Associations of eczema phenotypes with emotional and behavioural problems from birth until school age. The Generation R Study.

BACKGROUND: Eczema phenotypes and emotional and behavioural problems are highly prevalent in childhood, but their mutual relationship is not fully clear. OBJECTIVES: To examine the associations of eczema phenotypes with school-age emotional and behavioural problems, and the bidirectional associations of eczema and emotional and behavioural problems from birth until 10 years. METHODS: This study among 5265 individuals was embedded in a prospective population-based cohort study. Never, early transient, mid-transient, late transient and persistent eczema phenotypes were identified based on parent-reported, physician-diagnosed eczema from age 6 months until 10 years. Emotional (internalizing) and behavioural (externalizing) problems were measured repeatedly using the Child Behavior Checklist from age 1·5 to 10 years. Cross-lagged models were applied for bidirectional analyses. RESULTS: All eczema phenotypes were associated with more internalizing problems and attention problems at age 10 years, compared with never having eczema: range of Z-score differences 0·14 [95% confidence interval (CI) 0·01-0·27] to 0·39 (95% CI 0·18-0·60). Children with early transient eczema had more aggressive behaviour symptoms at age 10 years (Z = 0·16, 95% CI 0·05-0·27). Bidirectional analysis showed that eczema at 0-2 years was associated with more internalizing and externalizing problems at ages 3-6 and 10 years, while, inversely, only internalizing problems at 0-2 years were associated with an increased risk of eczema at age 10 years. CONCLUSIONS: Eczema phenotypes are very modestly associated with more somatic symptoms and attention problems at school age. Early transient eczema is associated with more aggressive behaviour symptoms. Directional effects seem to occur from early-life eczema to later-life internalizing and externalizing problems, rather than the reverse.

Most associations of early-life environmental exposures and genetic risk factors poorly differentiate between eczema phenotypes: the Generation R Study.

BACKGROUND: Childhood eczema is variable in onset and persistence. OBJECTIVES: To identify eczema phenotypes during childhood, and their associations with early-life environmental and genetic factors. METHODS: In this study of 5297 children from a multiethnic population-based prospective cohort study, phenotypes based on parent-reported physician-diagnosed eczema from age 6 months to 10 years were identified using latent class growth analysis. Information on environmental factors was obtained using postal questionnaires. Four filaggrin mutations were genotyped and a risk score was calculated based on 30 genetic variants. Weighted adjusted multinomial models were used for association analyses. RESULTS: We identified the following five eczema phenotypes: never (76%), early transient (8%), mid-transient (6%) and late transient (8%) and persistent eczema (2%). Early transient and persistent eczema were most common in first-born children, those with a parental history of eczema, allergy or asthma and those with persistent wheezing [range of odds ratio (OR): 1.37, 95% confidence interval (CI) 1.07-1.74 and OR 3.38, 95%CI 1.95-5.85]. Early transient eczema was most common in male children only (OR 1·49, 95% CI 1·18-1·89). Children with late transient or persistent eczema were more often of Asian ethnicity (OR 2·04, 95% CI 1·14-3·65 and OR 3·08, 95% CI 1·34-7·10, respectively). Children with early, late transient and persistent eczema more often had a filaggrin mutation or additional risk alleles (range OR: 1.07, 95%CI 1.02-1.12 and OR 2.21, 95%CI 1.39-3.50). Eczema phenotypes were not associated with maternal education, breastfeeding, day care attendance and pet exposure. CONCLUSIONS: Five eczema phenotypes were identified in a multiethnic paediatric population with limited differences in risk profiles, except for sex and ethnicity. What's already known about this topic? Two previous studies in longitudinal birth cohorts identified four and six different eczema phenotypes, predominantly in children of European ethnicity. What does this study add? Five eczema phenotypes were identified in a multiethnic paediatric population using latent class growth analysis. Children with early transient and persistent eczema were most often first-born children and had persistent wheezing, filaggrin mutation or additional risk alleles. Previously known eczema risk factors had limited differentiating capabilities for eczema phenotypes, except for the association of early transient eczema with male children, and late transient and persistent eczema with Asian ethnicity.

