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This Article Full Text (PDF) All Versions of this Article: chest.07-0455v1 132/4/1191    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 Google Scholar Google Scholar Articles by Wise, R. A. Articles by Crapo, R. O. Search for Related Content PubMed PubMed Citation Articles by Wise, R. A. Articles by Crapo, R. O.

Standardization of the Single-Breath Diffusing Capacity (DL_CO) in a Multicenter Clinical Trial

¹Johns Hopkins University School of Medicine, Baltimore, MD, USA ²Pfizer Global Research and Development, New London, CT ³LDS Hospital and University of Utah, Salt Lake City, UT, USA ⁴Ferraris Respiratory, Louisville, CO, USA ⁵University of Iowa Carver College of Medicine, Iowa City, IA, USA ⁶Duke University Medical Center, Durham, NC, USA

rwise{at}jhmi.edu

Abstract

BackgroundStandardization of the measurement of single-breath diffusing capacityis difficult to implement in multicenter trials as differences in equipment, training, and performance guidelines have led to high variability between and within centers. The safety assessment of inhalable insulin required the standardization of measurement of single-breath diffusing capacity in multicenter clinical trials to optimize test precision.

MethodsThis was an open-label, 24-week, parallel-group, outpatient study of inhaled human insulin in participants with type 1 diabetes randomly assigned treatment with daily premeal inhaled or subcutaneous insulin for 12 weeks, followed by subcutaneous insulin for 12 weeks. Monitoring of single-breath diffusing capacity using standardized methodology was performed. Standardization included uniform instrumentation, centrally trained study coordinators, and centralized data monitoring and review of quality control. Sites received feedback within 24 hours for any tests of unacceptable quality with recommendations for improvement.

Results226 study participants at 33 sites completed 11,335 DL_CO efforts during 4797 test sessions. 3607 (75.2%) and 4581 (95.5%) of all testing sessions yielded two American Thoracic Society-acceptable efforts that varied by less than 1 and 2 ml/min/mmHg, respectively. Only 65 sessions produced one or fewer acceptable efforts. The root mean square intrasubject coefficient of variation in DL_CO at the end of the comparative dosing phase was 6.01%.

ConclusionsThe standardized methodology employed in this study demonstrates the feasibility of collecting high-quality single-breath diffusing capacity data in the setting of a multicenter clinical trial with reliability comparable to spirometry.

Key Words: Respiratory function tests • diffusing capacity • methodology • inhaled human insulin • clinical trials