A Survey of Cystic Fibrosis Center Recommendations for Nebulizer Cleaning and Disinfection.

Background: Despite advancements in cystic fibrosis (CF) therapeutics, the persistence of chronic infections necessitates continued use of nebulized therapies. Though the Cystic Fibrosis Foundation recommends well-defined cleaning and disinfection of nebulizers to mitigate pathogen exposure risks, discrepancies between Cystic Fibrosis Foundation guidelines, manufacturers' instructions, and variability in center recommendations contribute to confusion and non-standardized practices.

Methods: A digital survey was distributed to directors, associate directors, and care coordinators of CF centers across the United States to investigate the methods, frequency, and educational practices surrounding nebulizer care they provide patients.

An adolescent with Wolfram syndrome and central sleep apnea.

Unlabelled: Wolfram syndrome is a rare autosomal recessive disorder affecting approximately 1 in 500,000 individuals. The disorder is most commonly caused by mutations in the gene, which encodes an endoplasmic reticulum protein, wolframin, which is thought to protect against endoplasmic reticulum stress-related apoptosis. The major clinical findings of Wolfram syndrome are diabetes mellitus and optic atrophy, both of which usually appear before 16 years of age.

Bacterial Surface Detachment during Nebulization with Contaminated Reusable Home Nebulizers.

Patients with chronic respiratory diseases use home nebulizers that are often contaminated with pathogenic microbes to deliver aerosolized medications. The conditions under which these microbes leave the surface as bioaerosols during nebulization are not well characterized. The objectives of this study were to (i) determine whether different pathogens detach and disperse from the nebulizer surface during aerosolization and (ii) measure the effects of relative humidity and drying times on bacterial surface detachment and aerosolization.

Two vs four puffs of albuterol: does dose change bronchodilator response?

Background: Reversible obstruction on spirometry may be used to diagnose asthma. As per 2005 American Thoracic Society (ATS) guidelines, our pulmonary center began using 360 µg (four puffs) of albuterol rather than 180 µg (two puffs) to determine reversibility on spirometry starting in 2009.

Hypothesis: We hypothesized that fewer patients would respond to two puffs of albuterol than four puffs during spirometric testing.

Repeated hot water and steam disinfection of Pari LC Plus® nebulizers alter nebulizer output.

Currently, cystic fibrosis patients require daily nebulized treatments to achieve optimal lung health. Growth of pathogenic bacteria in patient nebulizers is well known, and disinfection guidelines have been established. In this short communication, we sought to discover what effect, if any, repeated nebulization/disinfection cycles had on nebulizer output.

Early-life antibiotics attenuate regulatory T cell generation and increase the severity of murine house dust mite-induced asthma.

Introduction: Early-life exposure to antibiotics (ABX) has been linked to increases in asthma severity and prevalence in both children and laboratory animals. We explored the immunologic mechanisms behind this association using a mouse model of house dust mite (HDM)-induced asthma and early-life ABX exposure.

Methods: Mice were exposed to three short courses of ABX following weaning and experimental asthma was thereafter induced.

Regulation of IgE activity in inhalational tolerance via formation of IgG anti-IgE/IgE immune complexes.

Background: Allergic asthma is an inflammatory disorder of the airways that results from inappropriate production of IgE against harmless, environmental antigens. Sequestration of free IgE using humanized IgG anti-IgE is an effective therapy for asthma and other atopic disorders. However, the status of free IgE in subjects who have naturally developed immune tolerance to inhaled antigens has not been well studied.

Clinical Examination Does Not Predict Response to Albuterol in Ventilated Infants With Bronchiolitis.

Objective: Bronchiolitis is a common respiratory infection in infants that is sometimes treated with albuterol. Response to albuterol is determined by clinical assessment, but this subjective determination is potentially unreliable. In this study, we compared providers' clinical assessment of response to albuterol with the measurement of response by pulmonary mechanics in intubated, sedated, and ventilated infants.

An evaluation strategy for potential QTc prolongation with chronic azithromycin therapy in cystic fibrosis.

