Faculty Bibliography

Introduction: Multiple organisms have been recovered from the airways of patients with cystic fibrosis (CF). Aside from Pseudomonas aeruginosa (PA) and methicillin resistant Staphylococcus aureus (MRSA), influence on disease progression is not defined. Bronchiectasis is an established sequelea of CF airway disease; however, other airway anomalies have not been reported. Case Report: This is a 13 year-old female with CF (pancreatic insufficient) diagnosed at six months of age. She had a cough for four months, without the ability to expectorate sputum, as well as severe decline in pulmonary function, unresponsive to oral antibiotics and antifungals. Spirometry demonstrated a severe obstructive defect. The patient was hospitalized for further evaluation. Bronchoscopy was performed, and multiple small bronchial diverticula were present in the right and left lower lobar segmental airways (Figure 1). Otherwise, bronchoscopy demonstrated edematous and friable mucosa, thick secretions, and dynamic collapse of the large airways. Samples from bronchiolar lavage (BAL) fluid yielded Alcaligenes xylosoxidans and Trichosporon mucoides for which the patient was treated with piperacillin/tazobactam, sulfamethoxazole/trimethoprim, and voriconazole. The patient first grew Trichosporon mucoides from her BAL fluid one year prior to this presentation, when she also was hospitalized for pulmonary exacerbation; she subsequently was treated with a four month course of voriconazole and steroids, with a temporary improvement in pulmonary function and symptoms. Bronchoscopy performed by the same pulmonologist at that time did not show these bronchial diverticula; chest CT at that time showed diffuse tree-in-bud opacities in lower lobes and acinar nodules consistent with a fungal infection. Discussion: This case is significant because Trichosporon is a rare organism in patients with CF whom have not been transplanted, with only one documented case report in the literature. To our knowledge there have been no reported cases of bronchial diverticula in CF. Airway diverticula have been described in immunodeficiency and Mounier-Kuhn syndrome; however, in these reports, diverticula were restricted to the central airways. It is unclear whether the development of these bronchial diverticula is directly related to Trichosporon infection or to another etiology. It is also unclear how these diverticula may contribute to the patient's disease, potentially serving as a reservoir for pathogenic bacteria and fungi. (Figure presented)

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

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