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Measurement of lung volumes.

Measurements of lung volume play an integral role in the laboratory evaluation of patients with known or suspected lung disease. Several techniques are available to measure absolute lung volumes (containing residual volume). It should be noted that these techniques measure different theoretical volumes and may produce different results in patients with lung disease. Lung volume measurements are typically elevated in obstructive diseases and reduced in restrictive diseases, making them useful tests in diagnosing and distinguishing these two general classes of disease.

Humans

An analysis of a rebreathing method for measuring lung volume in the premature infant.

Functional residual capacity (FRC) and thoracic gas volume (TGV) were measured in 20 infants, of whom 11 were healthy preterm infants, 5 were recovering from the respiratory distress syndrome (RDS), and 4 had other pulmonary problems. In addition, some of the theoretical aspects of rebreathing techniques, including the lung to bag N2 difference at equilibrium, were studied by constructing a simple digital computer model of the system. In both the normal preterm infants and the post-RDS group, the TGV was significantly greater than the FRC (0.02 greater than P greater than 0.01), indicating the presence of trapped gas (Fig. 2). The mean time taken to reach equilibrium during rebreathng was 44 sec in the normal infants and 52 sec in the post-RDS group (Table 2). In one infant with generalized cystic lung disease, equilibrium was not achieved even after 3 min of rebreathing (Fig. 1). The computer-generated analysis of rebreathing for a normal 3-kg infant is shown in Figure 3, with an in vivo curve for comparison. The rapid equilibration of N2 was completed within 55 sec but, as in the in vivo experiments, there was a change in slope of the line afer 1.7 min. It can be seen from Table 3 that, if a small initial bag volume (11 ml) is used, 30 sec of rebreathing is adequate for equilibration only when FRC and dead space are normal, and errors would occur if either were enlarged. The computer study showed that the gradient for N2 between bag and lung at equilibrium is of the order of 0.2-0.37% which would cause a negligible error when calculating FRC and assuming that lung N2 is equal to the measured bag N2. The combined in vivo and computer studies served to validate the rebreathing technique as a method for measuring FRC, and have enabled it to be modified for use even in small or very sick infants with poor ventilation. The most useful procedure to employ would seem to be to use an initial bag volume of 150-200 ml and to continue the rebreathing for 1.5-2 min, with samples being taken for analysis at approximately 20-sec intervals.

Computers

[Errors in the lung volume measurement and its reproducibility by the method of helium displacement in the closed system].

On a mechanical model of the lungs systematic (constant) and accidental (random) errors in measuring the volume by the device (see article)-1, were determined and these amounted to +2.7 and identical to 2.2, respectively. The latter was three times as low as the mean-square reproducibility error, i.e. the degree of error in the physiological measurement of FRC. Different sources of errors in the measurement of FRC, among which particular attention is called to errors in defining the helium concentration at the end of the mixing process in closed system, are considered.

Diagnostic Errors

Lung volumes measured by helium dilution and by body plethysmography with mouth and oesophageal pressures: a comparative study in patients with lung disease.

A comparison was made between the helium dilution technique and body plethysmography--using both mouth pressure and oesophageal pressure against box pressure--for measuring functional residual capacity (FRC). In patients with restrictive lung disease (n = 9) no major differences in FRC were noted between the techniques. In patients with obstructive lung disease (n = 17), helium dilution underestimated FRC by a mean of 0.9 l and conventional body plethysmography (mouth-box pressure) overestimated it by 0.4 l in comparison with FRC obtained by oesophageal pressure against box pressure. The difference between the techniques increased with increasing lung volumes. It is concluded that conventional body plethysmography measures FRC more accurately than the helium dilution technique in patients with obstructive lung disease.

Female

Comparison of lung volume measurements by single breath helium and multiple breath nitrogen equilibration methods in normal subjects and COPD patients.

