scholarly journals Nonuniformity of Diffusing Capacity From Small Alveolar Gas Samples Is Increased in Smokers

1998 ◽  
Vol 5 (2) ◽  
pp. 101-108 ◽  
Author(s):  
DJ Cotton ◽  
JT Mink ◽  
BL Graham

BACKGROUND: Although centrilobular emphysema, and small airway, interstitial and alveoli inflammation can be detected pathologically in the lungs of smokers with relatively well preserved lung function, these changes are difficult to assess using available physiological tests. Because submaximal single breath washout (SBWSM) manoeuvres improve the detection of abnormalities in ventilation inhomogeneity in the lung periphery in smokers compared with traditional vital capacity manoeuvres, SBWSMmanoeuvres were used in this study to measure temporal differences in diffusing capacity using a rapid response carbon monoxide analyzer.OBJECTIVE: To determine whether abnormalities in the lung periphery can be detected in smokers with normal forced expired volumes in 1 s using the three-equation diffusing capacity (DLcoSB-3EQ) among small alveolar gas samples and whether the abnormalities correlate with increases in peripheral ventilation inhomogeneity.PARTICIPANTS AND DESIGN: Cross-sectional study in 21 smokers and 21 nonsmokers all with normal forced exhaled flow rates.METHODS: Both smokers and nonsmokers performed SBWSMmanoeuvres consisting of slow inhalation of test gas from functional residual capacity to one-half inspiratory capacity with either 0 or 10 s of breath holding and slow exhalation to residual volume (RV). They also performed conventional vital capacity single breath (SBWVC) manoeuvres consisting of slow inhalation of test gas from RV to total lung capacity and, without breath holding, slow exhalation to RV. DLcoSB-3EQ was calculated from the total alveolar gas sample. DLcoSB-3EQ was also calculated from four equal sequential, simulated aliquots of the total alveolar gas sample. DLcoSB-3EQ values from the four alveolar samples were normalized by expressing each as a percentge of DLcoSB-3EQ from the entire alveolar gas sample. An index of variation (DI) among the small-sample DLcoSB-3EQ values was correlated with the normalized phase III helium slope (Sn) and the mixing efficiency (Emix).RESULTS: For SBWSM, DIwas increased in smokers at 0 s of breath holding compared with nonsmokers, and correlated with age, smoking pack-years and Sn. The decrease in DIwith breath holding was greater in smokers and correlated with the change in Sn with breath holding. For SBWVCmanoeuvres, there were no differences due to smoking in Sn or Emix, but DIwas increased in smokers and correlated with age and smoking pack-years, but not with Sn.CONCLUSIONS: For SBWSMmanoeuvres the increase in DIin smokers correlated with breath hold time-dependent increases in Sn, suggesting that the changes in DIreflected the same structural alterations that caused increases in peripheral ventilation inhomogeneity. For SBWVCmanoeuvres, the increase in DIin smokers was not associated with changes in ventilation inhomogeneity, suggesting that the effect of smoking on DIduring this manoeuvre was due to smoke-related changes in alveolar capillary diffusion, rather than due solely to alterations in the distribution of ventilation.

1997 ◽  
Vol 4 (1) ◽  
pp. 27-33
Author(s):  
DJ Cotton ◽  
JT Mink ◽  
BL Graham

BACKGROUND: In smokers, ‘small airways’ narrowing alters the conventional, vital capacity single breath washout (SBWVC). Although, in some studies, the test predicts smokers at risk of developing chronic airflow limitation, its wide variability partly explains its poor positive predictive value. An alternative explanation for the test’s poor predictive value is that it may not accurately reflect small airway narrowing in the lung periphery.OBJECTIVE: To determine whether smoke-induced increases in ventilation inhomogeneity differ between SBWVCmanoeuvres, which augment topographical (apex-to-base) ventilation inhomogeneity, and submaximal manoeuvres (SBWSM), which enhance peripheral ventilation inhomogeneity.STUDY GROUP AND DESIGN: Cross-sectional study of 21 current smokers and 21 nonsmokers with similar age and forced expiratory volumes in 1 s (FEV1).METHODS: Smokers and nonsmokers performed SBW with either slow vital capacity inhalation and exhalation of test gas without breath holding (SBWVC); or slow inhalation of test gas from functional residual capacity to one-half inspiratory capacity and, after 0 s or 10 s of breath holding, slow exhalation to residual volume (SBWSM). For all SBW the normalized phase III helium slope (Sn), closing capacity (CC) as a percentage of total lung capacity (TLC) and mixing efficiency (Emix) were measured.RESULTS: For SBWVC, smoking had no effect on Snor Emix. However, CC/TLC was increased in smokers (P<0.05), but did not correlate with pack years or age. For SBWSM, smoking had no effect on Emixor CC/TLC, but resulted in a steeper Sn(P <0.05), which decreased more with breath holding (P<0.01) and correlated with pack years (P<0.05) at 0 s but not 10 s of breath holding.CONCLUSIONS: In smokers with normal FEV1, SBWSM manoeuvres reveal increases in breath hold time-dependent ventilation inhomogeneity in the lung periphery, not detected by conventional SBWVC.


