Early intervention with suplatast tosilate for prophylaxis of pediatric atopic asthma: A pilot study

The onset of asthma may be related to Th2 cytokine dominance at the time when food allergies occur several months after birth. This study investigated the effectiveness of early intervention with a Th2 cytokine inhibitor (suplatast tosilate) for prevention of asthma in infants with food allergies and atopic dermatitis. Suplatast tosilate dry syrup (6 mg/kg daily) or a histamine H₁-blocker (ketotifen fumarate dry syrup: 0.06 mg/kg daily) was administered randomly to 53 infants with atopic dermatitis caused by food allergies. The primary endpoints were the incidence of asthma and the time to the onset of wheezing. The peripheral blood Th1/Th2 ratio, total IgE level, and eosinophil count were measured before and after treatment. After 24 months of treatment, the prevalence of asthma was significantly lower in the suplatast group (20.8%) than in the ketotifen group (65.6%, p < 0.01). Additionally, the time from the start of treatment to the initial episode of wheezing for infants who developed asthma was significantly longer in the suplatast group than the ketotifen group (p < 0.01). Furthermore, the eosinophil count was significantly decreased by suplatast treatment (p < 0.05), and there was a significant difference between the suplatast and ketotifen groups with respect to both the eosinophil count (p < 0.01) and the Th1/Th2 ratio (p < 0.05). The results of the present pilot study suggest that suplatast tosilate is useful for the primary prevention of wheezing and asthma in children.     

Wheezing requiring hospitalization in early childhood: Predictive factors for asthma in a six-year follow-up

Although asthma is common after wheezing in early childhood, the risk factors for and the prevention of later asthma are poorly understood. During the present follow-up study, a range of possible predictive factors for school-age asthma was evaluated. The study group consisted of 82 children hospitalized for wheezing at age < 2 years in 1992–93. The baseline data were collected on entry to the study. In 1999, the children were re-examined at the median age of 7.2 years. A structured questionnaire was applied to chart the symptoms suggestive of asthma, and the children were examined clinically. An exercise challenge test, as well as skin prick tests (SPT) to common inhalant allergens, was performed. Asthma was present in 33 (40%) children, 30 (91%) having continuous medication for asthma. The significant asthma-predictive factors, present on entry to the study, were blood eosinophilia (p = 0.0008), atopic dermatitis (p = 0.0089), elevated total serum immunoglobulin E (IgE) (p = 0.0452), and a history of earlier episodes of wheezing in infancy (p = 0.0468). SPT positivity in early childhood was also associated with school-age asthma (p = 0.002). In contrast, respiratory syncytial virus (RSV) identification during the index episode of wheezing played a minor role as a predictive factor for asthma. In conclusion, if hospitalization for wheezing occurs in infancy, more than every third child will suffer from asthma at early school age; the risk is significantly increased with recurrent wheezing in infancy and the development of allergic manifestations.     

Ribavirin for respiratory syncytial virus bronchiolitis reduced the risk of asthma and allergen sensitization

Respiratory syncytial virus (RSV) bronchiolitis in early life is a risk factor for later development of asthma and atopy. Ribavirin is the only effective drug currently available against acute RSV bronchiolitis. However, the long-term effects of ribavirin remain unclear. We investigated a cohort of children hospitalized with RSV bronchiolitis from when they were under 2 yr old until they reached a mean age of 6.2 yr. In total, we enrolled 175 children in this study. Both the group treated with ribavirin and the group not treated with ribavirin included high-risk young children with congenital heart disease or chronic lung disease. Their respective age-matched controls, that we labeled groups A and B, both without ribavirin treatment, consisted of previously healthy subjects. Wheezing was either verified by physicians or estimated by a questionnaire. Allergen sensitization was judged by serum allergen-specific IgE levels. The cumulative incidence of physician-diagnosed asthma or recurrent wheezing in the ribavirin group (15%) was significantly lower than its incidence in the non-ribavirin-treated group (34%, p = 0.049), and in the control A group (43%, p = 0.005). Allergen sensitization was also least frequent in the ribavirin group. Ribavirin therapy was an independent factor in reducing the risk of developing asthma, asthma/recurrent wheezing, and sensitization to D. pteronyssinus / D. farinae. The long-term value of ribavirin for acute RSV bronchiolitis and its underlying mechanisms deserves further research.     

