Faculty Bibliography

Patients with Sickle Cell Disease (SCD) are living longer and subsequently more apt to develop cardiopulmonary dysfunction. NT-proBNP levels have been used in adults with SCD to assess for pulmonary hypertension and mortality. While the incidence of PH is low in pediatrics, it is reasonable to presume that NT-proBNP levels can be used to assess risk for the development of cardiopulmonary morbidity. We hypothesized that NT-proBNP levels would be increased in patients with SCD compared to age-adjusted healthy children; additionally, these levels would be associated with labs indicative of hemolysis and would demonstrate evidence of obstructive lung disease and cardiac dysfunction. We retrospectively evaluated patients with SCD, 8-18 years old, at a large, tertiary care children's hospital. NT-proBNP levels were assessed in correlation with hemolytic lab work, spirometry, and echocardiographic data. The age group 8-14 years old, 75% of our cohort's population, had a median NT-proBNP of 70pg/mL, greater than their age-adjusted counterparts (52pg/mL). NT-proBNP levels were associated with an increased degree of hemolysis when compared with hemoglobin (Hb) [r = -0.43, p < 0.0001], reticulocyte count [r = 0.25, p = 0.01] and lactate dehydrogenase (LDH) levels [r = 0.47, p < 0.0001]. An inverse trend was found between NT-proBNP and spirometric data. Lastly, a positive correlation was found between NT-proBNP and diastolic left ventricular size [r = 0.28, p = 0.047]. The correlations found suggest that NT-proBNP may be used prospectively to identify patients with SCD at increased risk for the development of cardiopulmonary dysfunction. This article is protected by copyright. All rights reserved.

OBJECTIVE: To examine the associations of bisphenol A (BPA) exposure with lung function measures and exhaled nitric oxide (FeNO) in children. STUDY DESIGN: We performed a cross-sectional analysis of a subsample of US children age 6-19 years who participated in the 2007-2010 National Health and Nutrition Examination Survey. We assessed univariate and multivariable associations of urinary BPA concentration with the predicted pulmonary function measures for age, sex, race/ethnicity and height (forced expiratory volume in 1 second [FEV1], forced vital capacity [FVC], forced expiratory flow 25%-75%, and FEV1 divided by FVC) and with FeNO. RESULTS: Exposure and outcome data were available for 661 children. Median BPA was 2.4 ng/mL (IQR: 1.3, 4.1). In multivariable analysis, a larger urinary BPA concentration was associated with significantly decreased percent predicted forced expiratory flow 25%-75% (%FEF2575) (3.7%, 95% CI 1.0, 6.5) and percent predicted FEV1 divided by FVC (%FEV1/FVC) (0.8%, 95% CI 0.1, 1.7) but not percent predicted FEV1, percent predicted FVC, or FeNO. A child in the top quartile of BPA compared with the bottom quartile had a 10% decrease in %FEF2575 (95% CI -1, -19) and 3% decrease in %FEV1/FVC (95% CI -1, -5). CONCLUSIONS: BPA exposure was associated with a modest decrease in %FEF2575 (small airway function) and %FEV1/FVC (pulmonary obstruction) but not FEV1, FVC, or FeNO. Explanations of the association cannot rule out the possibility of reverse causality.

