Relationship between induced sputum eosinophils and the clinical pattern of childhood asthma

BACKGROUND: The relationship between the clinical pattern of asthma and airway inflammation in childhood asthma is poorly characterised, yet underpins the treatment recommendations in current asthma guidelines. A study was undertaken to examine the relationship between airway inflammation and clinical asthma in children. METHODS: Children with asthma (n=146) and healthy controls (C, n=37) were recruited from primary and specialist clinics. Sputum induction and hypertonic saline challenge were performed. RESULTS: As the frequency of asthma episodes in the past 12 months increased, there were significant increases in sputum eosinophils (median; infrequent episodic (IE) 1.5%, frequent episodic (FE) 2.3%, persistent (P) 3.8%, control (C) 1.0%; p=0.002), sputum eosinophil cationic protein (ECP) (IE 113 ng/ml, FE 220, P 375, C 139; p=0.003), and desquamated bronchial epithelial cells (IE 2.0%, FE 6.0%, P 5.0%, C 2.5%; p=0.04). Treatment intensity was also associated with increased sputum eosinophils (p=0.005). The relationships between other severity markers (current symptoms, lung function) were less strong. CONCLUSION: Children with more frequent episodes of clinical asthma exhibit increasing airway inflammation that is characterised by sputum eosinophilia and bronchial epithelial desquamation. The results support clinical assessment by frequency of wheezing episodes over the past 12 months when determining anti-inflammatory treatment requirements, and indicate that current symptoms are determined by mechanisms in addition to sputum eosinophilia.     

Primary prevention of asthma and atopy during childhood by allergen avoidance in infancy: a randomised controlled study

BACKGROUND: Recent increases in the prevalence of asthma and atopy emphasise the need for devising effective methods for primary prevention in children at high risk of atopy. METHOD: A birth cohort of genetically at risk infants was recruited in 1990 to a randomised controlled study. Allergen avoidance measures were instituted from birth in the prophylactic group (n=58). Infants were either breast fed with mother on a low allergen diet or given an extensively hydrolysed formula. Exposure to house dust mite was reduced by the use of an acaricide and mattress covers. The control group (n=62) followed standard advice as normally given by the health visitors. At age 8, all 120 children completed a questionnaire and 110 (92%) had all assessments (skin prick test, spirometry, and bronchial challenges). RESULTS: In the prophylactic group eight children (13.8%) had current wheeze compared with 17 (27.4%) in the control group (p=0.08). Respective figures were eight (13.8%) and 20 (32.3%) for nocturnal cough (p=0.02) and 11 of 55 (20.0%) and 29 of 62 (46.8%) for atopy (p=0.003). After adjusting for confounding variables, the prophylactic group was found to be at a significantly reduced risk for current wheeze (odds ratio (OR) 0.26 (95% confidence interval (CI) 0.07 to 0.96)), nocturnal cough (OR 0.22 (95% CI 0.06 to 0.83)), asthma as defined by wheeze and bronchial hyperresponsiveness (OR 0.11 (95% CI 0.01 to 1.02)), and atopy (OR 0.21 (95% CI 0.07 to 0.62)). CONCLUSION: Strict allergen avoidance in infancy in high risk children reduces the development of allergic sensitisation to house dust mite. Our results suggest that this may prevent some cases of childhood asthma.     

Age at childhood infections and risk of atopy

BACKGROUND: It has been proposed that early age at exposure to common childhood infections is associated with a decreased risk of allergy. Previous studies on the possible association between allergy and infection with measles, mumps, rubella, and varicella have not been conclusive as most did not include information on exact age at exposure. The objective of our study was to investigate whether early age at exposure to these infections was associated with a decreased risk of atopy using information on exact age at infection. METHODS: The study population consisted of 889 pregnant women who participated in a national birth cohort study in Denmark and for whom detailed information on history of measles, rubella, varicella, and mumps before school entry (age 7 years) was available from school health records from Copenhagen. Atopic status was assessed serologically by a specific response to 11 common inhalant allergens using serum samples obtained from the women during pregnancy. RESULTS: Measles in the first year of life was associated with a higher risk of atopy than no measles before age 7 years (OR 3.36, 95% CI 1.47 to 7.68). There was no association between atopy and mumps, rubella, or varicella in the first 7 years of life or with measles acquired after the first year of life. The risk of atopy increased significantly with increasing number of childhood infections in the first 2 years of life (p(trend)=0.01). CONCLUSIONS: These findings do not support the suggestion that childhood exposure to measles, rubella, varicella, or mumps protects against atopy, even if acquired very early in life.     

