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Airway‐Parenchymal Interdependence

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Abstract

In this article, we discuss the interaction of the lung parenchyma and the airways as well as the physiological and pathophysiological significance of this interaction. These two components of the respiratory organ can be thought of as two independent elastic structures but in fact the mechanical properties of one influence the behavior of the other. Traditionally, the interaction has focused on the effects of the lung on the airways but there is good evidence that the opposite is also true, that is, that the mechanical properties of the airways influence the elastic properties of the parenchyma. The interplay between components of the respiratory system including the airways, parenchyma, and vasculature is often referred to as “interdependence.” This interdependence transmits the elastic recoil of the lung to create an effective pressure that dilates the airways as transpulmonary pressure and lung volume increase. By using a continuum mechanics analysis of the lung parenchyma, it is possible to predict the effective pressure between the airways and parenchyma, and these predictions can be empirically evaluated. Normal airway caliber is maintained by this pressure in the adventitial interstitium of the airway, and it attenuates the ability of airway smooth muscle to narrow airways. Interdependence has physiological and pathophysiological significance. Weakening of the forces of interdependence contributes to airway dysfunction and gas exchange impairment in acute and chronic airway diseases including asthma and emphysema. © 2012 American Physiological Society. Compr Physiol 2:1921‐1935, 2012.

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Figure 1. Figure 1.

Drawing showing the structures that balance the inward recoil of the lung. The contiguous intrapleural and interstitial virtual spaces (in light blue) are shown greatly enlarged for clarity. The inward recoil of the inflated lung (shown by the arrows) is supported by the outward recoil of the thoracic wall and the inward recoil of the airway tree. The interstitial pressure between the airways and parenchyma (Px) is normally very close to the pressure in the intrapleural space, Ppl.

Figure 2. Figure 2.

Volume versus transpulmonary pressure curves for dog lung (upper solid line), excised dog bronchus (lower solid line), and the predicted curve for the same bronchus in situ. This analysis illustrates three points. Firstly, the large bronchi are considerably less distensible than the lung, at least over this whole pressure range. The bronchial volume increases ≈3‐fold while the lung volume increases ≈8‐fold going from a Ptp of 0 to 20 cmH2O. Secondly, the maximal bronchial volume is reached at a much lower transpulmonary pressure than is the maximal lung volume (the plateau on the bronchial volume‐pressure curve is achieved at a Ptp of ≈8 cmH2O). Finally, the analysis shows that the in situ bronchus behaves almost exactly as if the Ptp is the effective distending pressure. The deviation of the solid (excised) and in situ (dashed) bronchial volume‐pressure curves represents the small difference between transpulmonary and transairway pressure due to the difference between pleural and interstitial pressure. Adapted, with permission, from Mead et al. ().

Figure 3. Figure 3.

Histologic section of small canine airway, showing the attachments of alveoli that also form the outer boundary of the airway. Bar is 0.5 mm.

Figure 4. Figure 4.

Pulmonary resistance plotted against lung volume (percent vital capacity) during inflation (interrupted lines) and deflation (solid lines) before (left panel) and after (right panel) administration of atropine. Prior to atropine, resistance decreases as lung volume increases but there is considerable hysteresis such that resistance is lower at any lung volume after inflation. Following abolition of airway smooth muscle (ASM) tone with atropine, there is both a decrease in resistance and an attenuation of hysteresis. Adapted, with permission, from Vincent et al. ().

Figure 5. Figure 5.

Illustration of the difference between uniform expansion of the lung and shear strain. A is a region of lung that can be uniformly expanded (B) or distorted (C). The bulk modulus is a measure of the lung's resistance to uniform expansion and is defined as the pressure needed to cause a given relative increase in volume. The shear modulus is a measure of the lungs resistance to shape change without a change in volume.

Figure 6. Figure 6.

(A) This schematic shows the effect of interaction between the lung parenchyma and airway. In these examples, the excised bronchus is illustrated by the solid bold line with diameter (De), the uniform hole in the parenchyma into which the airway must fit is shown by the thin solid line (Du), and the actual in situ diameter of the airway is shown by the interrupted line (Di). In Case a, the excised bronchus is smaller than the space within the parenchyma, so that Px will be negative relative to pleural pressure. In Case b, the excised bronchus is larger than the space within the parenchyma, so that Px will be positive. Ppl, pleural pressure; Pbr, intra airway pressure; and Palv, alveolar pressure. (B) The graphical solution to Eq. (1) for the normal situation where the excised bronchial diameter (De) is smaller than the uniform space within the parenchyma in which the airway is situated (Du). The relationships between Du and Di and transpulmonary pressure (Ptp), and between De and transmural pressure (Ptm) are plotted. The nonuniform behavior of the parenchymal hole at a constant transpulmonary pressure Ptp’ is given by the lines a and b, which is a plot of Δ Du/Du versus ΔPx from Eq. (1). Given values for Du and Di (points a and c) at Ptp’, point d on the De‐Ptm curve is determined. Alternatively, given the value for Du and De‐Ptm behavior (line f‐d), the value of Di (point c) is determined. ΔPx is the difference between peribronchial pressure and pleural pressure and μ is the shear modulus of the parenchyma. Adapted, with permission, from Lai‐Fook et al. ().

Figure 7. Figure 7.

The elastic loads (arbitrary units) impeding ASM shortening are plotted against fractional smooth muscle shortening. Data are for a 10th generation bronchus. The line labeled Ptp represents the load contributed by transpulmonary pressure. The influence of transpulmonary pressure decreases as the airway narrows due to the decreasing radius of curvature but ΔPx, which is related to the shear deformation of the parenchyma, increases as smooth muscle shortens. Modified, with permission, from Lambert et al. ().

