Intrapulmonary shunt and alveolar dead space in a cohort of patients with acute COVID-19 pneumonitis and early recovery.

BACKGROUND: Pathological evidence suggests that coronavirus disease 2019 (COVID-19) pulmonary infection involves both alveolar damage (causing shunt) and diffuse microvascular thrombus formation (causing alveolar dead space). We propose that measuring respiratory gas exchange enables detection and quantification of these abnormalities. We aimed to measure shunt and alveolar dead space in moderate COVID-19 during acute illness and recovery. METHODS: We studied 30 patients (22 males; mean±sd age 49.9±13.5 years) 3-15 days from symptom onset and again during recovery, 55±10 days later (n=17). Arterial blood (breathing ambient air) was collected while exhaled oxygen and carbon dioxide concentrations were measured, yielding alveolar-arterial differences for each gas (P A-aO2 and P a-ACO2 , respectively) from which shunt and alveolar dead space were computed. RESULTS: For acute COVID-19 patients, group mean (range) for P A-aO2 was 41.4 (-3.5-69.3) mmHg and for P a-ACO2 was 6.0 (-2.3-13.4) mmHg. Both shunt (% cardiac output) at 10.4% (0-22.0%) and alveolar dead space (% tidal volume) at 14.9% (0-32.3%) were elevated (normal: <5% and <10%, respectively), but not correlated (p=0.27). At recovery, shunt was 2.4% (0-6.1%) and alveolar dead space was 8.5% (0-22.4%) (both p<0.05 versus acute). Shunt was marginally elevated for two patients; however, five patients (30%) had elevated alveolar dead space. CONCLUSIONS: We speculate impaired pulmonary gas exchange in early COVID-19 pneumonitis arises from two concurrent, independent and variable processes (alveolar filling and pulmonary vascular obstruction). For most patients these resolve within weeks; however, high alveolar dead space in ∼30% of recovered patients suggests persistent pulmonary vascular pathology.

Prone positioning redistributes gravitational stress in the lung in normal conditions and in simulations of oedema.

NEW FINDINGS: What is the central question of this study? How does the interaction between posture and gravity affect the stresses on the lung, particularly in highly inflated gravitationally non-dependent regions, which are potentially vulnerable to increased mechanical stress and injury? What is the main finding and its importance? Changes in stress attributable to gravity are not well characterized between postures. Using a new metric of gravitational stress, we show that regions of the lung near maximal inflation have the greatest gravitational stresses while supine, but not while prone. In simulations of increased lung weight consistent with severe pulmonary oedema, the prone lung has lower gravitational stress in vulnerable, non-dependent regions, potentially protecting them from overinflation and injury. ABSTRACT: Prone posture changes the gravitational vector, and potentially the stress induced by tissue deformation, because a larger lung volume is gravitationally dependent when supine, but non-dependent when prone. To evaluate this, 10 normal subjects (six male and four female; age, means ± SD = 27 ± 6 years; height, 171 ± 9 cm; weight, 69 ± 13 kg; forced expiratory volume in the first second/forced expiratory volume as a percentage of predicted, 93 ± 6%) were imaged at functional residual capacity, supine and prone, using magnetic resonance imaging, to quantify regional lung density. We defined regional gravitational stress as the cumulative weight, per unit area, of the column of lung tissue below each point. Gravitational stress was compared between regions of differing inflation to evaluate differences between highly stretched, and thus potentially vulnerable, regions and less stretched lung. Using reference density values for normal lungs at total lung capacity (0.10 ± 0.03 g/ml), regions were classified as highly inflated (density < 0.13 g/ml, i.e., close to total lung capacity), intermediate (0.13 ≤ density < 0.16 g/ml) or normally inflated (density ≥ 0.16 g/ml). Gravitational stress differed between inflation categories while supine (-1.6 ± 0.3 cmH2 O highly inflated; -1.4 ± 0.3 cmH2 O intermediate; -1.1 ± 0.1 cmH2 O normally inflated; P = 0.05) but not while prone (-1.4 ± 0.2 cmH2 O highly inflated; -1.3 ± 0.2 cmH2 O intermediate; -1.3 ± 0.1 cmH2 O normally inflated; P = 0.39), and increased more with height from dependent lung while supine (-0.24 ± 0.02 cmH2 O/cm supine; -0.18 ± 0.04 cmH2 O/cm prone; P = 0.05). In simulated severe pulmonary oedema, the gradient in gravitational stress increased in both postures (all P < 0.0001), was greater in the supine posture than when prone (-0.57 ± 0.21 cmH2 O/cm supine; -0.34 ± 0.16 cmH2 O/cm prone; P = 0.0004) and was similar to the gradient calculated from supine computed tomography images in a patient with acute respiratory distress syndrome (-0.51 cmH2 O/cm). The non-dependent lung has greater gravitational stress while supine and might be protected while prone, particularly in the presence of oedema.