Relationship between asthma and gastro-oesophageal reflux.

Twenty patients with bronchial asthma who also had gastro-oesophageal reflux were investigated. The severity of their reflux was graded using symptom score of heartburn and regurgitation and by the following investigations: barium swallow and meal, fibreoptic endoscopy and biopsy, manometry and pH monitoring of the distal oesophagus, and an acid infusion test. Full lung function studies were performed and patients were entered into a double-blind crossover study using cimetidine to control their reflux in order to assess beneficial effects with respect to their respiratory problems. Eighteen patients completed the study. Significant improvements were seen in reflux and night time asthmatic symptoms, both these indices being measured on a scoring system. Home monitoring of peak flow values showed a statistical improvement for th last peak flow reading of the day. Fourteen patients felt that their chest symptoms had significantly improved during the cimetidine period.     

Human growth plate development in the fetal and neonatal period.

The development of the normal human upper tibial growth plate was studied at autopsy in 46 stillborns and 79 newborns of 20-41 weeks gestational age. During this time period, the histology of this plate evolves from a highly cellular structure with relatively poor columnar organization and matrix development to the well known structure seen later in postnatal life. The thickness of the growth plate, assessed in the area surrounding the longitudinal tibial axis, decreases continuously from 1.15 mm on the 20th week to 0.6 mm on the 38th week. This decrease results from losses of both matrix and cellular components, mostly of the latter. However, the relative fraction of area occupied by the matrix significantly increased (12%) and matrix area per cell increased 1.5 times over the last half of gestation, indicating a maturation process of the plate towards a more matrix-oriented structure with age. In this maturation process the number of cells per unit area does not change and the average size of the cells appears to decrease. Plate thickness does not decrease further in the final 3 weeks of pregnancy and increases in early neonatal life; this has no apparent influence on the tibial growth rate. In the period under study the relative anatomical participation of the upper tibial growth plate decreases from approximately 4% of the radiographic length of the tibia on the 20th week to less than 1% at term. Present data will provide fetal and neonatal growth plate standards needed to obtain a better understanding of this structure during both normal and abnormal conditions.     

Relationship between placental expression of the imprinted PHLDA2 gene, intrauterine skeletal growth and childhood bone mass

Alterations in expression of the imprinted gene PHLDA2 are linked to low birth weight in both humans and the mouse. However birth weight is a summary measure of fetal growth and provides little information on the growth rate of the fetus in early and late pregnancy. To examine the relation of PHLDA2 expression with rates of fetal growth and explore associations with the infant's body composition in early childhood, we measured PHLDA2 mRNA levels in the term placenta of 102 infants whose mothers were participating in the Southampton Women's Survey (SWS). Higher PHLDA2 expression was associated with a lower fetal femur growth velocity between 19 and 34 weeks gestation. In addition, higher placental PHLDA2 gene expression was associated with a lower child's bone mineral content at four years of age, measured using dual-energy X-ray absorptiometry. The results suggest that placental PHLDA2 may provide a biomarker for suboptimal skeletal growth in pregnancies uncomplicated by overt fetal growth restriction.     

The interaction between epidermal growth factor and matrix metalloproteinases induces the development of sweat glands in human fetal skin

BACKGROUND: The development of sweat glands is a very complicated biological process involving many factors. In this study, we explore the interrelationship among epidermal growth factor (EGF), matrix metalloproteinase 2 (MMP-2), matrix metalloproteinase 7 (MMP-7), and the development of sweat glands in human embryos. Furthermore, we hope to elucidate the mechanism(s) underlying the induction of epidermal stem cells into sweat gland cells. MATERIALS AND METHODS: Skin biopsies of human embryos obtained from spontaneous abortions at different gestational ages from 11 to 31 weeks were used in this study. The dynamic expression of EGF, MMP-2, MMP-7, and keratin-7 (K7) in developing sweat gland cells or extracellular stroma surrounding the sweat gland cells was examined with SP immunohistochemical methods. The localization of the cellular sources of MMP-2 and MMP-7 was examined with in situ hybridization. RESULTS: At 14-20 weeks of gestation, a gradual increase in EGF immunoreactivity was observed not only in developing sweat gland buds but also in extracellular stroma surrounding the buds, and the expression intensity of EGF peaked at 20-22 weeks of gestational age. All mRNA-positive buds or cells in developing sweat glands contained corresponding immunoreactive proteins. Positive immunostaining for K7 appeared in early sweat gland buds at 14-16 weeks of gestation, and from then on, the positive signal of K7 was concentrated in developing sweat gland cords or cells. CONCLUSIONS: The morphogenesis of sweat glands in human fetal skin begins at 14-16 weeks of gestational age, and is essentially complete by 24 weeks. There is a close relationship among EGF, extracellular matrix remodeling, and morphogenesis of the sweat glands. EGF is one of the inducers in the development and maturity of sweat gland buds or cells.     

