Ventilation heterogeneity measured by multiple breath inert gas testing is not affected by inspired oxygen concentration in healthy humans

Abstract

Multiple breath washout (MBW) and oxygen-enhanced MRI techniques use acute exposure to 100% oxygen to measure ventilation heterogeneity. Implicit is the assumption that breathing 100% oxygen does not induce changes in ventilation heterogeneity; however, this is untested. We hypothesized that ventilation heterogeneity decreases with increasing inspired oxygen concentration in healthy subjects. We performed MBW in 8 healthy subjects (4 women, 4 men; age = 43 ± 15 yr) with normal pulmonary function (FEV₁ = 98 ± 6% predicted) using 10% argon as a tracer gas and oxygen concentrations of 12.5%, 21%, or 90%. MBW was performed in accordance with ERS-ATS guidelines. Subjects initially inspired air followed by a wash-in of test gas. Tests were performed in balanced order in triplicate. Gas concentrations were measured at the mouth, and argon signals rescaled to mimic a N₂ washout, and analyzed to determine the distribution of specific ventilation (SV). Heterogeneity was characterized by the width of a log-Gaussian fit of the SV distribution and from S_acin and S_cond indexes derived from the phase III slope. There were no significant differences in the ventilation heterogeneity due to altered inspired oxygen: histogram width (hypoxia 0.57 ± 0.11, normoxia 0.60 ± 0.08, hyperoxia 0.59 ± 0.09, P = 0.51), S_cond (hypoxia 0.014 ± 0.011, normoxia 0.012 ± 0.015, hyperoxia 0.010 ± 0.011, P = 0.34), or S_acin (hypoxia 0.11 ± 0.04, normoxia 0.10 ± 0.03, hyperoxia 0.12 ± 0.03, P = 0.23). Functional residual capacity was increased in hypoxia (P = 0.04) and dead space increased in hyperoxia (P = 0.0001) compared with the other conditions. The acute use of 100% oxygen in MBW or MRI is unlikely to affect ventilation heterogeneity.NEW & NOTEWORTHY Hyperoxia is used to measure the distribution of ventilation in imaging and MBW but may alter the underlying ventilation distribution. We used MBW to evaluate the effect of inspired oxygen concentration on the ventilation distribution using 10% argon as a tracer. Short-duration exposure to hypoxia (12.5% oxygen) and hyperoxia (90% oxygen) during MBW had no significant effect on ventilation heterogeneity, suggesting that hyperoxia can be used to assess the ventilation distribution.

Keywords: hyperoxia; multiple breath washout; oxygen enhanced imaging; ventilation heterogeneity.

Fig. 1.

A: example tracing of the wash-in of argon in normoxia from one subject, MBW1. Argon signal is inverted and rescaled to mimic a nitrogen washout as described in Ref. . Data shown in B, C, and D are for one subject (subject MBW1) measured with O₂ = 12.5% (hypoxia), 21% (normoxia), and 90% (hyperoxia). B: example plots of the specific ventilation distribution in each O₂ concentration showing the fit to the 50-compartment model as described in Ref. . C: the plot of log mixed expired gas concentration (rescaled argon) against turnover (cumulative expired volume/FRC) from subject MBW1 is used to calculate lung clearance index (LCI) and curvilinearity. The horizontal solid line shows the point where “N₂” concentration is reduced to 2% of the inspired level in the normoxic plot, and the vertical solid line the associated LCI for this O₂ concentration. For curvilinearity the LCI/2 is determined, shown by the vertical dashed line, and then two regression slopes (shown as dashed lines just above the plotted points) between the range turnover = 0 and turnover = LCI/2 (vertical dashed line) and turnover = LCI/2 and turnover = LCI determined. Curvilinearity calculated as one minus the ratio of the two slopes. D: the plot of the phase III slope vs turnover. S_cond is calculated as the regression slope between turnovers 1.5 and 6. S_acin is determined as the value of the 1st breath minus the slope (i.e., S_cond), which accounts for the small contribution of the rate of rise due to convective inhomogeneities.

Fig. 2.

Top: mean of the recovered specific ventilation distribution in hypoxia, normoxia, and hyperoxia for each subject (n = 8). Bottom: width of the recovered specific ventilation distribution in hypoxia, normoxia, and hyperoxia for each subject. There are no significant changes in either mean or width of the distribution with different oxygen concentrations.

Fig. 3.

Lung clearance index (LCI) (top) and curvilinearity (bottom) in hypoxia, normoxia, and hyperoxia for each subject (n = 8). There are no significant changes in either LCI or curvilinearity with different oxygen concentrations.

Fig. 4.

S_cond (top) and S_acin (bottom) in hypoxia, normoxia, and hyperoxia for each subject (n = 8). There are no significant changes in either S_cond or S_acin with different oxygen concentrations.