Abnormal pulmonary perfusion heterogeneity in patients with Fontan circulation and pulmonary arterial hypertension.

KEY POINTS: The distribution of pulmonary perfusion is affected by gravity, vascular branching structure and active regulatory mechanisms, which may be disrupted by cardiopulmonary disease, but this is not well studied, particularly in rare conditions. We evaluated pulmonary perfusion in patients who had undergone Fontan procedure, patients with pulmonary arterial hypertension (PAH) and two groups of controls using a proton magnetic resonance imaging technique, arterial spin labelling to measure perfusion. Heterogeneity was assessed by the relative dispersion (SD/mean) and gravitational gradients. Gravitational gradients were similar between all groups, but heterogeneity was significantly increased in both patient groups compared to controls and persisted after removing contributions from large blood vessels and gravitational gradients. Patients with Fontan physiology and patients with PAH have increased pulmonary perfusion heterogeneity that is not explainable by differences in mean perfusion, gravitational gradients, or large vessel anatomy. This probably reflects vascular remodelling in PAH and possibly in Fontan physiology. ABSTRACT: Many factors affect the distribution of pulmonary perfusion, which may be disrupted by cardiopulmonary disease, but this is not well studied, particularly in rare conditions. An example is following the Fontan procedure, where pulmonary perfusion is passive, and heterogeneity may be increased because of the underlying pathophysiology leading to Fontan palliation, remodelling, or increased gravitational gradients from low flow. Another is pulmonary arterial hypertension (PAH), where gravitational gradients may be reduced secondary to high pressures, but remodelling may increase perfusion heterogeneity. We evaluated regional pulmonary perfusion in Fontan patients (n = 5), healthy young controls (Fontan control, n = 5), patients with PAH (n = 6) and healthy older controls (PAH control) using proton magnetic resonance imaging. Regional perfusion was measured using arterial spin labelling. Heterogeneity was assessed by the relative dispersion (SD/mean) and gravitational gradients. Mean perfusion was similar (Fontan = 2.50 ± 1.02 ml min-1  ml-1 ; Fontan control = 3.09 ± 0.58, PAH = 3.63 ± 1.95; PAH control = 3.98 ± 0.91, P = 0.26), and the slopes of gravitational gradients were not different (Fontan = -0.23 ± 0.09 ml min-1  ml-1  cm-1 ; Fontan control = -0.29 ± 0.23, PAH = -0.27 ± 0.09, PAH control = -0.25 ± 0.18, P = 0.91) between groups. Perfusion relative dispersion was greater in both Fontan and PAH than controls (Fontan = 1.46 ± 0.18; Fontan control = 0.99 ± 0.21, P = 0.005; PAH = 1.22 ± 0.27, PAH control = 0.91 ± 0.12, P = 0.02) but similar between patient groups (P = 0.13). These findings persisted after removing contributions from large blood vessels and gravitational gradients (all P < 0.05). We conclude that patients with Fontan physiology and PAH have increased pulmonary perfusion heterogeneity that is not explained by differences in mean perfusion, gravitational gradients, or large vessel anatomy. This probably reflects the effects of remodelling in PAH and possibly in Fontan physiology.

Measuring the efficiency of pulmonary gas exchange using expired gas instead of arterial blood: comparing the "ideal" Po2 of Riley with end-tidal Po2.

