Lansoprazole for children with poorly controlled asthma: a randomized controlled trial.

CONTEXT: Asymptomatic gastroesophageal reflux (GER) is prevalent in children with asthma. Untreated GER has been postulated to be a cause of inadequate asthma control in children despite inhaled corticosteroid treatment, but it is not known whether treatment with proton pump inhibitors improves asthma control. OBJECTIVE: To determine whether lansoprazole is effective in reducing asthma symptoms in children without overt GER. DESIGN, SETTING, AND PARTICIPANTS: The Study of Acid Reflux in Children With Asthma, a randomized, masked, placebo-controlled, parallel clinical trial that compared lansoprazole with placebo in children with poor asthma control who were receiving inhaled corticosteroid treatment. Three hundred six participants enrolled from April 2007 to September 2010 at 19 US academic clinical centers were followed up for 24 weeks. A subgroup had an esophageal pH study before randomization. INTERVENTION: Participating children were randomly assigned to receive either lansoprazole, 15 mg/d if weighing less than 30 kg or 30 mg/d if weighing 30 kg or more (n = 149), or placebo (n = 157). MAIN OUTCOME MEASURES: The primary outcome measure was change in Asthma Control Questionnaire (ACQ) score (range, 0-6; a 0.5-unit change is considered clinically meaningful). Secondary outcome measures included lung function measures, asthma-related quality of life, and episodes of poor asthma control. RESULTS: The mean age was 11 years (SD, 3 years). The mean difference in change (lansoprazole minus placebo) in the ACQ score was 0.2 units (95% CI, 0.0-0.3 units). There were no statistically significant differences in the mean difference in change for the secondary outcomes of forced expiratory volume in the first second (0.0 L; 95% CI, -0.1 to 0.1 L), asthma-related quality of life (-0.1; 95% CI, -0.3 to 0.1), or rate of episodes of poor asthma control (relative risk, 1.2; 95% CI, 0.9-1.5). Among the 115 children with esophageal pH studies, the prevalence of GER was 43%. In the subgroup with a positive pH study, no treatment effect for lansoprazole vs placebo was observed for any asthma outcome. Children treated with lansoprazole reported more respiratory infections (relative risk, 1.3 [95% CI, 1.1-1.6]). CONCLUSION: In this trial of children with poorly controlled asthma without symptoms of GER who were using inhaled corticosteroids, the addition of lansoprazole, compared with placebo, improved neither symptoms nor lung function but was associated with increased adverse events. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00442013.

Effects of obstructive sleep apnea and gastroesophageal reflux disease on asthma control in obesity.

BACKGROUND: Obesity is a risk factor for asthma. Obese asthmatics often have poor asthma control and respond poorly to therapy. It has been suggested that co-morbidities associated with obesity, such as reflux and obstructive sleep apnea, could be important factors contributing to poor asthma control in obese patients. OBJECTIVES: The purpose of this study was to determine if (1) reflux and/or (2) symptoms of sleep apnea contribute to poor asthma control in obesity. METHODS: We studied asthmatic subjects participating in a trial of reflux treatment. Participants underwent baseline evaluation of asthma symptoms and lung function. Overall 304 participants underwent esophageal pH probe testing; 246 participants were evaluated for obstructive sleep apnea symptoms. RESULTS: Of 402 participants in this trial, 51% were obese. Role of reflux in asthma control. Those with higher body mass index (BMI) reported a higher prevalence of reflux symptoms, but the prevalence of pH probe acid reflux was similar in all groups. Reflux was not associated with measures of asthma control in obese patients. Role of obstructive sleep apnea in asthma control. Symptoms and self-report of obstructive sleep apnea were more common with increasing BMI and associated with worse asthma control as measured by the Juniper Asthma Control questionnaire and Asthma Symptom Utility Index. CONCLUSIONS: Our data suggest that obstructive sleep apnea, but not gastroesophageal reflux disease, may contribute significantly to poor asthma control in obese patients.

Criteria to screen for chronic sinonasal disease.

