As an inflammatory airway disease, asthma is expected to be associated with an increase in airway blood flow. We therefore compared airway mucosal blood flow (Qaw) among normal subjects (n = 11) and patients with stable asthma receiving (n = 13) or not receiving (n = 10) long-term inhaled glucocorticosteroid (GS) therapy. Qaw was calculated from the uptake of dimethyl ether in the anatomic dead space minus the most proximal 50 ml (DS), and expressed as blood flow per ml DS. Mean (+/- SE) Qaw was 38.5 +/- 5. 3 microl . min-1 . ml-1 in normals, 68.2 +/- 7.9 microl . min-1 . ml-1 in GS-naive asthmatics (p < 0.01), and 55.4 +/- 5.3 microl . min-1 . ml-1 in GS-treated asthmatics (p < 0.05). Ten minutes after administration of 180 microg albuterol by metered dose inhaler, mean Qaw increased by 83 +/- 26% in normal subjects (p < 0.01), but did not change significantly in GS-naive (+5 +/- 8%) or GS-treated (+32 +/- 15%) asthmatics. These results demonstrate that Qaw is increased in stable asthmatics and resistant to further increase by a standard inhaled dose of a beta-adrenergic agonist.

The variability of three methods of calculating pulmonary capillary blood flow (Qc) and pulmonary tissue plus capillary blood volume (Vt) during rebreathing was assessed in normal humans by using as markers acetylene, ethyl iodide, and dimethyl ether. The methods of analysis were as follows. Method I, the timing of the disappearance curves of the soluble gases was corrected by assuming that the C18O-disappearance curve intercepted at unity at time O. Method II, it was assumed that the acetylene Qc calculated by method I was correct; ethyl iodide and dimethyl ether Vt were solved by an equation using the disappearance slopes of these gases and the acetylene Qc value, thereby avoiding dependence on extrapolated intercept values. Method III, Vt was calculated by solving for a unique value of Qc between pairs of disappearance slopes of acetylene and dimethyl ether, acetylene and ethyl iodide, and ethyl iodide and dimethyl ether. Among the three methods, method I gave the most reproducible values for Vt as determined with acetylene or dimethyl ether. Using method I, both acetylene and dimethyl ether were equally acceptable gases for measurement of Vt; acetylene was a better marker for Qc measurements.

We measured the uptake of the soluble inert gas dimethyl ether (DME) from a segment of the conducting airways to estimate mucosal blood flow (Qaw) noninvasively. The subjects inhaled, from the functional residual capacity position, a 300-ml gas mixture containing 35% DME, 8% helium, 35% oxygen, and the balance nitrogen; they held their breath for 5 s and then exhaled into a spirometer. During exhalation, the instantaneous concentrations of DME and helium were recorded together with expired gas volume. The maneuver was repeated with breathhold times of 5, 10, 15, and 20 s. We calculated Qaw using the time-dependent decrease in DME concentration in relation to the helium concentration in an expired volume fraction between 80 and 130 ml (representing an anatomic dead-space segment distal to the glottis) and the mean DME concentration. In 10 healthy nonsmokers, mean (+/- SE) Qaw was 8.0 +/- 1.3 ml/min, or 8 +/- 2 microliters/min/cm2 mucosal surface. We obtained a value of 12 +/- 3 microliters/min/cm2 in a validation experiment in sheep. Inhaled methoxamine (nebulized dose 10 mg) caused a 65 +/- 19% decrease (p < 0.05), and albuterol (nebulized dose 2.5 mg) a 92 +/- 17% increase (p < 0.05), in mean Qaw in seven subjects, with the maximum changes occurring immediately or 15 min postinhalation. We conclude that the DME uptake method is an acceptable noninvasive means of estimating airway mucosal blood flow in humans and its modification by vasoactive substances.

Our laboratory has previously developed and validated a noninvasive soluble gas uptake method to measure airway blood flow (Qaw) in humans (Onorato DJ, Demirozu MC, Breitenbücher A, Atkins ND, Chediak AD, and Wanner A. Am J Respir Crit Care Med 149: 1132-1137, 1994; Scuri M, McCaskill V, Chediak AD, Abraham WM, and Wanner A. J Appl Physiol 79: 1386-1390, 1995). The method has the disadvantage of requiring eight breath-hold maneuvers for a single Qaw measurement, a complicated data analysis, and the inhalation of a potentially explosive gas mixture containing dimethylether (DME) and O2. Because of these shortcomings, the method thus far has not been used in other laboratories. We now simplified the method by having the subjects inhale 500 ml of a 10% DME-90% N2 gas mixture to fill the anatomical dead space, followed by a 5- or 15-s breath hold, and measuring the instantaneous DME and N2 concentrations and volume at the airway opening during the subsequent exhalation. From the difference in DME concentration in phase 1 of the expired N2 wash-in curve multiplied by the phase 1 dead space volume and divided by the mean DME concentration and the solubility coefficient for DME in tissue, Qaw can be calculated by using Fick's equation. We compared the new method to the validated old method in 10 healthy subjects and found mean +/- SE Qaw values of 34.6 +/- 2.3 and 34.6 +/- 2.8 microl.min(-1).ml(-1), respectively (r = 0.93; upper and lower 95% confidence limit +2.48 and -2.47). Using the new method, the mean coefficient of variation for two consecutive measurements was 4.4% (range 0-10.4%); inhalation of 1.2 mg albuterol caused a 53 +/- 14% increase in Qaw (P = 0.02) and inhalation of 2.4 mg methoxamine caused a 32 +/- 7% decrease in Qaw (P = 0.07). We conclude that the new method provides reliable values of and detects the expected changes in Qaw with vasoactive drugs. The simplicity and improved safety of the method should improve its acceptability for the noninvasive assessment of Qaw in clinical research.

We examined the effect of animal strain, type of spasmogen, and mode of spasmogen administration on the pattern of lung mechanical responses in intubated and mechanically ventilated mice. We determined the response in inspiratory respiratory system resistance (R(rs)) and inspiratory static respiratory system compliance (C(rs)) to increasing doses of inhaled or intravenous carbachol or serotonin in Balb/C and C57BL/6 mice. R(rs) responsiveness was quantitated by calculating, by interpolation, the inhaled spasmogen concentration (PC(150)) and intravenous spasmogen dose (PD(150)) causing an increase in R(rs) to 150% of baseline. C(rs) responsiveness was calculated similarly for a decrease in C(rs) to 85% of baseline (PC(85) for inhaled and PD(85) for intravenous spasmogen). Baseline R(rs) and C(rs) were similar in all groups. R(rs) responsiveness to inhaled and intravenous carbachol and serotonin tended to plateau and was not different in the two strains. In contrast, C(rs) responses were variable and had a greater mean PC(85) for inhaled serotonin than carbachol in both strains and a greater fall in mean C(rs) at PC(150) for carbachol in Balb/C mice; no interstrain and interdrug differences in PD(85) were noted for intravenous spasmogens. Intravenous atropine attenuated the R(rs) response to high-dose inhaled and intravenous serotonin, suggesting the involvement of a vagal reflex. In contrast, atropine attenuated C(rs) responses only for intravenous serotonin in Balb/C mice. These results suggest that animal strain, spasmogen, and mode of administration determine the extent to which induced airflow resistance is accompanied by increases in elastic recoil.