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Study objectives: The single-breath diffusing capacity of the lung (DLCO) is a commonly performed pulmonary function test. The current American Thoracic Society (ATS) recommendations for reproducibility of DLCO measurements suggest that two measurements for the DLCO agree within 10% or 3 mL/min/mm Hg of the average value. The European Respiratory Society (ERS) recommends that two measurements should agree within 10%. The objectives of the present study were to examine whether the current reproducibility criteria were met in a general pulmonary function laboratory and to determine whether alternative criteria might be appropriate. Design: Cross-sectional study. Setting: University-based pulmonary function laboratory. Patients or Participants: Patients referred for spirometry, helium lung volumes, and DLCO measurement. Interventions: None. Measurements and results: In a sample of 6,193 patients referred for clinical testing, 98.3% had two DLCO values that fulfilled the current ATS criteria for reproducibility. The coefficient of variation (CV) and the percentage difference between two repeat measurements were inversely associated with the baseline DLCO and the FEV1. As the baseline DLCO (percentage of predicted) or FEV1 (percentage of predicted) decreased, there was an increase in the CV and the percentage difference. In contrast, the absolute difference between repeat measurements was relatively stable irrespective of the baseline DLCO or FEV1 values. Other patient factors, such as gender and race, were not associated with measurement variability. Using an absolute difference of 2 to 2.5 mL/min/mm Hg between two DLCO measurements as alternative criteria for reproducibility, 91.5% and 95.8% of the patient sample fulfilled these criteria, respectively. Conclusions: Reproducibility of the DLCO measurement is generally much better than current standards allow. Future standards should consider an absolute difference rather than a percentage difference criterion for DLCO reproducibility. (CHEST 2003; 123:1082–1089)

The 6-minute walk test is used in clinical practice and clinical trials of lung diseases; however, it is not clear whether replicate tests need to be performed to assess performance. Furthermore, little is known about the impact of walking course layout on test performance. We conducted 6-minute walks on 761 patients with severe emphysema (mean +/- SD FEV1% predicted = 26.3 +/- 7.2) who were participants in the National Emphysema Treatment Trial. Four hundred seventy participants had repeated walks on a separate day. The second test was improved by an average of 7.0 +/- 15.2% (66.1 +/- 146 feet, p < 0.0001, by paired t test), with an intraclass correlation coefficient of 0.88 between days. The course layout had an effect on the distance walked. Participants tested on continuous (circular or oval) courses had a 92.2-foot longer walking distance than those tested on straight (out and back) courses. Course length had no significant effect on walking distance. The training effect found in these patients with severe emphysema is less than in previous reports of patients with chronic obstructive pulmonary disease. Furthermore, the layout of the track may influence the 6-minute walk performance.

To assess the safety and potential efficacy of a mechanical ventilation strategy designed to reduce stretch-induced lung injury in acute respiratory distress syndrome.Prospective, randomized, controlled clinical trial.Eight intensive care units in four teaching hospitals.Fifty-two patients with acute respiratory distress syndrome.Traditional tidal volume patients: tidal volume 10-12 mL/kg ideal body weight, reduced if inspiratory plateau pressure was55 cm H2O (7.3 kPa). Small tidal volume patients: tidal volume 5-8 mL/kg ideal body weight, to keep plateau pressure30 cm H2O (4.0 kPa).Mean tidal volumes during the first 5 days in traditional and small tidal volume patients were 10.2 and 7.3 mL/kg, respectively (p.001), with mean plateau pressure = 30.6 and 24.9 cm H2O (3.3 kPa), respectively (p.001). There were no significant differences in requirements for positive end-expiratory pressure or FIO2, fluid intakes/outputs, requirements for vasopressors, sedatives, or neuromuscular blocking agents, percentage of patients that achieved unassisted breathing, ventilator days, or mortality.The reduced tidal volume strategy used in this study was safe. Failure to observe beneficial effects of small tidal volume ventilation treatment in important clinical outcome variables may have occurred because a) the sample size was too small to discern small treatment effects; b) the differences in tidal volumes and plateau pressures were modest; or c) reduced tidal volume ventilation is not beneficial.

The citalopram for Alzheimer’s disease trial evaluated citalopram for the management for agitation in Alzheimer’s disease patients. Sparse data was available from this elderly patient population. A nonlinear mixed effects population pharmacokinetic modeling approach was used to describe the pharmacokinetics of R- and S-citalopram and their primary metabolite (desmethylcitalopram). A structural model with 4 compartments (one compartment/compound) with linear oral absorption and elimination described the data adequately. Overall, the model showed that clearance of the R-enantiomer was slower than the clearance of the S-enantiomer. Without accounting for any patient-specific covariates, the population estimate of the metabolic clearance of citalopram was 8.6 (R-citalopram) and 14 L/h (S-citalopram). The population estimate of the clearance of desmethylcitalopram was 23.8 (R-Dcit) and 38.5 L/h (S-Dcit). Several patient-specific covariates were found to have a significant effect on the pharmacokinetics of R,S-citalopram and desmethylcitalopram. A significant difference in the metabolic clearance of R-citalopram between males and females (13 vs 9.05 L/h) was identified in this analysis. Both R- and S-citalopram metabolic clearance decreased with age. Additionally, consistent with literature reports S-citalopram metabolic clearance increased with increasing body weight and was significantly influenced by CYPC19 genotype, with a difference of 5.8 L/h between extensive/rapid and intermediate/poor metabolizers. R,S-desmethylcitalopram clearance increased with increasing body weight. This model may allow for the opportunity to delineate the effect of R- and S-citalopram on pharmacodynamics outcomes related to the management of agitation in Alzheimer’s disease. Electronic supplementary material The online version of this article (doi:10.1007/s10928-015-9457-6) contains supplementary material, which is available to authorized users.