Proton Pump Inhibitors in Children: the Good, the Bad, and the Ugly.

PURPOSE OF REVIEW: The evidence supporting or contesting the prescription of proton pump inhibitors (PPIs) for children and updates on side effects are reviewed. RECENT FINDINGS: PPIs remain an important therapeutic option for esophagitis and gastritis. However, recent studies demonstrate no benefit when prescribing PPIs for chronic cough, infantile reflux, asthma, or functional gastrointestinal disorders. Recent studies suggest adverse effects on microbiome diversity and immune function, resulting in increased rates of gastrointestinal infections, bone fractures, and atopic disorders. PPIs influence a variety of cell types within the in the innate and adaptive immune systems. PPI prescriptions in children may be indicated for select conditions; however, multiple side effects and immune effects have been described. While most of these side effects are rare and mild, some studies suggest enduring adverse effects. Future studies to elucidate the mechanism behind some of these immune and infectious complications will be beneficial.

Expanding the phenotype of congenital central hypoventilation syndrome impacts management decisions.

Congenital central hypoventilation syndrome (CCHS) is a neurocristopathy caused by pathogenic heterozygous variants in the gene paired-like homeobox 2b (PHOX2B). It is characterized by severe infantile alveolar hypoventilation. Individuals may also have diffuse autonomic nervous system dysfunction, Hirschsprung disease and neural crest tumors. We report three individuals with CCHS due to an 8-base pair duplication in PHOX2B; c.691_698dupGGCCCGGG (p.Gly234Alafs*78) with a predominant enteral and neural crest phenotype and a relatively mild respiratory phenotype. The attenuated respiratory phenotype reported here and elsewhere suggests an emergent genotype:phenotype correlation which challenges the current paradigm of invoking mechanical ventilation for all infants diagnosed with CCHS. Best treatment requires careful clinical judgment and ideally the assistance of a care team with expertise in CCHS.

Gene network analysis in a pediatric cohort identifies novel lung function genes.

Lung function is a heritable trait and serves as an important clinical predictor of morbidity and mortality for pulmonary conditions in adults, however, despite its importance, no studies have focused on uncovering pediatric-specific loci influencing lung function. To identify novel genetic determinants of pediatric lung function, we conducted a genome-wide association study (GWAS) of four pulmonary function traits, including FVC, FEV1, FEV1/FVC and FEF25-75% in 1556 children. Further, we carried out gene network analyses for each trait including all SNPs with a P-value of <1.0 × 10(-3) from the individual GWAS. The GWAS identified SNPs with notable trends towards association with the pulmonary function measures, including the previously described INTS12 locus association with FEV1 (pmeta=1.41 × 10(-7)). The gene network analyses identified 34 networks of genes associated with pulmonary function variables in Caucasians. Of those, the glycoprotein gene network reached genome-wide significance for all four variables. P-value range pmeta=6.29 × 10(-4) - 2.80 × 10(-8) on meta-analysis. In this study, we report on specific pathways that are significantly associated with pediatric lung function at genome-wide significance. In addition, we report the first loci associated with lung function in both pediatric Caucasian and African American populations.

Respiratory muscle force and lung volume changes in a population of children with sickle cell disease.

Sickle cell disease (SCD) is a disorder known to impact the respiratory system. We sought to identify respiratory muscle force and lung volume relationships in a paediatric SCD population. Thirty-four SCD-SS subjects underwent pulmonary function testing. Height, weight, age, and gender-adjusted percent predicted maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) values were compared to spirometry and lung volumes. Statistical analyses were performed using Pearson's correlation coefficient and paired two-tailed t-test. The mean ± standard deviation (SD) MIP and MEP was 69·6 ± 31·6 cm H2 O and 66·9 ± 22·9 cm H2 O, respectively, and mean ± SD percent predicted MIP (101·3 ± 45·9) exceeded MEP (72·1 ± 26·0) (P = 0·002). MIP correlated with forced vital capacity (FVC; r = 0·51, P = 0·001) and TLC (r = 0·54, P < 0·0001). MEP also correlated with FVC (r = 0·43, P = 0·011) and total lung capacity (TLC; r = 0·42, P = 0·013). Pearson's correlation coefficient testing yielded relationships between MIP and MEP (r = 0·64, P < 0·0001). SCD-SS patients showed correlations between respiratory muscle force and lung volume, and reduced percent predicted expiratory muscle force compared to inspiratory muscle force. Respiratory muscle strength may affect lung volumes in these patients, and expiratory muscles may be more susceptible than the diaphragm to SCD-induced vaso-occlusive damage.

