Single-breath Nitrogen Washout Curve Research Articles

A 4-Dimensional Model of the Alveolar Structure

The alveolar structure, a space-filling branching duct system with alveolar openings, is one of the most complicated structures in the living body. Although its deformation during ventilation is the basic knowledge for lung physiology, there has been no consensus on it because of technical difficulties of dynamic 3-dimensional observation in vivo. It is known that the alveolar duct wall (primary septa) in the fetal lung is deformed so as to obtain the largest inner space and the widest surface area, and that the secondary septa grow just before birth and their free ridges form the alveolar entrance rings (mouths) containing abundant elastin fibers. We have constructed a 4-dimensional alveolar model according to this morphogenetic process, where the alveolar deformation is modeled by a combination of springs and hinges, corresponding to elastin fibers at alveolar mouths and junctions of alveolar septa, respectively. The model includes a hypothesis that alveolar mouths are closed at minimum volume and that closed alveoli are stabilized by the alveolar lining liquid film containing a surfactant. Morphometric characteristics of the model were consistent with previous reports. Furthermore, the model explained how the alveolar number and size could change during ventilation. Using in vivo microscopy, we validated our model by an analysis of the dynamic inflation and deflation of subpleural alveoli. Our model, including the alveolar mouth-closure hypothesis, can explain the origin of phase IV in a single breath nitrogen washout curve (closing volume) and mechanism of alveolar recruitment/derecruitment.

A Novel Interpretation of Closing Volume Based on Single-Breath Nitrogen Washout Curve Simulation

Although closing volume is regarded as a clinical test for the early detection of peripheral airway closure, its grounds are not clear. There have been no simulation studies for phase IV in the single-breath nitrogen washout (SBNW) curve, even though several mathematical models for phase III have been proposed. We modeled the lung tissue deformation during slow expiration in which the tissue was regarded as a porous elastic body similar to a sponge. We assigned the maximum tissue density of lung parenchyma over which the lung tissue could not be contracted according to several experimental reports in literature. SBNW curves were then simulated by computing expired air volume and nitrogen concentration for respective acini in the lung model. The simulated SBNW curves well reproduced phase IV, cardiac oscillation, and its postural changes. We found that the higher lung compliance increased closing volume, but decreased residual volume. The smaller maximum tissue density generated larger closing volume and larger residual volume. It suggested that phase IV reflected the alveolar contractility, and the increase of closing volume in emphysema could be explained by an insufficient contraction of alveoli. We also found that the distribution of maximum tissue density affected the onset of Phase IV. A constant value of density generated a clear onset, but a wide distribution of it corresponding to peripheral airway closure obscured it. We suggest that the airway closure was not necessary for phase IV appearance in both normal and emphysematous lung.

Alveolar nitric oxideversusmeasures of peripheral airway dysfunction in severe asthma

Alveolar nitric oxide (NO) is a measure of peripheral airway inflammation in asthma, potentially associated with disease severity. The relationship between alveolar NO and physiological tests of peripheral airway (dys)function has not been investigated. The present authors hypothesised that peripheral airway inflammation and dysfunction are inter-related and associated with asthma severity. Alveolar NO was compared between 17 patients with mild-to-moderate asthma and 14 patients with severe asthma and related to total lung capacity (TLC), residual volume (RV)/TLC, thoracic gas volume (FRC), slope of the single breath nitrogen washout curve (dN2), closing capacity (CC)/TLC and fall in forced vital capacity at the provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second. In patients with severe asthma, strong correlations were found between alveolar NO and RV/TLC % pred, FRC % pred, dN2, and CC/TLC. Patients with oral steroid-dependent asthma had higher alveolar NO levels (2.7 ppb) compared with the other patients with severe (0.6 ppb) and mild-to-moderate asthma (0.3 ppb). The present authors conclude that alveolar nitric oxide is closely related to parameters of peripheral airway dysfunction in patients with severe asthma, and that oral steroid-dependent asthmatics have more peripheral airway disease than nonsteroid-dependent asthmatics. This suggests that patients on chronic oral steroid treatment have more extensive disease and require additional anti-inflammatory treatment to better target the peripheral airways.

Marijuana smoking, pulmonary function, and lung macrophage oxidant release

Pulmonary alveolar macrophages lavaged from tobacco smokers release increased levels of oxidants and have been implicated in the pathophysiology of emphysema. It is unknown whether lung macrophages recovered from marijuana smokers also liberate excessive levels of oxidants. To evaluate this possibility, pulmonary alveolar macrophages were obtained by bronchoalveolar lavage from nonsmokers, smokers of marijuana only, smokers of tobacco only, and smokers of tobacco plus marijuana. Spontaneous and stimulated superoxide anion release was measured by the superoxide dismutase-inhibitable reduction of ferricytochrome c. These findings were correlated with recent lung function tests. Superoxide anion production by macrophages, studies of small airway integrity (closing volume, closing capacity, and the slope of Phase III of the single-breath nitrogen washout curve), and evaluation of alveolar gas exchange (diffusing capacity of carbon monoxide) were similar in both nonsmokers and marijuana smokers. However, tobacco smoking was associated with both significantly higher levels of superoxide anion release by pulmonary alveolar macrophages and significant abnormalities of small airway function and alveolar diffusing capacity. Based on the results of this study, pulmonary alveolar macrophages of marijuana-only smokers do not produce increased amounts of oxidants when compared to macrophages of non-smoking subjects. This observation may account for the absence of abnormalities in small airway function and alveolar diffusing capacity in marijuana-only smokers, in contrast to the presence of such findings in smokers of tobacco, regardless of marijuana use.

