Effect of lung inflation and airway muscle tone on airway diameter in vivo

Abstract

How normal airway dimensions change with lung volume is of great importance in determining flow limitation during the normal forced vital capacity maneuver as well as in the manifestation of obstructive lung disease. The literature presents a confusing picture, with some results suggesting that airway diameter increases linearly with the cube root of lung volume and others showing a highly nonlinear relation. The effect of smooth muscle contraction on lung-airway interdependence is even less well understood. Recent morphological work explicitly assumes that airway basement membrane is nondistensible, although the lung volume at which this maximal airway size is reached is unknown. With smooth muscle contraction, folding of the epithelium and basement membrane accounts for the changes in luminal area. In this study, we measured the effect of lung inflation on relaxed and contracted airway areas by using high-resolution computed tomography at different transpulmonary pressures, each held for 2 min. We found that fully relaxed airways are quite distensible up to a pressure of 5-7 cmH2O (P < 0.001), where they reach a maximal size with no further distension up to an airway pressure of 30 cmH2O (P = 0.49). Thus relaxed airways clearly do not expand isotropically with the lung. With smooth muscle tone, the airways in different animals responded differently to lung inflation, with some animals showing minimal airway dilation up to an airway pressure of 20 cmH2O and others showing airways that were more easily dilated with lung expansion. However, maximal diameter of these moderately constricted airways was not usually achieved even up to an airway pressure of 30 cmH2O. Thus a transient deep inspiration in vivo would be expected to have only a small effect on contracted airways.

Effect of bronchial thermoplasty on airway distensibility

“…Consistent with previous work examining the pressure-area curves in canine airways [4], the relaxed airways were found to be quite distensible at pressures ,10 cmH 2 O and quite rigid above this pressure. Similarly, with airway contraction, this previous work also showed that the airways at low pressures could be quite stiff, only enlarging at the highest pressures.…”

“…Although it is possible that there was still some noncholinergic tone after the large-dose atropine, previous work in the dog model has showed that this is too small to detect with the imaging methods used [4].…”

“…The dogs were anaesthetised and ventilated as described above. On separate days, in random order, the dogs received a continuous intravenous infusion of methacholine (67 mg?min -1 ; Sigma Chemical, St Louis, MO, USA), a dose previously demonstrated to decrease the size of the airways to ,60% of baseline [4], or intravenous atropine (0.2 mg?kg -1 ), a dose previously shown to completely block vagal tone in dogs [4]. To standardise lung volume history, prior to each measurement, the airway pressure was increased to 35 cmH 2 O, held for 5 s and then decreased and maintained at the designated airway pressure for the duration of each set of scans.…”

“…The HRCT images were analysed using the airway analysis module of the Volumetric Image and Display Analysis (VIDA) image analysis software package (Dept of Radiology, Division of Physiologic Imaging, University of Iowa, Iowa City, IA, USA), as previously described and validated [4,11]. The HRCT images were transferred to a UNIX-based Sun workstation.…”

“…With smooth muscle tone, the airways do distend with increasing lung inflation, but maximal distension of even moderately constricted airways is not achieved, even at TLC [4]. This airway distension behaviour may be of more than academic interest, since the response to lung inflation and deep inspiration is known to be different in asthmatic subjects when compared to healthy individuals.…”