Vascular endothelial growth factor overexpression in induced sputum of children with bronchial asthma

Vascular endothelial growth factor (VEGF) induces angiogenesis and increases vascular permeability participating in narrowing of the airway lumen that follows lung injury. We sought to investigate the expression of VEGF in induced sputum during and after recovery from acute episodes of bronchial asthma in children. Eighteen asthmatic children with acute attacks of varying severity were subjected to VEGF estimation by an enzymatic immunoassay in induced sputum. They were followed up till complete remission of symptoms and signs and were then retested. VEGF was also estimated in sputum induced from age 34 and sex-matched healthy children enrolled as a control group. The sputum VEGF levels during acute asthma [median = 71 ng/ml; mean (s.d.) = 114.6 (121.8) ng/ml] were significantly higher than the levels estimated during remission [median = 50 ng/ml; mean (s.d.) = 45.7 (24.2) ng/ml] and both were higher than the corresponding levels of the control group [median = 36 ng/ml; mean (s.d.) = 31.3 (17.2) ng/ml]. VEGF levels during asthmatic episodes correlated positively to the recovery levels (r = 0.6, p = 0.009). The patients' VEGF expression did not vary with asthma severity, serum total IgE concentration, peripheral blood eosinophil count, or erythrocyte sedimentation rate of patients. Children on corticosteroids inhalation therapy at enrollment had sputum VEGF levels that were comparable to those on other therapies. The increased expression of sputum VEGF in asthmatic children reinforces the concept that it might have a pathogenetic role in bronchial asthma and may represent a biomarker of airway inflammation.     

Relationship between Vitamin D and Childhood Asthma: A Case–Control Study

Objective:

Studies determining the relationship between serum vitamin D status and childhood asthma have yielded controversial results. Findings indicated that vitamin D deficiency is associated with asthma and airway hyper responsiveness. The aim of this study was to assess the relationship between serum vitamin D status and childhood asthma.

Methods:

Data were obtained from 200 asthmatic children (age 3–12 years) and 200 healthy controls. Serum levels of 25(OH) vitamin D, total IgE, calcium, phosphorus, parathormone (PTH) and eosinophil count were measured in both asthmatic children and healthy controls. Also, the mean values of 25(OH) vitamin D were compared with asthma symptom severities.

Findings:

There was a significant decrease in the concentration of serum 25(OH) vitamin D in the asthmatic patients as compared with the controls (20.34±2.8 vs 25.39±4.1 ng/mL, 95%CI: 1.46–3.86, P=0.01). Out of total asthmatic subjects, 40 (20%) were vitamin D sufficient, 48 (24%) were insufficient, and 112 (56%) were deficient. Total IgE concentration was also significantly higher in asthmatic patients having vitamin D deficiency (132.4±20.1 IU/ml, 95%CI: 1.38–3.75, P=0.03). Comparing asthmatic patients with healthy controls, odds of having vitamin D level less than 20ng/mL was 2.47.

Conclusion:

Our findings suggest that vitamin D deficiency or insufficiency may be positively related to the prevalence of asthma in children.     

Exhaled nitric oxide in asthmatic children and adolescents after nasal allergen challenge

Epidemiological data suggest a comorbidity link between nasal and bronchial allergic disease. Exhaled nitric oxide (FENO) is a sensitive marker of bronchial inflammation and increases after bronchial allergen provocation. We studied FENO in 19 children and adolescents with allergic asthma and 10 controls before and 2, 6 and 24 h after a single nasal allergen challenge. The correlation between FENO and other markers of allergic inflammation, such as eosinophils in blood and eosinophil cationic protein (ECP) in serum and nasal lavage was also assessed. FENO remained unchanged 24 h post-challenge in both steroid and steroid-naive patients. At 6 h post-challenge, FENO decreased in both asthmatics and controls. The asthmatic subjects showed a positive correlation between FENO and blood eosinophils before (r=0.71, p=0.001) and after the challenge, and between FENO and ECP in nasal lavage (r=0.62, p=0.02) 2 h after the challenge. Mean ECP in nasal lavage increased post-challenge but not significantly. We conclude that a single nasal allergen challenge does not augment bronchial inflammation although FENO, is related to blood eosinophil count and to the nasal inflammatory response. Our data do not support the theory of a direct transmission of the nasal inflammation to the lower airways.     

