Key inflammatory markers in bronchoalveolar lavage predict bronchiectasis progression in young children with CF.

Introduction: Inflammation appears early in cystic fibrosis (CF) pathogenesis, with specific elevated inflammatory markers in bronchoalveolar lavage fluid (BALF) correlating with structural lung disease. Our aim was to identify markers of airway inflammation able to predict bronchiectasis progression over two years with high sensitivity and specificity.

Methods: Children with CF with two chest computed tomography (CT) scans and bronchoscopies at a two-year interval were included (n= 10 at 1 and 3 years and n= 27 at 3 and 5 years).

Nasal airway inflammatory responses and pathogen detection in infants with cystic fibrosis.

Background: Detecting airway inflammation non-invasively in infants with cystic fibrosis (CF) is difficult. We hypothesized that markers of inflammation in CF [IL-1β, IL-6, IL-8, IL-10, IL-17A, neutrophil elastase (NE) and tumor necrosis factor (TNF-α)] could be measured in infants with CF from nasal fluid and would be elevated during viral infections or clinician-defined pulmonary exacerbations (PEx).

Methods: We collected nasal fluid, nasal swabs, and hair samples from 34 infants with CF during monthly clinic visits, sick visits, and hospitalizations.

Pulmonary exacerbations in early cystic fibrosis lung disease are marked by strong modulation of CD3 and PD-1 on luminal T cells.

Background: In chronic cystic fibrosis (CF) lung disease, neutrophilic inflammation and T-cell inhibition occur concomitantly, partly due to neutrophil-mediated release of the T-cell inhibitory enzyme Arg1. However, the onset of this tonic inhibition of T cells, and the impact of pulmonary exacerbations (PEs) on this process, remain unknown.

Methods: Children with CF aged 0-5 years were enrolled in a longitudinal, single-center cohort study.

Diagnostic challenges in CFTR-related metabolic syndrome: Where the guidelines fall short.

Newborn screening (NBS) for cystic fibrosis (CF) has enabled earlier diagnosis and has improved nutritional and growth-related outcomes in children with CF. For those with a positive NBS for CF that do not meet the diagnostic criteria for CF, the clinical entity called CFTR-Related Metabolic Syndrome (CRMS) or CF Screen- Positive, Inconclusive Diagnosis (CFSPID) is used. Although most children with CRMS remain relatively asymptomatic, studies have shown that between 11% and 48% of these patients may eventually progress to a diagnosis of CF over time.

Cryoextraction via flexible bronchoscopy in children with tracheobronchial obstruction.

Background: Cryoextraction via flexible bronchoscopy (FB) can be used to alleviate airway obstruction due to blood clots, casts, mucus, and foreign bodies. There is limited literature regarding the utility of cryoextraction to restore airway patency in critically ill children, especially on extracorporeal membrane oxygenation (ECMO). The aims of this study were to describe the clinical course and outcomes of children who underwent cryoextraction via FB.

Sweat induction using Pilocarpine microneedle patches for sweat testing in healthy adults.

Background: The sweat test using pilocarpine iontophoresis remains the gold standard for diagnosing cystic fibrosis, but access and reliability are limited by specialized equipment and insufficient sweat volume collected from infants and young children. These shortcomings lead to delayed diagnosis, limited point-of-care applications, and inadequate monitoring capabilities.

Methods: We created a skin patch with dissolvable microneedles (MNs) containing pilocarpine that eliminates the equipment and complexity of iontophoresis.

Clinical Features of COVID-19 in Patients with Congenital Central Hypoventilation Syndrome.

The clinical course of COVID-19 in patients with congenital central hypoventilation syndrome (CCHS) is unknown. We conducted a cross-sectional questionnaire study in 43 patients with CCHS who had COVID-19. The median age of patients was 11 [interquartile range (IQR) 6-22] years and 53.

Impact of viral respiratory infections on pulmonary exacerbations in children with cystic fibrosis.

