Faculty Bibliography

Introduction: Pulmonary function evaluation in patients with cystic fibrosis (CF) has demonstrated disparity between spirometric and oscillometric assessments. Most studies have indicated that oscillometry may appear normal despite significant abnormalities on spirometry. However, normal values for impulse oscillometry (IOS) in pediatric populations are limited and vary by study. The present study assessed the role for IOS by assessment of both the acute response to bronchodilator and the chronic response to treatment. Methods: Patients hospitalized with exacerbations of CF were evaluated with both spirometry and oscillometry. Data were obtained pre and post bronchodilator administration and related to published normative data. When feasible, lung volumes were assessed by plethysmography. Serial testing was performed during and following standard therapy which included vigorous chest physical therapy and intravenous antibiotics targeted to the predominate organism isolated from sputum or bronchoscopy specimens. Results: Data were available in 5 patients with CF with age ranging from 5 to 44 years. Abnormal spirometry was evident in 4 subjects. Although FEV₁/FVC was mildly reduced in these subjects (68+5%), the predominant abnormality was reduction in vital capacity (50+12%). HRCT demonstrated severe mucous plugging in multiple airways and bronchoscopy in one patient confirmed total occlusion of the bronchial lumen form respiratory secretions. Despite these spirometric and radiographic abnormalities, oscillometric assessment of resistance assessed was within published normal limits in these subjects. However, a positive response to bronchodilator was observed in 3 patients and serial testing in one subject demonstrated further improvement in airway resistance by IOS. These changes in oscillometric data occurred with minimal change in FVC and FEV₁. Conclusions: Although IOS parameters in an individual patient may be within published normal limits, reduction in resistance may be apparent either acutely post bronchodilator or chronically following treatment. These improvements in IOS parameters may not be apparent on spirometry, providing a potential role for IOS in the evaluation of patients with CF. These data suggest that improvement in post bronchodilator measurements of airway resistance may be a useful adjunct to guide the appropriate length of treatment for CF exacerbations

SUMMARY: During the first 4 years of newborn screening (NBS) for Cystic Fibrosis (CF) in New York there was a statistically significant, twofold greater relative risk of an Immunoreactive Trypsinogen (IRT) level greater than 95% in African-American infants. The reason for this previously reported increase in IRT level in African-American infants is unclear. The positive predictive value of a screen positive result in this population was only 0.3%. The bulk of screen-positive African-American infants were in the top 0.2% (IRT) group, with no CF mutations isolated. Repeat IRT testing at 2-3 weeks of age may represent a suitable approach to decrease the false-positive rate in this population

Juvenile Xanthogranuloma (JXG) is a dendritic cell related histiocytic disorder which usually presents in the first year of life as a solitary cutaneous granuloma. Isolated presentation in the upper airway is very rare but can result in severe respiratory distress, especially in young children. We present the case of a 5-month-old male with an isolated subglottic JXG lesion. Endoscopic excision provided symptomatic relief and avoided the need for tracheostomy. The lesion has completely resolved 17 months later. Surgical excision without tracheostomy was the treatment of choice in two of the four additional cases of upper airway JXG presented in the literature. JXG has an excellent prognosis with spontaneous regression over time. Histology alone is frequently inadequate to differentiate JXG from the more common Langerhans Cell Histiocytosis (LCH), which carries a much less favorable prognosis. The evolving field of immunohistochemistry provides an essential tool to establish the correct diagnosis. The typical phenotype of JXG is Factor XIIIa+/Fascin+/CD68+/CD163+/CD14+/CD1a-/S100-

OBJECTIVE: The purpose of this work was to report on the first 2.5 years of newborn screening for cystic fibrosis in New York. METHODS: Directors of the 11 New York cystic fibrosis centers were asked to provide mutation data, demographic data, and selected laboratory results for each patient diagnosed by newborn screening and followed at their center. Summary data were also submitted from the New York newborn screening laboratory on the total number of patients screened, the number of positive screens, and the number of patients that were lost to follow-up. A second survey was submitted by each center regarding the availability of genetic counseling services at the center. RESULTS: A total of 106 patients with cystic fibrosis were diagnosed through newborn screening in the first 2.5 years and followed at the 11 Cystic Fibrosis Foundation-sponsored cystic fibrosis care centers in New York. Two screen-negative infants were subsequently diagnosed with cystic fibrosis when symptoms developed. The allele frequency of deltaF508 was 57.4%, which is somewhat lower than the allele frequency of deltaF508 in the US cystic fibrosis population of 70%. There were 90 non-Hispanic white (84%), 12 Hispanic, 2 Asian, and 1 black infants diagnosed with cystic fibrosis during this period. Five patients were diagnosed secondary to a positive screen based on a high immunoreactive trypsinogen and no mutations. CONCLUSIONS: Newborn screening for cystic fibrosis has been effectively conducted in New York using a unique screening algorithm that was designed to be inclusive of the diverse racial makeup of the state. However, this algorithm results in a high false-positive rate, and a large number of healthy newborns are referred for confirmatory sweat tests and genetic counseling. This experience indicates that it would be helpful to convene a working group of cystic fibrosis newborn screening specialists to evaluate which mutations should be included in a newborn screening panel

Congenital tracheal web is a rare entity often misdiagnosed as refractory asthma. Clinical suspicion based on patient history, examination, and pulmonary function tests should lead to its consideration. Bronchoscopy combined with CT imaging and multiplanar reconstruction is an accepted, highly sensitive means of diagnosis

Two adolescents presented with a history of dyspnea upon exertion and cough. In both cases, the chest X-ray and pulmonary function testing, including flow-volume loop, were normal. A bronchial tumor was diagnosed by CT scan, which was ordered after each patient had an episode of hemoptysis. The sedimentation rate was the only abnormal laboratory test in both cases. Mucoepidermoid carcinoma of the bronchus, a rare tumor in childhood, was found at pathology in both cases. There was no evidence of metastases to local lymph nodes or distal sites. There were 47 previously reported cases in children. Recurrent pneumonia and persistent cough were the most common presenting findings. These tumors are of low-grade malignant potential but they can become locally invasive, extending into cartilage and surrounding soft tissue. Prognosis is good with complete resection