Cord-blood respiratory syncytial virus antibodies and respiratory health in first 5 years of life.

OBJECTIVE: To determine the potential longer-term effects of maternal antenatal respiratory syncytial virus (RSV) vaccination, we examined the association between cord-blood RSV-neutralizing antibodies (RSV-NA) and RSV infections in the first 2 years of life, RSV-NA at 3 years, and respiratory health to age 5 years. METHODS: Two community-based Australian birth cohorts were combined. For children with at least one atopic parent, paired serum RSV-NA levels were compared in cord blood and at age 3 years. Weekly nasal swabs were collected in one cohort and during acute respiratory infections (ARI) in the other. Wheeze history up to age 5 years and physician-diagnosed asthma at 5 years was collected by parent report. RESULTS: In 264 children, each log10 increase of cord-blood RSV-NA level was associated with 37% decreased risk (adjusted incidence-rate-ratio [aIRR] 0.63; 95% confidence interval [CI]: 0.40-1.01) of RSV-ARI and 49% decreased risk (aIRR 0.51; 95% CI: 0.25-1.02) of RSV acute lower respiratory infections (ALRI) at 12-24 months of age. However, higher cord-blood RSV-NA was associated with increased risk of all-cause ALRI (aIRR 1.29; 95% CI: 0.99-1.69), wheeze-associated ALRI (aIRR 1.75; 95% CI: 1.08-2.82), and severe ALRI (aIRR 2.76; 95% CI: 1.63-4.70) at age 6-<12 months. Cord-blood RSV-NA was not associated with RSV-ARI in the first 6-months, RSV-NA levels at 3 years, or wheeze or asthma at 5 years. CONCLUSIONS: Higher levels of cord-blood RSV-NA did not protect against RSV infections during the first 6-months-of-life, time-to-first RSV-ARI, or wheeze or asthma in the first 5 years of life. Additional strategies to control RSV-related illness in childhood are needed.

Progressive increase of FcεRI expression across several PBMC subsets is associated with atopy and atopic asthma within school-aged children.

BACKGROUND: Antigen-specific IgE binds the Fcε receptor I (FcεRI) expressed on several types of immune cells, including dendritic cells (DCs). Activation of FcεRI on DCs in atopics has been shown to modulate immune responses that potentially contribute to asthma development. However, the extent to which DC subsets differ in FcεRI expression between atopic children with or without asthma is currently not clear. This study aimed to analyse the expression of FcεRI on peripheral blood mononuclear cells (PBMCs) from atopic children with and without asthma, and non-atopic/non-asthmatic age-matched healthy controls. METHODS: We performed multiparameter flow cytometry on PBMC from 391 children across three community cohorts and one clinical cohort based in Western Australia. RESULTS: We confirmed expression of FcεRI on basophils, monocytes, plasmacytoid and conventional DCs, with higher proportions of all cell populations expressing FcεRI in atopic compared to non-atopic children. Further, we observed that levels of FcεRI expression were elevated across plasmacytoid and conventional DC as well as basophils in atopic asthmatic compared to atopic non-asthmatic children also after adjusting for serum IgE levels. CONCLUSION: Our data suggest that the expression pattern of FcεRI on DC and basophils differentiates asthmatic from non-asthmatic atopic children. Given the significant immune modulatory effects observed as a consequence of FcεRI expression, this altered expression pattern is likely to contribute to asthma pathology in children.

Developmental regulation of type 1 and type 3 interferon production and risk for infant infections and asthma development.

