Long-term intersession variability for single-breath diffusing capacity.

BACKGROUND: Characterizing long-term diffusing capacity (DL(CO)) variability is important in assessing quality control for DL(CO) equipment and patient management. Long-term DL(CO) variability has not been reported. OBJECTIVES: It was the aim of this study to characterize long-term variability of DL(CO) in a cohort of biocontrols and to compare different methods of selecting a target value. METHODS: Longitudinal DL(CO) monitoring of biocontrols was performed as part of the inhaled insulin development program; 288 biocontrols were tested twice monthly for up to 5 years using a standardized technique. Variability, expressed either as percent change or DL(CO) units, was assessed using three different target values. RESULTS: The 90th percentile for mean intersession change in DL(CO) was between 10.9 and 15.8% (2.6-4.1 units) depending on the target value. Variability was lowest when the mean of all DL(CO) tests was used as the target value and highest when the baseline DL(CO) was used. The average of the first six DL(CO) tests provided an accurate estimate of the mean DL(CO) value. Using this target, the 90th percentile for mean intersession change was 12.3% and 3.0 units. Variability was stable over time and there were no meaningful associations between variability and demographic factors. CONCLUSIONS: DL(CO) biocontrol deviations >12% or >3.0 units, from the average of the first six tests, indicate that the instrument is not within quality control limits and should be carefully evaluated before further patient testing.

Bronchodilator response in patients with normal baseline spirometry.

BACKGROUND: Spirometry before and after bronchodilator is performed to assess air flow-limitation reversibility. In patients with normal baseline spirometry the frequency of a positive bronchodilator response, as defined by American Thoracic Society/European Respiratory Society criteria, has not been described. METHODS: We retrospectively analyzed adult patients tested in 2 academic pulmonary function testing laboratories over a 7-year period, with specific attention to patients who underwent bronchodilator testing after a normal baseline spirometry (FEV(1), FVC, and FEV(1)/FVC within normal limits). The frequency of a positive response to bronchodilator, defined as a 12% and 200 mL increase in either FEV(1) or FVC, was calculated and associated with demographic factors. RESULTS: Of the 1,394 patients with normal spirometry who were administered bronchodilator, 43 (3.1%) had a positive response. The percent of patients responding to bronchodilator were grouped according to pre-bronchodilator FEV(1): > lower limit of normal to 90% of predicted = 6.9%, 90-100% of predicted = 1.9%, and > 100% of predicted = 0%. An FEV(1)/FVC in the lowest 2 quartiles was associated with a higher frequency of bronchodilator response. Older patients were more likely to respond to bronchodilator, but no other demographic factors were associated with a positive bronchodilator response. CONCLUSIONS: In our study population the frequency of a positive bronchodilator response in patients with normal baseline spirometry is 3.1%. None of the patients with a pre-bronchodilator FEV(1) > 100% of predicted and only 1.9% of patients with an FEV(1) between 90% and 100% of predicted responded. Bronchodilator testing can be omitted in patients with normal spirometry and an FEV(1) above 90% of predicted, as they have a low probability of a positive response.

Intersession variability in single-breath diffusing capacity in diabetics without overt lung disease.

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.

The measure of treatment agreement between portable and laboratory blood gas measurements in guiding protocol-driven ventilator management.

BACKGROUND: Portable blood gas analyzer and monitor devices are increasingly being used to direct ventilator therapy. The purpose of this study was to evaluate the "measure of treatment agreement" between portable and laboratory blood gas measurements used in guiding protocol-driven ventilator management. MATERIALS AND METHODS: Using National Institutes of Health Acute Respiratory Distress Syndrome network ventilator management guidelines to manage patient care, measurements taken from the Nonin 8500 M pulse oximeter (SpO2), the Novametrix-610 end-tidal CO2 (ETCO2) detector, and the i-STAT 1 (SaO2, PO2, pH, PCO2) were compared with the recommended treatment from paired laboratory ABL-725 (SaCO2, PO2, pH, PCO2) measurements. RESULTS: Four hundred forty-six intubated adult intensive care unit patients were studied prospectively. Except for the ETCO2 (R2 = 0.460), correlation coefficients between portable and laboratory measurements were high (R2 > or = 0.755). Testing for equivalence, the Nonin-SpO2, iSTAT-PO2, iSTAT-pH, and iSTAT-PCO2 were deemed "equivalent" surrogates to paired ABL measurements. Testing for the limits of agreement found only the iSTAT-PCO2 to be an acceptable surrogate measurement. The measure of treatment agreement between the portable and paired laboratory blood gas measurements were Nonin-SpO2 (68%), iSTAT-SaO2 (73%), iSTAT-PO2 (97%), iSTAT-pH (88%), iSTAT-PCO2 (95%), and Novametrix-ETCO2 (60%). Only the iSTAT-PO2 and the iSTAT-PCO2 achieved the > or =95% treatment agreement threshold to be considered as acceptable surrogates to laboratory measurements. CONCLUSIONS: : The iSTAT-PO2 and -PCO2 were portable device measurements acceptable as surrogates to standard clinical laboratory blood gas measurements in guiding protocol-directed ventilator management. The "measure of treatment agreement," based on standardized decisions and measurement thresholds of a protocol, provides a simple method for assessing clinical validity of surrogate measurements.

