Alveolar macrophages and CC chemokines are increased in children with cystic fibrosis.

Airway inflammation is an important component of cystic fibrosis (CF) lung disease. We sought to determine whether alveolar macrophages were involved in early CF lung disease. Children with CF (median age 3.

Lung disease at diagnosis in infants with cystic fibrosis detected by newborn screening.

Rationale: The promise of newborn screening (NBS) for cystic fibrosis (CF) has not been fully realized, and the extent of improvement in respiratory outcomes is unclear. We hypothesized that significant lung disease was present at diagnosis.

Objectives: To determine the extent of lung disease in a geographically defined population of infants with CF diagnosed after detection by NBS.

Application of a shortened inhaled adenosine-5'-monophosphate challenge in young children using the forced oscillation technique.

Background: Adenosine-5'-monophosphate (AMP) is an indirect challenge agent thought to reflect allergic airway inflammation. The forced oscillation technique (FOT) is ideal for use in young children and is suitable for inhaled challenge studies in patients who are in this age group. We assessed the agreement between a shortened and a standard AMP challenge and the repeatability of the shortened AMP challenge using FOT as a primary outcome variable.

Management of childhood asthma in Western Australia.

Aims: The study aimed to determine how childhood asthma is managed in Western Australia by general practitioners (GPs) and specialist paediatricians.

Methods: A questionnaire survey was sent to 992 GPs and specialist paediatricians, asking about practice and preferences regarding maintenance management of childhood asthma and treatment of acute asthma. Questions about asthma in infants, pre-school and school-aged children were asked separately.

Microbial exposure, interferon gamma gene demethylation in naïve T-cells, and the risk of allergic disease.

The period of immune programming during early life presents a critical window of opportunity for the prevention of allergic diseases. There is mounting evidence that inappropriate immune programming may involve disruption of specific epigenetic modifications (switches) at immune-related genes. This novel area of research has great potential, as epigenetic changes are known to be sensitive to environmental factors and may therefore provide a mechanistic link for the observed association between specific environmental cues, faulty immune development, and the risk of allergic disease.

Children's environmental health: an under-recognised area in paediatric health care.

The knowledge that the environment in which we live, grow and play, can have negative or positive impacts on our health and development is not new. However the recognition that adverse environments can significantly and specifically affect the growth and development of a child from early intrauterine life through to adolescence, as well as impact their health later in adulthood, is relatively recent and has not fully reached health care providers involved in paediatric care.Over the past 15 years, world declarations and statements on children's rights, sustainable development, chemical safety and most recently climate change, have succeeded in cultivating a global focus on children's health and their right to a healthy environment.

Increased asthma and respiratory symptoms in children exposed to petrochemical pollution.

Background: Epidemiologic studies show statistical associations between levels of air pollutants and respiratory outcomes.

Objective: We sought to determine the effects of exposure to petrochemical pollution on the respiratory health of children.

Methods: Children aged 6 to 12 years living close to the petrochemical plants in La Plata, Argentina (n = 282), were compared with those living in a region with exposure to heavy traffic (n = 270) or in 2 relatively nonpolluted areas (n = 639).

Antibiotic use in the first year of life and risk of atopic disease in early childhood.

Background: Reduced post-natal microbial stimulation resulting from improvements in public health measures, smaller family size, and through increased antibiotic use has been postulated to account for the increasing prevalence of atopic diseases seen predominantly in developed countries.

Objective: To investigate use of antibiotics in the first year of life and subsequent development of atopic disease in early childhood.

Methods: A prospective birth cohort of 198 children at high atopic risk was recruited prenatally and followed for 5 years.

Attenuation of allergen-induced airway hyperresponsiveness is mediated by airway regulatory T cells.

Understanding the mechanisms involved in respiratory tolerance to inhaled allergens could potentially result in improved therapies for asthma and allergic diseases. Airway hyperresponsiveness (AHR) is a major feature of allergic asthma, thus the aim of the current study was to investigate mechanisms underlying suppression of allergen-induced AHR during chronic allergen exposure. Adult BALB/c mice were systemically sensitized with ovalbumin (OVA) in adjuvant and then challenged with a single 3 or 6 wk of OVA aerosols.

The involvement of histaminic and muscarinic receptors in the bronchoconstriction induced by myorelaxant administration in sensitized rabbits.

Background: Muscle relaxants cause bronchospasm via histamine release and/or by acting on the muscarinic receptors; we sought to characterize the respective importance of these pathways in the presence of bronchial hyperreactivity.

Methods: Ovalbumin-sensitized rabbits were randomly assigned to several protocol groups: Group C comprised untreated animals; in the other three groups, either H1 and H2 histaminic receptor blockade was performed, leaving the M1, M2, and M3 muscarinic receptors functional (Group M123), or combining this treatment with M3 muscarinic receptor blockade (Group M12), or with vagotomy (Group M3). Respiratory system impedance was measured over a 90-s period, during which succinylcholine, mivacurium or atracurium was administered.

Acquisition and eradication of P. aeruginosa in young children with cystic fibrosis.

When do infants and young children with cystic fibrosis acquire infection with Pseudomonas aeruginosa? Can this be eradicated when first detected? Children <6 yrs of age participated in an annual bronchoalveolar lavage (BAL)-based microbiological surveillance programme in Perth, Australia. When P. aeruginosa was detected, an eradication programme using combination treatment with i.

