Bronchoalveolar lavage findings suggest two different forms of childhood asthma

Background: It seems plausible that children with atopy and persistent asthma symptoms will, like their adult counterparts, have chronic airways inflammation. However, many young children with no other atopic features have episodic wheezing that is triggered solely by viral respiratory infections. Little is known as to whether airways inflammation occurs in these two asthma patterns during relatively asymptomatic periods.

Methods: Using a non-bronchoscopic bronchoalveolar lavage (BAL) procedure on children presenting for an elective surgical procedure, this study has investigated the cellular constituents of BAL fluid in children with a history of atopic asthma (AA) non-asthmatic atopic children (NAA) or viral associated wheeze (VAW).

Results: A total of 95 children was studied: 52 with atopic asthma (8.0 years, range 1.1-15.3, 36 male), 23 with non-asthmatic atopy (median age 8.3 years, range 1.7-13.6, 11 male) and 20 with VAW (3.1 years, range 1.0-8.2, 13 male). No complications were observed during the lavage procedure and no adverse events were noted post-operatively. Total lavage fluid recovered was similar in all groups and the total cell numbers were higher in the VAW group. Eosinophil (P< 0.005) and mast cell (/'<0.05) numbers were significantly elevated in the group with atopic asthma.

Conclusions: During relatively asymptomatic periods there is on-going airways inflammation, as demonstrated by eosinophil and mast cell recruitment, in children with asthma and atopy but not in children with viral associated wheeze or atopy alone. This strongly suggests that there are different underlying pathophysiologicai mechanisms in these two groups of children who wheeze.

Interleukin-4 and interleukin-4 soluble receptor α levels in bronchoalveolar lavage from children with asthma

Background: In asthma there is increased expression of the Th2-type cytokine interleukin-4 (IL-4). IL-4 is important in immunoglobulin isotype switching to immunoglobulin E and adhesion of eosinophils to endothelium.

Objectives: We hypothesized that levels of IL-4 in bronchoalveolar lavage (BAL) fluid would be increased in stable, atopic asthmatic children compared with controls and that levels of its physiologic inhibitor IL-4 soluble receptor α (IL-4sRα) would be correspondingly decreased.

Methods: One hundred sixteen children attending a children's hospital for elective surgery were recruited. A nonbronchoscopic BAL was performed, and IL-4 and IL-4sRα were measured in the BAL supernatants.

Results: There was no significant difference in IL-4 concentrations between atopic asthmatic children, atopic normal controls, and nonatopic normal controls [0.13 pg/mL (0.13 to 0.87) vs 0.13 pg/mL (0.13 to 0.41) vs 0.13 pg/mL (0.13 to 0.5), P = 0.65]. IL-4sRα levels were significantly increased in asthmatic patients compared with atopic controls [6.4 pg/mL (5.0 to 25.5) vs 5.0 pg/mL (5.0 to 9.9), P = 0.018], but not when compared with the nonatopic controls [5.2 pg/mL (5.0 to 10.6), P = 0.19].

Conclusions: Contrary to expectation, IL-4sRα levels are increased in BAL from stable asthmatic children compared with nonatopic controls, and we speculate that IL-4sRα is released by inflammatory cells in the airways to limit the proinflammatory effects of IL-4.

Structural change in multipartite entanglement sharing: A random matrix approach

We study the typical entanglement properties of a system comprising two independent qubit environments interacting via a shuttling ancilla. The initial preparation of the environments is modeled using random matrix techniques. The entanglement measure used in our study is then averaged over many histories of randomly prepared environmental states. Under a Heisenberg interaction model, the average entanglement between the ancilla and one of the environments remains constant, regardless of the preparation of the latter and the details of the interaction. We also show that, upon suitable kinematic and dynamical changes in the ancillaenvironment subsystems, the entanglement-sharing structure undergoes abrupt modifications associated with a change in the multipartite entanglement class of the overall system's state. These results are invariant with respect to the randomized initial state of the environments.