Maternal folic acid use during pregnancy, methylenetetrahydrofolate reductase gene polymorphism, and child's lung function and asthma.

BACKGROUND: Folic acid supplement use during pregnancy might affect childhood respiratory health, potentially mediated by methylenetetrahydrofolate reductase polymorphism C677T (MTHFR-C677T) carriership. OBJECTIVES: We examined the associations of maternal folic acid supplement use and folate, vitamin B12 and homocysteine concentrations during pregnancy with childhood lung function and asthma. METHODS: This study was embedded in a population-based prospective cohort study among 5653 children. Folic acid supplement use was assessed by questionnaires. Folate, vitamin B12 and homocysteine plasma concentrations were measured in early pregnancy and at birth. At age 10 years, forced expiratory volume in 1 second (FEV1 ), forced vital capacity (FVC), FEV1 /FVC, forced expiratory flow between 25% and 75% (FEF25-75 ), at 75% of FVC (FEF75 ), and asthma were examined. RESULTS: Maternal folic acid supplement use during pregnancy was associated with higher childhood FEV1 and FVC and with a lower FEV1 /FVC, compared with no folic acid supplement use. Among mothers carrying MTHFR-C677T variants, preconceptional start of folic acid supplement use was associated with lower FEV1 /FVC (-0.17 [-0.32, -0.02]) and FEF25-75 (-0.24 [-0.40, -0.07]). Among children carrying MTHFR-C677T wild-type, a higher vitamin B12 level at birth was associated with a lower FEV1 (-0.07 [-0.12, -0.01]) and FVC (-0.09 [-0.15, -0.04]). Folate and homocysteine concentrations were not consistently associated with lower childhood lung function or asthma. CONCLUSIONS: Preconceptional start of maternal folic acid supplement use and higher vitamin B12 concentrations at birth might adversely affect childhood lung function depending on MTHFR-C677T carriership. The clinical implications need to be evaluated.

IgE-expressing memory B cells and plasmablasts are increased in blood of children with asthma, food allergy, and atopic dermatitis.

Despite the critical role of soluble IgE in the pathology of IgE-mediated allergic disease, little is known about abnormalities in the memory B cells and plasma cells that produce IgE in allergic patients. We here applied a flow cytometric approach to cross-sectionally study blood IgE+ memory B cells and plasmablasts in 149 children with atopic dermatitis, food allergy, and/or asthma and correlated these to helper T(h)2 cells and eosinophils. Children with allergic disease had increased numbers of IgE+CD27- and IgE+CD27+ memory B cells and IgE+ plasmablasts, as well as increased numbers of eosinophils and Th2 cells. IgE+ plasmablast numbers correlated positively with Th2 cell numbers. These findings open new possibilities for diagnosis and monitoring of treatment in patients with allergic diseases.

Increased risk of asthma in overweight children born large for gestational age.

BACKGROUND: Being born large for gestational age (LGA) is a marker of increased growth velocity in fetal life and a risk factor for childhood overweight. Both being born LGA and childhood overweight may influence the development of asthma, although the role of overweight in the association between LGA and childhood asthma is unclear. Importantly, recent studies have suggested that the association between overweight and asthma may be related to non-allergic pathways. If this also applies to the association between LGA and asthma, the association between being born LGA and asthma may be different for atopic and non-atopic children. OBJECTIVE: We investigated the association of being LGA with the prevalence of asthma at age 8 in atopic and non-atopic children and the role of overweight in this association. METHODS: Complete data on asthma, anthropometry and atopy at age of 8 years, and potential confounders were available for 1608 participants of the PIAMA birth cohort. Odds ratios for the association between LGA and asthma in atopic and non-atopic children were estimated by logistic regression analysis adjusting for potential confounders. Overweight was assessed as a potential modifier of the association between LGA and asthma. RESULTS: Being born LGA was not significantly associated with asthma at age of 8 in atopic and non-atopic children. However, overweight at age of 8 years modified the association between asthma at age of 8 and LGA. In non-atopic children, children who were born LGA and were overweight at age of 8 years had a significantly increased odds of asthma compared to non-LGA, non-overweight children (adj OR 7.04; 95% CI 2.2-24). CONCLUSIONS: We observed that non-atopic children born LGA, who were overweight by 8 years have an increased risk of asthma. If confirmed, these findings suggest that non-atopic children born LGA may be identified early in life as a high-risk group for asthma.

