Forced Vital Capacity Z-scores Research Articles

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.

Small Airways Disease Affects Aerosol Deposition in Children with Severe Asthma: A Functional Respiratory Imaging Study.

Background: Small airways disease (SAD) in severe asthma (SA) is associated with high disease burden. Effective treatment of SAD could improve disease control. Reduced end-expiratory flows (forced expiratory flow [FEF]25-75 and FEF75) are considered sensitive indicators of SAD. Inhaled medication should be delivered to the smaller peripheral airways to treat SAD effectively. Aerosol deposition is affected by structural airway changes. Little is known about the effect of SAD on aerosol delivery to the smaller peripheral airways. Functional respiratory imaging (FRI) is a validated technique using 3D reconstructed chest computed tomography (CT) and computational fluid dynamics to predict aerosol deposition in the airways. Aim: This study aims to compare central and peripheral (= small airways) deposition between children with SA and SAD and children with SA without SAD, with different inhaler devices and inhalation profiles. Methods: FRI was used to predict the deposition of beclomethasone/formoterol dry powder inhaler (DPI), beclomethasone/formoterol pressurized metered dose inhaler with valved holding chamber (pMDI/VHC), and salbutamol pMDI/VHC for different device-specific inhalation profiles in chest-CT of 20 children with SA (10 with and 10 without SAD). SAD was defined as FEF25-75 and FEF75 z-score < -1.645 and forced vital capacity (FVC) z-score > -1.645. No SAD was defined as forced expiratory volume (FEV)1, FEF25-75, FEF75, and FVC z-score > -1.645. The intrathoracic, central, and peripheral airways depositions were determined. Primary outcome was difference in central-to-peripheral (C:P) deposition ratio between children with SAD and without SAD. Results: Central deposition was significantly higher (∼3.5%) and peripheral deposition was lower (2.9%) for all inhaler devices and inhalation profiles in children with SAD compared with children without SAD. As a result C:P ratios were significantly higher for all inhaler devices and inhalation profiles, except for beclomethasone administered through DPI (p = .073), in children with SAD compared with children without SAD. Conclusion: Children with SA and SAD have higher C:P ratios, that is, higher central and lower peripheral aerosol deposition, than children without SAD. The intrathoracic, central, and peripheral deposition of beclomethasone/formoterol using DPI was lower than using pMDI/VHC.

Correlation of diaphragmatic mobility and thickening assessed by lung ultrasound with severity of interstitial lung disease.

Studies conducted in interstitial lung disease (ILD) patients to assess diaphragmatic excursion and thickening fraction suggest a weak to strong correlation with pulmonary function parameters. However, diaphragmatic excursion velocity, a novel imaging marker, has not been correlated with pulmonary function and high-resolution computed tomography (HRCT) fibrosis score in ILD patients previously. We conducted a cross-sectional analytical study in 40 ILD patients during quiet (QB) and deep breathing (DB) to measure diaphragmatic thickening, excursion and excursion velocity using transthoracic ultrasound and correlated them with pulmonary function parameters and HRCT fibrosis score. Most diaphragm parameters in DB correlated more strongly with lung function parameters compared to quiet breathing. Right diaphragmatic excursion, during QB and DB, showed positive correlations with forced vital capacity (FVC) z-score (r = 0.591, 0.676) and diffusion capacity of the lung for carbon monoxide (DLCO) z-score (r = 0.437, 0.438), and negative correlations with HRCT fibrosis score (r = -0.439, -0.425), respectively. In addition, right diaphragmatic velocity exhibited positive correlations with FVC z-score (r = 0.388, 0.667) and DLCOz-score (r = 0.139, 0.412), and negative correlations with HRCT fibrosis score (r = -0.454, -0.445). Right diaphragm thickening fraction showed positive correlations with FVC z-score (r = 0.330, 0.460) and DLCOz-score (r = 0.400, 0.426), and negative correlations with HRCT fibrosis score (r = -0.199, -0.237). Similarly, right diaphragmatic thickness indicated positive correlations with FVC z-score (r = 0.526, 0.614) and DLCOz-score (r = 0.298, 0.298), and negative correlations with HRCT fibrosis score (r = -0.398, -0.401). Diaphragmatic excursion velocity during DB showed a weak to moderate correlation with pulmonary function parameters and HRCT fibrosis score and may be utilized as a surrogate marker in ILD patients unable to perform pulmonary function tests or undergo sequential HRCT thorax in follow-up.