BACKGROUND: Sinusitis and rhinitis are associated with uncontrolled asthma. There are no simple, validated tools to screen for these diseases. The objective of this study was to assess instruments to assist in the diagnosis of chronic sinonasal disease. METHODS: Participants without acute sinonasal symptoms underwent an extensive evaluation. The results were submitted to an expert panel that used the Delphi method to achieve consensus. Using the consensus diagnosis of the panel, we determined the sensitivity and specificity of test procedures to diagnose chronic sinonasal disease. We determined the reproducibility of the most sensitive and specific instrument in a separate cohort. RESULTS: Fifty-nine participants were evaluated, and the expert panel reached consensus for all (42 participants with chronic sinonasal disease, 17 participants without chronic sinonasal disease). A six-item questionnaire based on the frequency of nasal symptoms was the most sensitive tool used to diagnose sinonasal disease (minimum specificity, 0.90). Reproducibility testing in a separate cohort of 63 participants (41 chronic sinonasal disease with asthma, 22 chronic sinonasal disease without asthma) showed a concordance correlation coefficient of 0.91 (95% CI, 0.85 to 0.94) when this questionnaire was limited to five items (ie, excluding a question on smell). This five-item questionnaire had a sensitivity of 0.90 (95% CI, 0.77 to 0.97), a specificity of 0.94 (95% CI, 0.71 to 1.00), and an area under the receiver operating characteristic curve of 0.97 (95% CI, 0.93 to 1.0). Sinus CT scans and nasal endoscopy lacked sensitivity for use in the diagnosis of chronic sinonasal disease. CONCLUSIONS: We have developed a sensitive, specific, and reproducible instrument to screen for chronic sinonasal disease. Validation studies of this five-item questionnaire are needed, including in patients with asthma.

Randomized trial of the effect of drug presentation on asthma outcomes: the American Lung Association Asthma Clinical Research Centers.

BACKGROUND: Information that enhances expectations about drug effectiveness improves the response to placebos for pain. Although asthma symptoms often improve with placebo, it is not known whether the response to placebo or active treatment can be augmented by increasing expectation of benefit. OBJECTIVE: The study objective was to determine whether response to placebo or a leukotriene antagonist (montelukast) can be augmented by messages that increase expectation of benefit. METHODS: A randomized 20-center controlled trial enrolled 601 asthmatic patients with poor symptom control who were assigned to one of 5 study groups. Participants were randomly assigned to one of 4 treatment groups in a factorial design (ie, placebo with enhanced messages, placebo with neutral messages, montelukast with enhanced messages, or montelukast with neutral messages) or to usual care. Assignment to study drug was double masked, assignment to message content was single masked, and usual care was not masked. The enhanced message aimed to increase expectation of benefit from the drug. The primary outcome was mean change in daily peak flow over 4 weeks. Secondary outcomes included lung function and asthma symptom control. RESULTS: Peak flow and other lung function measures were not improved in participants assigned to the enhanced message groups versus the neutral messages groups for either montelukast or placebo; no differences were noted between the neutral placebo and usual care groups. Placebo-treated participants had improved asthma control with the enhanced message but not montelukast-treated participants; the neutral placebo group did have improved asthma control compared with the usual care group after adjusting for baseline difference. Headaches were more common in participants provided messages that mentioned headache as a montelukast side effect. CONCLUSIONS: Optimistic drug presentation augments the placebo effect for patient-reported outcomes (asthma control) but not lung function. However, the effect of montelukast was not enhanced by optimistic messages regarding treatment effectiveness.

Effects of alcohol on insulin-like growth factor I and insulin-like growth factor binding protein 3 in postmenopausal women.

BACKGROUND: Increased circulating insulin-like growth factor I (IGF-I) concentrations, frequently adjusted for IGF binding protein 3 (IGFBP-3), have been associated with increased risk of several types of cancer, including colon, prostate, and breast. Studies have suggested that alcohol may affect IGF-I or IGFBP-3; however, controlled feeding studies to assess alcohol's effects on IGF-I or IGFBP-3 have not been conducted. OBJECTIVE: To determine whether chronic, moderate alcohol intake affects serum IGF-I or IGFBP-3 concentrations, we performed a controlled, crossover feeding study. DESIGN: Fifty-three postmenopausal women were randomly assigned to consume 0 g (control), 15 g (one drink), or 30 g (2 drinks) alcohol daily for 8 wk and were rotated through the other 2 intake levels in random order. All foods and beverages were provided during the intervention. Individuals were monitored and calories adjusted to maintain constant weight, and serum was collected at the end of each diet period. RESULTS: Compared with the effects of 0 g alcohol/d, IGF-I concentrations were nearly unchanged by 15 g alcohol/d (0.8%; 95% CI: -3.2%, 3.5%) but decreased significantly by 4.9% (95% CI: -8.0%, -1.6%) with 30 g alcohol/d. IGFBP-3 concentrations significantly increased by 3.0% (95% CI: 0.4%, 5.6%) with 15 g alcohol/d but did not increase significantly with 30 g/d (1.8%; 95% CI: -0.9%, 4.5%). CONCLUSIONS: To our knowledge, this is the first published controlled diet study to find that in postmenopausal women, when weight is kept constant, alcohol consumption reduces the amount of serum IGF-I potentially available for receptor binding. These findings suggest that the effect of alcohol intake should be considered in studies of IGF-I, IGFBP-3, and cancer in postmenopausal women.