OBJECTIVE: Prior research on the physical health of children exposed to the World Trade Center (WTC) attacks has largely relied on parental report via questionnaire. We examined the impact of clinically-reported exposures on the physical health of children who lived and/or attended school in downtown Manhattan on September 11, 2001. STUDY DESIGN: We performed a cross-sectional study of 148 patients who presented to the WTC Environmental Health Center/Survivors Health Program, and were /=1day in their home between September 11 and 18, 2001; and 25.7% reported home dust exposure. New-onset nasal/sinus congestion was reported in 52.7%, while nearly one-third reported new gastroesophageal reflux (GERD) symptoms. Prehypertension or hypertension was identified in 45.5%. Multivariable regression with exposure variables, body mass index category, and age as covariates identified strongest associations of dust cloud with spirometry (17.1% decrease in maximum midexpiratory flow). Younger children experienced increased peripheral eosinophils (+0.098% per year, p=0.023), while older children experienced more new-onset GERD (OR 1.17, p=0.004), headaches (OR 1.10, p=0.011), and prehypertension (OR 1.09, p=0.024). Home dust exposure was associated with reduced high-density lipoprotein (-10.3mg/dL, p=0.027) and elevated triglycerides (+36.3mg/dL, p=0.033). CONCLUSIONS: While these findings cannot be assumed to generalize to all children exposed to the WTC attacks, they strongly suggest the need for more extensive study of respiratory, metabolic, and cardiovascular consequences.

Introduction. Youth as young as 11 are given responsibility to manage their asthma. Yet, little is known regarding early adolescents' asthma self-management behaviors. This study characterizes urban early adolescents' asthma self-management behaviors and perceived responsibility to manage asthma, exploring demographic differences and examining the relationship between asthma responsibility and disease management. Methods. About 317 Hispanic and African American/Black early adolescents (mean age = 12.71) with persistent, uncontrolled asthma reported prevention and symptom management steps, and responsibility for asthma care. We used Poisson, cumulative logistic, logistic, and linear mixed-effects regression models to assess the relationships among demographic predictors, prevention and management behaviors, and responsibility for asthma care. Results. Fifty percent took 7-9 prevention steps; few saw physicians when asymptomatic or took daily medication. When symptomatic, 92% used medication to treat symptoms and 56% sought medical attention. Controlling for asthma responsibility, fewer older youth reported observing how they feel when asthma is likely to start, observing symptom changes, or asking for help. More boys reported taking medication daily or upon trigger exposure. Controlling for age, gender, and race/ethnicity, those reporting more asthma responsibility were less likely to report taking management steps, seeking preventive care, asking for help, or going to a doctor/hospital for their asthma. Conclusions. Early adolescents' asthma self-management is suboptimal. With increasing age, they are less observant regarding their asthma and less likely to seek help. Although they perceive themselves to have greater responsibility for managing their asthma, early adolescents do less to care for their asthma, suggesting they are being given responsibility for asthma care prematurely

RATIONALE: Understanding factors that adversely impact asthma management is imperative to enhance pediatric asthma. While family functioning has been found to be associated with medication adherence, its relationship to other aspects of asthma management has not been studied. Moderate levels of asthma-related anxiety are associated with optimal asthma management in adults; this has yet to be studied in youth. This novel study tested whether family functioning and asthma-related anxiety predict prevention and management behaviors and perceived asthma responsibility among urban early adolescents. METHODS: 386 early adolescents (mean age=12.8; 56% male; 49% Hispanic; 34% African American) with persistent, uncontrolled asthma from 23 NYC public middle schools reported steps they take to prevent symptom onset and manage symptoms once they begin, and completed the Asthma Responsibility Questionnaire, the Youth Asthma-related Anxiety Scale, and validated measures assessing family functioning (i.e., warmth, communication, problem-solving, and conflict). We assessed whether the relationships between the outcomes (prevention, management, and responsibility) and predictors (asthma-related anxiety and family functioning) are non-linear using generalized additive models (GAM) controlling for cohort, asthma severity, age and gender. If there was no evidence for non-linearity, the linear relationships were evaluated using generalized mixed effects models for normal or Poisson data. RESULTS: There was no evidence for non-linearity with one exception mentioned below. Asthma responsibility was the construct most impacted by family functioning. Youth reported their caregiver is more responsible for asthma management if they also reported more communication with caregivers (p<.001), having warm/nurturing caregivers (p<.001), and less child-caregiver conflict (p<.001). Increased asthma-related anxiety was related to youth taking more steps to prevent (p<.001) and manage (p=.02) asthma. For prevention, the relationship was non-linear (df=2.4) - with anxiety above 2 (on a scale from 0-5), there was no additional increase in prevention steps. With increased asthma-related anxiety, youth felt they, not their caregivers, were more responsible for asthma management (p=0.015). CONCLUSIONS: Findings suggest a need for family-centered care to ensure caregivers remain connected to their early adolescent and do not transfer responsibility for managing asthma to their children prematurely. Also, clinicians should assess youths' anxiety as part of routine asthma care. When asthma-related anxiety is low, youth may benefit from increased awareness of the consequences of uncontrolled asthma. In contrast, when anxiety is elevated, clinicians should consider referring the family to a mental health provider to ensure the youth are not assuming responsibility prematurely as a means of coping with the anxiety

