental procedure to induce breathing at low lung volumes. CWS has been studied to model the physiology of restrictive chest wall diseases and diseases of the respiratory musculature as well as the impact of general anesthesia on lung function (4, 10, 11, 22, 28, 31, 32, 33, 36). CWS also has similarities to the mechanical mismatch that might occur when an oversized donor lung is transplanted into a smaller thoracic cavity of a recipient (11–13).

Normal subjects consistently show that maximal expiratory flows are substantially increased with CWS (4, 7, 8, 10, 11, 22, 28, 31, 32, 33, 36). CWS also increases lung elastic recoil and reduces pulmonary compliance (4, 10, 22, 31–33), possibly due to an alteration in surface tension of the air-liquid interface when the lung operates at lower volumes (32). This increase in lung recoil with CWS might explain the observed increase in maximal expiratory flows (32). The interdependence between the elasticity of the parenchyma and small airways is critical for pulmonary function (27, 30). CWS leads to a decrease in closing volume, suggesting that increased elastic recoil leads to dilation of small airways (4, 22, 33). However, the effect of CWS on airway structure has not been studied directly. We have developed and validated an automated airway segmentation algorithm from thoracic computer tomographic (CT) scans demonstrating high sensitivity for the detection of small airways (2).

In this study, we tested the hypothesis that CWS dilates airways via airway-parenchymal interdependence by comparing control and CWS airway dimensions derived from automated CT airway segmentation. Another objective was to extend CWS studies from normal subjects to subjects with chronic obstructive pulmonary disease (COPD) to test the secondary hypothesis that CWS mediates dilation in chronically obstructed small airways. The results of this study have been reported previously in abstract form (34, 35).

MATERIALS AND METHODS

Study subjects.

This study was approved by the University of Iowa Hospitals and Clinics Institutional Review Board (IRB ID No. 201207758). Inclusion criteria for study enrollment were as follows: 1) for healthy subjects: absence of cardiopulmonary disease, male, age 18–45 yr; and 2) for subjects with mild to moderate COPD (GOLD stage I–III): male, age 18–70. Females were specifically excluded due to anatomic differences that may interfere with CWS.

Study procedures.

All subjects underwent pulmonary function testing, including spirometry and plethysmography, with measurement of forced vital capacity (FVC), forced expiratory volume at 1 s (FEV₁), total lung capacity (TLC), residual volume (RV), expiratory reserve volume (ERV), functional residual capacity (FRC), airway resistance (R_aw), and specific airway resistance (sR_aw) during panting maneuvers. Pulmonary function tests were performed according to American Thoracic Society standards.

For subjects with COPD, we included measurements of closing volume (CV) utilizing the single-breath nitrogen washout test (SBNT), as previously described (6). CV was expressed as a ratio to vital capacity (VC), i.e., CV/VC.

After pulmonary function tests(PFTs), the subjects were then taken for computer tomographic (CT) scans of the chest, following the SPIROMICS study protocol (9). To allow for analyses of CT scans in control and the CWS state at the same absolute lung volume, we obtained CT scans at 50% of the baseline TLC (control-TLC) under the control of a spirometer. After completion of the control CT scans, the subjects were escorted back to the PFT laboratory, where they underwent CWS. Figure 1 shows the study flow. The chest was strapped using a commercially available standard floating vest (Stearns adult life vest, model no. 5094). The vest covered the chest and upper abdomen and was tightened to limit the strapped-TLC to a goal of ∼70% of the baseline-TLC (control-TLC) (11). The same protocol, including spirometry, plethysmography, and CT scans, as detailed above, was followed while the chest was strapped.

Fig. 1.

Diagram of study flow. The chest wall strapping (CWS) was applied before pulmonary functions tests (PFTs) were obtained, and the correct level of CWS was confirmed by measuring total lung capacity (TLC). After confirmation of CWS to a goal reduction of TLC (70% of control TLC; 10–15 min), full PFTs (30–45 min) were obtained. Following PFTs, the subject was brought to the CT scanner for imaging at 50% of control TLC. CWS was maintained throughout, until completion of the CT scan protocol (20–30 min).

CT scans at 50% of the baseline TLC (control-TLC) were obtained while the chest was strapped, as described above. CT lung volumes of control and CWS CT scans obtained at 50% of the baseline (control) TLC were analyzed by CT volumetry. For this purpose, lungs were segmented with a fully automated algorithm (20) and manually inspected for correctness. Based on the segmentation result, the lung volume was calculated. Because the inflation state of the lung affects airway dimensions (5), we proceeded with the automated airway segmentation algorithm only if CT volumetry did not differ by >25% between control and CWS CT scans.

