Faculty Bibliography

Endobronchial sarcoid lesions have previously been described and visualized upon bronchoscopy in adult patients with pulmonary sarcoid involvement. Endobronchial ultrasound-guided transbronchial fine-needle aspiration (EBUS-TBNA) has come into favor as the preferred method of diagnosis, but it remains a novel technique in pediatric pulmonology. We describe the first two known cases of visualized endobronchial sarcoid lesions in the pediatric population with pathological confirmation of sarcoidosis with endobronchial and EBUS-TBNA biopsies.

CF newborn screening (NBS) began in New York state (NYS) using an immunoreactive trypsinogen (IRT)-DNA algorithm in 2002. On 12/1/2017, NYS became the second in the US to implement enhanced NBS including CFTR sequencing (IRT-DNA-SEQ), with a primary goal of minimizing unnecessary referral of unaffected infants. Infants with high IRT (top 5%) were first screened for 39 CFTR variants using the Luminex xTAG CF39v2 panel. Those with one variant or ultra-high IRT (top 0.1%) were sequenced using MiSeqDx CF Clinical Sequencing Assay (Illumina) with confirmation by Sanger and supplemental testing for specific deletions. Infants with two potentially clinically significant variants were referred to accredited specialty care centers for diagnostic testing. The primary care provider and birth hospital were issued reports for all screen-negative infants, with a recommendation of genetic counseling for carriers. During the first year, >100 different reportable CFTR variants were identified, and 127 infants with two variants were referred. Using the previous IRT-DNA algorithm, 445 carriers and 177 infants with no variants would also have been referred, corresponding to an 83% reduction in referrals with the IRT-DNA-SEQ algorithm. Thirty-one infants have been confirmed to have CF. The median age at earliest consult among CF cases was 12 days (range 0-62), with >=93% seen within 30 days of life. Eighty-six infants with two variants and intermediate/low sweat chloride levels were classified as CFSPID/CRMS and are followed; 83/86 carried 1-2 variants of varying clinical consequence or uncertain significance, compared to only 2/31 CF cases. Such variants with low or variable penetrance complicate diagnosis and prompt long-term follow-up to monitor for symptoms related to CFTR dysfunction or "conversion" to CF. Furthermore, the ratio of CFSPID/CRMS to CF cases increased from 0.9:1 to 2.8:1 overall, and differed by center, ranging from 0.8:1 to 15:0. Sequencing increases lab workload, turnaround times and cost, but is balanced by reduction in follow-up by NBS staff and care centers, and an overall reduction in healthcare costs by elimination of diagnostic evaluation for most infants with false-positive screens. Identification of asymptomatic infants with two CFTR variants and intermediate/negative sweat chloride values poses new clinical and practical challenges for care teams and families

The effects of childhood exposure to perfluoroalkyl substances (PFASs) on lung function remain mostly unknown. Previous research indicates that children living or going to school near the World Trade Center (WTC) disaster were exposed to high levels of PFASs, among other toxic chemicals. To explore the effects of PFAS exposure on lung function, we measured serum PFASs in a cohort of children from the WTC Health Registry and a matched control group. Perfluorooctanesulfonate had the highest median concentrations in both groups (WTCHR = 3.72 ng/mL, Comparison = 2.75 ng/mL), while the lowest median concentrations were seen for perfluoroundecanoic acid (WTCHR = 0.12 ng/mL, Comparison = 0.01 ng/mL). Lung function outcomes were measured by spirometry, plethysmography, and oscillometry. Asthma diagnosis and serum eosinophil count were also recorded. We examined the relationships of each PFAS with lung function parameters and eosinophil count using linear regressions. Odds ratios for asthma were obtained for each PFAS using logistic regression. The effect of total PFASs on these outcomes was also assessed. All regression models were adjusted for sex, race/ethnicity, age, body mass index (BMI) and tobacco smoke exposure. We found that serum PFASs were not statistically associated with the measured lung function parameters, asthma diagnosis, or eosinophil count in this cohort (p < 0.05). These findings highlight the need for more longitudinal studies to explore the long-term effects of childhood PFAS exposure on lung function past adolescence and early adulthood.

