FEV1 Z-score Research Articles

Prenatal exposure to ambient fine particulate matter and child lung function in the CANDLE cohort

Background Ambient fine particulate matter (PM2.5) exposure adversely impacts child airway health; however, research on prenatal PM2.5 exposure, and child lung function is limited. We investigated these associations in the ECHO-PATHWAYS Consortium, focusing on the role of exposure timing during different phases of fetal lung development. Methods We included 675 children in the CANDLE cohort born between 2007 and 2011 in Memphis, TN, USA. Prenatal exposure to ambient PM2.5 was estimated using a spatiotemporal model based on maternal residential history and averaged over established prenatal periods of lung development. Forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) were measured by spirometry at age 8–9 years. We used linear regression and Bayesian Distributed Lag Interaction Models (BDLIM) to estimate associations between exposure and lung function z-scores, adjusting for maternal/child characteristics, prenatal/postnatal tobacco exposure, and birth year/season, and evaluating effect modification by child sex and allergic sensitization. Results The average ambient concentration of PM2.5 during pregnancy was 11.1 µg/m3 (standard deviation:1.0 µg/m3). In the adjusted linear regression and BDLIM models, adverse, but not statistically significant, associations were observed between exposure during the pseudoglandular (5–16 weeks of gestation) and saccular (24–36 weeks) phases of lung development and FEV1 and FVC. The strongest association was between a 2 μg/m3 higher concentration of PM2.5 during the saccular phase and FEV1 z-score (−0.176, 95% Confidence Interval [CI]: −0.361, 0.010). The FEV1/FVC ratio was not associated with PM2.5 in any exposure window. No effect modification by child sex or allergic sensitization was observed. Conclusions We did not find strong evidence of associations between prenatal ambient PM2.5 exposure and child lung function in a large, well-characterized study sample. However, there was a suggested adverse association between FEV1 and exposure during late pregnancy. The saccular phase of lung development might be an important window for exposure to PM2.5.

Long-Term Lung Function and Pseudomonas aeruginosa Infection in Genotyped Primary Ciliary Dyskinesia.

Rationale: Primary ciliary dyskinesia is a rare genetic disorder characterized by progressive lung disease. Pseudomonas aeruginosa is a major pathogen in this disease, known to impact lung function. Previous genotype-phenotype studies have been limited by cross-sectional designs, isolated adult or pediatric populations, small numbers, or short follow-up durations. Objectives: We aimed to explore long-term lung function in primary ciliary dyskinesia grouped by genotypes and ultrastructural defects, considering the influence of P. aeruginosa. Methods: In this retrospective, observational study, we analyzed 43 years of spirometry and 20 years of microbiology data. Using linear mixed-effects models, we estimated FEV1 z-score trends and compared them at ages 10, 25, and 50 years, while Generalized Estimating Equations were used to assess P. aeruginosa prevalence between groups. In a secondary analysis, we matched spirometry and microbiology samples to evaluate the influence of P. aeruginosa on lung function. Measurements and Main Results: We included 127 genotyped subjects, 6,691 spirometries and 10,082 microbiology samples. CCDC39 and CCDC40 variants showed early onset and sustained decline in lung function, while DNAH11 and HYDIN variants demonstrated relative stability. Lung function in the proximity of positive P. aeruginosa cultures were on average 0.06 z-score lower. Despite this, differences between groups remained largely unaffected by P. aeruginosa. Conclusion: Long-term lung function in primary ciliary dyskinesia follows discrete genotype specific profiles and appear independent of P. aeruginosa infection. We confirm and extend previous findings of CCDC39 and CCDC40 as variants associated with early onset severe lung function impairment persisting in the long term.

Fixed Airflow Obstruction in Asthma Can Be Identified Early by Low FEF25-75% and is Associated with Environmental Exposure.

