Faculty Bibliography

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

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)