Neonates include both full term and preterm infants up to 28 days of age. The heterogeneity and rapid physiologic change of neonates affect all aspects of pharmacokinetics such as absorption, distribution, metabolism, and elimination. This feature should be considered in determining the dose and regimen of drug therapy in neonates. However, the research on the safety and efficacy of specific drugs is limited due to ethical and technical issues. This review article focuses on the neonatal pharmacokinetics and the rationales of drug therapy in neonates based on findings of previous studies and empirical evidence.
Absorption ; Bronchiolitis ; Drug Administration Routes ; Drug Therapy* ; Humans ; Infant ; Infant, Newborn* ; Infant, Premature ; Metabolism ; Pharmacokinetics* ; Population Characteristics

OBJECTIVETo explore the role of intercellular adhesion molecule-1 (ICAM-1) and regulated upon activation normal T cell expressed and secreted (RANTES) in bronchiolitis and their correlation in the pathogenesis of this disorder.

METHODSThe expression of ICAM-1 was detected by flow cytometry on lymphocytes of peripheral blood in 28 infants with bronchiolitis, 23 infants with bronchopneumonia and 24 healthy infants. Serum level of RANTES was assayed using ELISA. The correlation between ICAM-1 and RANTES levels was evaluated using Pearson correlation coefficient.

RESULTSThe ICAM-1 level in the bronchiolitis group (35.0+/-10.3%) was much higher than that in the bronchopneumonia (29.9+/-8.6%; p<0.05) and the control groups (24.6+/-6.9%; p<0.01). The bronchopneumonia group had higher ICAM-1 level than the control group (p<0.05). The RANTES level in the bronchiolitis (32.1+/-6.0 ng/mL) and the bronchopneumonia groups (30.6+/-6.2 ng/mL) was significantly higher than that in the control group (27.1+/-5.1 ng/mL) (p<0.01, p<0.05, respectively), however, no significant difference was found between the bronchopneumonia and bronchiolitis groups. There was a positive correlation between ICAM-1 and RANTES levels in the bronchiolitis group (r=0.675, P<0.01).

CONCLUSIONSICAM-1 and RANTES are involved in the pathogenesis of bronchiolitis and show a synergistic effect.

Bronchiolitis ; etiology ; metabolism ; Chemokine CCL5 ; analysis ; physiology ; Child, Preschool ; Female ; Humans ; Infant ; Intercellular Adhesion Molecule-1 ; analysis ; physiology ; Male

OBJECTIVETo observe the effect of montelukast treatment on levels of serum leukotriene B4 and urinary leukotriene E4 in infants with bronchiolitis.

METHODSSeventy-five children who were diagnosed with bronchiolitis between June 2014 and December 2014 were randomly assigned into two groups, one with thirty-eight cases as the montelukast treatment group and another thirty-seven cases as the control group. All of the children were given routine medical treatment. The children in the montelukast treatment group were additionally given montelukast daily (4 mg once a day, for 7 days). The serum leukotriene B4 and urinary leukotriene E4 levels were measured using ELISA before and after treatment. The relationship between serum leukotriene B4 and urinary leukotriene E4 levels was analyzed by Peason correlation analysis.

RESULTSAfter 7 days of treatment, the serum leukotriene B4 and urinary leukotriene E4 levels in the montelukast treatment and control groups were significantly reduced compared with before treatment (P<0.05). The montelukast treatment group showed significantly lower serum leukotriene B4 and urinary leukotriene E4 levels than the control group (P<0.05). The remission time of cough, wheezing and lung wheezes and the length of hospital stay in the montelukast treatment group were significantly shortened compared with the control group (P<0.05). There was a positive correlation between serum leukotriene B4 and urinary leukotriene E4 levels (r=0.723, P<0.05).

CONCLUSIONSMontelukast has a reliable clinical curative efficacy for bronchiolitis in infants, possibly by decreasing serum leukotriene D4 and urinary leukotriene E4 levels.