This study aimed to identify environmental risk factors associated with asthmatic fixed airflow obstruction (FAO) and assess the relationship between small airway abnormalities defined by forced expiratory flow at 25-75% (FEF25-75%) and FAO. We analyzed data from 312han Chinese patients with stable asthma on standard treatment. Low FEF25-75% was defined as post-bronchodilator FEF25-75% z-score <-0.8435, and FAO as post-bronchodilator FEV1/FVC z-score <-1.645. Exposure levels were retrospectively analyzed in relation to FAO risk in asthmatics. Asthmatics were grouped by low FEF25-75% and FAO, and lung function, environmental exposure, daily symptoms, and exacerbations in the previous year were compared cross-sectionally across groups. In retrospective analyses, pack-years of smoking in male patients (adjusted odd ratio [95% confidence interval] 1.05 [1.03-1.07], P<0.001), biomass exposure for >20 years (2.65 [1.13-6.43], P=0.027), occupational exposure for >10 years (2.01 [1.06-3.86], P=0.035) and occupational exposure for >20 years (2.67 [1.24-5.91], P=0.013) were associated with asthmatic FAO. In cross-sectional analyses, compared with the normal FEF25-75%/ asthmatics without FAO (NON-FAO) group, the low FEF25-75%/ asthmatics with FAO (FAO) group had lower FEV1 z-scores and FEV1/FVC z-scores, more pack-years and years of biomass and occupational exposure, higher Asthma Control Questionnaire-5 and Chronic Obstructive Pulmonary Disease Assessment Test scores, and more frequent exacerbations. The low FEF25-75%/NON-FAO group showed the same trend, but to a lesser extent. Chronic airway inflammation is not the only driver of asthmatic FAO, and management and treatment targeting environmental risk factors (smoking and biomass and occupational exposures) may slow FAO progression in asthmatics. The FEF25-75% determined by the z-score is a reliable marker of small airway abnormalities, and patients with low FEF25-75% are at greater risk for FAO, requiring more frequent follow-up.

Variability in forced expiratory volume in 1 s in children with symptomatically well-controlled asthma

AimsSpirometry is used by many clinicians to monitor asthma in children but relatively little is understood about its variability over time. The aim of this study was to determine the...

Investigating genotype-phenotype correlations in primary ciliary dyskinesia: a sibling cohort study.

Primary Ciliary Dyskinesia (PCD) is a complex mostly autosomal recessive disorder characterized by dysfunction of primary motor cilia, leading to multisystemic manifestations, primarily affecting the rhino-sinopulmonary system. Despite advancements in understanding its pathogenesis, genotype-phenotype correlations are not fully elucidated. Utilizing sibling cohorts offers a promising approach to investigate these genotype-phenotype correlations in PCD. This retrospective cohort study, conducted from 2010 to 2023 at Soroka University Medical Center in Be'er-Sheva, Israel, included patients with a confirmed diagnosis of PCD. Variables and outcomes compared include typical presenting symptoms, lung function, structural changes in chest tomography (CT), and anthropometric data. Seventeen sibling patients from eight families met the inclusion criteria. At the last follow-up visit, the median age was 16 years. Genetic diagnosis revealed homozygous pathogenic variants including DNAH11, DNAAF3, DNAL1, and ZMYND10. Full concordance rates were observed for unexplained neonatal respiratory distress, chronic cough, and rhinosinusitis in patients with DNAH11 mutations. The family with the DNAAF3 mutation exhibited the lowest difference in Forced Expiratory Volume in 1 s (FEV1) Z-scores (0.48), but the highest differences in Forced Vital Capacity (FVC) Z-scores (3.39). High differences in FEV1 Z-scores were identified in the family with the DNAL1 mutation (2.06), while the lowest differences in FVC Z-scores (0.39) were observed in the same family. High concordance rates for certain mutations in clinical features suggest potential genotype-phenotype correlations, in contrast to weak concordance in lung function. Challenges remain in establishing direct correlations between genetic mutations and clinical outcomes.

Effect modification of glycemic control on association of lung function with all-cause and cardiovascular mortality in persons with type 2 diabetes – A retrospective cohort study

BackgroundPoor glucose control might deteriorate the impaired pulmonary function, which can ultimately lead to mortality. However, few studies have examined the effect modification of glucose control on the association between pulmonary function and mortality. This study aimed to examine the association of pulmonary function with mortality and determine the effect modification of glycemic level on the association of pulmonary function with mortality in persons with type 2 diabetes (T2DM). MethodsA retrospective cohort study included 3846 persons with T2DM with pulmonary function testing in Taiwan during 2002–2020. Expiratory volume in 1 s (FEV1) was measured as pulmonary function. Cox proportional hazards models were used and the effect modification of pulmonary function parameters and glucose control was assessed by their product terms. ResultsThere were 733 deaths during an average follow-up of 7.83 years. Significant associations of FEV1 and mortality were found (hazards ratio [HR] for FEV1 Z-scores of <0 to −1, <-1 to −2 and <−2: 1.47 [1.20, 1.80], 2.48 [1.95, 3.14] and 3.07 [1.74, 5.44] compared with participants with Z-score ≥0, respectively. All p for trend<0.001). Significant effect modifications were found and the association between FEV1 and mortality was stronger in persons with good glycemic control compared with poor glycemic control (FEV1–FPG effect modification, P = 0.01; FEV1–HbA1c effect modification, P = 0.03). ConclusionPulmonary function, measured by FEV1, is significantly associated with mortality in persons with T2DM. Significant effect modification of glucose control on the association between pulmonary function parameters and mortality was found.