A framework for airway tree reconstruction from CT scans based on graph optimization was used, as previously described (2). The approach consists of two main processing steps. First, potential airway branch and connection candidates were identified and represented by a graph structure with weighted nodes and edges, respectively. Second, an optimization algorithm was utilized for airway detection by selecting a subset of branches and connections based on graph weights derived from image features. This combination enabled extraction of 91.80% of reference airways in combination with a low false-positive rate (1.00%) in a previous validation study (2). A morphometric assessment of the airways was performed on the control and CWS scans using VIDA software (Vida Diagnostics, Iowa City, IA) for sensitivity analysis, as described previously (38). For the purposes of this investigation, data were collected along a defined anatomic pathway from the trachea to generations of the posterior/basal segmental and subsegmental bronchi of the right lower lobe (RB10). These measurements were compared for each subject at defined matched anatomic areas between the control and the CWS state.

Lung density histograms were generated to compare lung density distributions between the CT scan in the control and the CWS state for each subject.

Data analysis.

Descriptive statistics with means ± SD and SE were calculated from each group together with percentage change after CWS. Because each subject functioned as his own control, we used a paired t-test to compare control and CWS values. P < 0.05 was considered statistically significant.

RESULTS

CWS in normal subjects.

The study subjects in the normal cohort had a mean age of 28.8 ± 9 yr and a mean BMI of 24.7 ± 3 kg/m². CWS-TLC was reduced to 71% of control-TLC (Table 1). Expiratory reserve volume (ERV) showed the greatest reduction with CWS at 50% (1.9 ± 0.3 to 0.94 ± 0.3, P < 0.01).

Table 1.

Pulmonary function studies at the baseline (control) and CWS state for normal subjects and subjects with mild to moderate COPD

	Normal				COPD
Parameter	Control	CWS	%Δ	P value*	Control	CWS	%Δ	P value*
Lung volumes
TLC, liters	7.16 ± 0.9	4.83 ± 0.5	−32	<0.01	7.2 ± 1.0	5.66 ± 0.8	−21	0.03
RV, liters	1.80 ± 0.5	1.54 ± 0.5	−15	0.39	2.87 ± 0.2	2.49 ± 0.4	−13	0.1
ERV, liters	1.97 ± 0.3	0.94 ± 0.3	−52	<0.01	1.38 ± 0.8	0.9 ± 0.5	−35	0.3
FRC, liters	3.64 ± 0.3	2.48 ± 0.5	−32	<0.01	4.28 ± 0.8	3.5 ± 0.4	−18.	0.08
Spirometry
FVC, liters	5.60 ± 1.0	3.58 ± 0.6	−36	0.01	4.44 ± 1.1	3.15 ± 1.0	−29	0.09
FEV1, liters	4.35 ± 0.4	2.83 ± 0.4	−35	<0.01	2.58 ± 0.6	1.74 ± 0.5	−33	0.04
FEV1/FVC	0.78 ± 0.4	0.79 ± 0.2	+1	0.4	0.59 ± 0.03	0.55 ± 0.04	−6	0.2
FEF (50% control TLC)	3.56 ± 1.6	4.93 ± 2.1	+41	0.04	0.25 ± 0.1†	0.79 ± 0.4†	+316	0.04
FEF (65% control TLC)					1.12 ± 0.4	2.76 ± 0.9	+246	0.009
FEF/FVC (50% control TLC)	0.64 ± 0.2	1.38 ± 0.3	+215	<0.01	0.06 ± 0.03	0.25 ± 0.1	+416	<0.01
FEF50/FIF50	1.20 ± 0.8	1.58 ± 0.9	+32	0.49	0.51 ± 0.1	0.61 ± 0.2	+20	0.42
Airway resistance
Raw	1.13 ± 0.2	0.70 ± 0.1	−38	0.03	2.03 ± 1.3	1.69 ± 1.2	−17	0.68
sRaw	4.62 ± 0.8	1.98 ± 0.5	−57	<0.01	8.99 ± 3.9	6.09 ± 4.0	−32	0.28
CV
CV/VC (%)					29.01 ± 4	15.65 ± 9	+46	0.02

Values are means ± SD. CWS, chest wall strapped; COPD, chronic obstructive pulmonary disease; TLC, total lung capacity; RV, residual volume; ERV, expiratory reserve volume; FRC, functional residual capacity; FVC, forced vital capacity; FEV₁, forced expiratory volume at 1 s; FEF, forced expiratory flow; FIF, forced inspiratory flow; R_aw, airway resistance; sR_aw, specific airway resistance; CV, closing volume; VC, vital capacity. Boldfaced values are those values that were significant at the P < 0.05 level.