The validity of the single breath helium dilution method for accurate measurement of the total lung capacity (TLC) was investigated. Comparison was made with the multiple breath nitrogen equilibration technique in 22 normal subjects and 37 patients with chronic obstructive pulmonary disease (COPD). The single breath method underestimated the TLC in all the normal individuals and 33 of 37 patients with COPD. Possible explanations for the falsely low lung volumes include uneven distribution of inspired air due to closing volumes and induced bronchoconstriction.

Adult

Acute lung injury monitored with radiolabeled transferrin and lung volume measurements.

Anesthetized pigs (n = 12) were given oleic acid (OA) to induce acute lung injury. Three additional pigs were used as uninjured controls. Six of the animals were pretreated with terbutaline before OA infusion. 113mIn-labeled transferrin and 99mTc-labeled erythrocytes were used for tracing of extravascular plasma leakage. A computerized gamma camera supplied image analysis of the radioactivities over the heart and lungs. A lung transferrin index (LTI), which describes the net accumulation of plasma equivalents in the lung, was calculated. OA caused an immediate increase in LTI and concurrent, correlated decreases in functional residual capacity, lung thorax compliance and arterial PO2. LTI was also correlated to the content of plasma equivalents in lung tissue samples and also to the wet weight/dry weight-ratios of the same tissue samples. Finally, LTI was correlated to the calculated plasma loss from the circulation. Changes in all these parameters were correlated to the dose of OA. We conclude that this noninvasive double radioisotope technique can detect plasma protein leakage in lung injury of different degrees. We found no significant anti-edema effect of terbutaline.

Animals

Lung volumes measured by the forced rebreathing technique in children with airways obstruction.

Forced rebreathings may recruit trapped gas into the mixing process. Therefore, we assessed the validity and reproducibility of measurements of residual volume (RVN2) by forced rebreathing in a closed circuit using N2 as indicator gas (N2FR) in children with airways obstruction. Validity was studied from measurements of RV obtained by N2FR, by helium dilution during resting ventilation, and by body plethysmograph at low panting frequency in young patients (8-18 yrs, 13 with asthma, forced expiratory volume in one second (FEV1) 93.0 +/- 22.8% pred; 12 with cystic fibrosis (CF), FEV1 80.4 +/- 16.4% pred). Reproducibility of RVN2 was assessed from duplicate measurements in 73 patients with asthma before and after bronchodilation (FEV1 81.4 +/- 13.7 and 99.6 +/- 11.5% pred, respectively), and in nine patients with CF; the total lung capacity (TLC) was unaffected by bronchodilation; 3,797 +/- 830 ml and 3,807 +/- 843 ml, respectively. Gas dilution methods gave comparable results in all subjects but gave lower values than plethysmography in patients with cystic fibrosis. Reproducibility was satisfactory, median differences between duplicate measurements of RVN2 and TLCN2 varying between 13 and 46 ml, respectively. We conclude that N2FR is quickly performed and well-tolerated. Lung volumes are highly reproducible and agree well with those obtained with the helium dilution method. Deep inspirations do not seem to overcome gas trapping in patients with CF.

Adolescent

Lung volume measured by functional residual capacity in infants following first trimester amniocentesis or chorion villus sampling.

OBJECTIVE: To determine the incidence of respiratory problems and lung volume abnormalities in babies born after first trimester amniocentesis or chorion villus sampling. DESIGN: A prospective randomized study. SETTING: Harris Birthright Research Centre for Fetal Medicine, Paediatric Respiratory Laboratory, King's College Hospital. SUBJECTS: Babies of mothers who had undergone first trimester amniocentesis (n = 74) or chorion villus sampling (CVS) (n = 86) for fetal karyotyping because of advanced maternal age, parental anxiety or family history of chromosomal abnormality in the absence of parental chromosome re-arrangement. MAIN OUTCOMES: Respiratory distress in the neonatal period and lung volume as assessed by measurement of functional residual capacity (FRC). RESULTS: CVS was associated with a significantly higher incidence of neonatal respiratory distress, six infants in the CVS group but none in the amniocentesis group required admission to the special care baby unit because of respiratory distress (P less than 0.05). Although there was no significant difference in the mean FRC between the two groups (amniocentesis 29.7 ml/kg vs CVS 29.6 ml/kg) the overall incidence of FRC values less than 2.5th centile of the normal range was 9%. CONCLUSION: Both amniocentesis and CVS performed in the first trimester of pregnancy may impair antenatal lung growth.

