Faculty Bibliography

INTRODUCTION: Gastroesophageal reflux (GER) is common in children with airway disorders. Previous studies have shown an association between upper airway obstruction and GER in experimental animal models. However, the cause and effect relationship between intrathoracic airway obstruction (IAO) and GER is obscure. The goal of this study is to investigate the association between IAO and GER using the canine model. METHODS: In sedated dogs, a telemetric implant was placed subcutaneously (with one pressure sensor tip each in intrapleural space and abdomen) to monitor intrapleural pressure (IPP) and intrabdominal pressure (IAP). The IPP and the IAP were monitored intraoperatively and in conscious dogs on the 7th to 10th postoperative days. GER was assessed by determining the reflux index (RI), based on the intraesophageal pH recording performed continuously for a 24 hr period using a pH probe. After 2-3 weeks following placement of the telemetric implant, IAO was surgically created in the dog. After maintaining IAO for 2 weeks, the IPP, IAP, and pH measurements were monitored again following the same protocol as before IAO. RESULTS: After the creation of IAO, there was no significant change observed in the mean RI either in the distal (P = 0.716) or proximal (P = 0.962) esophageal lumens. The IPP became significantly more negative (P = 0.006) and the IAP turned significantly negative (P < 0.001) from being positive compared to the respective values before IAO. However, transdiaphragmatic pressure (Pdi) did not change significantly (P = 0.08). CONCLUSION: We conclude that moderate IAO does not cause GER in our animal model. It can be explained by the absence of significant change in Pdi after creation of IAO.

OBJECTIVES: Protracted bacterial bronchitis is defined as the presence of more than 4 weeks of chronic wet cough that resolves with appropriate antibiotic therapy, in the absence of alternative diagnoses. The diagnosis of protracted bacterial bronchitis is not readily accepted within the pediatric community, however, and data on the incidence of bacterial bronchitis in children are deficient. The objective of this study was to determine the frequency of bacterial bronchitis in children with chronic wet cough and to analyze their bronchoscopic findings. METHODS: We performed a retrospective review of charts of children who presented with chronic wet cough, unresponsive to therapy, before referral to the pediatric pulmonary clinic. RESULTS: A total of 197 charts and bronchoscopy reports were analyzed. Of 109 children who were 0 to 3 years of age, 33 (30.3%) had laryngomalacia and/or tracheomalacia. The bronchoscopy showed purulent bronchitis in 56% (110) cases and nonpurulent bronchitis in 44% (87). The bronchoalveolar lavage bacterial cultures were positive in 46% (91) of the children and showed nontypable Haemophilus influenzae (49%), Streptococcus pneumoniae (20%), Moraxella catarrhalis (17%), Staphylococcus aureus (12%), and Klebsiella pneumoniae in 1 patient. The chi(2) analysis demonstrated that positive bacterial cultures occurred more frequently in children with purulent bronchitis (74, 69.8%) than in children with nonpurulent bronchitis (19, 19.8%) (P < .001). CONCLUSIONS: Children who present with chronic wet cough are often found to have evidence of purulent bronchitis on bronchoscopy. This finding is often indicative of a bacterial lower airway infection in these children.

BACKGROUND: Human bocavirus (HBoV) is a newly identified human parvovirus for which seroepidemiology and antigenic properties remain undefined. METHODS: The HBoV VP2 gene, expressed from a baculovirus vector, produced virus-like particles (VLPs), which were used to raise rabbit anti-HBoV antisera and to develop an enzyme-linked immunosorbent assay (ELISA). The VLP-based ELISA was used to screen for HBoV-specific immunoglobulin G antibodies in a convenience sample of 270 serum specimens, mostly from children, obtained at Yale-New Haven Hospital; 208 specimens were also screened for erythrovirus B19-specific antibodies by a B19 VLP-based ELISA. RESULTS: Immunofluorescence and ELISA showed that human parvoviruses HBoV and B19 are antigenically distinct. By the HBoV VLP-based ELISA, 91.8% and 63.6% of serum specimens from infants in the first and second months of life, respectively, were found to be seropositive, as were 45.4% from 3-month-old infants and 25.0% from 4-month-old infants. The percentages of HBoV-seropositive children increased to 40.7%-60.0% for children 5-47 months of age and to >85% for individuals >or=48 months old. However, the overall percentage of B19-seropositive individuals was <40.5% for all age groups screened. CONCLUSIONS: HBoV infection is common during childhood, but a minority of children and young adults screened have evidence of B19 infection.

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

The causal relationship between gastroesophageal reflux (GER) and respiratory disorders is not well understood. Previous experimental studies that investigated this relationship were performed in anesthetized animals and used artificial acidification of esophagus for simulation of GER. In this study, we investigated the impact of GER on intrapleural pressures (IPP) in conscious, unanesthetized dogs. After the induction of appropriate anesthesia, 5 purpose-bred mongrel dogs underwent reflux-creating surgery (partial cardiomyectomy). The presence of GER was confirmed by determining the reflux index (RI) and the duration of longest reflux episode (DLRE) after 24-h intraesophageal pH-metry. IP was monitored before and after cardiomyectomy using a subcutaneously placed telemetric implant with its pressure-sensor catheter tip inserted into the pleural space. Partial cardiomyectomy resulted in a significant increase in RI from a preoperative mean value of 0.38 +/- 0.21 to 7.52 +/- 2.56%, and DLRE from 1.22 +/- 1.12 to 36.80 +/- 12.71 min, as recorded by the proximal sensor of the pH probe. A similar trend was observed at the distal sensor. After cardiomyectomy, the negative inspiratory IPP significantly increased from 17.2 +/- 7.9 to 28.4 +/- 9.7 mm Hg. A similar effect was observed in the negative expiratory IPP. The negative inspiratory IPP had a significant correlation with both RI (R = 0.932) and DLRE (R = 0.899). Cardiomyectomy causes GER, the severity of which correlates with negative inspiratory IPP in a dog model. The suggested model allows for the investigation of the pathologic association of GER with respiratory disorders in conscious animals.

