leukotriene-e4 and Respiratory-Sounds

Eosinophilic airways inflammation forms the pathophysiologic basis for a proportion of children at risk of developing recurrent wheezing. Early preventive measures and/or anti-inflammatory treatment may be guided by the identification of such children. We aimed to study the relationship between respiratory symptoms and indirect markers of airway inflammation.. We measured eosinophil protein X (EPX) and leukotriene E(4) (LTE(4)) in urine, as well as eosinophil cationic protein (ECP) in nasal lavages, in a random sample of 1-year-old children with a family history of atopy who participated in an international multicenter study on the prevention of allergy in Europe. For urine analyses, 10 children with upper respiratory illness and 19 healthy children without a family history of atopy were also enrolled. Endogenous urinary LTE(4) was separated by HPLC and determined by enzyme immunoassay with a specific antibody. The concentrations of nasal ECP and urinary EPX were determined by RIA analysis.. One hundred and ten children (mean age: 1.05+/-0.1 years) were enrolled. Prolonged coughing during the first year of life was reported in 29 children, wheezy breathing in 17 children, and dry skin in 33 children. A doctor's diagnosis of wheezy bronchitis was given to 17 children. Sensitization to dust mites (specific IgE > or =1.43 ML/units) was detected in two children. Children with a doctor's diagnosis of atopic dermatitis within the first 12 months of life (n=6) had significantly higher urinary EPX than children without this (66.7 vs 30.1 microg/mmol creatinine, P=0.01). Urinary excretion of EPX and LTE4 showed a weak correlation (r=0.22, P=0.02). There were no significant differences in urinary excretion of EPX and LTE(4) or nasal ECP between children with and without respiratory symptoms (P>0.1).. At the age of 1 year, urinary EPX is increased in children with atopic dermatitis. With regard to respiratory symptoms, urinary and nasal inflammatory parameters are not helpful in characterizing the phenotype of a single patient.

Topics: Animals; Biomarkers; Blood Proteins; Bronchitis; Cohort Studies; Cough; Dust; Eosinophil Granule Proteins; Eosinophil-Derived Neurotoxin; Europe; Family Health; Female; Humans; Immunoglobulin E; Infant; Infant Welfare; Leukotriene E4; Male; Mites; Nasal Lavage Fluid; Prevalence; Respiratory Hypersensitivity; Respiratory Sounds; Ribonucleases; Surveys and Questionnaires

Backround: Reliable biological markers for the differentiation of asthma phenotypes in preschool children with wheezing are lacking. The purpose of the study is to assess the relationship of urinary Leukotriene E4 (U-LTE4) to particular asthma phenotypes in preschool children with recurrent episodic (viral) wheezing following upper respiratory tract infections with or without atopic predisposition.. Ninety-six preschool patients with recurrent episodic wheezing participated, 52 atopic and 44 non-atopic, during exacerbation and in remission. Exacerbation was defined on clinical basis (wheeze in the presence of coryzal symptoms). Atopy was determined by specific serum IgE measurement and skin-prick testing. U-LTE4 was determined by enzyme immunoassay. Thirty-six age-matched, non-asthmatic, non-atopic children served as controls.. During exacerbation, U-LTE4 was significantly higher in all children with recurrent episodic wheezing in comparison to A: Remission: 642.20 ± 268 versus 399.45 ± 204, p value <0.001 and B:. 642.20 ± 268 versus 271.39 ± 83, p value <0.001. Atopic patients demonstrated significantly higher levels of U-LTE4 compared to non-atopic, both during exacerbation 872.13 ± 246 versus 613.15 ± 150, p value = 0.0013 and during remission 507.59 ± 182 versus 283.59 ± 160, p value <0.001. During remission, a highly significant difference of U-LTE4 was found when controls were compared to atopic patients: 271.39 ± 83 versus 507.59 ± 182, p value = 0.002 but not when compared to non-atopic ones: 271.39 ± 83 versus 283.59 ± 160, p value = 0.432.. U-LTE4 is strongly associated with the acute wheeze episode in preschool children, more so in atopics. Increased basal levels of U-LTE4 occur only in atopics. This suggests a potential role of U-LTE4 as a marker of atopic, virus-induced asthma in preschool children.

Topics: Asthma; Biomarkers; Child, Preschool; Diagnosis, Differential; Female; Humans; Hypersensitivity, Immediate; Leukotriene E4; Male; Respiratory Sounds; Respiratory Tract Infections; Virus Diseases

The persistence of wheezing after early wheezing episodes in infancy may be related to the virus involved and to the type of inflammation during the initial wheezing. The role of mast cell activation and leukotriene secretion in wheezing, and the relation to outcome, is not known. Our objective was to study markers of mast cell activation and leukotriene secretion from wheezing infants, and the relation to respiratory syncytial virus (RSV) infection and persistent wheezing. Urinary 9alpha,11beta-PGF(2), a marker of mast cell activation, and urinary leukotriene E4 were measured in 106 infants hospitalized for wheezing during their first year of life. Results were related to the presence of RSV infection and the persistence of wheezing at follow-up 20 months later. Levels of 9alpha,11beta-PGF(2) were higher in infants positive for RSV than in those with RSV negative wheezing, but both groups had higher levels than controls. Leukotriene E4 levels were higher in wheezing infants than in controls. Urinary 9alpha,11beta-PGF(2) levels were higher in infants with transient compared with persistent wheezing. We found a positive correlation between 9alpha,11beta-PGF(2) and leukotriene E4, strongest in infants with RSV negative disease and in infants with persistent wheezing. The results suggest that mast cells play an important role in infant wheezing, and may be a major source of leukotriene secretion in these infants. Mast cell activation and leukotriene secretion were not associated with persistent wheezing.