Does influenza vaccination improve pediatric asthma outcomes?

OBJECTIVE: Controversy exists regarding the effectiveness of influenza vaccination in preventing influenza-related asthma exacerbations in the pediatric population. While yearly influenza immunization is widely recommended for children with asthma, there is currently little evidence to support this practice. Several studies have demonstrated no measurable benefit in asthma outcomes. This study sought to determine whether influenza vaccination status is associated with indicators of asthma morbidity within the military pediatric population. METHODS: A survey was conducted of patients 3 to 18 years of age with a diagnosis of asthma enrolled in the pediatric clinics of Brooke Army Medical Center, Fort Sam Houston, Texas, and Wilford Hall Medical Center, Lackland Air Force Base, Texas. Management practices and outcomes for 80 children were evaluated. Data were analyzed using the statistical package SPSS version 12 (SPSS Inc., Chicago). Univariate analyses were performed to identify associations between influenza vaccination, selected demographic variables and asthma exacerbation defined by oral steroid prescription, hospital visits, and unscheduled clinic or emergency department visits for asthma symptoms. Logistic regression analyses were conducted to detect possible confounding variables. RESULTS: In the univariate analyses, current influenza vaccination status was associated with a significant reduction of oral steroid use in the 12 months before the survey. This relationship was appreciated to a lesser extent with emergency department or unscheduled clinic visits in the last 12 months. No significant differences were found regarding the distribution of influenza vaccination status across selected demographic variables. In the multivariate analyses, current influenza vaccination status was independently associated with significantly decreased odds of using oral steroids in the previous 12 months. There was no evidence of confounding or effect modification. CONCLUSIONS: This study suggests influenza vaccination is associated with fewer asthma exacerbations. After controlling for several potential confounding variables, administration of influenza vaccine was associated with a protective effect against indicators of asthma exacerbations. Our results indicate that children with asthma in the military beneficiary population may benefit from annual influenza vaccination.

Can equal access to care eliminate racial disparities in pediatric asthma outcomes?

A survey was given to the parents of 80 children with asthma between the ages of 3 and 18 years at the Pediatric Pulmonology Clinics of three military treatment facilities to evaluate asthma management and outcomes for different racial groups. Results demonstrated that management practices for the three groups were similar and that there were no significant differences in emergency department visits, prescription of oral steroids, or in the number of hospitalizations across the three groups. These findings suggest that equal access to care may allow children of different racial backgrounds to receive similar asthma care and achieve similar outcomes.

Ethics training for military medical trainees: the Brooke Army Medical Center experience.

Biomedical ethics training during graduate medical education programs is required by the Accreditation Council for Graduate Medical Education. Apart from this requirement, medical ethics education is an integral component of military medical practice. Although ethics education and training are required, tools to assess the effectiveness of ethics education are not well developed. Furthermore, although biomedical ethics education is mandated for new Army physician trainees, there has not been a systematic objective assessment of the effectiveness of that training. We report the concept underlying the design and implementation of a military biomedical ethics seminar for new Army physician trainees. Combining a didactic component and case analysis through small-group discussions, we emphasized providing tools to analyze ethical dilemmas both in the medical center environment and in the operational medicine environment. A total of 47 Army interns participated in the seminar. Eighty-nine percent of participants agreed or strongly agreed that the ethics orientation met expectations. Seventy-two percent agreed or strongly agreed that the information presented would affect their practice. Ninety-six percent thought that the small-group discussions were effective, and 80% thought that the presentations enhanced knowledge from medical school.