Introduction: Children with asthma and allergic rhinitis are often treated with a combination of inhaled and nasal corticosteroids. Safety data on this combination treatment in children are not available. This study evaluates adrenal function in children receiving combination therapy with nasal and inhaled corticosteroid using a low-dose adrenocorticotropin (ACTH) test. Methods: Twelve children aged 6–12 years with severe asthma and allergic rhinitis were given combination therapy with high-dose inhaled HFA-beclomethasone dipropionate (HFA-BDP) (320 micro-g/day for fi rst 2 months and 160 micro-g/day thereafter) and fl unisolide nasal spray (116 micro-g/day). A low-dose ACTH test was performed before treatment and 6 months later. Results: There was no significant change (mean plus/minus SD) in both baseline (7.78 plus/minus 5.34 before treatment and 7.53 plus/minus 4.02 after treatment, p = 0.42) and stimulated (22.58 ± 6.97 before treatment and 19.2 plus/minus 3.53, p = 0.09 after treatment) cortisol levels. Conclusion: Combination therapy with high-dose HFA-BDP and fl unisolide nasal spray did not cause suppression of adrenal function in pediatric patients with severe asthma and allergic rhinitis

Laryngeal exposure to acid and aspiration of gastric contents may lead to severe respiratory disorders. This study utilizes the canine model of Gastroesophageal reflux (GER) to identify whether lower esophageal dysfunction is associated with upper and lower airway pathology. MATERIALS AND METHODS: Five mongrel dogs underwent GER-creating surgery (partial cardiomyectomy). Laryngeal reflux finding score (RFS), lipid-laden macrophage index (LLMI) and BAL fluid cell differential were obtained before and after surgery. RESULTS: Partial cardiomyectomy in dogs significantly increased the Reflux index (RI) from 0.38 +/- 0.21% to 7.56 +/- 2.89% (P = 0.048), the duration of the longest reflux episode (DLRE) from 1.22 +/- 1.19 min to 66.2 +/- 42.03 min postoperatively (P = 0.049) and the total number of episodes in 24 hr from 2.06 +/- 1.03 to a postoperative value of 19.24 +/- 4.79. There was no statistically significant change in values for RFS, LLMI, and BAL fluid cell differential after the induction of GER. CONCLUSIONS: Acid reflux to the proximal esophagus of this animal model did not cause laryngeal exposure to acid or aspiration of gastric content. The results of this study suggest that presence of GER, secondary to lower esophageal dysfunction is not necessarily associated with upper and lower airway pathology.

BACKGROUND: Monitoring of intrapleural pressure (IPP) is used for evaluation of lung function in a number of pathophysiological conditions. We describe a telemetric method of non-invasive monitoring of the IPP in conscious animals intermittently or continuously for a prolonged period of time. MATERIALS AND METHODS: After IACUC approval, six mongrel dogs were used for the study. After sedation, each dog was intubated and anesthetized using 0.5% Isoflurane. A telemetric implant model TL11M2-D70-PCT from Data Science International was secured subcutaneously. The pressure sensor tip of the catheter from the implant was inserted into the pleural space, and the catheter was secured with sutures. The IPP signals were recorded at a sampling rate of 100 points/second for 30 to 60 min daily for 4 days. From these recordings, the total mean negative IPP (mmHg), and the total mean negative IPP for a standard time of 30 min were calculated. In addition, the actual inspiratory and expiratory pressures were also measured from stable recording of the IPP waveforms. RESULTS: In six dogs, the total mean +/- SD negative IPP was -10.8 +/- 10.6 mmHg. After normalizing with respect to acquisition time it was -13.2 +/- 11.2 mmHg/min. The actual inspiratory pressure was -19.7 +/- 15.3, and the expiratory pressure was -11.0 +/- 12.9. CONCLUSIONS: Our study demonstrates that telemetric monitoring of IPP can be performed reliably and non-invasively in conscious experimental animals. The values for IPP in our study are compatible with the results of other investigators who used different methods of IPP measurement. Further work may show this method to be helpful in understanding the pathophysiology of various breathing disorders

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

BACKGROUND: Human bocavirus (HBoV) is a newly identified human parvovirus that was originally identified in the respiratory secretions of children with respiratory tract disease. To further investigate the epidemiological profile and clinical characteristics of HBoV infection, we screened infants and children <2 years of age (hereafter referred to as "children") for HBoV. METHODS: Children for whom respiratory specimens submitted to a diagnostic laboratory tested negative for respiratory syncytial virus, parainfluenza viruses (types 1-3), influenza A and B viruses, and adenovirus, as well as asymptomatic children, underwent screening for HBoV by use of polymerase chain reaction (PCR). Respiratory specimens were obtained from the children from 1 January 2004 through 31 December 2004. RESULTS: Twenty-two (5.2%) of the 425 children who had a respiratory specimen submitted to the diagnostic laboratory and 0 of the 96 asymptomatic children were found to be positive for HBoV by PCR (P=.02). Fever, rhinorrhea, cough, and wheezing were observed in > or =50% of the HBoV-positive children. Of the 17 children who had chest radiography performed, 12 (70.6%) had abnormal findings. HBoV appeared to have a seasonal distribution. Nucleotide polymorphisms were detected in the viral capsid protein (VP) 1/VP2 genes. Two distinct HBoV genotypes circulated during the study period. CONCLUSIONS: HBoV is circulating in the United States and is associated with both upper and lower respiratory tract disease in infants and young children.