Does BMI Modify the Association between Vitamin D and Pulmonary Function in Children of the Mild Asthma Phenotype?

Vitamin D deficiency and obesity are global health problems that are associated with increased asthma risk in children. The purpose of this study was to investigate whether BMI modifies pulmonary function across vitamin D tertiles in pediatric asthma patients of the mild asthma phenotype. This cross-sectional study conducted from November 2016-September 2017 compared lung function variability as assessed by spirometry and nitric oxide in exhaled breath (FeNO) among 35 normal-weight and 26 overweight/obese Greek schoolchildren (5-12 years old) with mild asthma. Serum 25 (OH)D levels ≥ 30 ng/mL were defined as 'sufficient', 20-30 ng/mL 'insufficient', and <20 ng/mL 'deficient'. Stratification by BMI category, linear regression showed positive associations between D, % FVC (ß = 0.49, 95%CI: 0.05, 0.94), and % FEV1 (ß = 0.48, 95%CI: -0.01, 0.95) in the normal-weight only, adjusted for age, sex, regular exercise, and medication. FEV1 was 10% higher in the normal-weight D-sufficient group compared to those D-deficient (ß = 10.43, 95%CI: 0.54, 20.32). No associations were observed for the overweight/obese group or FeNO. In conclusion, BMI modified associations of vitamin D on airway mechanics in children of the mild asthma phenotype. Serum 25 (OH)D concentrations ≥ 30 ng/mL were associated with higher ventilation in central airways of normal-weight asthmatic children.

Plasma lipid biomarkers in relation to BMI, lung function, and airway inflammation in pediatric asthma.

INTRODUCTION: There is limited understanding of how plasma fatty acid levels affect pulmonary function in pediatric years. It has been speculated that polyunsaturated fatty acids influence asthma via anti or pro-inflammatory mechanisms. Metabolomics presents a new and promising resource for identifying molecular processes involved in asthma pathology. OBJECTIVES: We investigated the relationship of plasma fatty acid metabolites as biomarkers of the 'mild-asthma' phenotype and lung function including airway inflammation in children. METHODS: This cross-sectional study involved 64 children (5-12 years, 33 male) with mild-asthma phenotype attending an outpatient pediatric clinic in Athens, Greece. Clinical examination included spirometry (FVC, FEV1, FEV1/FVC, PEF, FEF25-75%) and Fractional exhaled Nitric Oxide (FeNO). Targeted metabolomic profiling was used to quantify plasma fatty acid composition. Associations between lipids and pulmonary function indices were investigated applying linear regression. RESULTS: Targeted GC-MS identified 25 unique plasma fatty acids in mild-asthmatic children. Linear regression revealed significant associations between linoleic, oleic, erucic, cis-11-eicosenoic, arachidic acids and FEV1, FVC, FEV1/FVC, PEF, FEF25-75% and FeNO in the overweight/obese group, adjusting for age and sex; and in the normo-weight between stearic and arachidic acids versus FEV1 and FEV1/FVC respectively. No associations were observed for arachidonic, α-linolenic, EPA and DHA. CONCLUSION: Metabolomics is a novel science that is useful to discover metabolic signatures specific to disease. Evaluation of fatty acid status could assist clinicians in decision-making about a dietary modification that can be used for personalized nutrition therapies to achieve better asthma control, optimum lung function, and therapeutic response in children.

Potential role of folate status on pulmonary function in pediatric asthma.

