Allergen Immunotherapy in Young Children.

PURPOSE OF REVIEW: Allergen immunotherapy (AIT) has been shown to be safe and effective in children and is a unique treatment strategy that has disease-modifying and preventative effects that are not shared with other treatment options for allergic diseases. This article reviews the present knowledge and relevant updates on AIT in children. RECENT FINDINGS: Although there is no definite lower age limit for starting AIT, clear indications for AIT are established and each case should be considered individually by weighing risks and benefits. Documented short- and long-term benefits of AIT in children with allergic disease include significant improvement of symptoms and quality of life, and decreased use of medications as well as preventing the development of new allergen sensitizations and the progression of allergic rhinitis to asthma. This review provides a comprehensive overview of the present knowledge and key updates on AIT in the pediatric population.

Impact of aortic aneurysm on hospitalizations in patients with marfan syndrome: a multi-institutional study.

Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder affecting 1 in 3,000 people. Cardiovascular involvement is a prominent feature of MFS, with aortic dissection and/or rupture being the leading cause of death. Advances in the medical and surgical care of patients with MFS have improved survival. Hospital resource utilization and outcomes have not been evaluated in a large population of patients with MFS. We sought to analyze pediatric hospital resource utilization and outcomes in patients with MFS. Nationally distributed data from 43 pediatric hospitals in the 2004-2011 Pediatric Health Information System database were used to identify patients admitted to the hospital with International Classification of Diseases-9th Revision codes for a diagnosis of MFS. Aortic aneurysm (AA) with or without dissection, length of stay (LOS), and hospital charges were determined. During the study period, there were 1,978 admissions in 1,228 patients with MFS. AA was present in 217 (11%) admissions in 188 (15%) patients (63% male). Mean age of patients with AA was 13.8 ± 5.9 years. Aortic dissection or rupture was present in 15 (7% with AA) admissions in 15 (8% with AA) patients (mean age 15.7 ± 5.2 years). Other cardiac diagnoses occurred more commonly in the AA cohort (p < 0.0001), regardless of the reason for admission. Cardiothoracic surgical procedures were performed in 116 AA admissions (53%). Mean LOS, hospital charges per admission, and charges per day were significantly higher in AA cohort compared to those without AA. In-hospital mortality for AA was 2%. The presence of AA in patients with MFS increases hospital resource utilization. Cardiothoracic surgeries are commonly performed in this cohort. Other cardiovascular diagnoses are more prevalent in patients with AA suggesting a more severe phenotype.

Ventricular Hypertrophy on Electrocardiogram Correlates with Obstructive Lesion Severity in Williams Syndrome.

OBJECTIVE: Williams syndrome (WS) is a congenital, multisystem developmental disorder affecting 1 in 8000 live births. Cardiovascular abnormalities are present in 80% of WS patients. The present study sought to characterize fully the electrocardiographic findings in WS and correlate findings with anatomic pathology. DESIGN: A retrospective review was performed of the electrocardiograms (ECGs) of patients with WS evaluated at the Children's Hospital of Philadelphia from January 1, 1980 through December 31, 2007. When available, the five most recent ECGs in each patient were evaluated. Ventricular hypertrophy was diagnosed based on previously reported voltage criteria in normal populations. RESULTS: There were 187 patients with 499 ECGs for evaluation. Median age at study ECG was 8.0 years (range 0.1-58.9); median number of ECGs per patient was 2.7 (range 1-5). Heart rate, PR interval, and QRS interval were normal for age. Right ventricular hypertrophy (RVH) was present on 44% (219/499) of ECGs. Left ventricular hypertrophy (LVH) was present on 30% (150/499) of ECGs. Fifty-seven percent (106/187) of subjects had ≥1 ECG demonstrating RVH, and 39% (72/187) had ≥1 ECG demonstrating LVH. The severity of right- and left-sided obstructive lesions correlated with the ECG presence of RVH (P < .0001, odds ratio 21.8) and LVH (P < .001, odds ratio 14.5-61), respectively. CONCLUSIONS: Electrocardiographic intervals in patients with WS follow expected trends seen in normal patients. Voltage criteria for RVH and LVH are commonly met on ECGs of patients with WS. The presence of ventricular hypertrophy on ECG in WS correlates with lesion severity.

ß-Blockers and angiotensin converting enzyme inhibitors: comparison of effects on aortic growth in pediatric patients with Marfan syndrome.

OBJECTIVES: Angiotensin converting enzyme inhibitors (ACEI) have been shown to decrease aortic growth velocity (AGV) in Marfan syndrome (MFS). We sought to compare the effect of ß-blockers and ACEI on AGV in MFS. STUDY DESIGN: We retrospectively reviewed all data from all patients with MFS seen at Arkansas Children's Hospital between January 1, 1976 and January 1, 2013. Generalized least squares were used to evaluate AGV over time as a function of age, medication group, and the interaction between the 2. A mixed model was used to compare AGV between medication groups as a function of age, medication group (none, ß-blocker, ACEI), and the interaction between the 2. RESULTS: A total of 67 patients with confirmed MFS were identified (34/67, 51% female). Mean age at first encounter was 13 ± 10 years, with mean follow-up of 7.6 ± 5.8 years. There were 839 patient encounters with a median of 10 (range 2-42) encounters per patient. AGV was nearly normal in the ß-blocker group, and was less than either the ACEI or untreated groups. The AGV was higher than normal in ACEI and untreated groups (P < .001 for both). CONCLUSIONS: ß-blocker therapy results in near-normalization of AGV in MFS. ACEI did not decrease AGV in a clinically significant manner.

9-cis-retinoic Acid and troglitazone impacts cellular adhesion, proliferation, and integrin expression in K562 cells.

Retinoids are established pleiotropic regulators of both adaptive and innate immune responses. Recently, troglitazone, a PPAR gamma agonist, has been demonstrated to have anti-inflammatory effects. Separately, retinoids and troglitazone are implicated in immune related processes; however, their combinatory role in cellular adhesion and proliferation has not been well established. In this study, the effect of 9-cis-retinoic acid (9-cis-RA) and troglitazone on K562 cellular adhesion and proliferation was investigated. Troglitazone exposure decreased K562 cellular adhesion to RGD containing extracellular matrix proteins fibronectin, FN-120, and vitronectin in a concentration and time-dependent manner. In the presence of troglitazone, 9-cis-retinoic acid restores cellular adhesion to levels comparable to vehicle treatment alone on fibronectin, FN-120, and vitronectin substrates within 72 hours. Due to the prominent role of integrins in attachment to extracellular matrix proteins, we evaluated the level of integrin α5 subunit expression. Troglitazone treatment results in decrease in α5 subunit expression on the cell surface. In the presence of both agonists, cell surface α5 subunit expression was restored to levels comparable to vehicle treatment alone. Additionally, troglitazone and 9-cis-RA mediated cell adhesion was decreased in the presence of a function blocking integrin alpha 5 inhibitor. Further, through retinoid metabolic profiling and HPLC analysis, our study demonstrates that troglitazone augments retinoid availability in K562 cells. Finally, we demonstrate that troglitazone and 9-cis-retinoic acid synergistically dampen cellular proliferation in K562 cells. Our study is the first to report that the combination of troglitazone and 9-cis-retinoic acid restores cellular adhesion, alters retinoid availability, impacts integrin expression, and dampens cellular proliferation in K562 cells.