Global Lung Function Initiative Reference Research Articles

Assessment of hyperinflation: comparison of GLI and ECSC lung volume reference equations

BackgroundAssessment of static hyperinflation severity is crucial to identify COPD patients eligible for lung volume reduction. The current recommendation of residual volume (RV)≥175% predicted may need reconsideration due to potential differences between the Global Lung Function Initiative (GLI) and the European Community for Steel and Coal (ECSC) reference equations for RV and concerns about using %predicted.MethodsWe compared the RV reference values derived from the GLI and ECSC using mathematical simulated data and used a receiver operating characteristic curve to establish a new GLI-derived z-score cut-off for RV using body plethysmography data of severe COPD patients.ResultsThe GLI reference equation for RV consistently yields a lower predicted RV for individuals with an average or below average height (females ≤163 cm and males ≤177 cm). Our clinical cohort consisted of 1011 patients with COPD (38% GOLD stage III and 59% stage IV). In this cohort, a GLI-derived RV z-score of ≥2.9 could accurately replace the ECSC-derived 175% predicted cut-off and for 200% predicted, a z-score of ≥3.5 was established.ConclusionThere are substantial differences in predicted RV values between the GLI and ECSC, with the GLI generally yielding a lower predicted RV in the majority of individuals. A GLI-derived RV z-score of ≥2.9 could be used to replace the currently used cut-off of ≥175% predicted to identify potential lung volume reduction candidates.

ERS technical standard: Global Lung Function Initiative reference values for exhaled nitric oxide fraction (F ENO50 ).

Elevated exhaled nitric oxide fraction at a flow rate of 50 mL·s-1 (F ENO50 ) is an important indicator of T-helper 2-driven airway inflammation and may aid clinicians in the diagnosis and monitoring of asthma. This study aimed to derive Global Lung Function Initiative reference equations and the upper limit of normal for F ENO50 . Available individual F ENO50 data were collated and harmonised using consensus-derived variables and definitions. Data collected from individuals who met the harmonised definition of "healthy" were analysed using the generalised additive models of location, scale and shape (GAMLSS) technique. Data were retrospectively collated from 34 782 individuals from 34 sites in 15 countries, of whom 8022 met the definition of healthy (19 sites, 11 countries). Overall, height, age and sex only explained 12% of the between-subject variability of F ENO50 (R2=0.12). F ENO device was neccessary as a predictor of F ENO50 , such that the healthy range of values and the upper limit of normal varied depending on which device was used. The range of F ENO50 values observed in healthy individuals was also very wide, and the heterogeneity was partially explained by the device used. When analysing a subset of data in which F ENO50 was measured using the same device and a stricter definition of health (n=1027), between-site heterogeneity remained. Available F ENO50 data collected from different sites using different protocols and devices were too variable to develop a single all-age reference equation. Further standardisation of F ENO devices and measurement are required before population reference values might be derived.

Periodontitis is associated with airflow obstruction in the Malmö Offspring Dental Study.

To investigate the association between periodontitis and lung function in the Malmö Offspring Dental Study. In all 1001 individuals (49.9% female, mean age: 44.6) from Malmö Offspring Dental Study were included. Periodontitis was assessed by a full-mouth examination protocol including bleeding on probing and classified according to the American Academy of Periodontology/Center for Disease Control definitions. Forced expiratory volume in 1 s (FEV1 ) and forced vital capacity (FVC) were expressed as absolute values and %predicted according to Global Lung Function Initiative reference values. FEV1 , FVC and FEV1 /FVC were analysed in relation to periodontal status using linear regression. Severe periodontitis was found in 7% of the population. Adjusted regression models showed significant associations between lung function and severe periodontitis with 2.1 unit lower FEV1 /FVC ratio (95% CI: -3.91, -0.23) and odds ratio (adjusted) of 2.56 (95% CI: 1.40, 4.75, p = .003) for airflow obstruction (FEV1 /FVC less than the lower limit of normal) if having severe periodontitis. Lower values of %predicted FEV1 and %predicted FVC, but not FEV1 /FVC, were found in individuals with >25% bleeding on probing. Severe periodontitis was associated with lower FEV1 /FVC ratio and airflow obstruction in the present cohort. More large-scale prospective studies and intervention studies are required for a comprehensive evaluation.

