This Article Full Text Full Text (PDF) All Versions of this Article: 200801-090OCv1 178/3/225    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Drummond, M. B. Articles by Wise, R. A. PubMed PubMed Citation Articles by Drummond, M. B. Articles by Wise, R. A.

Intersession Variability in Single-Breath Diffusing Capacity in Diabetics without Overt Lung Disease

¹ Division of Pulmonary and Critical Care Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland; ² Pfizer Global Research and Development, New London, Connecticut; ³ University of Iowa College of Medicine, Iowa City, Iowa; ⁴ University of Utah, and Pulmonary Division, LDS Hospital, Salt Lake City, Utah; and ⁵ Duke University Medical School, Durham, North Carolina

Correspondence and requests for reprints should be addressed to M. Bradley Drummond, M.D., The Johns Hopkins University School of Medicine, Division of Pulmonary/Critical Care Medicine, 5501 Hopkins Bayview Circle, JHAAC 4B.70, Baltimore, MD 21224. E-mail: mdrummo3{at}jhmi.edu

Rationale: American Thoracic Society guidelines state that a 10% or greater intersession change in diffusing capacity of the lung (DL_CO) should be considered clinically significant. However, little is known about the short-term intersession variability in DL_CO in untrained subjects or how variability is affected by rigorous external quality control.

Objectives: To characterize the intersession variability of DL_CO and the effect of different quality control methods in untrained individuals without significant lung disease.

Methods: Data were pooled from the comparator arms of 14 preregistration trials of inhaled insulin that included nonsmoking diabetic patients without significant lung disease. A total of 699 participants performed repeated DL_CO measurements using a highly standardized technique. A total of 948 participants performed repeated measurements using routine clinical testing.

Measurements and Main Results: The mean intersession absolute change in DL_CO using the highly standardized method was 1.45 ml/minute/mm Hg (5.64%) compared with 2.49 ml/minute/mm Hg (9.52%) in the routine testing group (P < 0.0001 for both absolute and percent difference). The variability in absolute intersession change in DL_CO increased with increasing baseline DL_CO values, whereas the absolute percentage of intersession change was stable across baseline values. Depending on the method, 15.5 to 35.5% of participants had an intersession change of 10% or greater. A 20% or greater threshold would reduce this percentage of patients to 1 to 10%.

Conclusions: Intersession variability in DL_CO measurement is dependent on the method of testing used and baseline DL_CO. Using a more liberal threshold to define meaningful intersession change may reduce the misclassification of normal variation as abnormal change.

Key Words: respiratory function testing • diffusing capacity • intersession variability • inhaled human insulin • methodology

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Intersession variability in single-breath diffusing capacity is poorly characterized in previous studies. What This Study Adds to the Field Our study shows that the current criterion of 10% for determining clinical change in diffusing capacity may be too sensitive, and we suggest a 20–25% threshold as more appropriate.