Eicosanoids in exhaled breath condensates in the assessment of childhood asthma

The value of measurements of eicosanoids in exhaled breath condensate (EBC) for the evaluation of childhood asthma is still inconclusive most likely because of the limited value of the methods used. In this case–control study in 48 asthmatic and 20 healthy children, we aimed to characterize the baseline profile of the inflammatory mediators cysteinyl leukotrienes (cysLTs), 9_α11_βPGF₂, PGE₂, PGF_2α, 8‐isoprostane (8‐iso‐PGF_2α) within EBC in asthmatic compared with healthy children using new methods. In addition, we investigated their relation to other inflammatory markers. The assessment included collection of EBC, measurement of fractional exhaled nitric oxide (FE_NO) and evaluation of urinary excretion of leukotriene E_4. cysLTs were measured directly in EBC by radioimmunoassay and prostanoids were measured using gas chromatography negative‐ion chemical ionization mass spectrometry. Only cysLT levels were significantly higher in asthmatic compared with healthy children (p = 0.002). No significant differences in cysLTs were found between steroid naïve and patients receiving inhaled corticosteroids. In contrast, FE_NO was significantly higher in steroid naïve compared with steroid‐treated asthmatic and healthy children (p = 0.04 and 0.024, respectively). The diagnostic accuracy of cysLTs in EBC for asthma was 73.6% for the whole group and 78.2% for steroid‐naïve asthmatic children. The accuracy to classify asthmatic for FE_NO was poor (62.9%) for the whole group, but improved to 79.9% when only steroid‐naïve asthmatic children were taken into consideration. cysLTs in EBC is an inflammatory marker which distinguishes asthmatics, as a whole group, from healthy 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.     

Extended-stay hospitalization for childhood asthma in Japan

Background:  While recent advances in asthma management have enabled adequate control to be frequently achieved in outpatient settings, children whose asthma remains poorly controlled despite outpatient treatment are often referred to extended-stay hospitals. The aim of the present study was to examine trends concerning extended-stay hospitalization and to evaluate the present status of this approach.
Methods:  A retrospective study was conducted to assess changes in the number of admissions among 408 children with extended stays at Kamiamakusa General Hospital between 1989 and 2005. Medical and laboratory data of 236 patients admitted since 1994 were obtained from clinical records.
Results:  The number of children with extended-stay hospitalizations since 2000 declined dramatically compared with the early 1990s, while the percentage of patients with complications of childhood asthma, such as severe atopic dermatitis, school absenteeism, and obesity, have increased significantly in the recent past. Practical benefits of extended-stay hospitalization were demonstrated by significant improvement of exercise performance and measurement of pulmonary function parameters and serum IgE concentrations by time of discharge. In addition to improvement in asthmatic symptoms, maintenance drug requirements and frequency of school absenteeism were reduced.
Conclusions:  The medical mission of extended-stay hospitalizations is currently limited due to the availability of improved pharmacotherapy. Some patients, however, with exceptionally severe asthma or psychological problems that interact with their medical condition still fare poorly under outpatient care and could benefit from group care. Further study is needed to identify the components of long-term programs essential to produce change.     

Definition of respiratory symptoms and disease in early childhood in large prospective birth cohort studies that predict the development of asthma

We have reviewed the prospective value of early respiratory symptoms for determining the risk of development of asthma later in life by using data from studies based on the general population, hospital population, and general practices. Although 'wheezing' in infancy generally has a good prognosis, it is an important risk factor for the development of asthma later in life. The prognostic value of 'coughing' and 'shortness of breath' in infancy for the later development of asthma is less clear. Despite the fact that no internationally accepted criteria for the definition of asthma in early childhood are available, many studies have been performed on this topic. We also investigated the outcome variables that were used to describe respiratory symptoms and disease in early childhood in the publications of nine large prospective birth cohort studies on the development of asthma. From seven of these studies, we reviewed the original questionnaires. We found that various studies used different outcome variables, but the data actually collected were similar. This is an important observation because it implies that comparisons between studies can be markedly improved by data sharing among investigators.     

儿童哮喘在青春期转归的影响因素

哮喘是儿童期最常见的慢性呼吸系统疾病,部分哮喘患儿在青春期缓解.哮喘患儿的转归一直备受关注,目前研究显示与儿童哮喘青春期转归有关的影响因素主要为性别、起病年龄、病情严重程度、特应性表现、气道高反应性、肺功能、生活环境等.     