Amniocentesis

Measurement of lung volumes from supine portable chest radiographs.

Lung volumes in supine nonambulatory patients are physiological parameters often difficult to measure with current techniques (plethysmograph, gas dilution). Existing radiographic methods for measuring lung volumes require standard upright chest radiographs. Accordingly, in 31 normal supine adults, we determined helium-dilution functional residual and total lung capacities and measured planimetric lung field areas (LFA) from corresponding portable anteroposterior and lateral radiographs. Low radiation dose methods, which delivered less than 10% of that from standard portable X-ray technique, were utilized. Correlation between lung volume and radiographic LFA was highly significant (r = 0.96, SEE = 10.6%). Multiple-step regressions using height and chest diameter correction factors reduced variance, but weight and radiographic magnification factors did not. In 17 additional subjects studied for validation, the regression equations accurately predicted radiographic lung volume. Thus, this technique can provide accurate and rapid measurement of lung volume in studies involving supine patients.

Adult

An apparatus for the measurement of lung volume and compliance in mice.

Pressure-volume (P-V) curves and total lung capacity (TLC) were measured in excised lung of mice using a water manometer and a closed system in which the humidity and temperature were controlled. In pathogen-free mice there are no significant differences in elastic properties of these lungs in relation to their age. The measured TLC in those normal mice was approximately 2.9 ml. This relatively simple apparatus which allows one to make sensitive and accurate measurements of pulmonary function in mice and other small animals.

Animals

Accuracy of measured and predicted residual lung volume on body density measurement.

The effects of measured and predicted residual lung volume on the accuracy of body density and percent fat (%Fat) were investigated. Adult fitness subjects (N = 46) had residual lung volume measured with the oxygen dilution method while those from an athlete sample (N = 134) utilized the nitrogen washout technique. Residual lung volume was also predicted with gender-specific regression equations using height and age and from 24% of vital capacity (%FVC). Residual lung volume alpha reliability for the average of four residual lung volume trials exceeded 0.90 (SEM less than = 161 ml) for the oxygen dilution method and 0.99 (SEM = 30 ml) for the average of two nitrogen washout measures. The standard errors for predicted residual lung volume were 579 and 355 ml, respectively, for the men and women in the adult sample and 288 ml for the trained athlete sample. Estimating residual lung volume from %FVC yielded a SEE of 318 ml for the trained athlete sample. Measured residual lung volume errors resulted in errors of 1.04%Fat, 0.87%Fat, and 0.21%Fat for the men, women, and trained athlete samples, respectively. In contrast, predicted residual lung volume measurement errors resulted in errors of 3.70%Fat, 2.85%Fat, and 1.98%Fat for the respective samples and 2.18%Fat when using %FVC with the trained athletes. Measured residual lung volume introduces little %Fat error while predicted residual lung volume introduces a substantial source of measurement error.

Adipose Tissue

Relationship of arterial-alveolar nitrogen tension to alveolar-arterial oxygen tension, lung volume, flow measurements, and diffusing capacity in cystic fibrosis.