Maternal psychiatric symptoms during pregnancy and risk of childhood atopic diseases.

BACKGROUND: Maternal psychiatric symptoms during pregnancy might affect the developing immune system and subsequent risk of childhood atopic diseases. OBJECTIVE: Our aim was to examine the associations of maternal psychiatric symptoms during pregnancy with allergic sensitization, allergy and eczema in children until age 10 years. METHODS: This study among 5205 children was performed in a population-based prospective cohort from foetal life onwards. We assessed maternal and paternal psychiatric symptoms (overall, depressive, anxiety) during pregnancy and at 36 months after delivery, and maternal psychiatric symptoms at 2 and 6 months after delivery using the Brief Symptom Inventory. Inhalant and food allergic sensitization were measured by skin prick tests, and physician-diagnosed inhalant and food allergy or eczema by questionnaires from birth until age 10 years. We used multivariate logistic regression, multinomial logistic regression or generalized estimating equation models where appropriate. RESULTS: We observed no association of maternal psychiatric symptoms during pregnancy with allergic sensitization. Maternal overall psychiatric, depressive and anxiety symptoms during pregnancy were associated with an increased risk of inhalant allergy only (adjusted odds ratio (95% confidence interval) 1.96 (1.44, 2.65), 1.58 (1.25, 1.98) and 1.61 (1.27, 2.03), respectively, per 1-unit increase). Maternal overall psychiatric and anxiety symptoms during pregnancy were associated with an increased risk of eczema (1.21 (1.05, 1.39) and 1.15 (1.02, 1.29), respectively, per 1-unit increase). Effect estimates did not materially change when maternal psychiatric symptoms after delivery, or paternal psychiatric symptoms during pregnancy and after delivery were taken into account. CONCLUSIONS AND CLINICAL RELEVANCE: Maternal psychiatric symptoms during pregnancy were associated with increased risks of childhood inhalant allergy and eczema, independent of maternal psychiatric symptoms after delivery and of paternal psychiatric symptoms.

Duration and exclusiveness of breastfeeding and risk of childhood atopic diseases.

BACKGROUND: Breastfeeding may have immune modulatory effects that influence the development of childhood allergic sensitization and atopic diseases. We aimed to examine the associations of breastfeeding with childhood allergic sensitization, inhalant or food allergy and eczema, and whether any association was affected by disease-related modification of the exposure or modified by maternal history of allergy, eczema, or asthma. METHODS: This study among 5828 children was performed in a population-based prospective cohort from fetal life onwards. We collected information on duration (<2 months, 2-4 months, 4-6 months, and ≥6 months) and exclusiveness (nonexclusive vs exclusive for 4 months) of breastfeeding in infancy by postal questionnaires. At age 10 years, inhalant allergic sensitization and food-allergic sensitization were measured by skin prick tests, and physician-diagnosed inhalant and food allergy by a postal questionnaire. Data on parental-reported eczema were available from birth until age 10 years. RESULTS: We observed no association of breastfeeding with any allergic sensitization, physician-diagnosed allergy, or combination of these outcomes. Shorter breastfeeding duration was associated with an overall increased risk of eczema (P-value for trend <.05). Nonexclusively breastfed children had an overall increased risk of eczema (adjusted odds ratio [95% confidence interval]: 1.11 [1.01, 1.23]), compared with children exclusively breastfed for 4 months. Risk period-specific sensitivity analyses, additional adjustment for ointment use for eczema at age 2 months, and cross-lagged modeling showed no consistent results for disease-related modification of the exposure. Results were not modified by maternal history of allergy, eczema, or asthma (lowest P-value for interaction=.13). CONCLUSION: Shorter duration or nonexclusiveness of breastfeeding is associated with a weak overall increased risk of eczema but not allergic sensitization or physician-diagnosed allergy at age 10 years.

