Diffusing capacity for nitric oxide: Reference values and dependence on alveolar volume

In Europe, two commercial devices are available to measure combined single-breath lung diffusing capacity for nitric oxide (DLNO) and carbon monoxide (DLCO) in one maneuver. Reference values were derived by pooling datasets from both devices, but agreement between devices has not been established.We conducted a randomised crossover trial in 35 healthy adults (age 40.0±15.5 years, 51% female) to compare DLNO (primary endpoint) between MasterScreen™ (Vyaire Medical, USA) and HypAir (Medisoft, Belgium) devices during a single visit under controlled conditions. Linear mixed models were used adjusting for device and period as fixed effects and random intercept for each participant.Difference in DLNO between HypAir and MasterScreen was 24.0 mL·min−1·mmHg−1 (95% CI 21.7 to 26.3). There was no difference in DLCO (−0.03 mL·min−1·mmHg−1, 95% CI −0.57 to 0.12) between devices while alveolar volume (VA) was higher on HypAir compared to MasterScreen™ (0.48 L, 95% CI 0.45 to 0.52). Disparity in the estimation of VA and the rate of NO uptake (KNO=DLNO/VA) could explain the discrepancy in DLNO between devices. Disparity in the estimation of VA and the rate of CO uptake (KCO=DLCO/VA) per unit of VA offset each other resulting in negligible discrepancy in DLCO between devices. Differences in methods of expiratory gas sampling and sensor specifications between devices likely explain these observations.These findings have important implications for derivation of DLNO reference values and comparison of results across studies. Until this issue is resolved reference values, established on the respective devices, should be used for test interpretation.

Download Full-text

Diffusing capacity dependent on lung volume and age in normal subjects

Journal of Applied Physiology ◽

10.1152/jappl.1994.76.6.2356 ◽

1994 ◽

Vol 76 (6) ◽

pp. 2356-2363 ◽

Cited By ~ 64

Author(s):

H. Stam ◽

V. Hrachovina ◽

T. Stijnen ◽

A. Versprille

Keyword(s):

Reference Values ◽

Linear Method ◽

Hemoglobin Concentration ◽

Normal Subjects ◽

Random Coefficients ◽

Diffusing Capacity ◽

Alveolar Volume ◽

Lung Volumes ◽

Conversion Method ◽

Older Subjects

In this study we determined reference values of total diffusing capacity of carbon monoxide (DLCO) and DLCO per liter alveolar volume (DLCO/VA) at total lung capacity (TLC) and at lung volumes below TLC in sitting position. In 55 healthy nonsmoking volunteers (20–85 yr old), we determined reference values at TLC level in which age was the only parameter. In a subgroup (n = 16) these references did not change by correction for normal variability in hemoglobin concentration. In all volunteers DLCO decreased and DLCO/VA increased with decreasing VA. The increase in DLCO/VA was linear and less in older subjects. We derived equations to calculate reference values of DLCO/VA for lung volumes at and below TLC with two methods: 1) “random coefficients linear” model, which calculates the reference values directly, and 2) a conversion method, which calculates DLCO/VA for lower VA levels from reference values at TLC. An advantage of the conversion method is the suitability of DLCO/VA reference values at TLC of other populations. A disadvantage is the greater standard deviation of these reference values compared with those obtained by the random coefficients linear method. DLCO can be found by multiplying DLCO/VA with VA.

Download Full-text

Reference values of pulmonary diffusing capacity for nitric oxide in an adult population

Nitric Oxide ◽

10.1016/j.niox.2007.10.002 ◽

2008 ◽

Vol 18 (1) ◽

pp. 70-79 ◽

Cited By ~ 45

Author(s):

Gerald S. Zavorsky ◽

Jiguo Cao ◽

Juan M. Murias

Keyword(s):

Nitric Oxide ◽

Reference Values ◽

Adult Population ◽

Diffusing Capacity ◽

Pulmonary Diffusing Capacity

Download Full-text

Transfer factor (diffusing capacity) standardized for alveolar volume: validation, reference values and applications of a new linear model to replace KCO (TL/VA)

CrossRef Listing of Deleted DOIs ◽

10.1183/09031936.96.09061269 ◽

1996 ◽

Vol 9 (6) ◽

pp. 1269-1277 ◽

Cited By ~ 30

Author(s):

D.J. Chinn ◽

J.E. Cotes ◽

R. Flowers ◽

A-M. Marks ◽

J.W. Reed

Keyword(s):

Linear Model ◽

Reference Values ◽

Transfer Factor ◽

Diffusing Capacity ◽

Alveolar Volume

Download Full-text

Assessing the applicability of the new Global Lung Function Initiative reference values for the diffusing capacity of the lung for carbon monoxide in a large population set

PLoS ONE ◽

10.1371/journal.pone.0245434 ◽

2021 ◽

Vol 16 (1) ◽

pp. e0245434

Author(s):

Pierre-Marie Wardyn ◽

Virginie de Broucker ◽

Cécile Chenivesse ◽

Annie Sobaszek ◽

Richard Van Bulck ◽

...