^†Measurement only available for 4 of 5 subjects;

^*comparison by paired t-test.

In Fig. 2A the flow/volume loops for each study subject are shown, where for each subject the expiratory flows in the control and CWS state are plotted against the absolute lung volume; 50% control TLC is marked as a vertical dashed line. CWS increased expiratory airflow at 50% of control-TLC by 38% (3.56 ± 1.6 vs. 4.93 ± 1.9 l/s, P = 0.04). CWS reduced specific airway resistance (sR_aw) by 52% (4.62 ± 0.8 vs. 1.98 ± 0.5 kPa/s, P < 0.01; Table 2).

Fig. 2.

Flow-volume loops in control and strapped states. The flow-volume loops for each study subject are shown, where the expiratory flows in the control and CWS states are plotted against absolute lung volume. The vertical lines denote 65% of control TLC and 50% of the control TLC, as indicated. A: normal subjects. B: subjects with mild to moderate chronic obstructive pulmonary disease (COPD). FEF, forced expiratory flow.

Table 2.

CT volumetry data for baseline (control) and CWS state and the ratio between both states (CWS/control)

Subjects	Control, liters	CWS, liters	Ratio (CWS/control)
Normal
Subject 1	3.977	4.0810	1.03
Subject 2	4.503	4.0116	0.89
Subject 3†	5.317	3.299	0.62
Subject 4	4.233	3.705	0.88
Subject 5	3.298	3.461	1.05
Subject 6	5.127	5.263	1.03
Mean (SD)*	4.227 ± 0.7	4.104 ± 0.7	0.97 (P = 0.5)*
COPD
Subject 7	4.270	4.577	1.07
Subject 8	5.266	5.379	1.02
Subject 9	4.519	5.055	1.11
Subject 10	4.144	5.530	1.25
Subject 11	5.230	4.618	0.87
Mean ± SD	4.686 ± 0.5	5.031 ± 0.4	1.07 (P = 0.3)*

Mean values reflect the normal subjects, excluding subject 3.

^†Subject 3 was excluded from airway dimension analysis, as the difference between control and CWS CT volumetry was >25%;

^*comparison by paired t-test.

In five subjects, control and CWS CT-scans at 50% control-TLC did not differ more than 25% on CT volumetry and were included in the airway structure analysis (Table 2). Mean CT volumetry in these five subjects was 4.2 ± 0.6 liters in control and 4.1 ± 0.5 liters in the CWS state (P = 0.9). Figure 3 shows a representative airway tree segmented from the control and CWS CT scans of subject 1. For each individual subject, CWS increased the number of detectable airways with diameters ≤2 mm. Across all subjects, CWS increased the average number of detectable airways with diameters of ≤ 2 mm by 32.5% (65 ± 10 vs. 86 ± 12, P = 0.01; Fig. 4). There were no significant differences between the control and CWS conditions for the average number of detectable airways with diameters between 2 and 4 mm or >4 mm.

Fig. 3.

Airway tree based on automated airway segmentation algorithm and lung volumes demonstrated for study subject 1. Red, control CT scanned at 50% of control TLC; green, strapped CT scanned at 50% of control TLC. Control CT images are shown in the coronal (A), sagittal (B), and axial plane (C). Strapped CT scan images are shown in the coronal (D), sagittal (E), and axial plane (F).

Fig. 4.

No. of detectable airways on automated airway segmentation comparing the baseline [control (CRL)] and chest wall strapped (CWS) state, stratified by airway segment diameter. A: airway segments ≤2 mm. B: airway segments 2–4 mm. C: airway segments >4 mm. D: all detectable airway segments combined. Each connected CRL-CWS pair represents 1 individual study subject. Means ± SE of airway counts for each CRL and CWS group are shown.

CWS in COPD.

