Background Asthma with neutrophil predominance is challenging to treat with corticosteroids. Novel treatment options for asthma include those that target innate immune activity. Recent literature has indicated a significant role for IL-1β in both acute and chronic neutrophilic asthma. Objective This study used inhaled endotoxin (LPS) challenge as a model of innate immune activation to a) assess the safety of the interleukin-1 receptor antagonist, anakinra, in conjunction with inhaled LPS and b) to test the hypothesis that IL-1 blockade will suppress acute neutrophil response to challenge with inhaled LPS. Methods In a phase I clinical study, 17 healthy volunteers completed a double-blinded, placebo controlled crossover study where they received 2 daily subcutaneous doses of 1 mg/kg anakinra (maximum dose of 100 mg) or saline (placebo). One hour after the second treatment dose, subjects underwent an inhaled LPS challenge. Induced sputum was assessed for neutrophils 4 hours after inhaled LPS. The effect of anakinra compared to placebo on airway neutrophils and airway pro-inflammatory cytokines after LPS challenge was compared using a linear mixed model approach. Results Anakinra pretreatment significantly diminished airway neutrophilia compared to placebo. LPS-induced IL-1β, IL-6, and IL-8 were significantly reduced during the anakinra treatment period compared to placebo. Subjects tolerated the anakinra treatment well, without increased frequency of infections that were attributable to anakinra treatment. Conclusions Anakinra effectively reduced airway neutrophilic inflammation and resulted in no serious adverse events in a model of inhaled LPS challenge. Anakinra is a potential therapeutic candidate for treatment of asthma with neutrophil predominance in diseased populations.

Primary immunodeficiencies (PID) comprise a diverse group of clinical disorders with varied genetic defects. Paradoxically, a substantial proportion of PID patients develop autoimmune phenomena in addition to having increased susceptibility to infections from their impaired immunity. Although much of our understanding comes from data gathered through experimental models, there are several well-characterized PID that have improved our knowledge of the pathways that drive autoimmunity. The goals of this review will be to discuss these immunodeficiencies and to review the literature with respect to the proposed mechanisms for autoimmunity within each put forth to date.

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BACKGROUND:Venous thromboembolic events (VTE) are a significant cause of mortality in hospitalized medical and surgical patients. Despite recommendations and guidelines, current evidence demonstrates that VTE prophylaxis remains underutilized in at‐risk patients. The process of providing VTE prophylaxis begins with assessing each patient's VTE risk. Using an individualized, point‐based protocol in the assessment process is a complex task, and might contribute to variability in VTE prescribing behavior. There are no published data on how reliably residents can perform risk assessment and prophylaxis using a point‐based VTE risk assessment tool.OBJECTIVE:Our aim was to determine inter‐rater reliability of a point‐based risk assessment tool by residents early in the academic year.DESIGN:The design was a cross‐sectional‐cohort observational study.SETTING:The site was an academic medical center.PATIENTS:Case‐based clinical vignettes were used.INTERVENTIONS:Verbal instructions were given to medical residents about how to apply our hospital's point‐based VTE risk assessment tool.MEASUREMENTS:Interobserver agreement was measured of: 1) risk score, 2) risk‐stratification, 3) identification of contraindications, 4) VTE prophylaxis plan, and 5) resident adherence to the protocol.RESULTS:The intra‐class correlation (ICC) for the total risk score was 0.66 and the kappa coefficient for risk stratification was 0.51. The kappa scores for absolute and relative contraindications were 0.29 and 0.23, respectively. The kappa score for the VTE plan was 0.28.CONCLUSIONS:We determined that, following brief instructions early in the academic year, a point‐based VTE risk assessment tool has only fair to moderate inter‐rater reliability, with suboptimal adherence to the protocol. Both might lead to underutilization of VTE prevention strategies. Journal of Hospital Medicine 2011. © 2011 Society of Hospital Medicine.