The independent role of prenatal and postnatal exposure to active and passive smoking on the development of early wheeze in children.

Maternal smoking during pregnancy increases childhood asthma risk, but health effects in children of nonsmoking mothers passively exposed to tobacco smoke during pregnancy are unclear. We examined the association of maternal passive smoking during pregnancy and wheeze in children aged ≤2 years.Individual data of 27 993 mother-child pairs from 15 European birth cohorts were combined in pooled analyses taking into consideration potential confounders.Children with maternal exposure to passive smoking during pregnancy and no other smoking exposure were more likely to develop wheeze up to the age of 2 years (OR 1.11, 95% CI 1.03-1.20) compared with unexposed children. Risk of wheeze was further increased by children's postnatal passive smoke exposure in addition to their mothers' passive exposure during pregnancy (OR 1.29, 95% CI 1.19-1.40) and highest in children with both sources of passive exposure and mothers who smoked actively during pregnancy (OR 1.73, 95% CI 1.59-1.88). Risk of wheeze associated with tobacco smoke exposure was higher in children with an allergic versus nonallergic family history.Maternal passive smoking exposure during pregnancy is an independent risk factor for wheeze in children up to the age of 2 years. Pregnant females should avoid active and passive exposure to tobacco smoke for the benefit of their children's health.

Overweight patterns throughout childhood and cardiometabolic markers in early adolescence.

BACKGROUND: Risk of cardiovascular and metabolic disease is higher in adults who were relatively thin at birth and had subsequent accelerated weight gain. This specific pattern of weight gain may relate to unfavorable cardiometabolic markers already in childhood. We prospectively assessed whether children with different patterns of overweight development from age 3 months to 11 years had distinct levels of cardiometabolic markers at age 12 years. SUBJECTS/METHODS: We used data of 1500 children participating in the PIAMA birth cohort that started in 1996/1997. Parents reported height and weight during 10 waves of follow-up from age 3 months to 11 years. Four distinct overweight development patterns were derived using longitudinal latent class analysis; 'never'; 'early transient'; 'gradually developing' and 'persistent' overweight. Cardiometabolic markers (total-to-high-density lipoprotein cholesterol (TC/HDLC) ratio, blood pressure (BP), glycated hemoglobin (HbA1c)) were assessed at age 12 years in 1500 children. RESULTS: Children who developed overweight gradually and children with persistent overweight throughout childhood, at age 12 years had a 2-3-fold higher risk of having high (>90th centile) TC/HDLC ratio, systolic and diastolic BP, compared with children who were never overweight. In children who gradually developed overweight, TC/HDLC ratio was 0.75 higher (95% confidence interval (CI) 0.54-0.96); systolic BP 4.90 mmHg higher (95% CI 2.45-7.36) and diastolic BP 1.78 mmHg higher (95% CI 0.07-3.49) than in children who never had overweight. Estimates for children with persistent overweight were similar. CONCLUSIONS: Children with gradually developing overweight, and those with persistent overweight had unfavorable cholesterol and blood pressure levels already at age 12 years, whereas children with early transient overweight avoided these unfavorable outcomes. Our results support the hypothesis that specific overweight patterns predispose to an adverse cardiometabolic profile, which is already apparent in early adolescence before progressing to adult cardiometabolic disease.

Genetic variation in uncontrolled childhood asthma despite ICS treatment.

