Slope Of Alveolar Plateau Research Articles

Single breath nitrogen test as predictor of lung function decline and COPD over an 8-year follow-up

BackgroundThe single breath nitrogen (SBN2) test was proposed for early detection of “small airways disease” in the seventies. Few longitudinal studies have subsequently evaluated the relationships between SBN2 test measurements and lung function decline or COPD incidence. AimThis study evaluates whether SBN2 test abnormalities may be significant predictors of lung function decline and COPD incidence over an 8-year follow-up. Study Design and MethodsIn this longitudinal study, 907 adults (20+ years old; 56% males) from the prospective Po River Delta epidemiological study underwent SBN2 test at baseline and spirometry testing at both baseline and follow-up 8-year apart. Multinomial and multiple regression models were used to assess associations of SBN2 indexes and rates of FEV1 decline or risk of COPD incidence over time, after adjusting for sex, height and baseline age, FEV1 and smoking status. COPD was defined according to either GOLD or ATS-ERS criteria. ResultsAmong SBN2 indexes, only the slope of alveolar plateau (N2-slope) was significantly associated with rates of FEV1 decline (7.93 mL/year for a one-unit change in N2-slope, p<0.0001), and with an increased risk of developing COPD as defined by GOLD (RR 1.81, 95%CI 1.29-2.52, mild; RR 2.78, 95%CI 1.70-4.53, moderate or severe obstruction) and ATS-ERS criteria (RR 1.62, 95%CI 1.14-2.29, mild; RR 3.40, 95%CI 1.72-6.73, moderate or severe obstruction). ConclusionIn this population-based study, N2-slope from SBN2 test is a significant predictor of lung function decline and COPD incidence over an 8-year follow-up, confirming the role of the “small airways disease” in the natural history of COPD.

Systematic errors and susceptibility to noise of four methods for calculating anatomical dead space from the CO2 expirogram

Anatomical dead space is usually measured using the Fowler equal area method. Alternative methods include the Hatch, Cumming, and Bowes methods, in which first, second, and third order polynomials, respectively, fitted to an expired CO2 volume vs expired volume curve, intercept the x-axis at the anatomical dead space. This study assessed systematic errors and susceptibility to noise of the Fowler, Hatch, Cumming, and Bowes dead spaces calculated over 40-80% of the CO2 expirogram. Simulated CO2 expirograms with 220 ml anatomical dead space and varying alveolar plateau slopes were generated digitally and zero-mean Gaussian noise added. CO2 expirograms were recorded in 10 anaesthetized human subjects. Anatomical dead space was calculated by the Fowler, Hatch, Cumming, and Bowes methods. The Fowler, Hatch, Cumming, and Bowes methods displayed systematic biases of -1.8%, 13.2%, 2.4%, and -1.3%, respectively, at a normalized simulated alveolar plateau slope of 1.6 litre(-1). At a noise level of 0.0066 vol/vol, the standard deviations of recovered simulated dead spaces were 70.6, 1.8, 2.4, and 3.7 ml, respectively. The Hatch, Cumming, and Bowes methods applied to human expirograms differed significantly from that of Fowler by 13, -4, and -11 ml, respectively. In the human study, the Hatch and Cumming methods yielded the lowest intra-individual dead space variability. The Fowler method shows greatest susceptibility to measurement noise and the Hatch method exhibits the largest systematic error. The Cumming method, which exhibits both low bias and low noise susceptibility, is preferred for estimating anatomical dead space from CO2 expirograms.

Single-breath test in lateral decubitus reflects function of single lungs grafted for emphysema

The slope of alveolar plateau for nitrogen derived from the single-breath test is useful to assess the function of bilateral lung grafts, but this technique is not applicable to patients with single-lung grafts due to the confounding influence of the native lung. We tested the hypothesis that the nitrogen slope measured in lateral decubitus with the graft in nondependent position may primarily reflect the distribution of ventilation in this lung. Fifteen patients with single-lung transplantation for emphysema, 10 healthy controls, and 7 patients with advanced emphysema performed single-breath washouts in right and left lateral decubitus; nitrogen slope was measured between 75 and 100% of expired volume. In 10 transplant recipients, the volume of each lung was measured in the two postures by computerized tomography. Nitrogen slope was unaffected by posture in normal controls and emphysema patients. On the other hand, nitrogen slope in transplant recipients was invariably smaller, with the graft in nondependent vs. in dependent position. Values of nitrogen slope with the graft in nondependent position were similar to those obtained in normal controls but significantly smaller than those obtained in emphysema patients. Computerized tomography studies in this position indicated that the volume expired below functional residual capacity was exclusively contributed by the graft. We conclude that, in patients with single-lung transplantation for emphysema, 1) measuring nitrogen slope in lateral decubitus allows to distinguish between the graft and the native lung, and 2) nitrogen slope obtained with the graft in nondependent position reflects ventilation distribution in this lung.