When using a new noninvasive method for measuring the efficiency of pulmonary gas exchange, a key measurement is the oxygen deficit, defined as the difference between the end-tidal alveolar Po2 and the calculated arterial Po2. The end-tidal Po2 is measured using a rapid gas analyzer, and the arterial Po2 is derived from pulse oximetry after allowing for the effect of the Pco2 on the oxygen affinity of hemoglobin. In the present report we show that the values of end-tidal Po2 and Pco2 are highly reproducible, providing a solid foundation for the measurement of the oxygen deficit. We compare the oxygen deficit with the classical ideal alveolar-arterial Po2 difference (A-aDO2) as originally proposed by Riley, and now extensively used in clinical practice. This assumes Riley's criteria for ideal alveolar gas, namely no ventilation-perfusion inequality, the same Pco2 as arterial blood, and the same respiratory exchange ratio as the whole lung. It transpires that, in normal subjects, the end-tidal Po2 is essentially the same as the ideal value. This conclusion is consistent with the very small oxygen deficit that we have reported in young normal subjects, the significantly higher values seen in older normal subjects, and the much larger values in patients with lung disease. We conclude that this noninvasive measurement of the efficiency of pulmonary exchange is identical in many respects to that based on the ideal alveolar Po2, but that it is easier to obtain.

Oxygen deficit is a sensitive measure of mild gas exchange impairment at inspired O2 between 12.5% and 21.

The oxygen deficit (OD) is the difference between the end-tidal alveolar Po2 and the calculated Po2 of arterial blood based on measured oxygen saturation that acts as a proxy for the alveolar-arterial Po2 difference. Previous work has shown that the alveolar gas meter (AGM100) can measure pulmonary gas exchange, via the OD, in patients with a history of lung disease and in normal subjects breathing 12.5% O2. The present study measured how the OD varied at different values of inspired O2. Healthy subjects were split by age (young 22-31; n = 23; older 42-90; n = 13). Across all inspired O2 levels (12.5, 15, 17.5, and 21%), the OD was higher in the older cohort 10.6 ± 1.0 mmHg compared with the young -0.4 ± 0.6 mmHg (P < 0.0001, using repeated measures ANOVA), the difference being significant at all O2 levels (all P < 0.0001). The OD difference between age groups and its variance was greater at higher O2 values (age × O2 interaction; P = 0.002). The decrease in OD with lower values of inspired O2 in both cohorts is consistent with the increased accuracy of the calculated arterial Po2 based on the O2-Hb dissociation curve and with the expected decrease in the alveolar-arterial Po2 difference due to a lower arterial saturation. The persisting higher OD seen in older subjects, irrespective of the inspired O2, shows that the measurement of OD remains sensitive to mild gas exchange impairment, even when breathing 21% O2.

Noninvasive measurement of pulmonary gas exchange: comparison with data from arterial blood gases.

A new noninvasive method was used to measure the impairment of pulmonary gas exchange in 34 patients with lung disease, and the results were compared with the traditional ideal alveolar-arterial Po2 difference (AaDO2) calculated from arterial blood gases. The end-tidal Po2 was measured from the expired gas during steady-state breathing, the arterial Po2 was derived from a pulse oximeter if the SpO2 was 95% or less, which was the case for 23 patients. The difference between the end-tidal and the calculated Po2 was defined as the oxygen deficit. Oxygen deficit was 42.7 mmHg (SE 4.0) in this group of patients, much higher than the means previously found in 20 young normal subjects measured under hypoxic conditions (2.0 mmHg, SE 0.8) and 11 older normal subjects (7.5 mmHg, SE 1.6) and emphasizes the sensitivity of the new method for detecting the presence of abnormal gas exchange. The oxygen deficit was correlated with AaDO2 ( R2 0.72). The arterial Po2 that was calculated from the noninvasive technique was correlated with the results from the arterial blood gases ( R2 0.76) and with a mean bias of +2.7 mmHg. The Pco2 was correlated with the results from the arterial blood gases (R2 0.67) with a mean bias of -3.6 mmHg. We conclude that the oxygen deficit as obtained from the noninvasive method is a very sensitive indicator of impaired pulmonary gas exchange. It has the advantage that it can be obtained within a few minutes by having the patient simply breathe through a tube.

