Tidal volume single breath washout of two tracer gases--a practical and promising lung function test

Background

Small airway disease frequently occurs in chronic lung diseases and may cause ventilation inhomogeneity (VI), which can be assessed by washout tests of inert tracer gas. Using two tracer gases with unequal molar mass (MM) and diffusivity increases specificity for VI in different lung zones. Currently washout tests are underutilised due to the time and effort required for measurements. The aim of this study was to develop and validate a simple technique for a new tidal single breath washout test (SBW) of sulfur hexafluoride (SF₆) and helium (He) using an ultrasonic flowmeter (USFM).

Methods

The tracer gas mixture contained 5% SF₆ and 26.3% He, had similar total MM as air, and was applied for a single tidal breath in 13 healthy adults. The USFM measured MM, which was then plotted against expired volume. USFM and mass spectrometer signals were compared in six subjects performing three SBW. Repeatability and reproducibility of SBW, i.e., area under the MM curve (AUC), were determined in seven subjects performing three SBW 24 hours apart.

Results

USFM reliably measured MM during all SBW tests (n = 60). MM from USFM reflected SF₆ and He washout patterns measured by mass spectrometer. USFM signals were highly associated with mass spectrometer signals, e.g., for MM, linear regression r-squared was 0.98. Intra-subject coefficient of variation of AUC was 6.8%, and coefficient of repeatability was 11.8%.

Conclusion

The USFM accurately measured relative changes in SF₆ and He washout. SBW tests were repeatable and reproducible in healthy adults. We have developed a fast, reliable, and straightforward USFM based SBW method, which provides valid information on SF₆ and He washout patterns during tidal breathing.     

Simultaneous helium and nitrogen single-breath washout: lung model simulation

By use of a model, simultaneous bolus and resident N2-washout curves are simulated to examine the effects of inhomogeneous lung elasticity and unequal critical airway closing pressure. Pathological conditions are divided into A, B, and C, where dominant lesions involve the upper, entire vertical, and lower regions, respectively. In elastic inhomogeneity, the He plateau (phase III) is upward, flat, or downward in conditions A, B, and C, respectively, depending on the vertical location of the lesion. Conversely, the N2 plateau is upward in three conditions, reflecting overall interregional and intraregional inhomogeneity. The terminal He rise (phase IV) has a clear relationship to the airway closure than the terminal N2 rise. The present study supports the previous prediction that the simultaneous bolus and N2-washout study provides additional information. This analysis will improve the means for assessing mechanical disorders in diseased lungs.     

Simultaneous convection compensation and solvent suppression in biomolecular NMR diffusion experiments

Thermal convection and high intensity solvent resonances can significantly hamper diffusion estimates in pulsed gradient spin-echo nuclear magnetic resonance diffusion experiments on biomolecule samples. To overcome these two problems, a new double functional NMR diffusion sequence, double echo PGSTE-WATERGATE, is presented. The new sequence provides excellent convection compensation and solvent suppression (with a suppression factor in excess of at least 10⁵ in a single scan) in biomolecular NMR diffusion experiments. Due to its stimulated echo nature, the new sequence is much less susceptible to spin–spin relaxation than Hahn spin-echo based sequences. Furthermore, the new sequence is not susceptible to spin diffusion due to the application of bipolar pulsed gradients. The new sequence is also much easier to set up compared to previously developed stimulated echo based convection compensation and solvent suppression sequence. The utility of the new sequence is demonstrated on an aqueous lysozyme sample.     

Nonuniformity of canine lung washout by high-frequency ventilation

Ethane washout during low tidal volume (25-100 ml) high-frequency (3-40 Hz) ventilation (HFV) was studied in seven excised dog lungs. The lungs were initially equilibrated with 1% ethane, and then the concentration of ethane was monitored by mass spectrometry from multiple anatomic sites along the tracheobronchial tree during washout. We observed that the lung changed from a uniform distribution of ethane concentrations to a nonuniform distribution by a three-phase process. The first phase was nearly complete within the first 15 s and probably corresponds to concentration gradients being established in the central airways. During the second phase of washout, which lasted for several minutes, the concentrations in the various alveolar regions diverged. In the final phase, the regional concentrations remained at fixed ratios, and washout from all sites in the lung was at a constant fractional rate. These data are consistent with a model in which the duration of the second phase and the magnitude of the regional concentration differences established in this phase are dependent on both the magnitude of differences between regional transport paths and the nature of regional coupling by a common transport path to the airway opening.     

A breath of fresh air in lung regeneration

Enhancing the ability of the lungs to regenerate following injury could revolutionize the treatment of a wide range of different diseases. In this issue, Kumar et al. (2011) and Ding et al. (2011) dissect the cellular and molecular mechanisms of murine lung regeneration following injury and provide insights into the basic biology of the organ with implications for development of future therapeutic approaches.     