OBJECTIVE: The aim of this study was to explore the relationship between plasma folate status and measures of airway disease (as reflected by spirometry) in children with asthma on a traditional Mediterranean diet. We hypothesized that folate deficiency is associated with lung function impairment in this group of children. METHODS: This cross-sectional study included 64 children with mild asthma (52% boys, mean age 8 ± 2 y) residing in Athens, Greece. Clinical assessments included spirometry and fractional exhaled nitric oxide (FeNO). Plasma 5-methyltetrahydrofolate (5-MTHF) was analyzed using high performance-liquid chromatography assay and examined in participants using quartiles (Q1-Q4). RESULTS: Of the 64 children, 45.3% were folate deficient (5-MTHF <10 nmol/L). A positive relationship was observed between 5-MTHF and forced vital capacity (FVC; ß = 0.79, 95% confidence interval (CI), 0.14-1.44; adjusted P = 0.019), forced expiratory volume in 1s (FEV1) (ß = 0.78; 95% CI, 0.01-1.55; adjusted P = 0.046), and peak expiratory flow (PEF; ß = 1.64; 95% CI, 0.14-3.15; adjusted P = 0.033) in girls only, adjusting for body mass index and regular exercise. Girls with low plasma folate concentrations (Q1), compared with girls with high concentrations (Q4) had 8.64% lower FVC (ß = -8.64; 95% CI, -16.18 to -1.09; adjusted P = 0.027), 10.35% FEV1 (ß = -10.35; 95% CI, -18.82 to -1.89; adjusted P = 0.019), and 18.72% PEF (ß = -18.72; 95% CI, -36.30 to -1.14; adjusted P = 0.038). CONCLUSION: The findings of this study highlighted the potential negative effects of folate deficiency on pulmonary function in girls with asthma, the importance of monitoring folate status in children with asthma, and early prevention strategies.

Application of Metabolomics in Pediatric Asthma: Prediction, Diagnosis and Personalized Treatment.

Asthma in children remains a significant public health challenge affecting 5-20% of children in Europe and is associated with increased morbidity and societal healthcare costs. The high variation in asthma incidence among countries may be attributed to differences in genetic susceptibility and environmental factors. This respiratory disorder is described as a heterogeneous syndrome of multiple clinical manifestations (phenotypes) with varying degrees of severity and airway hyper-responsiveness, which is based on patient symptoms, lung function and response to pharmacotherapy. However, an accurate diagnosis is often difficult due to diversities in clinical presentation. Therefore, identifying early diagnostic biomarkers and improving the monitoring of airway dysfunction and inflammatory through non-invasive methods are key goals in successful pediatric asthma management. Given that asthma is caused by the interaction between genes and environmental factors, an emerging approach, metabolomics-the systematic analysis of small molecules-can provide more insight into asthma pathophysiological mechanisms, enable the identification of early biomarkers and targeted personalized therapies, thus reducing disease burden and societal cost. The purpose of this review is to present evidence on the utility of metabolomics in pediatric asthma through the analysis of intermediate metabolites of biochemical pathways that involve carbohydrates, amino acids, lipids, organic acids and nucleotides and discuss their potential application in clinical practice. Also, current challenges on the integration of metabolomics in pediatric asthma management and needed next steps are critically discussed.

Sufficient vitamin D status positively modified ventilatory function in asthmatic children following a Mediterranean diet enriched with fatty fish intervention study.

Asthma in children is the most prevalent allergic disease worldwide that has become a major public health priority. The objective of this study was to examine the relationship between baseline serum vitamin D status, spirometry, and fractional exhaled nitric oxide levels (FeNO) in 64 Greek children with 'mild asthma' aged 5 to 12 years (51.6% male) in a dietary intervention study. We hypothesized that baseline serum vitamin D levels modify the beneficial response of fatty fish intake on pulmonary function in asthmatic children following a Mediterranean diet. The intervention group consumed 2 fatty fish meals/week (≥150 g cooked filleted fish/meal) as part of the Mediterranean diet for six months, and the control group consumed their usual diet. Baseline serum 25(OH)D was determined using enzyme-linked immunoassay and defined as sufficient levels of 25(OH)D ≥25 ng/mL. Only 36% of children were graded as sufficient in 25(OH)D levels on entry into the study with a higher proportion of girls insufficient than boys (61% vs 39% respectively). Participants with sufficient levels of serum 25(OH)D at baseline, consuming the intervention diet increased FEV1/FVC by 4.89 units (ß = 4.89; 95%CI: 1.19-8.61; p = 0.013) and FEF25-75% by 12.83 units (ß = 12.83; 95%CI: 4.27-21.40; p = 0.006) compared to controls. No significant differences in pulmonary function or FeNO were observed for those with insufficient levels of 25(OH) D in the intervention or control groups. In conclusion, sufficient serum vitamin D levels enhanced ventilatory function in response to a dietary intervention in asthmatic children.

Weight Status and Respiratory Health in Asthmatic Children.