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.

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.

Pulmonary function assessments and clinical correlates in children with sickle cell disease in Cape Town, South Africa

Objectives: Among children with sickle cell disease (SCD) in Africa, there are varied reports on pulmonary function assessments. Restrictive pulmonary function is common in children with SCD in Africa; however, reports from Africa are few. We aimed to describe pulmonary function and its clinical correlates in children with SCD in Cape Town, South Africa. Materials and Methods: A prospective cross-sectional study was carried out over seven months from October 2018 to April 2019 in children 6–16 years with SCD. Children with hemoglobin (Hb) genotypes, homozygous for the BS globin mutation, and sickle-beta0-thalassemia Hb were included in the study. Children were excluded if they had acute complications. Medical record review clinical, laboratory, and pulmonary function assessments were done. Data were entered into Excel and exported to Stata Version 16.0 statistical software for analysis. Results: A total of 25 participants were recruited, mean (standard deviation) age of 10 ± (3.0) years. Thirteen (53%) children were under ten years and 15 (60%) were male. The median/interquartile range age at diagnosis was 1.7 [0.8–3.0] years. SCD-related complications were common. A review of the medical records showed a third of the patients (32%) had at least one previous episode of acute chest syndrome, 20 (80%) had a history of vaso-occlusive crisis, and 15 (76%) had required at least one blood transfusion. Spirometry was performed on 19 (76%) of the participants 9 (47%) had abnormal lung function. The most common spirometry abnormality was a restrictive pattern (forced vital capacity (FVC) &lt; lower limit of normal (LLN)). No participant had a positive bronchodilator response. Older age was associated with a decrease in forced expiratory volume in the first second (FEV1) Z-score (−0.16, 95% confidence interval [CI] −0.31, −0.01; P = 0.04). Children on hydroxyurea similarly had reduced FEV1 Z-score (−1.5, 95%CI −2.88, −0.12; P = 0.04) and reduced FVC Z-score (−2.21, 95%CI −3.64, −0.79; P &lt; 0.001). Conclusion: Lung function abnormalities were common among children with SCD, with restrictive abnormality predominating. Asthma and obstructive airway abnormalities were uncommon in children with SCD in South Africa.

Galectin-3 levels in children with cystic fibrosis.

Cystic fibrosis (CF) is a multisystemic disease in which airway obstruction, infection, and inflammation play a critical role in the pathogenesis and progression of CF lung disease. The carbohydrate-binding protein Galectin-3 is increased in several inflammatory and fibrotic diseases and has recently been forwarded as a biomarker in these diseases. We aimed to define the role of serum Galectin-3 in children with CF by comparison with healthy subjects. This is a cross-sectional, case-control study. 143 CF and 30 healthy subjects were enrolled in the study. Peripheral blood and sputum concentrations of Galectins-3, interleukin (IL)-17A, IL-8, and neutrophil elastase (NE) were determined with commercial ELISA kits. There was no significant difference between the groups in age and gender (p = 0.592, p = 0.613, respectively). Serum Galectin-3 and NE concentrations were higher in the patient group than in healthy controls (p = 0.002, p < 0.001, respectively). There were no significant differences between groups according to IL-17A and IL-8 concentrations. Serum Galectin-3 was correlated with age (r = 0.289, p < 0.001) and body mass index (BMI) (r = 0.493, p < 0.001) in children with CF. Sputum Galectin-3 levels are negatively correlated with percent predictive forced expiratory volume in 1s (FEV1) (r = - 0.297, p = 0.029), FEV1 z-score, (r = - 0.316, p = 0.020), percent predictive forced vital capacity (FVC) (r = - 0.347, p = 0.010), and FVC z-score (r = - 0.373, p = 0.006). Conclusion: The study shows that serum Galectin-3 levels increased in clinically stable CF patients, and serum Galectin-3 response may depend on age, gender, and BMI. The sputum Galectin-3 was found to be negatively correlated with patients' lung functions. What is known: • Galectin-3 is a key regulator of chronic inflammation in the lung, liver, kidney, and tumor microenvironment. What is new: • Children with cystic fibrosis (CF) have higher serum Galectin-3 concentrations than healthy children. • Serum Galectin-3 expression influenced by age, BMI, and gender in children with CF.

