| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Guest Access | Sign In via User Name/Password
|
|
|
|||||||
Guest Access | Sign In via User Name/Password |
|||||||||
* From the Université de Caen–Basse-Normandie (Dr. Normand and Mr. Lavigne), Faculté de Médecine, Laboratoire de Physiologie, Caen, France; and CHU de Caen (Dr. Mouadil), Laboratoire des Explorations Fonctionnelles, Caen, France.
Correspondence to: Hervé Normand, MD, DSc, Laboratoire de Physiologie- UPRES-EA 3917, Faculté de Médecine de Caen, Ave de la Côte de Nacre, 14032 Caen Cedex, France; e-mail: normand-h{at}chu-caen.fr
Abstract
Study objectives: The aim of the study was to measure the single-breath diffusing capacity of the lung for carbon monoxide (DLCOsb) in healthy subjects in the following two conditions originally proposed by the American Thoracic Society (ATS) guidelines: relaxation against the shutter; and full inspiration without straining.
Setting: DLCOsb was measured in 76 young adults in duplicate, in the two conditions. Mouth pressure was recorded during all of the trials.
Results: The mean (± SD) value of the duplicate DLCOsb measurements was higher when measured with the patient in the nonrelaxed condition than in the relaxed condition (32.65 ± 7.65 vs 31.54 ± 7.11 mL/min/mm Hg, respectively; p < 0.001). The mean effective alveolar volume measured during the single-breath maneuver (VAeff) was also higher in the nonrelaxed condition (VAeff: nonrelaxed condition, 5,779 ± 1,093 mL; relaxed condition, 5,596 ± 1,097 mL; p < 0.001), at least as a consequence of a higher inspiratory volume (Vin) in the nonrelaxed condition (nonrelaxed condition, 4,378 ± 900 mL; relaxed condition, 4,232 ± 902 mL; p < 0.001). Asking the subject performing a DLCOsb maneuver to relax on the shutter during apnea lowers the DLCOsb value by approximately 3.4% in comparison to full inspiration without straining, at least in part because it results in a reduced Vin.
Conclusion: These data lend further support to the new European Respiratory Society/ATS Task Force recommendations (full inspiration maintained with near atmospheric intrapulmonary pressure).
Key Words: carbon monoxide • practice guidelines • pressure • pulmonary diffusing capacity • pulmonary gas exchange • respiratory system
Several factors relating to the equipment used, how the operation is performed, the methods of calculation, and a subject’s characteristics can influence the measurement of single-breath diffusing capacity of the lung for carbon monoxide (DLCOsb). Using DLCOsb as an index of pulmonary function requires that the technique be fully standardized. The European Respiratory Society (ERS)/American Thoracic Society (ATS) Task Force1 very recently proposed a standardized methodology for DLCOsb measurement based on earlier statements from the ERS and the ATS.23 Discrepancies between the two previous sets of recommendations included those for measuring alveolar pressure during apnea. During the maneuver, the patient is invited to produce a full inspiration to total pulmonary capacity before the shutter is closed. During the following 10 s of apnea, the patient may be instructed to release the inspiratory effort against the shutter or to maintain a full inspiratory position with a persistent inspiratory muscle contraction. In the first case, the muscle relaxation produces an increase in the alveolar pressure, depending on the pulmonary volume, the total respiratory compliance, and the effectiveness of the muscle relaxation. If the maneuver is performed with an open glottis, the mouth pressure represents the alveolar pressure; if not, the glottis forms an internal shutter, and so mouth pressure is not dependent on respiratory system compliance. In the second case, the alveolar pressure remains close to the atmospheric pressure. Using the data from the study by Smith and Rankin,4 it is possible to calculate a 17.4% decrease in DLCOsb during a Valsalva maneuver with an 86 cm H2O increase in mouth pressure. Suzuki et al5 have also demonstrated an 8% decrease in DLCOsb during a 30-cm H2O increase in mouth pressure. Even in healthy subjects, it is difficult to predict alveolar pressure during inspiratory muscle relaxation against the shutter, because at high pulmonary volume the respiratory system pressure-volume curve is flat, and a small deviation from the full inspiratory position may produce a large decrease in alveolar pressure even if the total respiratory compliance is normal. Furthermore, relaxation is difficult to achieve, and the residual effect of respiratory muscle activity (inspiratory or expiratory) on alveolar pressure may largely overcome the effects of the passive mechanical characteristics of the respiratory system. Finally, as the subject can relax on the closed glottis instead of the mechanical shutter of the respiratory apparatus, measuring the mouth pressure does not necessarily indicate whether the respiratory technician’s directions are being followed in the maneuver.