Effects of gas and other fume emitting heaters on the development of asthma during childhood

BACKGROUND: Several studies have shown adverse effects of gas cookers and heaters on respiratory health. The long term effects of early life exposure to these appliances are not known. This study investigated the effect of exposure to fume emitting heaters, currently and during the first year of life, on the risk of asthma outcomes. METHODS: A cross sectional study of schoolchildren (n = 627) aged 8-11 years was conducted in Belmont, Australia. Information on symptoms and heating types was collected by parent completed questionnaire. Atopy was assessed by skin prick tests and airway hyperresponsiveness (AHR) was assessed by histamine challenge test. RESULTS: There was no association between the current use of fume emitting heaters and any of the asthma outcomes. However, having been exposed to fume emitting heaters during the first year of life was associated with an increased risk of having AHR (relative risk (RR) 1.47, 95% confidence interval (CI) 1.06 to 2.03), recent wheeze (RR 1.44, 95% CI 1.11 to 1.86), and recent wheeze + AHR (RR 2.08, 95% CI 1.31 to 3.31). CONCLUSION: If confirmed in other settings, this finding would require a review of the range of heating types that are appropriate for use in households in which young children live.     

Relationship between leptin levels in maternal blood,amniotic fluid,arterial and venous cord blood and fetal growth

<正> Objective:To study the relationship between leptin concentration and fetal growth.Methods:Levels of leptin in maternal serum,amniotic fluid,arterial and venouscord blood of 65 normal parturients (gestational age 37-42weeks) were measured by ra-dioimmunoassay (RIA) method.At the same time,maternal blood lipids were detected.Neonates were divided into three groups:small for gestational age (SGA) group (n=10),appropriate for gestational age (AGA) group (n=45),large for gestational age(LGA) group (n=10).Statistical analysis was performed by t test,variance analysisand correlation analysis.Results:(1) There was no obvious correlation between leptin concentrations in ma-ternal serum and arterial/ venous cord blood,amniotic fluid,and also no correlationwith birth weight and placental weight (P>0.05).Maternal body mass index signifi-cantly correlated with birth weight and neonatal length and leptin levels in arterial andvenous cord blood (P<0.01).Leptin levels in arterial and venous cord blood positivelycorrelated significantly with placental and neonatal weight and body length (P<0.01)and negatively correlated with high density lipoprotein (P<0.01).There was no obvi-ous correlation between fetal gender and leptin concentrations in maternal serum,arteri-al and venous cord blood and amniotic fluid;(2) Leptin levels in arterial and venouscord blood,placental weight in LGA group were significantly higher than those in SGAand AGA group (P<0.05).Among three groups,leptin concentrations in maternalblood were significantly higher than those in arterial and venous cord blood (P<0.05).Conclusions:(1)Fetal leptin is synthesized in uterus,born of itself and placenta.Leptin levels in arterial and venous cord blood are related to the intrauterine growthpattern.It might positively regulate birth weight and body fat content.(2)Either mater-nal or fetal leptin was not correlated with fetal gender.There is no gender difference infetal leptin concentrations.     