BACKGROUND: Virus-associated febrile lower respiratory tract infections (fLRIs) during infancy have been identified as risk factors for persistent wheeze development. We hypothesized that variations in innate immune defense capacity during this period, as exemplified by production of type 1 and 3 interferons (T1/3IFNs), might be an underlying determinant of risk. OBJECTIVE: We sought to investigate relationships between postnatal development of innate interferon response capacity and susceptibility to early infections and persistent wheeze. METHODS: We studied a subset of subjects from a birth cohort at high risk for asthma/allergy and determined the capacity of cord blood cells (n = 151) to produce any of a panel of 17 T1/3IFNs in response to the viral mimic polyinosinic-polycytidylic acid using a sensitive PCR assay. We investigated relationships between neonatal interferon responses and lower respiratory tract infection history during infancy, wheezing history to 5 age years, and ensuing maturation of innate immune capacity by age 4 years (n = 160) and 10 years (n = 125). RESULTS: Although cohort subjects produced an average of 2.6 ± 0.3 of the 17 innate interferons tested at birth, 24% showed no T1/3IFN production. This nonproducer subgroup showed increased risk for infant fLRIs (odds ratio, 2.62; 95% CI, 1.14-6.06; P = .024) and persistent wheeze (odds ratio, 4.24; 95% CI, 1.60-11.24; P = .004) at age 5 years relative to those producing 1 or more T1/3IFNs, whereas risk for infant wheezy lower respiratory tract infections or "transient early wheeze" was unaffected. Moreover, infants who experienced fLRIs subsequently demonstrated accelerated development of T1/3IFN response capacity between 1 and 4 years of age. CONCLUSIONS: T1/3IFN response capacity appears strongly developmentally constrained at birth. Infants in whom this negative regulation is strongest manifest increased risk for severe respiratory tract infections during infancy and subsequent persistent wheeze.

Trajectories of childhood immune development and respiratory health relevant to asthma and allergy.

Events in early life contribute to subsequent risk of asthma; however, the causes and trajectories of childhood wheeze are heterogeneous and do not always result in asthma. Similarly, not all atopic individuals develop wheeze, and vice versa. The reasons for these differences are unclear. Using unsupervised model-based cluster analysis, we identified latent clusters within a prospective birth cohort with deep immunological and respiratory phenotyping. We characterised each cluster in terms of immunological profile and disease risk, and replicated our results in external cohorts from the UK and USA. We discovered three distinct trajectories, one of which is a high-risk 'atopic' cluster with increased propensity for allergic diseases throughout childhood. Atopy contributes varyingly to later wheeze depending on cluster membership. Our findings demonstrate the utility of unsupervised analysis in elucidating heterogeneity in asthma pathogenesis and provide a foundation for improving management and prevention of childhood asthma.

Airway Microbiota Dynamics Uncover a Critical Window for Interplay of Pathogenic Bacteria and Allergy in Childhood Respiratory Disease.

Repeated cycles of infection-associated lower airway inflammation drive the pathogenesis of persistent wheezing disease in children. In this study, the occurrence of acute respiratory tract illnesses (ARIs) and the nasopharyngeal microbiome (NPM) were characterized in 244 infants through their first five years of life. Through this analysis, we demonstrate that >80% of infectious events involve viral pathogens, but are accompanied by a shift in the NPM toward dominance by a small range of pathogenic bacterial genera. Unexpectedly, this change frequently precedes the detection of viral pathogens and acute symptoms. Colonization of illness-associated bacteria coupled with early allergic sensitization is associated with persistent wheeze in school-aged children, which is the hallmark of the asthma phenotype. In contrast, these bacterial genera are associated with "transient wheeze" that resolves after age 3 years in non-sensitized children. Thus, to complement early allergic sensitization, monitoring NPM composition may enable early detection and intervention in high-risk children.

Vitamin D over the first decade and susceptibility to childhood allergy and asthma.

BACKGROUND: Vitamin D (25(OH)D) deficiency has been implicated as a possible risk factor for asthma development, but studies at selected time points measuring 25(OH)D levels during childhood have yielded conflicting findings. Prospective studies tracking 25(OH)D levels during the initiation phase of asthma in early childhood have not been reported. OBJECTIVE: We sought to elucidate relationships between 25(OH)D levels from birth to age 10 years and susceptibility to allergic sensitization, respiratory tract infections, and asthma. METHODS: Asthma-, allergy-, and respiratory tract infection-associated phenotypes (including pathogen identification) were characterized in a high-risk birth cohort. Plasma 25(OH)D concentrations were quantified at birth and at clinical follow-ups at the ages of 0.5, 1, 2, 3, 4, 5, and 10 years, and relationships with clinical outcomes were examined. RESULTS: Cross-sectional analyses demonstrated inverse associations between 25(OH)D concentrations and the risk for concurrent sensitization at age 0.5, 2, and 3 years, and mixed-effects regression demonstrated inverse longitudinal associations of 25(OH)D levels with both sensitization and eczema. Multivariate regression modeling suggested that the number of 25(OH)D-deficient follow-ups was positively associated with risk for asthma/wheeze, eczema, and sensitization at 10 years; adjustment for sensitization (particularly by 2 years) in the asthma/wheeze models reduced 25(OH)D associations with these latter outcomes. 25(OH)D levels were also inversely associated with early nasopharyngeal colonization with Streptococcus species and age of first febrile lower respiratory illness, both of which are known asthma risk factors. CONCLUSION: 25(OH)D deficiency in early childhood is associated with increased risk for persistent asthma, potentially through modulating susceptibility to early allergic sensitization, upper respiratory tract colonization with bacterial pathogens, or both. These relationships are only evident if 25(OH)D status is monitored prospectively and longitudinally.