Association of early growth response-1 gene polymorphisms with total IgE and atopy in asthmatic children

Early growth response-1 ( Egr-1 ) is expressed in human airways and found to modulate tumor necrosis factor, immunoglobulin E (IgE), airway responsiveness, and interleukin-13-induced inflammation in mice. We investigated the effects of Chinese-tagging single nucleotide polymorphisms (SNPs) of Egr-1 on asthma traits in 298 Chinese asthmatic children and 175 controls, and a replication community cohort of 191 controls. Tag SNP (−4071 A→G) and three additional SNPs (−1427 C→T, −151 C→T and IVS1 −42 C→T) were genotyped by restriction fragment length polymorphism (RFLP). Significant associations were found between plasma total IgE concentration and −4071 A→G (p = 0.008) and IVS1 −42 C→T (p = 0.027) in asthmatic patients. After Bonferroni correction, only −4071 A→G showed significant association. Multivariate regression analysis confirmed this significant association with a standardized coefficient β of 0.156 (95% CI: 0.046–0.317; p = 0.009) in asthmatics among the three SNPs with age and gender-adjusted. In −4071 A→G, IgE_log was significantly higher in patients with the GG genotype than the AA genotype (p = 0.009). In addition, −4071 A→G was significantly associated with atopy (p = 0.016) and high total IgE concentration (p = 0.030) among asthmatics. Patients with the G allele had a 3.5-fold risk of having atopy and a 2.0-fold risk of having high total IgE concentration than those homozygous for the A allele. This is the first report to show significant association of Egr-1 polymorphisms with plasma total IgE and atopy in asthmatics. It may help to explore the pharmacogenetics of Egr-1 inhibitors.     

婴幼儿喘息性社区获得性肺炎患儿血清炎症因子的变化

目的 通过测定婴幼儿喘息性社区获得性肺炎(CAP)患儿血清炎症因子的变化,了解婴幼儿喘息性肺炎是否与哮喘有相似的免疫机制。方法 喘息性CAP 47例、非喘息性CAP 42例、正常对照30例婴幼儿纳入该研究。比较3组间外周血C反应蛋白、降钙素原、可溶性髓系细胞触发受体-1、γ干扰素、白细胞介素4、白细胞介素10及骨膜蛋白水平。结果 喘息性和非喘息性肺炎组血降钙素原、可溶性髓系细胞触发受体-1、白细胞介素4、白细胞介素10 含量均高于正常对照组(PPP结论 婴幼儿喘息性肺炎存在γ干扰素/白细胞介素4比值失衡,存在气道嗜酸性粒细胞炎症,提示婴幼儿喘息性肺炎与哮喘有相似的免疫机制。     

Increased serum IL-10/IL-12 ratio in wheezing infants

To investigate the association between various serum markers and atopic symptoms in the first year of life, and to evaluate the prognostic value of these markers for the development of wheezing and skin rash in the second year of life. Data of 86 children on the development of wheezing and skin rash in the first 2 years of life were collected prospectively, making use of parental completed questionnaires, weekly symptom cards, structured interview and physical examination. Serum markers (IL-10, IL-12, IL-13, eotaxin, sE-selectin, sICAM-1, sIL-2R) and total and specific IgE were determined at age 1. Children who developed wheezing in the first year of life had lower serum levels of IL-12 than children without symptoms (median 40.3 pg/ml vs. 49.0 pg/ml, p = 0.01) and a higher serum IL-10/IL-12 ratio (0.41 vs. 0.31, p = 0.001) at age 1. The IL-10/IL-12 ratio increased with an increasing number of wheezing episodes. Levels of sE-selectin in children with wheezing and in children with itchy skin rash in the first year of life were higher than in symptom free children (6.1 ng/ml and 5.9 ng/ml vs. 4.9 ng/ml, p = 0.01 and p = 0.03, respectively). Children who developed wheezing in the second year of life already had increased sICAM-1 levels at age 1. Children who developed wheezing in the first year of life showed a serum cytokine response that is skewed towards a T-helper 2 profile, with lower IL-12 levels and an increased IL-10/IL-12 ratio. Children who developed wheezing in the second year of life had elevated sICAM-1 levels at age 1. Follow-up of the children is needed to evaluate the prognostic value of various serum markers for the development of allergic disease in later childhood.     

