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This Article Full Text (PDF) Free All Versions of this Article: chest.06-1999v1 132/2/396    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Article Archive Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jensen, R. L. Articles by Crapo, R. O. Search for Related Content PubMed PubMed Citation Articles by Jensen, R. L. Articles by Crapo, R. O. Related Content Related Article Related Editorial

Sources of Long-Term Variability in Measurements of Lung Function: Implications for Interpretation and Clinical Trial Design

¹LDS Hospital and University of Utah, Salt Lake City, UT, USA ²Pfizer Global Research and Development, Groton, CT, USA

ldrjens1{at}ihc.com

Abstract

BackgroundThe objective of the study was to characterize the biological and technical components of variability associated with longitudinal measurements of forced expired volume in 1 second (FEV₁) and carbon monoxide diffusing capacity (DL_CO). Variability was apportioned to subject and instrument for five commercially available pulmonary function testing (PFT) systems (Collins CPL; Morgan Transflow Test PFT System; SensorMedics Vmax 22D; Jaeger USA Masterscreen Diffusion TP; Medical Graphics Profiler DX^TM System).

MethodsThis was a randomized, replicated cross-over, single-center methodology study in 11 healthy subjects, aged 20- 65 years. Spirometry and diffusing capacity measurements were performed at baseline, 3 and 6 months. Repetitive simulations of FEV₁ and DL_CO were performed on the same instruments on four occasions over a 90-day period using a spirometry waveform generator and a DL_CO simulator.

ResultsThe coefficient of variation associated with repetitive measurements of FEV₁ or DL_CO in subjects was consistently larger than that associated with repetitive simulated waveforms across the five instruments. Instrumentation accounted for 13- 58% of the total FEV₁ and 36- 70% of the total DL_CO variability observed in subjects. Sample size estimates of hypothetical studies designed to detect treatment group differences of 0.050 L in FEV₁ and 0.5 ml/min/mmHg in DL_CO varied as much as four times depending on the instrument utilized.

ConclusionsThese results provide a semi-quantitative 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 FEV₁ and DL_CO as endpoints.

Key Words: Clinical trial design • diffusing capacity • DL_CO • DL_CO simulator • pulmonary function testing • pulmonary waveform generator • spirometry • variability

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Instrument Accuracy and Reproducibility in Measurements of Pulmonary Function

Robert L. Jensen, John G. Teeter, Richard D. England, Heather J. White, Eve H. Pickering, and Robert O. Crapo
Chest 2007 132: 388-395. [Abstract] [Full Text] [PDF]

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				N. MacIntyre Finding Signals Amidst the Noise in Pulmonary Function Testing Chest, August 1, 2007; 132(2): 367 - 368. [Full Text] [PDF]

				R. L. Jensen, J. G. Teeter, R. D. England, H. J. White, E. H. Pickering, and R. O. Crapo Instrument Accuracy and Reproducibility in Measurements of Pulmonary Function Chest, August 1, 2007; 132(2): 388 - 395. [Abstract] [Full Text] [PDF]