Distinguishing benign from pathologic TH2 immunity in atopic children.

BACKGROUND: Although most children with asthma and rhinitis are sensitized to aeroallergens, only a minority of sensitized children are symptomatic, implying the underlying operation of efficient anti-inflammatory control mechanisms. OBJECTIVE: We sought to identify endogenous control mechanisms that attenuate expression of IgE-associated responsiveness to aeroallergens in sensitized children. METHODS: In 3 independent population samples we analyzed relationships between aeroallergen-specific IgE and corresponding allergen-specific IgG (sIgG) and associated immunophenotypes in atopic children and susceptibility to asthma and rhinitis, focusing on responses to house dust mite and grass. RESULTS: Among mite-sensitized children across all populations and at different ages, house dust mite-specific IgG/IgE ratios (but not IgG4/IgE ratios) were significantly lower in children with asthma compared with ratios in those without asthma and lowest among the most severely symptomatic. This finding was mirrored by relationships between rhinitis and antibody responses to grass. Depending on age/allergen specificity, 20% to 40% of children with allergen-specific IgE (sIgE) of 0.35 kU/L or greater had negative skin test responses, and these children also expressed the high sIgG/sIgE immunophenotype. sIgG1 from these children inhibited allergen-induced IgE-dependent basophil activation in a dose-dependent fashion. Profiling of aeroallergen-specific CD4(+) TH memory responses revealed positive associations between sIgG/sIgE ratios and IL-10-dependent gene signatures and significantly higher IL-10/TH2 cytokine (protein) ratios among nonsymptomatic children. CONCLUSION: In addition to its role in blocking TH2 effector activation in the late-phase allergic response, IL-10 is a known IgG1 switch factor. We posit that its production during allergen-induced memory responses contributes significantly to attenuation of inflammation through promoting IgG1-mediated damping of the FcεRI-dependent acute-phase reaction. sIgG1/sIgE balance might represent a readily accessible therapeutic target for asthma/rhinitis control.

The infant nasopharyngeal microbiome impacts severity of lower respiratory infection and risk of asthma development.

The nasopharynx (NP) is a reservoir for microbes associated with acute respiratory infections (ARIs). Lung inflammation resulting from ARIs during infancy is linked to asthma development. We examined the NP microbiome during the critical first year of life in a prospective cohort of 234 children, capturing both the viral and bacterial communities and documenting all incidents of ARIs. Most infants were initially colonized with Staphylococcus or Corynebacterium before stable colonization with Alloiococcus or Moraxella. Transient incursions of Streptococcus, Moraxella, or Haemophilus marked virus-associated ARIs. Our data identify the NP microbiome as a determinant for infection spread to the lower airways, severity of accompanying inflammatory symptoms, and risk for future asthma development. Early asymptomatic colonization with Streptococcus was a strong asthma predictor, and antibiotic usage disrupted asymptomatic colonization patterns. In the absence of effective anti-viral therapies, targeting pathogenic bacteria within the NP microbiome could represent a prophylactic approach to asthma.

Vitamin D in fetal development: findings from a birth cohort study.