Reference values for lung volumes in an Iranian population: introducing a new equation model.

BACKGROUND: Measurement of lung volumes, especially residual volume and total lung capacity are essential for assessment of restrictive lung disorders. Information regarding normative prediction values for lung volumes as measured by body plethysmography is scarce, and plethysmographic parameters are believed to be poorly reproducible. In this study, we report a comprehensive set of predictive equations for static lung volumes from a general population sample of urban Iranians as measured by body plethysmography. METHODS: Standardized measurements were carried out on 1487 healthy nonsmoking volunteers (845 men and 642 women), aged six to 85 years, living in Isfahan, Iran. Nonlinear multiple regression analysis was used to calculate prediction equations based on subjects' ages and heights for the subdivisions of lung volumes [total lung capacity, functional residual capacity, residual volume, and residual volume/total lung capacity (%)], separately for the two genders. The derived equations were used to calculate prediction values for the subjects. The two sets of predicted and measured values were compared by paired sample t-test. RESULTS: Prediction equations based on a new nonlinear model, (alpha(1) x age + alpha(2) x age(n) + beta x height + c) which best fitted our data are presented. The measured and predicted values closely resemble and there is no significant difference between the two sets. Since increments in total lung capacity, functional residual capacity, and residual volume disclose air trapping within the lungs, their upper limits of normal are as important as the lower limits. So, we have presented both for the equations. CONCLUSION: Despite the usual beliefs we found rather reproducible prediction equations with high coefficient of determination (r2) and low standard error of estimate (SEE) in Iranian population.

Longitudinal association of body mass index with lung function: the CARDIA study.

BACKGROUND: Lung function at the end of life depends on its peak and subsequent decline. Because obesity is epidemic in young adulthood, we quantified age-related changes in lung function relative to body mass index (BMI). METHODS: The Coronary Artery Risk Development in Young Adults (CARDIA) study in 1985-86 (year 0) recruited 5,115 black and white men and women, aged 18-30. Spirometry testing was conducted at years 0, 2, 5 and 10. We estimated 10 year change in FVC, FEV1 and FEV1/FVC according to baseline BMI and change in BMI within birth cohorts with initial average ages 20, 24, and 28 years, controlling for race, sex, smoking, asthma, physical activity, and alcohol consumption. MEASUREMENTS AND MAIN RESULTS: Participants with baseline BMI < 21.3 kg/m2 experienced 10 year increases of 71 ml in FVC and 60 ml in FEV1 and neither measure declined through age 38. In contrast, participants with baseline BMI > or = 26.4 kg/m2 experienced 10 year decreases of 185 ml in FVC and 64 ml in FEV1. FEV1/FVC increased with increasing BMI. Weight gain was also associated with lung function. Those who gained the most weight over 10 years had the largest decrease in FVC, but FVC increased with weight gain in those initially thinnest. In contrast, FEV1 decreased with increasing weight gain in all participants, with maximum decline in obese individuals who gained the most weight during the study. CONCLUSION: Among healthy young adults, increasing BMI in the initially thin participants was associated with increasing then stable lung function through age 38, but there were substantial lung function losses with higher and increasing fatness. These results suggest that the obesity epidemic threatens the lung health of the general population.

Socioeconomic status and lung function.

Poverty is a major social problem in the United States and throughout much of the world. Poverty and the broader term socioeconomic status (SES) are important determinants of overall health status and many pulmonary diseases. The purpose of this study was to review the medical literature from the past 20 years addressing the relationship between SES and lung function in both children and adults. There is a significant negative correlation between lung function (primarily FEV1 and FVC) and SES. This relationship exists even after adjusting for smoking status, occupational exposures, and race. The magnitude of the effect of low SES on lung function is variable, but FEV1 reductions of >300 mL in men and >200 mL in women have been reported. SES is an important determinant of lung function and an underrecognized contributor to pulmonary disease.