Pulmonary challenges of prolonged journeys to space: taking your lungs to the moon.

Space flight presents a set of physiological challenges to the space explorer which result from the absence of gravity (or in the case of planetary exploration, partial gravity), radiation exposure, isolation and a prolonged period in a confined environment, distance from Earth, the need to venture outside in the hostile environment of the destination, and numerous other factors. Gravity affects regional lung function, and the human lung shows considerable alteration in function in low gravity; however, this alteration does not result in deleterious changes that compromise lung function upon return to Earth. The decompression stress associated with extravehicular activity, or spacewalk, does not appear to compromise lung function, and future habitat (living quarter) designs can be engineered to minimise this stress. Dust exposure is a significant health hazard in occupational settings such as mining, and exposure to extraterrestrial dust is an almost inevitable consequence of planetary exploration. The combination of altered pulmonary deposition of extraterrestrial dust and the potential for the dust to be highly toxic likely makes dust exposure the greatest threat to the lung in planetary exploration.

Measurements of pulmonary gas exchange efficiency using expired gas and oximetry: results in normal subjects.

We are developing a novel, noninvasive method for measuring the efficiency of pulmonary gas exchange in patients with lung disease. The patient wears an oximeter, and we measure the partial pressures of oxygen and carbon dioxide in inspired and expired gas using miniature analyzers. The arterial Po2 is then calculated from the oximeter reading and the oxygen dissociation curve, using the end-tidal Pco2 to allow for the Bohr effect. This calculation is only accurate when the oxygen saturation is <94%, and therefore, these normal subjects breathed 12.5% oxygen. When the procedure is used in patients with hypoxemia, they breathe air. The Po2 difference between the end-tidal and arterial values is called the "oxygen deficit." Preliminary data show that this index increases substantially in patients with lung disease. Here we report measurements of the oxygen deficit in 20 young normal subjects (age 19 to 31 yr) and 11 older normal subjects (47 to 88 yr). The mean value of the oxygen deficit in the young subjects was 2.02 ± 3.56 mmHg (means ± SD). This mean is remarkably small. The corresponding value in the older group was 7.53 ± 5.16 mmHg (means ± SD). The results are consistent with the age-related trend of the traditional alveolar-arterial difference, which is calculated from the calculated ideal alveolar Po2 minus the measured arterial Po2. That measurement requires an arterial blood sample. The present study suggests that this noninvasive procedure will be valuable in assessing the degree of impaired gas exchange in patients with lung disease.

Carbon Dioxide Exposure Resulting From Hood Protective Equipment Used in Joint Arthroplasty Surgery.

BACKGROUND: To protect both the surgeon and patient during procedures, hooded protection shields are used during joint arthroplasty procedures. Headache, malaise, and dizziness, consistent with increased carbon dioxide (CO2) exposure, have been anecdotally reported by surgeons using hoods. We hypothesized that increased CO2 concentrations were causing reported symptoms. METHODS: Six healthy subjects (4 men) donned hooded protection, fan at the highest setting. Arm cycle ergometry at workloads of 12 and 25 watts (W) simulated workloads encountered during arthroplasty. Inspired O2 and CO2 concentrations at the nares were continuously measured at rest, 12 W, and 25 W. At each activity level, the fan was deactivated and the times for CO2 to reach 0.5% and 1.0% were measured. RESULTS: At rest, inspired CO2 was 0.14% ± 0.04%. Exercise had significant effect on CO2 compared with rest (0.26% ± 0.08% at 12 W, P = .04; 0.31% ± 0.05% at 25 W, P = .003). Inspired CO2 concentration increased rapidly with fan deactivation, with the time for CO2 to increase to 0.5% and 1.0% after fan deactivation being rapid but variable (0.5%, 12 ± 9 seconds; 1%, 26 ± 15 seconds). Time for CO2 to return below 0.5% after fan reactivation was 20 ± 37 seconds. CONCLUSION: During simulated joint arthroplasty, CO2 remained within Occupational Safety and Health Administration (OSHA) standards with the fan at the highest setting. With fan deactivation, CO2 concentration rapidly exceeds OSHA standards.

Microgravity and the respiratory system.