Seropositivity to celiac antigens in asymptomatic children with type 1 diabetes mellitus: association with weight, height, and bone mineralization

Background:  Screening for celiac disease (CD) in children with diabetes is controversial because no studies have demonstrated metabolic complications in asymptomatic, seropositive subjects or beneficial effects of dietary intervention.
Objective:  We hypothesized that seropositivity to celiac antigens is associated with decreased growth and bone mineralization in asymptomatic diabetic children.
Design/Methods:  Asymptomatic diabetic children were screened for seropositivity to tissue transglutaminase. Villous atrophy was assessed by small bowel biopsy in a subset of seropositive subjects. We compared measures of growth and bone mineralization in 30 seropositive subjects, and 34 matched seronegative controls.
Results:  Relative to seronegative controls, the seropositive subjects had reductions in insulin-like growth factor (IGF) binding protein 3 z scores (p < 0.05) and bone mineral density (BMD) z scores (p = 0.05). Weight, body mass index, IGF-I, and bone mineral apparent density (BMAD) z scores were marginally lower, but height z scores were comparable. Seropositive patients with severe villous atrophy had lower weight (−0.91 SDs), height (−1.1 SDs), BMD (−2.0 SDs), and BMAD (−2.0 SDs) z scores and significant increases in parathyroid hormone (all p < 0.05). Four patients with severe villous atrophy maintained strict gluten restriction for at least 12 months. Gluten restriction increased BMD and BMAD z scores.
Conclusions:  High-titer seropositivity to celiac antigens is associated with reductions in weight and BMD in diabetic children, justifying screening of high-risk patients. Results suggest that biopsy is required to confirm the diagnosis and assess the severity of CD; those with severe villous atrophy are more likely to have growth failure and osteopenia. Gluten restriction may reverse these complications.     

按哮喘预测指数分组治疗在5岁以下喘息儿童中的应用

目的 观察按哮喘预测指数（asthma predictive index, API）分组治疗在5 岁以下喘息儿童中的应用价值。方法 239 例5 岁以下喘息患儿,API 阳性组126 例,API 阴性组113 例,分别随机分为糖皮质激素吸入治疗组（ICS 治疗组）及孟鲁司特钠治疗组（LTRA 治疗组）。治疗开始4 周内2 组所用药物种类和剂量相同,在疾病稳定期（第4 周后）ICS 治疗组仅使用布地奈德混悬液雾化吸入治疗,LTRA 治疗组仅使用孟鲁司特钠口服治疗,评估记录各组患儿不同时间点哮喘症状评分。结果 API 阳性组及阴性组在治疗后的前4 周,ICS和LTRA 2 种方法均有效,哮喘症状评分与治疗前比较差异有统计学意义,但2 个治疗组间比较差异无统计学意义;在治疗24 周时,2 种治疗方法仍有效,但API 阳性组中LTRA 治疗组较ICS 治疗组更有效;在API 阴性组中,LTRA 治疗组与ICS 治疗组疗效比较差异无统计学意义。结论 5 岁以下的儿童喘息,在疾病稳定期,可根据不同的API 分组,选择不同治疗方案,以达到更有效地控制喘息的目的。     

The addition of rosiglitazone to insulin in adolescents with type 1 diabetes and poor glycaemic control: a randomized-controlled trial