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)

RATIONALE:As early as age 11 children begin to take responsibility for asthma self-management, yet very little is known about asthma management behaviors in early adolescents. In this study we characterize early adolescents' asthma prevention and management steps and their perceived responsibility; explore differences in asthma self-management and responsibility according to demographic characteristics; and investigate the role of perceived responsibility in prevention and management behaviors. METHODS:We utilized baseline data from a randomized controlled trial testing the efficacy of an asthma intervention. 317 African-American (41%) and Hispanic (59%) children (mean age=12.7) with persistent asthma answered 9 questions regarding prevention steps taken regularly (3-point Likert scale), 7 questions regarding steps taken to manage symptoms (yes/no), and the 10-item Asthma Responsibility Questionnaire (5-point Likert scale). Using generalized estimating equations, we modeled the total number of prevention and management steps taken and individual self-management items as a function of demographic characteristics, controlling for asthma severity. We then added responsibility to the model. Last we modeled asthma responsibility as a function of demographic characteristics controlling for severity. RESULTS:49% took 7-9 prevention steps; 31% took daily medication regularly; 34% did not take daily medication; only 24% saw a physician when asymptomatic. 61% took 6-7 management steps; 92% took medication, but only 26% asked for help. Older youth had lower odds of observing how they feel when asthma is likely to start (Odds ratio[OR]=0.82,p<0.05), observing symptoms to see if they improve or get worse (OR=0.71,p<0.05) and asking for help (OR=0.72,p<0.05). Boys had significantly higher odds of taking daily medication preventively (OR=1.52,p<0.05) and upon exposure to triggers (OR=1.62,p<0.05). Results were consistent when controlling for asthma severity and both asthma severity and responsibility. Controlling for age and asthma severity, early adolescents who reported taking more responsibility for managing their asthma were more likely to take fewer steps to manage their asthma once symptoms begin (Risk ratio=0.97,p<0.01), and had lower odds of seeking preventive care (OR=0.67,p<0.001), asking for help (OR=0.70, p<0.01), and going to a doctor or hospital to manage their asthma (OR=0.74,p<0.001); results were consistent when controlling for gender and race/ethnicity. CONCLUSIONS:Early adolescents' asthma self-management is suboptimal. Despite having persistent asthma, a minority took daily medication preventively or sought preventive medical care. With increasing age, children were less observant regarding their asthma and less likely to seek help. As early adolescents perceive themselves to have greater responsibility for managing their asthma, they have lower odds of taking certain self-management steps

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

The prevalence of childhood obesity has more than tripled over the past five decades. Obesity results in low lung volumes, likely through increased loading of the chest wall and abdomen. The prevalence of asthma in children has paralleled the rise in obesity; obesity may increase the severity of asthma, but a direct link has been difficult to establish. Obesity is a risk factor for obstructive sleep apnea (OSA) in children as well as adults. Obese children may be at increased risk for persistent OSA following adenotonsillectomy treatment for OSA. Severe obesity and OSA may lead to the obesity-hypoventilation syndrome, with hypoxia, hypercapnia, and reduced ventilatory drive. Obesity can increase a child's risk for complications of anesthesia and recovery from surgery