The structure of the lung, with its delicate network of airspaces and capillaries, means that gravity has a profound influence on its function. Studies of lung function in the absence of gravity provide valuable insight into how, for we Earth-bound individuals, its unavoidable effects shape our lung function. Gravity causes uneven ventilation in the lung through the deformation of lung tissue (the so-called Slinky effect), and uneven perfusion through a combination of the Slinky effect and the zone model of pulmonary perfusion. Both ventilation and perfusion exhibit persisting heterogeneity in microgravity, indicating important other mechanisms. However, gravity serves to maintain a degree of matching of these two processes, so that the ventilation/perfusion ratio, and thus gas exchange, remains efficient. Therefore, while both ventilation and perfusion are more uniform in spaceflight, gas exchange is seemingly no more efficient than on Earth. Despite the changes in lung function when gravity is removed, the lung continues to function well in weightlessness. Unlike many other organ systems, the lung does not appear to undergo structural adaptive changes when gravity is removed, and so there is no apparent degradation in lung function upon return to earth, even after 6 months in space.

Advances in functional and structural imaging of the human lung using proton MRI.

The field of proton lung MRI is advancing on a variety of fronts. In the realm of functional imaging, it is now possible to use arterial spin labeling (ASL) and oxygen-enhanced imaging techniques to quantify regional perfusion and ventilation, respectively, in standard units of measurement. By combining these techniques into a single scan, it is also possible to quantify the local ventilation-perfusion ratio, which is the most important determinant of gas-exchange efficiency in the lung. To demonstrate potential for accurate and meaningful measurements of lung function, this technique was used to study gravitational gradients of ventilation, perfusion, and ventilation-perfusion ratio in healthy subjects, yielding quantitative results consistent with expected regional variations. Such techniques can also be applied in the time domain, providing new tools for studying temporal dynamics of lung function. Temporal ASL measurements showed increased spatial-temporal heterogeneity of pulmonary blood flow in healthy subjects exposed to hypoxia, suggesting sensitivity to active control mechanisms such as hypoxic pulmonary vasoconstriction, and illustrating that to fully examine the factors that govern lung function it is necessary to consider temporal as well as spatial variability. Further development to increase spatial coverage and improve robustness would enhance the clinical applicability of these new functional imaging tools. In the realm of structural imaging, pulse sequence techniques such as ultrashort echo-time radial k-space acquisition, ultrafast steady-state free precession, and imaging-based diaphragm triggering can be combined to overcome the significant challenges associated with proton MRI in the lung, enabling high-quality three-dimensional imaging of the whole lung in a clinically reasonable scan time. Images of healthy and cystic fibrosis subjects using these techniques demonstrate substantial promise for non-contrast pulmonary angiography and detailed depiction of airway disease. Although there is opportunity for further optimization, such approaches to structural lung imaging are ready for clinical testing.

Particulate deposition in the human lung under lunar habitat conditions.

INTRODUCTION: Lunar dust may be a toxic challenge to astronauts. While deposition in reduced gravity is less than in normal gravity (1 G), reduced gravitational sedimentation causes particles to penetrate deeper in the lung, potentially causing more harm. The likely design of the lunar habitat has a reduced pressure environment and low-density gas has been shown to reduce upper airway deposition and increase peripheral deposition. METHODS: Breathing air and a reduced-density gas approximating the density of the proposed lunar habitat atmosphere, five healthy subjects inhaled 1 -microm diameter aerosol boluses at penetration volumes (V(p)) of 200 ml (central airways), 500 ml, and 1000 ml (lung periphery) in microgravity during parabolic flight, and in 1 G. RESULTS: Deposition in the lunar habitat was significantly less than for Earth conditions (and less than in 1 G with the low-density gas) with a relative decrease in deposition of -59.1 +/- 14.0% (-46.9 +/- 11.7%), -50.7 +/- 9.2% (-45.8 +/- 11.2%), and -46.0 +/- 8.3% (-45.3 +/- 11.1%) at V(p) = 200, 500, and 1000 ml, respectively. There was no significant effect of reduced density on deposition in 1 G. DISCUSSION: While minimally affected by gas density, deposition was significantly less in microgravity than in 1 G for both gases, with a larger portion of particles depositing in the lung periphery under lunar conditions than Earth conditions. Thus, gravity, and not gas properties, mainly affects deposition in the peripheral lung, suggesting that studies of aerosol transport in the lunar habitat need not be performed at the low density proposed for the atmosphere in that environment.