Genetic variation may partly explain asthma treatment response heterogeneity. We aimed to identify common and rare genetic variants associated with asthma that was not well controlled despite inhaled corticosteroid (ICS) treatment. Data of 110 children was collected in the Children Asthma Therapy Optimal trial. Associations of genetic variation with measures of lung function (FEV1%pred), airway hyperresponsiveness (AHR) to methacholine (Mch PD20) and treatment response outcomes were analyzed using the exome chip. The 17q12-21 locus (containing ORMDL3 and GSMDB) previously associated with childhood asthma was investigated separately. Single-nucleotide polymorphisms (SNPs) in the 17q12-21 locus were found nominally associated with the outcomes. The strongest association in this region was found for rs72821893 in KRT25 with FEV1%pred (P=3.75*10(-5)), Mch PD20 (P=0.00095) and Mch PD20-based treatment outcome (P=0.006). No novel single SNPs or burden tests were significantly associated with the outcomes. The 17q12-21 region was associated with FEV1%pred and AHR, and additionally with ICS treatment response.

Maternal fatty acid levels during pregnancy, childhood lung function and atopic diseases. The Generation R Study.

BACKGROUND: Maternal fatty acid status during pregnancy might influence foetal immunological development and subsequently the risk of childhood atopic diseases. OBJECTIVE: To examine the associations of maternal fatty acid levels during pregnancy with airway resistance and inflammation, asthma and eczema, in school-age children. METHODS: This study among 4976 subjects was embedded in a population-based prospective cohort study. We measured maternal plasma glycerophospholipid fatty acid levels by gas chromatography during the second trimester of pregnancy (mean gestational age: 20.7 (± 1.1) weeks). At the age of 6 years, airway resistance and inflammation were measured by interrupter technique (Rint) and fractional exhaled nitric oxide (FeNO), and current physician-diagnosed asthma and eczema were assessed by ISAAC-based questionnaires. Multiple linear and logistic regression models were adjusted for socio-demographic, lifestyle and anthropometric factors. RESULTS: We did not observe consistent associations of maternal total polyunsaturated fatty acid (PUFA), total n-6 PUFA, total n-3 PUFA levels and n-6/n-3 PUFA ratio during pregnancy with child's Rint and FeNO. Higher maternal total PUFA and total n-6 PUFA levels were associated with a decreased risk of childhood asthma (odds ratios (95% confidence interval): 0.76 (0.60, 0.97) and 0.71 (0.52, 0.96) per standard deviation score (SDS) increase of total PUFA and total n-6 PUFA levels, respectively) and with an increased risk of childhood eczema (1.16 (1.05, 1.28) and 1.21 (1.07, 1.37)). The observed associations were partly explained by Linoleic acid (LA, C18:2n-6) levels. Maternal total n-3 PUFA levels and n-6/n-3 PUFA ratio were not associated with current asthma and eczema. The observed associations were not explained by child's PUFA intake. CONCLUSIONS AND CLINICAL RELEVANCE: Higher maternal total PUFA and total n-6 PUFA levels during pregnancy seem to influence the risk of atopic diseases in childhood. The underlying mechanisms need to be further explored.

Associations of maternal and fetal 25-hydroxyvitamin D levels with childhood lung function and asthma: the Generation R Study.

BACKGROUND: Exposure to low levels of vitamin D in fetal life might be a risk factor for childhood asthma. OBJECTIVE: We examined whether 25-hydroxyvitamin D levels in mid-gestation and at birth were associated with higher airway resistance and inflammation, and increased risks of wheezing and asthma in school-age children. METHODS: We performed a population-based prospective cohort study among 3130 mothers and their children. Maternal blood samples in mid-gestation and umbilical cord blood samples at birth were used to determine 25-hydroxyvitamin D levels. At age of 6, airway resistance (Rint) was measured by interrupter technique and airway inflammation by fractional exhaled nitric oxide (FENO) using NIOX chemiluminescence analyser. Wheezing and asthma were prospectively assessed by annual questionnaires until age 6. RESULTS: Maternal levels of 25-hydroxyvitamin D in mid-gestation were not associated with Rint, FeNO, wheezing patterns, or asthma. Children in the lowest tertile of 25-hydroxyvitamin D levels at birth had a higher Rint (Z-score (95% confidence interval [95% CI]): -0.42 (-0.84, -0.01), P-value for trend< 0.05), compared to those in the highest tertile group. The effect estimate attenuated when child's current 25-hydroxyvitamin D level was taken into account [Z-score (95% CI): -0.55 (-1.08, 0.01)]. CONCLUSION AND CLINICAL RELEVANCE: Low levels of 25-hydroxyvitamin D at birth were associated with a higher airway resistance in childhood. Additional adjustment for child's current 25-hydroxyvitamin D level reduced the effect size of the association. Further studies are needed to replicate these findings and to examine mechanisms underlying the observed association and the long-term consequences.

