Update on Biomarkers of Vasculopathy in Juvenile and Adult Myositis.

PURPOSE OF REVIEW: Although rare, idiopathic inflammatory myopathies (IIM) comprise a heterogeneous group of autoimmune conditions in adults and children. Increasingly, vasculopathy is recognised to be key in the underlying pathophysiology and plays a crucial role in some of the more challenging complications including calcinosis, gastrointestinal involvement and interstitial lung disease. The exciting prospect of development of biomarkers of vasculopathy would enable earlier detection and monitoring of these complications and possible prevention of their potentially devastating consequences. The purpose was to review the current literature on biomarkers of vasculopathy in IIM and offer insight as to the biomarkers most likely to have an impact on clinical care. RECENT FINDINGS: Multiple candidate biomarkers have been studied including circulating endothelial cells (CEC), microparticles (MP), soluble adhesion markers (ICAM-1, ICAM-3, VCAM-1), selectin proteins (E-, L-, P-selectin), coagulation factors, angiogenic factors, cytokines (including (IL-6, IL-10, TNF-α, IL-18) and interferon (IFN)-related biomarkers (including IFNα, IFN-ß, IFNγ, galectin-9, interferon signature and interferon-related chemokines (MCP-1, IP-10 and MIG). There is a growing body of evidence of the potential role of biomarkers in detecting and monitoring the vasculopathy in IIM, detecting disease activity and predicting disease flares and overall prognosis. Exciting progress has been made in the search for biomarkers of vasculopathy of IIM; however, none of the studies are validated and further research is required.

Primary airway epithelial cell culture and asthma in children-lessons learnt and yet to come.

Until recently the airway epithelial cell (AEC) was considered a simple barrier that prevented entry of inhaled matter into the lung parenchyma. The AEC is now recognized as having an important role in the inflammatory response of the respiratory system to inhaled exposures, and abnormalities of these responses are thought to be important to asthma pathogenesis. This review first explores how the challenges of studying nasal and bronchial AECs in children have been addressed and then summarizes the results of studies of primary AEC function in children with and without asthma. There is good evidence that nasal AECs may be a suitable surrogate for the study of certain aspects of bronchial AEC function, although bronchial AECs remain the gold standard for asthma research. There are consistent differences between children with and without asthma for nasal and bronchial AEC mediator release following exposure to a range of pro-inflammatory stimulants including interleukins (IL)-1ß, IL-4, and IL-13. However, there are inconsistencies between studies, e.g., release of IL-6, an important pro-inflammatory cytokine, is not increased in children with asthma relative to controls in all studies. Future work should expand current understanding of the "upstream" signalling pathways in AEC, study AEC from children before the onset of asthma symptoms and in vitro models should be developed that replicate the in vivo status more completely, e.g., co-culture with dendritic cells. AECs are difficult to obtain from children and collaboration between centers is expected to yield meaningful advances in asthma understanding and ultimately help deliver novel therapies.

Chest auscultatory signs in infants presenting to A&E with bronchiolitis.

BACKGROUND: Anecdotally it has been noted that the traditional chest signs associated with bronchiolitis appear inconsistently in infants clinically diagnosed with bronchiolitis. We wished to explore this more formally. OBJECTIVE: The aim of this study was to assess whether the auscultatory chest signs at presentation in infants with bronchiolitis were influenced by age or by the underlying pathogen. MATERIALS AND METHODS: We conducted a prospective opportunistic cohort study, recruiting infants less than 12 months old who presented with bronchiolitis to the Emergency Department of the Royal Hospital for Sick Children in Edinburgh. RESULTS: Eighty-six infants were recruited. Infants who presented with wheeze were significantly older [26.6 (±1.9) weeks] than those without wheeze [17.3 (±2.1) weeks] (analysis of variance, P=0.002). Those who presented without any chest signs on auscultation were younger than those with chest signs [15.1 (±2.6) weeks compared with 24.4 (±1.7) weeks] (analysis of variance, P=0.006). We did not detect any difference in any of the auscultatory chest signs (crackles, wheeze or absence of signs) depending on the virus responsible for bronchiolitis. CONCLUSION: Clinical signs associated with bronchiolitis vary according to age. Infants older than 6 months are more likely to present with wheeze and infants less than 4 months old are likely to present without chest signs on auscultation.