Measurement of intraindividual airway tone heterogeneity and its importance in asthma

Abstract

While airways have some degree of baseline tone, the level and variability of this tone is not known. It is also unclear whether there is a difference in airway tone or in the variability of airway tone between asthmatic and healthy individuals. This study examined airway tone and intraindividual airway tone heterogeneity (variance of airway tone) in vivo in 19 individuals with asthma compared with 9 healthy adults. All participants underwent spirometry, body plethysmography, and high-resolution computed tomography at baseline and after maximum bronchodilation with albuterol. Airway tone was defined as the percent difference in airway diameter after albuterol at total lung capacity compared with baseline. The amount of airway tone in each airway varied both within and between subjects. The average airway tone did not differ significantly between the two groups (P = 0.09), but the intraindividual airway tone heterogeneity did (P = 0.016). Intraindividual airway tone heterogeneity was strongly correlated with airway tone (r = 0.78, P < 0.0001). Also, it was negatively correlated with the magnitude of the distension of the airways from functional residual capacity to total lung capacity at both baseline (r = -0.49, P = 0.03) and after maximum bronchodilation (r = -0.51, P = 0.02) in the asthma, but not the healthy group. However, we did not find any relationship between intraindividual airway tone heterogeneity and conventional lung function outcomes. Intraindividual airway tone heterogeneity appears to be an important characteristic of airway pathophysiology in asthma.

Keywords: airways; bronchodilation; distensibility.

Fig. 1.

Baseline airway tone for all measured airways in each individual with asthma (A) and healthy controls (B). Each column represents one subject, and each circle or triangle represents one airway. The thick horizontal line represents mean airway tone for that subject. An airway in which albuterol did not change airway diameter is depicted with “zero” tone. *Baseline airway tone is defined as 100 − [(Airway diameter at TLC baseline)/(Airway diameter at TLC relaxed)] × 100.

Fig. 2.

Baseline airway tone in the asthma and the healthy groups. ○, mean airway tone for all airways in each study participant in the asthma group; △, mean airway tone for all airways in each healthy participant. The horizontal lines represent the mean airway tone for all the subjects in each group. No significant difference between the two groups was found (P = 0.09). *Baseline airway tone is defined as 100 − [(Airway diameter at TLC baseline)/(Airway diameter at TLC relaxed)] × 100.

Fig. 3.

Intraindividual airway tone heterogeneity in the asthma and the healthy groups. ○, mean intraindividual airway tone heterogeneity for all airways in each study participant in the asthma group; △, mean airway tone for all airways in each healthy participant. The horizontal lines represent the mean intraindividual airway tone heterogeneity for all the subjects in each group. A significant difference in intraindividual airway tone heterogeneity between the two groups was found (P = 0.016). *Intraindividual airway tone heterogeneity is defined as the statistical variance of airway tone for all the airways assessed within each subject.

Fig. 4.

Relationship between airway wall thickness (as a fraction of airway diameter) at TLC and airway tone heterogeneity. A: baseline. B: after maximum bronchodilation with albuterol. These figures clearly demonstrate that the statistically significant correlation between wall thickness and heterogeneity at baseline (P = 0.01) is eliminated after maximum bronchodilation (P = 0.22). These results strongly support the notion that the relationship at baseline is due to the presence of airway tone.