AIM/OBJECTIVE:Children with severe uncontrolled asthma (SUA) have a high burden of symptoms and increased frequency of asthma exacerbations. Reflux esophagitis and eosinophilic esophagitis are important co-morbid factors for SUA. Both are associated with the presence of eosinophils in esophageal mucosa. We hypothesized that esophageal eosinophils are frequently present and correlate with the presence of airway eosinophils in children with SUA. METHOD/METHODS:We performed a retrospective analysis of a prospective database of children who underwent "triple endoscopy" (sleep laryngoscopy, bronchoscopy with bronchoalveolar lavage [BAL] and endobronchial biopsy [EBB], and esophagogastroduodenoscopy with esophageal biopsy [EsB]) at our Aerodigestive Center for evaluation of SUA. Children with known cystic fibrosis, primary ciliary dyskinesia, and aspiration-related lung disease were excluded. RESULT/RESULTS:Twenty-four children (21 males) ages 2-16 years were studied. Elevated BAL eosinophils were found in 10 (42%) patients, endobronchial eosinophils in 16 (67%); 7 (29%) had endobronchial eosinophils without elevated BAL eosinophils. Esophageal eosinophils were found in 11 (46%) patients. There was a correlation between the amount of eosinophils in BAL and EBB (R = 0.43, P = 0.05) airway eosinophils, defined as elevated BAL and/or EBB eosinophils, correlated with esophageal eosinophils (R = 0.41, P = 0.047). CONCLUSION/CONCLUSIONS:We concluded that airway and esophageal eosinophils are frequently present in children with SUA.

OBJECTIVES/OBJECTIVE:To compare lung function in a representative sample of World Trade Center (WTC)-exposed children with matched comparisons, and examine relationships with reported exposures. STUDY DESIGN/METHODS:Study population consisted of 402 participants. Oscillometry, spirometry, and plethysmography were performed on WTC Health Registry (WTCHR) respondents who were ≤8 years of age on September 11, 2001 (n = 180) and a sociodemographically matched group of New York City residents (n = 222). We compared lung function by study arm (WTCHR and comparison group) as well as dust cloud (acute); home dust (subchronic); and other traumatic, nondust exposures. RESULTS:In multivariable models, post-9/11 risk of incident asthma was higher in the WTCHR participants than in the comparison group (OR 1.109, 95% CI 1.021, 1.206; P = .015). Comparing by exposure rather than by group, dust cloud (OR 1.223, 95% CI 1.095, 1.365; P < .001) and home dust (OR 1.123, 95% CI 1.029, 1.226; P = .009) exposures were also associated with a greater risk of incidence of post-9/11 asthma. No differences were identified for lung function measures. CONCLUSIONS:Although we cannot exclude an alternative explanation to the null findings, these results may provide some measure of reassurance to exposed children and their families regarding long-term consequences. Further study with bronchodilation and/or methacholine challenge may be needed to identify and further evaluate effects of WTC exposure. Biomarker studies may also be more informative in delineating exposure-outcome relationships. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov: NCT02068183.

PURPOSE: Reflux esophagitis (ReE) and eosinophilic esophagitis (EoE) are associated with the presence of eosinophils in esophageal mucosa and are considered to be important co-morbid factors for chronic cough and asthma in adults. We hypothesize that esophageal eosinophils related to ReE and EoE are present in children with refractory asthma and chronic cough and correlate with airway eosinophilia. METHODS: We performed a retrospective analysis of medical records of children who underwent "triple endoscopy" (sleep laryngoscopy, bronchoscopy with bronchoalveolar lavage (BAL) and endobronchial biopsy (EBB), and esophagogastroduodenoscopy with esophageal biopsy (EsB)) at our Aerodigestive Center for evaluation of refractory asthma and cough. Inclusion criteriawere cough for 8 weeks or more with no response to trial of antibiotics and systemic/inhaled corticosteroids (ICS), poor control of asthma symptoms, and/or airflowlimitations and air trapping despite use ICS or ICS/long-acting beta-agonist combination. Children with known cystic fibrosis, primary ciliary dyskinesia and aspiration into airway were excluded. RESULTS: Thirty-two children (22 males) met inclusion criteria. Nineteen had refractory asthma and 13 had chronic cough. There were no significant complications recorded after procedures including EBB. Eosinophils (>1%) were present in BAL of 8 (25%) children. EBB showed eosinophils in 17 (53%) children. There were a total of 19 children with eosinophils isolated from the airway (either BAL or EBB), 4 (21%) had them in BAL alone, 8 (42%) in EBB only, and 7 (37%) in both BAL and EBB. EoE was diagnosed in 6 children (19%) and ReE in 13 (41%). EsB revealed esophageal eosinophils in 47% of children. Presence of eosinophils in EsB was related to presence of eosinophils in EBB chi² (1, N = 32), p = 0.026, but not BAL (p=0.89). CONCLUSIONS: ReE and EoE with esophageal eosinophils was present in 47% of children with refractory asthma and chronic cough. There is a significant relationship between airway and esophageal eosinophils, which becomes evident only when EBB is performed for detection of airway eosinophils. Further research is required for understanding the association of airway and esophageal eosinophilia in the development and management of refractory asthma and cough