Any increase in alveolar pressure is liable to decrease DLCOsb at least through a decrease in capillary blood volume.6 To a lesser degree, an alveolar pressure increase may decrease DLCOsb through the increase in the alveolar pressure of O2.7
An earlier ATS recommendation let the patient relax on the shutter or on the glottis or maintain a full inspiration, as follows: "the subject ... should either try to relax against a closed glottis or a closed valve during the breath-hold or else maintain a full inspiratory position without straining. Excessive positive or negative intrathoracic pressure (ie, obvious Valsalva or Muller maneuvers) should be avoided during breath-hold."2 The new recommendation issued by the ERS/ATS Task Force1 indirectly avoids relaxation, as follows: "The intrapulmonary pressure during the breath hold should thus be near atmospheric, and this is best accomplished by having the subject voluntarily maintain full inspiration using only the minimal effort necessary."
The aim of the study was to measure DLCOsb in a group of healthy subjects in the two conditions originally proposed in the ATS guidelines (ie, relaxation against the shutter and full inspiration without straining), and to determine how the instruction is carried out and whether it affects the measurement. Our results support the ERS/ATS Task Force choice of standardization of single-breath determination of carbon monoxide uptake in the lung.
Materials and Methods
Subjects and Protocol
Data were collected on medical students during practical teaching sessions following a procedure that was approved by the University Council. The 86 students in the class (second year of medical school) gave their informed consent and served as volunteers, but only the data of the 76 students (50 women and 26 men; age range, 18 to 30 years; mean [± SD] age, 20.4 ± 1.4 years) with no history of cardiac or respiratory disease were used in the study.
The tests were conducted between 10:00 AM and 1:30 pm. All measurements were completed in 2 months. The linearity of the carbon monoxide and helium analyzers was checked before the session. Error was < 1% full scale for both analyzers.
As the measurements were taken during a teaching session, the students had to come to the laboratory in pairs. Subjects underwent whole-body plethysmography. Then the first student of the pair trained for the DLCOsb measurements undergoing five practice trials in condition 1 (relaxed or nonrelaxed) followed by five practice trials in condition 2 (relaxed or nonrelaxed). In order to reproduce the usual conditions of respiratory functional testing, no effort was made for the students to achieve a precise mouth pressure, and no visual feedback control of mouth pressure was given. The aim was to have them "clinically" relax in the relaxed condition (this was hardest to obtain). The instructions were explained with reference to respiratory physiology, as follows: "you relax if your lungs empty spontaneously when the shutter opens." Subjects were also encouraged to let their shoulders droop and their abdomen puff out. Since all of them were familiar with the respiratory physiology, they were reminded that relaxing on the shutter should increase mouth pressure, while maintaining an inspiratory effort without straining ought to leave the mouth at atmospheric pressure.
Two technically acceptable measurements of DLCOsb were then made in each condition in the same order as for training (condition 1 then condition 2). The second student of the pair subsequently underwent with the same sequence (five training trials in each condition then two technically acceptable measurements of DLCOsb in each condition) except that the order was reversed for the two conditions (condition 2 then condition 1). Condition 1 was relaxed for half of the pair of students, and nonrelaxed for the other half.
With this scheme, the same number of students began with one or the other condition. The data of 10 students were not included in the study because of medical problems (most had asthma), but the randomization scheme was affected only very slightly (ie, 40 healthy volunteers began in the relaxed condition and 36 healthy volunteers began in the nonrelaxed condition).
Hemoglobin and Carboxyhemoglobin
Hemoglobin (Hb) and carboxyhemoglobin (COHb) were measured in duplicate on blood capillary microsamples both before and after the DLCOsb measurements using two different oximeters (model OSM3; Radiometer; Copenhagen, Denmark; and model OMNI6; AVL; Graz, Austria). The mean pretest and posttest values are reported.
Whole-Body Plethysmography
Intrathoracic gas volume was measured near functional residual capacity with a barometric whole-body plethysmograph (CompactLab; Jaëger; Wuerzburg, Germany) during low-frequency panting (typically 1 Hz); then while still connected to the pneumotachograph, the subject inspired to total lung capacity (TLC), allowing the measurement of inspiratory capacity and the calculation of TLC.
Training for Respiratory Muscle Relaxation and Inspiratory Position Maintenance
Subjects performed exactly five practice trials for the breathholding maneuver in each condition. The mouthpiece, the first connector, and the mouth pressure transducer were the same as those used with the DLCOsb measurement system, but the DLCOsb apparatus was replaced with a valve that was closed up manually during apnea for about 8 to 10 s. Instructions on how to perform the breathholding maneuver were the same as for actual DLCOsb tests. Subjects were instructed either to relax on the shutter or to actively maintain full inspiration, without trying to force the shutter open. Fifteen to 30 s were allowed between trials. No comments were made to the subjects between the trials.