Development and validation of predictive equations for spirometry in Portuguese children.

There are no data on lung function reference values for Portuguese children, and the contribution from the Portuguese data set in the Global Lung Function Initiative (GLI) is scant. We aimed to estimate new up-to-date reference values for Portuguese children by fitting a multivariable regression model to a general population sample. Further, we intended to assess the external validity of the obtained reference values and to compare them to the GLI reference values. A random sample of 858 children from 20 primary schools were screened by health questionnaire, physical examination, and spirometry. Spirometric parameters recorded were FVC, FEV1, and FEF25-75. Multiple regression models were used to derive reference equations. Overall, 481 children, aged between 7 and 12 years, 267 boys (55.5%), were included. Boys had higher values for FVC and FEV1 than girls (P< .05). The strongest correlation was found for FVC with height (r= 0.71 for boys and 0.70 for girls), while the lowest correlation was observed in both sexes for FEF25-75 with age (r= 0.23). Height was the most significant predictor of FVC, FEV1, and FEF25-75 in our models. Weight and body mass index were not significant predictors for boys but had a significant effect on girls' equations for all spirometry parameters. Compared to obtained reference equations with GLI, they performed better for FVC in boys, FEV1 in girls, and FEF25-75 in both boys and girls. We offer up-to-date reference values of spirometry for Portuguese children that can be used in clinical practice and research.

Comparison of different reference values for lung function: implications of inconsistent use among centers

BackgroundFor interpretation of pulmonary function tests (PFTs), reference values based on sex, age, height and ethnicity are needed. In Norway, the European Coal and Steel Community (ECSC) reference values remain widely used, in spite of recommendations to implement the more recent Global Lung Function Initiative (GLI) reference values.ObjectiveTo assess the effects of changing from ECSC to GLI reference values for spirometry, DLCO and static lung volumes, using a clinical cohort of adults with a broad range in age and lung function.MethodsPFTs from 577 adults (18–85 years, 45% females) included in recent clinical studies were used to compare ECSC and GLI reference values for FVC, FEV1, DLCO, TLC and RV. Percent predicted and lower limit of normal (LLN) were calculated. Bland-Altman plots were used to assess agreement between GLI and ECSC % predicted values.ResultsIn both sexes, GLI % predicted values were lower for FVC and FEV1, and higher for DLCO and RV, compared to ECSC. The disagreement was most pronounced in females, with mean (SD) difference 15 (5) percent points (pp) for DLCO and 17 (9) pp for RV (p < 0.001). With GLI, DLCO was below LLN in 23% of the females, with ECSC in 49% of the females.ConclusionsThe observed differences between GLI and ECSC reference values are likely to entail significant consequences with respect to criteria for diagnostics and treatment, health care benefits and inclusion in clinical trials. To ensure equity of care, the same reference values should be consistently implemented across centers nationwide.

Validation of the Global Lung Function Initiative 2012 Spirometry Reference Values in a Healthy Italian Working Population.

Several studies showed important differences in the interpretation of spirometry based on different reference values, in particular by comparing European Respiratory Society (ERS) 1993 and Global Lung Function Initiative (GLI) 2012. The validation of new reference values in local populations is essential before they can be used in an appropriate manner. This study aimed to investigate the fit of GLI reference values in a healthy Italian working population. Spirometry data were collected in 1355 workers during their health surveillance medical examination conducted for exposure to chemical and biological risk factors. A single portable spirometer that met the ATS/ERS recommendations for occupational testing was used and calibrated daily. Average z-score were -0.13 (with a median of -0.17), -0.25 (with a median of -0.24), and 0.18 (with a median of 0.17) for FEV1, FVC, and FEV1/FVC ratio, respectively. Considering only the normal-weighted workers, the average z-scores were -0.07 (with a median of -0.16), -0.15 (with a median of -0.16), and 0.07 (with a median of 0.02) for FEV1, FVC, and FEV1/FVC ratio, respectively. GLI 2012 reference values fit the Italian data satisfactorily, resulting as more accurate than ERS 1993, especially in women, normal-weighted subjects, aged 30-50 years, and for height &lt; 165 cm.