Pulmonary function outcomes after tuberculosis treatment in children: a systematic review and meta-analysis

BackgroundDespite tuberculosis (TB) being a curable disease, current guidelines fail to account for the long-term outcomes of post-tuberculosis lung disease—a cause of global morbidity despite successful completion of effective treatment....

Lifestyle Intervention Improves Physical Fitness and Quality of Life in Children with Bronchopulmonary Dysplasia

Abstract Background: Exercise capacity in children with bronchopulmonary dysplasia (BPD) is lower compared to healthy peers. We aimed to improve maximal exercise capacity using a combined lifestyle intervention in children with BPD. Methods: This semi-cross-over randomized controlled trial investigated the effects of a combined intervention of high-intensity interval training, healthy diet recommendations, and psychological support in children with BPD. Effects were measured on (sub) maximal exercise capacity, lung function, muscle strength, core stability, physical activity levels, quality of life, fatigue, fear of exercise, caloric intake, energy balance, and body composition using a generalized estimation approach. Results: Fourteen children with BPD, median age 8.0 years (interquartile range: 7.7–8.9), 8 males, participated. At baseline, all patients had peak oxygen (VO2)/kg, forced vital capacity (FVC), and forced expiratory volume in 1 s (FEV1) within normal limits. These parameters did not increase significantly after the intervention compared to the control period (effect size peak VO2/Kg + 3.1 ml/kg/min [95% confidence interval (CI) −0.4–6.7], P = 0.076, FVC z-score + 0.67 [95% CI − 0.1–1.4] P = 0.082, and FEV1 z-score + 0.53 [95% CI − 0.13–1.19] P = 0.117). Peak load and peak ventilation on the maximal cardiopulmonary exercise test and walked distance on the 6-min walking test increased significantly compared to the control period (respectively, +14 watt [95% CI 10–18], P &lt; 0.001, +7 L/min [95% CI 2–12], P = 0.009 and + 45 m [95% CI 1–90], P = 0.046). Both self-reported and parent-reported quality of life improved significantly in five domains (including the physical functioning domain). Conclusion: A 12-week combined lifestyle intervention improved peak load and peak ventilation, walk distance, and quality of life in children with BPD.

Period and cohort effects: consequences on spirometric lung function in Norway during the 20th century.

Several factors can influence measured lung function over time. The aim of this study was to investigate period and cohort effects on spirometric measures in a large general population sample in Norway during the 20th century, using Global Lung Function Initiative (GLI-2012) equations as a reference. 36 466 subjects (born 1894-1969) from four cross-sectional surveys conducted between 1965 and 1999 were included, with harmonised data on smoking habits, respiratory symptoms, lung diseases, education and spirometry. Changes in forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) z-scores in healthy subjects across surveys were explored to investigate period effects. Linear mixed-effects models of FEV1 and FVC z-scores on birth cohort, with survey as random effect, were used to investigate cohort effects, both in subjects of the total population and in healthy ones. Relatively higher FEV1 and FVC z-scores in healthy subjects were found in the first survey (1965-1970) compared to the more recent ones (1988-1999), suggesting period effects. FEV1 and FVC z-scores increased significantly with birth cohort from 1894 to 1935, after adjustment for covariates. A more stable trend of FEV1 and FVC z-scores with birth cohort was evidenced for subjects born more recently (1945-1969). An increase of lung function with year of birth was observed in Norwegian subjects during the first half of the 20th century. The impact of period effects on lung function decreased from 1965 to 1999.

Longitudinal lung function in urban firefighters: A group-based multi-trajectory modelling approach.