Objective:  To evaluate the effect of rosiglitazone, an insulin sensitizer, on glycaemic control and insulin resistance in adolescents with type 1 diabetes mellitus (T1DM)
Research design and methods:  Randomized, double-blind, placebo-controlled crossover trial of rosiglitazone (4 mg twice daily) vs. placebo (24 wk each, with a 4 wk washout period). Entry criteria were diabetes duration >1 yr, age 10–18 yr, puberty (≥Tanner breast stage 2 or testicular volume >4 mL), insulin dose ≥1.1 units/kg/day, and haemoglobin A1c (HbA1c) >8%. Responses to rosiglitazone were compared with placebo using paired t -tests.
Results:  Of 36 adolescents recruited (17 males), 28 completed the trial. At baseline, age was 13.6 ± 1.8 yr, HbA1c 8.9 ± 0.96%, body mass index standard deviation scores (BMI-SDS) 0.94 ± 0.74 and insulin dose 1.5 ± 0.3 units/kg/day. Compared with placebo, rosiglitazone resulted in decreased insulin dose (5.8% decrease vs. 9.4% increase, p = 0.02), increased serum adiponectin (84.8% increase vs. 26.0% decrease, p < 0.01), increased cholesterol (+0.5 mmol/L vs. no change, p = 0.02), but no significant change in HbA1c (−0.3 vs. −0.1, p = 0.57) or BMI-SDS (0.08 vs. 0.04, p = 0.31). Insulin sensitivity was highly variable in the seven subjects who consented to euglycaemic hyperinsulinaemic clamps. There were no major adverse effects attributable to rosiglitazone.
Conclusion:  The addition of rosiglitazone to insulin did not improve HbA1c in this group of normal weight adolescents with T1DM.     

Nitrites in induced sputum as a simple and cheap non-invasive marker of airway inflammation for asthmatic schoolchildren

To determine if there are differences in the nitric oxide metabolites (nitrites) in sputum of patients with persistent asthma and healthy schoolchildren, we performed a case-control study in a tertiary care hospital in Arequipa, Perú. Nitrites in induced sputum samples were measured using the Griess assay in 30 persistent asthmatics (mean age of 10.1 yr) and 30 controls (mean age of 11.9 yr). The mean ± s.d. of nitrites among asthmatics was significantly higher than the controls (16.30 ± 8.6 vs. 10.25 ± 4.68 nmol/ml, respectively, p = 0.001). Moreover, the nitrite level in the sputum in children with severe persistent asthma was higher than in the level found in the moderate and mild asthmatics (32.83 ± 9.48 vs. 18.10 ± 1.96 vs. 11.84 ± 4.73 nmol/ml, respectively, p < 0.01 for linear trend). This study showed for the first time in children that asthmatics have significantly higher levels of nitrites in induced sputum than healthy controls and that the level of nitrite correlates with the severity of the asthma. Nitrite levels in sputum, a simple and cheap, non-invasive method, may be a good alternative to measure the severity of inflammation in asthmatic children.     

Time trends of the prevalence of asthma and allergic disease in Austrian children

After a substantial increase in the prevalence of atopic disease in Europe, recent studies indicate that a plateau has been reached. However, variation across countries and age groups exists. We studied the prevalence and time trends of asthma and allergic disease among schoolchildren in Austria, a country with traditionally low rates of asthma, hay fever, and eczema. As part of the International Study of Asthma and Allergies in Childhood (ISAAC), symptoms and physician diagnoses of asthma and allergic disease of 13,399 Austrian children aged 6–7 yr and 1516 children aged 12–14 yr were surveyed between 1995 and 1997. A similar survey was conducted between 2001 and 2003. Among children aged 6–7 yr, significant increases were seen in the prevalence of physician-diagnosed asthma (+16%; p = 0.013), hay fever (+22%; p < 0.001), and eczema (+37%; p < 0.001) between 1995 and 2003. These changes were paralleled by an increase in the prevalence of symptoms typical for hay fever (itchy eyes and runny nose), but not by an increase in wheeze. Among children aged 12–14 yr, the lifetime prevalence of diagnosed asthma increased by 32%, of hay fever by 19%, and of eczema by 28% (all, p < 0.001). These changes were paralleled by increases in the prevalence of wheezing as documented by both questions before and after a video showing wheezing children but not by symptoms typical for hay fever such as itchy eyes and runny nose. In conclusion, in Austria, contrary to other European countries, the prevalence of asthma and allergic disease increased among schoolchildren. Additional studies are needed to continue monitoring the dynamics of the prevalence of asthma and allergic disease in Austria and to explore trends in their risk factors.     