Topics: Eosinophil-Derived Neurotoxin; Eosinophils; Female; Humans; Infant; Leukocyte Count; Leukotriene E4; Leukotrienes; Male; Mast Cells; Regression Analysis; Respiratory Sounds; Respiratory Syncytial Virus Infections

Respiratory syncytial virus (RSV) infection is a risk factor for the development of asthma. It is very hard to distinguish bronchiolitis with respiratory virus infection from allergic asthma at first wheezing attack in early childhood. To distinguish wheezing children with RSV bronchiolitis from asthmatic children, we measured leukotriene E(4)(LTE(4)) in urine and ECP in nasopharyngeal aspiration (NPA) at first day of admission with wheezing attack. Thirty-two non-atopic children younger than the age of 3 yr with RSV induced bronchiolitis, 35 atopic asthmatic children with/without respiratory viral infection, and 23 children who exhibited no evidence of atopy, asthma, or virus infections as controls were selected in this study. We measured urinary LTE(4) and ECP level in NPA from subjects. Urinary LTE(4) concentrations in children with asthma were significantly higher than urinary LTE(4) in bronchiolitis and in controls (240.8 +/- 129.8 vs. 162.8 +/- 73.9 vs. 85.1 +/- 31.6 pg/ml). Children with RSV infection demonstrated higher urinary LTE(4) levels compared to children without RSV infection among asthmatic children. ECP in NPA was significantly correlated with urinary LTE(4) (r = 0.57, p < 0.01) in children entered this study who had detectable levels for both LTE(4) and ECP. In summary, Urinary LTE(4) concentrations may be suggested to useful mediators for differential diagnosis of wheezy diseases in early childhood. RSV infection also is associated with synergizing LT biosynthesis and this study demonstrated ECP in NPA was significantly correlated with urinary LTE(4) and may suggest that cysteinyl leukotriene initiate the production of ECP in early childhood, which could contribute to the development of wheeze.

Topics: Asthma; Bronchiolitis; Case-Control Studies; Child, Preschool; Diagnosis, Differential; Eosinophil Cationic Protein; Female; Humans; Infant; Leukotriene E4; Male; Nasopharynx; Respiratory Sounds; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Suction

Cysteinyl leukotrienes (cystLTs) are important mediators of wheeze in atopic asthma, but the role of cystLTs in the pathogenesis of preschool viral wheeze (PVW) is unclear. Therefore, evidence for increased production of cystLTs in PVW was sought. Urinary leukotriene E4 (uLTE4) and serum total immunoglobulin (Ig)E were measured in children (1-5 yrs) with PVW during an acute attack (n=44) and in the convalescent phase (n=19), and compared with normal controls (n=15). The effect of atopic sensitisation was assessed in a separate group of atopic controls (n=6) in whom only uLTE4 was measured. The levels of uLTE4 were similar in normal and atopic controls and increased in acute PVW (median (interquartile range) 165 (101-285) versus 125 (82-163) ng x mM creatinine(-1)). Stratification by IgE showed that whereas uLTE4 was increased in 23 children with acute PVW and IgE > 95th percentile (median 211 (118-312) ng x mM creatinine(-1)), uLTE4 was not increased in the 21 children with acute PVW and IgE < or = 95th percentile. In the convalescent phase, uLTE4 fell in the subgroup with high IgE but not in the subgroup with low IgE. It is concluded that increased cysteinyl leukotriene production during acute preschool viral wheeze is associated with high serum immunoglobulin E.

Topics: Child, Preschool; Female; Humans; Hypersensitivity, Immediate; Immunoglobulin E; Infant; Leukotriene E4; Male; Respiratory Sounds; Virus Diseases

It is not clear why certain infants wheeze during viral upper respiratory tract infections (URTIs) but it is possible that they have a tendency to mount an exaggerated inflammatory response leading to production of mediators that induce airway narrowing. We studied nasal tumour necrosis factor-alpha (TNF alpha) and urinary leukotriene E4 (LTE4) production during infection and after recovery in 31 wheezy infants (median age 6.2 months). Urinary LTE4 production was not altered during wheezy episodes or URTIs. However, the concentration of TNF alpha in nasal lining fluid (NLF) was significantly increased during acute episodes of wheeze compared to recovery (median [interquartile range] of 293 [42-1753] vs 0 [0-203] pg/ml NLF). TNF alpha was detectable more often and in higher concentration when wheezing was due to respiratory syncytial virus. TNF alpha was also present in 7/30 asymptomatic wheezy infants who had recovered from infection (> 100 pg/ml NLF) and in 4/7 non-wheezy siblings during URTIs (> 200 pg/ml NLF). This suggests that upregulation of TNF alpha production is not the only factor that makes some infants wheeze.

Topics: Child, Preschool; Female; Humans; Infant; Leukotriene E4; Male; Nasal Mucosa; Respiratory Sounds; Respiratory Tract Infections; Tumor Necrosis Factor-alpha