Pulmonary Function before and after Hematopoietic Cell Transplant in People Living with Sickle Cell Disease

Background People living with sickle cell disease (SCD) have increasing access to hematopoietic cell transplant (HCT). However, there are insufficient data on the effects of HCT, and other curative therapies, on pulmonary function in this population. Unlike patients with cancer, individuals with SCD have a lifelong genetic condition with recurring vaso-occlusive events and inflammatory processes known to cause significant pulmonary morbidity. Therefore, studies that report lung function after transplant in cancer survivors may not apply to individuals with SCD. Indeed, data are needed to evaluate the late lung health effects of HSCT in the SCD population. We hypothesized that percent predicted forced expiratory volume in one second (FEV-1), a pulmonary function outcome measure which has been found to be associated with early death in SCD, would be stable one-year post HCT. Methods People living with SCD who underwent first-time HCT, including HLA-matched sibling and haploidentical HCT, at the NIH Clinical Center from 2004 to 2019 with Hgb SS, SC, Sbeta+ thalassemia, and Sbeta0 thalassemia with available pulmonary function data were included in this study. Global Lung Function Initiative reference equations were used, and descriptive statistics were calculated for FEV-1, forced vital capacity (FVC), FEV-1/FVC, total lung capacity (TLC), and diffusing capacity of the lungs for carbon monoxide (DLCO) for patients with pre- and one-year post-HCT. Generalized estimating equations were employed to evaluate inter-individual changes in percent-predicted FEV-1 pre- and one-year post-HCT. Results Seventy-seven people living with SCD (HgbSS n=69 [90%], HgbSC 2 [3%], HbSbeta+ 2 [3%], HbSbeta0 4 [5%]) underwent non-myeloablative HCT (HLA-matched sibling n=53 [69%%] and haplo-identical n=24 [31%]) . Of these, 42 (42%) were female with median (25th, 75th percentile) age 31.0 (24.0, 37.0) years; there were four patients less than 18 years old. Median (25th, 75th) percent predicted forced expiratory volume in one second (FEV-1) was 68.4% (61.3%, 79.1%) at baseline and 69.9% (60.5%, 78.2%) one-year post-HCT; baseline median (25th, 75th) percent predicted DLCO was 48.0 (43.0, 54.0) and 48.0 (45.0, 56.0) one-year post-HCT. There was no significant change in percent predicted FEV-1 (0.88 (0.78, 2.55; p=0.30) one-year post-HCT. Conclusion Pulmonary function remained stable in people living with SCD one-year post-HCT. Allogeneic HCT for SCD may cease the cycle of vaso-occlusive injury to the lung tissue and airway system and prevent continued damage. In addition, it is possible that without the ongoing injury, lung healing may also occur over time. Multicenter studies with longer follow-up are needed to evaluate the long-term lung health effects of HCT on individuals with SCD. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Influences of Two FEV1 Reference Equations (GLI-2012 and GIRH-2017) on Airflow Limitation Classification Among COPD Patients.

ObjectiveTo explore the clinical effects of different forced expiratory volume in 1s (FEV1) reference equations on chronic obstructive pulmonary disease (COPD) airflow limitation (AFL) classification.MethodsWe conducted a COPD screening program for residents over 40 years old from 2019 to 2021. All residents received the COPD screening questionnaire (COPD-SQ) and spirometry. Postbronchodilator FEV1/FVC (forced vital capacity) <0.7 was used as the diagnostic criterion of COPD and two reference equations of FEV1 predicted values were used for AFL severity classification: the European Respiratory Society Global Lung Function Initiative reference equation in 2012 (GLI-2012) and the Guangzhou Institute of Respiratory Health reference equation in 2017 (GIRH-2017). Clinical characteristics of patients in GOLD (Global Initiative for Chronic Obstructive Pulmonary Disease) 1–4 grades classified by the two reference equations were compared.ResultsAmong 3524 participants, 659 subjects obtained a COPD-SQ score of 16 or more and 743 participants were found to have AFL. The COPD-SQ showed high sensitivity (59%) and specificity (91%) in primary COPD screening. Great differences in COPD severity classification were found when applying the two equations (p < 0.001). Compared with GIRH-2017, patients with AFL classified by GLI-2012 equations were significantly severer. The relationship between symptom scores, acute exacerbation (AE) history distributions and COPD severities classified by the two equations showed a consistent trend of positive but weak correlation. Group A, B, C and D existed in all GOLD 1 to 3 COPD patients, but in GOLD 4, only Groups B and D existed. However, no clear significant differences were found in symptoms, AE risk assessments, risk factors exposure and even the combined ABCD grouping under the two equations.ConclusionThere were significant differences in COPD AFL severity classification with GLI-2012 and GIRH-2017 FEV1 reference equations. But these severity estimation differences did not affect symptoms, AE risk assessments and ABCD grouping of patients at all GOLD grades.