The subjects’ mean age was 65 and their average BMI was 25.9 kg/m². TLC during CWS was reduced to 79% of control TLC (7.2 ± 1.15 vs. 5.66 ± 0.82 liter, P = 0.03, Table 1B). ERV demonstrated the greatest reduction with CWS (35%, 1.38 ± 0.8 to 0.90 ± 0.5, P = 0.3), while RV was reduced by 13% (2.87 ± 0.12 vs. 2.49 ± 0.45 liter, P = 0.39) and FRC by 18.4% (4.28 ± 0.87 vs. 3.5 ± 0.47, P = 0.08).

Figure 2B shows the flow/volume loops for each study subject, where the expiratory flows in the control and CWS states are plotted against absolute lung volume. The vertical lines denote 65% of control TLC and 50% of the control TLC. Forced expiratory flow (FEF) at 50% of control TLC was 3.16-fold higher (0.25 ± 0.05 vs. 0.79 ± 0.39 l/s, P = 0.04). However, this observation was available in only four subjects, as subject 9 demonstrated negligible flow at 50% of control TLC (Table 2 and Fig. 1B). FEF at 65% of control TLC was present in all subjects with COPD and was 2.46-fold higher with CWS (1.12 ± 0.4 vs. 2.76 ± 0.9 l/s, P = 0.009). CWS reduced sR_aw by 32.3% (8.99 ± 3.95 vs. 6.09 ± 4.03 kPa/s, P = 0.28; Table 2). Closing volume divided by vital capacity was reduced by 39% (29 ± 4 vs. 15 ± 9%, P = 0.02).

CT-derived volumes at 50% of control TLC were comparable on average (4.7 ± 0.6 liters in control vs. 5.0 ± 0.5 liters in CWS, P = 0.93; Table 2). For each individual subject with COPD, CWS consistently increased the mean number of detectable airways with diameters of ≤2 mm. On average, CWS increased the number of detectable small airways by 79% (59 ± 19 vs. 104 ± 16, P = 0.01; Fig. 4). There were no significant differences between the control and CWS conditions for the mean number of detectable airways with diameters 2–4 mm or >4 mm.

Airway segmentation along an anatomical pathway.

A morphometric assessment of the airways was performed along a defined anatomic pathway from the trachea to generations of the posterior/basal segmental and subsegmental bronchi of the right lower lobe (RB10) for sensitivity analysis (Fig. 5). This approach demonstrated that matched anatomic areas in the segments corresponding to the smallest detectable airways were larger in the CWS compared with the control state (diameter of 2.4 ± 0.5 vs. 2.8 ± 0.2 mm, P = 0.1 for normal subjects; 2.2 ± 0.3 vs. 2.8 ± 0.6 mm, P = 0.04 for subjects with COPD; Table 3). For subjects with COPD, the matched tracheal segments were significantly larger during CWS compared with the control state (average diameter of 18.5 ± 1.7 vs. 19.2 ± 1.6 mm, P = 0.01).

Fig. 5.

Airway segmentation along an anatomic pathway [trachea to generations of the posterior-basal segmental and subsegmental bronchi of the right lower lobe (RB10)]. A morphometric assessment of the airways was performed on the control and CWS scans using VIDA software (Vida Diagnostics, Iowa City, IA), as described previously (38). These measurements were compared for each subject at defined matched anatomic areas between the control and the CWS state.

Table 3.

Airway segmentation along an anatomic pathway [trachea to generations of the posterior-basal segmental and subsegmental bronchi of the right lower lobe (RB10)]

	Airway Diameter
Subjects	Control	CWS	P value*
Normals
Anatomically matched airway segments
Trachea (∼18 mm)	17.7 ± 1.8	18.7 ± 0.3	0.3
∼11 mm	11.3 ± 0.7	11.4 ± 0.6	0.3
∼4 mm	4.4 ± 0.5	4.4 ± 0.4	0.8
∼2 mm	2.4 ± 0.5	2.8 ± 0.2	0.1
COPD
Anatomically matched airway segments
Trachea (∼19 mm)	18.5 ± 1.7	19.2 ± 1.6	0.01
∼10 mm	10.5 ± 1.2	10.4 ± 0.9	0.4
∼4 mm	4.3 ± 0.3	4.4 ± 0.2	0.2
∼2 mm	2.2 ± 0.3	2.6 ± 0.4	0.04

Values are means means ± SD. A morphometric assessment of the airways was performed on the control and CWS scans using VIDA software (Vida Diagnostics, Iowa City, IA), as described previously (25). These inner diameter measurements were compared for each subject at defined matched anatomic areas between the control and the CWS state. Boldfaced values are those values that were significant at the P < 0.05 level.

