Publications of Z Lazar

Lack of heritability of exhaled volatile compound pattern: an electronic nose twin study

Electronic noses can distinguish various disorders by analyzing exhaled volatile organic compound (VOC) pattern; however it is unclear how hereditary and environmental backgrounds affect the exhaled VOC pattern. A twin study enrolling monozygotic (MZ) and dizygotic (DZ) twins is an ideal tool to separate the influence of these factors on the exhaled breath pattern. Exhaled breath samples were collected in duplicates from 28 never smoking twin pairs (in total 112 samples) without lung diseases and processed with an electronic nose (Cyranose 320). Univariate quantitative hereditary modeling (ACE analysis) adjusted for age and gender was performed to decompose the phenotypic variance of the exhaled volatile compound pattern (assessing principal components (PCs) derived from electronic nose data) into hereditary (A), shared (C), and unshared (E) environmental effects. Exhaled VOC pattern showed good intra-subject reproducibility as assessed with the Bland-Altman plot. Significant correlations were found between exhaled VOC patterns of both MZ and DZ twins. The hereditary background did not influence the VOC pattern. The shared environmental effect on PC 1, 2 and 3 was estimated to be 93%, 94% and 54%, respectively. The unshared (unique) environmental influence explained a smaller variance (7%, 6% and 46%). For the first time using the twin design, we have shown that the environmental background largely affects the exhaled volatile compound pattern in never smoking volunteers without respiratory disorders. Further studies should identify these environmental factors and also assess their influence on exhaled breath patterns in patients with lung diseases.

Genetic and environmental factors on the relation of lung function and arterial stiffness

Background An association between reduced lung function and increased cardiovascular risk has been reported, but the underlying mechanisms are unknown. The aim of this study was to assess the heritability of lung function and to estimate its genetic association with arterial stiffness. Methods 150 monozygotic and 42 dizygotic healthy Hungarian and American Caucasian twin pairs (age 43 ± 17 years) underwent spirometry (forced vital capacity/FVC/, forced expiratory volume in 1 s/FEV1/; MIR Minispir, USA); and their brachial and central augmentation indices (AIx), and aortic pulse wave velocity (PWV) were measured by oscillometric Arteriograph (TensioMed Ltd, Budapest, Hungary). Phenotypic correlations and bivariate Cholesky decomposition models were applied. Results Age-, sex-, country- and smoking-adjusted heritability of FEV1, percent predicted FEV1, FVC and percent predicted FVC were 73% (95% confidence interval /CI/: 45–85%), 28% (95% CI: 0–67%), 68% (95% CI: 20–81%) and 45% (95% CI: 0–66%), respectively. Measured and percent predicted FVC and FEV1 values showed no significant phenotypic correlations with AIx or aortic PWV, except for phenotypic twin correlations between measured FEV1, FVC with brachial or aortic augmentation indices which ranged between −0.12 and −0.17. No genetic covariance between lung function and arterial stiffness was found. Conclusions Lung function is heritable and the measured FVC and FEV are phenotypically, but not genetically, associated with augmentation index, a measure of wave reflection. This relationship may in turn reveal further associations leading to a better mechanistic understanding of vascular changes in various airway diseases.

Genetic influence on the relation between exhaled nitric oxide and pulse wave reflection

Nitric oxide has an important role in the development of the structure and function of the airways and vessel walls. Fractional exhaled nitric oxide (FENO) is inversely related to the markers and risk factors of atherosclerosis. We aimed to estimate the relative contribution of genes and shared and non-shared environmental influences to variations and covariation of FENO levels and the marker of elasticity function of arteries. Adult Caucasian twin pairs (n = 117) were recruited in Hungary, Italy and in the United States (83 monozygotic and 34 dizygotic pairs; age: 48 ± 16 SD years). FENO was measured by an electrochemical sensor-based device. Pulse wave reflection (aortic augmentation index, Aixao) was determined by an oscillometric method (Arteriograph). A bivariate Cholesky decomposition model was applied to investigate whether the heritabilities of FENO and Aixao were linked. Genetic effects accounted for 58% (95% confidence interval (CI): 42%, 71%) of the variation in FENO with the remaining 42% (95%CI: 29%, 58%) due to non-shared environmental influences. A modest negative correlation was observed between FENO and Aixao (r = -0.17; 95%CI:-0.32,-0.02). FENO showed a significant negative genetic correlation with Aixao (rg = -0.25; 95%CI:-0.46,-0.02). Thus in humans, variations in FENO are explained both by genetic and non-shared environmental effects. Covariance between FENO and Aixao is explained entirely by shared genetic factors. This is consistent with an overlap among the sets of genes involved in the expression of these phenotypes and provides a basis for further genetic studies on cardiovascular and respiratory diseases.