The accumulation of evidence implicating a role for adenosine in the pathogenesis of asthma has led to investigations into all adenosine receptor subtypes as potential therapeutic targets for the treatment of asthma. Selective A 1 receptor antagonists are currently in preclinical development since adenosine has been shown experimentally to mediate various features of asthma through this receptor such as bronchoconstriction, mucus secretion and inflammation. The A 2A receptor is expressed on most inflammatory cells implicated in asthma, and as A 2A stimulation activates adenylate cyclase and consequently elevates cAMP, selective A 2A receptor agonists have now reached clinical development. However, initial reports concerning their efficacy are inconclusive. A 2B receptor antagonists are also under investigation based on the rationale that inhibiting the effects of adenosine on mast cells would be beneficial, in addition to other reported pro-inflammatory effects mediated by the A 2B receptor on cells such as airway smooth muscle, epithelial cells and fibroblasts. Whilst the effects in pre-clinical models are promising, their efficacy in the clinical setting has also yet to be reported. Finally, adenosine A 3 receptor stimulation has been demonstrated to mediate inhibitory effects on eosinophils since it also elevates cAMP. However, some experimental reports suggest that A 3 antagonists mediate anti-inflammatory effects, thus the rationale for A 3 receptor ligands as therapeutic agents remains to be determined. In conclusion, establishing the precise role of adenosine in the pathogenesis of asthma and developing appropriate subtype selective agonists/antagonists represents an exciting opportunity for the development of novel therapeutics for the treatment of asthma.

Objectives Systemic juvenile idiopathic arthritis (sJIA) is a childhood arthritis with features of autoinflammation and high risk of macrophage activation syndrome (MAS). IL-18 has been shown to have key roles in sJIA and MAS. We aimed to examine IL-18 levels in sJIA in relation to disease activity and history of MAS and other disease biomarkers namely S100 proteins and CXCL9. Methods Total IL-18, CXCL9 and S100 proteins levels were determined in 40 sJIA patients, and IL-18 levels were compared between patients with regards to disease activity, history of MAS, and other biomarkers. Results Total IL-18 levels were significantly higher in patients with active sJIA (median 16 499 pg/ml; interquartile range (IQR) 4816–61 839), and remained persistently elevated even in the majority of patients with inactive disease (1164 pg/ml; IQR 587–3444). Patients with history of MAS had significantly higher IL-18 levels (13 380 pg/ml; IQR 4212–62 628) as compared with those without MAS history (956.5 pg/ml; IQR 276.3–4262.5). Total IL-18 performed well with area under the curve of 0.8145 and 0.84 in predicting disease activity and history of MAS, respectively. We observed moderate correlation between IL-18 and CXCL9 (R = 0.56), S100A8/A9 (R = 0.47) and S100A12 (R = 0.46). The correlation was stronger for ferritin (R = 0.74) and overall for those with active disease. Conclusion Total IL-18 levels were elevated in the majority of sJIA patients regardless of clinical features, but were higher in patients with active disease and history of MAS. Change in IL-18 may reflect increased disease activity or development of MAS.

Optimizing the timing and safety for the placement of a tracheostomy in infants with bronchopulmonary dysplasia (BPD) has not been determined. The purpose of the present study was to describe the data from a single institution about the efficacy and safety of tracheostomy placement in infants with BPD needing long-term respiratory support. We established a service line for the comprehensive care of infants with BPD and we collected retrospective clinical data from this service line. We identified patients that had a trachostomy placed using the local Vermont-Oxford database, and obtained clinical data from chart reviews. We identified infants who had a tracheostomy placed for the indication of severe BPD only. Safety and respiratory efficacy was assessed by overall survival to discharge and the change in respiratory supportive care from just before placement to 1-month post-placement. Twenty-two patients (750 ± 236 g, 25.4 ± 2.1 weeks gestation) had a tracheostomy placed on day of life 177 ± 74 which coincided with a post-conceptual age of 51 ± 10 weeks. At placement these infants were on high settings to support their lung disease. The mean airway pressure (MAP) was 14.3 ± 3.3 cmH(2) O, the peak inspiratory pressure was 43.7 ± 8.0 cmH(2) O, and the FiO(2) was 0.51 ± 0.13. The mean respiratory severity score (MAP × FiO(2) ) 1 month after tracheostomy was significantly (P = 0.03) lower than prior to tracheostomy. Survival to hospital discharge was 77%. All patients with tracheostomies that survived were discharged home on mist collar supplemental oxygen. In conclusion, the high survival rate in these patients with severe BPD and the decreased respiratory support after placement of a tracheostomy suggests that high ventilatory pressures should not be a deterrent for placement of a tracheostomy. Future research should be aimed at determining optimal patient selection and timing for tracheostomy placement in infants with severe BPD.

Organisms within the Hardjo serovar of Leptospira species are harbored in cattle throughout the world, causing abortion in pregnant animals as well as being shed in the urine, thereby providing sources of zoonotic infection for humans. We recently showed that sterile immunity in vaccinated cattle is associated with induction of a type 1 (Th1) cell-mediated immune response. Here naïve and previously vaccinated pregnant cattle were challenged with a virulent strain of serovar Hardjo and subsequently evaluated for expression of a type 1 immune response. Lymphocytes that responded in a recall response to antigen by undergoing blast transformation were evident in cultures of peripheral blood mononuclear cells (PBMC) from vaccinated cattle throughout the postchallenge test period while those from naïve cattle were evident at one time point only. Nevertheless, beginning at 2 weeks after challenge, gamma interferon (IFN-␥) was measured in supernatants of antigen-stimulated PBMC cultures from nonvaccinated animals although the amount produced was always less than that in cultures of PBMC from vaccinated animals. IFN-␥ ؉ cells were also evident in antigenstimulated cultures of PBMC from vaccinated but not from nonvaccinated animals throughout the postchallenge period. The IFN-␥ ؉ cells included CD4 ؉ and WC1 ؉ ␥␦ T cells, and a similar proportion of these two subpopulations were found among the dividing cells in antigen-stimulated cultures as ascertained by carboxyfluorescein succinimidyl ester loading. Finally, while naïve and vaccinated animals had similar levels of antigen-specific immunoglobulin G1 (IgG1) following challenge, vaccinated animals had twofold-more IgG2. In conclusion, while infection may induce a type 1 response we suggest that it is too weak to prevent establishment of chronic infection.