Associations between respiratory pathogens and lung function in primary ciliary dyskinesia: cross-sectional analysis from the PROVALF-PCD cohort.

Respiratory pathogens are frequently isolated from airway samples in primary ciliary dyskinesia (PCD) patients. Few studies have investigated associations between these pathogens and lung function, with current management based on evidence from cystic fibrosis. We investigated the association between commonly isolated respiratory pathogens and lung function in PCD patients. Using a cross-sectional design, we prospectively collected clinical and concurrent microbiology data from 408 participants with probable or confirmed PCD, aged ≥5 years, from 12 countries. We used Global Lung Function Initiative 2012 references to calculate forced expiratory volume in 1 s (FEV1) z-scores. For 351 patients (86%) with complete data, we assessed the association of the four most frequently isolated pathogens with lung function by fitting multilevel linear models with country as random intercept, adjusted for age at diagnosis, age at lung function, use of antibiotic prophylaxis and body mass index z-scores. Individuals with Pseudomonas aeruginosa growth in culture had significantly lower FEV1 z-scores (β= -0.87, 95% CI -1.40- -0.34), adjusted for presence of Haemophilus influenzae, methicillin-sensitive Staphylococcus aureus and Streptococcus pneumoniae, and for covariates. When stratified by age, associations remained strong for adults but not for children. Results were similar when ciliary defects by transmission electron microscopy were included in the models and when restricting analysis to only confirmed PCD cases. We found that P. aeruginosa was associated with worse lung function in individuals with PCD, particularly adults. These findings suggest that it is prudent to aim for P. aeruginosa eradication in the first instance, and to treat exacerbations promptly in colonised patients.

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.

Longitudinal lung function trajectories in response to azithromycin therapy for chronic lung disease in children with HIV infection: a secondary analysis of the BREATHE trial

BackgroundChronic lung disease (CLD) is common among children with HIV (CWH) including in those taking antiretroviral therapy (ART). Azithromycin has both antimicrobial and anti-inflammatory effects and has been effective in improving lung function in a variety of lung diseases. We investigated lung function trajectories among CWH with CLD on ART enrolled in a randomized controlled trial of adjuvant azithromycin. We also investigated factors that modified the effect of azithromycin on lung function.MethodsThe study used data from a double-blinded placebo-controlled trial conducted in Malawi and Zimbabwe of 48 weeks on azithromycin (BREATHE: ClinicalTrials.gov NCT02426112) among CWH aged 6 to 19 years taking ART for at least six months who had a forced expiratory volume in one second (FEV1) z-score <-1.0. Participants had a further follow-up period of 24 weeks after intervention cessation. FEV1, forced vital capacity (FVC) and FEV1/FVC were measured at baseline, 24, 48 and 72-weeks and z-scores values calculated. Generalized estimating equations (GEE) models were used to determine the mean effect of azithromycin on lung-function z-scores at each follow-up time point.ResultsOverall, 347 adolescents (51% male, median age 15 years) were randomized to azithromycin or placebo. The median duration on ART was 6.2 (interquartile range: 3.8–8.6) years and 56.2% had an HIV viral load < 1000copies/ml at baseline. At baseline, the mean FEV1 z-score was − 2.0 (0.7) with 44.7% (n = 155) having an FEV1 z-score <-2, and 10.1% had microbiological evidence of azithromycin resistance. In both trial arms, FEV1 and FVC z-scores improved by 24 weeks but appeared to decline thereafter. The adjusted overall mean difference in FEV1 z-score between the azithromycin and placebo arms was 0.004 [-0.08, 0.09] suggesting no azithromycin effect and this was similar for other lung function parameters. There was no evidence of interaction between azithromycin effect and baseline age, lung function, azithromycin resistance or HIV viral load.ConclusionThere was no observed azithromycin effect on lung function z-scores at any time point suggesting no therapeutic effect on lung function.Trial registrationClinicalTrials.gov NCT02426112. First registered on 24/04/2015.