Figure 8. Figure 8.

Result showing the relative independence of airway narrowing along the axis of an airway. A 12‐mm diameter airway was stimulated locally with 1, 10, and 100 mg/mL histamine, and the resultant size was measured with high resolution CT. With the highest histamine dose, the airway was completely closed, but the closure was localized to a very short region. Less than 1 cm along the axis, the airway is almost fully open. The coin is shown for scale perspective. Adapted, with permission, from reference ().



Figure 1.

Drawing showing the structures that balance the inward recoil of the lung. The contiguous intrapleural and interstitial virtual spaces (in light blue) are shown greatly enlarged for clarity. The inward recoil of the inflated lung (shown by the arrows) is supported by the outward recoil of the thoracic wall and the inward recoil of the airway tree. The interstitial pressure between the airways and parenchyma (Px) is normally very close to the pressure in the intrapleural space, Ppl.



Figure 2.

Volume versus transpulmonary pressure curves for dog lung (upper solid line), excised dog bronchus (lower solid line), and the predicted curve for the same bronchus in situ. This analysis illustrates three points. Firstly, the large bronchi are considerably less distensible than the lung, at least over this whole pressure range. The bronchial volume increases ≈3‐fold while the lung volume increases ≈8‐fold going from a Ptp of 0 to 20 cmH2O. Secondly, the maximal bronchial volume is reached at a much lower transpulmonary pressure than is the maximal lung volume (the plateau on the bronchial volume‐pressure curve is achieved at a Ptp of ≈8 cmH2O). Finally, the analysis shows that the in situ bronchus behaves almost exactly as if the Ptp is the effective distending pressure. The deviation of the solid (excised) and in situ (dashed) bronchial volume‐pressure curves represents the small difference between transpulmonary and transairway pressure due to the difference between pleural and interstitial pressure. Adapted, with permission, from Mead et al. ().



Figure 3.

Histologic section of small canine airway, showing the attachments of alveoli that also form the outer boundary of the airway. Bar is 0.5 mm.



Figure 4.

Pulmonary resistance plotted against lung volume (percent vital capacity) during inflation (interrupted lines) and deflation (solid lines) before (left panel) and after (right panel) administration of atropine. Prior to atropine, resistance decreases as lung volume increases but there is considerable hysteresis such that resistance is lower at any lung volume after inflation. Following abolition of airway smooth muscle (ASM) tone with atropine, there is both a decrease in resistance and an attenuation of hysteresis. Adapted, with permission, from Vincent et al. ().



Figure 5.

Illustration of the difference between uniform expansion of the lung and shear strain. A is a region of lung that can be uniformly expanded (B) or distorted (C). The bulk modulus is a measure of the lung's resistance to uniform expansion and is defined as the pressure needed to cause a given relative increase in volume. The shear modulus is a measure of the lungs resistance to shape change without a change in volume.



Figure 6.

(A) This schematic shows the effect of interaction between the lung parenchyma and airway. In these examples, the excised bronchus is illustrated by the solid bold line with diameter (De), the uniform hole in the parenchyma into which the airway must fit is shown by the thin solid line (Du), and the actual in situ diameter of the airway is shown by the interrupted line (Di). In Case a, the excised bronchus is smaller than the space within the parenchyma, so that Px will be negative relative to pleural pressure. In Case b, the excised bronchus is larger than the space within the parenchyma, so that Px will be positive. Ppl, pleural pressure; Pbr, intra airway pressure; and Palv, alveolar pressure. (B) The graphical solution to Eq. (1) for the normal situation where the excised bronchial diameter (De) is smaller than the uniform space within the parenchyma in which the airway is situated (Du). The relationships between Du and Di and transpulmonary pressure (Ptp), and between De and transmural pressure (Ptm) are plotted. The nonuniform behavior of the parenchymal hole at a constant transpulmonary pressure Ptp’ is given by the lines a and b, which is a plot of Δ Du/Du versus ΔPx from Eq. (1). Given values for Du and Di (points a and c) at Ptp’, point d on the De‐Ptm curve is determined. Alternatively, given the value for Du and De‐Ptm behavior (line f‐d), the value of Di (point c) is determined. ΔPx is the difference between peribronchial pressure and pleural pressure and μ is the shear modulus of the parenchyma. Adapted, with permission, from Lai‐Fook et al. ().



Figure 7.

The elastic loads (arbitrary units) impeding ASM shortening are plotted against fractional smooth muscle shortening. Data are for a 10th generation bronchus. The line labeled Ptp represents the load contributed by transpulmonary pressure. The influence of transpulmonary pressure decreases as the airway narrows due to the decreasing radius of curvature but ΔPx, which is related to the shear deformation of the parenchyma, increases as smooth muscle shortens. Modified, with permission, from Lambert et al. ().



Figure 8.

Result showing the relative independence of airway narrowing along the axis of an airway. A 12‐mm diameter airway was stimulated locally with 1, 10, and 100 mg/mL histamine, and the resultant size was measured with high resolution CT. With the highest histamine dose, the airway was completely closed, but the closure was localized to a very short region. Less than 1 cm along the axis, the airway is almost fully open. The coin is shown for scale perspective. Adapted, with permission, from reference ().

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Peter D. Paré, Wayne Mitzner. Airway‐Parenchymal Interdependence. Compr Physiol 2012, 2: 1921-1935. doi: 10.1002/cphy.c110039