Quality control ofD_L,COinstruments in global clinical trials

Abstract

High inter-and intra-laboratory variability exists for the single-breath diffusing capacity of the lung for carbon monoxide (DL,CO) test. To detect small changes in diffusing capacity in multicentre clinical trials, accurate measurements are essential. The present study assessed whether regular DL,CO simulator testing maintained or improved instrument accuracy and reduced variability in multicentre trials.The 125 pulmonary function testing laboratories that participated in clinical trials for AIR1 Inhaled Insulin validated and monitored the accuracy of their DL,CO measuring devices using a DL,CO simulator, which creates known target values for any device. Devices measuring a simulated DL,CO different from target by .3 mL?min-1?mmHg -1 failed testing and were serviced.Device accuracy was assessed over time and with respect to differences in several variables. Initially, 31 (25%) laboratories had a DL,CO device that failed simulator testing. After fixing or replacing devices, 124 (99%) laboratories had passing devices. The percentage of failed tests significantly decreased over time. Differences in geographical region, device type, breath-hold time, temperature and pressure were not associated with meaningful differences in DL,CO device accuracy.Regular diffusing capacity of the lung for carbon monoxide simulator testing allows pulmonary function testing laboratories to maintain the accuracy of their diffusing capacity measurements, leading to reduced variability across laboratories in multicentre clinical trials.

Association of the transfer coefficient of the lung for carbon monoxide with emphysema progression in male smokers

“…Thirdly, the same diffusion testing equipment was used. This is especially important since it is known that large variability may exist in KCO measurements between different lung function laboratories [29]. Fourthly, only heavy smoking, but relatively healthy participants were included.…”

Single-Breath Diffusing Capacity for Carbon Monoxide Instrument Accuracy Across 3 Health Systems

“…Large errors can be observed if the technician does not allow adequate washout of the dead space or if gas leaks in the system are not identified. Biological/patient sources of error can include a failure to inhale to total lung capacity, prolonged inhalation or exhalation time, maintaining airway pressure during the breath-hold that is significantly higher or lower than atmospheric pressure, leaks at the mouth or nose 9 It is important to minimize inaccuracy and variability in D LCO testing so changes due to disease process or changes due to therapeutic interventions can be detected. The clinical utility of D LCO measurement will be enhanced by maintaining accurate instruments.…”

“…6,7 Significant intralaboratory variability has been primarily attributed to inaccuracy of gas or volume measurement with variations in temperature, barometric pressure, and breath-hold time contributing less to measurement inaccuracy. 6,[8][9][10][11] Significant inter-laboratory variability in D LCO measurement has been reported and attributed to differences in devices, software, test gases, and testing procedure. 6,7,9,12,13 This study was designed to assess D LCO instrument performance and quantify inter-laboratory variability in D LCO measurement in Utah and southern Idaho.…”

“…6,[8][9][10][11] Significant inter-laboratory variability in D LCO measurement has been reported and attributed to differences in devices, software, test gases, and testing procedure. 6,7,9,12,13 This study was designed to assess D LCO instrument performance and quantify inter-laboratory variability in D LCO measurement in Utah and southern Idaho. Our hypothesis was that interlaboratory variability is large and that poorly performing instruments could be identified using a D LCO simulator (Hans Rudolph, Inc, Kansas City, Missouri) that are not identified with use of standard laboratory quality control measures.…”

Verification of equipment for measuring the diffusion capacity of the lung for carbon monoxide: Fig. 1—

“…The JENSEN et al [1] study represents a tremendous and successful effort on quality assurance and quality control as part of a large clinical study. The study or probably more likely the presentation of the study by JENSEN et al [1] has a few limitations seen from a metrological point of view to which I want to draw attention.…”