Urban firefighters are routinely exposed to both physical and chemical hazards that can negatively impact lung health, but it is unclear if firefighters experience accelerated decline in spirometry parameters due to chronic exposure and acute insults. This study aimed to describe sub-groups of firefighters with differing spirometry trajectories and examine the relationship between the identified trajectories and demographic, lifestyle and occupational characteristics. Data from six waves of the Respiratory Function Measurement and Surveillance for South Australian Metropolitan Fire Service Study (2007-2019) were used to identify spirometry parameter z-score trajectories, using group-based multi-trajectory modelling (GBMTM). Analysis of variance and chi-square statistics were used to assess trajectory group differences in baseline self-reported demographic, lifestyle and occupational characteristics. In the 669 included firefighters, we identified five trajectories for the combination of Forced Expiratory Volume in the first second z-score (FEV1 z), Forced Vital Capacity z-score (FVCz) and the ratio of FEV1 and FVC z-score (FEV1 /FVCz). There were three stable trajectories of low, average and very high lung function and two declining trajectories of average and high lung function. Analysis of subgroup characteristics revealed no significant differences between expected and actual group proportions for the occupational characteristics of years of service and respiratory protection use. Significant differences were seen in respiratory health and body mass index. GBMTM defined distinct, plausible spirometry trajectory sub-groups. Firefighter longitudinal spirometry trajectory group membership was associated with BMI and respiratory disease or symptoms but not with self-reported smoking history or occupational factors.

Clinical and Immunological Markers of Pulmonary Impairment Among People With HIV in India.

BackgroundDespite antiretroviral therapy, chronic lung diseases remain an important source of morbidity and mortality in people with HIV (PWH). We sought to identify clinical and immunological markers of pulmonary impairment among PWH in India.MethodsTwo hundred ten adult PWH receiving antiretroviral therapy (ART) were prospectively evaluated for 3 years. Plasma concentrations of interleukin (IL)-6, IL-10, tumor necrosis factor alpha, D-dimer, C-reactive protein, soluble (s)CD14, and sCD163 were measured at enrollment. We used multivariable linear and logistic regression to measure the association of baseline and time-varying clinical and immunological variables with spirometry-defined chronic obstructive pulmonary disease (COPD), restrictive spirometry pattern (RSP), preserved ratio impaired spirometry (PRISm), forced expiratory volume in 1 second (FEV1), and forced vital capacity (FVC) during the third year of follow-up.ResultsAfter adjusting confounders, females were 7 times more likely to have RSP (95% CI, 2.81 to 17.62; P < .001) and 22 times more likely to have PRISm (95% CI, 7.42 to 69.92; P < .001) compared with men. Higher IL-6 concentrations were associated with lower FEV1 z-scores (β, −0.14 per log-higher; 95% CI, −0.29 to 0.008; P = .06) and higher odds of COPD (adjusted odds ratio [aOR], 2.66 per log-higher; 95% CI, 1.16 to 6.09; P = .02). Higher D-dimer concentrations were associated with lower FVC z-scores (β, −0.40 per log-higher; 95% CI, −0.78 to −0.01; P = .04). Conversely, higher IL-10 concentrations were associated with lower odds of PRISm (aOR, 0.76 per log-higher; 95% CI, 0.59 to 0.99; P = .04).ConclusionsFemale sex, higher concentrations of IL-6 and D-dimer, and lower concentrations of IL-10 were associated with pulmonary impairment in adult PWH receiving ART in India.

Daytime predictors of nocturnal hypercapnic hypoventilation in children with neuromuscular disorders.

To examine objective daytime predictors of nocturnal hypercapnic hypoventilation (NHH) and identify a forced vital capacity (FVC) z-score cut off that predicts NHH using the 2012 Global Lung Function Initiative (GLI) reference equations in pediatric neuromuscular patients. Single-centre retrospective medical record review. Tertiary pediatric hospital in Australia. Children (<18 years old) with a neuromuscular disorder (NMD) who had a diagnostic sleep study over a 5-year period. Fifty children were included, median age 11.9 years (interquartile range [IQR]: 4.5-14.3). The majority of children had a diagnosis of Duchenne Muscular Dystrophy (32%). NHH was diagnosed in 18 children (36%). Multivariate logistic regression analysis performed for the entire cohort confirmed a statistically significant association between NHH and scoliosis (odds ratio [OR]: 3.3, p = 0.03), but not age (OR: 1.01, p = 0.26), body mass index z-score (OR: 0.86, p = 0.26) or use of a wheelchair for mobility (OR: 1.25, p = 0.72). For the subset of 29 children who had spirometry testing (median age 12.9 years [IQR: 10.2-14.3]), FVC z-score was the only statistically significant predictor of NHH (OR: 0.45, p = 0.02). NHH was predicted by an FVC z-score <-3.24 (sensitivity 78%, specificity 73%), or FVC <60% predicted (sensitivity 78%, specificity 73%). There was a strong positive correlation between FVC and forced expiratory volume in 1 s z-scores (rp = 0.98, p = 0.00) and FVC and peak expiratory flow z-scores (rp = 0.72, p = 0.00). Children with a NMD and scoliosis or a lower FVC z-score have increased odds of having NHH.