Acetates ; therapeutic use ; Bronchiolitis ; drug therapy ; metabolism ; Humans ; Infant ; Leukotriene B4 ; blood ; Leukotriene E4 ; urine ; Quinolines ; therapeutic use

Objective To explore the effect and mechanism of hesperidin in treating the lung injury in the mouse model of respiratory syncytial virus (RSV)-induced bronchiolitis. Methods A mouse model of RSV-induced bronchiolitis was established,and 60 BALB/c mice were assigned into a control group,a model group,a low-dose hesperidin (18 mg/kg) group,a high-dose hesperidin (36 mg/kg) group,and a high-dose hesperidin (36 mg/kg)+Jagged1(1 mg/kg) group by random number table method,with 12 mice in each group. Corresponding doses of drugs were administrated for intervention,and the control group and model group were administrated with the same amount of saline.The bronchoalveolar lavage fluid (BALF) samples were collected and alveolar macrophages were isolated.ELISA was employed to detect the levels of interleukin (IL)-4,IL-6,tumor necrosis factor-α (TNF-α),and IL-10 in BALF,and flow cytometry to detect the M1/M2 polarization of macrophages.qRT-PCR and Western blotting were respectively conducted to detect the mRNA and protein levels of inducible nitric oxide synthase (iNOS),arginase 1 (Arg-1),Jagged1,and Notch1 in the lung tissue. Results Compared with the control group,the modeling of RSV-induced bronchiolitis elevated the IL-4,IL-6,and TNF-α levels,increased the proportion of M1-type macrophages and the lung inflammation and mucus secretion scores,and up-regulated the mRNA and protein levels of iNOS,Jagged1,and Notch1 in BALF (all P<0.001).Meanwhile,the modeling lowered the IL-10 level,decreased the proportion of M2-type macrophages,and down-regulated the mRNA and protein levels of Arg-1 (all P<0.001).Compared with the model group,low- and high-dose hesperidin lowered the IL-4,IL-6,TNF-α levels,decreased the proportion of M1-type macrophages and the lung inflammation and mucus secretion scores,and down-regulated the mRNA and protein levels of iNOS,Jagged1,and Notch1 in BALF (all P<0.05).Moreover,hesperidin elevated the IL-10 level,increased the proportion of M2-type macrophages,and up-regulated the mRNA and protein levels of Arg-1 (all P<0.001).Using recombinant Jagged1 protein to activate Notch1 signaling pathway can significantly attenuate the promotion of high-dose hesperidin on M2 macrophage polarization and amelioration of lung inflammation damage (all P<0.01). Conclusion Hesperidin may alleviate the lung inflammation damage in mice with RSV-induced bronchiolitis by inhibiting the Jagged1/Notch1 signaling pathway and promoting the M2-type polarization of macrophages.
Animals ; Mice ; Bronchiolitis/metabolism* ; Hesperidin/metabolism* ; Interleukin-10/pharmacology* ; Interleukin-4/pharmacology* ; Interleukin-6/metabolism* ; Jagged-1 Protein/pharmacology* ; Lung Injury/metabolism* ; Macrophages ; Mice, Inbred BALB C ; RNA, Messenger/metabolism* ; Tumor Necrosis Factor-alpha/metabolism*

PURPOSE: The purpose of this study was to evaluate the efficacy and metabolism of inhaled steroids to prevent recurrent wheezing after bronchiolitis. METHODS: Sixty two patients were randomly divided into study (n=31) and control (n=31) groups. All of them received budesonide 500 microgram and salbutamol 1.25 mg 4 times a day via nebulizer during admission period (5.5+/-2.5 days). After discharge, the study group patients received fluticasone 50 microgram twice a day with metered dose inhaler with mask spacer for 12 weeks, and the control group received none of inhaled steroids. Serum cortisol and dehydroepiandrosterone sulfate (DHEA-S) concentrations were measured at admission and at the end of the inhaled corticosteroid (ICS) therapy. Weight and height of all patients were checked during the follow-up period. RESULTS: Atopic dermatitis of the patient and allergy family history proved statistically significant. Among high risk group patients, the attack rate of recurrent wheezing in the study group was significantly reduced as compared with the control group. Cortisol levels checked at the end of the ICS therapy were not significantly different from the level checked at admission. In the study group, there was no statistically significant difference between dehydroepiandrosterone sulfate (DHEA-S) level at admission and at the end of the ICS therapy. There was no statistically significant difference of height and weight SDS (standard deviation score) between baseline and 12 weeks later. CONCLUSION: This study suggest that inhaled corticosteroid can be used prophylactically for reducing recurrent wheezing after bronchiolitis in high risk group for asthma.
Albuterol ; Asthma ; Bronchiolitis* ; Budesonide ; Dehydroepiandrosterone Sulfate ; Dermatitis, Atopic ; Follow-Up Studies ; Humans ; Hydrocortisone ; Hypersensitivity ; Masks ; Metabolism ; Metered Dose Inhalers ; Nebulizers and Vaporizers ; Respiratory Sounds* ; Steroids ; Fluticasone