The analysis of volatile organic compounds in exhaled breath and biomarkers in exhaled breath condensate in children - clinical tools or scientific toys?

Current monitoring strategies for respiratory diseases are mainly based on clinical features, lung function and imaging. As airway inflammation is the hallmark of many respiratory diseases in childhood, noninvasive methods to assess the presence and severity of airway inflammation might be helpful in both diagnosing and monitoring paediatric respiratory diseases. At present, the measurement of fractional exhaled nitric oxide is the only noninvasive method available to assess eosinophilic airway inflammation in clinical practice. We aimed to evaluate whether the analysis of volatile organic compounds (VOCs) in exhaled breath (EB) and biomarkers in exhaled breath condensate (EBC) is helpful in diagnosing and monitoring respiratory diseases in children. An extensive literature search was conducted in Medline, Embase and PubMed on the analysis and applications of VOCs in EB and EBC in children. We retrieved 1165 papers, of which nine contained original data on VOCs in EB and 84 on biomarkers in EBC. These were included in this review. We give an overview of the clinical applications in childhood and summarize the methodological issues. Several VOCs in EB and biomarkers in EBC have the potential to distinguish patients from healthy controls and to monitor treatment responses. Lack of standardization of collection methods and analysis techniques hampers the introduction in clinical practice. The measurement of metabolomic profiles may have important advantages over detecting single markers. There is a lack of longitudinal studies and external validation to reveal whether EB and EBC analysis have added value in the diagnostic process and follow-up of children with respiratory diseases. In conclusion, the use of VOCs in EB and biomarkers in EBC as markers of inflammatory airway diseases in children is still a research tool and not validated for clinical use.

A common variant in RAB27A gene is associated with fractional exhaled nitric oxide levels in adults.

BACKGROUND: Exhaled nitric oxide (FeNO) is a biomarker for eosinophilic inflammation in the airways and for responsiveness to corticosteroids in asthmatics. OBJECTIVE: We sought to identify in adults the genetic determinants of fractional exhaled nitric oxide (FeNO) levels and to assess whether environmental and disease-related factors influence these associations. METHODS: We performed a genome-wide association study of FeNO through meta-analysis of two independent discovery samples of European ancestry: the outbred EGEA study (French Epidemiological study on the Genetics and Environment of Asthma, N = 610 adults) and the Hutterites (N = 601 adults), a founder population living on communal farms. Replication of main findings was assessed in adults from an isolated village in Sardinia (Talana study, N = 450). We then investigated the influence of asthma, atopy and tobacco smoke exposure on these genetic associations, and whether they were also associated with FeNO values in children of the EAGLE (EArly Genetics & Lifecourse Epidemiology, N = 8858) consortium. RESULTS: We detected a common variant in RAB27A (rs2444043) associated with FeNO that reached the genome-wide significant level (P = 1.6 × 10(-7) ) in the combined discovery and replication adult data sets. This SNP belongs to member of RAS oncogene family (RAB27A) and was associated with an expression quantitative trait locus for RAB27A in lymphoblastoid cell lines from asthmatics. A second suggestive locus (rs2194437, P = 8.9 × 10(-7) ) located nearby the sodium/calcium exchanger 1 (SLC8A1) was mainly detected in atopic subjects and influenced by inhaled corticosteroid use. These two loci were not associated with childhood FeNO values. CONCLUSIONS AND CLINICAL RELEVANCE: This study identified a common variant located in RAB27A gene influencing FeNO levels specifically in adults and with a biological relevance to the regulation of FeNO levels. This study provides new insight into the biological mechanisms underlying FeNO levels in adults.