The predictive role of lung clearance index on FEV1 decline in cystic fibrosis.

The lung clearance index (LCI) is a sensitive lung function index that is used to detect early lung disease changes in children with cystic fibrosis (CF). This study aimed to define the predictive role of baseline LCI, along with other potential factors on the change in forced expiratory volume in one second (FEV1) during one-year follow-up in CF patients who had a percent predicted (pp) FEV1≥80. LCI was concurrently performed on 57 CF patients who had ppFEV1 ≥80 at month zero. The ppFEV1 decline was evaluated prospectively during the one year follow up. The primary outcome of ppFEV1 decline in the study group in one year was dichotomized according to the median value for the decline in ppFEV1, which was 3.7. The LCI value predicting ppFEV1 decline at the end of one year was calculated with receiver operating characteristic curve analysis. Regression analysis was performed. Furthermore, a decision tree was constructed using classification and regression tree methods to better define the potential effect of confounders on the ppFEV1 decline. The LCI value for predicting ppFEV1 decline >3.7% at the end of one year was 8.2 (area under the curve: 0.80) Multivariable regression analysis showed that the absence of the F508del mutation in at least one allele, LCI >8.2 and initial FEV1 z-score were predictors of a ppFEV1 decline >3.7 (p<0.001). Factors altering ppFEV1 decline>3.7% at the end of one-year evaluated by decision trees were as follows: initial FEV1 z-score, type of CFTR mutation, LCI value and initial weight-for-age z-score. LCI is sensitive for predicting ppFEV1 decline in patients with ppFEV1 ≥80 along with the initial FEV1-z-score and type of CFTR mutation.

Long-term lung function follow-up of preterm infants less than 32 weeks of gestational age.

Preterm infants, particularly those with bronchopulmonary dysplasia (BPD), are at risk of lung development problems. Over the last decades, lung protective strategies have been used, decreasing the risk of chronic lung disease. To evaluate the pulmonary function test (PFT) of preterm infants born after the introduction of lung protective strategies and to assess perinatal determinants of impaired lung function in this population. A prospective, observational, single-center study was conducted in the neonatal unit of a high-complexity hospital. The study included newborns withless than 32 weeks gestational age born between 2012 and 2014, who were followed up until they reach school age. For the main outcome, two groups were stablished: no BPD or grade 1 BPD (no BPD/1) and grade 2 or 3 BPD (BPD 2/3). Out of 327 patients, 116 were included. BPD was diagnosed in 49.1% (47), with 50.9% (29) classified as grade 1, 35.1% (20) as grade 2, and 14.0% (8) as grade 3. Mean age at PFT was 8.59 years (SD 0.90). Mean FEV1% was 95.36% (SD 13.21) and FEV1 z-score -0.36 (SD 1.12); FVC% 97.53% (SD 12.59) and FVC z-score -0.20 (SD 1.06); FEV1/FVC ratio 85.84% (SD 8.34) and z-score -0.24 (SD 1.34). When comparing patients with no BPD/1 and BPD 2/3, we observed differences in all pulmonary function parameters, which persisted after adjusting for gestational age. No differences in PFT were observed between patients without BPD and those with grade 1 BPD. Most patients (76.7%, 89) had normal spirometry pattern, with obstructive pattern observed in 12.9% (15), restrictive pattern in 9.5% (11), and mixed pattern in 0.9% (1) of patients. Preterm infants with BPD 2/3 showed a decrease in all pulmonary function parameters compared to preterm infants with no BPD/1; an effect that was independent of gestational age. Among patients with BPD who had an altered PFT pattern, the most common pattern was obstructive, followed by restrictive and then, mixed.