Simultaneous diffusion and brightness measurements and brightness profile visualization from single fluorescence fluctuation traces of GFP in living cells

Fluorescence correlation spectroscopy (FCS) and photon-counting histogram (PCH) analysis use the same experimental fluorescence intensity fluctuations, but each analytical method focuses on a different property of the signal. The time-dependent decay of the correlation of fluorescence fluctuations is measured in FCS yielding, for instance, molecular diffusion coefficients. The amplitude distribution of these fluctuations is calculated by PCH analysis yielding information about the molecular brightness of fluorescent species. Analysis of both FCS and PCH results in the molecular concentration of the sample. Using a previously described global analysis procedure we report here precise, simultaneous measurements of diffusion constants and brightness values from single fluorescence fluctuation traces of green-fluorescent protein (GFP, S65T) in the cytoplasm of Dictyostelium cells. The use of a polynomial profile in PCH analysis, describing the detected three-dimensional shape of the confocal volume, enabled us to obtain well fitting results for GFP in cells. We could visualize the polynomial profile and show its deviation from a Gaussian profile.     

An overview of oxygen transport in plants: diffusion and convection

The movement of gases within plants is crucial for species that live in flood-prone areas with limited soil oxygen. These plants adapt to hypoxia/anoxia not by using oxygen more efficiently, but by ensuring a steady oxygen supply to their cells. Wetland plants typically form gas-filled spaces (aerenchyma) in their tissues, providing a low-resistance pathway for gas movement between shoots and roots, especially when the shoots are above water, and the roots are submerged. Oxygen movement in plant roots is mainly through diffusion. However, in certain species, such as emergent and floating-leaved plants, pressurized flows can also facilitate the movement of gases within their stems and rhizomes. Three types of pressurized (convective) flows have been identified: humidity-induced pressurization (positive pressure), thermal osmosis (positive pressure with air flow against the heat gradient), and venturi-induced suction (negative pressure) caused by wind passing over broken culms. A clear diel variation in pressurized flows exists, with higher pressures and flows during the day and negligible pressures and flows during the night. This article discusses some key aspects of these mechanisms for oxygen movement.     

Effect of lung volume on breath holding

The mechanism by which large lung volume lessens the discomfort of breath holding and prolongs breath-hold time was studied by analyzing the pressure waves made by diaphragm contractions during breath holds at various lung volumes. Subjects rebreathed a mixture of 8% CO2-92% O2 and commenced breath holding after reaching an alveolar plateau. At all volumes, regular rhythmic contractions of inspiratory muscles, followed by means of gastric and pleural pressures, increased in amplitude and frequency until the breakpoint. Expiratory muscle activity was more prominent in some subjects than others, and increased through each breath hold. Increasing lung volume caused a delay in onset and a decrease in frequency of contractions with no consistent change in duty cycle and a decline in magnitude of esophageal pressure swings that could be accounted for by force-length and geometric properties. The effect of lung volume on the timing of contractions most resembled that of a chest wall reflex and is consistent with the hypothesis that the contractions are a major source of dyspnea in breath holding.     

Serial determination of lung volume in small animals by nitrogen washout

This report describes the design of an apparatus and the procedures used to serially measure the total lung capacity and the functional residual capacity of small animals utilizing the N2-washout technique. The calibration data indicate that the technique is accurate to within 1 ml and has a variance of less than 5%. The in vivo lung volume measurements of rats were validated by comparing them with values obtained with a water-displacement technique; the means were within 0.3 ml. Examples of the precision and changes in lung volume of animals during studies are included to demonstrate the reliability and usefulness of the technique.     

Theoretical basis of single breath gas absorption tests

Absorption of gas from alveoli is examined in a simplified model of the respiratory system during a stylized single breath consisting of constant inspiratory flow, constant expiratory flow, and breathholding. The equations describing gas behavior are general since they are based upon conservation of mass. The equations simplify considerably when gases that are not soluble in pulmonary tissue and/or blood are utilized. In a three-compartment model, diffusing capacity of the lung for carbon monoxide (D _CO ) will be underestimated except when both uneven distribution of lung volume andD _CO are present; under most circumstances, the standard clinical 10-s method [9] is at least as accurate as any other. When pulmonary capillary blood flow is calculated by the one point method [2] in a one-compartment lung, it is underestimated; in the three-compartment model, it is underestimated except when both uneven distribution of . and lung volume are present. The multiple single breath method [2] accurately measuresD _CO and . Measurement of pulmonary tissue volume is improved by correcting the value of the intercept of acetylene absorption to the time when carbon monoxide apparently began rather than utilizing the beginning of inspiration.Nomenclature D _CO diffusing capacity of the lung for CO (ml CO, STPD/min/mm Hg) - pulmonary capillary blood flow rate (L/min) - V _t pulmonary tissue volume (L) - V _A alveolar compartment volume (L) - V _Ao alveolar compartment volume at conclusion of inspiratory flow (L) - inspiratory flow rate (L/sec) - expiratory flow rate (L/sec) - Bunsen coefficient of pulmonary tissue for test gas (ml test gas/ml tissue/atm) - Bunsen coefficient of pulmonary tissue for test gas (ml test gas/ml blood/atm) - F _A fractional pressure of test gas in the alveolar compartment (atm)