Breast milk fatty acid composition has a long-term effect on the risk of asthma, eczema, and sensitization.

BACKGROUND: Levels of n-3 polyunsaturated fatty acids (PUFAs) and n-6 PUFAs in breast milk are associated with the development of allergic diseases up to school age. However, it is unknown whether this relationship persists when the child becomes older. We therefore studied the association between levels of n-3 PUFAs and n-6 PUFAs in breast milk of allergic- and nonallergic mothers and asthma, eczema and sensitization up to the age of 14 years. METHODS: The study was nested in the ongoing PIAMA birth cohort. At the child's age of 3 months, 276 mothers provided a breast milk sample. Asthma (N total = 269) and eczema (N total = 274) were self-reported up to the child's age of 14 years. Specific serum IgE levels were measured at the ages of 4, 8 and 12 years (N total = 216). Generalized estimating equations analyses were used to take account of repeated observations. RESULTS: Asthma up to the age of 14 years is less prevalent in children of allergic mothers receiving breast milk with higher levels of n-3 long chain polyunsaturated (LCP) fatty acids (OR 0.50; 95% CI 0.31-0.79), and more prevalent in children of nonallergic mothers receiving breast milk with higher levels of n-6LCP (OR 1.86; 95% CI 1.14-3.03). Weaker associations in similar direction were observed for eczema and sensitization. Direction of associations were consistent and of similar magnitude throughout childhood. CONCLUSION: The association between breast milk fatty acid composition and asthma, eczema and sensitization persists up to the age of 14 years in children of both allergic and nonallergic mothers.

Multicomponent gas analysis using broadband quantum cascade laser spectroscopy.

We present a broadband quantum cascade laser-based spectroscopic system covering the region between 850 and 1250 cm(-1). Its robust multipass cavity ensures a constant interaction length over the entire spectral region. The device enables the detection and identification of numerous molecules present in a complex gas mixture without any pre-treatment in two minutes. We demonstrate that we can detect sub-ppmv concentration of acetone in presence of 2% of water at the same wavenumber region.

Exercise capacity, daily activity, and severity of fatigue in term born young adults after neonatal respiratory failure.

Little is known about long-term effects of neonatal intensive care on exercise capacity, physical activity, and fatigue in term borns. We determined these outcomes in 57 young adults, treated for neonatal respiratory failure; 27 of them had congenital diaphragmatic hernia with lung hypoplasia (group 1) and 30 had normal lung development (group 2). Patients in group 2 were age-matched, with similar gestational age and birth weight, and similar neonatal intensive care treatment as patients in group 1. All patients were born before the era of extracorporeal membrane oxygenation, nitric oxide administration, and high frequency ventilation. Exercise capacity was measured by cycle ergometry, daily physical activity with an accelerometry-based activity monitor, and fatigue by the fatigue severity scale. Median (range) VO2peak in mL/kg/min was 35.4 (19.6-55.0) in group 1 and 37.6 (15.7-52.7) in group 2. There was a between-group P-value of 0.65 for exercise capacity. Daily activity and fatigue were also similar in both groups. So, residual lung hypoplasia did not play an important role in this cohort. There were no significant associations between exercise capacity and perinatal characteristics. Future studies need to elucidate whether exercise capacity is impaired in patients with more severe lung hypoplasia who nowadays survive.

Perinatal risk factors for wheezing phenotypes in the first 8 years of life.