Serum magnesium levels in asthmatic children during and between exacerbations

OBJECTIVE: To determine, if possible, whether magnesium deficiency exists in children with asthma during acute attacks and between exacerbations. SETTING: Emergency Department Clinic and Outpatient Pediatric Clinic of Jordan University of Science and Technology, Irbid. METHODS: A total of 174 known asthmatic children who presented to the emergency department in acute attack (group 1) and 94 asthmatic children who presented to outpatient clinics for follow-up of asthma (group 2) had their serum magnesium levels assayed and compared with 232 patients without asthma (controls; group 3). Exclusion criteria were history of renal disease, cardiac disease, malabsorption, diuretic use, alcoholism, and pregnancy. RESULTS: There were no differences between study groups, although male patients had a slightly lower level of magnesium than female patients. CONCLUSION: After removing the confounder of sex, serum magnesium levels in asthmatic children during acute attacks and between exacerbations are not significantly different from those of controls.     

Additive effect of eosinophilia and atopy on exhaled nitric oxide levels in children with or without a history of respiratory symptoms

Although atopy and blood eosinophilia both influence exhaled nitric oxide (eNO) measurements, no study has quantified their single or combined effect. We assessed the combined effect of atopy and blood eosinophilia on eNO in unselected schoolchildren. In 356 schoolchildren (boys/girls: 168/188) aged 9.0-11.5 yr, we determined eNO, total serum IgE, blood eosinophil counts and did skin prick tests (SPT) and spirometry. Parents completed a questionnaire on their children's current or past respiratory symptoms. Atopy was defined by a SPT >3 mm and eosinophilia by a blood cell count above the 80th percentile (>310 cells/ml). eNO levels were about twofold higher in atopic-eosinophilic subjects than in atopic subjects with low blood eosinophils [24.3 p.p.b. (parts per billion) vs. 14.1 p.p.b.] and than non-atopic subjects with high or low blood eosinophils (24.3 p.p.b. vs. 12.2 p.p.b. and 10.9 p.p.b.) (p <0.001 for both comparisons). The additive effect of atopy and high eosinophil count on eNO levels remained unchanged when subjects were analyzed separately by sex or by a positive history of wheeze (n=60), respiratory symptoms other than wheeze (n=107) or without respiratory symptoms (n=189). The frequency of sensitization to Dermatophagoides (Dpt or Dpf) was similar in atopic children with and without eosinophilia (66.2% and 67.4%, respectively); eosinophilia significantly increased eNO levels in Dp-sensitized children as well in children sensitized to other allergens. In a multiple linear regression analysis, eNO levels were mainly explained by the sum of positive SPT wheals and a high blood eosinophil count (t=4.8 and 4.3, p=0.000), but also by the presence of respiratory symptoms (especially wheeze) and male sex (t=2.6 and 2.0, p=0.009 and 0.045, respectively). Measuring eNO could be a simple, non-invasive method for identifying subjects at risk of asthma in unselected school populations.     

Asthma in patients with atopic dermatitis

Objective  This cross-sectional study was designed to estimate the frequency of asthma in patients with atopic dermatitis (AD), and its related factors. Methods  The study population consisted of 236 patients with AD who were referred to Children Medical Center in 1997–2002 and their diagnosis was based on Hanifin & Rajka criteria. Severity of AD was categorized based on Severity Scoring of Atopic Dermatitis (SCORAD) index. Asthma was diagnosed with medical history and clinical examination (three or more episodes of wheezing and/or dyspnea and/or cough after 1 year old). The patients were divided in two groups according to having or not having asthma. Results  The mean age of patients with AD was 38.67±2.68 month and the mean age at onset of asthma was 20±2.5 month. The frequency of asthma in AD patients was 27.5%. The mean of SCORAD in nonasthmatic patients was 52.27 ± 2.52 and in asthmatic patients was 56.2± 4.2 (P= 0.4). The mean of duration of breastfeeding in asthmatic patients was 12.2±1.6 month and in non-asthmatic patients was 11.16±6.3 month (P = 0.87). There was no significant difference between asthmatic patients and others in serum IgE levels (P = 0.65) and blood eosinophil count. (P = 0.49) Conclusion  These results confirmed that development of asthma in patients with AD is more than normal population and AD can be a significant predisposing factor to developing asthma but the causative factors are not clear.     