In this study,we explored the effect of adiposity as measured by BMI on lung function in 72 asthmatic school children (5-12 years) using baseline data from the Mediterranean diet enriched with fatty fish intervention study. Bronchial function was assessed using spirometry and fractional exhaled nitric oxide (FeNO). BMI categories were classified as normal and overweight/obese based on International Obesity Task Force cut-offs. Weak correlations were observed between BMI and FVC (p = 0.013) and FEV1 (p = 0.026). Median FeNO was lower in the overweight/obese as compared to normal weight group (p = 0.027). Linear regression showed an increment in FEF25-75% in the overweight/obese group as compared to normal weight after controlling for confounders namely age, height, sex, regular physical activity, medication and KIDMED score (p = 0.043; ß = 11.65 units, 95% CI 0.36-22.94), although with no effect on FeNO. In conclusion, the findings of this study suggest that excess body weight could impact pulmonary dynamics in childhood asthma.

Urinary organic acids as biomarkers in the assessment of pulmonary function in children with asthma.

Childhood asthma prevalence continues to rise despite advancements in prevention and medical management strategies. The purpose of this study was to investigate correlations between urinary organic acids and pulmonary diagnostic tests, asthma control in Greek asthmatic children. We hypothesized that urinary organic acids are positively associated with poor pulmonary function in children with asthma. Seventy-two children, 5 to 12 years old with asthma were recruited from a pediatric asthma clinic in Athens, Greece. Pulmonary function was assessed using spirometry and exhaled nitric oxide analysis. Asthma control was measured qualitatively using the Asthma Control Questionnaire. Targeted metabolomic analysis of 34 urinary organic acids in children was conducted by gas chromatography-mass spectrometry. A statistically significant difference between girls and boys was found for asthma control score (P = .02), lactic acid (P = .03), but not for any other organic acids (P > .05). Statistically significant correlations were found between lactic acid and Forced Expiratory Volume in 1 second (FEV1) (P = .02), Forced Vital Capacity (FVC) (P = .03); 4- hydroxyphenylacetic acid and FEV1 (P = .01), FVC (P = .01); 5-hydroxyindoleacetic acid and FEV1/FVC (P = .03), eNO (P = .05); glycolic acid with Peak Expiratory Flow (PEF) (P = .03); and malic acid with asthma control (P = .02). In conclusion, metabolomics was used to determine correlations between urinary organic acids and conventional pulmonary diagnostic tests in Greek asthmatic children. Metabolomics could be a promising approach for asthma research and in detection of novel biomarkers for asthma monitoring and therapeutic targets for childhood asthma. This study contributes towards a better understanding of the biochemical pathways involved in asthma.

RespDoc: a new clinical decision support system for childhood asthma management based on Fraction of Exhaled Nitric Oxide (FeNO) measurements.

The use of Fraction of Exhaled Nitric Oxide (FeNO) for measurement of inflammation in the respiratory system is a good way to assess the level of asthma in children. In this paper we present a new Clinical Decision Support System (CDSS) for Childhood Asthma Management based on FeNO, which is named RespDoc. The core of RespDoc is a decision making algorithm and a patient's monitoring process that are extensively analyzed in the paper. The performance of RespDoc is tested through the process and assessment of archived patients' data.

Spirometric reference values in greek children and adolescents.

AIM: This study was performed to describe the relationship among anthropometric parameters and lung function in Greek children, to produce reference values for spirometry and to compare these results with other data sets. PATIENTS AND METHODS: Spirometric values were measured with electronic portable Spirometer Spirolab II (MIR) in 414 healthy, nonsmoking Greek children, aged 6-18 years. Multiple linear regression analysis was performed for each spirometric parameter against age, height, weight and body mass index (BMI). RESULTS: The highest correlation was found with height. Predictive equations for: forced expiratory volume in the first sec (FEV(1)), forced vital capacity (FVC), forced expiratory flow from 25%-75% of the vital capacity (FEF(25-75%)) and peak expiratory flow (PEF) with standing height as the dependent variable are presented for both sexes. Our reference values are close to those of other European children. CONCLUSION: The developed predictive equations can be used in clinical practice in Greece and in other neighboring Balkan countries.