Measurement of airway mucosal blood flow with dimethylether: validation with microspheres

Abstract

We have recently developed a noninvasive dimethylether (DME) uptake technique to estimate airway mucosal blood flow (Qaw) in humans (12). Because it was not feasible to validate the technique directly, we undertook the present study to compare Qaw as measured by DME (QDME) and by color-coded microspheres (QM) as a standard in seven anesthetized sheep prepared with a carotid and a left atrial catheter. QDME was determined by measuring DME uptake with multiple breath holds after passive inflation with a DME-helium gas mixture, simulating the technique used in humans. After the microspheres were injected into the left atrium, the sheep were killed and the tracheal segment corresponding to the dead space from which DME uptake was determined was removed, and its mucosa was stripped and processed for microsphere counts. Mean QDME was 35.6 ml.min-1.100 g-1 wet tissue (range 9.6-98.0 ml.min-1.100 g-1) and mean QM was 29.1 ml.min-1.100 g-1 (range 7.7-91.5 ml.min-1.100 g-1). There was a strong correlation between QDME and QM (r = 0.89; P = 0.01). Intravenous nitroglycerin and vasopressin caused comparable increases and/or decreases in QDME and QM (r = 0.87; P = 0.02). This suggests that the noninvasive DME uptake method measures Qaw accurately and supports its validity in human studies.

Inhaled corticosteroids: effects on the airway vasculature in bronchial asthma

“…Using a recently invented noninvasive method for airway blood flow measurements, these findings subsequently have been confirmed in human subjects. By measuring the uptake of an inhaled, soluble inert gas (dimethyl ether) [91,92], airway mucosal blood flow (comprising ,70% of total airway blood flow) has been shown to be increased in patients with stable bronchial asthma [5,29,93,94]. Calculated as in the volume of the conducting airways from the trachea to the terminal bronchioles (disregarding the most proximal 50 mL), mean airway blood flow values were 24-77% higher in asthmatics than in healthy controls [5,94].…”

Immediate sensory nerve-mediated respiratory responses to irritants in healthy and allergic airway-diseased mice

“…Chamber air also contained acetone vapor. Uptake of acetone vapor was monitored throughout exposure to provide a continuous measure of URT perfusion rates (11,28,29,35). The pressure drop across the URT was also measured during exposure to assess airway flow resistance throughout the exposure.…”

Inhaled corticosteroids reduce asthma-associated airway hyperperfusion through genomic and nongenomic mechanisms

“…These findings have now been confirmed in human subjects using recently invented noninvasive methods for airway blood flow measurements [20][21][22][23]. By measuring the uptake of an inhaled, soluble inert gas (dimethyl-ether, DME) [24,25], mean airway mucosal blood flow values (comprising about 70% of total airway blood flow) were 24% to 77% higher in patients with stable asthma than in healthy controls [20,23]. Using acetylene rather than DME for 6 measurements, airway blood flow has been confirmed to be elevated in patients with mild persistent and moderate asthma compared with healthy subjects [26].…”

“…Thus, with the advent of a noninvasive method to measure airway blood flow [20,25], airway blood flow changes might be assessed independent of lung function as an index of disease severity and to quantitate the response to anti-inflammatory therapy. Reported reduction of airway blood flow by anti-inflammatory therapy in asthmatics [22,37] and a positive correlation between exhaled nitric oxide and airway blood flo w levels [26] lend support to this concept.…”