Can we assess asthma severity using expiratory capnography in a pediatric emergency department?

Asthma is a common presenting problem in pediatric emergency departments (EDs). Accurate evaluation of asthma severity is important for acutely ill children, and pulmonary function tests are the current gold standard. Peak expiratory flow rates (PEFR) are possible in some children, but FEV1 (forced expiratory volume in one second) requires specialized equipment and a respiratory technician, a combination not available in most EDs. Both these manoeuvres require cooperation and are difficult to perform in young children. Clinical scores and oxygen saturations are simpler and more widely applicable, but are poor severity markers unless airflow is markedly decreased. 1 Similarly, transcutaneous or expired carbon dioxide (CO2) levels, or blood gas analysis are mainly useful in severe asthma. The ideal measure of airway obstruction should be simple, non-invasive, objective and valid in mild and severe asthma. It should also be effort-independent, therefore feasible in young and acutely ill asthmatic children. Capnography is a technique that provides both a waveform and a numerical value for the partial pressure of expired CO2 during each respiratory cycle (Fig. 1). Capnographs capture 2 key respiratory parameters: the rate of rise of [CO2] during the final phase of alveolar gas exhalation (alveolar plateau slope), and the Q angle, the angle between the initial rapid expiratory [CO2] rise and the alveolar plateau. This angle is normally very distinct, approaching 90°, but in asthma, airway obstruction and air trapping delay the mixing of alveolar and dead space gases, which results in a slower rise in [CO2] in expired air, an increased Q angle and a greater slope of alveolar plateau. 2

Multibreath washout analysis: modelling the influence of conducting airway asymmetry

The contributions of respiratory and conducting airway asymmetry, gas exchange, and non-uniform ventilation to the sloping alveolar plateau in phase III of the gas washout curve are investigated using mathematical models of the human lung. The models range from fully symmetric, to a detailed asymmetric conducting airway model coupled with 29 445 lumped parameter respiratory airway models. A gas transport equation is solved in the models using a Lagrange-Galerkin method. The alveolar slope is normalised by the mean expired gas concentration to give S n. The model results confirm that first breath S n is influenced mainly by respiratory airway asymmetry, and that at near-normal levels of ventilation the conducting airway asymmetry contributes a significant amount to further increases in S n. Gas exchange moderates the plot of S n against breath number, such that it approaches a plateau in later breaths. Non-uniform flow also alters S n, indicating that an accurate description of the pleural pressure gradient will be necessary for more accurate simulations.

A human acinar structure for simulation of realistic alveolar plateau slopes.

We simulated the intra-acinar contribution to phase III slope (S(acin)) for gases of differing diffusivities (He and SF(6)) by solving equations of diffusive and convective gas transport in multi-branch-point models (MBPM) of the human acinus. We first conducted a sensitivity study of S(acin) to asymmetry and its variability in successive generations. S(acin) increases were greatest when asymmetry and variability of asymmetry were increased at the level of the respiratory bronchioles (generations 17-18) for He and at the level of the alveolar ducts (generations 20-21) for SF(6), corresponding to the location of their respective diffusion fronts. On the basis of this sensitivity study and in keeping with reported acinar morphometry, we built a MBPM that actually reproduced experimental S(acin) values obtained in normal subjects for He, N(2), and SF(6). Ten variants of such a MBPM were constructed to estimate intrinsic S(acin) variability owing to peripheral lung structure. The realistic simulation of S(acin) in the normal lung and the understanding of how asymmetry affects S(acin) for different diffusivity gases make S(acin) a powerful tool to detect structural alterations at different depths in the lung periphery.

An Algebraic Solution to Dead Space Determination According to Fowler's Graphical Method

According to Fowler's method, anatomical dead space (VD) can be determined graphically or computer-aided by iteration procedures by which phase III of a fraction–volume expirogramF(V) is back-extrapolated by a straight lineR(V). Whereas Fowler visually partitioned phase II into two equal areas bordered byF(V),R(V), andVD, in the present paper the area betweenF(V) andR(V) is set equal to the area of a trapezoid, one side of which is the unknownVDto be determined. We obtained two algebraic equations for both possible conditions, nonsloping and sloping alveolar plateau, and, as the main result, an even more general third equation that includes both Bohr's and Fowler's solution. The formulas exactly represent Fowler's graphical method and can be applied to all gases which are applicable in dead space determination. The derived equations were tested in experimental situations, showing equality between values of dead space determined by using the algebraic solution and the graphical method. Their major advantage is facilitating and speeding up computer-aided on-line determinations ofVD.