Birth cohort studies provide an invaluable resource for studies of the influence of the fetal environment on health in later life. It is uncertain to what extent maternal vitamin D status influences fetal development. Using an unselected community-based cohort of 901 mother-offspring pairs (the Western Australian Pregnancy Cohort [Raine] Study), we examined the relationship between maternal vitamin D deficiency at 18 weeks' pregnancy and long-term health outcomes of offspring who were born in Perth, Western Australia (32° South), in 1989-1991. Vitamin D deficiency (serum 25-hydroxyvitamin D [25(OH)D] <50 nmol/L) was present in 36% (323 of 901) of the pregnant women. After adjusting for relevant covariates, maternal vitamin D deficiency during pregnancy was associated with impaired lung development in 6-year-old offspring, neurocognitive difficulties at age 10, increased risk of eating disorders in adolescence, and lower peak bone mass at 20 years. In summary, vitamin D may have an important, multifaceted role in the development of fetal lungs, brain, and bone. Experimental animal studies support an active contribution of vitamin D to organ development. Randomized controlled trials of vitamin D supplementation in pregnant women with long-term follow-up of offspring are urgently required to examine whether the correction of vitamin D deficiency in pregnant women is beneficial for their offspring and to determine the optimal level of maternal serum 25(OH)D for fetal development.

Anti-infective proteins in breast milk and asthma-associated phenotypes during early childhood.

BACKGROUND: The impact of breast milk feeding on susceptibility to asthma in childhood is highly controversial, due in part to failure of the majority of studies in the area to adequately account for key confounders exemplified by respiratory infection history, plus the effects of recall bias. METHODS: As part of a prospective cohort study on the role of respiratory infections in asthma development in high-risk children, we measured the concentration of a panel of anti-infective proteins in maternal milk samples and analyzed associations between these and subsequent atopy-, infection-, and asthma-related outcomes prospectively to age 10 years. RESULTS: We observed significant but transient inverse associations between the concentration of milk proteins and susceptibility to upper respiratory infections in year 1 only, and parallel but positive transient associations with early lower respiratory infections and atopy. No associations were seen with asthma-related outcomes. CONCLUSIONS: Breast milk feeding may influence the expression of inflammatory symptoms associated with respiratory infections and atopy in early life, but these effects appear to be inconsistent and transient. The heterogeneous nature of breast-feeding effects suggests it may influence systemic immunoinflammatory function at several different levels.

Vitamin D deficiency at 16 to 20 weeks' gestation is associated with impaired lung function and asthma at 6 years of age.

RATIONALE: Vitamin D deficiency is associated with chronic lung disease. We have previously shown in an in vivo mouse model that maternal vitamin D deficiency is associated with alterations in early life lung structure and function. However, there are limited data to support a relationship between maternal vitamin D deficiency during the early stages of lung development and postnatal lung function in human populations. OBJECTIVES: To assess the association between maternal vitamin D deficiency, postnatal lung function, and asthmatic status in a longitudinal birth cohort. METHODS: Serum was collected at 16 to 20 weeks' gestation at the time of recruitment in a community-based prospective birth cohort for measurement of vitamin D (25[OH]D). Lung function was assessed by spirometry according to American Thoracic Society guidelines in children at 6 and 14 years of age. Demographic and clinical history data were collected by questionnaire at recruitment and at the follow-up visits. MEASUREMENTS AND MAIN RESULTS: FVC Z-scores in both sexes (ß, 0.007 [95% confidence interval (CI), 0.001-0.013]; P = 0.02) and FEV1 Z-scores in girls (ß, 0.007 [95% CI, 0.001-0.013]; P = 0.02) were positively associated with maternal serum 25(OH)D at 6 years of age. These associations were mostly absent at 14 years of age. Maternal vitamin D deficiency was positively associated with asthma at 6 years of age but only in boys (odds ratio, 3.03 [95% CI, 1.02-9.02]; P = 0.04). CONCLUSIONS: This study supports the notion that vitamin D deficiency during lung development may impact on postnatal lung growth and increase the risk of developing lung disease.

Low maternal serum vitamin D during pregnancy and the risk for postpartum depression symptoms.

