A. R. Elliott

Susceptibility to high-altitude pulmonary edema is associated with a more uniform distribution of regional specific ventilation

High-altitude pulmonary edema (HAPE) is a potentially fatal condition affecting high-altitude sojourners. The biggest predictor of HAPE development is a history of prior HAPE. Magnetic resonance imaging (MRI) shows that HAPE-susceptible (with a history of HAPE), but not HAPE-resistant (with a history of repeated ascents without illness) individuals develop greater heterogeneity of regional pulmonary perfusion breathing hypoxic gas (O2 = 12.5%), consistent with uneven hypoxic pulmonary vasoconstriction (HPV). Why HPV is uneven in HAPE-susceptible individuals is unknown but may arise from regionally heterogeneous ventilation resulting in an uneven stimulus to HPV. We tested the hypothesis that ventilation is more heterogeneous in HAPE-susceptible subjects (n = 6) compared with HAPE-resistant controls (n = 7). MRI specific ventilation imaging (SVI) was used to measure regional specific ventilation and the relative dispersion (SD/mean) of SVI used to quantify baseline heterogeneity. Ventilation heterogeneity from conductive and respiratory airways was measured in normoxia and hypoxia (O2 = 12.5%) using multiple-breath washout and heterogeneity quantified from the indexes Scond and Sacin, respectively. Contrary to our hypothesis, HAPE-susceptible subjects had significantly lower relative dispersion of specific ventilation than the HAPE-resistant controls [susceptible = 1.33 ± 0.67 (SD), resistant = 2.36 ± 0.98, P = 0.05], and Sacin tended to be more uniform (susceptible = 0.085 ± 0.009, resistant = 0.113 ± 0.030, P = 0.07). Scond was not significantly different between groups (susceptible = 0.019 ± 0.007, resistant = 0.020 ± 0.004, P = 0.67). Sacin and Scond did not change significantly in hypoxia (P = 0.56 and 0.19, respectively). In conclusion, ventilation heterogeneity does not change with short-term hypoxia irrespective of HAPE susceptibility, and lesser rather than greater ventilation heterogeneity is observed in HAPE-susceptible subjects. This suggests that the basis for uneven HPV in HAPE involves vascular phenomena.NEW & NOTEWORTHY Uneven hypoxic pulmonary vasoconstriction (HPV) is thought to incite high-altitude pulmonary edema (HAPE). We evaluated whether greater heterogeneity of ventilation is also a feature of HAPE-susceptible subjects compared with HAPE-resistant subjects. Contrary to our hypothesis, ventilation heterogeneity was less in HAPE-susceptible subjects and unaffected by hypoxia, suggesting a vascular basis for uneven HPV.

Characterizing Lung Disease in Cystic Fibrosis with Magnetic Resonance Imaging and Airway Physiology

Translational investigations in cystic fibrosis (CF) have a need for improved quantitative and longitudinal measures of disease status. To establish a non-invasive quantitative MRI technique to monitor lung health in patients with CF and correlate MR metrics with airway physiology as measured by multiple breath washout (MBW). Data were collected in 12 CF patients and 12 healthy controls. Regional (central and peripheral lung) measures of fractional lung water density (FLD: air to 100% fluid) were acquired both at FRC and TLC on a 1.5T MRI. The median FLD (mFLD) and the FRC-to-TLC mFLD ratio were calculated for each region at both lung volumes. Spirometry and MBW data were also acquired for each subject. Ventilation inhomogeneities were quantified by the lung clearance index (LCI) and by indices Scond* and Sacin* that assess inhomogeneities in the conducting (central) and acinar (peripheral) lung regions, respectively. MBW indices and mFLD at TLC (both regions) were significantly elevated in CF (p<0.01) compared to controls. The mFLD at TLC (central: R = 0.82) and the FRC-to-TLC mFLD ratio (peripheral: R = -0.77) were strongly correlated with Scond* and LCI. CF patients had high lung water content at TLC when compared to controls. This is likely due to the presence of retained airway secretions and airway wall edema (more water) and to limited expansions of air trapping areas (less air) in CF subjects. FRC-to-TLC ratios of mFLD strongly correlated with central ventilation inhomogeneities. These combined measures may provide a useful marker of both retained mucus and air trapping in CF lungs.

Upper airway dynamic imaging during tidal breathing in awake and asleep subjects with obstructive sleep apnea and healthy controls

We used magnetic resonance imaging (MRI) to quantify change in upper airway dimension during tidal breathing in subjects with obstructive sleep apnea (OSA, N = 7) and BMI‐matched healthy controls (N = 7) during both wakefulness and natural sleep. Dynamic MR images of the upper airway were obtained on a 1.5 T MR scanner in contiguous 7.5 mm‐thick axial slices from the hard palate to the epiglottis along with synchronous MRI‐compatible electroencephalogram and nasal/oral flow measurements. The physiologic data were retrospectively scored to identify sleep state, and synchronized with dynamic MR images. For each image, the upper airway was characterized by its area, and linear dimensions (lateral and anterior–posterior). The dynamic behavior of the upper airway was assessed by the maximum change in these parameters over the tidal breath. Mean upper airway caliber was obtained by averaging data over the tidal breath. There was no major difference in the upper airway structure between OSA and controls except for a narrower airway at the low‐retropalatal/high‐retroglossal level in OSA than in controls. Changes in upper airway size over the tidal breath ((maximum − minimum)/mean) were significantly larger in the OSA than in the control group in the low retropalatal/high retroglossal region during both wakefulness and sleep. In the four OSA subjects who experienced obstructive apneas during MR imaging, the site of airway collapse during sleep corresponded to the region of the upper airway where changes in caliber during awake tidal breathing were the greatest. These observations suggest a potential role for dynamic OSA imaging during wakefulness.

Ventilation Heterogeneity Measured by Multiple Breath Inert Gas Testing Is Not Affected By Inspired Oxygen Concentration in Healthy Humans

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 Sacin and Scond 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), Scond (hypoxia 0.014 ± 0.011, normoxia 0.012 ± 0.015, hyperoxia 0.010 ± 0.011, P = 0.34), or Sacin (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.