BACKGROUND: A novel data-driven approach was used to identify wheezing phenotypes in pre-schoolchildren aged 0-8 years, in the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort. Five phenotypes were identified: never/infrequent wheeze, transient early wheeze, intermediate onset wheeze, persistent wheeze and late onset wheeze. It is unknown which perinatal risk factors drive development of these phenotypes. OBJECTIVE: The objective of the study was to assess associations of perinatal factors with wheezing phenotypes and to identify possible targets for prevention. METHODS: In the PIAMA study (n = 3963), perinatal factors were collected at 3 months, and wheezing was assessed annually until the age of 8 years. Associations between perinatal risk factors and the five wheezing phenotypes were assessed using weighted multinomial logistic regression models. Odds ratios were adjusted for confounding variables and calculated with 'never/infrequent wheeze' as reference category. RESULTS: Complete data were available for 2728 children. Risk factors for transient early wheeze (n = 455) were male gender, maternal and paternal allergy, low maternal age, high maternal body mass index, short pregnancy duration, smoking during pregnancy, presence of older siblings and day-care attendance. Risk factors for persistent wheeze (n = 83) were male gender, maternal and paternal allergy, and not receiving breastfeeding for at least 12 weeks. Intermediate onset wheeze (n = 98) was associated with a lower birth weight and late onset wheeze (n = 45) with maternal allergy. CONCLUSION AND CLINICAL RELEVANCE: We identified different risk factors for specific childhood wheezing phenotypes. Some of these are modifiable, such as maternal age and body mass index, smoking, day-care attendance and breastfeeding, and may be important targets for prevention programmes.

Neonatal folate, homocysteine, vitamin B12 levels and methylenetetrahydrofolate reductase variants in childhood asthma and eczema.

OBJECTIVES: To assess the associations of folate, homocysteine and vitamin B12 levels of children at birth and their methylenetetrahydrofolate reductase (MTHFR) variants with asthma and eczema in childhood. METHODS: This study was embedded in a population-based prospective cohort study (n = 2,001). Neonatal cord blood folate, homocysteine and vitamin B12 levels were measured, and MTHFR C677T and A1298C genotyped. Wheezing and physician-diagnosed eczema were annually obtained by questionnaire until 4 years. At 6 years, we collected information on physician-diagnosed asthma ever and self-reported eczema ever, measured fractional exhaled nitric oxide (FeNO), and interrupter resistance (Rint). Data were analysed with generalized estimating equations or logistic regression: continuous outcomes with linear regression models. RESULTS: Folate, homocysteine and vitamin B12 levels of children at birth were not associated with wheezing or eczema until 4 years, asthma and eczema ever, or FeNO or Rint at 6 years. In children carrying C677T mutations in MTHFR, higher folate levels were associated with an increased risk of eczema (repeated eczema until 4 years: OR 1.40 (95% CI 1.09-1.80) (SD change) P-interaction = 0.003, eczema ever at 6 years: OR 1.41 (0.97-2.03) P-interaction = 0.011). No interactions between MTHFR and child folate and homocysteine levels were observed for wheezing and asthma. CONCLUSIONS: Folate, homocysteine and vitamin B12 levels of children at birth did not affect asthma- and eczema-related outcomes up to the age of 6 years. Further studies are warranted to establish the role of MTHFR variants in these associations.

Exhaled nitric oxide and the risk of wheezing in infancy: the Generation R Study.

We assessed whether exhaled nitric oxide fraction (F(eNO)), a marker of eosinophilic airway inflammation, at 6 months was associated with the risk of wheezing during the first 2 yrs of life. In the Generation R birth cohort, pre- and post-natal risk factors for respiratory morbidity and respiratory symptoms were assessed by questionnaires at 6 and 24 months. In 428 infants, off-line mixed oral/nasal F(eNO) was successfully measured during tidal breathing at 6 months. Complete data on F(eNO) and respiratory symptoms within the first 6 months of life were available for 294 infants. F(eNO) was higher in males, was positively associated with age and was negatively associated with upper and lower respiratory symptoms within the first 6 months. Logistic regression analysis showed that for every ppb increase of F(eNO) measured at 6 months, infants had a 1.06 (95% confidence interval 1.01-1.11)-fold increased risk of wheezing in the second year of life. High F(eNO) (>17.5 ppb) showed a limited added value in predicting wheezing in the second year. We conclude that F(eNO) at 6 months is positively associated with the risk of wheezing, but has limited added value in predicting wheezing in the second year of life in individual children.