Passing quantum correlations to qubits using any two-mode state

We draw an explicit connection between the statistical properties of an entangled two-mode continuous variable (CV) resource and the amount of entanglement that can be dynamically transferred to a pair of noninteracting two-level systems. More specifically, we rigorously reformulate entanglement-transfer process by making use of covariance matrix formalism. When the resource state is Gaussian, our method makes the approach to the transfer of quantum correlations much more flexible than in previously considered schemes and allows the straightforward inclusion of the effects of noise affecting the CV system. Moreover, the proposed method reveals that the use of de-Gaussified two-mode states is almost never advantageous for transferring entanglement with respect to the full Gaussian picture, despite the entanglement in the non-Gaussian resource can be much larger than in its Gaussian counterpart. We can thus conclude that the entanglement-transfer map overthrows the

Controllable Gaussian-Qubit Interface for Extremal Quantum State Engineering

We study state engineering through bilinear interactions between two remote qubits and two-mode Gaussian light fields. The attainable two-qubit states span the entire physically allowed region in the entanglement-versus-global-purity plane. Two-mode Gaussian states with maximal entanglement at fixed global and marginal entropies produce maximally entangled two-qubit states in the corresponding entropic diagram. We show that a small set of parameters characterizing extremally entangled two-mode Gaussian states is sufficient to control the engineering of extremally entangled two-qubit states, which can be realized in realistic matter-light scenarios.

Teleporting bipartite entanglement using maximally entangled mixed channels

The ability to teleport entanglement through maximally entangled mixed states as defined by concurrence and linear entropy is studied. We show how the teleported entanglement depends on the quality of the quantum channel used, as defined through its entanglement and mixedness, as well as the form of the target state to be teleported. We present new results based on the fidelity of the teleported state as well as an experimental setup that is immediately implementable with currently available technology.

Atopy, home environment and the risk of childhood-onset type 1 diabetes: a population-based case-control study

Background: The marked increases in the incidence of type 1 diabetes in recent decades strongly suggest the role of environmental influences. These environmental influences remain largely unknown.

Cytopathogenesis of Sendai virus in well-differentiated primary pediatric bronchial epithelial cells

Sendai virus (SeV) is a murine respiratory virus of considerable interest as a gene therapy or vaccine vector, as it is considered nonpathogenic in humans. However, little is known about its interaction with the human respiratory tract. To address this, we developed a model of respiratory virus infection based on well-differentiated primary pediatric bronchial epithelial cells (WD-PBECs). These physiologically authentic cultures are comprised of polarized pseudostratified multilayered epithelium containing ciliated, goblet, and basal cells and intact tight junctions. To facilitate our studies, we rescued a replication-competent recombinant SeV expressing enhanced green fluorescent protein (rSeV/eGFP). rSeV/eGFP infected WD-PBECs efficiently and progressively and was restricted to ciliated and nonciliated cells, not goblet cells, on the apical surface. Considerable cytopathology was evident in the rSeV/eGFP-infected cultures postinfection. This manifested itself by ciliostasis, cell sloughing, apoptosis, and extensive degeneration of WD-PBEC cultures. Syncytia were also evident, along with significant basolateral secretion of proinflammatory chemokines, including IP-10, RANTES, tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), interleukin 6 (IL-6), and IL-8. Such deleterious responses are difficult to reconcile with a lack of pathogenesis in humans and suggest that caution may be required in exploiting replication-competent SeV as a vaccine vector. Alternatively, such robust responses might constitute appropriate normal host responses to viral infection and be a prerequisite for the induction of efficient immune responses.

Respiratory viral infection in lower airways of asymptomatic children.

Aim: The aim of this study was to determine if asthmatic children have viruses more commonly detected in lower airways during asymptomatic periods than normal children. Methods: Fifty-five asymptomatic children attending elective surgical procedures (14 with stable asthma, 41 normal controls) underwent non-bronchoscopic bronchoalveolar lavage. Differential cell count and PCR for 13 common viruses were performed. Results: Nineteen (35%) children were positive for at least one virus, with adenovirus being most common. No differences in the proportion of viruses detected were seen between asthmatic and normal ‘control’ children. Viruses other than adenovirus were associated with higher neutrophil counts, suggesting that they caused an inflammatory response in both asthmatics and controls (median BAL neutrophil count, 6.9% for virus detected vs. 1.5% for virus not detected, p = 0.03). Conclusions: Over one-third of asymptomatic children have a detectable virus (most commonly adenovirus) in the lower airway; however, this was not more common in asthmatics. Viruses other than adenovirus were associated with elevated neutrophils suggesting that viral infection can be present during relatively asymptomatic periods in asthmatic children.