Single-breath Nitrogen Washout Research Articles

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.

Single-Breath Nitrogen Washout: Effects of Alterations of Lung Volumes and Elastic Recoil

Strapping of the chest causes decreased lung volumes and increased elastic recoil pressure. Such strapping was used in conjunction with single-breath nitrogen washout to study the effects of changes in these factors on the dynamics of the small airways. Studies consisted of simultaneous measurements of the quasistatic lung pressure-volume curve and single-breath nitrogen washout. Strapping caused significant reductions in all lung volumes and in lung compliance at 50 percent of the total lung capacity (TLC). The volume of phase 4 was not changed; however, the ratio of closing capacity to control TLC decreased from 29.9 +/- 6 percent to 24.2 +/- 4 percent with strapping (P less than 0.02). This observation indicates that the onset of closing volumes occurred at a lower absolute lung volume during strapping, compared with control. The closing pressure of 2.1 +/- 0.8 cm H2O was not altered by strapping of the chest. The slope of phase 3 of the single-breath nitrogen-washout test and the average alveolar concentration of nitrogen were increased during strapping. A similar phenomenon occurred in three subjects who performed the single-breath nitrogen-washout test following partial vital capacities. A reduction of the onset of closure of the airways without a change in closing pressure suggests that restrictions of the chest wall caused no change in mechanical properties of the small airways. Elevation of the slope of the alveolar plateau is probably due to exaggeration of the apex-to-base nitrogen difference consequent to the strapping-associated decreased lung and alveolar compliance.

Evaluation of early airway disease in smokers: cost effectiveness of pulmonary function testing.

We studied 73 young adults who were presently cigarette smokers to evaluate whether the identification of abnormalities in pulmonary function tests had a detectable influence on modification of smoking habits. Utilizing rate schedules for these tests presently applicable in Rochester, New York, we determined the potential cost to these subjects and community relative to the number of subjects who stopped smoking as a result of test findings. Subjects were evaluated by questionnaire and function testing including spirometry, flow-volume curves, body plethysmography and single breath nitrogen washout test (SBN2). Functional abnormalities were present in 75% of subjects screened. The SBN2 test was most sensitive, identifying 97% of subjects with any abnormality. The presence of common respiratory symptoms was found to be highly predictive of test abnormalities. Subjects were informed of results and counseled. At six-month follow-up, 7% of subjects with abnormal test results had stopped smoking. Utilizing even our most cost-effective test, the SBN2, it would cost +1,392 for each "benefit" defined as one subject not smoking for six months. Application of these screening techniques is unlikely to be effective in altering smoking habits in the absence of continued physician support.

"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.

STUDIES ON INTRA-PULMONARY GAS DISTRIBUTION IN THE EXTREMELY OBESE

Intrapulmonary gas distribution was studied in 10 extremely obese patients: (1) during spontaneous breathing awake; (2) during anaesthesia with controlled ventilation and zero end-expiratory pressure (ZEEP), and (3) as under (2) but with a positive end-expiratory pressure of approximately 15 cmH2O (PEEP). Gas distribution was assessed quantitatively by means of a multiple-breath nitrogen wash-out technique and subsequent fractional analysis, which permitted the calculation of nitrogen wash-out delay (NWOD). Gas distribution was also analyzed by means of a single-breath nitrogen wash-out in order to determine the slope of the alveolar plateau. Gas distribution was within normal limits during spontaneous breathing, judged from multiple-breath as well as single-breath wash-out. With anaesthesia and ZEEP, NWOD was higher, indicating less efficient gas mixing, and the slope of the alveolar plateau was twice as steep as during spontaneous breathing. With PEEP, distribution of inspired gas improved (lowered NWOD and flatter slope). Theoretical considerations and clinical experiments led to the conclusion that uneven distribution in the anaesthetized obese is caused both by regional differences in the pulmonary time constants (as in obstructive lung disease) and by airway closure.

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.

Emptying patterns of the lung studied by multiple-breath N2 washout.

