Specific Migratory Dendritic Cells Rapidly Transport Antigen from the Airways to the Thoracic Lymph Nodes

Antigen transport from the airway mucosa to the thoracic lymph nodes (TLNs) was studied in vivo by intratracheal instillation of fluorescein isothiocyanate (FITC)-conjugated macromolecules. After instillation, FITC+ cells with stellate morphology were found deep in the TLN T cell area. Using flow cytometry, an FITC signal was exclusively detected in CD11cmed-hi/major histocompatibility complex class II (MHCII)hi cells, representing migratory airway-derived lymph node dendritic cells (AW-LNDCs). No FITC signal accumulated in lymphocytes and in a CD11chiMHCIImed DC group containing a CD8αhi subset (non–airway-derived [NAW]-LNDCs). Sorted AW-LNDCs showed long MHCIIbright cytoplasmic processes and intracytoplasmatic FITC+ granules. The fraction of FITC+ AW-LNDCs peaked after 24 h and had reached baseline by day 7. AW-LNDCs were depleted by 7 d of ganciclovir treatment in thymidine kinase transgenic mice, resulting in a strong reduction of FITC-macromolecule transport into the TLNs. Compared with intrapulmonary DCs, AW-LNDCs had a mature phenotype and upregulated levels of MHCII, B7-2, CD40, and intracellular adhesion molecule (ICAM)-1. In addition, sorted AW-LNDCs from FITC-ovalbumin (OVA)–instilled animals strongly presented OVA to OVA-TCR transgenic T cells. These results validate the unique sentinel role of airway DCs, picking up antigen in the airways and delivering it in an immunogenic form to the T cells in the TLNs

Gender does not influence the response to the combination of salmeterol and fluticasone propionate in COPD

AbstractThe prevalence of chronic obstructive pulmonary disease (COPD) in women is increasing worldwide. Women may have greater susceptibility to COPD progression than men, and differences in efficacy and safety of respiratory medications by gender are largely unexplored. We aimed to determine whether the response to treatment in women with COPD differed from men in a large, 1-year double-blind trial (‘TRISTAN’). In a sensitivity analysis, we compared 539 male and 180 female COPD patients, who were randomized to the salmeterol/fluticasone combination 50/500mcg bid or placebo for 12 months. Combination therapy improved pre-treatment FEV1 significantly more than placebo in women by 152ml (95% confidence interval 95–208) and in men by 127ml (94–159). Similarly, a reduction in COPD exacerbation rates of 31% in women (9–48%) and of 23% in men (8–35%) was observed. Combination therapy reduced COPD exacerbations requiring treatment with oral corticosteroids by 36% in women and by 41% in men. Finally, combination treatment produced a better improvement in health status than placebo with a decrease in the SGRQ scores in women by −2.3 (−4.6 – 0.1) and in men by −2.1 (−3.5 to −0.8). No gender interaction was found for any outcome. Treatments were well tolerated with no difference in the frequency of adverse events in women and men. In this trial, therapy with the salmeterol/fluticasone combination produced significant improvements compared to placebo on all main endpoints and the magnitude of these improvements was similar for both men and women

Sensor networks for ambient intelligence

Due to rapid advances in networking and sensing technology we are witnessing a growing interest in sensor networks, in which a variety of sensors are connected to each other and to computational devices capable of multimodal signal processing and data analysis. Such networks are seen to play an increasingly important role as key enablers in emerging pervasive computing technologies. In the rst part of this paper we give an overview of recent developments in the area of multimodal sensor networks, paying special attention to ambient intelligence applications. In the second part, we discuss how the time series generated by data streams emanating from the sensors can be mined for temporal patterns, indicating cross-sensor signal correlations. I

Searching for Temporal Patterns in AmI Sensor Data

Abstract. Anticipation is a key property of human-human communication, and it is highly desirable for ambient environments to have the means of anticipating events to create a feeling of responsiveness and intelligence in the user. In a home or work environment, a great number of low-cost sensors can be deployed to detect simple events: the passing of a person, the usage of an object, the opening of a door. The methods that try to discover re-usable and interpretable patterns in temporal event data have several shortcomings. Using a testbed that we have developed for this purpose, we first contrast current approaches to the problem. We then extend the best of these approaches, the T-Pattern algorithm, with Gaussian Mixture Models, to obtain a fast and robust algorithm to find patterns in temporal data. Our algorithm can be used to anticipate future events, as well as to detect unexpected events as they occur.

Short-Term Cigarette Smoke Exposure Enhances Allergic Airway Inflammation in Mice

Rationale: Epidemiologic studies suggest that tobacco smoke contributes to the prevalence and occurrence of exacerbations in asthma. The effect of active smoking in adolescents with atopy is poorly understood. Objectives: We developed an experimental model to investigate the influence of smoking on antigen-induced airway inflammation and airway responsiveness in mice that were previously sensitized. Methods: Ovalbumin (OVA)-sensitized BALB/c mice were exposed to air or mainstream smoke (S days/week) and to phosphate-buffered saline (PBS) or OVA aerosol (3 times/week) for 2 weeks (n = 8 for each group). Results: Airway responsiveness to intravenously injected carbachol was increased (p < 0.05) in smoke- and OVA-exposed mice compared with all other groups. There was an additive effect of smoke and OVA exposure on total cell numbers, macrophages, and dendritic cells in bronchoalveolar lavage fluid and on CD4(+) and CD8(+) T lymphocytes and dendritic cells in lung tissue (p < 0.05 compared with mice exposed to smoke and PBS and to mice exposed to air and OVA). Concurrent smoke and OVA exposure augmented OVA-specific IgE in serum compared with air and OVA exposure. In lavage fluid supernatant, eotaxin was increased in air- and OVA-exposed mice. The further increase observed in the group exposed to both OVA and cigarette smoke came close to formal significance (p = 0.06). Thymus- and activation-regulated chemokine was augmented in mice exposed to either smoke or OVA, without additional effect. Conclusions: Our data indicate that acute concurrent exposure to allergen and mainstream cigarette smoke enhances airway inflammation and airway responsiveness in previously sensitized mice

Allergen-induced changes in bone-marrow progenitor and airway dendritic cells in sensitized rats

Eosinophilic airway inflammation is orchestrated by T-helper (Th)-2 lymphocytes. We have previously demonstrated that dendritic cells (DC) are essential for the presentation of antigen to these Th2 cells leading to airway inflammation. Here, we have examined the presence of DC in the lungs, the kinetics of appearance, and the possible involvement of the bone-marrow progenitor for DC in a rat model of ovalbumin (OVA)-induced airway inflammation. Sensitized rats were exposed to 0, 1, 3, or 7 consecutive daily OVA aerosols. Control rats were sham sensitized and/or exposed to phosphate-buffered saline (PBS), and bronchoalveolar lavage (BAL) was performed 24 h after the last challenge. DC were identified in BAL fluid as low-density, low-autofluorescence, CD3 � , CD45RA � , OX62 � , OX6 � cells that had long surface extensions and strong costimulatory activity. Low but detectable amounts of BAL DC were seen in sensitized, unexposed animals. After three OVA exposures, the inflammatory infiltrate consisted of CD4 �-activated T cells, eosinophils, and monocytes. The number of BAL DC was significantly increased in OVA-sensitized/OVA-exposed animals compared with sham-sensitized or PBS-exposed animals. The kinetics of DC increase closely parallelled those in other inflammatory cells. Bone-marrow cells taken from the OVAsensitized and-exposed group were grown in the DC growth factor granulocyte macrophage colony-stimulating factor for 6 d and the yield of OX62 � OX6 � DC was 60 % higher compared with PBS-exposed o