Determinants of lung function across childhood in the Severe Asthma Research Program (SARP) 3

Children with asthma are at risk for low lung function extending into adulthood, but understanding of clinical predictors is incomplete. We sought to determine phenotypic factors associated with FEV1 throughout childhood in the Severe Asthma Research Program 3 pediatric cohort. Lung function was measured at baseline and annually. Multivariate linear mixed-effects models were constructed to assess the effect of baseline and time-varying predictors of prebronchodilator FEV1 at each assessment for up to 6 years. All models were adjusted for age, predicted FEV1 by Global Lung Function Initiative reference equations, race, sex, and height. Secondary outcomes included postbronchodilator FEV1 and prebronchodilator FEV1/forced vital capacity. A total of 862 spirometry assessments were performed for 188 participants. Factors associated with FEV1 include baseline Feno (B, -49 mL/log2 PPB; 95% CI, -92 to -6), response to a characterizing dose of triamcinolone acetonide (B, -8.4 mL/1% change FEV1 posttriamcinolone; 95% CI, -12.3 to -4.5), and maximal bronchodilator reversibility (B, -27 mL/1% change postbronchodilator FEV1; 95% CI, -37 to -16). Annually assessed time-varying factors of age, obesity, and exacerbation frequency predicted FEV1 over time. Notably, there was a significant age and sex interaction. Among girls, there was no exacerbation effect. For boys, however, moderate (1-2) exacerbation frequency in the previous 12 months was associated with -20 mL (95% CI, -39 to -2) FEV1 at each successive year. High exacerbation frequency (≥3) 12 to 24 months before assessment was associated with -34 mL (95% CI, -61 to -7) FEV1 at each successive year. In children with severe and nonsevere asthma, several clinically relevant factors predict FEV1 over time. Boys with recurrent exacerbations are at high risk of lower FEV1 through childhood.

Evaluation of the Global Lung Function Initiative reference equations in Belgian adults

BackgroundOver the past decade, the Global Lung Function Initiative (GLI) Network has published all-age reference equations on spirometry, diffusing capacity of the lung for carbon monoxide (DLCO) and lung volumes.MethodsWe evaluated the appropriateness of these equations in an adult Caucasian population. Retrospective lung function data on subjects who performed tests prior to a diagnostic sleep investigation were analysed. From the medical records, lung healthy, lifetime nonsmoking, nonobese subjects were selected, resulting in a population of 1311 subjects (68% male; age range 18–88 years).ResultsMultiple linear regression analysis revealed that lung function z-scores did not differ between subjects with and without sleep apnoea but did depend on height and age. The average forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) z-score was 0 but exhibited an inverse association with height in both sexes (p<0.01). Values of FEV1 and FVC in both sexes were larger than predicted (mean±sd z-score +0.30±0.96 or 104±13% pred; p<0.01). Overall, static lung volumes and DLCO were adequately predicted. However, DLCO z-scores were inversely associated with height in males and age in females (p<0.01). For all lung function indices, the observed scatter was reduced compared with the prediction. Therefore, for all indices <5% of the data were below the GLI-proposed lower limit of normal (LLN) threshold.ConclusionGLI reference equations provide an adequate fit in Belgian adults. However, the GLI-proposed LLN is too low for our Antwerp population, resulting in underdiagnosis of disease. Furthermore, airway obstruction and diffusion disorders might be misclassified due to height and age associations.

