Updated reference values for static lung volumes from a healthy population in Austria.

BACKGROUND: Reference values for lung volumes are necessary to identify and diagnose restrictive lung diseases and hyperinflation, but the values have to be validated in the relevant population. Our aim was to investigate the Global Lung Function Initiative (GLI) reference equations in a representative healthy Austrian population and create population-derived reference equations if poor fit was observed. METHODS: We analysed spirometry and body plethysmography data from 5371 respiratory healthy subjects (6-80 years) from the Austrian LEAD Study. Fit with the GLI equations was examined using z-scores and distributions within the limits of normality. LEAD reference equations were then created using the LMS method and the generalized additive model of location shape and scale package according to GLI models. RESULTS: Good fit, defined as mean z-scores between + 0.5 and -0.5,was not observed for the GLI static lung volume equations, with mean z-scores > 0.5 for residual volume (RV), RV/TLC (total lung capacity) and TLC in both sexes, and for expiratory reserve volume (ERV) and inspiratory capacity in females. Distribution within the limits of normality were shifted to the upper limit except for ERV. Population-derived reference equations from the LEAD cohort showed superior fit for lung volumes and provided reproducible results. CONCLUSION: GLI lung volume reference equations demonstrated a poor fit for our cohort, especially in females. Therefore a new set of Austrian reference equations for static lung volumes was developed, that can be applied to both children and adults (6-80 years of age).

The effect of body compartments on lung function in childhood and adolescence.

BACKGROUND: There is an association between body composition and lung function, assessed by spirometry, but the effects of body compartments on static lung volumes and its changes during lung growth remain to be explored. We aimed to investigate the association of appendicular lean mass, reflecting skeletal muscle mass, and fat mass on forced and static lung function measures in childhood and adolescence. METHODS: In total, 1489 children and adolescents (6-18 years) of the observational, longitudinal (first and second visit within 4 years), general population-based LEAD study have been investigated. The association of appendicular lean mass and fat mass indices (ALMI and FMI; assessed by dual-energy X-ray absorptiometry) on lung function by spirometry (FEV1, FVC) and body plethysmography (TLC, RV, FRC) was investigated cross-sectionally. Longitudinal associations between lung function and body compartment changes between the two visits were analyzed. FINDINGS: The ALMI is positively associated with FEV1, FVC, and TLC. Contrary, FMI is inversely associated with lung function measures including FRC and RV. During the phase of lung growth, higher gain in muscle mass is associated with higher increases of FVC and TLC. INTERPRETATION: This study demonstrates the different effects of muscle and fat mass on forced expiratory and static lung volumes. Achieving and maintaining muscle mass in childhood and adolescence might become an important preventive strategy for lung health in adulthood.

Supranormal lung function: Prevalence, associated factors and clinical manifestations across the lifespan.

BACKGROUND AND OBJECTIVE: It is now well established that there are different life-long lung function trajectories in the general population, and that some are associated with better or worse health outcomes. Yet, the prevalence, clinical characteristics and risk factors of individuals with supranormal FEV1 or FVC values (above the upper-limit of normal [ULN]) in different age-bins through the lifetime in the general population are poorly understood. METHOD: To address these questions, we investigated the prevalence of supranormal FEV1 and FVC values in the LEAD (Lung, hEart, sociAl and boDy) study, a general population cohort in Austria that includes participants from 6 to 82 years of age. RESULTS: We found that: (1) the prevalence of supranormal pre-bronchodilator FEV1 and FVC values was 3.4% and 3.1%, respectively, and that these figures remained relatively stable through different age-bins except for participants >60 years., in whom they increased (5.0% and 4.2%, respectively). Approximately 50% of supranormal individuals had both increased FEV1 and FVC values; (2) supranormal spirometric values were consistently accompanied by higher static lung volumes and lower specific airway resistance through the lifespan, indicating better overall lung function; and (3) multivariate regression analysis identified that female sex, higher muscle mass (FFMI), less diabetes and fewer respiratory symptoms were consistently associated with supranormal FEV1 and FVC values. CONCLUSION: Supranormal FEV1 and/or FVC values occur in about 3% of the general population in different age bins and are associated with better health markers.

Prevalence of restrictive lung function in children and adults in the general population.

