Extracellular Vesicles and Asthma—More Than Just a Co-Existence

Extracellular vesicles (EVs) are membranous structures, which are secreted by almost every cell type analyzed so far. In addition to their importance for cell-cell communication under physiological conditions, EVs are also released during pathogenesis and mechanistically contribute to this process. Here we summarize their functional relevance in asthma, one of the most common chronic non-communicable diseases. Asthma is a complex persistent inflammatory disorder of the airways characterized by reversible airflow obstruction and, from a long-term perspective, airway remodeling. Overall, mechanistic studies summarized here indicate the importance of different subtypes of EVs and their variable cargoes in the functioning of the pathways underlying asthma, and show some interesting potential for the development of future therapeutic interventions. Association studies in turn demonstrate a good diagnostic potential of EVs in asthma.     

Household endotoxin reduction in the Louisa Environmental Intervention Project for rural childhood asthma

Endotoxin exacerbates asthma. We designed the Louisa Environmental Intervention Project (LEIP) and assessed its effectiveness in reducing household endotoxin and improving asthma symptoms in rural Iowa children. Asthmatic school children (N = 104 from 89 homes) of Louisa and Keokuk counties in Iowa (aged 5-14 years) were recruited and block-randomized to receive extensive (education + professional cleaning) or educational interventions. Environmental sampling collection and respiratory survey administration were done at baseline and during three follow-up visits. Mixed-model analyses were used to assess the effect of the intervention on endotoxin levels and asthma symptoms in the main analysis and of endotoxin reduction on asthma symptoms in exploratory analysis. In the extensive intervention group, dust endotoxin load was significantly reduced in post-intervention visits. The extensive compared with the educational intervention was associated with significantly decreased dust endotoxin load in farm homes and less frequent nighttime asthma symptoms. In exploratory analysis, dust endotoxin load reduction from baseline was associated with lower total asthma symptoms score (Odds ratio: 0.52, 95% confidence interval: 0.29-0.92). In conclusion, the LEIP intervention reduced household dust endotoxin and improved asthma symptoms. However, endotoxin reductions were not sustained post-intervention by residents.     

A Potent Mimetic of the Siglec-8 Ligand 6’-Sulfo-Sialyl Lewisx

Siglecs are members of the immunoglobulin gene family containing sialic acid binding N-terminal domains. Among them, Siglec-8 is expressed on various cell types of the immune system such as eosinophils, mast cells and weakly on basophils. Cross-linking of Siglec-8 with monoclonal antibodies triggers apoptosis in eosinophils and inhibits degranulation of mast cells, making Siglec-8 a promising target for the treatment of eosinophil- and mast cell-associated diseases such as asthma. The tetrasaccharide 6’-sulfo-sialyl Lewis^x has been identified as a specific Siglec-8 ligand in glycan array screening. Here, we describe an extended study enlightening the pharmacophores of 6’-sulfo-sialyl Lewis^x and the successful development of a high-affinity mimetic. Retaining the neuraminic acid core, the introduction of a carbocyclic mimetic of the Gal moiety and a sulfonamide substituent in the 9-position gave a 20-fold improved binding affinity. Finally, the residence time, which usually is the Achilles tendon of carbohydrate/lectin interactions, could be improved.     

Adenosine Signaling in Mast Cells and Allergic Diseases

Adenosine is a nucleoside involved in the pathogenesis of allergic diseases. Its effects are mediated through its binding to G protein-coupled receptors: A1, A2a, A2b and A3. The receptors differ in the type of G protein they recruit, in the effect on adenylyl cyclase (AC) activity and the downstream signaling pathway triggered. Adenosine can produce both an enhancement and an inhibition of mast cell degranulation, indicating that adenosine effects on these receptors is controversial and remains to be clarified. Depending on the study model, A1, A2b, and A3 receptors have shown anti- or pro-inflammatory activity. However, most studies reported an anti-inflammatory activity of A2a receptor. The precise knowledge of the adenosine mechanism of action may allow to develop more efficient therapies for allergic diseases by using selective agonist and antagonist against specific receptor subtypes.     

基于一种新型强迫振荡仪器的呼吸道阻抗测量研究

强迫振荡技术被越来越多地应用于呼吸系统力学研究中。为了检验一种新型强迫振荡仪器的临床应用前景,设计了一组实验用于测量哮喘病人和正常人,从而证明这种新型的仪器对哮喘病诊断是否有帮助。实验征集了5个哮喘病人和5个正常人。测量结果表明:所测得的呼吸系统阻抗在两组人之间有明显差异,展示了这种新仪器在哮喘病诊断中的应用潜力。     

Observation‐based metrics for residential dampness and mold with dose–response relationships to health: A review

An important proportion of respiratory illness is considered attributable to residential dampness or mold (D/M). Developing health‐protective D/M guidelines has been challenging, in part because unhealthy levels of indoor D/M cannot be defined using available microbiological measurements. This review paper explores reported multilevel, observation‐based (eg visual or olfactory) D/M metrics for potential in defining unhealthy levels of residential D/M. For many of the 33 multilevel residential D/M metrics identified, health risks generally increased as observed D/M increased. Although some metrics seemed too complex for practical use, simple metrics had among the strongest associations with health outcomes. Available findings suggest the feasibility of setting observation‐based D/M thresholds to trigger remedial action, using further improved D/M metrics without microbiological measurements (at least until the actual dampness‐related agents that cause illness are better quantified). Additional data would allow setting health‐protective D/M thresholds more precisely. Also, metrics could better reflect hidden D/M by more strongly emphasizing mold odor, which has demonstrated strong associations with health effects.     

Differential effects of air conditioning type on residential endotoxin levels in a semi‐arid climate

Residential endotoxin exposure is associated with protective and pathogenic health outcomes. Evaporative coolers, an energy‐efficient type of air conditioner used in dry climates, are a potential source of indoor endotoxins; however, this association is largely unstudied. We collected settled dust biannually from four locations in homes with evaporative coolers (n=18) and central air conditioners (n=22) in Utah County, Utah (USA), during winter (Jan‐Apr) and summer (Aug‐Sept), 2014. Dust samples (n=281) were analyzed by the Limulus amebocyte lysate test. Housing factors were measured by survey, and indoor temperature and relative humidity measures were collected during both seasons. Endotoxin concentrations (EU/mg) were significantly higher in homes with evaporative coolers from mattress and bedroom floor samples during both seasons. Endotoxin surface loads (EU/m²) were significantly higher in homes with evaporative coolers from mattress and bedroom floor samples during both seasons and in upholstered furniture during winter. For the nine significant season‐by‐location comparisons, EU/mg and EU/m² were approximately three to six times greater in homes using evaporative coolers. A plausible explanation for these findings is that evaporative coolers serve as a reservoir and distribution system for Gram‐negative bacteria or their cell wall components in homes.     

MicroRNA in United Airway Diseases

The concept of united airway diseases (UAD) has received increasing attention in recent years. Sustained and increased inflammation is a common feature of UAD, which is inevitably accompanied with marked gene modification and tight gene regulation. However, gene regulation in the common inflammatory processes in UAD remains unclear. MicroRNA (miRNA), a novel regulator of gene expression, has been considered to be involved in many inflammatory diseases. Although there are an increasing number of studies of miRNAs in inflammatory upper and lower airway diseases, few miRNAs have been identified that directly link the upper and lower airways. In this article, therefore, we reviewed the relevant studies available in order to improve the understanding of the roles of miRNAs in the interaction and pathogenesis of UAD.