鼻炎与支气管哮喘发病的关系

目的探讨小儿鼻炎与支气管哮喘发病的关系。方法鼻炎患者130例分成2组,单纯鼻炎组60例,鼻炎并哮喘组70例,分析两组年龄、性别、既往湿疹史、毛细支气管炎史、吸烟家族史、哮喘家族史、变应原检测、外周血总IgE及嗜酸性粒细胞(EOS)计数等方面的差别。并用Logistic回归分析进一步确定鼻炎患者发生哮喘的危险因素。结果将两组比较,发现既往毛细支气管炎史、哮喘家族史、母亲哮喘及变应原屋尘、粉尘螨阳性在鼻炎并哮喘组中更多见。此外,外周血总IgE和EOS计数在鼻炎并哮喘组高于单纯鼻炎组。Logistic回归分析发现,外周血总IgE和EOS计数增高是鼻炎并哮喘的重要的危险因素。结论若鼻炎患者存在既往毛细支气管炎史、哮喘家族史、变应原检测阳性,尤其是外周血总IgE和EOS计数增高者,应视为哮喘的前驱表现,需及早防治。     

Ratio of eosinophil cationic protein/eosinophil count as a new marker in children with acute asthma

BACKGROUND: It is a matter of concern whether serum eosinophil cationic protein (ECP) can be considered as a disease marker in children with acute asthma being treated without corticosteroids. METHODS: Fourteen children (nine male, five female, aged 6-12 years) with acute asthmatic exacerbation, administered the appropriate drugs, with the exception of systemic or inhaled corticosteroids, were examined. They were all free from apparent asthmatic attacks during a follow-up period of 1 month. Serum ECP, eosinophil count and forced expiratory volume in 1 s (FEV1) were measured at referral, on the day of discharge, 1 week and 4 weeks after discharge, respectively. RESULTS: The ratio of ECP/eosinophil count (ECP:Eo ratio), expressed as micrograms of ECP (microgram/L)/the number of eosinophil (/microL) x 1000, was also evaluated as a marker of eosinophil activation. Compared with the value at referral, FEV1 (% predicted) significantly increased on the day of discharge (P < 0.05), 1 week after (P < 0.05) and 4 weeks after discharge (P < 0.05). However, serum ECP concentrations showed no significant changes during the follow-up period. Eosinophil count showed no significant changes on the day of discharge or 1 week after discharge, but significantly increased 4 weeks after discharge (P < 0.05). In contrast, the ECP:Eo ratio significantly decreased on the day of discharge (P < 0.05), 1 week after (P < 0.05) and 4 weeks after discharge (P < 0.05). CONCLUSION: These data suggest that serum ECP is a poor disease marker in asthmatic children with acute exacerbation who receive no corticosteroid therapy, probably due to marked changes in the eosinophil count. However, the ECP:Eo ratio might be a better marker than serum ECP in such patients.     

Vascular endothelial growth factor overexpression in induced sputum of children with bronchial asthma

Vascular endothelial growth factor (VEGF) induces angiogenesis and increases vascular permeability participating in narrowing of the airway lumen that follows lung injury. We sought to investigate the expression of VEGF in induced sputum during and after recovery from acute episodes of bronchial asthma in children. Eighteen asthmatic children with acute attacks of varying severity were subjected to VEGF estimation by an enzymatic immunoassay in induced sputum. They were followed up till complete remission of symptoms and signs and were then retested. VEGF was also estimated in sputum induced from age 34 and sex-matched healthy children enrolled as a control group. The sputum VEGF levels during acute asthma [median = 71 ng/ml; mean (s.d.) = 114.6 (121.8) ng/ml] were significantly higher than the levels estimated during remission [median = 50 ng/ml; mean (s.d.) = 45.7 (24.2) ng/ml] and both were higher than the corresponding levels of the control group [median = 36 ng/ml; mean (s.d.) = 31.3 (17.2) ng/ml]. VEGF levels during asthmatic episodes correlated positively to the recovery levels (r = 0.6, p = 0.009). The patients' VEGF expression did not vary with asthma severity, serum total IgE concentration, peripheral blood eosinophil count, or erythrocyte sedimentation rate of patients. Children on corticosteroids inhalation therapy at enrollment had sputum VEGF levels that were comparable to those on other therapies. The increased expression of sputum VEGF in asthmatic children reinforces the concept that it might have a pathogenetic role in bronchial asthma and may represent a biomarker of airway inflammation.     