BACKGROUND: Restrictive lung function (RLF) is characterized by a reduced lung expansion and size. In the absence of lung volume measurements, restriction can be indirectly assessed with restrictive spirometric patterns (RSP) by spirometry. Prevalence data on RLF by the golden standard body plethysmography in the general population are scarce. Therefore, we aimed to evaluate the prevalence of RLF and RSP in the general population by body plethysmography and to determine factors influencing RLF and RSP. METHODS: Pre-bronchodilation lung function data of 8891 subjects (48.0% male, age 6-82 years) have been collected in the LEAD Study, a single-centered, longitudinal, population-based study from Vienna, Austria. The cohort was categorized in the following groups based on the Global Lung Initiative reference equations: normal subjects, RLF (TLC < lower limit of normal (LLN)), RSP (FEV1/FVC ≥ LLN and a FVC < LLN), RSP only (RSP with TLC ≥ LLN). Normal subjects were considered those with FEV1, FVC, FEV1/FVC and TLC between LLN and ULN (upper limit of normal). RESULTS: The prevalence of RLF and RSP in the Austrian general population is 1.1% and 4.4%. Spirometry has a positive and negative predictive value of 18.0% and 99.6% to predict a restrictive lung function. Central obesity was associated with RLF. RSP was related to smoking and underweight. CONCLUSIONS: The prevalence of true restrictive lung function and RSP in the Austrian general population is lower than previously estimated. Our data confirm the need for direct lung volume measurement to diagnose true restrictive lung function.

Using Body Composition Groups to Identify Children and Adolescents at Risk of Dyslipidemia.

The impact of body composition on the early origin of chronic diseases is an increasingly appreciated phenomenon. Little is known about the characteristics of children with varying body composition. The aim of this study was to investigate serum lipid profiles and other characteristics in relation to body composition. The data of 1394 participants (aged 6 to <18 years) of the observational general population-based Austrian LEAD Study have been analyzed. Body composition groups were defined by appendicular lean mass (ALMI) and fat mass (FMI) indices assessed by DXA. Serum lipid profiles (triglycerides, LDL-c, HDL-c) and other characteristics (e.g., prematurity, smoke exposure, physical activity, nutrition) were investigated in these body composition groups. Different body composition groups, which are not distinguishable by BMI, exist. Children with high ALMI and high FMI showed higher triglycerides and LDL-c, but lower HDL-c levels. In contrast, levels did not differ between those with high FMI but low (or normal) ALMI, and other body composition groups. BMI should be interpreted cautiously, and body composition should be measured by more precise techniques. In particular, children and adolescents with high FMI who have concomitantly high ALMI should be followed closely in future studies to investigate whether they are at increased risk of cardiovascular problems.

Reference charts for body composition parameters by dual-energy X-ray absorptiometry in European children and adolescents aged 6 to 18 years-Results from the Austrian LEAD (Lung, hEart, sociAl, boDy) cohort.

BACKGROUND: DXA is a widely used technique to assess body composition. Reference values based on a large general population cohort of European children and adolescents were missing. The aim of this study was to provide age- and sex-specific reference percentiles of body composition parameters for European children and adolescents and to compare them to the American NHANES cohort. Additionally, exponents accounting best for height biases were analysed. METHODS: DXA scans of 1573 participants, aged 6 to 18 years, recruited from 2011 to 2019 by the Austrian LEAD study, a representative population-based cohort, have been used to create reference charts using the LMS model. RESULTS: Reference charts displaying percentile curves and the corresponding reference values are provided. Fat mass parameters were higher in females, while lean mass parameters were higher in males. Compared to the NHANES cohort medians of FMI and LMI were always lower. For FMI, BMI, LMI and ALMI the best fitting exponent were 2.5, 3, 3 and 3.5 respectively CONCLUSIONS: The present study provides reference charts for children and adolescents aged 6 to 18 years, for body composition parameters assessed by DXA. The charts enable comparison to a European general-population cohort and indicate that reference populations should be chosen with caution.

Reference values of body composition parameters and visceral adipose tissue (VAT) by DXA in adults aged 18-81 years-results from the LEAD cohort.

