James C. Slaughter

Effects of ambient air pollution on symptom severity and medication use in children with asthma

BACKGROUND Exposure to air pollutants has been investigated as a possible cause of asthma attacks in children. OBJECTIVE To investigate the short-term effects of air pollutants on a panel of 133 children with asthma who enrolled in the Childhood Asthma Management Program. METHODS During screening, the children completed daily diary cards for an average of 58 days to indicate their medication use and asthma severity. We used ordinal logistic regression to compare the odds of a more serious relative to a less serious asthma attack, and we used a Poisson model to analyze medication use. In both analyses we accommodate dependence in the data and different periods of observation for study subjects. RESULTS Our results indicate that a 10-microg/m3 increase in particulate matter less than or equal to 2.5 microm (PM2.5) lagged 1 day was associated with a 1.20 times increased odds of having a more serious asthma attack [95% confidence interval (CI), 1.05 to 1.37] and a 1.08-fold increase in medication use (95% CI, 1.01 to 1.15). A 10-microg/m3 increase in particulate matter less than or equal to 10 microm (PM10) increased the odds of a more serious asthma attack (odds ratio = 1.12; 95% CI, 1.04 to 1.22) and also increased medication use (relative risk = 1.05; 95% CI, 1.00 to 1.09). CONCLUSIONS Increases in PM2.5 and PM10 are significantly associated with an increased risk of more severe asthma attacks and medication use in Seattle area children with asthma. We also found associations with carbon monoxide, but we believe that carbon monoxide is a marker for exposure to combustion byproducts.

Efficacy of Esophageal Impedance/pH Monitoring in Patients With Refractory Gastroesophageal Reflux Disease, on and off Therapy

BACKGROUND & AIMS Intraluminal impedance monitoring has given new dimensions to the diagnosis of reflux disease. However, there is no defined algorithm for evaluating refractory reflux symptoms. We studied whether combined impedance/pH monitoring in patients on therapy can predict acid reflux in patients off therapy and whether testing should be carried out when patients are on or off therapy. METHODS Thirty-nine adults (mean age, 50 years; 24 female) with refractory reflux symptoms were evaluated by impedance/pH monitoring while on therapy, followed by wireless pH monitoring while off therapy. Non-acid reflux events in patients on therapy were correlated with acid reflux parameters studied off therapy. In addition, the likelihood of test abnormalities on and off therapy was determined. RESULTS In 25 of 39 patients (64%) on therapy, impedance testing was normal, with a median of 69 events (interquartile, 63.0-78.0). The percentage of time at pH <4 was within the normal range for all patients who were on therapy. The pH test results were abnormal in 28 of 39 patients (72%) when studied off therapy. Ninety-three of patients with abnormal impedance on therapy also had abnormal acid reflux off therapy. When both groups were off therapy, the patients with abnormal impedance parameters on therapy had significantly higher median (interquartile) 2-day baseline levels of esophageal acid exposure (8.7%, 6.9%-12.5%), compared with those of patients with normal impedance parameters while on therapy (6.0%, 2.8%-9.4%; P = .026). CONCLUSIONS Abnormal impedance in patients on therapy predicts acid reflux in patients off therapy. In patients with refractory reflux, combined impedance/pH monitoring might provide the single best strategy for evaluation of reflux symptoms.

Iron deficiency accelerates Helicobacter pylori–induced carcinogenesis in rodents and humans

Gastric adenocarcinoma is strongly associated with Helicobacter pylori infection; however, most infected persons never develop this malignancy. H. pylori strains harboring the cag pathogenicity island (cag+), which encodes CagA and a type IV secretion system (T4SS), induce more severe disease outcomes. H. pylori infection is also associated with iron deficiency, which similarly augments gastric cancer risk. To define the influence of iron deficiency on microbial virulence in gastric carcinogenesis, Mongolian gerbils were maintained on iron-depleted diets and infected with an oncogenic H. pylori cag+ strain. Iron depletion accelerated the development of H. pylori-induced premalignant and malignant lesions in a cagA-dependent manner. H. pylori strains harvested from iron-depleted gerbils or grown under iron-limiting conditions exhibited enhanced virulence and induction of inflammatory factors. Further, in a human population at high risk for gastric cancer, H. pylori strains isolated from patients with the lowest ferritin levels induced more robust proinflammatory responses compared with strains isolated from patients with the highest ferritin levels, irrespective of histologic status. These data demonstrate that iron deficiency enhances H. pylori virulence and represents a measurable biomarker to identify populations of infected persons at high risk for gastric cancer.