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.     

Wheezing in early life and asthma at school age: Predictors of symptom persistence

Early childhood wheezing is associated with asthma later in life. However, the high spontaneous recovery rate and the lack of firm predictors for persistence of wheezing complicates the development of evidence-based guidelines for long-term management of wheezy infants and toddlers. Our aim was to define variables that could be used to identify wheezy individuals younger than 3 years of age who would continue to be symptomatic at school age. The method used was a questionnaire-based cross-sectional survey of 2027 randomly chosen, 6–13-year-old school children. Altogether 1829 (90%) questionnaires were returned. Emergency medical care had been sought for 186 (10.2%) children for wheezing during the first 3 years of life, and only 17.2% of these children had received similar emergency treatment during the 12 months preceding the survey. The total proportion of children with current asthma at school age was 11.4%. A logistic regression analysis indicated that for the early wheezers, a family history of asthma, an itchy rash or food allergy, and exposure to tobacco smoke at home before the age of 3 years, were all independently associated with symptom persistence until school age. Among all wheezy children younger than 3 years, those who have a history of food allergy, itchy rash, asthma occurrence in a sibling or parent, or are exposed to tobacco smoke during the first years of life are at highest risk for symptom persistence until school age.     

Association analysis of brain-derived neurotrophic factor gene polymorphisms in asthmatic children

Brain-derived neurotrophic factor (BDNF) has been described to modulate airway hyper-responsiveness and inflammation and was involved in late allergic reaction in asthma and higher levels of circulating BDNF were present in allergic asthmatics. In BDNF gene, Val66Met and C-270T polymorphisms were described. There were, however, very few studies analyzing BDNF gene polymorphisms in asthma. The aim of this study was to analyze the possible relationship between these two polymorphisms in the BDNF gene and asthma. Fifty-six pediatric asthmatic patients were analyzed, aged from 6 to 18. The diagnosis of atopic asthma was based on clinical manifestation, lung function test and increased immunoglobulin E level, and/or positive skin prick tests. The control group consisted of 109 healthy subjects. The polymorphisms were genotyped with the use of polymerase chain reaction–restriction fragment length polymorphism method. We did not observe an association of Val/Met polymorphism and the presence of asthma. However, we observed that Val allele is much more frequent in the male group of asthmatic patients (p = 0.06). For −270C/T polymorphism, we found significant differences between asthmatic patients and the control group (p = 0.041 for genotypes and p = 0.005 for alleles). The results may suggest a relationship between the BDNF gene and asthma and male gender of asthmatic children.     

Early life factors related to clinical manifestations of atopic disease but not to skin-prick test positivity in young children

The relative influence of early life events in the development of IgE-mediated allergy is still undetermined. We investigated early life factors in relation to skin-prick test positivity (SPT) and clinical manifestations of atopic disease in a population-based sample of 201 Italian children (3 months−5 years), after considering their interactions with known determinants of allergy. Among them, 143 children had SPT performed to common allergens. Threatened abortions, general anesthesia at delivery, prematurity, birthweight < 2500 g, maternal smoking, dampness and gas heating exposure were all significantly related to an increased risk of frequent rhinitis in the absence of cold (18%). In utero smoking, threatened abortions, fetal health complications, infantile colic, maternal smoking in childhood (satisfactorily correlated with maternal expired CO during the survey) and respiratory infections were all independent determinants of frequent wheezing (23%). Doctor's diagnosis of asthma (3%) was related to in utero smoking, being born in spring, infantile colic and respiratory infections. A simultaneous exposure to in utero smoking and infantile colic put the infants to a fourfold higher risk of frequent wheezing and to a ninefold risk of asthma, respectively. Having a pet and washing blankets at < 60°C were inversely related to frequent wheezing. Data confirmed also that maternal phenotype influences the inheritance of atopic disease. No event, except a low intake of fruit (< 3/week), was significantly associated with positive SPT (20%) or eczema. Besides allergic sensitization, other events, which occur early in life, seem critical to the development of IgE-mediated allergy.     

