MECHANISMS UNDERLYING THE INABILITY OF LUNG INFLATION TO RELAX ASTHMATIC AIRWAYS

Abstract

S410 INTRODUCTION: One theory proposed to explain airway hyperresponsiveness in asthma is the impairment in the ability of inspiration to stretch the airway smooth muscle. A deep inspiration (DI) reduces airway tone in normal subjects, while in asthmatic subjects, this response to a DI is frequently absent. Normally, the airways are tethered open by parenchymal attachments. As a deep inspiration expands the lungs, these parenchymal attachments pull open the airways by mechanical forces and dilate the airways. There are at least two possibilities for the failure of a deep inspiration to dilate the airways. One is that the tethering forces are inadequate to sufficiently pull open the airways. Another possibility is an exaggeration of the airway contractile mechanisms. In the latter case, the deep inspiration may temporarily dilate the airways, but on release of the deep inspiration back to functional residual capacity (FRC), the airway constriction is re-established. We used high resolution computed tomography (HRCT), to examine the ability of a deep inspiration to dilate the airways of asthmatic compared to normal subjects. METHODS: After IRB approval, we first examined whether a DI can dilate the airways in 5 asthmatics compared to 5 normals. Additionally, in 3 normals and 3 asthmatics, we examined whether airways remained dilated after a DI. All subjects performed a modified (absence of deep breaths) methacholine (Mch) challenge up to 2.5 mg/ml and HRCT was used to measure airway size at various lung volumes in vivo. RESULTS: 233 airways were measured in the 16 subjects (range: 1.7mm-11.4mm in diameter). At FRC, Mch decreased airway area similarly in the normal and the asthmatic subjects (Figure 1 and Figure 2, p>0.05). A DI was able to dilate the airways in the normal and asthmatic subjects to a similar extent (Figure 1, p=0.83). However, on return to FRC, the airways of the asthmatic subjects were significantly more constricted than the normal subjects (Figure 2, p=0.003).Figure 1: The increase in size at TLC as a percent pre-challenge FRC in (squares) and (diamond) subjects after challengeFigure 2: The increase in lumenal at TLC and on return to FRC as percent of pre-challenge FRC in (squares) and asthmatic subjects after Mch challenge compared to pre-DI FRCDISCUSSION: In mild asthmatics, a DI dilated the airways to a similar extent as in normal subjects. However, on return to resting lung volume, while the airways of the normal subjects were slightly dilated, the airways of the asthmatics were significantly further constricted. Therefore, the inability to dilate the airways with a DI during bronchoconstriction is more likely related to the effects that stretch may have on the contractile state of the smooth muscle in vivo. Supported in part by a grant from the International Anesthesia Research Society