Eotaxin in Exhaled Breath Condensate of Allergic Asthma Patients with Exercise-Induced Bronchoconstriction

&lt;i&gt;Background:&lt;/i&gt; Eosinophils are the key inflammatory cells in asthma, and more and more evidence suggests their crucial role in exercise-induced bronchoconstriction (EIB). Eotaxin, as the most important chemotactic factor for eosinophils, plays an important role in the pathogenesis of asthma. &lt;i&gt;Objectives:&lt;/i&gt; The aim of the study was to evaluate the changes in eotaxin levels in exhaled breath condensate (EBC) following intensive exercise in allergic asthmatics. &lt;i&gt;Methods:&lt;/i&gt; The study was performed in a group of 27 asthmatics (17 with EIB, 13 without EIB) and 9 healthy volunteers. Changes induced by intensive exercise in the concentrations of eotaxin in EBC during the 24 h after an exercise test were assessed. The possible correlations of these measurements with the results of other tests commonly associated with eosinophilic airway inflammation were also determined. &lt;i&gt;Results:&lt;/i&gt; In asthmatic patients with EIB, a statistically significant increase in eotaxin concentrations in EBC collected during the first 24 h after an exercise test – with maximal increase after 6 h – was revealed. A statistically significant correlation between the maximum increase in eotaxin concentrations in EBC after exercise, and an increase in either serum eosinophil cationic protein or F&lt;sub&gt;ENO&lt;/sub&gt; 24 h after exercise in the group of asthmatics with EIB, was observed. &lt;i&gt;Conclusions:&lt;/i&gt; Our results confirm connections between EIB and airway eosinophilic inflammation. The increase of eotaxin in asthmatic airways, by promoting the migration and activation of eosinophils, may play an important role in upregulation and sustaining of the airway inflammation observed in EIB in asthmatic patients.</jats:p

Yarning about fall prevention: Community consultation to discuss falls and appropriate approaches to fall prevention with older Aboriginal and Torres Strait Islander people

Background: Fall related injury is an emerging issue for older Indigenous people worldwide, yet few targeted fall prevention programs are currently available for Indigenous populations. In order to inform the development of a new Aboriginal-specific fall prevention program in Australia, we conducted community consultation with older Aboriginal people to identify perceptions and beliefs about falls, and to identify desired program elements. Methods: Yarning Circles were held with Aboriginal and Torres Strait Islander people aged 45 years and over. Each Yarning Circle was facilitated by an Aboriginal researcher who incorporated six indicative questions into each discussion. Questions explored the impact of falls on Yarning Circle participants, their current use of fall prevention services and investigated Yarning Circle participant's preferences regarding the design and mode of delivery of a fall prevention program. Results: A total of 76 older Aboriginal people participated in ten Yarning Circles across six sites in the state of New South Wales. Participants associated falls with physical disability, a loss of emotional well-being and loss of connection to family and community. Many participants did not use existing fall prevention services due to a lack of availability in their area, having no referral provided by their GP and/or being unaware of fall prevention programs in general. Program elements identified as important by participants were that it be Aboriginal-specific, group-based, and on-going, with the flexibility to be tailored to specific communities, with free transport provided to and from the program. Conclusions: Older Aboriginal people reported falls to be a priority health issue, with a significant impact on their health and well-being. Few older Aboriginal people accessed prevention programs, suggesting there is an important need for targeted Aboriginal-specific programs. A number of important program elements were identified which if incorporated into prevention programs, may help to address the rising burden of falls

Supplementary Material for: Vitamin D₃ Treatment Decreases Frequencies of CD16-Positive and TNF-α-Secreting Monocytes in Asthmatic Patients

Background: Previously, we demonstrated that glucocorticoid (GC) treatment of asthmatic patients resulted in decreasing frequencies of monocyte subsets expressing CD16 and capable of releasing TNF-α. Here, we wished to analyze whether the active form of vitamin D, i.e. vitamin D3, referred to as 1α,25-dihydroxyvitamin D3 [1,25-(OH)2D3] can exert GC-like proapoptotic effects on CD16-positive monocytes and thus decrease the proinflammatory potential of these cells. Finally, we set out to investigate whether the addition of 1,25-(OH)2D3 would facilitate the use of lower doses of GC without decreasing their anti-inflammatory properties. Methods: Peripheral blood mononuclear cells collected from healthy individuals and asthmatic patients were cultured with 1,25-(OH)2D3 and/or varying doses of GC in the presence or absence of caspase inhibition. The cells were either directly stained for extracellular markers or prestimulated with lipopolysaccharide for the assessment of intracellular cytokine production and then analyzed by flow cytometry. Results: We found that 1,25-(OH)2D3 alone (and in combination with GC) decreased the frequency of CD14++CD16+ and CD14+CD16++ monocytes from asthmatic patients and significantly diminished TNF-α production by the monocytes. With regard to the CD14+CD16++ subset, the monocyte-depleting effects of 1,25-(OH)2D3 were abrogated in the presence of pan-caspase inhibitor, suggesting a proapoptotic mechanism of 1,25-(OH)2D3 action. Interestingly, we found that a combined treatment of 1,25-(OH)2D3 and GC allowed for a 5-fold reduction of the GC dose while maintaining their anti-inflammatory effects. Conclusions: This study has revealed novel immunomodulatory properties of 1,25-(OH)2D3 directed against monocyte subsets capable of TNF-α production. In addition, our data suggest that the introduction of 1,25-(OH)2D3 to anti-inflammatory therapy would possibly allow for the use of lower doses of GC

Glucocorticoids upregulate decreased IL-7 receptor expression in asthmatic patients and simian immunodeficiency virus-infected non-human primates

Signaling through interleukin-7 receptor (IL-7R) is essential for regulation of T-cell homeostasis and survival. Previously, we and others have found diminished IL-7R levels in simian immunodeficiency virus (SIV) - infected non-human primates and human immunodeficiency virus (HIV) - infected patients. To date, it remains unknown whether changes in IL-7R expression could also be linked to non-infectious inflammatory diseases such as asthma or anti-inflammatory drug use. Here, we investigated through flow cytometry the levels of IL-7R expression on CD4+ and CD4- T-cells in asthmatic patients in relation to disease severity, immune status and glucocorticoid (GC) use. In addition, we sought to evaluate the effects of in vivo and in vitro GC treatment on IL-7R expression in both asthmatic patients and SIV-infected non-human primates. We demonstrated that expression of IL-7R on peripheral blood CD4+ T-cells was significantly decreased in clinically stable GC-naive mild and moderate asthmatic patients. Accordingly, the development of asthmatic reaction following bronchial allergen challenge performed in sensitized subjects was associated with a significant drop in levels of IL-7R on circulating CD4+ T-cells. In contrast, CD4+ T-cells from both, mild and moderate, but not severe asthmatics, treated with inhaled GC displayed levels of IL-7R similar to that seen in healthy controls. We did not find significant differences with serum or sputum interleukin-7 levels among healthy controls and GC-na\uefve and GC-treated asthmatic patients. Furthermore, both in vitro GC treatment and short-term oral GC administration to asthmatic patients resulted in a significant enhancement of IL-7R. Similarly, we demonstrated that GC-stimulated T-cells from SIV-infected non-human primates up-regulated IL-7R expression. Accordingly, experimental short-term systemic in vivo administration of GC to SIV-infected macaques led to enhancement of IL-7R expression on circulating T-cells. Our data indicate that GC bear potential to recover diminished IL-7R expression, as well in asthma as in lentiviral infection