Pulmonary function in children with cystic fibrosis was assessed by the arterial-alveolar PN2 difference adjusted to sublingual temperature. The resulting values were compared with the alveolar-arterial PO2 difference, arterial PCO2, and standard measurements of lung volume, flow, and diffusing capacity. The arterial-alveolar PN2 difference was nearly one half of the PO2 difference, both early in the disease and at a more advanced stage. Analysis taking into account the O2 dissociation curve and the possibility that alveolar temperature is higher than sublingual temperature suggested that all of the PO2 difference could be explained in terms of ventilation-perfusion imbalance in gas-filled units of the lung. Reduction of fractional CO uptake with increasing PN2 difference suggested that the decrease in diffusing capacity in cystic fibrosis may be explained by ventilation-perfusion inequality. A significant relationship between arterial PCO2 and the PN2 difference supported the view that ventilation-perfusion inequality is the cause of CO2 retention when present. The PN2 and PO2 differences were abnormal before the standard tests of lung volume and flow, but in general, the correlation was excellent. Because the PN2 difference was not superior to the PO2 difference in detecting early disease, and because the technical problems in its measurement are considerable, it is not recommended as a routine measurement.

Adolescent

Inductive plethysmography--a facilitated postural calibration technique for rapid and accurate tidal volume determination in low birth weight premature newborns.

Inductive plethysmography is a noninvasive method of measuring lung volumes in infants. This technique, however, has had very limited use in premature newborns because of the difficulty of calibrating the device with regard to the small tidal volumes (VT) in such infants. The present study describes a facilitated calibration of the inductive plethysmograph in low birth weight infants. The technique depends on generating significantly different compartmentalization of VT into rib cage and abdominal components by changing the infant's position from supine to upright. Linear regression analyses were performed to compare VT measurements made in 9 premature infants with the inductive plethysmograph and the pneumotachygraph; an overall Z-transformed correlation of 501 breath-to-breath comparisons yielded an r value of 0.80; the mean VT (pneumotachygraph) was 13.9 +/- 4.7 ml SD; the mean VT (inductive plethysmograph) was 14.3 +/- 5.1 ml SD. It is concluded that inductive plethysmography is an accurate method to measure VT in small premature infants. Moreover, the ease of the two-position technique for calibration of the device gives the inductive plethysmograph greater utility as a clinical and research tool for measuring lung volumes in premature infants.

Calibration

Measurement of lung gas volume and regional density by computed tomography in dogs.

To determine if computed tomography (CT) can accurately measure lung volume, we compared lung gas volume measured by helium dilution with the equivalent volume calculated from CT total lung volume and density in 13 supine dogs. CT lung gas volume underestimated helium volume by 34% (range: -63 to 0%). Studies of wooden lung phantoms varying in density from 0.082g/cc to 0.776g/cc showed that only 15% of this error could be mimicked by the phantoms. The rest of the discrepancy is attributed to the lung's irregular borders, and the sharp density gradients surrounding and within the lung that result in x-ray beam hardening, sampling limitations, and partial volume measurement errors. Serial biweekly measurements in three dogs for 14 weeks showed CT gas volume to be highly reproducible with less scatter than seen in the helium measurements. Density in the lungs of all dogs showed a uniform gradual decrease from approximately 0.60g/cc at the dependent surface to 0.20g/cc at the superior surface with relatively constant density at any horizontal level. These studies show that whereas CT underestimates gas volume in the lungs, serial measurements are highly reproducible in experimental studies and are a promising technique to monitor diseases or response to therapy. Density gradients in the lungs were sufficiently uniform so that disruption of the normal gradient may be an indicator of early lung disease.

Animals

Measurement of lung volume with 81Krm in a dynamic scintigram.

The meaning of 81Krm counts obtained in a dynamic series of gated lung ventilation scans was evaluated in terms of flow rate, lung volume, or the flow/volume ratio. Flow and volume signals were recorded together with scintigraphic events in 29 subjects breathing 81Krm and after its decay, 127Xe as a tracer of lung volume. Gated ventilation scans and respiratory signals were reconstructed. Statistical analyses were carried out for linear regressions between total normalized counts detected by the gamma camera and (1) flow rate, (2) lung volume and (3) flow/volume ratio. Inspiration and expiration were analysed separately. For both isotopes, the best correlation was obtained between counts and lung volume (r greater than 0.93). No correlation was obtained between counts and flow rate or flow/volume ratio. Thus, we conclude that 81Krm count variations in gated scans correlate well with tidal volume.

Humans