Effect of systemic venous hypertension on pulmonary function and lung water

We studied the effects of systemic venous hypertension (SVH) of 25 cmH2O, with and without fluid overload (100 ml.kg-1.h-1 x 4 h), on the lung water content and pulmonary function of anesthetized dogs. SVH was produced by inflating a balloon in the right atrium. Pulmonary extravascular water (PEW) was measured by gravimetric techniques taking the water content of trapped blood into consideration. Subdivisions of lung volume, pulmonary resistance, dynamic compliance, and the single-breath nitrogen washout curve were performed in a body plethysmograph. Vascular pressures, serum oncotic pressure, and arterial blood gases were also measured. Systemic venous hypertension alone produced no change in lung water content (control PEW = 3.46 +/- 0.16; SVH PEW = 3.44 +/- 0.18 g H2O/g dry tissue, mean +/- SD) or alterations in pulmonary function. Fluid overload alone produced an insignificant increase in PEW (4.24 +/- 0.72 g H2O/g dry tissue) and decreases in vital capacity and functional residual capacity. SVH in combination with fluid overload resulted in a significant increase in lung water (4.78 +/- 1.03 g H2O/g dry tissue) and decreases in functional residual capacity, vital capacity, dynamic compliance, and arterial blood oxygen tension as well as increased pulmonary resistance. We conclude that SVH favors the formation of pulmonary edema under conditions of increased pulmonary transcapillary fluid exchange and may particularly augment airway edema.

Pulmonary Function Abnormalities in Thalassemia Patients on a Hypertransfusion Program

Pulmonary function tests were performed in 12 thalassemia patients on a hypertransfusion program (age 18.4 +/- 2.6 SEM years) to determine the presence of any abnormalities of lung function. These included spirometry, expiratory flow rates, body plethysmography, single-breath nitrogen washout, single breath carbon monoxide diffusing capacity, and arterial blood gases. Only one patient had normal pulmonary function. Arterial hypoxemia was present in ten of 12 patients at rest. The total lung capacity (TLC) was normal. The residual volume was abnormally increased in five of 12 patients. The slope of phase III of single breath nitrogen washout curve was abnormal in five of 12 patients, but the closing volume was normal. The maximal expiratory flow rate at 60% total lung capacity was decreased in four of 12 patients, suggesting the presence of small airway disease. The single breath carbon monoxide diffusing capacity was normal in all patients. These pulmonary function abnormalities did not correlate with age or the cumulative amount of iron via blood transfused. The small airway obstruction, hyperinflation; and hypoxemia observed in thalassemia patients on a hypertransfusion program may result from the basic disease, iron deposition in the lungs, or other factors.

Inflection points of lung pressure-volume curves using a three-balloon-catheter system.

We measured the pressure-volume curves (PV curves) of the lung simultaneously at three levels in the esophagus below the tracheal bifurcation using the three-short-balloon-catheter system in 11 normal seated men and compared the inflection points (IP's) of three PV curves with the closing volume (CV) on the single-breath nitrogen washout curve. The mean pressure gradient from the top of the uppermost balloon to the top of the lowermost balloon (10 cm apart) was 0.58 +/- 0.06 cmH2O/cm at 60% total lung capacity (TLC). The IP was dependent on depth within the esophagus; i.e., the lung volume at IP (VIP) of the uppermost balloon was the smallest and the transpulmonary pressure (Ptp) at IP (PIP) of that balloon was the largest of the three IP's. VIP's were significantly larger than CV's and the mean absolute difference between the VIP of the uppermost balloon and the closing capacity (CC) was 0.9 liter. These results suggest that IP may not exactly reflect airway closure.

"Small airways disease" in children: no test is best.

Tests claimed to detect small airway disease were evaluated in children. Fifty-two subjects who were normal, 30 with cystic fibrosis (CF), and 35 with asthma were selected on the basis of normal spirometry, informed consent being obtained from them and their parents. Tests undertaken were measurement of maximum expiratory flow volume curves breathing air and a helium-oxygen gas mixture, single breath nitrogen washout curves, lung volumes, and, except in the normal subjects, measurement of arterial oxygen tension. Closing volumes were normal in most children with CF and asthma, whereas the slope of the alveolar plateau was abnormal in 83%. Maximum expiratory flow rate at 50% of total lung capacity was reduced in 65% and maximum mid-expiratory flow rate in 57%; residual volume increased in 51%, and results of other tests were abnormal in less than 50% of children. There was evidence suggesting that lung disease was more patchy in children with mild CF than in those with interval phase asthma. These tests do not detect specific pathological processes in small airways but reflect the consequences of small airway abnormalities, which may vary in the same disease as well as in different diseases. No one test alone appears most useful. Together they contribute to understanding the functional abnormalities present in each individual.