Instrument accuracy and reproducibility in measurements of pulmonary function.

BACKGROUND: The objective of the study was to quantify the accuracy and reproducibility of five commercially available pulmonary function test (PFT) instruments (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]; and Medical Graphics Profiler DX System [Medical Graphics Corp; St. Paul, MN]) that are associated with spirometry and the measurement of pulmonary diffusing capacity. METHODS: In a multifactor, single-center, repeated-measures, full factorial 90-day study, a pulmonary waveform generator and a single-breath simulator of diffusing capacity of the lung for carbon monoxide (Dlco) were used to perform simulations of FVC and Dlco maneuvers. Accuracy was assessed as the difference between the observed and simulated values. Reproducibility was determined as the coefficient of variation of all measurements made during the study. RESULTS: All instruments demonstrated a high degree of accuracy in the measurement of FVC and FEV(1). Overall, the accuracies associated with the measurement of peak flow, forced expiratory flow, mid-expiratory phase, and diffusing capacity were generally lower and more variable among the instruments tested. The coefficients of variation of Dlco measurements over 90 days were higher than those observed for spirometry. CONCLUSIONS: This study demonstrates the feasibility of assessing the accuracy and reproducibility of modern PFT instruments using simulation testing. Our results provide an assessment of the component of PFT accuracy and reproducibility that is due to instrumentation alone.

Peak expiratory flow is not a quality indicator for spirometry: peak expiratory flow variability and FEV1 are poorly correlated in an elderly population.

BACKGROUND: Peak forced expiratory flow (PEF) and FEV(1) are spirometry measures used in diagnosing and monitoring lung diseases. We tested the premise that within-test variability in PEF is associated with corresponding variability in FEV(1) during a single test session. METHODS: A total of 2,464 healthy adults from the Health, Aging, and Body Composition Study whose spirometry results met American Thoracic Society acceptability criteria were screened and analyzed. The three "best" test results (highest sum of FVC and FEV(1)) were selected for each subject. For those with acceptable spirometry results, two groups were created: group 1, normal FEV(1)/FVC ratio; group 2, reduced FEV(1)/FVC ratio. For each subject, the difference between the highest and lowest PEF (DeltaPEF) and the associated difference between the highest and lowest FEV(1) (DeltaFEV(1)) were calculated. Regression analysis was performed using the largest PEF and best FEV(1), and the percentage of DeltaPEF (%DeltaPEF) and percentage of DeltaFEV(1) (%DeltaFEV(1)) were calculated in both groups. RESULTS: Regression analysis for group 1 and group 2 showed an insignificant association between %DeltaPEF and %DeltaFEV(1) (r(2) = 0.0001, p = 0.59, and r(2) = 0.040, p = 0.15, respectively). For both groups, a 29% DeltaPEF was associated with a 1% DeltaFEV(1). CONCLUSION: Within a single spirometry test session, %DeltaPEF and %DeltaFEV(1) contain independent information. PEF has a higher degree of intrinsic variability than FEV(1). Changes in PEF do not have a significant effect on FEV(1). Spirometry maneuvers should not be excluded based on peak flow variability.

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.

Standardization of the single-breath diffusing capacity in a multicenter clinical trial.

BACKGROUND: Standardization of the measurement of single-breath diffusing capacity of the lung for carbon monoxide (DLCO) is 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 DLCO in multicenter clinical trials to optimize test precision. METHODS: This was an open-label, 24-week, parallel-group, outpatient study of inhaled human insulin in participants with type 1 diabetes who were randomly assigned to receive treatment with daily premeal inhaled or subcutaneous (SC) insulin for 12 weeks, followed by SC insulin for 12 weeks. Monitoring of single-breath DLCO 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 h for any tests of unacceptable quality with recommendations for improvement. RESULTS: A total of 226 study participants at 33 sites completed 11,335 DLCO efforts during 4,797 test sessions; 3,607 (75.2%) and 4,581 (95.5%) of all testing sessions yielded two American Thoracic Society-acceptable efforts that varied by < 1 and 2 mL/min/mm Hg, respectively. Only 65 sessions produced one or fewer acceptable efforts. The root mean square intrasubject coefficient of variation in DLCO at the end of the comparative dosing phase was 6.01%. CONCLUSIONS: The standardized methodology employed in this study demonstrates the feasibility of collecting high-quality single-breath DLCO data in the setting of a multicenter clinical trial with reliability that is comparable to spirometry.