Determination of DL CO and cardiac output from expired gas slopes with cardiogenic oscillations

Effects of ‘cardiogenic oscillations’ on alveolar plateau gas concentration slope measurements, constant expiratory pulmonary capillary blood flow, and D l CO determination have not been previously described. We examined cardiogenic oscillations during constant expiratory maneuvers to assess factors influencing magnitude of oscillations as well as effect of oscillatory phase at the start and end of exhalation measurement period on alveolar gas slope. Five normal volunteers performed repeated single breath constant exhalation vital capacity maneuvers using test gas containing 2 physiologically ‘inert’ gases: Helium (He M w 4) and argon (Ar M w 40). The mixture contained 3 absorbable gases, acetylene (C 2H 2 M w 26), carbon monoxide (C 18O M w 30), and oxygen. Alveolar plateau slope, magnitude of cardiogenic oscillations, relative signal to noise ratios, and effect of cardiogenic oscillation phase on measured slope were determined for each gas. Cardiogenic oscillations were present for all inert gases. Oscillations were less evident for CO. However, the effects on calculated Q̇c and D l CO were negligible. cardiac oscillations of considerable magnitude are seen during single breath constant exhalation maneuvers and affect constant expiratory gas slope calculations. Cardiogenic oscillation phase does not have a significant effect on measured Q̇c and D l CO using constant expiratory techniques.

Effects of some indoor environmental factors on respiratory symptoms and lung function in a sample of young non smokers in North Italy

We evaluated the effects of some indoor environmental factors in a non smoking subsample (n=381, age 8–19 years) of the general population living in the Po River Delta. Each subject completed an interviewer-administered standardized questionnaire on respiratory symptoms and risk factors. Acceptable maneuvers of forced vital capacity and slope of alveolar plateau of nitrogen were obtained in 96% and 59% of the subjects, respectively. In the houses there were more frequently natural gas for cooking (86%) than bottled gas (14%) and central heating (82%) than stove (18%). As regards passive smoking exposure, 18% of subjects had both parents smoking, 50% had one parent smoking. Significantly higher prevalence rates of wheeze, dyspnea, diagnosis of asthma were found in subjects of both sexes using bottled gas for cooking in comparison to those using natural gas, when also exposed to passive smoking. An insignificant trend towards higher symptom rates was shown by those using stove, instead of central heating. Lung function was affected only in females: those with both parents smoking had reduced forced expirograms, those with bottled gas for cooking or stove for heating had a decreased peak expiratory flow. Interactions of stove and passive smoking on peak expiratory flow and on slope of alveolar plateau were statistically significant. These findings confirm the mild adverse respiratory effects of certain home environment factors shown by other epidemiologic surveys in North Europe and in the USA. They have been a basis for the implementation, under the auspices of National Research Council and Electric Energy Authority, of future specific studies in which continuous monitoring of indoor pollutants and repeated recording of symptoms and lung function in North and Central Italy will be performed.

Multiple-breath washout experiments in rat lungs

Multiple-breath washouts were performed on 30 Wistar rats postmortem in a study in which breaths of 90% O2-5% He-5% SF6 were given. Preliminary comparison of alveolar plateau slopes obtained from anesthetized rats in vivo and postmortem showed that ventilation distribution remains the same within 1 h after the animals were killed. For maneuvers with different preinspiratory lung volumes and end-inspiratory breathholding, we computed the normalized N2 slope (Sn) and Fowler and Bohr dead spaces [VDF(n) and VDB(n), respectively] as a function of breath number (n). For all maneuvers analyzed, Sn of all gases increased in the first two or three breaths and reached a horizontal asymptote thereafter. The value of Sn decreased, both with increasing preinspiratory lung volume and breath hold of 4 s. The fact that the horizontal Sn asymptote is reached after only two or three breaths suggests the absence of convection-dependent inhomogeneities (CDI) in rat lungs. This contrasts with multiple-breath washout experiments in humans, where interregional (gravity-dependent CDI) and intraregional CDI generate a marked increase in Sn throughout the entire washout. Also, in contrast with results in humans, VDF and VDB were independent of n. The present work suggests that rats may be used to study diffusion- and convection-dependent inhomogeneities without the influence of CDI or gas exchange.

