Global Lung Function Initiative Reference Research Articles

ERS technical standard: Global Lung Function Initiative reference values for multiple breath washout indices.

Multiple breath washout is a lung function test based on tidal breathing that assesses lung volume and ventilation distribution. The aim of this analysis was to use the Global Lung Function Initiative methodology to develop all-age reference equations for the multiple breath washout indices lung clearance index (LCI) and functional residual capacity (FRC). Multiple breath washout data from healthy individuals were collated from sites. Data were re-analysed using the latest software versions. Reference equations were derived using the lambda-mu-sigma (LMS) method using the generalised additive models of location shape and scale programme in R. The impact of equipment type, inert tracer gas, and equipment dead space volume on the derived reference ranges were investigated. Data from 23 sites (n=3647 test occasions) were submitted. Reference equations were derived from 1581 unique observations from participants between the ages of 2 and 81 years. Equipment type, inert tracer gas, and equipment dead space volume did not significantly affect the prediction equations for either LCI or FRC. Reference equations for LCI include age as the only predictor, whereas sex-specific reference equations for FRC included height and age. Global Lung Function Initiative reference equations for multiple breath washout variables provide a standard for reporting and interpretation of LCI and FRC.

Implications of the 2022 lung function update and GLI global reference equations among patients with interstitial lung disease

BackgroundLung function testing remains a cornerstone in the assessment and management of interstitial lung disease (ILD) patients. The clinical implications of the Global Lung function Initiative (GLI) reference equations and...

Implications of Global Lung Function Initiative Spirometry Reference Equations in Northeast Asian Patients With COPD

Accurate spirometry interpretation is critical in the diagnosis and management of chronic obstructive pulmonary disease (COPD). With increasing efforts for a unified approach by the Global Lung Function Initiative (GLI), this study evaluated the application of race-specific 2012-GLI and race-neutral 2022-GLI reference equations compared to Choi's reference equations, which is derived and widely used in South Korea, for spirometry interpretation in Northeast Asian patients with COPD. What are the effects of applying race-specific 2012-GLI, race-neutral 2022-GLI, and Choi's reference equations on the diagnosis, severity grade, and clinical outcome associations of COPD STUDY DESIGN AND METHODS: Serial spirometry data from the Korea COPD Subgroup Study (KOCOSS) consisting of 3,477 patients were utilized for re-analyses using 2012-GLI, 2022-GLI, and Choi's reference equations. The COPD diagnosis and severity categorization, associations with disease manifestations and health outcomes, and longitudinal trajectories of lung function were determined. Although there was strong concordance in COPD diagnosis comparing 2012-GLI, and 2022-GLI reference equations to Choi's reference equations, a notable portion of patients were reclassified to milder disease severity (17.0% and 23.4% for 2012-GLI and 2022-GLI reference equations, respectively). Relationships between FEV1 percent-predicted values calculated using 2012-GLI, 2022-GLI, and Choi's equations with clinical outcomes including dyspnea severity, exercise capacity, health-related quality of life, and frequency of exacerbations remain consistently significant. Similar annual decline rates of FEV1 and FVC percent-predicted were observed among the reference equations used, except for slower annual decline rate of FEV1 in Choi's equation compared to 2022-GLI race-neutral equation. Application of GLI reference equations for spirometry interpretation in Northeast Asian patients with COPD has potential implications on disease severity grade for clinical management and trial participation, and maintains consistent significant relationships with key disease outcomes.

Pulmonary Function after Nonmyeloablative Hematopoietic Cell Transplant for Sickle Cell Disease.