Keyword(s):

Carbon Monoxide ◽

Lung Function ◽

Reference Values ◽

Lung Diseases ◽

Normal Population ◽

Large Population ◽

Interstitial Lung Diseases ◽

Diffusing Capacity ◽

Alveolar Volume ◽

Z Scores

Background The single-breath diffusing capacity of the lung for carbon monoxide (DLCO) interpretation needs the comparison of measured values to reference values. In 2017, the Global Lung Function Initiative published new reference values (GLI-2017) for DLCO, alveolar volume (VA) and transfer coefficient of the lung for carbon monoxide (KCO). We aimed to assess the applicability of GLI-2017 reference values for DLCO on a large population by comparing them to the European Community of Steel and Coal equations of 1993 (ECSC-93) widely used. Methods In this retrospective study, spirometric indices, total lung capacity, DLCO, VA and KCO were measured in adults classified in 5 groups (controls, asthma, chronic bronchitis, cystic fibrosis, and interstitial lung diseases (ILD)). Statistical analysis comparing the 2 equations sets were stratified by sex. Results 4180 tests were included. GLI-2017 z-scores of the 3 DLCO indices of the controls (n = 150) are nearer to 0 (expected value in a normal population) than ECSC-93 z-scores. All groups combined, in both genders, DLCO GLI-2017 z-scores and %predicted are significantly higher than ECSC z-scores and %predicted. In the ILD group, differences between the 2 equation sets depend on the DLCO impairment severity: GLI-2017 z-scores are higher than ECSC z-scores in patients with no or “mild” decrease in DLCO, but are lower in “moderate” or “severe” decrease. Conclusion GLI-2017 reference values for DLCO are more suitable to our population and influence the diagnostic criteria and severity definition of several lung diseases.

Download Full-text

The need for race-specific reference equations for pulmonary diffusing capacity for nitric oxide

BMC Pulmonary Medicine ◽

10.1186/s12890-021-01591-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Gerald Stanley Zavorsky ◽

Ahmad Saleh Almamary ◽

Mobarak Khalid Alqahtani ◽

Shi Huh Samuel Shan ◽

Douglas Shawn Gardenhire

Keyword(s):

Nitric Oxide ◽

Racial Differences ◽

Breath Hold ◽

Specific Reference ◽

Regression Equations ◽

Diffusing Capacity ◽

Alveolar Volume ◽

Pulmonary Diffusing Capacity ◽

Pilot Data ◽

Reference Equations

Abstract Background Few reference equations exist for healthy adults of various races for pulmonary diffusing capacity for nitric oxide (DLNO). The purpose of this study was to collect pilot data to demonstrate that race-specific reference equations are needed for DLNO. Methods African Americans (blacks) were chosen as the comparative racial group. In 2016, a total of 59 healthy black subjects (27 males and 32 females) were recruited to perform a full battery of pulmonary function tests. In the development of DLNO reference equations, a white reference sample (randomly drawn from a population) matched to the black sample for sex, age, and height was used. Multiple linear regression equations for DLNO, alveolar volume (VA), and pulmonary diffusing capacity for carbon monoxide (DLCO) using a 5–6 s breath-hold were developed. Results Our models demonstrated that sex, age2, race, and height explained 71% of the variance in DLNO and DLCO, with race accounting for approximately 5–10% of the total variance. After normalizing for sex, age2, and height, blacks had a 12.4 and 3.9 mL/min/mmHg lower DLNO and DLCO, respectively, compared to whites. The lower diffusing capacity values in blacks are due, in part, to their 0.6 L lower VA (controlling for sex and height). Conclusion The results of this pilot data reveal small but important and statistically significant racial differences in DLNO and DLCO in adults. Future reference equations should account for racial differences. If these differences are not accounted for, then the risk of falsely diagnosing lung disease increase in blacks when using reference equations for whites.