Changes in the nitrogen concentration seen during the single-breath nitrogen washout reflect changes in relative flow (V) from units with differing ventilation/volume ratios (V/V0). The multiple-breath washout provides sufficient data for the V for units with varying V/V0 to be plotted as a function of the volume expired. Flow from the dead space may also be determined. In young normals the emptying patterns are narrow and unimodal throughout the alveolar plateau with little or no flow from the dead space at the end of the breath. Older normals show more flow from the dead space, particularly toward the end of the breath, and some show a high V/V0 mode early in the breath. Patients with obstructive lung disease have a high flow from the dead space which is present throughout the breath. A well ventilated mode at the end of the breath is seen in some obstructed subjects. Patients with cystic fibrosis showed a poorly ventilated mode appearing at the end of the breath as well as a very high dead space.

The acute effects of chrysotile asbestos exposure on lung function

Lung function was determined in 23 men 1.5 months after an intense 5-month exposure to chrysotile asbestos using spirometry, plethysmography for determination of lung volumes and specific conductance, single breath nitrogen washout for determination of closing volume, and rest and postexercise arterial blood gas analysis. Although no man showed evidence of restriction, 12 of the 23 had documented airflow obstruction. Eight months following exposure, 16 of the 23 had a repeat pulmonary evaluation. This included the repetition of all previous testing and determination of the diffusion capacity for carbon monoxide and pulmonary compliance. Three men developed airflow obstruction, as determined by the closing volume, during the interval of study. Seventeen of the 23 had airflow obstruction documented on either the initial or follow-up study. Of these 17, 12 were nonsmokers, current light smokers (less than 10 pack years), or ex light smokers. It is concluded that acute intense chrysotile asbestos exposure causes airflow obstruction.

Volume of isoflow: effect of distribution of ventilation.

Volume of isoflow was determined in smokers and nonsmokers following one (VisoV1) and three (VisoV3) inhalations 80% helium 20% oxygen. In addition, distribution of ventilation was measured by single breath nitrogen washout and end-tidal helium concentration was determined following 1-3 breaths of a helium-oxygen mixture. In all subjects (smokers and non smokers), VisoV1 was significantly higher than VisoV3. Furthermore, VisoV1 was abnormal in 55.6% of smokers, whereas VisoV3 was abnormal in only 38.9%. Differences between VisoV1 and VisoV3 (VisoV1 - VisoV3 = deltaVisoV) were significantly larger in smokers. Non-uniform distribution of ventilation was associated with larger values of delta VisoV and lower end-tidal helium concentrations. VisoV1 is a more effective method than VisoV3 in distinguishing smokers with small airways obstruction from nonsmokers. This enhanced sensitivity can be explained by the observation that the effects of maldistribution of ventilation upon helium concentration in the late expirate are minimized after three breaths of a helium-oxygen mixture.

Hypoxemia of cirrhosis: Detection of abnormal small pulmonary vascular channels by a quantitative radionuclide method

Abnormal pulmonary perfusion pathways found at autopsy in patients with hepatic cirrhosis have been suggested as a major cause of hypoxemia in cirrhosis. However, these abnormal vascular channels have been difficult to document during life. In the present study, the pathophysiology of hypoxemia (arterial oxygen tension [PaO 2] 48.5 to 68 mm Hg) in three patients with hepatic cirrhosis was investigated utilizing conventional cardiopulmonary tests and a special radionuclide technic for the detection of shunting through small dilated pulmonary vessels. Pulmonary function tests revealed normal spirometry and lung volumes; normal closing volume and single-breath nitrogen washout; abnormal diffusing capacity (41 to 68 per cent of predicted); increased venous admixture on 100 per cent oxygen (O 2) (8.1 to 29 per cent); and a decrease in PaO 2 after change from the supine to the sitting position and after exercise. Cardiac catheterization revealed normal pulmonary arterial pressures at rest and during exercise, increased cardiac outputs and no intracardiac shunts. Chest roentgenograms and pulmonary angiograms were within normal limits. Utilizing a quantitative radionuclide technic, 10 per cent, 46 per cent and 70.5 per cent of intravenously injected technetium 99m-macroaggregated albumin ( 99mTc-MAA) particles traversed the pulmonary vasculature and lodged in endorgan systemic capillary beds in the three patients with cirrhosis compared with ⩽6 per cent in eight control subjects. The results of the quantitative radionuclide study document the presence of dilated pulmonary capillaries and/or arteriovenous communications which are too small to be detected angiographically. These abnormal vascular channels can account for the observed hypoxemia primarily on the basis of diffusion/perfusion imbalance and to a lesser extent by true shunting. A similar mechanism may be responsible for the hypoxemia commonly found in other patients with cirrhosis.

