Functional imaging of airway narrowing

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Abstract

The report will focus on studies that illustrate how high resolution computed tomography can be used to provide new insights into airway and lung function, that cannot be obtained with any other methodology in humans or animal models. In one series of experiments, we have clearly demonstrated that even large cartilaginous airways are capable of complete closure in vivo. These unequivocal in vivo results invalidate the ubiquitous concept that there is a limit to airway narrowing in normal subjects. In another series of experiments, we have investigated potential reasons why asthmatic subjects might show airway constriction following deep inspiration instead of the normal dilation. Experimental results show that a constrictor response to deep inspiration can be generated in normal airways simply by minimizing tidal stresses. The absence of these normal rhythmic stresses alters the smooth muscle throughout the airway tree, such that subsequent large stresses lead to a further constriction. These results also offer a possible mechanism by which the response to deep inspiration is altered in asthmatic subjects. By allowing accurate measurement of the size of individual airways, computed tomography with modern commercially available scanners thus provides a unique opportunity to evaluate specific hypotheses regarding mechanisms underlying lung disease.

Introduction

In this chapter we will focus on the use of high resolution computed tomography (HRCT) to visualize airway size in vivo. Although other imaging modalities have potential to see into the lung in vivo, none presently have the convenience, the accessibility nor the resolution required to visualize airways. Although magnetic resonance imaging (MRI) avoids the potential concern about ionizing radiation, there is insufficient signal from airway walls to visualize anything but the largest airways. Inhaling hyperpolarized noble gases can provide a much stronger signal in MRI, but such experiments are technically cumbersome, costly and not generally available.

This report will review studies that illustrate the insights that can be obtained with HRCT as used in animals and humans. While several investigators have used HRCT to examine contraction of airways to various bronchoconstrictors (Okazawa et al., 1996, Kee et al., 1996, McNitt-Gray et al., 1997, Goldin et al., 1998, Han et al., 2000, Amirav et al., 2001), in this report we will focus on work from our laboratory that demonstrates the unique ability of HRCT to dissect mechanisms of airway contraction in vivo. Specifically, we will describe the use of HRCT to study the ability of individual airways to contract to closure. A second group of experiments deals with the effect of deep inspiration on individual airways. There are no other methods that allow this kind of insight or investigation of airway behavior in vivo.

Section snippets

Maximal contraction

When airways constrict in vitro, they generally do not exhibit a plateau effect to an agonist challenge, but continue to constrict to increasing concentrations of agonist until complete airway closure occurs (Armour et al., 1984, DeJongste et al., 1988). Thus, any apparent limitation in airway narrowing in vivo must be due to mechanisms not directly related to limitations associated with airway smooth muscle contraction. The appearance of a plateau in vivo (Woolcock et al., 1984, Sterk et al.,

Effects of deep inspiration (DI) on airway constriction

It has been known for many years that the response of asthmatic subjects to a deep inspiration differs from that observed in normal healthy subjects (Gayrard et al., 1975, Fish et al., 1977, Fish et al., 1981, Orehek et al., 1980, Beaupre and Orehek, 1982, Wheatley et al., 1989, Bousquet et al., 1996). A deep inspiration causes a fall in airway resistance in normal subjects, whereas asthmatic subjects demonstrate either no change or a slight increase in airway resistance. Skloot et al. (1995)

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