Respiratory symptoms and lung function among inmates in a Nigerian prison: a cross sectional study

BackgroundPrisoners in low- and middle-income countries are vulnerable to poor lung health from multiple adverse conditions confronted within the prison such as overcrowding, poor ventilation and exposure to second hand smoke. Evidence for poor lung health in this disadvantaged group is needed to inform policy on prison conditions in this region. We assessed the respiratory symptoms and lung function measured by spirometry among prisoners in Enugu, Nigeria and explored the associations between them.MethodsThis was a cross‑sectional study among prison inmates aged 16–76 years. We assessed frequency of respiratory symptoms in the preceding one-year, previous respiratory diagnosis, tobacco smoking status and spirometry. The relationships between respiratory symptoms, smoking status and spirometry pattern were determined using the Chi‑square test.ResultsOf 245 participants, 170 (69.4%) reported at least one respiratory symptom. In all, 214 (87.3%) performed spirometry and 173 (80.8%) had good quality spirometry tests. Using the Global Lung Function Initiative (GLI) predicted values for ‘African Americans’, spirometry results were abnormal in 41 (23.7%) of the participants and when the GLI reference values for ‘Other’ ethnic groups was applied, 78 (45.1%) had abnormal results. Restrictive impairment was most common occurring in 21 (12.1%) and 59 (34.1%) respectively based on the two reference values, and obstructive pattern was found in 18 (10.4%) and 13 (7.5%) respectively. There was no significant association between abnormal spirometry pattern and presence of respiratory symptoms or smoking status. No previous diagnosis for asthma, or bronchitis/chronic obstructive pulmonary disease (COPD) had been made in any of the participants.ConclusionsWe reported high rates of respiratory symptoms and abnormal lung function with under-diagnosis of chronic respiratory diseases among inmates in Enugu prison. The restrictive abnormalities based on GLI equations remain unexplained. There is need for improvement in prison facilities that promote lung health and enhanced access to diagnosis and treatment of respiratory non-communicable disease.

Restrictive spirometry versus restrictive lung function using the GLI reference values.

BackgroundRestrictive lung function may indicate various underlying diseases. The aim of this study was to evaluate the accuracy of different restrictive spirometry patterns (RSPs) to identify restrictive lung function (total lung capacity [TLC] < lower limit of normal [LLN]) according to reference values by the Global Lung Function Initiative (GLI) in a wide age‐ranged, general population sample.MethodsA general population sample (n = 607, age 23–72 years, smokers 18.8%) with proper dynamic spirometry and TLC measurements, was included. Accuracy of two main categories of RSP to identify TLC < LLN were evaluated: traditional RSPs (definition 1: FVC < 80% of predicted and FEV1/FVC ≥ 0.7 and definition 2: FVC < LLN and FEV1/FVC ≥ LLN) and RSPs defined by Youden's method (definition 3: FVC < 85.5% of predicted and FEV1/FVC ≥ LLN and definition 4: FVC Z‐score < −1.0 and FEV1/FVC ≥ LLN).ResultsThe prevalence of restrictive lung function (TLC < LLN) was 5.3%. The most accurate cut‐offs for FVC to identify TLC < LLN were 85.5% for FVC% of predicted, and −1.0 for FVC Z‐score. The traditional RSP definitions 1 and 2 had higher specificity (95.0% and 96.9%) but substantially lower sensitivity compared to RSP definitions 3 and 4.ConclusionBased on the GLI reference values, the RSP definition FVC < LLN and FEV1/FVC ≥ LLN yielded the highest specificity and may appropriately be used to rule out restrictive lung function. The RSP definition with the most favourable trade‐off between sensitivity and specificity, FVC < 85.5% of predicted and FEV1/FVC ≥ LLN, may serve as an alternative with higher sensitivity for screening.

Pulmonary function of healthy Korean children from three independent birth cohorts: Validation of the Global Lung Function Initiative 2012 equation