Chronic azithromycin therapy is recommended for CF patients with persistent Pseudomonas aeruginosa colonization. Other macrolide antibiotics have been reported to cause QT prolongation, but cardiac effects of azithromycin have not been studied in pediatric populations. We analyzed changes in QTc interval after starting chronic azithromycin in a pediatric CF population.

Cbl-b Deficiency in Mice Results in Exacerbation of Acute and Chronic Stages of Allergic Asthma.

Mice sensitized to ovalbumin (OVA) develop allergic airway disease (AAD) with short-term daily OVA aerosol challenge; inflammation resolves with long-term OVA aerosol exposure, resulting in local inhalational tolerance (LIT). Cbl-b is an E3 ubiquitin ligase involved with CD28 signaling; Cbl-b(-/-) effector T cells are resistant to regulatory T cell-mediated suppression in vitro and in vivo. The present study utilized Cbl-b(-/-) mice to investigate the role of Cbl-b in the development of AAD and LIT.

Long-Term Exposure to House Dust Mite Leads to the Suppression of Allergic Airway Disease Despite Persistent Lung Inflammation.

Background: Allergic asthma is a major cause of worldwide morbidity and results from inadequate immune regulation in response to innocuous, environmental antigens. The need exists to understand the mechanisms that promote nonreactivity to human-relevant allergens such as house dust mite (HDM) in order to develop curative therapies for asthma. The aim of our study was to compare the effects of short-, intermediate- and long-term HDM administration in a murine asthma model and determine the ability of long-term HDM exposure to suppress allergic inflammation.

Regulatory B cells in allergic airways disease and asthma.

B cells have long been known to participate in both innate and adaptive immune responses by contributing to antigen presentation and by producing antigen-specific antibodies. Recent evidence shows that certain B-cell subsets can also inhibit T-cell immune responses. Like regulatory T cells (Treg), these regulatory B cells (Breg) appear to comprise several subpopulations.

Transient occult cardiotoxicity in children receiving continuous beta-agonist therapy.

Background: Continuous beta-agonist therapy, typically in the form of inhaled albuterol, is the first line therapy for the treatment of acute and severe bronchospasm in children. Although this treatment is commonly used, concerns about cardiotoxicity have been raised. We aimed to investigate the cardiotoxic effects of continuous beta-agonist therapy in children.

Bromelain Inhibits Allergic Sensitization and Murine Asthma via Modulation of Dendritic Cells.

The incidence of atopic conditions has increased in industrialized countries. Persisting symptoms and concern for drug side-effects lead patients toward adjunctive treatments such as phytotherapy. Previously, we have shown that Bromelain (sBr), a mixture of cysteine proteases from pineapple, Ananas comosus, inhibits ovalbumin (OVA)-induced murine model of allergic airway disease (AAD).

Bromelain limits airway inflammation in an ovalbumin-induced murine model of established asthma.

Context: Allergic asthma continues to increase despite new pharmacological advances for both acute treatment and chronic-disease management. Asthma is a multifactorial disease process with genetic, allergic, infectious, environmental, and dietary origins. Researchers are investigating the benefits of lifestyle changes and alternative asthma treatments, including the ability of bromelain to inhibit inflammation.

β2-adrenergic receptor haplotype linked to intubation and mechanical ventilation in children with asthma.

Background And Aims: Children with asthma and respiratory failure comprise a small but significant subset of children with acute asthma. In addition to clinical and historical factors that have been associated with respiratory failure, there may also be genetic factors that predispose some asthmatic children to intubation and mechanical ventilation. However, this has not previously been assessed in this population.

Pulmonary mechanics following albuterol therapy in mechanically ventilated infants with bronchiolitis.

Background And Aims: Bronchiolitis is a common cause of critical illness in infants. Inhaled β(2)-agonist bronchodilators are frequently used as part of treatment, despite unproven effectiveness. The purpose of this study was to describe the physiologic response to these medications in infants intubated and mechanically ventilated for bronchiolitis.