1994 ◽  
Vol 76 (4) ◽  
pp. 1494-1501 ◽  
Author(s):  
G. R. Soparkar ◽  
J. T. Mink ◽  
B. L. Graham ◽  
D. J. Cotton

The dynamic changes in CO concentration [CO] during a single breath could be influenced by topographic inhomogeneity in the lung or by peripheral inhomogeneity due to a gas mixing resistance in the gas phase of the lung or to serial gradients in gas diffusion. Ten healthy subjects performed single-breath maneuvers by slowly inhaling test gas from functional residual capacity to one-half inspiratory capacity and slowly exhaling to residual volume with target breath-hold times of 0, 1.5, 3, 6, and 9 s. We calculated the three-equation single-breath diffusing capacity of the lung for CO (DLSBCO-3EQ) from the mean [CO] in both the entire alveolar gas sample and in four successive equal alveolar gas samples. DLSBCO-3EQ from the entire alveolar gas sample was independent of breath-hold time. However, with 0 s of breath holding, from early alveolar gas samples DLSBCO-3EQ was reduced and from late alveolar gas samples it was increased. With increasing breath-hold time, DLSBCO-3EQ from the earliest alveolar gas sample rapidly increased, whereas from the last alveolar gas sample it rapidly decreased such that all values from the small alveolar gas samples approached DLSBCO-3EQ from the entire alveolar sample. These changes correlated with ventilation inhomogeneity, as measured by the phase III He concentration slope and the mixing efficiency, and were larger for maneuvers with inspired volumes to one-half inspiratory capacity vs. total lung capacity.(ABSTRACT TRUNCATED AT 250 WORDS)


1992 ◽  
Vol 73 (6) ◽  
pp. 2623-2630 ◽  
Author(s):  
D. J. Cotton ◽  
M. B. Prabhu ◽  
J. T. Mink ◽  
B. L. Graham

In patients with airflow obstruction, we found that ventilation inhomogeneity during vital capacity single-breath maneuvers was associated with decreases in the three-equation single-breath CO diffusing capacity of the lung (DLcoSB-3EQ) when breath-hold time (tBH) decreased. We postulated that this was due to a significant resistance to diffusive gas mixing within the gas phase of the lung. In this study, we hypothesized that this phenomenon might also occur in normal subjects if the breathing cycle were altered from traditional vital capacity maneuvers to those that increase ventilation inhomogeneity. In 10 normal subjects, we examined the tBH dependence of both DLcoSB-3EQ and the distribution of ventilation, measured by the mixing efficiency and the normalized phase III slope for helium. Preinspiratory lung volume (V0) was increased by keeping the maximum end-inspiratory lung volume (Vmax) constant or by increasing V0 and Vmax. When V0 increased while Vmax was kept constant, we found that the tBH-independent and the tBH-dependent components of ventilation inhomogeneity increased, but DLcoSB-3EQ was independent of V0 and tBH. Increasing V0 and Vmax did not change ventilation inhomogeneity at a tBH of 0 s, but the tBH-dependent component decreased. DLcoSB-3EQ, although independent of tBH, increased slightly with increases in Vmax. We conclude that in normal subjects increases in ventilation inhomogeneity with increases in V0 do not result in DLcoSB-3EQ becoming tBH dependent.


1963 ◽  
Vol 41 (1) ◽  
pp. 1283-1292
Author(s):  
Edith Rosenberg

The single breath diffusing capacity for CO, DL, and the permeability of the lungs, K, were measured in six male and two female medical students at various lung volumes. The subjects rested 15 minutes before each test and the expired alveolar volume as well as breath-holding time and inspired volume were recorded on a spirogram. The test gas used consisted of 0.3% CO, 0.3% SF6, 20% O2, and the balance N2. The sample of alveolar gas expired after breath-holding was analyzed for CO and SF6 on a vapor fractometer using a 2-meter molecular sieve column. DL varied with the surface area of the subjects as well as with the alveolar volume at which the test was performed. K, on the other hand, was independent of the size of the subjects and decreased towards a constant value as lung volume became large. K should, therefore, be more reproducible than DL. The average permeability of the eight subjects used in this study was 0.0715 ml CO per second per ml of alveolar volume. In every experiment, alveolar volumes were also calculated from the SF6 dilution. These values, VD, were compared to alveolar volumes calculated from the maximum lung volumes, VA. For the males there was no measurable difference between alveolar volumes calculated by these two methods when 2 liters or more of test gas were inspired. It is suggested that the replacement of the measurement of DL in pulmonary function laboratories by an evaluation of K and VD may transform the single breath diffusing capacity test into a useful diagnostic tool.


