Rhinovirus infections in infancy and early childhood.

Rhinovirus (RV) infections occur early and recurrently in life, imposing a significant burden of disease on infants and young children. They are the most frequent causative agents of both upper and lower respiratory tract infections in this age group and are associated with a broad variety of clinical outcomes, ranging from asymptomatic infections to severe respiratory disease requiring hospitalisation. In addition to their impact on short-term morbidity, RVs are also debated as important pathogens in the development of recurrent wheeze and/or asthma.

A new double-tracer gas single-breath washout to assess early cystic fibrosis lung disease.

In cystic fibrosis (CF), tests for ventilation inhomogeneity are sensitive but not established for clinical routine. We assessed feasibility of a new double-tracer gas single-breath washout (SBW) in school-aged children with CF and control subjects, and compared SBW between groups and with multiple-breath nitrogen washout (MBNW). Three SBW and MBNW were performed in 118 children (66 with CF) using a side-stream ultrasonic flowmeter setup.

Applicability of independent component analysis on high-density microelectrode array recordings.

Emerging complementary metal oxide semiconductor (CMOS)-based, high-density microelectrode array (HD-MEA) devices provide high spatial resolution at subcellular level and a large number of readout channels. These devices allow for simultaneous recording of extracellular activity of a large number of neurons with every neuron being detected by multiple electrodes. To analyze the recorded signals, spiking events have to be assigned to individual neurons, a process referred to as "spike sorting.

Comparison of online single-breath vs. online multiple-breath exhaled nitric oxide in school-age children.

Introduction: Standards for online multiple-breath (mb) exhaled nitric oxide (eNO) measurements and studies comparing them with online single-breath (sb) eNO measurements are lacking, although eNOmb requires less cooperation in children at school age or younger.

Methods: Online eNOmb and eNOsb were measured in 99 healthy children and (in order to observe higher values) in 21 children with suspected asthma at a median age of 6.1 and 11.

Breastfeeding and lung function at school age: does maternal asthma modify the effect?

Rationale: The evidence for an effect of breastfeeding on lung function is conflicting, in particular whether the effect is modified by maternal asthma.

Objectives: To explore the association between breastfeeding and school-age lung function.

Methods: In the Leicestershire Cohort Studies we assessed duration of breastfeeding (not breastfed, ≤3 months, 4-6 months, and >6 months), other exposures, and respiratory symptoms by repeated questionnaires.

Genetic interactions in the β-adrenoceptor/G-protein signal transduction pathway and survival after coronary artery bypass grafting: a pilot study.

Background: In heart failure, β-adrenergic receptor (βAR) stimulation desensitizes the receptor, uncouples the downstream Gαs protein, and diminishes signal transduction. We tested the hypotheses that haplotype-tagging single-nucleotide polymorphisms (htSNPs) within the Gαs gene (GNAS) (i) are functionally active and alter Gαs expression, (ii) influence survival after coronary artery bypass grafting (CABG), and (iii) interact with βAR SNPs.

Methods: Amplification of GNAS intron 1 was followed by cloning, reporter assays, electrophoretic mobility shift assays, and western blots.

The GNB3 C825T polymorphism influences platelet aggregation in human whole blood.

Background: Platelet aggregation varies among individuals; and genetic factors may alter platelet activation through G-protein-coupled receptors, thus influencing results of point-of-care platelet aggregometry in whole blood. We tested the hypothesis that the C825T polymorphism of the gene GNB3 encoding the G-protein β-3 subunit and the platelet GPIIIa Pl(A1)/(A2) polymorphism of the glycoprotein IIIa influence platelet aggregation.

Methods: Evoked [thrombin receptor activating peptide (TRAP), ADP, TXA(2) agonist U46619, epinephrine, and collagen] platelet aggregation in whole blood was measured using impedance aggregometry (Multiplate) in 143 healthy individuals (age: 40.

Daily exhaled nitric oxide measurements and asthma exacerbations in children.

Background: Fractional exhaled Nitric Oxide (FeNO) is a biomarker for eosinophilic airway inflammation and can be measured at home on a daily basis. A short-term increase in FeNO may indicate a higher risk of future asthma exacerbations.

Objective: To assess changes in FeNO before and after asthma exacerbations compared to a stable control period.

Transfemoral aortic valve implantation under sedation and monitored anaesthetic care--a feasibility study.

Surgical aortic valve replacement is the conventional treatment for symptomatic aortic valve stenosis; however, the technique of transfemoral transcatheter aortic valve implantation has recently been developed for older patients at high risk for surgery. We assessed whether this procedure could be safely performed under sedation in 100 patients. Their predicted surgical mortality was 21.

Role of the GNAS1 T393C polymorphism in patients with glioblastoma multiforme.

The T393C polymorphism of the GNAS1 locus, which encodes the Gαs protein, has recently been found to be associated with patient outcome in various malignancies. We investigated the association between GNAS1 genotype and survival among patients suffering from glioblastoma multiforme (GBM). One hundred and sixty-two patients with GBM were retrospectively investigated.

Long-term course of lung clearance index between infancy and school-age in cystic fibrosis subjects.

Multiple breath washout (MBW) measurements have recently been shown to be sensitive for detection of early cystic fibrosis (CF) lung disease, with the lung clearance index (LCI) being the most common measure for ventilation inhomogeneity. The aim of this observational study was to describe the longitudinal course of LCI from time of clinical diagnosis during infancy to school-age in eleven children with CF. Elevated LCI during infancy was present in seven subjects, especially in those with later clinical diagnosis.

Exposure to moderate air pollution during late pregnancy and cord blood cytokine secretion in healthy neonates.