Single-breath washout experiments in rat lungs

Single-breath washouts were performed on 30 Wistar rats postmortem in studies in which breaths of 90% O2-5% He-5% SF6 were given. We investigated the effects of variations in preinspiratory lung volume, inspired volume, end-inspiratory breath-hold time, and inspiratory and expiratory flows on the alveolar plateau slopes for N2, He, and SF6. The main result is that the slope for He was always larger than the slope for SF6, except for large breath-hold times (approximately 15 s), contrary to previous findings in other species. Slopes for the three gases decreased with increasing inspiratory and expiratory flows when flows were greater than 1 ml/s. There was a strong correlation between the magnitude of a slope and its curvilinearity, suggesting that the concentration heterogeneity in the lung that causes the slope is due to interaction between diffusion and convection. The results seem incompatible with heterogeneities of parenchymal elasticity, which have been said to contribute to alveolar slopes in dog lungs but appear to be completely explainable as the result of diffusion-convection interaction in an asymmetric lung structure that has acini widely spread along the tracheobronchial tree.

Diffusivity, respiratory rate and tidal volume influence inert gas expirograms

We modified, and developed software for, a computer-controlled quadrupole mass spectrometer to measure complete breath-by-breath expirograms of helium (He) and sulfur hexafluoride (SF 6) exhaled during the infusion of saline saturated with the inert gases. He and SF 6 have similar blood solubilities but very different gas phase diffusivities allowing examination of the influence of gas phase diffusivity on steady state inert gas expirograms. We studied six normal human volunteers in nine separate studies and examined the influence of tidal volume (V t) and breathing frequency (f) on the airways dead space (V d aw) and alveolar plateau slope (phase III) for the inert gases and CO 2. The experimental data showed a reduction in V d aw with rapid shallow breathing, while phase III slope increased by a factor of two to three. We critically evaluated the data and methodology of these and previously reported studies of continuous and single breath washout of He and SF 6. In general the 15 to 20 ml differences in V d aw between He and SF 6 were in keeping with previous studies by others. The ratio of phase III slopes of SF 6 to He reported by us previously (Scherer et al., J. Appl. Physiol. 64: 1022–1029, 1988) was 3.13. In the current study, which includes the analysis of more than 400 He and SF 6 breaths, the ratio of SF 6 to He slope was 1.85. The difference between the two studies was largely related to the improved methodology of the current study, particularly for the measurement of He. The results support the conclusion that diffusivity is an important component of both phase II and phase III of the expirogram. However, the difference in phase III between He and SF 6 is somewhat less than previously reported.

Respiratory Effects of Occupational Exposure in a General Population Sample in North Italy

We assessed the effects of occupational exposure in a general population sample living in an unpolluted rural area of North Italy. In the age range of 18 to 64 yr, there were 417 participants who reported any exposure to dusts, chemicals, or gases and 1,218 who reported no exposure. Each subject completed a standardized interviewer-administered questionnaire (CNR-questionnaire). A variable proportion of participants succeeded in performing flow-volume curves, diffusing capacity of carbon monoxide, and slope of alveolar plateau of nitrogen. There was no significant difference for symptom prevalence rates between exposed and nonexposed in men and women who smoke. In nonsmoking women, those exposed showed significantly higher prevalence rates for exertional dyspnea and asthma. Regarding lung function, in exposed male smokers there was a significantly higher slope of the alveolar plateau. In exposed female nonsmokers, FEV1 and forced expiratory flows were significantly lower. Multiple logistic models in the overall group, accounting for age, smoking, and pack-years, showed that work exposure was associated significantly with higher risks for all symptoms in men (e.g., odds ratio: 2.76 for dyspnea, 2.31 for asthma, 1.69 for cough, and 1.64 for phlegm); in females, the association was significant for dyspnea (OR = 3.74) and asthma (OR = 3.29). Exposed men also had a significantly higher risk for %FEV1 or FEV1/FVC% below 70 (OR = 1.45). Our findings confirm those of the other few epidemiologic surveys in general population samples and contribute to the suggestion of a causal association between occupational exposure and chronic obstructive pulmonary disease.