Differences and agreement between two portable hand-held spirometers across diverse community-based populations in the Prospective Urban Rural Epidemiology (PURE) study.

Portable spirometers are commonly used in longitudinal epidemiological studies to measure and track the forced expiratory volume in first second (FEV1) and forced vital capacity (FVC). During the course of the study, it may be necessary to replace spirometers with a different model. This raise questions regarding the comparability of measurements from different devices. We examined the correlation, mean differences and agreement between two different spirometers, across diverse populations and different participant characteristics. From June 2015 to Jan 2018, a total of 4,603 adults were enrolled from 628 communities in 18 countries and 7 regions of the world. Each participant performed concurrent measurements from the MicroGP and EasyOne spirometer. Measurements were compared by the intra-class correlation coefficient (ICC) and Bland-Altman method. Approximately 65% of the participants achieved clinically acceptable quality measurements. Overall correlations between paired FEV1 (ICC 0.88 [95% CI 0.87, 0.88]) and FVC (ICC 0.84 [0.83, 0.85]) were high. Mean differences between paired FEV1 (-0.038 L [-0.053, -0.023]) and FVC (0.033 L [0.012, 0.054]) were small. The 95% limits of agreement were wide but unbiased (FEV1 984, -1060; FVC 1460, -1394). Similar findings were observed across regions. The source of variation between spirometers was mainly at the participant level. Older age, higher body mass index, tobacco smoking and known COPD/asthma did not adversely impact on the inter-device variability. Furthermore, there were small and acceptable mean differences between paired FEV1 and FVC z-scores using the Global Lung Initiative normative values, suggesting minimal impact on lung function interpretation. In this multicenter, diverse community-based cohort study, measurements from two portable spirometers provided good correlation, small and unbiased differences between measurements. These data support their interchangeable use across diverse populations to provide accurate trends in serial lung function measurements in epidemiological studies.

Spirometric phenotypes from early childhood to young adulthood: a Chronic Airway Disease Early Stratification study.

BackgroundThe prevalences of obstructive and restrictive spirometric phenotypes, and their relation to early-life risk factors from childhood to young adulthood remain poorly understood. The aim was to explore these phenotypes and associations with well-known respiratory risk factors across ages and populations in European cohorts.MethodsWe studied 49 334 participants from 14 population-based cohorts in different age groups (≤10, >10–15, >15–20, >20–25 years, and overall, 5–25 years). The obstructive phenotype was defined as forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) z-score less than the lower limit of normal (LLN), whereas the restrictive phenotype was defined as FEV1/FVC z-score ≥LLN, and FVC z-score <LLN.ResultsThe prevalence of obstructive and restrictive phenotypes varied from 3.2–10.9% and 1.8–7.7%, respectively, without clear age trends. A diagnosis of asthma (adjusted odds ratio (aOR=2.55, 95% CI 2.14–3.04), preterm birth (aOR=1.84, 1.27–2.66), maternal smoking during pregnancy (aOR=1.16, 95% CI 1.01–1.35) and family history of asthma (aOR=1.44, 95% CI 1.25–1.66) were associated with a higher prevalence of obstructive, but not restrictive, phenotype across ages (5–25 years). A higher current body mass index (BMI was more often observed in those with the obstructive phenotype but less in those with the restrictive phenotype (aOR=1.05, 95% CI 1.03–1.06 and aOR=0.81, 95% CI 0.78–0.85, per kg·m−2 increase in BMI, respectively). Current smoking was associated with the obstructive phenotype in participants older than 10 years (aOR=1.24, 95% CI 1.05–1.46).ConclusionObstructive and restrictive phenotypes were found to be relatively prevalent during childhood, which supports the early origins concept. Several well-known respiratory risk factors were associated with the obstructive phenotype, whereas only low BMI was associated with the restrictive phenotype, suggesting different underlying pathobiology of these two phenotypes.