PURPOSE: Vitamin D plays an important role in calcium homeostasis and bone metabolism. It is associated with various diseases such as cardiovascular, immune, allergic and infectious disease. The aim of this study was to investigate the difference in clinical manifestations according to the concentration of vitamin D in mild bronchiolitis. METHODS: We performed a retrospective review of medical records of patients with mild bronchiolitis from November 2016 to April 2017 in Daegu Fatima Hospital. Mild bronchiolitis was classified by the modified Tal's score method. Patients were divided into 2 groups according to a 25-hydroxyvitamin D level of 20 ng/mL. We analyzed the clinical characteristics and laboratory data from the 2 groups. RESULTS: Of the 64 patients, 19 were included in the deficiency group and 45 in the normal group. Vitamin D levels were 11.7±4.9 ng/mL in the deficiency group and 28.8±5.0 ng/mL in the normal group. There were no differences in clinical features between both groups. However, the vitamin D deficiency group had significantly longer hospitalization than the normal group (6.78±2.74 days vs. 5.3±1.7 days, P=0.045). In the deficiency group, the incidence of previous respiratory diseases was significantly higher (P=0.001). No significant difference in blood and respiratory virus tests was observed. CONCLUSION: Low vitamin D levels in mild bronchiolitis were associated with longer hospitalization and prior respiratory disease. Vitamin D may affect the course of mild bronchiolitis.
Bronchiolitis* ; Calcium ; Communicable Diseases ; Daegu ; Homeostasis ; Hospitalization ; Humans ; Incidence ; Medical Records ; Metabolism ; Methods ; Retrospective Studies ; Vitamin D Deficiency ; Vitamin D* ; Vitamins*

BACKGROUNDBronchiolitis obliterans syndrome (BOS) often develops in transplant patients and results in injury to the respiratory and terminal airway epithelium. Owing to its rising incidence, the pathogenesis of BOS is currently an area of intensive research. Studies have shown that injury to the respiratory epithelium results in dysregulation of epithelial repair. Airway epithelial regeneration is supported by stromal cells, including fibroblasts. This study aimed to investigate whether the supportive role of lung fibroblasts is altered in BOS.

METHODSSuspensions of lung cells were prepared by enzyme digestion. Lung progenitor cells (LPCs) were separated by fluorescence-activated cell sorting. Lung fibroblasts from patients with BOS or healthy controls were mixed with sorted mouse LPCs to compare the colony-forming efficiency of LPCs by counting the number of colonies with a diameter of ≥50 μm in each culture. Statistical analyses were performed using the SPSS 17.0 software (SPSS Inc., USA). The paired Student's t-test was used to test for statistical significance.

RESULTSLPCs were isolated with the surface phenotype of CD31-CD34-CD45- EpCAM+Sca-1+. The colony-forming efficiency of LPCs was significantly reduced when co-cultured with fibroblasts isolated from patients with BOS. The addition of SB431542 increased the colony-forming efficiency of LPCs to 1.8%; however, it was still significantly less than that in co-culture with healthy control fibroblasts (P < 0.05).

CONCLUSIONThe epithelial-supportive capacity of fibroblasts is impaired in the development of BOS and suggest that inefficient repair of airway epithelium could contribute to persistent airway inflammation in BOS.

Animals ; Benzamides ; pharmacology ; Bronchiolitis Obliterans ; metabolism ; pathology ; Cells, Cultured ; Coculture Techniques ; Dioxoles ; pharmacology ; Fibroblasts ; cytology ; drug effects ; metabolism ; physiology ; Flow Cytometry ; Humans ; Mice ; Stem Cells ; cytology ; drug effects ; metabolism

OBJECTIVETo study the pulmonary pathology in patients died of fatal human influenza A(H1N1) infection.