Background: Viral respiratory infections trigger pulmonary exacerbations (PEs) in children with cystic fibrosis (CF), but their clinical impact is not well understood.

Methods: A retrospective review of pediatric patients with CF who underwent nasopharyngeal respiratory viral panel testing during hospitalization for a PE between 2011 and 2018 was conducted. Patients were dichotomized into viral-positive and viral-negative groups.

Macrophage PD-1 associates with neutrophilia and reduced bacterial killing in early cystic fibrosis airway disease.

Background: Macrophages are the major resident immune cells in human airways coordinating responses to infection and injury. In cystic fibrosis (CF), neutrophils are recruited to the airways shortly after birth, and actively exocytose damaging enzymes prior to chronic infection, suggesting a potential defect in macrophage immunomodulatory function. Signaling through the exhaustion marker programmed death protein 1 (PD-1) controls macrophage function in cancer, sepsis, and airway infection.

Pilot study of inflammatory biomarkers in matched induced sputum and bronchoalveolar lavage of 2-year-olds with cystic fibrosis.

Background: In this pilot study, we investigated whether induced sputum (IS) could serve as a viable alternative to bronchoalveolar lavage (BAL) and yield robust inflammatory biomarkers in toddlers with cystic fibrosis (CF) featuring minimal structural lung disease.

Methods: We collected IS, BAL (right middle lobe and lingula), and blood, and performed chest computed tomography (CT) scans from 2-year-olds with CF (N = 11), all within a single visit. Inflammatory biomarkers included 20 soluble immune mediators and neutrophil elastase (NE), as well as frequency and phenotype of T cells, monocytes/macrophages, and neutrophils.

Access and Utilization of Asthma Medications Among Patients Who Receive Care in Federally Qualified Health Centers.

Objectives: To describe access to and use of prescription asthma medications, and to assess factors associated with asthma exacerbation, healthcare utilization, and health status among asthma patients treated at Federally Qualified Health Centers.

Methods: This is a retrospective cross-sectional study. We analyzed data from the 2014 National Health Center Patient Survey.

Impaired ventilation during 6-min walk test in congenital central hypoventilation syndrome.

Background: Patients with congenital central hypoventilation syndrome (CCHS) can develop hypoxemia and hypercapnia during exercise. However, there is limited literature on cardiorespiratory responses during submaximal exercise and their correlation with paired-like homeobox 2B (PHOX2B) genotype.

Objectives: To assess oxygen saturation (SpO ), end-tidal carbon dioxide (ETCO ), heart rate (HR), and 6-min walk distance (6MWD) during a 6-min walk test (6MWT) in CCHS subjects and to correlate them with PHOX2B genotypes and assisted ventilation (AV) via tracheostomy.

Administration of pilocarpine by microneedle patch as a novel method for cystic fibrosis sweat testing.

The sweat test is the gold standard for the diagnosis of cystic fibrosis (CF). The test utilizes iontophoresis to administer pilocarpine to the skin to induce sweating for measurement of chloride concentration in sweat. However, the sweat test procedure needs to be conducted in an accredited lab with dedicated instrumentation, and it can lead to inadequate sweat samples being collected in newborn babies and young children due to variable sweat production with pilocarpine iontophoresis.

Bronchoscopic interventions for plastic bronchitis in children without structural heart disease.

Plastic bronchitis (PB) is a rare and life-threatening complication encountered in several disease states that leads to airway obstruction by branching casts. PB is most often reported in children with cyanotic congenital heart disease where recurrence is common, and mortality is high. There is limited data on optimal management strategies or recurrence of non-structural heart disease-related PB in children.

Variable phenotypes in congenital central hypoventilation syndrome with nonpolyalanine repeat mutations.

Study Objectives: Congenital central hypoventilation syndrome (CCHS) is a rare disorder affecting the autonomic nervous system that is caused by variants in the paired-like homeobox 2B () gene. About 10% of patients with CCHS have nonpolyalanine repeat mutations (NPARM) that are associated with severe phenotypes requiring continuous assisted ventilation, Hirschsprung's disease, and increased neural crest tumor risk. However, some patients with NPARM have milder phenotypes.