Cardiogenic mixing increases aerosol deposition in the human lung in the absence of gravity.

RATIONALE: Exposure to extraterrestrial dusts is an almost inevitable consequence of any proposed planetary exploration. Previous studies in humans showed reduced deposition in low-gravity compared with normal gravity (1G). However, the reduced sedimentation means that fewer particles deposit in the airways, increasing the number of particles transported to the lung periphery where they eventually deposit albeit at a smaller rate than in 1G. In this study, we determined the role that gravity and other mechanisms such as cardiogenic mixing play in peripheral lung deposition during breath holds. METHODS: Eight healthy subjects inhaled boluses of 0.5 µm-diameter particles to penetration volumes (Vp) of 300 and 1200ml that were followed by breath holds of up to 10 sec. Tests were performed in 1G and during short periods of microgravity (µG) aboard the NASA Microgravity Research Aircraft. Aerosol deposition and dispersion were calculated from these data. RESULTS: Results show that, for both Vp, deposition in 1G was significantly higher than in µG. In contrast, while dispersion was significantly higher in 1G compared to µG at Vp=1200ml, there was no significant gravitational effect on dispersion at Vp=300ml. Finally, for each G level and Vp, deposition and dispersion significantly increased with increasing breath-hold time. CONCLUSION: The most important finding of this study is that, even in the absence of gravity, aerosol deposition in the lung periphery increased with increasing residence time. Because the particles used in this study were too large to be significantly affected by Brownian diffusion, the increase in deposition is likely due to cardiogenic motion effects.

Assessing the calculation of conductive and acinar ventilatory heterogeneity indices Scond and Sacin from multiple-breath washout data.

Sensor errors resulting in elevated values of N2 concentration [N2] in commercial multiple-breath washout (MBW) devices have been shown to prolong the washout and result in erroneously high functional residual capacity (FRC) and lung clearance index (LCI) values. The errors also affect the indices of conductive and acinar ventilatory heterogeneity (Scond and Sacin) although the mechanism by which this change in values occurs remains unclear. Exploring these effects also provides a timely opportunity to examine the appropriateness of the algorithm used to calculate these indices. Using a two-compartment model with differing specific ventilation (SV) such that the lower SV unit empties late, noise-free MBW were simulated both corrected and uncorrected for the recent sensor error. Scond was calculated using regression of normalized phase III slope (SnIII) against lung turnover (TO) from a TO range starting at 1.5 and ending at an upper turnover (TOupper) between 4 and 8 (default 6) over a range of simulated values. The principal effect of the sensor error was that as the MBW proceeded the phase III slope of successive breaths was normalized by an increasingly overestimated [N2], resulting in SnIII values that fell precipitously at high TO, greatly reducing Scond. Reanalysis of previously published data and of simulated data showed a large proportional bias in Scond, whereas Sacin was only minimally affected. In adult subject data, reducing TOupper below 5.5 was associated with a large drop of up to ∼60% in Scond calculated from data corrected for sensor error. Raising the upper TO limit elevated Scond by ∼20% but with a large concomitant increase in variability. In contrast to Scond, Sacin was relatively unaffected by changes in TOupper with changes of <3%. This work serves to emphasize that the upper limit of TO of 6 represents an appropriate upper limit for the calculation of Scond.NEW & NOTEWORTHY Sensor errors that elevated values of N2 concentration in commercial multiple-breath washout (MBW) devices resulted in errors in calculated parameters including Scond and Sacin. We examined the mechanism of the change in values produced by these errors and explored the appropriateness of the calculation of Scond and Sacin. This work serves to emphasize that the current algorithm in use is appropriate for the calculation of Scond and Sacin.

The spatial-temporal dynamics of pulmonary blood flow are altered in pulmonary arterial hypertension.