Phenotypic changes to the endogenous antigen-specific CD8+ T cell response correlates with the development and resolution of allergic airway disease.

The role of CD8(+) T cells in the pathogenesis of asthma remains controversial, as both pro- and anti-inflammatory functions have been suggested. This study was designed to examine the endogenous CD8(+) T cell response in a biphasic ovalbumin (OVA)-induced model of allergic airway disease (AAD) and its subsequent resolution with the development of local inhalational tolerance (LIT). We observed increases in OVA-specific CD8(+) T cell numbers in the local lung compartments (bronchoalveolar lavage, lung tissue, hilar lymph node) at AAD and LIT; systemic compartments (spleen, inguinal lymph node) displayed no such increases in CD8(+) T cell numbers.

Clinical features cannot distinguish allergic from non-allergic asthma in children.

Objective: Environmental allergens are a major trigger of asthma, but not all asthmatics are allergic. This study was designed to review clinical characteristics in children with allergic and non-allergic asthma, based on responsiveness to allergy skin tests, in order to identify a combination of features that could distinguish allergic from non-allergic asthma in children.

Methods: Medical records of 321 children who had allergy skin testing were reviewed, and demographic and clinical data were compared between allergic and non-allergic patients.

Beta-adrenergic receptor polymorphisms associated with length of ICU stay in pediatric status asthmaticus.

Background: During severe exacerbations, asthmatic children vary significantly in their response to high-dose continuous β(2) -adrenergic receptor (ADRβ(2) ) agonist therapy. Genetic polymorphisms have been identified within the ADRβ(2) that may be functionally relevant, but few studies have been performed in this population. Our hypothesis was that genotypic differences are associated with magnitude of response to ADRβ(2) agonist treatment during severe asthma exacerbations in children.

Factors associated with the development of severe asthma exacerbations in children.

Background: Asthma exacerbations are one of the most common causes of hospitalization in children and account for approximately 10,000 intensive care unit (ICU) admissions per year in the United States. Despite the prevalence of this disease in children, the factors associated with the development of these severe exacerbations are largely unknown.

Methods: A retrospective case-control study was conducted involving all eligible children admitted to the hospital with asthma for a 1-year period.

Identifying an at-risk population of children with recurrent near-fatal asthma exacerbations.

Background: Children are frequently admitted to hospitals for treatment of severe asthma exacerbations. Anecdotally, a cohort of these children are thought to have multiple readmissions to the intensive care unit (ICU), yet this group of children has not been characterized. The purpose of this study was to examine the factors related to recurrent ICU admissions in children with asthma.

Advances in treating acute asthma exacerbations in children.

Purpose Of Review: Asthma continues to be a major chronic disease in children, and acute asthma exacerbations are common. Although the basic therapy of asthma exacerbations has not changed, recent studies have demonstrated improved outcomes with different modes of delivery of medications, improved patients' self-management of their asthma, and recognition of risk factors for severe exacerbations.

Recent Findings: Recent studies in children have shown that written action plans based on symptom recognition are more effective than action plans based on peak expiratory flows.

Beta2-adrenergic receptor polymorphisms affect response to treatment in children with severe asthma exacerbations.

Background: beta(2)-adrenergic receptor (AR) agonists are the mainstay of treatment for severe asthma exacerbations, one of the most common causes of critical illness in children. Genotypic differences in the beta(2)-AR gene, particularly at amino acid positions 16 and 27, have been shown to affect the response to beta(2)-AR agonist therapy. Our hypothesis is that genotypic differences contribute to patient response to beta(2)-AR agonist treatment during severe asthma exacerbations in children.

Severe exacerbations in children with mild asthma: characterizing a pediatric phenotype.

Background: NHLBI guidelines classify asthma in children as intermittent, mild persistent, moderate persistent, and severe persistent asthma based on baseline symptoms and pulmonary function. However, this may not capture the spectrum of asthma in children, since even mild baseline disease can have significant effects on quality of life. Our objective was to describe a population of children with mild asthma admitted to the ICU with severe exacerbations.