Associations of prenatal exposure to phthalates and their mixture with lung function in Mexican children

Early life phthalates exposure has been associated with adverse respiratory outcomes. However, evidence linking prenatal phthalates exposure and childhood lung function has been inconclusive. Additionally, few studies have examined phthalates exposure as a mixture and explored sexually dimorphic associations. We aimed to investigate sex-specific associations of prenatal phthalates mixtures with childhood lung function using the PROGRESS cohort in Mexico (N = 476). Prenatal phthalate concentrations were measured in maternal urine collected during the 2nd and 3rd trimesters. Children’s lung function was evaluated at ages 8–13 years. Individual associations were assessed using multivariable linear regression, and mixture associations were modeled using repeated holdout WQS regression and hierarchical BKMR; data was stratified by sex to explore sex-specific associations. We identified significant interactions between 2nd trimester phthalates mixture and sex on FEV1 and FVC z-scores. Higher 2nd trimester phthalate concentrations were associated with higher FEV1 (β = 0.054, 95 %CI: 0.005, 0.104) and FVC z-scores (β = 0.074, 95 % CI: 0.024, 0.124) in females and with lower measures in males (FEV1, β = −0.017, 95 %CI: −0.066, 0.026; FVC, β = −0.014, 95 %CI: −0.065, 0.030). This study indicates that prenatal exposure to phthalates is related to childhood lung function in a sex-specific manner.

Analyses of 1236 genotyped primary ciliary dyskinesia individuals identify regional clusters of distinct DNA variants and significant genotype-phenotype correlations.

Primary ciliary dyskinesia (PCD) represents a group of rare hereditary disorders characterised by deficient ciliary airway clearance that can be associated with laterality defects. We aimed to describe the underlying gene defects, geographical differences in genotypes and their relationship to diagnostic findings and clinical phenotypes. Genetic variants and clinical findings (age, sex, body mass index, laterality defects, forced expiratory volume in 1 s (FEV1)) were collected from 19 countries using the European Reference Network's ERN-LUNG international PCD Registry. Genetic data were evaluated according to American College of Medical Genetics and Genomics guidelines. We assessed regional distribution of implicated genes and genetic variants as well as genotype correlations with laterality defects and FEV1. The study included 1236 individuals carrying 908 distinct pathogenic DNA variants in 46 PCD genes. We found considerable variation in the distribution of PCD genotypes across countries due to the presence of distinct founder variants. The prevalence of PCD genotypes associated with pathognomonic ultrastructural defects (mean 72%, range 47-100%) and laterality defects (mean 42%, range 28-69%) varied widely among countries. The prevalence of laterality defects was significantly lower in PCD individuals without pathognomonic ciliary ultrastructure defects (18%). The PCD cohort had a reduced median FEV1 z-score (-1.66). Median FEV1 z-scores were significantly lower in CCNO (-3.26), CCDC39 (-2.49) and CCDC40 (-2.96) variant groups, while the FEV1 z-score reductions were significantly milder in DNAH11 (-0.83) and ODAD1 (-0.85) variant groups compared to the whole PCD cohort. This unprecedented multinational dataset of DNA variants and information on their distribution across countries facilitates interpretation of the genetic epidemiology of PCD and indicates that the genetic variant can predict diagnostic and phenotypic features such as the course of lung function.

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.

Urinary eosinophil-derived neurotoxin is associated with reduced lung function in pediatric asthma.

Eosinophil-derived neurotoxin (EDN) is a biomarker for eosinophilic activation. Urinary (u) EDN may allow non-invasive monitoring of asthma, but clinical recommendations are lacking. We assessed the potential of uEDN as a marker of disease activity in pediatric asthma. We assessed urine samples of 371 children from the German ALLIANCE study cohort, from which we had: 169 preschool wheezers (<6 years), 80 asthmatics (≥6 years), and 122 healthy controls using the ImmunoCAP™ EDN Assay. Creatinine (Cr)-adjusted uEDN values were analyzed using correlations, association tests, (non) parametric statistics, multiple linear, and multivariable regression. uEDN/uCr values were higher in atopic versus non-atopic preschool-aged subjects (p = .035) and associated with the sum of allergen-specific IgE in younger (r = 0.24, p = .003), and older subjects (r = 0.23, p = .043). uEDN/uCr was marginally a good determinant for atopy (p = .078, for subjects aged <6 years, and p = .058 for subjects ≥6 years). Children with the T2-high phenotype had higher uEDN/uCr (p < .001) versus T2-low-irrespective of using uEDN/uCr or blood eosinophils in combination to allergen sIgE for disease phenotyping. uEDN/uCr significantly correlated with reduced lung function among asthmatics (FEV1 z-scores: r = -0.30, p = .007, and FEV1/FVC z-scores: r = -0.24, p = .038). Using multivariable modeling, uEDN/uCr was an independent determinant of FEV1 (p = .038), and to a lesser extent, FEV1/FVC (p = .080). uEDN/uCr may serve as a non-invasive biomarker for clinical features such as lung function in pediatric asthma. We highlight the utility of uEDN/uCr as a biomarker that can be easily assessed using widely available robust diagnostic immunoassays.