Negative impact of the noseclip on high-frequency respiratory impedance measurements.

The noseclip is conventionally used in lung function testing to prevent leakage via the nasal compartments. However, some subjects exhibit a velum-opening reflex which may affect results. We performed forced oscillation measurements at frequencies (8-256 Hz) that include the first antiresonance, comparing the noseclip with a cotton wool nose plug to eliminate upper airway contribution.

Interleukin-10/interleukin-5 responses at birth predict risk for respiratory infections in children with atopic family history.

Rationale: Respiratory infections in early life are associated with risk for wheezing bronchiolitis, especially in children at high risk of atopy. The underlying mechanisms are unknown, but are suspected to involve imbalance(s) in host defense responses against pathogens stemming from functional immaturity of the immune system in this age group.

Objectives: To assess the contribution of eosinophil-trophic IL-5, and the potent antiinflammatory cytokine IL-10, to risk for infection in early life.

Susceptibility of children to environmental pollutants.

Children are more vulnerable to adverse environmental exposures. The unique ways in which they interact with their environment and their dynamic developmental physiology mean that they generally receive a higher dose of toxicant for a given level of environmental exposure. In addition, children are frequently more likely to suffer adverse health outcomes from exposures.

Allergen-enhanced thrombomodulin (blood dendritic cell antigen 3, CD141) expression on dendritic cells is associated with a TH2-skewed immune response.

Background: Dendritic cells (DCs) are important in allergic diseases such as asthma, although little is known regarding the mechanisms by which DCs induce T(H)2-polarized responses in atopic individuals. It has been suggested that intrinsic properties of allergens can directly stimulate T(H)2 polarizing functions of DCs, but little is known of the underlying mechanisms.

Objective: To identify novel genes expressed by house dust mite (HDM) allergen-exposed DCs.

Definition, assessment and treatment of wheezing disorders in preschool children: an evidence-based approach.

There is poor agreement on definitions of different phenotypes of preschool wheezing disorders. The present Task Force proposes to use the terms episodic (viral) wheeze to describe children who wheeze intermittently and are well between episodes, and multiple-trigger wheeze for children who wheeze both during and outside discrete episodes. Investigations are only needed when in doubt about the diagnosis.

Early identification of atopy in the prediction of persistent asthma in children.

The long-term solution to the asthma epidemic is thought to be prevention, and not treatment of established disease. Atopic asthma arises from gene-environment interactions, which mainly take place during a short period in prenatal and postnatal development. These interactions are not completely understood, and hence primary prevention remains an elusive goal.

Lung function in infants with cystic fibrosis diagnosed by newborn screening.

Rationale: Progressive lung damage in cystic fibrosis (CF) starts in infancy, and early detection may aid preventative strategies.

Objectives: To measure lung function in infants with CF diagnosed by newborn screening and describe its association with pulmonary infection and inflammation.

Methods: Infants with CF (n = 68, 6 weeks to 30 months of age) and healthy infants without CF (n = 49) were studied.

Disease surveillance using bronchoalveolar lavage.

The role of pulmonary infection and inflammation in the pathogenesis of destructive lung disease in cystic fibrosis (CF) is undisputed. The use of bronchoscopy and bronchoalveolar lavage (BAL) has demonstrated that these processes may begin early in life and be present in the absence of overt clinical symptoms. Some children diagnosed following newborn screening can be infected with Pseudomonas aeruginosa in infancy.

Acute Influenza A infection induces bronchial hyper-responsiveness in mice.

This study aimed to determine whether the route of administration of methacholine (MCh) influenced the pattern of airway hyper-responsiveness (AHR) in mice. BALB/c mice were inoculated with a 50-microL volume containing 10(4.5)-pfu Influenza virus A/Mem/1/71(H3N1) or media.

The bimodal quasi-static and dynamic elastance of the murine lung.

The double sigmoidal nature of the mouse pressure-volume (PV) curve is well recognized but largely ignored. This study systematically examined the effect of inflating the mouse lung to 40 cm H2O transrespiratory pressure (Prs) in vivo. Adult BALB/c mice were anesthetized, tracheostomized, and mechanically ventilated.

Gender-specific effects of cytokine gene polymorphisms on childhood vaccine responses.

Cytokine gene polymorphisms affect vaccine responses and gender-specific effects are known for many phenotypes. Therefore, this study investigated gender-specific effects of cytokine gene polymorphisms on vaccine responses. In 263 2-year-old subjects selected for parental history of atopy, boys with IL-4 C-589T and IL-4Ralpha I50V genotypes associated with atopy had increased Diptheria Toxoid (DiphTox) and Tetanus Toxoid (TetTox) responses compared with the remaining alleles (IL-4 C-589T: DipTox p=0.

High tidal volume ventilation in infant mice.

Infant mice were ventilated with either high tidal volume (V(T)) with zero end-expiratory pressure (HVZ), high V(T) with positive end-expiratory pressure (PEEP) (HVP), or low V(T) with PEEP. Thoracic gas volume (TGV) was determined plethysmographically and low-frequency forced oscillations were used to measure the input impedance of the respiratory system. Inflammatory cells, total protein, and cytokines in bronchoalveolar lavage fluid (BALF) and interleukin-6 (IL-6) in serum were measured as markers of pulmonary and systemic inflammatory response, respectively.