Global fluctuation dispersion (FDglobal), a spatial-temporal metric derived from serial images of the pulmonary perfusion obtained with MRI-arterial spin labeling, describes temporal fluctuations in the spatial distribution of perfusion. In healthy subjects, FDglobal is increased by hyperoxia, hypoxia, and inhaled nitric oxide. We evaluated patients with pulmonary arterial hypertension (PAH, 4F, aged 47 ± 15, mean pulmonary artery pressure 48 ± 7 mmHg) and healthy controls (CON, 7F, aged 47 ± 12) to test the hypothesis that FDglobal is increased in PAH. Images were acquired at ∼4-5 s intervals during voluntary respiratory gating, inspected for quality, registered using a deformable registration algorithm, and normalized. Spatial relative dispersion (RD = SD/mean) and the percent of the lung image with no measurable perfusion signal (%NMP) were also assessed. FDglobal was significantly increased in PAH (PAH = 0.40 ± 0.17, CON = 0.17 ± 0.02, P = 0.006, a 135% increase) with no overlap in values between the two groups, consistent with altered vascular regulation. Both spatial RD and %NMP were also markedly greater in PAH vs. CON (PAH RD = 1.46 ± 0.24, CON = 0.90 ± 0.10, P = 0.0004; PAH NMP = 13.4 ± 6.1%; CON = 2.3 ± 1.4%, P = 0.001 respectively) consistent with vascular remodeling resulting in poorly perfused regions of lung and increased spatial heterogeneity. The difference in FDglobal between normal subjects and patients with PAH in this small cohort suggests that spatial-temporal imaging of perfusion may be useful in the evaluation of patients with PAH. Since this MR imaging technique uses no injected contrast agents and has no ionizing radiation it may be suitable for use in diverse patient populations.NEW & NOTEWORTHY Using proton MRI-arterial spin labeling to obtain serial images of pulmonary perfusion, we show that global fluctuation dispersion (FDglobal), a metric of temporal fluctuations in the spatial distribution of perfusion, was significantly increased in female patients with pulmonary arterial hypertension (PAH) compared with healthy controls. This potentially indicates pulmonary vascular dysregulation. Dynamic measures using proton MRI may provide new tools for evaluating individuals at risk of PAH or for monitoring therapy in patients with PAH.

Noninvasive Assessment of Impaired Gas Exchange with the Alveolar Gas Monitor Predicts Clinical Deterioration in COVID-19 Patients.

BACKGROUND AND OBJECTIVE: The COVID-19 pandemic magnified the importance of gas exchange abnormalities in early respiratory failure. Pulse oximetry (SpO2) has not been universally effective for clinical decision-making, possibly because of limitations. The alveolar gas monitor (AGM100) adds exhaled gas tensions to SpO2 to calculate the oxygen deficit (OD). The OD parallels the alveolar-to-arterial oxygen difference (AaDO2) in outpatients with cardiopulmonary disease. We hypothesized that the OD would discriminate between COVID-19 patients who require hospital admission and those who are discharged home, as well as predict need for supplemental oxygen during the index hospitalization. METHODS: Patients presenting with dyspnea and COVID-19 were enrolled with informed consent and had OD measured using the AGM100. The OD was then compared between admitted and discharged patients and between patients who required supplemental oxygen and those who did not. The OD was also compared to SpO2 for each of these outcomes using receiver operating characteristic (ROC) curves. RESULTS: Thirty patients were COVID-19 positive and had complete AGM100 data. The mean OD was significantly (p = 0.025) higher among those admitted 50.0 ± 20.6 (mean ± SD) vs. discharged 27.0 ± 14.3 (mean ± SD). The OD was also significantly (p < 0.0001) higher among those requiring supplemental oxygen 60.1 ± 12.9 (mean ± SD) vs. those remaining on room air 25.2 ± 11.9 (mean ± SD). ROC curves for the OD demonstrated very good and excellent sensitivity for predicting hospital admission and supplemental oxygen administration, respectively. The OD performed better than an SpO2 threshold of <94%. CONCLUSIONS: The AGM100 is a novel, noninvasive way of measuring impaired gas exchange for clinically important endpoints in COVID-19.

Increased intrapulmonary shunt and alveolar dead space post-COVID-19.