Pregnancy is a time of vulnerability for vitamin D insufficiency, and there is an emerging literature associating low levels of 25(OH)-vitamin D with depressive symptoms. However, the link between 25(OH)-vitamin D status in pregnancy and altered risk of postnatal depressive symptoms has not been examined. We hypothesise that low levels of 25(OH)-vitamin D in maternal serum during pregnancy will be associated with a higher incidence of postpartum depressive symptoms. We prospectively collected sera at 18 weeks gestation from 796 pregnant women in Perth (1989-1992) who were enrolled in the Western Australian Pregnancy Cohort (Raine) Study and measured levels of 25(OH)-vitamin D. Women reported postnatal depressive symptoms at 3 days post-delivery. Women in the lowest quartile for 25(OH)-vitamin D status were more likely to report a higher level of postnatal depression symptoms than women who were in the highest quartile for vitamin D, even after accounting for a range of confounding variables including season of birth, body mass index and sociodemographic factors. Low vitamin D during pregnancy is a risk factor for the development of postpartum depression symptoms.

Maternal vitamin D status during pregnancy and bone mass in offspring at 20 years of age: a prospective cohort study.

It is uncertain whether the vitamin D status of pregnant women influences bone mass of their children. Cohort studies have yielded conflicting results; none have examined offspring at skeletal maturity. This longitudinal, prospective study investigated the association between maternal vitamin D status and peak bone mass of offspring in 341 mother and offspring pairs in the Western Australian Pregnancy Cohort (Raine) Study. Maternal serum samples collected at 18 weeks gestation were assayed for 25-hydroxyvitamin D (25OHD). Outcomes were total body bone mineral content (BMC) and bone mineral density (BMD) measured by dual-energy X-ray absorptiometry in offspring at 20 years of age. The mean (± SD) maternal serum 25OHD concentration was 57.2 ± 19.2 nmol/L; 132 women (38.7%) were vitamin D-deficient (25OHD <50 nmol/L). After adjustment for season of sample collection, maternal factors, and offspring factors (sex, birth weight, and age, height, lean mass, and fat mass at 20 years), maternal 25OHD concentration was positively associated with total body BMC and BMD in offspring, with a mean difference of 19.2 (95% confidence interval [CI], 5.6-32.7) g for BMC and 4.6 (95% CI, 0.1-9.1) mg/cm(2) for BMD per 10.0 nmol/L of maternal 25OHD. Maternal vitamin D deficiency was associated with 2.7% lower total body BMC (mean ± SE) (2846 ± 20 versus 2924 ± 16 g, p = 0.004) and 1.7% lower total body BMD (1053 ± 7 versus 1071 ± 5 mg/cm(2) , p = 0.043) in the offspring. We conclude that vitamin D deficiency in pregnant women is associated with lower peak bone mass in their children. This may increase fracture risk in the offspring in later life.

Maternal vitamin D levels during pregnancy and offspring eating disorder risk in adolescence.

OBJECTIVE: To determine if maternal vitamin D concentrations at 18 weeks gestation predict offspring eating disorder risk in adolescence. METHOD: Participants were 526 Caucasian mother-child dyads from the Western Australian Pregnancy Cohort (Raine) Study. The Raine Study has followed participants from 18 weeks gestation to 20 years of age. Maternal serum 25(OH)-vitamin D concentrations were measured at 18 weeks pregnancy and grouped into quartiles. Offspring eating disorder symptoms were assessed at ages 14, 17 and 20 years. Core analyses were limited to female offspring (n = 308). RESULTS: Maternal 25(OH)-vitamin D quartiles were a significant predictor of eating disorder risk in female offspring, in multivariate logistic regression models. Vitamin D in the lowest quartile was associated with a 1.8-fold increase in eating disorder risk relative to concentrations in the highest quartile. This association also accounted for the relationship between offspring season of birth and eating disorder risk. Results were significant after adjusting for sociodemographic characteristics, body mass index and depressive symptoms. DISCUSSION: This is the first study to link low gestational vitamin D to increased eating disorder risk in female offspring of Caucasian mothers. Research is needed to extend these findings and to consider how gestational vitamin D may relate to the pathogenesis of eating disorders.

Maternal vitamin D levels and the autism phenotype among offspring.