Serum eosinophil cationic protein and interleukin-5 in children with bronchial asthma and acute bronchiolitis

The aim of our study was to evaluate the clinical applicability of serum eosinophil cationic protein (ECP), interleukin-5 (IL-5) and total eosinophil counts in childhood asthma and bronchiolitis. These parameters were measured in 44 children aged 12-84 months with moderate and mild asthma during symptomatic and asymptomatic phases of disease. Fifteen of the patients were included at the time of admission to hospital due to an acute asthmatic attack, and ten of these were also examined one month after discharge. None of the patients were treated with glucocorticoids or cromoglycate at any time during the study. Serum ECP was significantly increased in the children with acute asthma compared to children with stable moderate asthma, stable mild asthma, as well as to controls. There was no difference between the groups with stable asthma or between stable asthma and controls, and there was large overlap between all groups of asthmatics and controls. Detectable levels of circulating IL-5 were demonstrated in eight of 15 children with acute asthma, with significantly higher levels in atopic children, whereas all samples from children with stable asthma and controls were negative. The results suggest that even though serum ECP and IL-5 increases during acute asthmatic attacks, these parameters cannot alone be used to discriminate between different groups of young children with stable asthma, nor between asthmatics and healthy controls. In addition, the same parameters of eosinophil inflammation were examined in serum samples from 25 children aged 1-17 months undergoing their first episode of acute bronchiolitis. Children with acute respiratory syncytial virus (RS V) bronchiolitis had significantly higher levels of serum ECP than those with RSV negative disease, whereas the total eosinophil counts were significantly decreased in all patients with acute bronchiolitis. Serum IL-5 was only detected in two children with acute bronchiolitis. The results suggest that the inflammation in RSV bronchiolitis differs from that induced by other viruses.     

Peripheral blood eosinophil counts and eosinophil cationic protein content of respiratory secretions in bronchiolitis: relationship to severity of disease

Infants and young children with acute viral respiratory illness were studied to determine the association of peripheral blood eosinophil counts and concentrations of eosinophil cationic protein (ECP) in nasopharyngeal secretions with the development and severity of bronchiolitis. Subjects included those with upper respiratory illness (URI) alone, pneumonia or bronchiolitis. Controls consisted of healthy infants, and those hospitalized with non-respiratory illnesses. While peripheral blood eosinophil counts were suppressed in all infected infants greater than two months of age, eosinophil counts in patients with bronchiolitis were significantly greater than in those with URI alone. ECP concentrations were significantly greater among individuals with bronchiolitis than other infected infants. For bronchiolitis cases with detectable peripheral blood eosinophils, eosinophil counts correlated weakly and inversely with oxygen saturations. In contrast, ECP concentrations were strongly inversely correlated with initial oxygen saturation. ECP concentrations were also significantly correlated with peripheral blood eosinophil counts. Viral infections suppress peripheral blood eosinophil counts in infants greater than two months of age, although the effect is somewhat overcome in patients with bronchiolitis. The form and severity of bronchiolitis is much more strongly related to degranulation of eosinophils in the respiratory tract than to peripheral blood eosinophil counts.     

Effect of a clinical pathway on the hospitalisation rates of children with asthma: a prospective study.

AIM: To determine the effect of implementing a clinical pathway, using evidence-based clinical practice guidelines, for the emergency care of children and adolescents with asthma. METHODS: A prospective, before-after, controlled trial was conducted, which included patients aged 1-18 years who had acute exacerbations of asthma treated in a tertiary care paediatric emergency department. Data were collected for identical 2-month seasonal periods before and after implementation of the clinical pathway to determine hospitalisation rate and other outcomes. For 2 weeks after emergency visits, the rate at which patients returned to emergency care for worsening asthma was evaluated. A multidisciplinary panel, using national guidelines and a systematic review, developed the pathway. RESULTS: 267 patients were studied. The rate of hospitalisation was significantly lower in the post-implementation group (10/74; 13.5%) than in the pre-implementation control group (53/193; 27.5%; p = 0.02; number needed to treat 7.1). All reduction in hospitalisation occurred in children with moderate to severe asthma exacerbation. After implementation of the clinical pathway, the rate of administration of oral corticosteroids to patients with moderate or severe exacerbations increased from 71% to 92% (p = 0.01), and significantly more patients received beta2-agonists in the first hour (p = 0.02). No significant change in relapse to acute care occurred within 2 weeks (p = 0.19). CONCLUSIONS: An evidence-based clinical pathway for children and adolescents with moderate to severe exacerbations of acute asthma markedly decreases their rate of hospitalisation without increased return to emergency care.     