Download Full-text

Ventilation Heterogeneity in Asthma and COPD: The Value of the Poorly Communicating Fraction as the Ratio of Total Lung Capacity to Alveolar Volume

Respiration ◽

10.1159/000513954 ◽

2021 ◽

pp. 1-7

Author(s):

Roberta Pisi ◽

Marina Aiello ◽

Luigino Calzetta ◽

Annalisa Frizzelli ◽

Veronica Alfieri ◽

...

Keyword(s):

Total Lung Capacity ◽

Airflow Obstruction ◽

Diffusing Capacity ◽

Body Plethysmography ◽

Alveolar Volume ◽

Asthmatic Patients ◽

Lung Capacity ◽

Copd Patients ◽

Ventilation Heterogeneity ◽

Patient Groups

Background: The ventilation heterogeneity (VH) is reliably assessed by the multiple-breath nitrogen washout (MBNW), which provides indices of conductive (Scond) and acinar (Sacin) VH as well as the lung clearance index (LCI), an index of global VH. VH can be alternatively measured by the poorly communicating fraction (PCF), that is, the ratio of total lung capacity by body plethysmography to alveolar volume from the single-breath lung diffusing capacity measurement. Objectives: Our objective was to assess VH by PCF and MBNW in patients with asthma and with COPD and to compare PCF and MBNW parameters in both patient groups. Method: We studied 35 asthmatic patients and 45 patients with COPD. Each patient performed spirometry, body plethysmography, diffusing capacity, and MBNW test. Results: Compared to COPD patients, asthmatics showed a significantly lesser degree of airflow obstruction and lung hyperinflation. In asthmatic patients, both PCF and LCI and Sacin values were significantly lower than the corresponding ones of COPD patients. In addition, in both patient groups, PCF showed a positive correlation with LCI (p < 0.05) and Sacin (p < 0.05), but not with Scond. Lastly, COPD patients with PCF >30% were highly likely to have a value ≥2 of the mMRC dyspnea scale. Conclusions: These results showed that PCF, a readily measure derived from routine pulmonary function testing, can provide a comprehensive measure of both global and acinar VH in asthma and in COPD patients and can be considered as a comparable tool to the well-established MBNW technique.

Download Full-text

The effect of conductive ventilation heterogeneity on diffusing capacity measurement

Journal of Applied Physiology ◽

10.1152/japplphysiol.00917.2007 ◽

2008 ◽

Vol 104 (4) ◽

pp. 1094-1100 ◽

Cited By ~ 9

Author(s):

Sylvia Verbanck ◽

Daniel Schuermans ◽

Sophie Van Malderen ◽

Walter Vincken ◽

Bruce Thompson

Keyword(s):

Carbon Monoxide ◽

Vital Capacity ◽

Experimental Situation ◽

Normal Subjects ◽

Diffusing Capacity ◽

Capacity Measurement ◽

Alveolar Volume ◽

Estimation Errors ◽

Single Breath ◽

Ventilation Heterogeneity

It has long been assumed that the ventilation heterogeneity associated with lung disease could, in itself, affect the measurement of carbon monoxide transfer factor. The aim of this study was to investigate the potential estimation errors of carbon monoxide diffusing capacity (DlCO) measurement that are specifically due to conductive ventilation heterogeneity, i.e., due to a combination of ventilation heterogeneity and flow asynchrony between lung units larger than acini. We induced conductive airway ventilation heterogeneity in 35 never-smoker normal subjects by histamine provocation and related the resulting changes in conductive ventilation heterogeneity (derived from the multiple-breath washout test) to corresponding changes in diffusing capacity, alveolar volume, and inspired vital capacity (derived from the single-breath DlCO method). Average conductive ventilation heterogeneity doubled ( P < 0.001), whereas DlCO decreased by 6% ( P < 0.001), with no correlation between individual data ( P > 0.1). Average inspired vital capacity and alveolar volume both decreased significantly by, respectively, 6 and 3%, and the individual changes in alveolar volume and in conductive ventilation heterogeneity were correlated ( r = −0.46; P = 0.006). These findings can be brought in agreement with recent modeling work, where specific ventilation heterogeneity resulting from different distributions of either inspired volume or end-expiratory lung volume have been shown to affect DlCO estimation errors in opposite ways. Even in the presence of flow asynchrony, these errors appear to largely cancel out in our experimental situation of histamine-induced conductive ventilation heterogeneity. Finally, we also predicted which alternative combination of specific ventilation heterogeneity and flow asynchrony could affect DlCO estimate in a more substantial fashion in diseased lungs, irrespective of any diffusion-dependent effects.

Download Full-text