Longitudinal follow-up of the changing gender ratio in asthma from childhood to adulthood: role of delayed manifestation in girls

Boys suffer more often from asthma than girls, while in adults the gender ratio is reversed. It is not clear when exactly this change occurs and by what mechanism. From a cohort of all 5030 German 4th grade pupils (age 10 years) in Munich, 274 children with current asthma were identified (164 males, 110 females) through a questionnaire, and skin prick tests were performed. These subjects were re-evaluated at ages14 and 20 years with a questionnaire. A random sample (n = 1000) of all 3538 German children without current asthma at age 10 was also re-evaluated at age 20 (controls). At age 20, only 24.5% (21 males, eight females) of the initial asthma group still had symptoms, and their gender ratio remained male dominated. In the controls, 4.8% (48/1000) had current asthma at age 20 and these were predominantly female: 6.4% (31/485) of control girls vs. 3.3% (17/515) of boys (p = 0.022). Half of the new asthma cases had had no symptoms or diagnoses until age 10, and atopy at age 10 was not associated with subsequent asthma in these. Asthma at age 10 has no better prognosis in boys than in girls, and the mechanism of the changing gender ratio appears to be late incidence of asthma among girls. Because the latter constitute a considerable part of adult asthma cases, it appears important to further explore this asthma phenotype and the risk factors associated with it.     

Hospital admissions for childhood asthma in Rogaland,Norway, from 1984 to 2000

AIM: The prevalence of childhood asthma is increasing, and it is important to monitor factors related to hospital admissions in order to understand the different aspects of the disease. The aim of this study was to investigate admissions for childhood asthma to Rogaland Central Hospital, Norway, in order to elucidate time trends related to rates of admissions and treatment modalities. METHODS: A population-based study was conducted in which data extracted from the medical records, including number of admissions, length of hospitalization, medication and symptom scores, were recorded for children aged 1 to 14 y admitted to hospital for asthma during four periods, of two years each, from 1984/1985 to 1999/2000. RESULTS: For all the children there was an increase in annual admission rates for asthma from 1984/1985 to 1989/1990 and stabilization thereafter, but there were substantial differences between age groups. For children of 1 or 2 y of age the annual admission rate increased from 43/10000 in the first period to 104/10000 in the last period (p < 0.001), with an increase in both primary admissions and re-admissions. For children aged 3 and 4 y, the admission rates increased from the first to the second period, and then declined to an annual admission rate of 40/10000 in 1999/2000. For older children, the admission rate was low and stable. There was a gradual increase in the use of inhaled corticosteroids both prior to admission and at discharge, and the percentage of children receiving systemic corticosteroids at admission increased from 19% to 45% (p < 0.001). The average hospital in-days decreased from 3.4 to 1.9 (p < 0.001). CONCLUSION: A disturbingly high and increasing rate of both primary admissions and re-admissions for asthma has been observed in children aged 1 and 2 y, which seemed to be unaffected by changes in treatment modalities during the period. The decrease in admissions for children aged 3 and 4 y may have been influenced by the increased use of inhaled corticosteroids.     

儿童肥胖与哮喘在生命早期的共同危险因素

儿童哮喘与肥胖是当今世界的两项重大健康问题.在过去的几十年里,两者的发病率均有明显的升高.尽管已有大量的临床和基础研究发现两者的相关性及可能的发病机制,但两者是如何相关联的仍不甚清楚.肥胖与哮喘均有着生命早期的起源,这些起源的共同部分包括共同的基因片段、产前营养、肠道菌群的定植、出生体质量的情况以及生活方式等.     

Influence of outdoor NO2 exposure on asthma in childhood: Meta‐analysis

Background: It has long been assumed that the development of childhood asthma is related to exposure to environmental chemicals, but it has thus far not been possible to unequivocally establish this suspected relationship using individual studies. Moreover, studies of children have been scanty and unreliable due to the large diversity of research environments and subject cohorts. The aim of the current study was to clarify this relationship for one factor by means of a meta‐analysis of studies investigating the influence of NO₂ exposure on symptomatology of childhood asthma. Methods: Two electronic databases ( MEDLINE and EMBASE ) were searched for literature on relationships between environmental chemical exposure and development of childhood asthma using the MeSH terms ‘nitrogen dioxide’ and ‘asthma’. This was done according to the MOOSE guidelines for meta‐analyses of observational studies. Results: A total of 130 papers were retrieved, of which 12 met the selection criteria. These papers described observational studies from seven countries. Study subjects were 97 932 ordinary children aged 0–18 years. Using random model analysis, the odds ratio (OR) for asthma development due to an increment of 10 p.p.b. NO₂ was 1.135 with a 95% confidence interval [CI] of 1.031–1.251 (P= 0.01), while the OR for wheezing symptoms was 1.052 with a 95%CI of 1.020–1.085 (P= 0.001). It is therefore evident that NO₂ exposure does influence the development of asthma in ordinary children. Conclusions: Exposure to NO₂ in the air significantly influences the development of childhood asthma and symptoms of wheezing.     