Bronchoalveolar lavage in asthmatic children: Evidence of neutrophil activation in mild-to-moderate persistent asthma

Little information is available on cell profiles and mediator production in the lower airways of children with asthma by comparison with the adult population. To study the bronchoalveolar lavage (BAL) cell profiles and production of eosinophil cationic protein (ECP) and myeloperoxidase (MPO) in childhood bronchial asthma, a retrospective study was performed in 29 children (13 allergic asthmatic children and 16 controls). Six of the asthmatics had mild-to-moderate persistent disease and seven had intermittent asthma. The BAL cell count and ECP and MPO values of asthmatic children were compared with those from 16 controls. The asthmatic patients had higher values than controls for the total cell count (p=0.08), for neutrophils (p=0.02), and for ECP and MPO (p<0.001). MPO levels (p=0.04), neutrophil count (p=0.06), and ECP values (p=0.06) were higher in patients with mild-to-moderate persistent asthma than in those with intermittent asthma. Our results demonstrate that neutrophil-mediated inflammation is greater in patients with more severe asthma.     

Potassium disturbance associated with an inpatient childhood asthma pathway

BackgroundPaediatric asthma exacerbations in Alberta are treated via standardized order sets known as the Alberta Acute Childhood Asthma Pathway (ACAP). This pathway is utilized in paediatric tertiary hospitals and in remote and rural locations. Incidence, magnitude, and risk factors for hypokalemia in inpatients receiving salbutamol for asthma exacerbations via this pathway are presently unknown.ObjectiveEstablish incidence, magnitude, and risk factors for hypokalemia associated with salbutamol therapy as directed by a paediatric asthma pathway.MethodsRetrospective cohort study using visit-level electronic medical data. Inpatients aged <18 years old receiving salbutamol via the ACAP with at least one potassium level were included. Hypokalemia was defined as mild (3.0 ≤ [K⁺] < 3.5 mEq/L), moderate (2.5 ≤ [K⁺] < 3.0 mEq/L), or severe ([K⁺] < 2.5 mEq/L), as measured in serum or blood gas. Binomial logistic regression was utilized to examine risk factors for hypokalemia, route of administration, location of lowest [K⁺], nil per os (NPO) status during admission, potassium supplementation, gender, and age.ResultsThere were 821 patients screened for analysis and 433 patients were analyzed after exclusions. There was an incidence of hypokalemia of 38.8%. Of patients experiencing hypokalemia, 71.4% were mild, 25.6% moderate, and 3.0% severe. Risk factors included nebulized salbutamol, patient location (emergency department or paediatric intensive care unit), and age (>5 years) although these risk factors may actually represent patients receiving higher doses of salbutamol.ConclusionsThe majority of the 38.8% of children experiencing hypokalemia associated with the ACAP were mild. Routine monitoring of potassium status in children receiving salbutamol per standardized pathway is recommended for children with described risk factors, and ideally within the first 12 hours of presentation.     

Comparative effect of triamcinolone, nedocromil and montelukast on asthma control in children: A randomized pragmatic study

Asthma severity can be judged by measurements of symptoms, lung function, and medication requirements. The objective was to compare the effect of a 4-wk monotherapy with low-dose triamcinolone, montelukast and nedocromil on asthma control, lung function, eosinophil blood count, and bronchial hyper-reactivity in children with mild to moderate asthma allergic to dust mite. Two hundred fifty-six children, aged 6-18 yr, with mild to moderate asthma, participated in an 8-wk study. This was a three-arm, randomized no blinding or placebo pragmatic trial comparing the effect of triamcinolone acetonide (400 microg/day), inhaled nedocromil and montelukast sodium on clinical parameters of asthma [score, forced expiratory volume in 1 s (FEV(1))], PC20H, and eosinophil blood count. Two hundred forty-six children completed the study. After 4 wk of treatment with triamcinolone and montelukast, FEV(1) and PC20H significantly increased, and mean total symptoms score and mean number of eosinophil count in serum significantly decreased. Triamcinolone had a stronger effect on PC20H than montelukast. Nedocromil improved total asthma symptoms score and lung function. There was a reduction in the daytime and night-time symptom scores after treatment with all three drugs. Triamcinolone and montelukast had a stronger effect on asthma symptoms than nedocromil. There were statistically significant differences in reduction of nocturnal asthma symptoms between the triamcinolone and nedocromil groups (p < 0.001) and between montelukast and nedocromil (p = 0.001) groups, but not between the triamcinolone and montelukast groups. There was a reduction in beta-agonists use after treatment with all three drugs, with the strongest effect of triamcinolone. The study showed the strongest effect of low-dose inhaled steroids on clinical symptoms, lung function, bronchial hyper-reactivity and eosinophil blood count when compared to other asthma medications.     