Pulmonary function in obese patients scheduled for jejuno-ileostomy.

Preoperative pulmonary parameters were evaluated in 37 extremely obese but otherwise healthy patients. They were on average 100.9% overweight. X-ray of the chest, electrocardiograms, and residual volume, vital capacity, total lung capacity, maximum breathing capacity, forced expired volume in 1 second, and related ratios were all within the normal range. The alveolar-arterial oxygen gradient and the arterial carbon dioxide tension were also within the normal range. The only abnormal finding was a substantially reduced arterial oxygen tension. It is suggested that the measurement of functional residual capacity, closing volume, and the slope of the alveolar plateau (phase III in the single breath nitrogen washout technique) might give more valuable information.

Studies on Intra‐Pulmonary Gas Distribution in the Extremely Obese Influence of Anaesthesia and Artificial Ventilation with and without Positive End‐Expiratory Pressure

Intrapulmonary gas distribution was studied in 10 extremely obese patients: (1) during spontaneous breathing awake; (2) during anaesthesia with controlled ventilation and zero end-expiratory pressure (ZEEP), and (3) as under (2) but with a positive end-expiratory pressure of approximately 15 cmH2O (PEEP). Gas distribution was assessed quantitatively by means of a multiple-breath nitrogen wash-out technique and subsequent fractional analysis, which permitted the calculation of nitrogen wash-out delay (NWOD). Gas distribution was also analyzed by means of a single-breath nitrogen wash-out in order to determine the slope of the "alveolar plateau." Gas distribution was within normal limits during spontaneous breathing, judged from multiple-breath as well as single-breath wash-out. With anaesthesia and ZEEP, NWOD was higher, indicating less efficient gas mixing, and the slope of the "alveolar plateau" was twice as steep as during spontaneous breathing. With PEEP, distribution of inspired gas improved (lowered NWOD and flatter slope). Theoretical considerations and clinical experiments led to the conclusion that uneven distribution in the anaesthetized obese is caused both by regional differences in the pulmonary time constants (as in obstructive lung disease) and by airway closure.

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.

Early Detection of Chronic Obstructive Pulmonary Disease Using Radionuclide Lung-Imaging Procedures

One hundred subjects answered a respiratory questionnaire and underwent a physical examination, tests of pulmonary function, and three radionuclide lung-imaging procedures. The results of the radionuclide procedures were compared with each other and with pulmonary function tests and other diagnostic findings to determine their relative sensitivity for detecting evidence of early obstructive airway disease. Perfusion lung imaging was less sensitive than most of the other diagnostic tests evaluated. The aerosol and xenon lung-imaging procedures revealed abnormalities with approximately the same frequency as each other, but more often than any one group of pulmonary function tests, including spirometric data, maximal expiratory flow-volume curves, alveolararterial oxygen gradient, or indices derived from single-breath nitrogen washout. We concluded that xenon and aerosol lung-imaging studies are sensitive and useful screening procedures for detecting evidence of early localized obstructive airway disease and for locating regional abnormalities in the airways of patients with respiratory disease.

