Sources of long-term variability in measurements of lung function: implications for interpretation and clinical trial design.
BACKGROUND
The objective of the study was to characterize the biological and technical components of variability associated with longitudinal measurements of FEV(1) and carbon monoxide diffusing capacity (Dlco). Variability was apportioned to subject and instrument for five commercially available pulmonary function testing (PFT) systems: Collins CPL (Ferraris Respiratory; Louisville, CO); Morgan Transflow Test PFT System (Morgan Scientific; Haverhill, MA); SensorMedics Vmax 22D (VIASYS Healthcare; Yorba Linda, CA); Jaeger USA Masterscreen Diffusion TP (VIASYS Healthcare; Yorba Linda, CA); and Medical Graphics Profiler DX System (Medical Graphics Corporation; St. Paul, MN).


METHODS
This was a randomized, replicated cross-over, single-center methodology study in 11 healthy subjects aged 20 to 65 years. Spirometry and Dlco measurements were performed at baseline, 3 months, and 6 months. Repetitive simulations of FEV(1) and Dlco were performed on the same instruments on four occasions over a 90-day period using a spirometry waveform generator and a Dlco simulator.


RESULTS
The coefficient of variation associated with repetitive measurements of FEV(1) or Dlco in subjects was consistently larger than that associated with repetitive simulated waveforms across the five instruments. Instrumentation accounted for 13 to 58% of the total FEV(1) and 36 to 70% of the total Dlco variability observed in subjects. Sample size estimates of hypothetical studies designed to detect treatment group differences of 0.050 L in FEV(1) and 0.5 mL/min/mm Hg in Dlco varied as much as four times depending on the instrument utilized.


CONCLUSIONS
These results provide a semiquantitative assessment of the biological and technical components of PFT variability in a highly standardized setting. They illustrate how instrument choice and test variability can impact sample size determinations in clinical studies that use FEV(1) and Dlco as end points.
Jensen
Robert L
RL
Pulmonary Laboratory, LDS Hospital and University of Utah, Eighth Ave and C St, Salt Lake City, UT 84143, USA. ldrjens1@ihc.com
Teeter
John G
JG
England
Richard D
RD
Howell
Heather M
HM
White
Heather J
HJ
Pickering
Eve H
EH
Crapo
Robert O
RO
D000328:Adult; D000368:Aged; D002245:Carbon Dioxide / Q000378:metabolism*; D003198:Computer Simulation; D018592:Cross-Over Studies; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume / Q000502:physiology*; D006801:Humans; D008168:Lung / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011653:Pulmonary Diffusing Capacity / Q000502:physiology; D012016:Reference Values; D015203:Reproducibility of Results; D013147:Spirometry / Q000379:methods; D013997:Time Factors
D002245:Carbon Dioxide