Sloping alveolar plateaus of He and SF 6 measured in excised cat lungs ventilated at constant volume by pressure changes

Single-breath washout experiments with He and SF 6 were performed in excised cat lungs placed in a closed, liquid-filled reservoir, where lung volume was clamped by the surrounding liquid and breathing was accomplished by hyperbaric pressure changes ( pressure breathing) produced by a piston pump. Under these conditions the flow into each lung unit was assumed to be proportional to its volume, and sequential filling and emptying of lung units by convection probably did not occur. Thus, implicitly, gravity-dependent patterns of sequential filling and emptying of lung regions were also excluded. Different lung volumes ( V l = 50%, 75%, 100% TLC , where TLC is total lung capacity), tidal volumes ( V t = 21%, 34%, 47% TLC and durations of post-inspiratory apnea ( t a = 0, 1, 2, 4, 8 sec ) were applied. The expirograms showed that the slopes of the alveolar plateau (S) were significantly positive for both He and SF 6. For t a = 0 sec S He ranged from 8.7 to 62.8% and S SF6 ranged from 24.4 to 87.8% (S is expressed in % per unit V e/TLC, where V e is expired volume). The ratio S SF6/S He was larger than unity for each combination of V l and V t. Further, for t a = 0 sec both S He and S SF6 showed a tendency to decrease with increasing V l and with increasing V t. For t a = 8 sec both S He and S SF6 were close to zero. Additional single-breath washout experiments were performed with the same cat lungs by applying normal breathing where lung volume was not clamped and asynchronous unequal ventilation might have occured. For comparable values of V l and V t, there were no clear differences between the slopes obtained at normal breathing and those obtained at pressure breathing. We conclude that asynchronous unequal ventilation plays only a minor role in the sloping alveolar plateau during normal breathing, and that the mechanism underlying the sloping alveolar plateau is diffusion dependent.

Alveolar slope and dead space of He and SF6 in dogs: comparison of airway and venous loading

Series (Fowler) dead space (VD) and slope of the alveolar plateau of two inert gases (He and SF6) with similar blood-gas partition coefficients (approximately 0.01) but different diffusivities were analyzed in 10 anesthetized paralyzed mechanically ventilated dogs (mean body wt 20 kg). Single-breath constant-flow expirograms were simultaneously recorded in two conditions: 1) after equilibration of lung gas with the inert gases at tracer concentrations [airway loading (AL)] and 2) during steady-state elimination of the inert gases continuously introduced into venous blood by a membrane oxygenator and partial arteriovenous bypass [venous loading (VL)]. VD was consistently larger for SF6 than for He, but there was no difference between AL and VL. The relative alveolar slope, defined as increment of partial pressure per increment of expired volume and normalized to mixed expired-inspired partial pressure difference, was larger by a factor of two in VL than in AL for both He and SF6. The He-to-SF6 ratio of relative alveolar slope was generally smaller than unity in both VL and AL. Whereas unequal ventilation-volume distribution combined with sequential emptying of parallel lung regions appears to be responsible for the sloping alveolar plateau during AL, the steeper slope during VL is attributed to the combined effects of continuing gas exchange and ventilation-perfusion inequality coupled with sequential emptying. The differences between He and SF6 point at the contributing role of diffusion-dependent mechanisms in intrapulmonary gas mixing.

The sloping alveolar plateau of tracer gases washed out from mixed venous blood in man.

We have investigated the slope of the alveolar plateau for inert tracer gases that were washed out from mixed venous blood. Two pairs of tracer gases were used (He, SF6) and (C2H2, Freon 22). The gases of each pair share almost the same blood-gas partition coefficient but they have different diffusive properties in the gas phase. The experiments were performed in healthy subjects at rest and at three levels of exercise (75, 150, 225 W). Each experiment started with the alveolar washin of the tracer gases by adding these gases to inspired air. This washin was continued for several minutes in order to dissolve sufficient amounts of the tracer gases in the body tissues. Subsequently, the tracer gases were washed out. In this paper, the slopes of the alveolar plateaus are defined as the relative increase of the concentration per second. Steeper slopes were found for the heavier gases (SF6 and Freon 22) in comparison with those for the lighter gases of the two pairs (He and C2H2). This finding may be ascribed to the contribution of diffusion-limited gas mixing in the lung to the slope of the alveolar plateau. For each gas, the slope for the first expiration during washout (alveolar washout) was considerably smaller than that for the later part of washout (mixed venous washout), and the difference amounts to about 56% and 76% of the slope during mixed venous washout at rest and at the highest level of exercise, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Single Breath Nitrogen Test in an Epidemiologic Survey in North Italy: Reliability, Reference Values and Relationships with Symptoms