Blood eosinophils, leukotriene C4 generation, and bronchial hyperreactivity in formerly preterm infants.

Infants born prematurely are known to display longstanding bronchial hyperreactivity. The mechanism responsible for this is still unclear. Eosinophils are thought to play a central part in the development of bronchial hyperreactivity in asthma. It was the aim of this study to assess the relation of bronchial hyperresponsiveness to potential markers of eosinophilic inflammation in peripheral blood. Eosinophil count, the concentration of serum eosinophilic cationic protein, the capacity of purified eosinophils to generate leukotriene C4, and bronchial reactivity was studied in 24 non-atopic children born prematurely, 12 healthy controls, and 12 children with asthma aged 6 to 9 years. There was no difference in serum concentrations on eosinophil cationic protein and eosinophil counts. However, eosinophils from the 15 formerly preterm infants with significant bronchial hyperreactivity generated significantly higher amounts of leukotriene C4 than normal controls and prematurely born children without bronchial hyperreactivity. Levels of leukotriene C4 in this group were comparable with those obtained with eosinophils from patients with asthma. In contrast with cells from the other groups, eosinophils from the children with bronchial hyperreactivity born prematurely show no enhancement of leukotriene C4 generation on prestimulation with platelet activating factor. It is concluded that bronchial hyperreactivity of children born prematurely is accompanied by the prestimulation of eosinophils.     

Inflammatory mediators, cell counts in nasal lavage and computed tomography of the paranasal sinuses in atopic children

OBJECTIVE: The aims of this study were to evaluate inflammatory cells, the profile of inflammatory mediators in nasal lavage (NL), and the involvement of the paranasal mucosa in atopic infants with no symptoms of sinusitis. METHODS: 48 atopic patients with allergic rhinitis (AR), and 33/48 patients with asthma were studied; the control group consisted of 13 nonatopic children. Those individuals with acute, chronic or recurrent sinusitis were excluded. The involvement of the paranasal mucosa was assessed by coronal computed tomography (CT) and graded by a standard protocol (0-30). A CT score greater than or equal to 12 indicated extensive involvement. Nasal lavage was used to quantify total and differential nasal cell counts. An aliquot of the supernatant was used for determining inflammatory mediators: interleukin-8 (IL-8), myeloperoxidase (MPO), and eosinophil cationic protein (ECP). Albumin was used as a marker for increased vascular permeability. These measurements were performed on all of the atopic patients and in 6/13 patients in the control group. The three groups were submitted to spirometry and complete blood cell count. RESULTS: Extensive involvement of the paranasal mucosa was observed in 7/33 (21%) of asthmatic patients (Group I) and 2/15 (13%) of those with allergic rhinitis (Group II). The highest CT score in the control group (Group III) was 7. Total cell and eosinophil count/ml and albumin concentration in nasal fluid were higher in asthmatic patients whose CT score was greater than 12. Interleukin-8 concentration, number of neutrophils and epithelial cells/ml in nasal fluid were similar in the three groups. A positive correlation between CT score, peripheral blood eosinophilia, number of eosinophils/ml and eosinophil cationic protein concentration was found in the nasal fluid of atopic children (n=48). There was an association between number of neutrophils and titers of interleukin-8 and myeloperoxidase, and between interleukin-8 and eosinophil count. CONCLUSIONS: in asthmatic patients with no symptoms of sinusitis, the extensive involvement of the paranasal mucosa is associated with blood and nasal lavage eosinophilia and cellular activation. Neutrophil infiltration and activation were not related to increased involvement of the paranasal mucosa.     

Circadian variation of exhaled nitric oxide and urinary eosinophil protein X in asthmatic and healthy children.