Hospitalizations for childhood asthma in Athens, Greece, from 1978 to 2000

Trends in rates of asthma admissions among children have shown a variety of patterns in different countries in the last decades. We undertook the present study to determine the time trends in asthma admissions and readmissions of children in Athens, Greece. Data were obtained retrospectively from hospital registries of the three main children's hospitals in Athens from 1978 to 2000. Children admitted with the diagnoses of asthma, asthmatic bronchitis or wheezy bronchitis were included. Hospital admission rate for asthma among children 0-14 yr from 1978 to 2000 rose by 271% (p <0.001). The rise in rates among those aged 0-4 and 5-15 yr were 250% and 276%, respectively. The mean annual increase in admission rate was 12.2% for 1978-1987, 4.7% for 1988-1993 and 0.6% for 1994-2000. The readmission rate among children 0-14 yr was increased from 15.3% to 23.3%. A positive correlation between admission and readmission rates in all age groups was observed. In conclusion, our findings show an increase in the childhood asthma admission rate in Athens in late 1970's and during the 1980's, which has decelerated in the 1990's, particularly in the second-half of the decade. The readmission rate paralleled that of admissions over the entire study period.     

IRF‐1 SNPs influence the risk for childhood allergic asthma: A critical role for pro‐inflammatory immune regulation

Background

Allergic and non‐allergic childhood asthma has been characterized by distinct immune mechanisms. While interferon regulating factor 1 (IRF‐1) polymorphisms (SNPs) influence atopy risk, the effect of SNPs on asthma phenotype‐specific immune mechanisms is unclear. We assessed whether IRF‐1 SNPs modify distinct immune‐regulatory pathways in allergic and non‐allergic childhood asthma (AA/NA).

Methods

In the CLARA study, asthma was characterized by doctor's diagnosis and AA vs NA by positive or negative specific IgE. Children were genotyped for four tagging SNPs within IRF‐1 (n = 172). mRNA expression was measured with qRT‐PCR. Gene expression was analyzed depending on genetic variants within IRF‐1 and phenotype including haplotype estimation and an allelic risk score.

Results

Carrying the risk alleles of IRF‐1 in rs10035166, rs2706384, or rs2070721 was associated with increased risk for AA. Carrying the non‐risk allele in rs17622656 was associated with lower risk for AA but not NA. In AA carrying the risk alleles, an increased pro‐inflammatory expression of ICAM3, IRF‐8, XBP‐1, IFN‐γ, RGS13, RORC, and TSC2 was observed. NOD2 expression was decreased in AA with risk alleles in rs2706384 and rs10035166 and with risk haplotype. Further, AA with risk haplotype showed increased IL‐13 secretion. NA with risk allele in rs2070721 compared to non‐risk allele in rs17622656 showed significantly upregulated calcium, innate, mTOR, neutrophil, and inflammatory‐associated genes.

Conclusion

IRF‐1 polymorphisms influence the risk for childhood allergic asthma being associated with increased pro‐inflammatory gene regulation. Thus, it is critical to implement IRF‐1 genetics in immune assessment for childhood asthma phenotypes.     

Association between neopterin in cord blood, urinary neopterin in early childhood and the development of atopic dermatitis, asthma and hay fever.

It is generally accepted that the increased prevalence of atopic disease is due to a disturbed balance of T-helper (Th)1/Th2-type immunity. Upon stimulation by the Th1-type cytokine interferon (IFN)-gamma, human monocytes/macrophages release large amounts of neopterin. Thus, the determination of neopterin concentrations is an indirect measure of the levels of IFN-gamma and allows us to monitor Th1-type immune response. We evaluated whether neopterin concentrations in the neonatal cord blood could be a valuable marker predicting atopic disease in early childhood and whether there is a difference in actually determined urinary neopterin concentrations in children with and without atopic disease. Five hundred and five children born during 1997-1999 were enrolled, with cord blood neopterin data available at birth. The International study of asthma and allergies in childhood (ISAAC) questionnaire was used to assess the prevalence of wheezy bronchitis (asthma), atopic dermatitis and allergic rhinitis. Morning urinary samples were collected and urinary neopterin concentration was measured by high-pressure liquid chromatography. By the average age of 6 yr, the prevalence of atopic disease in the last 12 months was 31%. There was no significant correlation between cord blood and urinary neopterin concentrations at age 6 yr, and between cord blood neopterin and later atopic disease. Urinary neopterin concentrations were significant lower in children with a family history of atopic disease (p = 0.02). In this study, cord blood neopterin concentration was not a predictor for atopic disease in early childhood. Family history of atopic disease was associated with lower urinary neopterin levels at age 6 yr, which might mirror a Th1/Th2 imbalance.