Various pathologic processes alter the normal pattern of ventilation distribution (that is, the uniformity with which an inhaled breath is distributed to all the alveoli). For this reason, tests that detect abnormal patterns of ventilation distribution are fairly nonspecific and rarely of diagnostic importance. Their major contribution is that such abnormal patterns almost always are associated with alterations in ventilation-perfusion relationships (see page 66-67). Abnormal distribution of ventilation also contributes to the frequency dependence of compliance (see page 81).
There are several tests of ventilation distribution. Some are complex and require sophisticated equipment and complex analysis. This chapter discusses only the simplest procedure, the single-breath nitrogen (SBN2) test.
8A. SINGLE-BREATH NITROGEN TEST
Procedure
The testing equipment and procedure are illustrated in Figure 8-1. The subject exhales to residual volume (RV) and then inhales a full breath of 100% oxygen from the bag on the left. A slow, complete exhalation is directed by the one-way valve through the orifice past the nitrogen meter into the spirometer. The orifice ensures that expiratory flow will be steady and slow (<0.5 L/s), and we recommend its use. The nitrogen meter continuously records the nitrogen concentration of the expired gas as it enters the spirometer. With simultaneous plotting of the expired nitrogen concentration against expired volume, the normal graph shown in Figure 8-1 and in Figure 8-2A is obtained.
FIG. 8-1. Equipment required to perform the single-breath nitrogen washout test. A plot of exhaled nitrogen concentration (N2 conc) against exhaled volume is shown at the lower right.
FIG. 8-2. Results of single-breath nitrogen washout tests on a normal subject (A), a subject with early chronic obstructive pulmonary disease (COPD; B), and a subject with severe COPD (C). Closing volume (when present) is identified by an arrow. The various phases are identified on A. The slope of phase III is given below each curve.
Normal Results
The plot in Figure 8-2A is from a seated normal subject. There are four important portions of the normal graph: phases I through IV.
To understand this graph, we need to consider how the inhaled oxygen is normally distributed in the lungs of a seated subject. At RV, the alveolar nitrogen concentration can be considered uniform (roughly 80%) throughout the lung and alveolar gas is present in the trachea and upper airway (Fig. 8-3A). At RV, the alveoli (circles in Fig. 8-3A) in the more gravitationally dependent regions of the lung are at a smaller volume than those in the apical portions. Thus, the apical alveoli contain a larger volume of nitrogen at the same concentration. Therefore, as the subject inhales 100% oxygen, the apical alveoli receive proportionately less oxygen than the more dependent basal alveoli and the alveolar nitrogen is less diluted than in the basal regions. Therefore, the nitrogen concentration is higher in the apical region. The result is a gradual decrease in nitrogen concentration farther down the lung, and the most diluted alveolar gas is at the base (Fig. 8-3B). At the end of inspiration, the trachea and proximal airways contain only oxygen.
The events during expiration in the normal subject (Fig. 8-2A) are as follows. The initial gas passing the nitrogen meter comes from the trachea and upper airway and contains 100% oxygen. Thus, phase I shows 0% nitrogen. As expiration continues during phase II, alveolar gas begins washing out the dead space oxygen and the nitrogen concentration gradually increases.
FIG. 8-3. Normal distribution of a breath of oxygen inhaled from residual volume and the resulting gravity-dependent alveolar nitrogen concentration (N2 conc). A. Lung at residual volume. B. Lung after a maximal inspiration to total lung capacity.
Phase III consists entirely of alveolar gas. During a slow expiration, initially gas comes predominantly from the dependent alveolar regions, where the nitrogen concentration is lowest. As expiration continues, increasing amounts of gas come from the more superior regions, where nitrogen concentrations are higher. This sequence of events produces a gradually increasing nitrogen concentration during phase III. The normal slope of phase III is 1.0 to 2.5% nitrogen per liter expired. This value increases in the elderly.
An abrupt increase in nitrogen concentration occurs at the onset of phase IV. This reflects the decreased emptying of the dependent regions of the lung. Most of the final expiration comes from the apical regions, which have a higher concentration of nitrogen. The onset of phase IV is said to reflect the onset of airway closure in the dependent regions, and it is often called the closing volume. Whether airway closure actually occurs at this volume is debatable [1]. Normally, phase IV occurs with approximately 15% of the vital capacity still remaining. This value increases during normal aging, up to values of 25% vital capacity.
8B. CHANGES IN THE SINGLE-BREATH NITROGEN TEST IN DISEASE
In obstructive lung disease, the SBN2 test is altered in two ways (Fig. 8-2B). The lung volume at which phase IV occurs (closing volume) increases. In addition, the slope of phase III increases. This occurs because the normal pattern of gas distribution, including the vertical gradient of nitrogen concentration described prEV1ously, is gradually abolished. Disease occurs unevenly throughout the lung. Regions of greater disease with high airway flow resistance empty less completely and hence receive less oxygen, and thus their nitrogen concentration is well above normal levels. Because the diseased areas empty more slowly than the more normal regions, the slope of phase III is greatly increased.
In more advanced obstructive disease (Fig. 8-2C), there is no longer a phase IV. It becomes lost in the very steep slope of phase III.
8C. INTERPRETATION OF THE SINGLE-BREATH NITROGEN TEST
The more nonuniform the distribution of ventilation, the steeper the slope of phase III. There are associated increases in the nonuniformity of the perfusion of the alveolar capillaries. The impact of these changes on arterial blood gases is noted in section 6A, page 63.
It was thought that the increase in phase IV volume would be a useful, sensitive indicator of early airway disease. Unfortunately, it was not, and phase IV is rarely measured now. However, for many years phase III has been recognized as an excellent index of nonuniform ventilation. As shown in Figure 8-2, with the progress of obstructive airway disease, the slope of phase III progressively increases.
However, any measure of ventilation distribution is nonspecific. Increases in phase III are not limited to cases of airway obstruction. Increases also occur in pulmonary fibrosis, congestive heart failure, sarcoidosis, and other conditions in which airway disease is not the principal abnormality.
In conclusion, consideration of the distribution of ventilation tells much about lung physiology. Disorders of ventilation distribution are extremely important in the pathophysiology of conditions such as chronic bronchitis, asthma, and emphysema. In clinical practice, however, tests of ventilation distribution add very little to a basic battery of spirometry and tests of lung volumes, diffusing capacity, and arterial blood gases.
REFERENCE
1. Hyatt RE, Okeson GC, Rodarte JR. Influence of expiratory flow limitation on the pattern of lung emptying in normal man. J Appl Physiol 35:411-419,1973.