METHODSEight cases of fatal human influenza A (H1N1) infection, including 2 autopsy cases and 6 paramortem needle puncture biopsies, were enrolled into the study. Histologic examination, immunohistochemitry, flow cytometry and Western blotting were carried out.

RESULTSThe major pathologic changes included necrotizing bronchiolitis with surrounding inflammation, diffuse alveolar damage and pulmonary hemorrhage. Influenza viral antigen expression was detected in the lung tissue by Western blotting. Immunohistochemical study demonstrated the presence of nuclear protein and hemagglutinin virus antigens in parts of trachea, bronchial epithelium and glands, alveolar epithelium, macrophages and endothelium. Flow cytometry showed that the apoptotic rate of type II pneumocytes (32.15%, 78.15%) was significantly higher than that of the controls (1.93%, 3.77%).

CONCLUSIONNecrotizing bronchiolitis, diffuse alveolar damage and pulmonary hemorrhage followed by pulmonary fibrosis in late stage are the major pathologic changes in fatal human influenza A (H1N1) infection.

Adolescent ; Adult ; Aged ; Alveolar Epithelial Cells ; pathology ; Antigens, Viral ; metabolism ; Apoptosis ; Autopsy ; Biopsy, Needle ; Bronchiolitis, Viral ; pathology ; Child ; Child, Preschool ; Female ; Hemagglutinin Glycoproteins, Influenza Virus ; metabolism ; Humans ; Influenza A Virus, H1N1 Subtype ; immunology ; Influenza, Human ; metabolism ; mortality ; pathology ; virology ; Lung ; immunology ; metabolism ; pathology ; Male ; Middle Aged ; Nuclear Proteins ; metabolism ; Pulmonary Alveoli ; pathology ; Pulmonary Fibrosis ; pathology ; Young Adult

OBJECTIVETo observe the correlation factor about early-life RSV bronchiolitis and sequential recurrent wheezing for two years.

METHODSFollow up the RSV bronchiolitis patients for two years in order to analyze the occurrence of wheezing post-bronchiolitis. Single and multiple logistic regression analysis were used to determined the risk factors such as individual atopy history and familial atopy history, pet feeding, breast milk, secondhand smoke for RSV bronchiolitis and subsequent wheezing.

RESULTS(1) Not breast feeding, exposure to cigarette smoke and the deficiency of VitA, D were the significant risk factors contributed to the RSV branchiolitis. (2) Exposure to cigarette smoke, the deficiency of VitA, D, the personal history of atopy and the family history of atopy were the significant risk factors contributed to the post-bronchiolitis wheezing in children. (3) Those patients who eosinophilia, high serum IgE, RANTES and decreased TH1 to TH2 Ratio were more likely to have wheezing after RSV bronchiolitis.

CONCLUSION(1) Not breast feeding, exposure to cigarette smoke and the deficiency of VitA, D were the significant risk factors contributed to the RSV bronchiolitis. (2) Exposure to cigarette smoke, the deficiency of VitA, D, the personal history of atopy and the family history of atopy were the significant risk factors contributed to the post-bronchiolitis wheezing in children.

Breast Feeding ; Bronchiolitis ; complications ; immunology ; metabolism ; virology ; Case-Control Studies ; Child ; Child, Preschool ; Female ; Follow-Up Studies ; Humans ; Infant ; Male ; Respiratory Sounds ; etiology ; immunology ; Respiratory Syncytial Virus Infections ; complications ; immunology ; metabolism ; virology ; Respiratory Syncytial Virus, Human ; physiology ; Risk Factors ; Tobacco Smoke Pollution ; adverse effects ; Vitamin A ; metabolism ; Vitamin D ; metabolism

Acetates ; administration & dosage ; therapeutic use ; Asthma ; drug therapy ; etiology ; metabolism ; Bronchiolitis, Viral ; drug therapy ; Cysteine ; metabolism ; Humans ; Infant ; Infant, Newborn ; Leukotriene Antagonists ; administration & dosage ; therapeutic use ; Leukotrienes ; biosynthesis ; Nasopharynx ; secretion ; Quinolines ; administration & dosage ; therapeutic use ; Respiratory Syncytial Virus Infections ; drug therapy ; metabolism ; virology ; Risk Factors