Caution About Overinterpretation of Symptom Indexes in Reflux Monitoring for Refractory Gastroesophageal Reflux Disease

BACKGROUND & AIMS Symptom index (SI) and symptom association probability (SAP) are indexes used to analyze data collected from ambulatory pH and/or impedance monitoring and quantify the association between symptoms and reflux events. However, their characteristics are not well defined. We measured factors that affect SI and SAP values to determine their utility in assessing patients with refractory gastroesophageal reflux disease (GERD). METHODS We conducted a cross-sectional study of 254 patients with poor responses to proton pump inhibitor (PPI) therapy. Participants underwent esophagogastroduodenoscopy and wireless pH (n = 127) or impedance/pH monitoring when they were not receiving PPI therapy (n = 41) or impedance/pH monitoring while they received twice-daily PPI therapy (n = 86). SI and SAP values were calculated individually; ranges of values for each cell in the 2 × 2 contingency table were determined. Monte Carlo simulation was conducted to determine how varying reflux and symptom rates within the contingency table impacted the expected value and variability in SI and SAP. RESULTS At best, only 33% of patients who were refractory to PPI therapy had positive SI or SAP scores for acid or nonacid reflux events. Abnormal SAP (>95%) and SI (>50%) scores required high rates of reflux. At reflux rates less than 10%, observed in 70% of the studied population, SI and SAP values were largely determined by chance occurrences, rather than the relationship between symptoms and reflux. The values for each index varied significantly day-to-day. CONCLUSIONS SI or SAP indexes can be overinterpreted, unless patients with gastroesophageal reflux disease who are refractory to PPI therapy have high rates of reflux.

Association between particulate matter and emergency room visits, hospital admissions and mortality in Spokane, Washington.

There is conflicting evidence regarding the association between different size fractions of particulate matter (PM) and cardiac and respiratory morbidity and mortality. We investigated the short-term associations of four size fractions of particulate matter (PM1, PM2.5, PM10, and PM10–2.5) and carbon monoxide with hospital admissions and emergency room (ER) visits for respiratory and cardiac conditions and mortality in Spokane, Washington. We used a log-linear generalized linear model to compare daily averages of PM and carbon monoxide with daily counts of the morbidity and mortality outcomes from January 1995 to June 2001. We examined pollution lags ranging from 0 to 3 days and compared our results to a similar log-linear generalized additive model. Effect estimates tended to be smaller and have larger standard errors for the generalized linear model. Overall, we saw no association with respiratory ER visits and any size fraction of PM. However, there was a suggestion of greater respiratory effect from fine PM when compared to coarse fraction. Carbon monoxide was associated with both all respiratory ER visits and visits for asthma at the 3-day lag. We feel that carbon monoxide may be serving as a marker for combustion-derived pollutants, which is one large component of the diverse air pollutant mixture. We also found no association with any size fraction of PM or CO with cardiac hospital admissions or mortality at the 0- to 3-day lag. We found no consistent associations between any size fraction of PM and cardiac or respiratory ER visits or hospital admissions.

A New pH Catheter for Laryngopharyngeal Reflux: Normal Values

Laryngopharyngeal reflux (LPR) represents a challenging field. Therapeutic studies of proton pump inhibitors in LPR have shown mixed results. The Restech pH catheter (Respiratory Technology Corp., San Diego, CA) is a minimally invasive device for detection of oropharyngeal acid reflux. The aim of this study was to provide normative data using this device in both distal esophagus and oropharynx.

High economic burden of caring for patients with suspected extraesophageal reflux.

OBJECTIVES:Extraesophageal symptoms are common manifestations of gastroesophageal reflux disease (GERD). Lack of a definitive diagnostic or treatment standards complicate management, which often leads to multiple specialty consultations, procedures, pharmaceuticals and diagnostic tests. The aim of this study was to determine the economic burden associated with extraesophageal reflux (EER).METHODS:Direct costs of evaluation were estimated for patients referred with symptoms attributed to EER between 2007 and 2011. Medicare payment for evaluation and management and pharmaceutical prices was used to calculate first year and overall costs of evaluating and treating extraesophageal symptoms attributed to reflux.RESULTS:Overall, 281 patients were studied (cough (50%), hoarseness (23%), globus/post-nasal drainage (15%), asthma (9%), and sore throat (3%)). Over a median (interquartile range) of 32 (16–46) months follow-up, patients had a mean (95% confidence interval) of 10.1 (9.4–10.9) consultations with specialists and underwent 6.4 (3–9) diagnostic procedures. Overall, the mean initial year direct cost was

Cross-Reactive and Potent Neutralizing Antibody Responses in Human Survivors of Natural Ebolavirus Infection

5,438 per patient being evaluated for EER. Medical and non-medical components contributed

Reactive oxygen species from NADPH oxidase contribute to altered pulmonary vascular responses in piglets with chronic hypoxia-induced pulmonary hypertension

5,154 and

Tumor necrosis factor receptor 1-dependent depletion of mucus in immature small intestine: a potential role in neonatal necrotizing enterocolitis

283. Of the overall cost, 52% were attributable to the use of proton pump inhibitors. During the initial year, direct costs were 5.6 times higher than those reported for typical GERD (