Race-Neutral Equations and Pulmonary Function Test Interpretation in Two Pediatric Cohorts

ObjectivesTo investigate the changes in predicted lung function measurements when using race-neutral equations in children, based upon the new Global Lung Initiative (GLI) reference equations utilizing a race-neutral approach in interpreting spirometry results compared with the 2012 race-specific GLI equations. Study designWe analyzed data from two multicenter prospective cohorts comprised of healthy children and children with history of severe (requiring hospitalization) bronchiolitis. Spirometry testing was done at the 6-year physical exam and 677 tests were analyzed using new GLI Global and 2012 GLI equations. We used multivariable logistic regression, adjusted for age, height, and sex, to examine the association of race with the development of new impairment or increased severity (FEV1 z-score≤-1.645) as per 2022 ATS guidelines. ResultsCompared with the race-specific GLI, the race-neutral equation yielded increases in the median FEV1 and FVC percent predicted in White children but decreases in these two measures in Black children. The prevalence of obstruction increased in White children by 21% and the prevalence of possible restriction increased in Black children by 222%. Compared with White race, Black race was associated with increased prevalence of new impairments (aOR 7.59; 95%CI, 3.00-19.67; p<0.001) and increased severity (aOR 35.40; 95%CI, 4.70-266.40; p=0.001). Results were similar across both cohorts. ConclusionsAs there are no biological justifications for the inclusion of race in spirometry interpretation, use of race-neutral spirometry reference equations led to an increase in both the prevalence and severity of respiratory impairments among Black children.

Comparison of clinical features of cystic fibrosis patients eligible but not on CFTR modulators to ineligible for CFTR modulators.

Cystic fibrosis transmembrane conductance regulator (CFTR) modulator drugs target the underlying defect and improve CFTR function. They are a part of standard care in many countries, but not all patients are eligible for these drugs due to age and genotype. Here, we aimed to determine the characteristics of non-eligible patients for CFTR modulators in the CF registry of Turkey (CFRT) to highlight their clinical needs. This retrospective cohort study included CF patient data from the CFRT in 2021. The decision of eligibility for the CFTR modulator was determined according to the 'Vertex treatment-Finder' on the Vertex® website. Demographic and clinical characteristics of patients were compared between eligible (group 1) and ineligible (group 2) groups for CFTR modulators. Among the study population (N = 1527), 873 (57.2%) were in group 1 and 654 (42.8%) were in group 2. There was no statistical difference between groups regarding sex, meconium ileus history, diagnoses via newborn screening, FEV1 z-score, CF-associated complications, organ transplant history, and death. Patients in group 2 had a higher incidence of pancreatic insufficiency (87.7% vs. 83.2%, p = .010), lower median height z-scores (-0.87 vs. -0.55, p < .001), lower median body mass index z-scores (-0.65 vs. -0.50, p < .001), longer days receiving antibiotics due to pulmonary exacerbation (0 [interquartile range, IQR: 0-2] vs. 0 [IQR: 0-7], p = 0.001), and more non-invasive ventilation support (2.6% vs. 0.9%, p = 0.008) than patients in group 1. The ineligible group had worse clinical outcomes than the eligible group. This highlights their need for life-changing drugs to improve clinical outcomes.

The role of 14-3-3β in acute asthma in children and analysis of the risk factors for asthma exacerbation

Objective To investigate the role of 14-3-3β in acute asthma exacerbations in children and analyze the risk factors for asthma exacerbations. Methods This study recruited 101 children with acute asthma exacerbations, 101 children with stable asthma, and 65 healthy children. Serum 14-3-3β was compared among the three groups. Factors such as asthma family history, skin prick test, serum-specific IgE test, coinfections, and clinical indicators (FeNO, FEV1, white blood cells, eosinophils, and serum IgE level) were compared between the asthma groups. Risk factors associated with acute asthma exacerbations were identified using multivariate logistic regression models. ROC curve was drawn to determine the diagnostic sensitivity and specificity of 14-3-3β. Results Serum 14-3-3β was significantly greater in the acute asthma group than in the stable asthma and control groups. Serum 14-3-3β was higher in severe acute asthma group than in mild-moderate asthma group. There were no significant differences in serum 14-3-3β levels between stable asthma and control groups (p > .05). Multivariate logistic regression analysis revealed that serum 14-3-3β level, FeNO, coinfection, and FEV1 z-score significantly increased the odds of acute asthma exacerbations in children. The optimal 14-3-3β cutoff value (39.79 ng/mL), had a sensitivity of 69.3% and specificity of 94.1% for predicting acute asthma exacerbations. Conclusions 14-3-3β is elevated in children with acute exacerbations of asthma, and increases with exacerbation severity. 14-3-3β, FeNO, FEV1, and coinfection could be independent risk factors for predicting asthma exacerbations. The optimal 14-3-3β cutoff value for predicting asthma exacerbations was 39.79 ng/mL.