1996 ◽  
Vol 80 (4) ◽  
pp. 1126-1132 ◽  
Author(s):  
G. K. Prisk ◽  
A. M. Lauzon ◽  
S. Verbanck ◽  
A. R. Elliot ◽  
H. J. Guy ◽  
...  

We performed single-breath wash-in tests for He and SF6 in four subjects exposed to 14 days of microgravity (microG) during the Spacelab flight Spacelab Life Sciences-2. Subjects inspired a vital capacity breath of 5% He-1.25% SF6-balance O2 and then exhaled to residual volume at 0.5l/s. The tests were also performed with a 10-s breath hold at the end of inspiration. Measurements were also made with the subjects standing and supine in 1 G. Phase III slope was measured after the dead-space washout and before the onset of airway closure. In all subjects in 1 G, whether standing or supine, phase III slope for SF6 was significantly steeper than that for He. However, in microG, the slopes became the same. Furthermore, after breath holding in microG, the SF6 slopes were significantly flatter than those for He. On return to 1 G, the changes were reversed, and there was no difference between preflight and postflight values. Because most of the phase III slope reflects events occurring in the acinar regions of the lung, the results suggest that microG causes conformational changes in the acini or changes in cardiogenic mixing in the lung periphery, but in either case the mechanism is unclear.


1993 ◽  
Vol 75 (2) ◽  
pp. 927-932 ◽  
Author(s):  
D. J. Cotton ◽  
M. B. Prabhu ◽  
J. T. Mink ◽  
B. L. Graham

In normal seated subjects we increased single-breath ventilation inhomogeneity by changing both the preinspiratory lung volume and breath-hold time and examined the ensuing effects on two different techniques of measuring the diffusing capacity of the lung for carbon monoxide (DLCO). We measured the mean single-breath DLCO using the three-equation method (DLCOSB-3EQ) and also measured DLCO over discrete intervals during exhalation by the "intrabreath" method (DLCOexhaled). We assessed the distribution of ventilation using the normalized phase III slope for helium (SN). DLCOSB-3EQ was unaffected by preinspiratory lung volume and breath-hold time. DLCOexhaled increased with increasing preinspiratory lung volume and decreased with increasing breath-hold time. These changes correlated with the simultaneously observed changes in ventilation inhomogeneity as measured by SN (P < 0.01). We conclude that measurements of DLCOexhaled do not accurately reflect the mean DLCO. Intrabreath methods of measuring DLCO are based on the slope of the exhaled CO concentration curve, which is affected by both ventilation and diffusion inhomogeneities. Although DLCOexhaled may theoretically provide information about the distribution of CO uptake, the concomitant effects of ventilation nonuniformity on DLCOexhaled may mimic or mask the effects of diffusion nonuniformity.


1999 ◽  
Vol 79 (5) ◽  
pp. 456-466 ◽  
Author(s):  
Fiona Manning ◽  
Elizabeth Dean ◽  
Jocelyn Ross ◽  
Raja T Abboud

Abstract Background and Purpose. Body positioning exerts a strong effect on pulmonary function, but its effect on other components of the oxygen transport pathway are less well understood, especially the effects of side-lying positions. This study investigated the interrelationships between side-lying positions and indexes of lung function such as spirometry, alveolar diffusing capacity, and inhomogeneity of ventilation in older individuals. Subjects and Methods. Nineteen nonsmoking subjects (mean age=62.8 years, SD=6.8, range=50–74) with no history of cardiac or pulmonary disease were tested over 2 sessions. The test positions were sitting and left side lying in one session and sitting and right side lying in the other session. In each of the positions, forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), single-breath pulmonary diffusing capacity (DLCO/VA), and the slope of phase III (DN2%/L) of the single-breath nitrogen washout test to determine inhomogeneity of ventilation were measured. Results. Compared with measurements obtained in the sitting position, FVC and FEV1 were decreased equally in the side-lying positions, but no change was observed in DLCO/VA or DN2%/L. Conclusion and Discussion. Side-lying positions resulted in decreases in FVC and FEV1, which is consistent with the well-documented effects of the supine position. These findings further support the need for prescriptive rather than routine body positioning of patients with risks of cardiopulmonary compromise and the need to use upright positions in which lung volumes and capacities are maximized.