The usefulness of single breath nitrogen test (SBN2) was evaluated in a cross-sectional epidemiologic survey on a general population sample (n = 3,289) of North Italy. Each subject was submitted to CNR standardized questionnaire and to lung function testing using automated equipment (Hewlett-Packard 47804S). Acceptable closing volume (CV) and slope of alveolar plateau (DN2%/L) tracings were performed by only 1,370 and 1,982 subjects respectively, in comparison with the 2,638 diffusing capacity and the 3,079 forced vital capacity acceptable maneuvers. Prediction equations were computed on normal subjects for CV indices, with the exception of DN2%/L: they were similar to those found in other studies. Significant differences among smoking categories were found for all the SBN2 parameters in males, but only for DN2%/L in females. The latter was also able to distinguish either subjects with airway obstruction from those without it or symptomatic from asymptomatic individuals, but DN2%/L did not give more information than Vmax75, a sensitive index of flow volume curve. Our results suggest that the place of SBN2 in large scale epidemiologic testing has not been justified.

Prevalence of respiratory symptoms in an unpolluted area of northern Italy

Using a multistage stratified geographic cluster sample of households living in an unpolluted area of Northern Italy (near Venice), we enrolled 3289 inhabitants (aged 8-64 yr) for a longitudinal respiratory study. During the first cross-sectional survey, before the start of operation of a large oil-burning thermoelectric power plant, they completed a standardized administered questionnaire and performed several lung function tests. In the whole sample, dyspnoea grade 1 (11%), chronic cough and chronic phlegm (9%) were the most frequent respiratory symptoms; all the symptoms except dyspnoea were more prevalent in males than in females. Smokers (S) showed higher prevalence rates than ex-smokers (ES) and nonsmokers (NS), especially in males. In both sexes, the frequency of respiratory symptoms increased with increasing smoking as assessed by pack-years. An inverse relationship between prevalence of symptoms and socio-economic status was also observed. All tests of lung function were significantly impaired in S compared with NS in males; single-breath CO diffusing capacity and slope of alveolar plateau but not spirometric indices were significantly impaired in female S compared to female ES and NS. Finally, our prevalence rates were lower than in other epidemiological surveys: this result may be ascribed to the low levels of air pollution measured in the area.

Pulmonary follow-up of moderately low birth weight infants with and without respiratory distress syndrome

Pulmonary function was measured in 18 children aged 6 to 9 years who had been born prematurely (mean birth weight 1760 +/- 555 g) and who had each received greater than 100 hours (mean 177 +/- 74 hours) of mechanical ventilation for respiratory distress syndrome (RDS). We used as controls 26 children aged 6 to 7 years who had been born prematurely (mean birth weight 1636 +/- 554 g) but who had required no treatment for pulmonary disease. Results for total lung capacity, FEV1, ratios of functional residual capacity and residual volume to total lung capacity, specific airway conductance, and alveolar plateau slope did not differ in the RDS and control groups. Eight of the 18 children in the RDS group had had radiologic evidence of bronchopulmonary dysplasia at 30 days and oxygen dependence at 30 days, but did not differ from the control group for any of the indices of pulmonary function. However, FEV1 and specific airway conductance were significantly reduced in the premature control group compared with children born at term. Therefore, factors associated with prematurity rather than combined effects of RDS and its treatment determined pulmonary function at age 6 to 9 years.

Cardiogenic oscillation and phase III caused by pressure-volume heterogeneity: a model

The effect of heterogeneity of pressure-volume (PV) behavior of lung units and the effect of the pulsations of the heart on expired N2 following a single breath of O2 were studied mathematically in a model of the lung. The lung was pictured as consisting of three compartments, one of high compliance (HC) and another of low compliance (LC), both affected by cardiac pulsations, and a third, nonoscillatory compartment (NC). Three sigmoid PV curves were assigned to the three compartments, for both acini and airway (generation 10-23), so that total compliance summed up to 200 ml/cmH2O. Bifurcation of NC was at generation 5/6 and that of HC and LC at any chosen generation. A steepness constant, K, was defined to characterize the sharply descending portion of the sigmoid PV curve. For a ratio of the steepness constant for the oscillatory compartments, KHC/KLC = 1, a sloping alveolar plateau was produced. The plateau was concave for KHC/KLC greater than 1 and slightly convex for KHC/KLC less than 1. Cardiogenic oscillations (CO) of the expired N2 were produced by alternate flows from either NC or HC and LC. CO diminished in fast expiration, and a phase shift between the heart pulsation and the CO was seen; both agree with experimental findings.