Matricellular Protein Periostin Promotes Pericyte Migration in Fibrotic Airways

Introduction: Periostin is a matricellular protein that is currently used as a biomarker for asthma. However, its contribution to tissue remodeling in allergic asthma is currently unknown. We have previously demonstrated that tissue-resident mesenchymal stem cells known as pericytes are a key cell type involved in airway remodeling. This is thought to be caused the uncoupling of pericytes from the microvasculature supporting the large airways, facilitated by inflammatory growth factors and cytokines. It is hypothesized that periostin may be produced by profibrotic pericytes and contribute to the remodeling observed in allergic asthma.Methods: Lung sections from mice with allergic airway disease driven by exposure to house dust mite (HDM) were stained using an anti-periostin antibody to explore its involvement in fibrotic lung disease. Human pericytes were cultured in vitro and stained for periostin to assess periostin expression. Migration assays were performed using human pericytes that were pretreated with TGF-β or periostin. ELISAs were also carried out to assess periostin expression levels in bronchoalveolar lavage fluid as well as the induction of periostin production by IL-13.Results: Immunostaining indicated that pericytes robustly express periostin, with increased expression following treatment with TGF-β. Migration assays demonstrated that pericytes treated with periostin were more migratory. Periostin production was also increased in HDM exposed mice as well as in cultured pericytes treated with IL-13.Conclusion: Periostin is produced by pericytes in response to TGF-β or IL-13, and periostin plays a key role in inducing pericyte migration. The increase in periostin expression in TGF-β or IL-13 treated pericytes suggests that IL-13 may trigger periostin production in pericytes whilst TGF-β modulates periostin expression to promote pericyte migration in the context of tissue fibrosis.

A study of bronchial asthma in school going children in Southern part of Rajasthan

Background: Asthma is a chronic and common inflammatory disease involving mainly large airways of lungs. Childhood asthma is common chronic illness among school going children and is usually underdiagnosed and undertreated. The aim of the present study was to find out of the prevalence of Bronchial asthma in school going children of age group 6-12 years in southern part of Rajasthan (India), and its relation with gender, socio-economic status and heredity.Methods: A questionnaire-based study has been carried out in 1500 children of 6 to 12 years age group in four schools of Udaipur city (Rajasthan, India) with a response rate of 60.23% (904/1500).Results: The overall prevalence of asthma observed is 4.75% (43/904). The prevalence is higher among boys (5.55%) as compared to girls (3.75%). Further the prevalence is higher in upper (7.18%) and upper middle class (7.14%) children as compared to lower middle (4.84%) and upper lower class (2.01%) socioeconomic status. The children with positive family history of asthma also have higher prevalence (26.31%) of asthma.Conclusions: The prevalence of childhood asthma in Udaipur city is relatively lower and supports the already reported relation with gender, socioeconomic status and heredity.

Feasibility of an Inhalable Ultrasound Contrast Agent to Enhance Airway Imaging

Introduction: Ultrasound is a relatively inexpensive and non-ionizing imaging modality, but is under-utilized in large airway assessments due to poor image quality. No commercially available contrast agents currently exist for sonographic evaluation of the respiratory system, nor has a respiratory route of microbubble contrast agent (MCA) administration been previously described for the enhancement of airway imaging. Methods: We conducted a feasibility study to assess proof-of-concept for an inhalable ultrasound MCA composed of lipid-encapsulated decaflourobutane gas. The MCA was nebulized and administered as an aerosol through the lumen of an ex vivo porcine trachea, with image enhancement evaluated by comparing images pre- and post-exposure. Additionally, primary human bronchial epithelial (hBE) cells from three donors were differentiated at an air-liquid interface and exposed apically to 25 μL of undiluted MCA or vehicle control to assess contrast agent-induced cytotoxicity and inflammation. Basolateral medium was collected 24-hours post-exposure and lactate dehydrogenase (LDH) and interleukin-8 (IL-8) concentrations were measured as biomarkers of cytotoxicity and inflammation, respectively. Results: Contrast microbubbles remained intact following nebulization and enhanced sonographic delineation of ex vivo porcine tracheal walls, indicating adherence of the nebulized MCA to the lumenal mucosa. No significant cytotoxic or inflammatory effects were observed in cultured hBE cells following exposure to MCA. Conclusions: We present proof-of-concept for an inhaled MCA for the enhancement of sonographic evaluations of the large airways. Pending further safety and efficacy evaluations, inhaled MCA may be feasible for clinical ultrasound applications, such as enhancing ultrasound-guided tracheal intubation, detecting airway bleeds, or monitoring large airway diseases in pediatric populations.

Effects of (a Combination of) the Beta2-Adrenoceptor Agonist Indacaterol and the Muscarinic Receptor Antagonist Glycopyrrolate on Intrapulmonary Airway Constriction

Expression of bronchodilatory β2-adrenoceptors and bronchoconstrictive muscarinic M3-receptors alter with airway size. In COPD, (a combination of) β2-agonists and muscarinic M3-antagonists (anticholinergics) are used as bronchodilators. We studied whether differential receptor expression in large and small airways affects the response to β2-agonists and anticholinergics in COPD. Bronchoprotection by indacaterol (β2-agonist) and glycopyrrolate (anticholinergic) against methacholine- and EFS-induced constrictions of large and small airways was measured in guinea pig and human lung slices using video-assisted microscopy. In guinea pig lung slices, glycopyrrolate (1, 3 and 10 nM) concentration-dependently protected against methacholine- and EFS-induced constrictions, with no differences between large and small intrapulmonary airways. Indacaterol (0.01, 0.1, 1 and 10 μM) also provided concentration-dependent protection, which was greater in large airways against methacholine and in small airways against EFS. Indacaterol (10 μM) and glycopyrrolate (10 nM) normalized small airway hyperresponsiveness in COPD lung slices. Synergy of low indacaterol (10 nM) and glycopyrrolate (1 nM) concentrations was greater in LPS-challenged guinea pigs (COPD model) compared to saline-challenged controls. In conclusion, glycopyrrolate similarly protects large and small airways, whereas the protective effect of indacaterol in the small, but not the large, airways depends on the contractile stimulus used. Moreover, findings in a guinea pig model indicate that the synergistic bronchoprotective effect of indacaterol and glycopyrrolate is enhanced in COPD.