Extrinsic allergic alveolitis from bird exposure. Studies on the immediate hypersensitivity reaction.

Six patients with extrinsic allergic alveolitis had weak immediate and strong late reactions of intracutaneous injection of bird serum. Biopsy of the late reaction revealed vasculitis and immunoglobulin and complement deposition in one. The antibody responsible for the immediate hypersensitivity could be transferred in serum. It was short lasting (4 hr) and resistant to heat and 2-mercaptoethanol. No evidence of an immediate reaction in the lungs could be detected following inhalation challenge as judged by examination of spirometry, flow volume loops and single breath nitrogen washout curves.

Computer analysis of the single-breath nitrogen washout curve.

A computerized system has been developed to analyze the parameters that can be derived from the nitrogen washout curve. Analog signals for air flow, volume, and nitrogen concentration are entered either on-line or off-line into a 24,000 mini-computer. The program calculates vital capacity, total lung capacity, and residual volume, as well as the slope of phase III, closing volume in liters, total lung capacity, residual volume, closing capacity, closing volume/vital capacity ratio, and closing capacity/total lung capacity ratio. Validation tests showed excellent correlation between hand- and computer-calculated values of closing volume(r=0.864), vital capacity (r=0.997), total lung capacity (r=0.991), and slope of phase III (R=0.926). We concluded that the computerized system for analysis of the expired nitrogen washout curve is as reliable as hand calculations and is immeasurably faster.

Changes in the single-breath nitrogen washout curve on exposure to 17,600 ft

Seventeen volunteers were exposed to 17,600 ft after an acclimatization period, at 9,800 ft. Single-breath nitrogen washout curves were done at base camp (2,600 ft), on days 2 and 4 at 9,800 ft, and on days 1, 2,3 4, and 7 at 17,600 ft. There was a significant 39% increase in the slope of phase III on day 2 at 9,800 ft, accompanied by a 125 ml mean increase in anatomic dead space (Vd) and a marked decrease in cardiac oscillations. By day 4 at 9,800 ft phase III slopes were reduced and were not significantly different from base-line controls, while cardiac oscillations were increased and Vd decreased from day 2. Subsequent exposure to 17,600 ft produced another significant increase in phase III slope to 87% above control, which by day 7 had decreased significantly to 63% above control. Cardiac oscillations were again diminished and Vd increased. These changes cannot be accounted for by changes in gas density, nor by the decrease in PIOO2 per se, since this alone would decrease the range of PaNN2. They suggest a pathophysiologic lung lesion which impairs gas mixing and increases asynchronous emptying during early altitude exposure. high-altitude pulmonary edema; gas-mixing impairment at altitude Submitted on November 7, 1974

Phase IV volume of the single-breath nitrogen washout curve on exposure to altitude.

ArticlePhase IV volume of the single-breath nitrogen washout curve on exposure to altitude.G W Gray, I D Rennie, C S Houston, and A C BryanG W Gray, I D Rennie, C S Houston, and A C BryanPublished Online:01 Aug 1973https://doi.org/10.1152/jappl.1973.35.2.227MoreSectionsPDF (879 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByLung Function and Gas Exchange9 November 2013CON: Most Climbers Do Not Develop Subclinical Interstitial Pulmonary EdemaHigh Altitude Medicine & Biology, Vol. 12, No. 2Pulmonary Edema in Healthy Subjects in Extreme ConditionsPulmonary Medicine, Vol. 2011High-Altitude MedicineDo Changes in Lung Function Predict High-Altitude Pulmonary Edema at an Early Stage?Medicine & Science in Sports & Exercise, Vol. 38, No. 9Pulmonary extravascular fluid accumulation in recreational climbers: a prospective studyThe Lancet, Vol. 359, No. 9303Low Pulmonary Diffusing Capacity in Subjects With Acute Mountain SicknessChest, Vol. 111, No. 1Subclinical Pulmonary Edema with Hypobaric HypoxiaENVIRONMENTAL EFFECTS ON VENTILATION-PERFUSION DISTRIBUTIONThe Relationship between Acute Mountain Sickness and Pulmonary Ventilation at 2,835 Meters (9,300 ft)Chest, Vol. 75, No. 1 More from this issue > Volume 35Issue 2August 1973Pages 227-30 https://doi.org/10.1152/jappl.1973.35.2.227PubMed4723031History Published online 1 August 1973 Published in print 1 August 1973 Metrics

Stratified inhomogeneity and regional inhomogeneity.

The diffusion in the lungs is sufficiently rapid to obliterate a measurable concentration gradient during a normal breathing cycle. The shape of the alveolar plateau in the single breath nitrogen washout curve is due mainly to the mechanical factors and some other possibilities. In this paper, the author points out and demonstrates some of these factors and suggests the possible answers to part of this complex and controversial problem.

Vertical gradient of alveolar size in lungs of dogs frozen intact.

Vertical gradient of alveolar size in lungs of dogs frozen intact.