Pulmonary function changes related to acute and chronic administration of inhaled insulin.

The need for frequent insulin injections to achieve optimal glycemic control remains a major barrier to initiating and maintaining insulin therapy in diabetes. The inhaled route of insulin administration offers many potential advantages. However, there are ongoing concerns regarding the pulmonary safety of inhaled insulin. Published studies reporting pulmonary safety and data submitted to the Food and Drug Administration were reviewed. All studies were open-label, included adult subjects with type 1 and 2 diabetes, and excluded patients with underlying lung disease. Inhaled insulin was compared with subcutaneous insulin and oral agents. Inhaled insulin is associated with small, consistent reductions in lung function, primarily forced expiratory volume in 1 s (FEV(1)) and diffusion capacity for carbon monoxide (DL(CO)). The small reductions in lung function occurred early (within 12 weeks) and did not progress over time. The magnitudes of the reductions were 30-50 mL for FEV(1) and 0.5-1.0 standard units for DL(CO). Collectively, the data indicate that inhaled insulin is safe in studies with duration up to 4 years. The Food and Drug Administration requires monitoring of lung function on a regular basis.

A statistical rationale for the use of forced expired volume in 6 s.

The purpose of the study was to determine the best surrogate for FVC when performing spirometry to detect obstruction or restriction. Volume-time curves from 3,539 participants in the Family Heart Study with acceptable quality test sessions were analyzed. An index of the variability of each timed volume (FEVx) from 1 to 12 s was determined for each subject. The least within-test session variability was seen for forced expired volume in 6 s (FEV(6)) and forced expired volume in 7 s (for both, mean range was 95 mL). The sensitivity and specificity for detecting obstruction and restriction when substituting the FEV(6) for the FVC were then determined before and after allowing for measurement errors of 50 mL (approximately the lower limit of spirometers ability to detect volume). Sensitivity was 76% before the 50-mL error analysis and 95% after. Specificity was 98% before the 50-mL error analysis and 99.5% after. We conclude that use of FEV(6) to replace the FVC for spirometry testing will result in improved reproducibility, with no significant loss of sensitivity or specificity, after allowing a 50-mL measurement error, for detecting obstruction or restriction.

Periodontitis and airway obstruction.

BACKGROUND: The objective of this study was to examine the relationship between airway obstruction and periodontal disease. METHODS: Participants were a subset of 860 community- dwelling, well functioning elderly (aged 70 to 79, blacks and whites, males and females) selected from 2,732 participants enrolled in the Health, Aging, and Body Composition Study (Health ABC). The periodontal evaluations occurred over years 2 and 3 of the study and included four indices of periodontal health: plaque index (PI), gingival index (GI), probing depth (PD), and loss of attachment (LOA). The pulmonary evaluation took place in year 1: conducted according to American Thoracic Society criteria, based on the forced expiratory volume/forced vital capacity (FEV1/FVC) ratio and then using the percent of predicted FEV1 to categorize severity. RESULTS: GI (P = 0.023) and LOA (P = 0.009) were significantly better in participants with normal pulmonary function compared to those with airway obstruction after adjusting for age, race, gender, and field center. When stratified by smoking status and after adjusting for age, race, gender, center, and pack-years, there was a significant association between periodontal health and airway obstruction in former smokers. Within this group, those with normal pulmonary function had significantly better GI (P = 0.036) and LOA (P = 0.0003) scores than those with airway obstruction. All periodontal indices were elevated in smokers regardless of pulmonary status; however, the current smoker group was too small to detect a periodontitis effect. CONCLUSION: While the present cross-sectional study cannot provide direct inference of cause and effect, it does reveal a significant association between periodontal disease and airway obstruction, particularly in former smokers.

Spirometric reference values for the 6-s FVC maneuver.