^*Comparison by paired t-test.

CT lung density analysis.

In normal subjects and in subjects with COPD, we observed a shift toward more negative Hounsfield units with CWS. Representative lung density histograms are shown in Fig. 5.

DISCUSSION

In this study of normal and COPD subjects, chest wall strapping (CWS) increased expiratory airflow and the number of detectable small airways consistently and significantly via automated CT segmentation. This small-airway dilation was likely augmented via radial traction from the increased elastic recoil of the parenchymal tissues during CWS, allowing more small airways to reach the detection threshold of the automated CT airway segmentation algorithm. This is supported by our results of physiological tests of small-airway function: lower specific airway resistance, lower residual volume, and lower closing volume with CWS.

Consistent with prior studies of CWS, we observed increased expiratory flows with CWS (4, 7, 8, 10, 11, 22, 28, 31, 32, 33, 36). We have extended this observation to subjects with mild to moderate COPD, where we demonstrate substantial increases in expiratory airflow for the same absolute lung volume with CWS. To our knowledge, this is the first study to examine the effect of CWS on airway structure using computed tomography and advanced segmentation approaches. Consistent with the results of improved small-airway function, we also found that CWS increased the number of detectable small airways via an automated CT airway segmentation algorithm in both normal subjects and subjects with COPD (Fig. 4). We validated this finding with a separate airway segmentation approach that compared matched anatomic areas of the airway tree between control and CWS conditions (Fig. 5 and Table 3).

The term dysanapsis was introduced by Green et al. (21) and Mead (26) to quantify physiological variations in the tracheobronchial tree vs. lung parenchyma geometries due to different patterns of lung growth. Mead (26) relied on a dysanapsis ratio (DR), defined as the ratio of an airway size index (maximal mid-vital capacity expiratory flow) to a lung size index (forced vital capacity) multiplied by static lung recoil to quantify dysanapsis. This DR captured relative differences in airway size vs. lung size between males and females. This dysanapsis as defined by Mead (26) reflects a relationship between airway size and lung size based on different patterns of growth during lung development and thus focuses on a static structural difference between the airway tree and lung parenchyma. As an extension of this original definition of dysanapsis, we propose a more dynamic view of dysanapsis: dynamic airway structure changes (small-airway dilation) observed with the reduction in lung volume, as seen during CWS. This concept of dysanapsis assumes that the lung adjusts to breathing conditions so that (airway) function is optimized over time scales ranging from a few breaths to several years, for example, when a breathing pattern changes from deep breaths during strenuous exercise to more shallow breaths during sleep, or during diving to depth in water, or a substantial increase in body mass index over years. For any of these conditions, the lung may change its operational volume, but it may adjust and optimize its airway structure and function via dysanapsis. Furthermore, dysanapsis may be a compensatory mechanism to prevent atelectasis in the setting of low lung volumes. The ratio of FEF (at 50% of the control TLC) to FVC in our data set could be considered as a “dysanapsis ratio”. This ratio shows substantial change from baseline to CWS state (+215% in normal subjects and +416% in subjects with COPD following CWS; Table 2).

Our data suggest that dysanapsis could have implications for nonpharmacological treatment of small-airway diseases such as COPD or bronchiolitis obliterans (11). Small-airway disease is critical in the pathology and progression of COPD. CT-assessed functional small-airway disease was strongly associated with FEV₁ decline in subjects with mild to moderate COPD (3). Furthermore, McDonough et al. (25) demonstrated that widespread airway narrowing, along with the destruction of smaller conducting airways, precedes the onset of detectable emphysematous changes in COPD. In that study, as COPD severity increased, there were less detectable airways in the 2- to 2.5-mm range on CT scans. Our data indicate that CWS increases the number small airways (≤2 mm) detected by CT imaging and segmentation and demonstrated improvement in small-airway function based in spirometric and plethysmographic indices. It is unclear, however, whether a longer application of CWS would reduce FEV₁ decline over time or the risk of progression to emphysema in subjects with mild to moderate COPD based on its immediate effect on small-airway function. Interestingly, in the Multiethnic Study of Atherosclerosis lung study, subjects with higher BMIs (i.e., conceptually, the more chest wall strapped a subject is; see Refs. 11 and 29) had a lower risk of emphysema on CT (1). CWS is conceptually similar to transplantation of an oversized lung into a smaller thoracic cavity due to a size mismatch between donor and recipient (14). We have previously reported supranormal expiratory airflows, lower risk of bronchiolitis obliterans, and improved survival associated with oversized lung transplantation (11–18). Bronchiolitis obliterans is a small-airway disease mainly affecting airways with diameters of <2 mm (37).