Recent Advances in Pathophysiology and Management of Transient Tachypnea of Newborn.

Transient tachypnea of newborn (TTN) results from failure of the newborn to effectively clear the fetal lung fluid soon after birth. TTN represents the most common etiology of respiratory distress in term gestation newborns and sometimes requires admission to the neonatal intensive care unit. TTN can lead to maternal-infant separation, the need for respiratory support, extended unnecessary exposure to antibiotics and prolonged hospital stays.

Pulmonary Disease Burden in Primary Immune Deficiency Disorders: Data from USIDNET Registry.

Purpose: Pulmonary manifestations are common in patients with primary immunodeficiency disorders (PIDs) but the prevalence, specific diseases, and their patterns are not well characterized.

Methods: We conducted a retrospective analysis of pulmonary diseases reported in the database of the United States Immunodeficiency Network (USIDNET), a program of the Immune Deficiency Foundation. PIDs were categorized into 10 groups and their demographics, pulmonary diagnoses and procedures, infections, prophylaxis regimens, and laboratory findings were analyzed.

Atrial Septal Defects Accelerate Pulmonary Hypertension Diagnoses in Premature Infants.

Between 4 and 16% of extremely premature infants have late pulmonary hypertension (PH) (onset >30 days of life), and infants with PH have a higher risk of tracheostomy and death. Atrial septal defects (ASD) increase pulmonary blood flow and may promote PH in at-risk infants. The objective of this study was to determine if infants with ASD develop PH sooner than those without ASD.

Elastase Exocytosis by Airway Neutrophils Is Associated with Early Lung Damage in Children with Cystic Fibrosis.

Rationale: Neutrophils are recruited to the airways of individuals with cystic fibrosis (CF). In adolescents and adults with CF, airway neutrophils actively exocytose the primary granule protease elastase (NE), whose extracellular activity correlates with lung damage. During childhood, free extracellular NE activity is measurable only in a subset of patients, and the exocytic function of airway neutrophils is unknown.

Myeloperoxidase oxidation of methionine associates with early cystic fibrosis lung disease.

Cystic fibrosis (CF) lung disease progressively worsens from infancy to adulthood. Disease-driven changes in early CF airway fluid metabolites may identify therapeutic targets to curb progression.CF patients aged 12-38 months (n=24; three out of 24 later denoted as CF screen positive, inconclusive diagnosis) received chest computed tomography scans, scored by the Perth-Rotterdam Annotated Grid Morphometric Analysis for CF (PRAGMA-CF) method to quantify total lung disease (PRAGMA-%Dis) and components such as bronchiectasis (PRAGMA-%Bx).

Serial Stimulated Jitter Analysis In Juvenile Myasthenia Gravis.

Introduction: Clinical and electrophysiological studies to measures disease activity in juvenile myasthenia gravis (JMG) are limited.

Methods: Retrospective review of the clinical profile, Myasthenia Gravis Foundation of America (MGFA) scores, serial stimulated jitter analysis (Stim-JA) of the orbicularis oculi muscle, grip strength, and spirometry of patients with JMG who were followed in a multidisciplinary clinic was performed.

Results: Thirteen patients with JMG (9 females) with mean age of 13.

Difference between SF and N multiple breath washout kinetics is due to N back diffusion and error in N offset.

Measurement of lung clearance index (LCI) by multiple breath washout (MBW) is a sensitive method for monitoring lung disease in patients with cystic fibrosis (CF). To compare nitrogen MBW (N-MBW) and sulfur hexafluoride MBW (SF-MBW), we connected these two gas analysis systems in series to obtain truly simultaneous measurements, with no differences other than the gas used. Nonsmoking healthy controls (HC) and subjects with CF were recruited at two institutions.