BACKGROUND: Increasing attention has been drawn on the assessment of body composition phenotypes, since the distribution of soft tissue influences cardio-metabolic risk. Dual-energy X-ray absorptiometry (DXA) is a validated technique to assess body composition. European reference values from population-based cohorts are rare. AIMS: To provide age- and sex-related reference values of body composition parameters and visceral adipose tissue (VAT) mass, and for lean mass index (LMI) with regard to fat mass index (FMI) quantities and BMI categories. METHODS: GE-Lunar Prodigy DXA scans of 10.894 participants, aged 18-81 years, recruited from 2011 to 2019 by the Austrian LEAD study, a population-based cohort study, have been used to construct reference curves using the LMS method. Parameters assessed are FMI, LMI, appendicular LMI, fat mass ratios android/gynoid and trunk/limbs, and VAT. RESULTS: All lean mass and fat mass parameters indicating central fat accumulation were higher in men, whereas other fat mass indices were higher in women. LMI differed between each FMI subgroup (low vs. normal, low vs. high, normal vs. high), and BMI category in all ages and LMI increased with FMI and BMI classes. VAT mass was higher in men compared with women and increased across all age groups within both sexes. CONCLUSION: The present study provides age- and sex-related reference values for European adults aged 18-81 years for body composition parameters and VAT mass for Lunar Prodigy DXA. In addition, this study reports LMI reference values with regard to fat mass quantities, showing a positive association with increasing FMI percentiles and BMI categories.

Blood eosinophil count in the general population: typical values and potential confounders.

There is growing interest in blood eosinophil counts in the management of chronic respiratory conditions such as asthma and chronic obstructive pulmonary disease (COPD). Despite this, typical blood eosinophil levels in the general population, and the impact of potential confounders on these levels have not been clearly defined.We measured blood eosinophil counts in a random sample of 11 042 subjects recruited from the general population in Austria. We then: 1) identified factors associated with high blood eosinophil counts (>75th percentile); and 2) excluded subjects with these factors to estimate median blood eosinophil counts in a "healthy" sub-population (n=3641).We found that: 1) in the entire cohort, age ≤18 years (OR 2.41), asthma (OR 2.05), current smoking (OR 1.72), positive skin prick test (OR 1.64), COPD (OR 1.56), metabolic syndrome (OR 1.41), male sex (OR 1.36) and obesity (OR 1.16) were significantly (p<0.05) associated with high blood eosinophil counts (binary multivariable logistic regression analysis), and had an additive effect; and 2) after excluding these factors, in those older than 18 years, blood eosinophil counts were higher in males than in females (median 120 (5%-95% CI: 30-330) versus 100 (30-310) cells·µL-1, respectively) and did not change with age.Median blood eosinophil counts in adults are considerably lower than those currently regarded as normal, do not change with age beyond puberty, but are significantly influenced by a variety of factors which have an additive effect. These observations will contribute to the interpretation of blood eosinophil levels in clinical practice.

Marked differences in prediabetes- and diabetes-associated comorbidities between men and women-Epidemiological results from a general population-based cohort aged 6-80 years-The LEAD (Lung, hEart, sociAl, boDy) study.

BACKGROUND: Based on biological and behavioural diversity sex and gender may affect comorbidities associated with prediabetes and diabetes. Besides evaluating the prevalence of prediabetes and diabetes (using fasting plasma glucose and HbA1c levels), the primary aim of the study is to investigate sex and gender differences in the prevalence of comorbidities in subjects with prediabetes and diabetes and to identify possible risk factors associated with prediabetes and diabetes. DESIGN: This observational, population-based cohort study included 11.014 subjects aged 6-80 years. Examinations included blood samples, ankle-brachial index, ECG, dual-energy X-ray absorptiometry scan and an interviewer-administered questionnaire. RESULTS: Across all ages, prevalence of prediabetes was 20.2% (male 23.6%; female 17.1%), and 5.4% for diabetes (male 7.3%; female 3.7%). The prevalence of prediabetes ranged from 4.4% (6-<10 years) up to 40.4% (70+ years) in men and from 4.8% up to 42.3% in women. Comorbidity profile was markedly different between male and female, particularly in those with prediabetes: women more often suffered from arrhythmia, noncoronary artery disease, osteoporosis, increased systemic inflammatory biomarkers and depression, while men with prediabetes more often showed angina pectoris, myocardial infarction and media sclerosis. CONCLUSIONS: The unexpected 4.6% prevalence of prediabetes in children aged 6-10 underscores the need for population-based studies across all ages and the onset of prevention of diabetes at a young age. Marked differences have been found in comorbidities as men with prediabetes and diabetes more often suffer from cardiovascular disease, while women more often show arrhythmia, noncoronary artery disease, increased systemic inflammatory biomarkers and depression.