What constitutes an obstructive ventilatory impairment in a pediatric population? A study design.

There is no clear consensus as to what constitutes an obstructive ventilatory impairment (OVI) in pediatric populations. To determine the percentage of children/adolescents having an OVI among those addressed for spirometry after taking into account the definitions advanced by some international scholarly societies [British Columbia (BC), British thoracic-society (BTS), Canadian thoracic society (CTS), European respiratory society and American thoracic society (ERS-ATS), global initiative for asthma (GINA), Irish college of general practitioners (ICGP), national asthma council (NAC), national institute of clinical excellence (NICE), Société de pneumologie de langue française, Société pédiatrique de pneumologie et allergologie (SPLF-SP2A), and South African thoracic society (SATS)]. This bi-centric cross-sectional study involves two medical structures in Sousse/Tunisia, and will encompass children/adolescents aged 6-18 years. A medical questionnaire will be administered, clinical and anthropometric data will be collected, and the spirometric data will be measured by two spirometers. The following six definitions of OVI will be applied: i) GINA: Forced expiratory volume in 1 second (FEV1) < 80% and a FEV1/forced vital capacity (FVC) ≤ 0.90; ii) ICGP: FEV1/FVC < 0.70; iii) ERS-ATS or BTS or SATS or SPLF-SP2A or NAC: FEV1/FVC z-score < -1.645; iv) NICE: FEV1/FVC < 0.70 or FEV1/FVC z-score < -1.645; v) CTS: FEV1/FVC < 0.80 or a FEV1/FVC z-score < -1.645; and vi) ERS: "FEV1 z-score or FEV1/FVC z-score" < -1.645 or "FEV1 or FEV1/FVC" < 0.80. The percentage of children/adolescents having an OVI will significantly vary between the six definitions. The frequency of OVI in a pediatric population will depend on the definition chosen.

Effect of fluticasone propionate/formoterol and fluticasone furoate/vilanterol on adolescents with chronic bronchial obstruction

BackgroundThe combination of inhaled corticosteroid and long-acting beta-agonist (ICS/LABA) has shown superiority in improving lung function (FEV1) compared with ICS. The clinical effect of ICS/LABA depends on the fine-particle fraction (FPF) and the pulmonary deposition. ObjectiveWe sought to compare the efficacy of two combinations of an inhaled corticosteroid (ICS) and a long-acting beta agonist (LABA), fluticasone propionate/formoterol and fluticasone furoate/vilanterol, in asthmatic adolescents with chronic bronchial obstruction. MethodsFluticasone propionate/formoterol (FP/FORM) (125/5 μg 2 doses twice daily via the k-haler®) and fluticasone furoate/vilanterol (FF/VI) (92/22 μg once daily via the Ellipta®) were administered to adolescents aged 12 to 17 years who required regular anti-asthmatic medication and had a forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) ratio below -1.65 SD in a 2-sequence, 16-week crossover trial. The primary efficacy end point was change in FEV1 compared to baseline. Secondary end points were FEV1/FVC, maximal expiratory flow at 50% of the forced vital capacity (MEF50), impulse oscillometry indices respiratory resistance at 5 Hz (R5), difference of R5 and R20 (R5−20), area of reactance (AX), and Asthma Control Test. ResultsBoth ICS/LABA combinations resulted in a significant improvement in FEV1 and MEF50 Z-scores without any significant difference between FP/FORM and FF/VI. Forty percent of patients achieved a normal prebronchodilator FEV1/FVC Z-score with either treatment. AX or R5−20 did not improve significantly with either treatment. ConclusionBoth ICS/LABA combinations demonstrated significant improvements in FEV1 Z-score. Over one-third of the asthmatic adolescents with prolonged bronchial obstruction achieved a normal prebronchodilator FEV1/FVC level.