Peptides as surface coatings of nanoparticles that penetrate human cystic fibrosis sputum and uniformly distribute in vivo following pulmonary delivery.

Therapeutic delivery of drug and gene delivery systems have to traverse multiple biological barriers to achieve efficacy. Mucosal administration, such as pulmonary delivery in cystic fibrosis (CF) disease, remains a significant challenge due to concentrated viscoelastic mucus, which prevents drugs and particles from penetrating the mucus barrier. To address this problem, we used combinatorial peptide-presenting phage libraries and next-generation sequencing (NGS) to identify hydrophilic, net-neutral charged peptide coatings that enable penetration through human CF mucus ex vivo with ~600-fold better penetration than control, improve uptake into lung epithelial cells compared to uncoated or PEGylated-nanoparticles, and exhibit enhanced uniform distribution and retention in the mouse lung airways. These peptide coatings address multiple delivery barriers and effectively serve as excellent alternatives to standard PEG surface chemistries to achieve mucus penetration and address some of the challenges encountered using these chemistries. This biomolecule-based strategy can address multiple delivery barriers and hold promise to advance efficacy of therapeutics for diseases like CF.

Feasibility study of a combined lifestyle behaviors and asthma self-management intervention for school-aged children.

PURPOSE: The purpose of this study is to test the feasibility of delivering an intervention that combines healthy lifestyle behaviors related to weight management with asthma self-management, the Living Healthy with Asthma intervention, to children who have asthma. METHODS AND DESIGN: Using a mixed design, the feasibility study of the 12-week Living Healthy with Asthma intervention was conducted with a single group of children diagnosed with asthma. Pretest and posttest data were collected on asthma-related (self-management, metered dose inhaler [MDI] skill, asthma severity, quality of life [QOL]), and healthy lifestyle variables (body mass index [BMI], dietary quality). A matched comparison sample was drawn from a separate study that tested the same asthma self-management component (single intervention) used in the feasibility study to determine if the Living Healthy with Asthma intervention worked as well as the single intervention for improving children's asthma self-management. RESULTS: Thirteen school-aged children were enrolled in the feasibility study. There were significant reductions in BMI z-scores (P = 0.007), and improvements in vegetable servings (P = 0.03), MDI skill (P = 0.005), children's QOL (P < 0.001), and parents' QOL (P = 0.03). When comparing the feasibility group with the matched comparison group (n = 13), there were no significant differences in asthma self-management, MDI skill, or asthma severity after the interventions. PRACTICE IMPLICATIONS: Findings supported the feasibility of implementing the combined intervention, and it was not inferior to the single intervention-which supports nurses' efforts to help families manage multiple health problems.

Hospitalizations Due to Respiratory Syncytial Virus Outside of the Typical Season.

Objective: Respiratory Syncytial Virus (RSV) is the most common cause of bronchiolitis and viral lower respiratory tract infections in children. It is associated with annual winter epidemics across the United States, typically October through April. Our objective is to describe the clinical characteristics of children hospitalized outside the typical RSV season and to compare them with those admitted during the season. Methods: A retrospective chart review was conducted of all patients who were hospitalized at Children's Hospital of Austin from May 2000 to September 2006 and had a positive RSV antigen test. Descriptive statistics, tests of differences, and associations between patients diagnosed in the off-season versus typical season were conducted. Results: A total of 850 charts of RSV-positive cases were reviewed. Of these, 45 patients (5.3%) were admitted during the off-season. The following variables were statistically significantly associated with diagnosis in the off-season versus typical season: mean birth weight (2704 g vs. 3204 g respectively, p=0.0001); gestational age at birth less than 36 weeks (OR=4.35; 95% CI: 2.2, 8.6); history of neonatal intensive care unit (NICU) admission at birth (OR=6.04; 95% CI: 2.9, 12.5); and multiple birth (OR=3.38; 95% CI: 1.2, 9.2). Conclusions: Infants with RSV infection outside of the typical season were more likely to have been premature, of lower birth weight, the products of multiple births, and admitted to the NICU at birth.

Comparison of two methods of delivering continuously nebulized albuterol.

OBJECTIVE: To compare the relative delivery of 2 methods for providing continuously nebulized albuterol (CNA): a small-volume nebulizer plus infusion pump versus a large-volume nebulizer. DESIGN: An open, randomized comparison of 3 hours of CNA administration using an in vitro lung model with a follow-up particle size assessment of the large-volume nebulizer. METHODS: Six different nebulizers of each type were connected to a lung model via a volume-limited mechanical ventilator and infant ventilator circuitry. Albuterol was nebulized at 10 mg/h for 3 hours in random order. The small-volume nebulizer used was the Airlife Misty Neb (Baxter, Valencia, CA); the large-volume nebulizer was the HEART Nebulizer (Vortran Medical, Orangevale, CA). One large-volume nebulizer was operated over 8 hours for the output and particle sizing study. RESULTS: The small-volume nebulizer delivered a greater amount of albuterol (mean +/- SD percentage of total nebulized) to the model lung (5.75 +/- 1.38% vs. 4.12 +/- 0.67%; p < 0.025) than the large-volume nebulizer, but demonstrated greater variability. Although total output was not maintained after 8 hours of nebulization with the large-volume nebulizer, the percent of particles in the respirable range remained consistent. CONCLUSIONS: The large-volume nebulizer evaluated in this study maintains consistent output up to 8 hours and provides an acceptable method for delivering CNA through an infant ventilator circuit.

Growth and bone density in children with mild-moderate asthma: a cross-sectional study in children entering the Childhood Asthma Management Program (CAMP).

OBJECTIVES: We sought to determine whether mild-moderate persistent asthma sufficient to produce a decrease in baseline lung function is associated with an adverse effect on growth and bone mineral density (BMD) in children. METHODS: This was a cross-sectional study of 1041 children, 5 to 12 years old (32% ethnic/racial minorities and 40% female), enrolled into the Childhood Asthma Management Program (CAMP). Measures of asthma severity included: Spirometry; bronchial hyperresponsiveness; duration of asthma symptoms; and symptom-based assessment of severity. Multiple regression analyses were used to relate the asthma severity on the primary outcome variables: Height by stadiometry and BMD by dual energy radiographic absorptiometry. RESULTS: The mean +/- SD height percentile was 56.0 +/- 28.5 percentile for the population. The only significant relationship between asthma severity and height percentile was with methacholine bronchoprovocation in girls (beta 2.98, P =.019, covariate multiple regression). The mean +/- SD BMD was 0.65 +/- 0.10 g/cm(2) for the population. The past use of corticosteroids did not adversely affect either growth or BMD. CONCLUSIONS: We found that mild-moderate asthma of as long as 4 to 7 years duration in children does not produce an adverse effect on linear growth or BMD.