Inhaled drug airflow patterns and particles deposition in the paediatric respiratory tract.

PURPOSE: The effectiveness of inhaled drugs is strictly related to areas reachable by drug particles. Unless particles reach the desired part of the bronchial tree, their influence might not meet the expectations. Consequently, the disease progress might not be stopped or even slowed down. Therefore, the primary objective of this research was to analyze the airflow patterns and particle deposition of a standard inhaled drug using computational fluid dynamics. METHODS: The study was devoted to the analysis of the particle diameter influence on their deposition areas within the entire respiratory tract. Two patient-specific respiratory tract models, for 6 and 12-year-old patients, were reconstructed based on the computed tomography examinations. Numerical analyses were carried out as stationary ones with the constant inflow of the particles of various diameters (within the range of 1-50 µm). It was proven that depending on the particle size, their deposition within the respiratory tract varies significantly. RESULTS: The vast majority of the particles with diameters over 20 µm is gathered on the walls of the throat, whereas particles of diameters 5-15 µm are accumulated mainly on the trachea walls, leaving the alveoli insufficiently supplied with the drug particles. CONCLUSIONS: The inhaled drug size cannot be treated as negligible factor during the drug spraying. An improper distribution of the particles might not inhibit the symptoms of the asthma. Numerical simulations may improve drugs selection and visualize their distribution along the airways, which might accelerate asthma treatment personalization.

Klotho and fibroblast growth factors 19 and 21 serum concentrations in children and adolescents with normal body weight and obesity and their associations with metabolic parameters.

BACKGROUND: Fibroblast growth factor 19 (FGF19), fibroblast growth factor 21 (FGF21) and Klotho are regulators of energy homeostasis. However, in the pediatric population, the relationships between obesity, metabolic disorders and the aforementioned factors have not been clearly investigated. We analyzed the role of FGF19, FGF21 and Klotho protein in children with normal body weight as well as in overweight and obese subjects and explored their associations with insulin resistance (IR) and metabolic syndrome (MS) and its components. METHODS: This was a cross-sectional study conducted in a group of hospitalized children and adolescents. Laboratory investigations included serum analysis of FGF19, FGF21, and Klotho with ELISA kits as well as the analysis of the lipid profile and ALT serum concentrations. Moreover, each subject underwent an oral glucose tolerance test (OGTT) with fasting insulinemia measurement to detect glucose tolerance abnormalities and calculate the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) index. Furthermore, the clinical analysis included blood pressure measurement, body fat percentage estimation and assessment of the prevalence of MS and its components. RESULTS: The study was conducted with 174 children/adolescents aged 6-17 years with normal body weight (N = 48), obesity (N = 92) and overweight (N = 34). Klotho concentration was significantly higher in the obese children [median 168.6 pg/ml (90.2 to 375.9)]) than in the overweight [131.3 pg/ml (78.0 to 313.0)] and normal-body-weight subjects [116.6 pg/ml (38.5 to 163.9)] (p = 0.0334) and was also significantly higher in insulin-resistant children than in insulin-sensitive children [185.3 pg/ml (102.1 to 398.2) vs 132.6 pg/ml (63.9 to 275.6), p = 0.0283]. FGF21 was elevated in patients with MS compared to the FGF21 levels in other subjects [136.2 pg/ml (86.5 to 239.9) vs 82.6 pg/ml (41.8 to 152.4), p = 0.0286]. The multivariable model showed that FGF19 was an independent predictor of IR after adjusting for pubertal stage and BMI Z-score. CONCLUSIONS: Klotho levels were associated with body weight status in children and adolescents. Moreover, Klotho, FGF19 and FGF21 concentrations correlated with IR status and/or components of MS.