Mouth Pressure Measurement
Mouth pressure was measured with a ± 70 cm H2O pressure transducer (model scx 142, 1,000 decimeters; SenSym ICT; Milpitas, CA) connected to an amplifier (model 20–4615-50; Gould; Cleveland, OH). The pressure port was connected to the respiratory circuitry close to the mouth with a 3-cm-long tube so as to minimize the dead space to the transducer. The pressure signals were recorded (model TA11; Gould). Calibration was performed with a water column for every subject. For each practice or actual DLCOsb trial, mouth pressure was measured as the mean pressure during the trial.
Transfer Factor
Subjects remained seated at rest for 5 min before the DLCOsb measurement began. There was a 5-min break between the trials. Subjects were instructed to perform the breathholding maneuver according to the ERS recommendations.3 For each condition, DLCOsb was calculated as the mean of the first two technically acceptable trials (ie, full inspiration in < 2.5 s to > 85% of vital capacity (VC), uninterrupted smooth expiration immediately following shutter opening with a time of sample collection of < 3 s). The test gas contained 21.2% O2, 0.28% CO, 9% He, balance N2 (all ± 2% relative). All of the tests were performed on the same commercial apparatus (MasterLab transfer; Jaëger), with identical settings, including a 0.75-L washout volume, a 0.75-L sample volume, a 9-s occlusion time (breathholding time, 9.3 to 11.3 s). The anatomic dead space was calculated as 2.2 x body weight (in kilograms); corrections were applied for instrumental dead spaces, and for CO2 and H2O absorption according to ATS, assuming the alveolar fraction of CO2 to be 0.05. The CO analyzer (infrared) and He analyzer (thermal conductivity) were calibrated before each set of trials.
The DLCOsb was corrected individually for COHb according to ATS recommendations, with COHb-adjusted DLCOsb = measured DLCOsb (1 – [% COHb/100]) assuming a linear increase as the tests were repeated. This seemed to be a reasonable assumption, as the mean calculated increase in COHb per test (0.65 ± 0.1%) was similar whether the subject performed four, five, or six tests. No correction was made for Hb values. The reproducibility criteria of 10% between tests was not used for acceptability. However, the study was also a teaching session in which the students had to measure their own DLCOsb and to meet the ERS reproducibility criteria; therefore, for some subjects, additional trials were performed. The results of these trials are not reported, but the total number of tests was used for calculating the COHb correction as the final blood sampling was taken at the end of the session.
After the measurements were completed in the students, a simulation of the breathholding maneuver with a 3-L syringe at pressures of up to 50 cm H2O was performed in order to verify the efficiency of the closing valve and the ability of the measuring system to measure inspiratory volume during a single breath (Vin) under conditions of increased pressure. The syringe was put in place of the subject and was used to simulate a DLCOsb test. The increased pressure was set by pushing the piston of the syringe against the closed shutter and was measured with the same transducer as that for mouth pressure. The DLCOsb per unit of alveolar volume (KCOsb) was calculated for each trial as the ratio of DLCOsb and effective alveolar volume measured during the single-breath maneuver (VAeff), which were measured during the trial.
Data Analysis
Data analysis was performed with two statistical software packages (Excel; Microsoft; Redmond, WA; and SigmaStat; SYSTAT; Point Richmond, CA). Comparisons were made with two-tailed paired t tests, linear correlation, and 
2 statistics where appropriate.8 All values are given as the mean ± SD.
Results
Fifty-two subjects performed the required four acceptable DLCOsb tests. Eighteen subjects had to repeat one test owing to a technical error. Six subjects had to repeat two tests. Fourteen subjects had to perform one additional test to achieved the ERS reproducibility criteria, and 2 subjects had to perform two additional tests for the same reason. No subject performed more than six tests in total. The DLCOsb was significantly lower in the relaxed condition than in the nonrelaxed condition (31.54 ± 7.11 vs 32.65 ± 7.65 mL/min/mm Hg, respectively [3.4% decrease]; p < 0.001), but there was no difference in KCOsb between the two conditions (Table 1 ). Indeed, the VAeff, although close to the plethysmographic measurements of TLC, was significantly lower in the relaxed than in the nonrelaxed condition (5,596 ± 1,097 vs 5,779 ± 1,093 mL, respectively; p < 0.001). This lower VAeff appeared to be due partly to the performance of the maneuver, as the Vin was also significantly lower in the relaxed condition than in the nonrelaxed condition (4,232 ± 902 vs 4,378 ± 900 mL, respectively; p < 0.001). However, when considering subjects whose Vin when measured in the relaxed condition was > 97% of the Vin measured in the nonrelaxed condition, (n = 43), the difference in DLCOsb between the two conditions was not lower despite a reduction in the difference between VAeff and very similar Vin (Table 2 ).