We tested whether maternal vitamin D insufficiency during pregnancy is related to the autism phenotype. Serum 25(OH)-vitamin D concentrations of 929 women were measured at 18 weeks' pregnancy. The mothers of the three children with a clinical diagnosis of autism spectrum disorder had 25(OH)-vitamin D concentrations above the population mean. The offspring of 406 women completed the Autism-Spectrum Quotient in early adulthood. Maternal 25(OH)-vitamin D concentrations were unrelated to offspring scores on the majority of scales. However, offspring of mothers with low 25(OH)-vitamin D concentrations (<49 nmol/L) were at increased risk for 'high' scores (≥2SD above mean) on the Attention Switching subscale (odds ratio: 5.46, 95% confidence interval: 1.29, 23.05). The involvement of maternal vitamin D during pregnancy in autism requires continued investigation.

Respiratory impedance and bronchodilator responsiveness in healthy children aged 2-13 years.

BACKGROUND: The forced oscillation technique (FOT) can be used in children as young as 2 years of age and in those unable to perform routine spirometry. There is limited information on changes in FOT outcomes in healthy children beyond the preschool years and the level of bronchodilator responsiveness (BDR) in healthy children. We aimed to create reference ranges for respiratory impedance outcomes collated from multiple centers. Outcomes included respiratory system resistance (R(rs)) and reactance (X(rs)), resonant frequency (Fres), frequency dependence of R(rs) (Fdep), and the area under the reactance curve (AX). We also aimed to define the physiological effects of bronchodilators in a large population of healthy children using the FOT. METHODS: Respiratory impedance was measured in 760 healthy children, aged 2-13 years, from Australia and Italy. Stepwise linear regression identified anthropometric predictors of transformed R(rs) and X(rs) at 6, 8, and 10 Hz, Fres, Fdep, and AX. Bronchodilator response (BDR) was assessed in 508 children after 200 µg of inhaled salbutamol. RESULTS: Regression analysis showed that R(rs), X(rs), and AX outcomes were dependent on height and sex. The BDR cut-offs by absolute change in R(rs8), X(rs8), and AX were -2.74 hPa s L(-1), 1.93 hPa s L(-1), and -33 hPa s L(-1), respectively. These corresponded to relative and Z-score changes of -32%; -1.85 for R(rs8), 65%; 1.95 for X(rs8), and -82%; -2.04 for AX. CONCLUSIONS: We have established generalizable reference ranges for respiratory impedance and defined cut-offs for a positive bronchodilator response using the FOT in healthy children.

Maternal serum vitamin D levels during pregnancy and offspring neurocognitive development.

OBJECTIVES: To determine the association between maternal serum 25(OH)-vitamin D concentrations during a critical window of fetal neurodevelopment and behavioral, emotional, and language outcomes of offspring. METHODS: Serum 25(OH)-vitamin D concentrations of 743 Caucasian women in Perth, Western Australia (32°S) were measured at 18 weeks pregnancy and grouped into quartiles. Offspring behavior was measured with the Child Behavior Checklist at 2, 5, 8, 10, 14, and 17 years of age (n range = 412-652). Receptive language was assessed with the Peabody Picture Vocabulary Test-Revised at ages 5 (n = 534) and 10 (n = 474) years. Raw scores were converted to standardized scores, incorporating cutoffs for clinically significant levels of difficulty. RESULTS: χ(2) analyses revealed no significant associations between maternal 25(OH)-vitamin D serum quartiles and offspring behavioral/emotional problems at any age. In contrast, there were significant linear trends between quartiles of maternal vitamin D levels and language impairment at 5 and 10 years of age. Multivariate regression analyses, incorporating a range of confounding variables, found that the risk of women with vitamin D insufficiency (≤46 nmol/L) during pregnancy having a child with clinically significant language difficulties was increased close to twofold compared with women with vitamin D levels >70 nmol/L. CONCLUSIONS: Maternal vitamin D insufficiency during pregnancy is significantly associated with offspring language impairment. Maternal vitamin D supplementation during pregnancy may reduce the risk of developmental language difficulties among their children.

Antibacterial antibody responses associated with the development of asthma in house dust mite-sensitised and non-sensitised children.

