On the relationship between response to inhaled methacholine and airway dimensions

- Bronchoconstrictor protocol proposed for ranking subjects based on airway size.
- Scale factors were derived to extend measured airway dimensions to the entire lung.
- Inhalation dosimetry used to quantitate airway tissue sensitivity to methacholine.
- Methacholine protocol modified to be independent of airway tissue sensitivity.
- Linear relation seen between response to modified protocol and airway diameters.

Site-specific dosimetry was used to address the hypothesis that, given the airway dimensions of one subject, the airway dimensions of a second subject can be obtained by comparing responses to a modified bronchoconstrictor inhalation-protocol. Fourteen healthy, nonsmoking subjects received a high-resolution computed tomography (HRCT) scan prior to performing a methacholine challenge and measurement of change in forced-expiratory-volume-in-one-second, (∆FEV1). Scale factors of average length (L) and diameter (d) of the first six tracheobronchial airway generations were used to construct typical path lungs. The Multiple Path Particle Dosimetry (MPPD) model calculated surface density of methacholine. Airway circumference change, ∆C/C0, was used to calculate ∆FEV1 in terms of airway smooth muscle sensitivity, K (cm/µg/cm2). Virtual protocols were modeled such that fractional changes in ∆FEV1,“∆Y”, were independent of K. Eight subjects responded to methacholine with ∆FEV1 >3% and Ks from 0.011 to 35.8. For one virtual protocol, the linear relations between ∆Y and length and diameter scale factors had R2s respectively of 0.49 and 0.57. Within the limits of these measurements, the hypothesis is demonstrated; - any continuously increasing function of ∆Y vs. scale factor being sufficient to allow (without HRCT scans) classification of subjects according to airway size.