Asthmatic symptoms and the frequency of admissions to hospital because of acute asthma tend to increase in the early morning hours, and it is therefore possible that airway inflammation increases during the night. To elucidate the hypothetical circadian variation of airway inflammation, we measured concentrations of exhaled nitric oxide (FeNo), urinary eosinophil protein X excretion (EPX), and forced expiratory volume in the first second (FEV1) in 20 asthmatic and 6 nonatopic nonasthmatic children every 3 h during a 21-h period. Compared with control subjects, asthmatic subjects had higher FeNo (median, 22.7 versus 10.3 ppb, p = 0.016) and lower FEV1 % predicted (median, 91.0 versus 101.9%, p = 0.045), but did not differ significantly in EPX (median, 153.8 versus 148.7 microg/mmol creatinine, p = 0.83) at 7 AM. However, differences in gender and age do not allow direct comparisons between asthmatic and control children. FeNo and EPX demonstrated a cosinelike circadian rhythm (log FeNo, p = 0.0001; log EPX, p = 0.0001) with lowest levels at 7 PM and highest at 7 AM. This was also the case for FEV1 % (p = 0.01). No difference in the amplitude of circadian rhythm was observed between asthmatic and healthy control children for log FeNo (p = 0.35), log EPX (p = 0.57), and FEV1 % (p = 0.17). A stratified analysis showed a significant circadian rhythm in the control group for log FeNo (p = 0.014) and log EPX (p = 0.0001). Our results therefore suggest a circadian rhythm of inflammatory markers, which peaks in the early morning. Rhythmicity of EPX excretion and FeNo in healthy children suggests a physiologic mechanism; however, pathologic effects during the night might occur under conditions of asthma-specific inflammation.     

Persistent increase in plasma and urinary leukotrienes after acute asthma.

Leukotrienes may mediate bronchoconstriction in asthma. Cysteinyl leukotriene production rises in vivo after allergen challenge, but few reports describe leukotriene concentrations in clinical asthma or in children. Using high performance liquid chromatography/radioimmunoassay, plasma and urinary leukotrienes in asthmatic children (aged 5-10 years) were measured during an acute exacerbation (peak expiratory flow (PEF) < 65%, n = 10) and one month later (PEF 74-169%, n = 9), and in non-atopic normal children (aged 1.3-13.2 years). In the asthmatics, geometric mean (95% confidence interval) plasma leukotriene B4 (LTB4) was 746 pg/ml (398 to 1403) acutely and 1026 pg/ml (662 to 1593) in remission, compared with 369 pg/ml (167 to 728) in the normal children (n = 14). Plasma cysteinyl leukotrienes were low or undetectable, but urinary leukotriene E4 (LTE4) was higher in the asthmatics during an acute episode (210 pmol/mmol creatinine, 101 to 454) and at follow up (179 pmol/mmol, 110 to 293), compared with the normal children (98 pmol/mmol, 81 to 118, n = 41). This persistent increase in plasma LTB4 and urinary LTE4 concentrations one month after a severe asthmatic episode suggests leukotriene production is related to chronic inflammation rather than to acute bronchoconstriction.     

Increased serum concentrations of soluble tumor necrosis factor receptors p55 and p75 in early onset neonatal sepsis

Sepsis and pneumonia are major causes of morbidity and mortality in the neonatal period. The symptoms are variable and unspecific. So far, no reliable diagnostic test for neonatal infection has been found. In this study we measured serum levels of soluble tumor necrosis factor receptors (sTNFR) p55 and p75 in non-infected and infected neonates, and evaluated the diagnostic value of these mediators as tests for early detection of neonates with sepsis or pneumonia. Blood was collected on admission and after 3–4 days from 161 neonates consecutively admitted to the Neonatal Intensive Care Unit (NICU) during the first week of life. Twenty two neonates suffered from infection and 127 were classified as non-infected (controls). Samples were analyzed for p55 and p75, C-reactive protein (CRP) and white blood cell count with differential. Both preterm and term infected neonates had initially higher concentrations of p55 (both p<0.01) and p75 (p=0.01 and p=0.05, respectively) than controls. In non-infected neonates p55 levels decreased in the perinatal period, whereas p75 levels remained stable. Levels of both p55 and p75 decreased in neonates with infection during the perinatal period. CRP was a more specific parameter than p55 and p75 (CRP: 97%, p55: 65% and p75: 75%) whereas the sensitivity of all three parameters was at similar levels (CRP: 59%, p55: 70% and p75: 67%). We conclude that assessment of sTNFR may not improve accuracy in the diagnosis of early onset neonatal sepsis compared to the use of CRP.