BACKGROUND: Infants who develop house dust mite (HDM) allergy and HDM-sensitised children with severe persistent asthma have low antibody responses to the P6 antigen of Haemophilus influenzae. OBJECTIVE: To measure the development of antibody to two ubiquitous bacteria of the respiratory mucosa in a prospective birth cohort at high risk of allergic disease and to assess which responses are associated with asthma and atopy. METHODS: IgG1 and IgG4 antibody to H influenzae (P4 and P6) and Streptoccocus pneumoniae (PspA and PspC) surface antigens was measured in yearly blood samples of children aged 1-5 years. IgE to the P6 antigen was examined for the 5-year group. The children were stratified based on HDM sensitisation and asthma at 5 years of age. RESULTS: HDM-sensitised children had lower IgG1 antibody titres to the bacterial antigens, and early responses (<3 years and before the development of HDM sensitisation and asthma) corrected for multiple antigens were significantly reduced for P4, P6 and PspC (p=0.008, p=0.004 and p=0.028, respectively). Similar associations with asthma were also found (p=0.008, p=0.004 and p=0.032 for P4, P6 and PspC, respectively). The IgG4 antibody titre and prevalence were similar in both HDM-sensitised and non-sensitised groups, but sensitised children had a slower downregulation of the IgG4 response. Children with asthma (27/145 at 5 years) had lower anti-P6 IgE responses (p<0.05). CONCLUSIONS: HDM-sensitised children have early defective antibody responses to bacteria that are associated with asthma. Surprisingly, antibacterial IgE was associated with a reduced risk for asthma.

Exhaled breath temperature in healthy children is influenced by room temperature and lung volume.

BACKGROUND: Exhaled breath temperature (EBT) has been proposed for the non-invasive assessment of airway inflammation. Previous studies have not examined the influence of room temperature or lung size on the EBT. OBJECTIVE: This study aimed to address these issues in healthy children. METHODS: We assessed the effects of room temperature and lung volume in 60 healthy children aged 9-11 years (mean age 10.3 years, 33 male). Static lung volumes were assessed using multiple breath nitrogen washout. Questionnaire and skin prick tests were also used to establish respiratory health in the children. We obtained the EBT parameters of slope, end plateau temperature (PLET) and normalized plateau temperature (nPLET; plateau temperature minus inspired air temperature), and ascertained physiological factors influencing EBT. RESULTS: End plateau temperature was shown to be proportionally affected by room temperature (r = 0.532, P < 0.001) whereas slope and nPLET decreased with increasing room temperature (r = -0.392 P < 0.02 and r = -0.507 P = 0.002). After adjusting for room temperature, height and age, the total lung capacity (r(2) = 0.435, P = 0.006) and slow vital capacity (SVC; r(2) = 0.44, P = 0.005) were found to be the strongest predictors of end PLET in healthy children. When all factors were included in a multiple regression model, SVC and room temperature were the only predictors of plateau and nPLET. Slope was only influenced by room temperature. CONCLUSIONS: Exhaled breath temperature measurements are highly feasible in children with a 95% success rate in this healthy population. Room temperature and SVC significantly influence EBT variables in healthy children. Further studies are required to investigate the ability of EBT to assess airway inflammation in children with respiratory disease. Pediatr. Pulmonol. 2011; 46:1062-1068. © 2011 Wiley Periodicals, Inc.

Do early-life viral infections cause asthma?

Epidemiologic associations between viral lower respiratory infections (LRIs) and asthma in later childhood are well known. However, the question of whether such infections cause asthma or unmask asthma in a susceptible host has still not been settled. Most early evidence centered on the role of the respiratory syncytial virus; however, recent studies highlight a potential role for human rhinovirus as a risk factor for asthma. The links between early-life viral LRI and subsequent asthma are generally via wheeze; however, the presence of wheeze does not give any information about why the child is wheezing. Wheeze in early life is, at best, a fuzzy phenotype and not specific for subsequent asthma. The risk of asthma after viral LRI is increased in the presence of allergic sensitization in early life and if the infection is more severe. Atopy-associated mechanisms also appear to be involved in viral-induced acute exacerbations of asthma, especially in prolonging symptomatology after the virus has been cleared from the lungs. Breaking the nexus between viral respiratory infections and asthma may be possible with interventions designed to inhibit atopy-related effectors mechanisms from participating in the host response to respiratory viral infections.