Background/objectives: Ambient air pollution can alter cytokine concentrations as shown in vitro and following short-term exposure to high air pollution levels in vivo. Exposure to pollution during late pregnancy has been shown to affect fetal lymphocytic immunophenotypes. However, effects of prenatal exposure to moderate levels of air pollutants on cytokine regulation in cord blood of healthy infants are unknown.

Respiratory symptoms in preterm infants: burden of disease in the first year of life.

Objective: While respiratory symptoms in the first year of life are relatively well described for term infants, data for preterm infants are scarce. We aimed to describe the burden of respiratory disease in a group of preterm infants with and without bronchopulmonary dysplasia (BPD) and to assess the association of respiratory symptoms with perinatal, genetic and environmental risk factors.

Methods: Single centre birth cohort study: prospective recording of perinatal risk factors and retrospective assessment of respiratory symptoms during the first year of life by standardised questionnaires.

A novel aspect of GNAS imprinting: higher maternal expression of Gαs in human lymphoblasts, peripheral blood mononuclear cells, mammary adipose tissue, and heart.

The human GNAS gene is imprinted in a tissue-specific manner, being expressed primarily from the maternal allele in pituitary, thyroid, renal proximal tubules, and gonads, but is supposed to be biallelically expressed with an equal allelic expression in most other tissues. We analysed allelic expression of Gαs using Pyrosequencing. By genotyping the GNAS T393C polymorphism we quantified mRNA transcripts in lymphoblasts (Ly, n=11), peripheral blood mononuclear cells (PBMC, n=18), mammary adipose tissue (MAT, n=23) and heart tissue (HT, n=44).

Associations between fluctuations in lung function and asthma control in two populations with differing asthma severity.

Background: Lung function is a major criterion used to assess asthma control. Fluctuation analyses can account for lung function history over time, and may provide an additional dimension to characterise control. The relationships between mean and fluctuations in lung function with asthma control, exacerbation and quality of life were studied in two independent data sets.

Fluctuation phenotyping based on daily fraction of exhaled nitric oxide values in asthmatic children.

Background: Fraction of exhaled nitric oxide (Feno), a marker of airway inflammation, has been proposed to be useful for asthma management, but conclusions are inconsistent. This might be due to the failure of mean statistics to characterize individual variability in Feno values, which is possibly a better indicator of asthma control than single measurements.

Objective: We characterized fractal fluctuations in daily Feno values over time and the relationship between Feno values and symptom scores.

Validation of the Asthma Predictive Index and comparison with simpler clinical prediction rules.

Background: The loose and stringent Asthma Predictive Indices (API), developed in Tucson, are popular rules to predict asthma in preschool children. To be clinically useful, they require validation in different settings.

Objective: To assess the predictive performance of the API in an independent population and compare it with simpler rules based only on preschool wheeze.

Complexity and emergent phenomena.

Complex biological systems operate under non-equilibrium conditions and exhibit emergent properties associated with correlated spatial and temporal structures. These properties may be individually unpredictable, but tend to be governed by power-law probability distributions and/or correlation. This article reviews the concepts that are invoked in the treatment of complex systems through a wide range of respiratory-related examples.

Aquaporin 5 gene promoter--1364A/C polymorphism associated with 30-day survival in severe sepsis.

Background: Because the aquaporin (AQP) 5 promoter -1364A/C polymorphism is associated with altered AQP5 expression, this association could have an impact on key mechanisms in sepsis, such as cell migration, activity of the rennin-angiotensin- aldosterone system (RAAS), and water transport across biologic membranes. Therefore, we tested the hypothesis that the AQP5 promoter -1364A/C polymorphism is associated with increased 30-day survival in severe sepsis.

Methods: In a prospective study, adults with severe sepsis (N = 154) were genotyped for the AQP5 promoter -1364A/C polymorphism.

Tidal volume single breath washout of two tracer gases--a practical and promising lung function test.

Background: Small airway disease frequently occurs in chronic lung diseases and may cause ventilation inhomogeneity (VI), which can be assessed by washout tests of inert tracer gas. Using two tracer gases with unequal molar mass (MM) and diffusivity increases specificity for VI in different lung zones. Currently washout tests are underutilised due to the time and effort required for measurements.

Predicting future risk of asthma exacerbations using individual conditional probabilities.

Background: Determination of future risk of exacerbations is a key issue in the management of asthma. We previously developed a method to calculate conditional probabilities (π) of future decreases in lung function by using the daily fluctuations in peak expiratory flow (PEF).

Objective: We aimed to extend calculation of π values to individual patients, validated by using electronically recorded data from 2 past clinical trials.

Temporal complexity in clinical manifestations of lung disease.

In this review, we summarize results of recent research on the temporal variability of lung function, symptoms, and inflammatory biomarkers. Specifically, we demonstrate how fluctuation analysis borrowed from statistical physics can be used to gain insight into neurorespiratory control and complex chronic dynamic diseases such as asthma viewed as a system of interacting components (e.g.

GNAS1 T393C polymorphism and disease progression in patients with malignant melanoma.

Background: Once metastasized, despite a variety of therapeutic options, the prognosis of patients with malignant melanoma (MM) is still poor. Therefore, the search for reliable markers to identify patients with high risk of disease progression is of high clinical importance. We have recently shown that TT genotypes of the single-nucleotide polymorphism (SNP) T393C in the gene GNAS1 are significantly associated with better outcome in a variety of carcinomas.

Compact voltage and current stimulation buffer for high-density microelectrode arrays.

We report on a compact (0.02 mm(2) ) buffer for both voltage and current stimulation of electrogenic cells on a complementary metal-oxide semiconductor microelectrode array. In voltage mode, the circuit is a high-current class-AB voltage follower, based on a local common-mode feedback (LCMFB) amplifier.