Respiratory Status of Los Angeles Firemen: One-Month Follow-Up after Inhalation of Dense Smoke

A standardized respiratory questionnaire and detailed pulmonary function tests were administered to 21 Los Angeles firemen one month following exposure to the combustion products of polyvinylchloride, which had produced transient hypoxemia in 19 of the firemen. The results of these studies were compared with those obtained in a sample of nonfiremen residing in the Los Angeles area who were matched by computer with the firemen for anthropomorphic characteristics and smoking status. The frequency of respiratory symptoms, the results of spirometric and plethysmographic studies, and the single-breath nitrogen washout were similar in the firemen, compared with the matched sample, whereas closing volume was higher in the matched controls. These findings suggest that although fighting fires may result in acute pulmonary injury secondary to discrete episodes of inhalation of smoke, it does not appear to predispose to the development of chronic respiratory symptoms or chronic functional respiratory impairment.

Uneven ventilation in smokers

A body plethysmographic technique designed to detect small degrees of uneven ventilation in the lungs is presented. The technique is based on the same theoretical model as the frequency dependence of compliance. It has the advantage of requiring little time, no cooperation by the subject and no computation. Signs of uneven ventilation were found in 3 of the 42 normal controls, in 6 of 51 light smokers and in 66 of 103 heavy smokers. The data are compared with measurements of closing volume, of the slope of phase III of the single breath nitrogen washout and of maximal mid-expiratory flow rate.

Dose-Related Dilatation of Airways after Inhalation of Metaproterenol Sulfate

Studies concerning the ability of an inhaled beta2-agonist to produce dose-related bronchodilatation are conflicting. In five asthmatic, five bronchitic, and five normal subjects, specific airway conductance (Gaw/VL), flow-volume curves, and single-breath nitrogen washout were recorded after noncummulative inhalation of 0.65 mg, 1.30 mg, 1.95 mg, and, in some subjects, 2.60 mg of metaproterenol sulfate. Bronchodilatation appeared to be dose-related and was best assessed by using Gaw/VL; in all but one subject with chronic bronchitis, there was a significant linear relationship between log dose and precent change in Gaw/VL. Measurements of flow rate could demonstrate significant log dose-responses in eight subjects, maximum midexpiratory flow being the most sensitive measurement of flow rate, followed in order by forced expiratory volume in one second, flow at 50 percent of forced vital capacity, peak expiratory flow rate, and flow at 75 percent of forced vital capacity. No log dose-respone curve could be observed by using the single-breath nitrogen-washout technique. This demonstration of significant log dose-responses to inhaled metaproterenol is consistent with the response to drugs acting upon receptors and suggests that patients may benefit from increasing doses of bronchodilators.

Xenon and nitrogen single-breath washout curves in patients with airway obstruction

In patients with chronic obstructive lung disease, we determined single-breath N2 and 133 Xe washout curves, and regional distributions of volumes (Vr) and of 133Xe boluses inhaled at residual volume (VIRV). Patients suffering from emphysema with minimal airway obstruction demonstrated large closing volumes and apicobasal distribution gradients, apparently because of a steep pulmonary recoil pressure-volume curve. In one subject with basal small airway disease there was no vertical gradient in regional residual volume; closing volume was increased with the 133Xe technique but almost absent with the N2 technique. Patients with moderate-to-severe airway obstruction had upward-sloping alveolar plateaus without distinct phase IV, and small apicobasal differences in Vr and VIRV. The latter resulted probably from increased regional differences in time constants counteracting the influence of gravity. Finally, patients with severe airway obstruction and basal emphysema demonstrated a rising N2 but a descending 133Xe plateau; the gradient for VIRV was normal, and reversed for Vr. This pattern was attributed to nongravitational differences in time constants causing a first in-first out distribution.

Ventilatory disturbance in children with obstructive lung disease.

Mellis, C. M. and Landau, L. I. (1976). Aust. paediat. J., 12, 77–82. Ventilatory disturbance in children with obstructive lung disease. Disease in the small airways leads to alteration in the slope of phase III of the single breath nitrogen washout following a breath of 100% oxygen. Normal children and those with asthma and cystic fibrosis were studied by this technique. Measurement of the slope of phase III of the single breath washout appeared to be a sensitive indicator of abnormal pulmonary function in children with these diseases. Results obtained in many children with cystic fibrosis suggested that the upper lung regions were predominantly affected.

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.