Prenatal exposure to metal mixtures and lung function in children from the New Hampshire Birth Cohort Study

BACKGROUND AND AIM: Prenatal environmental exposure to metals and metalloids (referred to as “metals”) has been associated with childhood lung development, but limited data exist on metal mixtures. We aimed to investigate the association between gestational exposure to metal mixtures and childhood lung function among 267 maternal-child dyads from the New Hampshire Birth Cohort Study. METHODS: Maternal ~24-28-week gestational urinary arsenic speciation, aluminum, cadmium, cobalt, chromium, copper, iron, mercury, manganese, molybdenum, nickel, tin, lead, antimony, selenium, thallium, uranium, vanadium and zinc concentration were assessed using inductively coupled plasma mass spectroscopy (ICP-MS). Forced vital capacity (FVC), forced expiratory volume in the first second of exhalation (FEV1), and forced expiratory flow between 25% and 75% of FVC (FEF25-75) standardized z-scores were obtained at a median age of 7.4 years. We used quantile g-computation for each outcome and urinary metals adjusted for maternal smoking status, children’s age, sex and height. RESULTS:Urinary concentrations of cobalt, lead, nickel, cadmium, and chromium were inversely associated with lung function z-scores. Arsenic concentrations were inverse associated specifically with FVC and FEV1 z-scores. In contrast, lung function z-scores increased with vanadium, molybdenum, and thallium urine concentrations. CONCLUSIONS:Our findings suggest that prenatal exposure to metal mixtures impact lung function, with varying direction and magnitudes of effects. KEYWORDS: mixture, heavy metals, children’s environmental health, respiratory outcomes, biomarkers of exposure

Reduced Forced Vital Capacity and the Number of Chest Wall Surgeries are Associated with Decreased Exercise Capacity in Children with Congenital Heart Disease.

Low forced vital capacity (FVC) is associated with decreased exercise capacity in CHD. Multiple prior cardiac surgeries have been associated with low FVC. We seek to understand the relationship between low FVC, number of cardiac surgeries and cardiopulmonary response leading to decreased exercise capacity. Retrospective chart review of demographics, surgical history and exercise testing including spirometry was performed in patients with CHD. Single ventricle patients were excluded. Low FVC was defined as a Z-score below the lower limit of normal. Exercise parameters were expressed as a percent of predicted. There were 93 patients with 2 ventricle CHD identified over 34months with cardiopulmonary exercise testing. The FVC Z-score directly correlated with peak V̇O2% (R2 = 0.07, p < 0.05), and the O2 pulse% (R2 = 0.25, p < 0.0001). The VE/VCO2 was inversely related to the FVC Z-score (R2 = 0.11, p < 0.01). Patients with minimum three prior surgeries had decreased peak VO2% (63.7 vs. 72.8, p < 0.05), decreased peak O2 pulse% (80.8 vs. 97.9, p < 0.01) and a lower mean FVC Z-score (- 1.9 vs - 0.38, p < 0.01). The FVC Z-score and number of surgeries both predicted peak V̇O2% in multivariate analysis. Our study demonstrated that low FVC and three or more prior cardiac surgeries were associated with lower exercise capacity and lower stroke volume response. More cardiac surgeries were also associated with low FVC. However, both low FVC and the number of surgeries were independent predictors of exercise capacity.

Prenatal exposure to arsenic and lung function in children from the New Hampshire Birth Cohort Study

Prenatal arsenic exposure is associated with an increased risk of lung cancer along with multiple non-carcinogenic outcomes, including respiratory diseases in arsenic-contaminated areas. Limited epidemiologic data exist on whether in utero arsenic exposure influences lung development and subsequent respiratory health. We investigated the association between gestational arsenic exposure and childhood lung function in the New Hampshire Birth Cohort Study. Urinary arsenic speciation including inorganic arsenic (iAs), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA) and arsenobetaine was measured in maternal urine samples collected during pregnancy and spirometry was performed in offspring at a median age of 7.4 years. Forced vital capacity (FVC), forced expiratory volume in the first second of exhalation (FEV1), and forced expiratory flow between 25% and 75% of FVC (FEF25-75) standardized z-scores were assessed in linear models as dependent variables with the log2-transformed summation of urinary arsenic species (ΣAs = iAs + MMA + DMA) corrected for specific gravity as an independent variable and with adjustment for maternal smoking status, children’s age, sex and height. Among the 358 children in the study, a doubling of ΣAs was associated with a −0.08 (ß) decrease in FVC z-scores (95% confidence interval (CI) from −0.14 to −0.01) and −0.10 (ß) (95% CI from −0.18 to −0.02) decrease in FEV1 z-scores. The inverse association appeared stronger among those mothers with lower secondary methylation index (urinary DMA/MMA), especially among girls. No association was observed for FEF25-75 z-scores. Our results suggest that gestation arsenic exposure at levels relevant to the general US population during the vulnerable period of lung formation may adversely affect lung function in childhood.