Rationale: Sickle cell disease (SCD) is a monogenetic condition with recurring vasoocclusive events causing lifelong pulmonary morbidity and mortality. There is increasing access to curative therapies, such as hematopoietic cell transplant (HCT), for people living with SCD. However, more information on pulmonary function in adults with SCD after HCT is needed to best guide decisions for HCT and post-HCT care. Objectives: To test the hypothesis that forced expiratory volume in 1 second (FEV1) and other pulmonary function testing (PFT) parameters remain stable 3 years after HCT. Methods: People living with SCD undergoing nonmyeloablative HCT in a prospective cohort at the NIH Clinical Center from 2004 to 2019 were evaluated for enrollment. Global Lung Function Initiative reference equations and descriptive statistics were calculated before HCT and annually for 3 years. Six-minute-walk distance (6MWD) testing was performed. Generalized estimating equations were employed to evaluate interindividual changes in PFT parameters and 6MWD. Results: Of 97 patients with SCD undergoing HCT, 41 (42%) were female with median (25th, 75th percentile) age 31.8 (24.8, 38.0) years. Each year of measurement included the following numbers of subjects available for analysis with PFTs: baseline (n = 97), Year 1 (n = 91), Year 2 (n = 72), and Year 3 (n = 55); and the following numbers of subjects available for analysis with 6MWD: baseline (n = 79), Year 1 (n = 73), Year 2 (n = 57), and Year 3 (n = 41). Pre-HCT FEV1 was median (25th, 75th percentile) 68.3% (61.3%, 80.3%) and 69.2% (60.8%, 77.7%) 3 years after HCT, and pre-HCT diffusing capacity of the lung for carbon monoxide (DlCO) was 60.5% (53.0%, 66.3%) and 64.6% (55.1%, 73.4%) 3 years after HCT. Generalized estimating equations estimated that DlCO percent predicted increased significantly by 3.7% (95% confidence interval, 1.0%, 6.3%), and the 6MWD significantly increased by 25.9 (6.6, 45.2) meters 3 years after HCT, whereas there was no significant change in percent predicted FEV1 or FVC compared with before HCT. Conclusions: Overall, PFT results remained stable and there was an improvement in DlCO and 6MWD in this predominantly adult cohort undergoing nonmyeloablative HCT for SCD. Allogeneic HCT for SCD may cease the cycle of vasoocclusive pulmonary injury and prevent continued damage. Multicenter studies are needed to evaluate the long-term lung health effects of HCT for SCD in adults and children.

Comparison of race-specific and race-neutral GLI spirometric reference equations with an Indian reference equation

BackgroundDespite the increasing popularity and use of Global Lung Function Initiative (GLI) spirometric reference equations, the appropriateness of the race-specific and race-neutral GLI spirometric reference models among the Indian population has not been systematically investigated. MethodsIn this cross-sectional analysis, we used spirometric measurements of 1123 healthy Indian adults (≥18 years of age). We computed reference values and z-scores for forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and FEV1/FVC from race-specific and race-neutral GLI reference equations as well as from a widely used Indian reference equation. We studied heterogeneity between GLI equations and the Indian equations using Bland-Altman analysis, and the differences between the reference and observed values were compared using the Friedman test. ResultsIn Bland-Altman analysis, significant heterogeneity in FVC and FEV1 between race-specific and Indian equations was observed (bias: 10.4 % and 14.1 %, respectively), with less bias for FEV1/FVC (3.76 %). The race-neutral equations showed almost similar bias (9.8 %, 13.8 %, and 3.8 % for FVC, FEV1, and FEV1/FVC, respectively). Median differences in race-specific reference values from observed values for FVC and FEV1 were 0.49L and 0.44L, respectively, decreasing slightly with race-neutral equations (0.46L and 0.43L) whereas Indian models showed minimal differences (FVC: 0.10L, FEV1: 0.05L). Z-scores for FVC and FEV1 were significantly different between race-specific and race-neutral GLI equations, and both differed from Indian equations. ConclusionBoth race-specific and race-neutral GLI reference equations are significantly different from the Indian equations, which underscores the importance of determining the suitability of global reference models before being used indiscriminately.

Which reference equation should we use for interpreting spirometry values for First Nations Australians? A cross-sectional study.

To evaluate the suitability of the Global Lung Function Initiative (GLI)-2012 other/mixed and GLI-2022 global reference equations for evaluating the respiratory capacity of First Nations Australians. Cross-sectional study; analysis of spirometry data collected by three prospective studies in Queensland, the Northern Territory, and Western Australia between March 2015 and December 2022. Opportunistically recruited First Nations participants in the Indigenous Respiratory Reference Values study (Queensland, Northern Territory; age, 3-25 years; 18 March 2015 - 24 November 2017), the Healthy Indigenous Lung Function Testing in Adults study (Queensland, Northern Territory; 18 years or older; 14August 2019 - 15 December 2022) and the Many Healthy Lungs study (Western Australia; five years or older; 10 October 2018 - 7November 2021). Goodness of fit to spirometry data for each GLI reference equation, based on mean Z-score and its standard deviation, and proportions of participants with respiratory parameter values within 1.64 Z-scores of the mean value. Acceptable and repeatable forced expiratory volume in the first second (FEV1) values were available for 2700 First Nations participants in the three trials; 1467 were classified as healthy and included in our analysis (1062 children, 405 adults). Their median age was 12 years (interquartile range, 9-19 years; range, 3-91 years), 768 (52%) were female, and 1013 were tested in rural or remote areas (69%). Acceptable and repeatable forced vital capacity (FVC) values were available for 1294 of the healthy participants (88%). The GLI-2012 other/mixed and GLI-2022 global equations provided good fits to the spirometry data; the race-neutral GLI-2022 global equation better accounted for the influence of ageing on FEV1 and FVC, and of height on FVC. Using the GLI-2012 other/mixed reference equation and after adjusting for age, sex, and height, mean FEV1 (estimated difference, -0.34; 95% confidence interval [CI], -0.46 to -0.22) and FVC Z-scores (estimated difference, -0.45; 95% CI, -0.59 to -0.32) were lower for rural or remote than for urban participants, but their mean FEV1/FVC Z-score was higher (estimated difference, 0.14; 95% CI, 0.03-0.25). The normal spirometry values of healthy First Nations Australians may be substantially higher than previously reported. Until more spirometry data are available for people in urban areas, the race-neutral GLI-2022 global or the GLI-2012 other/mixed reference equations can be used when assessing the respiratory function of First Nations Australians.