STUDY OBJECTIVES: The guidelines of the National Lung Health Education Program for COPD screening proposed a shorter FVC maneuver (forced expiratory volume at 6 s of exhalation [FEV(6)]). Although reference values for FEV(6) are available from the third National Health and Nutrition Examination Survey, forced expiratory flow between 25% and 75% of FVC (FEF(25-75%)) reference values for the shorter 6-s maneuver are not available and are needed. In particular, calculation of largest observed volume during the first 6 s of an FVC maneuver (FVC(6)), from a shortened FVC maneuver, is necessary because the FEF(25-75%) measurement is based on a percentage of FVC or, for a shorter maneuver, FVC(6). DESIGN: We reanalyzed the raw volume-time curves from the third National Health and Nutrition Examination Survey to calculate FVC(6), forced expiratory volume at 0.5 s of exhalation, forced expiratory volume at 3 s of exhalation, ratio of the FEV(1) to largest observed volume during the first 6 s of an FVC maneuver expressed as a percentage (FEV(1)/FEV(6)%), and forced expiratory flow between 25% and 75% of the largest observed volume during the first 6 s of an FVC maneuver (FEF(25-75%6)) in addition to the previously reported values for FEV(1), FEV(6), and FEV(1)/FEV(6)%. PATIENTS OR PARTICIPANTS: Using the same normal, asymptomatic, nonsmoking reference population from a previous study, reference values for these parameters were derived from best values. RESULTS: A total of 2,261 white, 2,564 African-American, and 2,666 Mexican-American subjects aged 8 to 80 years were included in the analysis. Fifty-four subjects from the previous study were not included due to missing raw volume-time curves. CONCLUSIONS: These reference values, utilizing the FVC(6), provide investigators with the means of evaluating the relative merits of using the shorter FVC maneuver as a surrogate for the traditional FVC. They are needed particularly for calculating FEF(25-75%), as statistically significant differences were observed between the FEF(25-75%) and FEF(25-75%6).

Validity of the American Thoracic Society and other spirometric algorithms using FVC and forced expiratory volume at 6 s for predicting a reduced total lung capacity.

OBJECTIVES: (1) To compare the performance of three spirometric algorithms developed to predict whether the total lung capacity (TLC) is reduced vs normal or increased, (2) to determine if forced expiratory volume at 6 s (FEV(6)) can be substituted for FVC in these algorithms, and (3) to determine if ascertainment bias was present in patients referred for the measurement of spirometry and TLC compared to patients referred for spirometry only. METHODS: We analyzed the results of 219 consenting consecutive patients referred to a New Zealand tertiary hospital respiratory laboratory for spirometry and TLC measurements. Spirometry results from 370 patients referred for spirometry but not lung volumes were used to test for potential ascertainment bias. Spirometry results were analyzed using the lower limit of normal (LLN) values from the third National Health and Nutrition Examination Study reference equations. The equations of Goldman and Becklake, and Crapo were used to classify TLC as normal or abnormal. Receiver operator characteristic curves were used to produce an algorithm using the LLN for FVC and FEV(6). The performances of previous algorithms and our own algorithms were analyzed for predicting a reduced lung volume against the "gold standard," plethysmographic TLC. RESULTS: All three algorithms predicted a reduced TLC with an accuracy of approximately 50%. In contrast, all algorithms predicted TLC was either normal or increased with an accuracy of > or = 99% regardless of the reference set used. The algorithms based on FEV(6) performed equally as well as the FVC algorithms. No ascertainment bias was found. CONCLUSIONS: This study provides evidence that spirometry-based algorithms can accurately predict when TLC is either normal or increased, and can also increase the a priori probability that TLC is reduced to approximately 50%. FEV(6) is equivalent to FVC in these predictions.

Standards and interpretive issues in lung function testing.

Pulmonary function tests are most useful when performed with good technique and with an accurate system. Using standard techniques in performing the tests minimizes diagnostic and therapeutic errors. This report discusses the rationale and limits of standardization and offers practical suggestions for using available standards to increase confidence in test results.

Diffusing capacity: how to get it right.

The carbon monoxide diffusing capacity test (D(LCO)) is a commonly performed pulmonary function test that requires technical expertise and attention to detail to get acceptable results. With the advent of automated devices and powerful computer programs, D(LCO) measurement has rapidly gained wide clinical acceptance. But there are many subtle aspects to performing the test that can diminish its accuracy and repeatability. The clinician must ensure: that the D(LCO) instrument is correctly calibrated; that inhalation is least 90% of the largest previously measured vital capacity; that the patient executes a quick, smooth inhalation within 2 seconds; that the breath-hold is 9-11 seconds; that the breath-hold is without straining (no Valsalva or Müller maneuvers); that exhalation is quick and smooth; that a representative gas sample is obtained from the correct portion of the exhalation; and that at least 5 minutes elapse between D(LCO) tests. At least 2 but no more than 5 D(LCO) tests should be conducted, and testing is complete when 2 tests are within 10% or 3 D(LCO) units (mL CO/min/mm Hg) of each other. The reported D(LCO) value is the average of the first 2 tests that meet the reproducibility criteria, but if 5 tests are performed and no 2 meet the reproducibility criteria, the reported value is the average of the 2 tests with the highest inspiratory volumes. These quality controls will help laboratories achieve consistent high D(LCO) accuracy.