"Poor Effort" Does Not Account for Reduced Forced Vital Capacity in Asthmatic Children.

Purpose: Poor forced vital capacity (FVC) effort has been considered to be the main reason for FVC reduction by the ATS/ERS guideline; however, this has rarely been mentioned in previous studies. The present study aims to determine whether reduced FVC in asthmatic children is correlated to poor FVC effort.Methods: A total of 209 asthmatic children within 5–13 years old were included and divided into reduced FVC (“restricted,” n = 66) and typical obstruction group (“obstructed,” n = 143). Forced expiratory flows before and after bronchodilation were recorded in asthmatic children. The differences in clinical characteristics, spirometric results, FVC effort, and bronchodilator response were compared between two groups. Exhalation time (ET) was divided into effective ET (ETe) and plateau ET (ETp) by the start point of exhalation plateau on the time-volume curve. FVC effort was assessed by ET, ETp, and back extrapolated volume (EV)/FVC (%).Results: Asthmatic children in the restricted group had significantly higher slow vital capacity (SVC)/FVC (%), higher EV/FVC (%), shorter ET, shorter ETe, and longer ETp, when compared with those with obstructed. In the obstructed group, ET (r = 0.201, P = 0.016) and ETe (r = 0.496, P < 0.001) positively correlated with FVC, and ETp (r = −0.224, P = 0.007) negatively correlated with FVC. In the restricted group, FVC positively correlated with ETe (r = 0.350, P = 0.004) but not ET and ETp. FVC z-score significantly correlated with total IgE (n = 51, r = −0.349, P = 0.012) and with FEF25−75% z-score (n = 66, r = 0.531, P < 0.001) in the restricted group. The further logistic regression revealed that the risk of restricted increased by 1.12 (95% CI, 1.04–1.22, P = 0.005) with every 1% increase in %ΔFVC. In subjects with restricted and bronchodilation tests, %ΔFVC was significantly associated with FeNO (n = 29, r = 0.386, P = 0.039), FEF25−75% z-score (n = 29, r = −0.472, P = 0.010), and SVC/FVC (%) (n = 19, r = 0.477, P = 0.039) but not with EV/FVC (%), ET, ETe, or ETp (P > 0.05).Conclusion: These findings suggested that “poor FVC effort” does not account for the FVC reduction in asthmatic children. Short ET and high SVC/FVC (%) are characteristics of reduced FVC.

Relationships between lung function and clinical findings in school-age survivors of preterm birth

Purpose: Survivors of preterm birth are at high risk of chronic pulmonary disease. We examined lung function in the school-age children born preterm and investigated the relationship between lung function and clinical parameters. Methods: Thirty children born preterm were enrolled and divided into 2 groups: 14 very preterm (<32-week gestational age [GA]) and 16 moderate-to-late preterm (32- to 36-week GA). Pulmonary function tests (PFTs) were performed repeatedly during school-age and PFT parameters were compared with age-matched controls. The relationship between PFT and clinical parameters was also studied. Results: PFT parameters in the very preterm group were persistently reduced compared with age-matched controls (P<0.05). Half of the children had been diagnosed with asthma at the visit for the first PFT. Seventy-seven percent of patients in the very preterm group had bronchial hyperresposiveness. Birth weight, duration of oxygen therapy and mechanical ventilation in the neonatal in tensive care unit, and body weight at age 1 were associated with forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), or forced expiratory flow between 25% and 75% of expired vital capacity (FEF25%-75%) z-scores. Multiple regression analysis re vealed that body weight at age 1 was an independent predictor of FEV1 and FVC z-scores, and duration of oxygen therapy was inde pendently associated with FEF25%-75% z-scores (P<0.01 for all). Conclusion: No catch-up in lung function was observed in school-age children born very preterm. Lower body weight at age 1 might be an independent risk factor for reduced FEV1 and FVC, whereas long-term oxygen therapy might be associated with reduced FEF25%-75%. (Allergy Asthma Respir Dis 2021;9:69-75)