Accurate measurements of airway mucosal blood flow, a new biomarker of asthma: Comparison of two soluble gases

Abstract

Rationale Airway mucosal vasculature participates in absorption of inhaled drugs and inflammatory processes. We tested two soluble gases, HFA 134a and acetylene to determine non-invasively airway mucosal vascularity as a marker of airway inflammation. Methods Six steroid naive asthmatics and six healthy subjects were tested. Deadspace volume was assessed using Fowler's method. Subjects inhaled to TLC one soluble gas mixture containing 0.3% acetylene and another containing HFA 134a which were exhaled into a spirometer through a critical flow orifice to standardize flow. Instantaneous concentrations of these gases in the anatomical dead-space fraction were measured at the airway opening using a mass spectrometer. Time dependent uptake was assessed by increasing breathold times between 2.5 and 20 secs. Results Mean percentage uptake of acetylene and HFA 134a was for asthmatic subjects, median 25.1% (15.76%-31.79%) and 3.87% (2.0%7.48%) compared to normal subjects, median 14.4% (6.10%-20.83%) ( p<0.05) and 2.25% (0.9% - 5.37%) ( p<0.05) respectively. Mean time dependent percentage uptake of acetylene with three randomly performed breatholds at 2.5, 5 and 10 seconds breatholds was for asthmatic subjects 32.12%, 35.7% and 39.22% respectively and for healthy subjects 26.0%, 27.71% and 36.12% respectively. Time dependent uptake was not seen with HFA 134a. Conclusions Lack of time dependent uptake of HFA 134a renders it unsuitable to determine airway mucosal blood flow (AMBF). Our results demonstrated acetylene is the better gas to determine AMBF as a marker of airway inflammation. It has the potential to evaluate new and existing treatments with utility across the range of asthma severity and other inflammatory airway diseases.