产妇血清、脐动、静脉及羊水中瘦素水平与胎儿生长发育关系

目的 :探讨瘦素水平与胎儿宫内生长发育的关系。方法 :采用放射免疫测定法 ,分别检测 65例孕 3 7～ 42周分娩产妇血清及脐动、静脉、羊水中的瘦素水平 ,同时测定产妇血脂水平。根据不同出生体重分为小于胎龄儿 ( SGA)组 ( n=1 0 )、适于胎龄儿 ( AGA)组 ( n=45)及超于胎龄儿 ( L GA)组 ( n=1 0 ) ,对结果进行相关性分析。结果 :( 1 )产妇血清瘦素水平与胎儿出生体重、胎盘重量、脐动、静脉及羊水中的瘦素水平均无明显相关性 ( P均 >0 .0 5) ;产妇的体重指数与胎儿出生体重、身长、脐动、静脉瘦素水平均呈显著正相关( P均 <0 .0 1 ) ;脐动静脉瘦素水平与胎盘重量、胎儿出生体重、身长均呈正相关 ( P均 <0 .0 1 ) ,与高密度脂蛋白呈负相关 ( P<0 .0 1 ) ;羊水瘦素水平与胎儿出生体重、胎盘重量、母体重及血脂水平均无相关性 ;产妇血清及脐动、静脉、羊水瘦素水平均与胎儿性别无相关性。 ( 2 )三组的脐动、静脉瘦素水平及胎盘重量 L GA组 ,高于 AGA及 SAG组 ( P均 <0 .0 5) ;AGA组又比 SAG组高 ( P<0 .0 5) ;三组的产妇血清及羊水瘦素水平无显著差异( P>0 .0 5) ;三组脐动、静脉瘦素水平均低于产妇血清瘦素水平 ( P<0 .0 5)。男、女婴的脐动、静脉、羊水及产妇血清瘦素水平无显著性差异。结论 :( 1 )胎儿的     

Relationship between air pollution, lung function and asthma in adolescents

BACKGROUND: The interrelationships between air pollution, lung function and the incidence of childhood asthma have yet to be established. A study was undertaken to determine whether lung function is associated with new onset asthma and whether this relationship varies by exposure to ambient air pollutants. METHODS: A cohort of children aged 9-10 years without asthma or wheeze at study entry were identified from the Children's Health Study and followed for 8 years. The participants resided in 12 communities with a wide range of ambient air pollutants that were measured continuously. Spirometric testing was performed and a medical diagnosis of asthma was ascertained annually. Proportional hazard regression models were fitted to investigate the relationship between lung function at study entry and the subsequent development of asthma and to determine whether air pollutants modify these associations. RESULTS: The level of airway flow was associated with new onset asthma. Over the 10th-90th percentile range of forced expiratory flow over the mid-range of expiration (FEF(25-75), 57.1%), the hazard ratio (HR) of new onset asthma was 0.50 (95% CI 0.35 to 0.71). This protective effect of better lung function was reduced in children exposed to higher levels of particulate matter with an aerodynamic diameter <2.5 microm (PM(2.5)). Over the 10th-90th percentile range of FEF(25-75), the HR of new onset asthma was 0.34 (95% CI 0.21 to 0.56) in communities with low PM(2.5) (<13.7 microg/m(3)) and 0.76 (95% CI 0.45 to 1.26) in communities with high PM(2.5) (> or = 13.7 microg/m(3)). A similar pattern was observed for forced expiratory volume in 1 s. Little variation in HR was observed for ozone. CONCLUSION: Exposure to high levels of PM(2.5) attenuates the protective effect of better lung function against new onset asthma.     

In utero supplemental fetal feeding in an animal model: effects on fetal growth and development

That the fetus swallows amniotic fluid and has the capability of intestinal absorption of protein and carbohydrate is known, but its significance in fetal nutrition is not clear. We have infused nutrient solutions of dextrose and amino acids intra-amniotically in a chronic third-trimester fetal rabbit model and examined the effects on fetal growth and development. Over a 5-day period, 26 fetal rabbits received graded doses of dextrose in water with or without amino acids infused continuously into the amniotic space. At the time of delivery, fetal body, liver, and brain weight, crown-rump length, and brain protein content were significantly higher in the infused rabbits than in noninfused controls. Amniotic fluid, serum, and gastric content glucose levels were significantly higher in infused fetuses. There was a linear relationship between nonprotein calories administered and fetal growth within the infused group. No toxicity of infusates in the fetus was noted, although technical complications relating to the infusion apparatus were common. We conclude that third-trimester intra-amniotic infusion of nutrient solutions enhances fetal growth in this rabbit model. We speculate that this technique may be of value in the antenatal treatment of growth-retarded fetuses.