Increased intrapulmonary shunt (QS/Qt) and alveolar dead space (VD/VT) are present in early recovery from 2019 Novel Coronavirus (COVID-19). We hypothesized patients recovering from severe critical acute illness (NIH category 3-5) would have greater and longer lasting increased QS/Qt and VD/VT than patients with mild-moderate acute illness (NIH 1-2). Fifty-nine unvaccinated patients (33 males, aged 52 [38-61] yr, body mass index [BMI] 28.8 [25.3-33.6] kg/m2; median [IQR], 44 previous mild-moderate COVID-19, and 15 severe-critical disease) were studied 15-403 days postacute severe acute respiratory syndrome coronavirus infection. Breathing ambient air, steady-state mean alveolar Pco2, and Po2 were recorded simultaneously with arterial Po2/Pco2 yielding aAPco2, AaPo2, and from these, QS/Qt%, VD/VT%, and relative alveolar ventilation (40 mmHg/[Formula: see text], VArel) were calculated. Median [Formula: see text] was 39.4 [35.6-41.1] mmHg, [Formula: see text] 92.3 [87.1-98.2] mmHg; [Formula: see text] 32.8 [28.6-35.3] mmHg, [Formula: see text] 112.9 [109.4-117.0] mmHg, AaPo2 18.8 [12.6-26.8] mmHg, aAPco2 5.9 [4.3-8.0] mmHg, QS/Qt 4.3 [2.1-5.9] %, and VD/VT16.6 [12.6-24.4]%. Only 14% of patients had normal QS/Qt and VD/VT; 1% increased QS/Qt but normal VD/VT; 49% normal QS/Qt and elevated VD/VT; 36% both abnormal QS/Qt and VD/VT. Previous severe critical COVID-19 predicted increased QS/Qt (2.69 [0.82-4.57]% per category severity [95% CI], P < 0.01), but not VD/VT. Increasing age weakly predicted increased VD/VT (1.6 [0.1-3.2]% per decade, P < 0.04). Time since infection, BMI, and comorbidities were not predictors (all P > 0.11). VArel was increased in most patients. In our population, recovery from COVID-19 was associated with increased QS/Qt in 37% of patients, increased VD/VT in 86%, and increased alveolar ventilation up to ∼13 mo postinfection. NIH severity predicted QS/Qt but not elevated VD/VT. Increased VD/VT suggests pulmonary microvascular pathology persists post-COVID-19 in most patients.NEW & NOTEWORTHY Using novel methodology quantifying intrapulmonary shunt and alveolar dead space in COVID-19 patients up to 403 days after acute illness, 37% had increased intrapulmonary shunt and 86% had elevated alveolar dead space likely due to independent pathology. Elevated shunt was partially related to severe acute illness, and increased alveolar dead space was weakly related to increasing age. Ventilation was increased in the majority of patients regardless of previous disease severity. These results demonstrate persisting gas exchange abnormalities after recovery.

Impact of Supine Versus Semirecumbent Body Posture on the Distribution of Ventilation in Acute Respiratory Distress Syndrome.

In some patients with acute respiratory distress syndrome (ARDS), a paradoxical improvement in respiratory system compliance (CRS) has been observed when assuming a supine (head of bed [HOB] 0°) compared with semirecumbent (HOB 35-40°) posture. We sought to test the hypothesis that mechanically ventilated patients with ARDS would have improved CRS, due to changes in ventilation distribution, when moving from the semirecumbent to supine position. We conducted a prospective, observational ICU study including 14 mechanically ventilated patients with ARDS. For each patient, ventilation distribution (assessed by electrical impedance tomography) and pulmonary mechanics were compared in supine versus semirecumbent postures. Compared with semirecumbent, in the supine posture CRS increased (33 ± 21 vs. 26 ± 14 mL/cm H2O, p = 0.005), driving pressure was reduced (14 ± 6 vs. 17 ± 7 cm H2O, p < 0.001), and dorsal fraction of ventilation was decreased (48.5 ± 14.1% vs. 54.5 ± 12.0%, p = 0.003). Posture change from semirecumbent to supine resulted in a favorable physiologic response in terms of improved CRS and reduced driving pressure-with a corresponding increase in ventral ventilation, possibly related to reduced ventral overdistension.