|
|
Differences between the first and second trial were similar for both conditions and for all parameters (Table 3 ). However, in both conditions KCOsb was slightly lower in the second trial (as was DLCOsb in the nonrelaxed condition).
|
|
The DLCOsb measured in healthy subjects instructed to relax on the shutter is 3.4% lower than that when subjects are encouraged to maintain full inspiration with near-atmospheric intrapulmonary pressure. An increase in DLCOsb with negative inspiratory pressure has been shown on several occasions,910 but studies of the effect of an increase in alveolar pressure on DLCOsb are scarce. Ogilvie et al11 reported a decrease in DLCOsb in two of three subjects during a Valsalva maneuver. Smith and Rankin4 measured a 17.4% decrease in DLCOsb during a Valsalva maneuver with an average mouth pressure (and presumably alveolar pressure) of 86 cm H2O. Suzuki et al5 showed an 8% decrease in DLCOsb for a mouth pressure of 30 cm H2O. As our aim was to observe the effect of the instruction given to the subject during a standard DLCOsb measurement, we did not measure the intrathoracic pressure, because the catheter used for the pressure recording might have disrupted the course of the maneuver.
However, the frequency histogram of the mean mouth pressure measured during the relaxed trials shows wide scattering (Fig 1 ). For instance, 29 of the 76 subjects had a mouth pressure < 10 cm H2O during the relaxed condition, while their mean Vin/VC ratio was 91.6 ± 3.3%. This is much lower than the value that can be predicted from the normal slope of the volume-pressure curve of the respiratory system as measured in the mid-volume range.12 As the volume-pressure slope of the respiratory system decreases at high lung volume, the actual alveolar pressure in the fully relaxed condition against a shutter would be even higher. Thus, even after practicing, the verbal instruction "relax on the shutter" was probably not correctly followed by all the subjects. It is not possible to guess whether subjects who had low mouth pressure relaxed on a closed glottis or maintained an inspiratory muscle activity.
|
|
Our study shows that the two conditions result in different values for DLCOsb, so it was obviously better to recommend one or the other instead of leaving the patient or respiratory technician to decide.2 Since the intraindividual coefficients of variation for DLCOsb and KCOsb are not different between the two conditions, they cannot be used in selecting a standard. However several differences suggest that the choice of the nonrelaxed condition1 was a preferable standard. The main reason is that it is harder for the maximum inspiration criteria to be met in the relaxed condition. The mean Vin/VC ratio was 92.1 ± 2.3% in the relaxed condition, whereas it reached 95.5 ± 4.8% in the nonrelaxed condition (p < 0.001). The other reason is the ability to perform each condition. As shown in Table 4, mouth pressure variability is greater in the relaxed condition. The instruction given to subjects was to relax on the shutter. The subjects, all of them students in medicine, were familiar with the respiratory mechanics and knew that the maneuver should result in increased mouth pressure. There is evidence that many subjects failed to follow this instruction. Although the study was not designed to determine whether the subjects actually did relax, there is no reason to believe that relaxation on a closed glottis would have occurred with less variability.
The last reason has to do with the repeatability of the maneuver. Despite the corrections applied for the increase in COHb, in both conditions a difference in KCOsb persisted between the first and second measurements. However, although there was no indication that the maneuver was performed any differently in the nonrelaxed condition, there was a decrease in breathhold time in the relaxed condition, despite the practice trials, indicating that there was still a modification in the way the maneuver was performed for the second test in that condition.
Although statistically significant, the average difference between the two conditions is slight in healthy subjects and probably not clinically significant. Therefore, reference equations based on relaxed measurements still appear to be usable. However, the effect of relaxation might be different in patients whose respiratory system mechanical properties have deteriorated, and so monitoring the alveolar pressure during apnea or, failing that, monitoring mouth pressure might improve the reproducibility of the measurement.
In conclusion, asking the subject who is performing a DLCOsb maneuver to relax on the shutter during apnea results in a decrease in the DLCOsb value by approximately 3.4%, at least in part because it weakens the preapnea inspiratory maneuver. Our data lend further support to the new ERS/ATS Task Force recommendation2 encouraging subjects performing DLCOsb measurements to maintain a full inspiratory position with near-atmospheric intrapulmonary pressure.
Footnotes
Abbreviations: ATS = American Thoracic Society; COHb = carboxyhemoglobin; DLCOsb = single-breath diffusing capacity of the lung for carbon monoxide; ERS = European Respiratory Society; Hb = hemoglobin; KCOsb = single-breath carbon monoxide diffusing capacity of the lung per unit of alveolar volume; TLC = total lung capacity; VAeff = effective alveolar volume measured during the single-breath maneuver; VC = vital capacity; Vin = inspiratory volume during a single breath
The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.
Received for publication October 27, 2005. Accepted for publication January 6, 2006.
References
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
