Candice Bjornson

Inconclusive Diagnosis of Cystic Fibrosis After Newborn Screening

OBJECTIVES: To prospectively study infants with an inconclusive diagnosis of cystic fibrosis (CF) identified by newborn screening (NBS; “CF screen positive, inconclusive diagnosis” [CFSPID]) for disease manifestations. METHODS: Infants with CFSPID and CF based on NBS from 8 CF centers were prospectively evaluated and monitored. Genotype, phenotype, repeat sweat test, serum trypsinogen, and microbiology data were compared between subjects with CF and CFSPID and between subjects with CFSPID who did (CFSPID→CF) and did not (CFSPID→CFSPID) fulfill the criteria for CF during the first 3 years of life. RESULTS: Eighty-two subjects with CFSPID and 80 subjects with CF were enrolled. The ratio of CFSPID to CF ranged from 1:1.4 to 1:2.9 in different centers. CFTR mutation rates did not differ between groups; 96% of subjects with CFSPID and 93% of subjects with CF had 2 mutations. Subjects with CFSPID had significantly lower NBS immunoreactive trypsinogen (median [interquartile range]:77 [61–106] vs 144 [105–199] μg/L; P < .0001) than did subjects with CF. Pseudomonas aeruginosa and Stenotrophomonas maltophilia were isolated in 12% and 5%, respectively, of subjects with CFSPID. CF was diagnosed in 9 of 82 (11%) subjects with CFSPID (genotype and abnormal sweat chloride = 3; genotype alone = 4; abnormal sweat chloride only = 2). Sweat chloride was abnormal in CFSPID→CF patients at a mean (SD) age of 21.3 (13.8) months. CFSPID→CF patients had significantly higher serial sweat chloride (P < .0001) and serum trypsinogen (P = .009) levels than did CFSPID→CFSPID patients. CONCLUSIONS: A proportion of infants with CFSPID will be diagnosed with CF within the first 3 years. These findings underscore the need for clinical monitoring, repeat sweat testing at age 2 to 3 years, and extensive genotyping.

Tracheostomy in children: A population-based experience over 17 years

Tracheostomy is a lifesaving intervention with numerous complications.

Croup-treatment update.

LEARNING OBJECTIVES After completion of this article, the reader will be able to: 1. Discuss the epidemiology of croup in the pediatric population. 2. Identify the common etiological agents for croup, and describe the pathophysiology resulting in typical symptoms of croup. 3. Recognize clinical features that support alternate diagnoses and the potential complications of croup. 4. Describe 4 levels of clinical severity of croup. 5. Discuss the role of laboratory and radiological investigations in a child with croup. 6. Know the indications for hospital admission in a child with croup. 7. Discuss the role of nonpharmaceutical interventions in a child with croup (mist, oxygen). 8. Discuss the role of epinephrine and corticosteroids in a child with croup.

Croup in children

Croup develops in more than 80 000 Canadian children each year, making it the second most common cause of respiratory distress in the first decade of life.[1][1],[2][2] It affects boys more than girls (1.4:1) and young children between 6 months and 3 years of age more commonly than younger infants,

Munchausen's syndrome presenting as hemoptysis in a 12-year-old girl.

The case of Munchausens syndrome presenting as hemoptysis in a 12-year-old girl is presented. The features of Munchausens syndrome are reviewed. Munchausens syndrome should be included in the differential diagnosis of hemoptysis in a child, especially when accompanied by a dramatic presentation, changing symptoms and negative diagnostic investigations.

Congenital central hypoventilation syndrome; Safety of early transition to non‐invasive ventilation

Congenital central hypoventilation syndrome (CCHS) is a rare disorder of autonomic dysregulation, characterized by alveolar hypoventilation especially during sleep. As a result, lifelong ventilatory assistance is necessary in these patients. Many infants and children initially require positive pressure ventilation via tracheostomy for support. Associated complications and psychosocial pressure may prompt early transition to non‐invasive ventilation. We present the details of a patient with CCHS who successfully transitioned from tracheostomy to bilevel positive airway pressure ventilation at an early age of 3 years. Pediatr Pulmonol. 2014; 49:410–413.

Pulmonary surfactant dysfunction in pediatric cystic fibrosis: Mechanisms and reversal with a lipid-sequestering drug

BACKGROUND Airway surfactant is impaired in cystic fibrosis (CF) and associated with declines in pulmonary function. We hypothesized that surfactant dysfunction in CF is due to an excess of cholesterol with an interaction with oxidation. METHODS Surfactant was extracted from bronchial lavage fluid from children with CF and surface tension, and lipid content, inflammatory cells and microbial flora were determined. Dysfunctional surfactant samples were re-tested with a lipid-sequestering agent, methyl-β-cyclodextrin (MβCD). RESULTS CF surfactant samples were unable to sustain a normal low surface tension. MβCD restored surfactant function in a majority of samples.Mechanistic studies showed that the dysfunction was due to a combination of elevated cholesterol and an interaction with oxidized phospholipids and their pro-inflammatory hydrolysis products. CONCLUSION We confirm that CF patients have impaired airway surfactant function which could be restored with MβCD. These findings have implications for improving lung function and mitigating inflammation in patients with CF.

Telephone Out Patient Score: The Derivation and Validation of a Telephone Follow-up Assessment Tool for Use in Clinical Research in Children With Croup.

Objective The objective was to derive a simple clinical scoring instrument for assessing children with croup by telephone for use in clinical research studies. Methods We reviewed published literature on croup scores, surveyed experienced pediatric emergency nurses and physicians, and conducted a prospective cohort study. Score items were derived from published literature and surveys of experienced clinicians. We enrolled children with croup attending an urban pediatric emergency department. Families of children enrolled were contacted daily by telephone and asked standardized questions about their child’s clinical symptoms and family functioning. Data from this survey were used to derive the clinical score. Results We identified 11 unique croup scores from the literature and interviewed 6 experienced clinicians. We enrolled 330 children and achieved complete follow-up for 301. Of the various groupings of items and duration of assessment, the 2-item score (barky cough and stridor) was the simplest and most reliable. Three days of follow-up yielded optimal correlations. Conclusions We derived a 2-item Telephone Out Patient score assessed daily for 3 days after an emergency department visit. Validation of this score in a future, independent prospective cohort is needed.

Surfactant Dysfunction in ARDS and Bronchiolitis is Repaired with Cyclodextrins

Objectives Acute respiratory distress syndrome (ARDS) is caused by many factors including inhalation of toxicants, acute barotrauma, acid aspiration, and burns. Surfactant function is impaired in ARDS and acute airway injury resulting in high surface tension with alveolar and small airway collapse, edema, hypoxemia, and death. In this study, we explore the mechanisms whereby surfactant becomes dysfunctional in ARDS and bronchiolitis and its repair with a cyclodextrin drug that sequesters cholesterol. Methods We used in vitro model systems, a mouse model of ARDS, and samples from patients with acute bronchiolitis. Surface tension was measured by captive bubble surfactometry. Results Patient samples showed severe surfactant inhibition even in the absence of elevated cholesterol levels. Surfactant was also impaired in ARDS mice where the cholesterol to phospholipid ratio (W/W%) was increased. Methyl-β-cyclodextrin (MβCD) restored surfactant function to normal in both human and animal samples. Model studies showed that the inhibition of surfactant was due to both elevated cholesterol and an interaction between cholesterol and oxidized phospholipids. MβCD was also shown to have anti-inflammatory effects. Conclusions Inhaled cyclodextrins have potential for the treatment of ARDS. They could be delivered in a portable device carried in combat and used following exposure to toxic gases and fumes or shock secondary to hemorrhage and burns.