Global Lung Function Initiative (GLI) 2012 equations were developed to resolve the age-related disparity in interpreting spirometry results. Local validation of the equation is needed, especially in Northeast Asian children. This study evaluated the GLI equation in Korean children. Spirometry indices (FEV1, FVC, FEV1/FVC, and FEF25%-75%) and clinical information were gathered from three population-based birth cohorts. Predicted GLI reference values and z scores of spirometry results were calculated for 1239 healthy children. The mean, standard deviation of z scores were compared with the expected 0 and 1. Probabilities of falling below the lower limit of normal (LLN) (z score: -1.64) were compared with the expected value 5%. GLI z scores were assessed according to low (<-2), normal (≥-2 and ≤2), and high (>2) BMI z score groups. Mean z scores significantly differed from 0 for FEV1/FVC in males (mean [95% confidence interval]: 0.18 [0.08, 0.27]) and forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) in females (-0.23 [-0.31, -0.15] and -0.26 [-0.36, -0.16], respectively). The standard deviation was larger than 1 for all variables in males and FVC and FEV1/FVC in females. The probability of falling below the LLN was significantly larger than 5% for FEV1 (12.13% [9.64, 14.77]), FVC (15.86% [13.06, 18.81]), and forced expiratory flow at 25%-75% of forced vital capacity (FEF25%-75%) (7.31% [5.29, 9.49]) in males and FVC (11.91% [9.40, 14.60]) in females. FEV1 and FVC z scores increased across low to high body mass index (BMI) groups, and FEV1/FVC decreased from low to high BMI groups. GLI equations marginally differ from real-world values, which should be considered by pulmonologists in practice or research.

Reduced exercise tolerance in mild chronic obstructive pulmonary disease: The contribution of combined abnormalities of diffusing capacity for carbon monoxide and ventilatory efficiency

The combination of both reduced resting diffusing capacity of the lung for carbon monoxide (DLCO ) and ventilatory efficiency (increased ventilatory requirement for CO2 clearance [V˙E /V˙CO2 ]) has been linked to exertional dyspnoea and exercise intolerance in chronic obstructive pulmonary disease (COPD) but the underlying mechanisms are poorly understood. The current study examined if low resting DLCO and higher exercise ventilatory requirements were associated with earlier critical dynamic mechanical constraints, dyspnoea and exercise limitation in patients with mild COPD. In this retrospective analysis, we compared V˙E /V˙CO2 , dynamic inspiratory reserve volume (IRV), dyspnoea and exercise capacity in groups of patients with Global Initiative for Chronic Obstructive Lung Disease stage 1 COPD with (1) a resting DLCO at or greater than the lower limit of normal (≥LLN; Global Lung Function Initiative reference equations [n=44]) or (2) below the <LLN (n=33), and age- and sex-matched healthy controls (n=81). Spirometry and resting lung volumes were similar in the two COPD groups. During exercise, V˙E /V˙CO2 (nadir and slope) was consistently higher in the DLCO  < LLN compared with the other groups (all p < 0.05). The DLCO  < LLN group had lower IRV and greater dyspnoea intensity at standardized submaximal work rates and lower peak work rate and oxygen uptake than the other two groups (all p < 0.05). Reduced exercise capacity in patients with DLCO  < LLN was related to higher ventilatory requirements, a faster rate of decline in dynamic IRV and greater dyspnoea during exercise. These simple measurements should be considered for the clinical evaluation of unexplained exercise intolerance in individuals with ostensibly mild COPD.

Hb-adjusted DLCO with GLI reference predicts long-term survival after HSCT in children.

This study aimed to evaluate the pretransplant diffusing capacity as a predictor of outcomes in pediatric allogeneic hematopoietic stem cell transplantation (allo-HSCT). Retrospective cohort study of 176 children followed outcomes for 5 years after allo-HSCT. We conducted an analysis of PFTs include spirometry, body plethysmography, and diffusing capacity prior to allo-HSCT. We analyzed the probabilities of overall survival (OS), disease-related mortality (DRM), and non-relapse mortality (NRM). Of all carbon monoxide diffusing capacity (DLCO) parameters obtained using the Global Lung Function Initiative (GLI)-2017, univariate analysis showed that the grade 3, 4 of DLCOadj and Category III, IV of LFS significantly increase NRM (p = 0.003 and p = 0.008). Multivariate analysis indicated that a significant increase in the risk of NRM is associated with grades 3, 4 DLCOadj (hazard ratio [HR] = 4.90, p = 0.020). Kaplan-Meier analyses showed that a significant stepwise increase in NRM was observed with both worse pretransplant DLCOadj grades and LFS categories (p < 0.001 and p = 0.003). A compromised pretransplant diffusing capacity and a high LFS significantly increase the risk of NRM. Especially, DLCOadj before transplantation can be used as an important predictor of NRM after allo-HSCT in children with malignancy.

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

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. 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. 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. GLI-2017 reference values for DLCO are more suitable to our population and influence the diagnostic criteria and severity definition of several lung diseases.