The mechanisms of increased lung elastic recoil with CWS have not been conclusively defined. Possible mechanisms for the increased lung elastic recoil with CWS include airway closure and atelectasis, distortion of the lung architecture, and an increase in alveolar surface tension due to changes in surfactant function. Regional ventilation, as assessed by Xenon washin/washout studies, demonstrated less inhomogeneity during CWS, with no evidence of atelectasis (33). In our data set, we observed a shift toward more negative Hounsfield units with CWS, suggesting that CWS decreased average radio density with improvement in regional aeration (Fig. 6). This is contrary to what would have been expected if CWS resulted in atelectasis or microatelectasis. Another possible explanation for the decrease in lung CT density would be hemodynamic effects, since the higher intrathoracic pressures associated with CWS might decrease cardiac preload and thus decrease thoracic blood volume. Observations from previous studies suggest that CWS increases lung elastic recoil by increasing alveolar surface forces via changes in surfactant function (19, 23, 24, 39).

Fig. 6.

Lung density histograms in the control (baseline) and strapped state. A: a normal subject (subject 1). B: a subject with COPD (subject 7). These images are representative for all study subjects, who showed a comparable pattern.

Limitations.

The main limitation of this study is that elastic recoil of the lung was not measured. However, the increase in lung elastic recoil has been well characterized in many previous studies (4, 10, 22, 31–33). Furthermore, the reductions in lung volume with CWS in the COPD group were somewhat modest. However, previous studies of CWS suggested that the reduction in ERV resulting in breathing at lower lung volumes mediated the increase in elastic recoil and when ERV is reduced to a threshold of 20–30%. Further reductions in ERV are associated with an increase in maximum expiratory flows (4). On average, ERV was reduced by 35% in our COPD group. Closing volumes were obtained only for the COPD subjects in this study. Nonetheless, previous studies in healthy subjects demonstrated decreased closing volume with CWS (4, 22, 33). Finally, only the immediate physiological effects of CWS were measured in this study, making it unclear how CWS might impact other clinical outcomes over longer time scales in patients with COPD. Future studies of CWS should include male and female subjects, assess possible changes of lung shape with CWS, account for possible regional variation in the effect of CWS, and include an investigation of possible effects on lung perfusion and thoracic blood volume in addition to an assessment of the long-term effects of CWS. Furthermore, the association between CWS and increased airway hyperresponsiveness needs to be considered, and investigations of CWS in subjects with COPD should include different COPD phenotypes and severities and assess long-term effects.

Conclusions.

In this study of normal and COPD subjects, chest wall strapping consistently and significantly increased the number of detectable small airways using automated CT airway segmentation. Small-airway dilation via increased radial traction offers a potential mechanistic explanation. The concept of dysanapsis expresses the physiological variation in the geometry of the tracheobronchial tree and lung parenchyma based on growth and development. We propose a dynamic concept to dysanapsis in which CWS leads to breathing at lower lung volumes with a corresponding increase in the size of small airways. Dynamic dysanapsis could have implications for nonpharmacological treatments of small-airway disease, such as COPD or bronchiolitis obliterans.

GRANTS

This work was supported in part by National Heart, Lung, and Blood Institute Grant R01-HL-111453 (R. R. Beichel) as well as a PILOT grant from the Institute for Clinical and Translational Science at the University of Iowa via the National Center for Advancing Translational Sciences Grant UL1-TR-000442 (M. Eberlein).

DISCLOSURES

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

AUTHOR CONTRIBUTIONS

H.T. and M.E. performed experiments; H.T., C.B., E.A., D.W.K., R.R.B., and M.E. analyzed data; H.T., C.B., E.A., D.W.K., S.P.B., J.Z., R.G.B., R.R.B., and M.E. interpreted results of experiments; H.T., R.R.B., and M.E. drafted manuscript; H.T., C.B., E.A., D.W.K., S.P.B., J.Z., R.G.B., R.R.B., and M.E. approved final version of manuscript; C.B., E.A., D.W.K., S.P.B., J.Z., R.G.B., R.R.B., and M.E. edited and revised manuscript; M.E. conceived and designed research; M.E. prepared figures.