Spirometry Interpretation After Implementation of Race-Neutral Reference Equations in Children

The implications of adopting race-neutral reference equations on spirometry interpretation in children remain unknown. To examine how spirometry results and patterns change when transitioning from Global Lung Function Initiative (GLI) race-specific reference equations (GLIR, 2012) to GLI race-neutral reference equations (GLIN, 2023). Cross-sectional study of spirometry tests conducted in children aged 6 to 21 years between 2012 and 2022 at 2 large academic pediatric institutions in the US. Data were analyzed from September 2023 to March 2024. Data on participant characteristics and raw test measurements were collected. Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/FVC z scores and percent predicted were calculated using both GLIR and GLIN. In addition, test results were categorized into normal, obstructive, suspected restrictive, mixed, suspected dysanapsis, and uncategorized patterns based on z scores calculated using GLIR or GLIN. For each spirometry result, the difference between z scores and percent predicted when transitioning from GLIR to GLIN was calculated. The proportion of tests with a normal pattern and individual spirometry patterns changed by GLI reference equation applied were also examined. Data from 24 630 children were analyzed (mean [SD] age, 12.1 [3.8] years). There were 3848 Black children (15.6%), 19 503 White children (79.2%), and 1279 children of other races (5.2%). Following implementation of GLIN, FEV1 and FVC z scores decreased in Black children (mean difference, -0.814; 95% CI, -0.823 to -0.806; P < .001; and -0.911; 95% CI, -0.921 to -0.902; P < .001, respectively), while FEV1 and FVC z scores slightly increased (0.073; 95% CI, 0.069 to 0.076; P < .001). Similar changes were found when using percent predicted. In Black children, the number of tests with a normal pattern decreased from 2642 (68.7%) to 2383 (61.9%) (χ21 = 204.81; P < .001), mostly due to tests with a normal pattern transitioning to a suspected restrictive or uncategorized pattern. Opposite, albeit smaller, changes in spirometry results and patterns were seen in White children. In adjusted models, Black children had approximately 3-fold higher odds than White children of changing spirometry pattern following the implementation of GLIN (adjusted odds ratio, 3.15; 95% CI, 2.86 to 3.48; P < .001). Pronounced differences in spirometry results and patterns were found when switching between GLI reference equations, which markedly differed by race. These findings suggest that the implementation of GLIN is likely to change the treatment of children with chronic lung diseases that are more prevalent in underrepresented minorities, such as asthma.

Assessment of hyperinflation: comparison of Global Lung Function Initiative and European Community for Steel and Coal lung volume reference equations.

Assessment of static hyperinflation severity is crucial to identify COPD patients eligible for lung volume reduction. The current recommendation of residual volume ≥175% predicted may need to be reconsidered owing to potential differences between the Global Lung Function Initiative (GLI) and the European Community for Steel and Coal (ECSC) reference equations for residual volume and concerns about using percentage of predicted. We compared the residual volume reference values derived from the GLI and ECSC equations using mathematically simulated data and used a receiver operating characteristic curve to establish a new GLI-derived z-score cut-off for residual volume using body plethysmography data from patients with severe COPD. The GLI reference equation for residual volume consistently yields a lower predicted residual volume 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 (graded using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria as 38% GOLD 3 and 59% GOLD 4). In this cohort, a GLI-derived residual volume z-score of ≥2.9 could accurately replace the ECSC-derived 175% predicted cut-off and a z-score of ≥3.5 was established for the 200% predicted cut-off. There are substantial differences in predicted residual volume values between the GLI and ECSC equations, with the GLI generally yielding a lower predicted residual volume in the majority of individuals. A GLI-derived residual volume 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.