Jenna C. Podjasek

Autoimmune cytopenias in common variable immunodeficiency.

Common variable immunodeficiency (CVID) is a humoral immunodeficiency whose primary diagnostic features include hypogammaglobulinemia involving two or more immunoglobulin isotypes and impaired functional antibody responses in the majority of patients. While increased susceptibility to respiratory and other infections is a common thread that binds a large cross-section of CVID patients, the presence of autoimmune complications in this immunologically and clinically heterogeneous disorder is recognized in up to two-thirds of patients. Among the autoimmune manifestations reported in CVID (20–50%; Chapel et al., 2008; Cunningham-Rundles, 2008), autoimmune cytopenias are by far the most common occurring variably in 4–20% (Michel et al., 2004; Chapel et al., 2008) of these patients who have some form of autoimmunity. Association of autoimmune cytopenias with granulomatous disease and splenomegaly has been reported. The spectrum of autoimmune cytopenias includes thrombocytopenia, anemia, and neutropenia. While it may seem paradoxical “prima facie” that autoimmunity is present in patients with primary immune deficiencies, in reality, it could be considered two sides of the same coin, each reflecting a different but inter-connected facet of immune dysregulation. The expansion of CD21 low B cells in CVID patients with autoimmune cytopenias and other autoimmune features has also been previously reported. It has been demonstrated that this unique subset of B cells is enriched for autoreactive germline antibodies. Further, a correlation has been observed between various B cell subsets, such as class-switched memory B cells and plasmablasts, and autoimmunity in CVID. This review attempts to explore the most recent concepts and highlights, along with treatment of autoimmune hematological manifestations of CVID.

Mortality in hypereosinophilic syndrome: 19 years of experience at Mayo Clinic with a review of the literature

BACKGROUND Information in the literature regarding causes of mortality in patients with hypereosinophilic syndrome (HES) is limited. METHODS This was a retrospective review of the morbidities and causes of death in HES patients at Mayo Clinic. RESULTS Overall, out of the 247 diagnosed HES patients, 23 died during the 19 years that this review encompassed. The cause of death was identified in 15 patients (65%): cardiac dysfunction in 5 (33%), infection in 3 (20%), unrelated malignancy in 3 (20%), thromboembolic phenomena in 2 (13%), and vascular disease in 2 (13%). CONCLUSION Targeted monitoring of the at-risk end organs, combined with early treatment, may have the ability to improve survival and reduce morbidity in HES patients.

Outcomes of stepping down asthma medications in a guideline-based pediatric asthma management program

BACKGROUND Little is known about outcomes after stepping down asthma medications within an asthma management program. OBJECTIVE To determine outcomes of stepping down asthma medications in a pediatric asthma management program. METHODS We performed a retrospective study of 5- to 18-year-old children with asthma in an integrated primary care practice in the United States. Data were included on participants from March 1, 2009, until December 31, 2011. We first determined whether a child was eligible for step down and next recorded whether a step-down attempt was made and if the attempt was successful. In addition to descriptive statistics for the sample demographics and the outcomes of stepping down, univariate and multivariate analyses were performed to determine predictors of successful asthma medication step-down attempts. RESULTS Of the 477 children sampled for this study, 264 (55.3%) had a guideline-eligible opportunity to step down asthma medications. An attempted step down occurred in only 89 (33.7%) of children who had guideline-eligible opportunities. A total of 166 children (34.8%) attempted a step down of asthma medication at least once (including those guideline ineligible to step down). Of children with follow-up, 96 (71.6%) of step-down attempts were successful. Time of year (any season except fall) when the step down was attempted predicted successful step down in univariate and multivariate analysis (odds ratio = 3.81; 95% confidence interval, 1.23-11.85; P = .02). Being guideline eligible for step down predicted successful step down in univariate analysis only (odds ratio = 2.51; 95% confidence interval, 1.16-5.43; P = .02). CONCLUSION Our findings from this sample of children participating in an asthma management program suggest that stepping down asthma medication based on National Asthma Education and Prevention Program 3 guidelines is frequently successful.

Have expert guidelines made a difference in asthma outcomes

Purpose of reviewTo analyze and summarize research from 2011 to 2012 that examines the relationship of guideline implementation and asthma outcomes. Recent findingsEvidence of an unmet need for better asthma management was reported in two large survey studies from the US and Europe. Interventional studies of guideline implementation were often limited by lack of uptake of the intervention (i.e. educational program, computer-assisted assessment). Even studies in which there was uptake to the intervention, asthma outcomes often did not improve. Certain interventions (specific electronic asthma management tools, provider education workshops, community-wide interventional programs, and parental educational programs) were associated with improved asthma outcomes. Observational studies, likewise, revealed that evidence of guideline implementation did not necessarily translate into improved asthma outcomes. SummaryAsthma guideline implementation studies are frequently associated with a limited impact on asthma outcomes. Understanding the gaps between guideline recommendations and translation to clinical practice remains an important opportunity to improve asthma outcomes.

The FACT score in predicting pneumococcal antibody levels in asthmatics

Abstract Background: There is no measure currently available to identify asthmatics with potential immune incompetence. Objective: We propose use of a novel scoring system called the FACT score, which is formulated based on four parameters: (1) Family history of asthma, (2) Atopic conditions, (3) Bacterial colonization and (4) Th1 versus Th2 immune profile. Methods: This was a cross-sectional study involving 16 asthmatics and 14 non-asthmatics. The first two parameters of the FACT score were obtained via a chart review and interview. For the third parameter, nasopharyngeal swab samples were cultured. The ratio of interleukin-5 to interferon-gamma for each patient was measured by peripheral blood mononuclear cells cultured with house dust mite. Antibodies to 23 pneumococcal antigens were used for humoral immunity. Results: The FACT scores for asthmatics (mean ± SD: 5.2 ± 1.87) were higher than those for non-asthmatics (mean ± SD: 3.3 ± 1.5) (p = 0.008). Of the 16 asthmatics, 7 (44%) had 12 or more positive serotype-specific polysaccharide antibodies, whereas 12 of 14 (86%) of non-asthmatics subjects had 12 or more positive serotype-specific polysaccharide antibodies (p = 0.014). Overall, the FACT score was inversely correlated with the number of positive serotype-specific antibody levels [rho (ρ) = -0.38, p = 0.04]. The proportions of subjects with 12 or more positive serotype-specific antibodies among non-asthmatics and asthmatics below and above the median of the FACT scores were 86, 50 and 38%, respectively (p = 0.052). Conclusions: The FACT score may help us identify a subset of asthmatics with immune incompetence. Study findings need to be replicated in a larger study.