Increasing the hospitalization of asthma in children not in adults – from a national survey in Taiwan 1996–2002

Prevalence of asthma has risen gradually in past 30 yr in Taiwan, but less is known about the trend of asthma hospitalization and different hospitalization patterns between children and adult groups in the Chinese population. The implementation of National Health Insurance (NHI) in Taiwan was in 1995, and it covered health care for >96% of the population. Using NHI data from 1996 to 2002, we investigated the admission rate, length of stay, cost and the readmission rate of hospitalization with primary diagnosis of asthma in this period. We also compare the difference between the children group (<18 yr old) and adult group (≥18 yr old). The average incidence of hospitalization in the age group below 18 was 105.0 cases per 100,000 children, and was 116.7 per 100,000 population in the adult group during that period. It increased by 6.5% annually in the children group, though it was 0.1% annually in the adult group. The hospitalization days were 3.6 ± 2.4 days in the children group, and were 8.2 ± 8.9 days of those age ≥18 (p < 0.0001). The hospitalization cost was $288.7 ± $292.9 and $717.5 ± $1409.4, respectively (p < 0.0001). Autumn was the most frequent admission season in the children group, but the winter season was the most common in the adult group. The average readmission rate in this period was 20.4%. It was 13.0% in the children group, and was 22.6% in the adult group (p < 0.0001). The general hospitalization rate of asthma in the children group was lower than the adult group. It increased significantly in the children group from 1996 to 2002, but the admission cost rose prominently in the adult group during the same period. The hospitalization days, admission cost, and readmission rate were also significantly lower in the children group.     

The prevalence, characteristics of and early life risk factors for eczema in 10-year-old children

Eczema is a common infantile disease but its nature and extent during later childhood remains unclear. In a whole-population birth cohort study (n = 1456) we examined prevalence and characteristics of eczema amongst 10-year-old children. At this age 1373 (94%) children completed ISAAC questionnaires, 1043 (72%) skin prick testing and 953 (65%) serum inhalant IgE antibody screening. At 10 years of age prevalence of eczema ever was 41.0% and for current eczema was 13.7% (combined current itchy rash and eczema ever). Most current eczema (71.0%) began before 4 years of age, but was associated with low morbidity at 10 years. Amongst children with diagnosed eczema at 4 years of age, 56.3% had current eczema at 10 years. Atopy (positive skin test) and other allergic states were associated with current eczema (p < 0.001). Risk factor analysis for current eczema identified independent significance for atopy (p = 0.01), rhinitis (p = 0.04) and food allergy (p = 0.01) at 4 years, plus maternal asthma (p = 0.03). Diagnosed rhinitis at 4 years emerged as a significant predictor of persistent disease. Eczema is not simply a transient infantile condition but a common problem at 10 years of age, often reflecting persistent disease from early childhood. Inherited predisposition towards atopy is the predominant risk factor for this state.     

Association of cord blood cytokine levels with wheezy infants in the first year of life

As antenatal environment may influence the development of atopy-predisposing immune response, cord blood cytokine productions may be an important predictor for wheezing. We investigated cord blood cytokines in a prospective birth cohort, intensively monitored for wheezy infant outcome at 1 yr. Cord blood serum samples from 269 children were assayed for interleukin (IL)-1β, -2, -4 to -8, -10, -12 (p70), -13, and -17, interferon-γ, tumor necrosis factor-α, granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor (G-CSF), monocyte chemotactic protein-1, and macrophage inflammatory protein-1β. Associations between family histories, antenatal and perinatal factors, cord blood cytokine concentrations, and wheezy infant outcomes (wheezing more than two times) were analyzed. In cord blood sera from 269 children, there were associations between high levels of IL-6, -8 and G-CSF concentrations, and cesarean section. Data at 1 yr were obtained from 213 infants, including 33 wheezy infants. Risk of wheezing was related to gestational age, birth weight, cesarean section, and maternal eczema, but not to bacterial/viral infection during pregnancy, maternal asthma, maternal smoking, or paternal history. High level of cord blood IL-8 concentration had a significant association with wheezy infant outcomes at 1 yr (p = 0.025). By using multivariate logistic regression analysis, birth weight [odds ratio(OR) = 0.998, 95% confidence interval (CI) = 0.997–1.000] and maternal eczema (OR = 5.356, 95% CI = 1.340–21.41), but no other factors, were significant predictors of wheezy infants. Birth weight, gestational age, and maternal history were important risk factors for wheezing in the first year of life. Several cord blood cytokine productions were influenced by cesarean section, and IL-8 may be a predictor for recurrent wheezing at 1 yr.     