The impact of changing to the Global Lung Function Initiative reference equations for transfer factor in paediatrics.

The Global Lung Function Initiative (GLI) all-age reference equations for carbon monoxide transfer factor were published in 2017 and endorsed by the European Respiratory Society and American Thoracic Society. In order to understand the impact of these new reference equations on the interpretation of results in children referred from haematology and oncology paediatric services, we retrospectively analysed transfer factor results from any paediatric patient referred from haematology/oncology in the period 2010–2018. We examined transfer factor of the lung for carbon monoxide (TLCO), transfer coefficient of the lung for carbon monoxide (KCO) and alveolar volume (VA) from 241 children (age range 7–18 years, 130 male). The predicted values from Rosenthal and GLI were plotted against height. The difference in interpretation of results was analysed by looking at the percentage of patients below the lower limit of normal for each parameter. Overall, the Rosenthal predicted values for TLCO were higher than those predicted by GLI. Predicted KCO using Rosenthal was higher in all observations. In contrast, the Rosenthal predicted VA was generally lower than the GLI value. The GLI predicted values for transfer factor show considerable differences compared with currently used paediatric UK reference values, differences that will have a significant impact on interpretation of results.

"Official ERS technical standards: Global Lung Function Initiative reference values for the carbon monoxide transfer factor for Caucasians." Sanja Stanojevic, Brian L. Graham, Brendan G. Cooper, Bruce R. Thompson, Kim W. Carter, Richard W. Francis and Graham L. Hall on behalf of the Global Lung Function Initiative T LCO working group. Eur Respir J 2017; 50: 1700010.

"Official ERS technical standards: Global Lung Function Initiative reference values for the carbon monoxide transfer factor for Caucasians." Sanja Stanojevic, Brian L. Graham, Brendan G. Cooper, Bruce R. Thompson, Kim W. Carter, Richard W. Francis and Graham L. Hall on behalf of the Global Lung Function Initiative T LCO working group. Eur Respir J 2017; 50: 1700010.

Assessment of Global Lung Function Initiative (GLI) reference equations for diffusing capacity in relation to respiratory burden in the Swedish CArdioPulmonary bioImage Study (SCAPIS).

The Global Lung Function Initiative (GLI) has recently published international reference values for diffusing capacity of the lung for carbon monoxide (D LCO). Lower limit of normal (LLN), i.e. the 5th percentile, usually defines impaired D LCO We examined if the GLI LLN for D LCO differs from the LLN in a Swedish population of healthy, never-smoking individuals and how any such differences affect identification of subjects with respiratory burden.Spirometry, D LCO, chest high-resolution computed tomography (HRCT) and questionnaires were obtained from the first 15 040 participants, aged 50-64 years, of the Swedish CArdioPulmonary bioImage Study (SCAPIS). Both GLI reference values and the lambda-mu-sigma (LMS) method were used to define the LLN in asymptomatic never-smokers without respiratory disease (n=4903, of which 2329 were women).Both the median and LLN for D LCO from SCAPIS were above the median and LLN from the GLI (p<0.05). The prevalence of D LCO <GLI LLN (and also <SCAPIS LLN) was 3.9%, while the prevalence of D LCO >GLI LLN but <SCAPIS LLN was 5.7%. Subjects with D LCO >GLI LLN but <SCAPIS LLN (n=860) had more emphysema (14.3% versus 4.5%, p<0.001), chronic airflow limitation (8.5% versus 3.9%, p<0.001) and chronic bronchitis (8.3% versus 4.4%, p<0.01) than subjects (n=13 600) with normal D LCO (>GLI LLN and >SCAPIS LLN). No differences were found with regard to physician-diagnosed asthma.The GLI LLN for D LCO is lower than the estimated LLN in healthy, never-smoking, middle-aged Swedish adults. Individuals with D LCO above the GLI LLN but below the SCAPIS LLN had, to a larger extent, an increased respiratory burden. This suggests clinical implications for choosing an adequate LLN for studied populations.

Changes in FEV1 over time in COPD and the importance of spirometry reference ranges: the devil is in the detail.

A discussion of two landmark papers highlighting the use of spirometry as a sensitive measure of the rate of decline in FEV1 in COPD, and the importance of using the Global Lung Function Initiative reference data http://bit.ly/2C0Nhqa