1989 ◽  
Vol 66 (6) ◽  
pp. 2511-2515 ◽  
Author(s):  
A. B. Crawford ◽  
D. J. Cotton ◽  
M. Paiva ◽  
L. A. Engel

We examined the effect of airway closure on ventilation distribution during tidal breathing in six normal subjects. Each subject performed multiple-breath N2 washouts (MBNW) at tidal volumes of 1 liter over a range of preinspiratory lung volumes (PILV) from functional residual capacity (FRC) to just above residual volume. All subjects performed washouts at PILV below their measured closing capacity. In addition five of the subjects performed MBNW at PILV below closing capacity with end-inspiratory breath holds of 2 or 5 s. We measured the following two independent indexes of ventilation maldistribution: 1) the normalized phase III slope of the final breaths of the washout (Snf) and 2) the alveolar mixing efficiency of those breaths of the washout where 80–90% of the initial N2 had been cleared. Between a mean PILV of 0.28 liter above closing capacity and that 0.31 liter below closing capacity, mean Snf increased by 132% (P less than 0.005). Over the same volume range, mean alveolar mixing efficiency decreased by 3.3% (P less than 0.05). Breath holding at PILV below closing capacity resulted in marked and consistent decreases in Snf and increases in alveolar mixing efficiency. Whereas inhomogeneity of ventilation decreases with lung volume when all airways are patent (J. Appl. Physiol. 66: 2502–2510, 1989), airway closure increases ventilation inequality, and this is substantially reduced by short end-inspiratory breath holds. These findings suggest that the predominant determinant of ventilation distribution below closing capacity is the inhomogeneous closure of airways subtending regions in the lung periphery that are close together.


1963 ◽  
Vol 41 (5) ◽  
pp. 1283-1292 ◽  
Author(s):  
Edith Rosenberg

The single breath diffusing capacity for CO, DL, and the permeability of the lungs, K, were measured in six male and two female medical students at various lung volumes. The subjects rested 15 minutes before each test and the expired alveolar volume as well as breath-holding time and inspired volume were recorded on a spirogram. The test gas used consisted of 0.3% CO, 0.3% SF6, 20% O2, and the balance N2. The sample of alveolar gas expired after breath-holding was analyzed for CO and SF6 on a vapor fractometer using a 2-meter molecular sieve column. DL varied with the surface area of the subjects as well as with the alveolar volume at which the test was performed. K, on the other hand, was independent of the size of the subjects and decreased towards a constant value as lung volume became large. K should, therefore, be more reproducible than DL. The average permeability of the eight subjects used in this study was 0.0715 ml CO per second per ml of alveolar volume. In every experiment, alveolar volumes were also calculated from the SF6 dilution. These values, VD, were compared to alveolar volumes calculated from the maximum lung volumes, VA. For the males there was no measurable difference between alveolar volumes calculated by these two methods when 2 liters or more of test gas were inspired. It is suggested that the replacement of the measurement of DL in pulmonary function laboratories by an evaluation of K and VD may transform the single breath diffusing capacity test into a useful diagnostic tool.


2001 ◽  
Vol 91 (2) ◽  
pp. 637-644 ◽  
Author(s):  
Per M. Gustafsson ◽  
Ola Eiken ◽  
Mikael Grönkvist

The effects of increased gravity in the head-to-foot direction (+Gz) and pressurization of an anti-G suit (AGS) on total and intraregional intra-acinar ventilation inhomogeneity were explored in 10 healthy male subjects. They performed vital capacity (VC) single-breath washin/washouts of SF6 and He in +1, +2, or +3 Gz in a human centrifuge, with an AGS pressurized to 0, 6, or 12 kPa. The phase III slopes for SF6 and He over 25–75% of the expired VC were used as markers of total ventilation inhomogeneity, and the (SF6 − He) slopes were used as indicators of intraregional intra-acinar inhomogeneity. SF6 and He phase III slopes increased proportionally with increasing gravity, but the (SF6 − He) slopes remained unchanged. AGS pressurization did not change SF6 or He slopes significantly but resulted in increased (SF6 − He) slope differences at 12 kPa. In conclusion, hypergravity increases overall but not intraregional intra-acinar inhomogeneity during VC breaths. AGS pressurization provokes increased intraregional intra-acinar ventilation inhomogeneity, presumably reflecting the consequences of basilar pulmonary vessel engorgement in combination with compression of the basilar lung regions.


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