Correlation of nitrites in breath condensates and lung function in asthmatic children

We aimed to evaluate the value of exhaled breath condensates in monitoring airway inflammation in childhood asthma before and after high altitude climate therapy.
Forty-eight asthmatic children on regular anti-asthma treatment with a normal FEV₁ and positive skin prick test for house dust mites were recruited. All children had been referred to an alpine clinic for high altitude climate therapy, because of persistent asthmatic symptoms despite use of daily anti-inflammatory treatment. Subjects were assessed on their arrival and before departure from the alpine clinic. Spirometry, bronchial provocation tests and measurements of nitrites in breath condensates were performed.
Median levels of nitrites were significantly higher before than after high altitude climate therapy (1.27 vs. 0.93 μ m ; p = 0.008). In addition, MEF₅₀ improved significantly (p < 0.0005). There was a significant correlation between nitrites in breath condensates and MEF₅₀ (r = −0.63, p < 0.0001), symptoms (r = 0.47, p = 0.0007) and airway hyper-reactivity (AHR) (r = −0.41, p = 0.004).
In summary, we found a reduction in nitrites in breath condensates after a high altitude climate therapy. Significant correlations were found between nitrites and MEF₅₀, AHR and symptoms. We conclude that the measurement of nitrites may be feasible to objectively assess airway inflammation in asthmatic children in order to detect ongoing inflammation in children with normal FEV₁ but persistent symptoms.     

Eosinophil cationic protein and interleukin-8 levels in bronchial lavage fluid from children with asthma and infantile wheeze

It has been shown previously that airway eosinophils characterize childhood asthma and neutrophils contribute to the pathophysiology of both infantile wheezing and asthma. Therefore, eosinophil cationic protein (ECP) and interleukin‐8 (IL‐8) levels in bronchoalveolar lavage fluid (BALF) from asthmatics (n = 16) and infantile wheezers (n = 30) were analyzed as markers of eosinophil‐ and neutrophil‐mediated inflammation. To aid the interpretation, a control group of children (n = 10) with no lower airway pathology were included. Disease severity was assessed by using a symptom score. Surprisingly, no significant difference was found in IL‐8 or ECP levels among asthma, infantile wheeze, and control groups. Asthma was characterized by: a correlation between ECP levels and eosinophil counts (r = 0.618, p = 0.014); a correlation between neutrophil number and IL‐8 levels (r = 0.747, p = 0.002); and increasing IL‐8 levels with symptom score (p = 0.03). In infantile wheezers, IL‐8 levels were poorly related to neutrophil number but were significantly increased when neutrophils were > 10%. Although detectable levels were found in all but one symptomatic infant, IL‐8 concentrations did not reflect the symptom score in infantile wheeze. ECP was unexpectedly correlated to neutrophil percentages (Rho = 0.832, p = 0.001), and a threshold of ECP > 20 ng/ml was associated with persistent symptoms in these infantile wheezers. Hence, in accordance with BALF cellularity, activation of eosinophils was suggested by raised levels of ECP in childhood asthma, but not in infantile wheeze. Neutrophil‐mediated inflammation appeared to better reflect the severity of asthma than that of infantile wheeze. Although its meaning remains to be elucidated, ECP was suggested to be a helpful indicator of persistent infantile wheeze. However, its utility as a marker predicting ongoing asthma remains to be established.