Relationship between serum leptin levels and alcohol consumption in a controlled feeding and alcohol ingestion study.

We examined serum leptin levels in a controlled feeding and alcohol ingestion study to elucidate potential mechanisms by which alcohol may affect cancer and immunologically related health risks. A total of 53 healthy, nonsmoking postmenopausal women completed a random-order, three-period crossover design study in which each woman received zero (0 g of alcohol), one (15 g of alcohol), or two (30 g alcohol) drinks per day. After accounting for differences in body mass index, women who consumed 15 or 30 g of alcohol per day had 7.3% (95% confidence interval [CI] = 3.0% to 15.1%) and 8.9% (95% CI = 1.6% to 16.7%) higher serum leptin levels, respectively (P(trend) =.018), than women who consumed 0 g of alcohol per day. Younger women (i.e., 49-54 years) demonstrated a statistically significantly larger association of alcohol consumption level with the increase in serum leptin levels than older women (i.e., 55-79 years) (24.4%, 95% CI = 9.3% to 42.0% versus 3.7%, 95% CI = -4.1% to 12.1% increase in serum leptin levels for 30 g of alcohol per day relative to 0 g of alcohol per day for the lowest age quartile compared with the three highest age quartiles combined; P =.022). These results indicate that moderate alcohol consumption (15-30 g of alcohol per day) increases serum leptin levels in postmenopausal women and may predispose moderate drinkers to the morbidities associated with chronic elevations of this hormone including cancer.

Consumption of watermelon juice increases plasma concentrations of lycopene and beta-carotene in humans.

Watermelon is a rich natural source of lycopene, a carotenoid of great interest because of its antioxidant capacity and potential health benefits. Assessment of bioavailability of lycopene from foods has been limited to tomato products, in which heat processing promotes lycopene bioavailability. We examined the bioavailability of lycopene from fresh-frozen watermelon juice in a 19-wk crossover study. Healthy, nonsmoking adults (36-69 y) completed three 3-wk treatment periods, each with a controlled, weight-maintenance diet. Treatment periods were preceded by "washout" periods of 2-4 wk during which lycopene-rich foods were restricted. All 23 subjects consumed the W-20 (20.1 mg/d lycopene, 2.5 mg/d beta-carotene from watermelon juice) and C-0 treatments (controlled diet, no juice). As a third treatment, subjects consumed either the W-40 (40.2 mg/d lycopene, 5.0 mg/d beta-carotene from watermelon juice, n = 12) or T-20 treatment (18.4 mg/d lycopene, 0.6 mg/d beta-carotene from tomato juice, n = 10). After 3 wk of treatment, plasma lycopene concentrations for the W-20, W-40, T-20 and C-0 treatments were (least squares means +/- SEM) 1078 +/- 106, 1183 +/- 139, 960 +/- 117 and 272 +/- 27 nmol/L, respectively. Plasma concentrations of beta-carotene were significantly greater after W-20 (574 +/- 49 nmol/L) and W-40 (694 +/- 73 nmol/L) treatments than after the C-0 treatment (313 +/- 27 nmol/L). Plasma lycopene concentrations did not differ at wk 3 after W-20, W-40 and T-20 treatments, indicating that lycopene was bioavailable from both fresh-frozen watermelon juice and canned tomato juice, and that a dose-response effect was not apparent in plasma when the watermelon dose was doubled.

Effects of moderate alcohol intake on fasting insulin and glucose concentrations and insulin sensitivity in postmenopausal women: a randomized controlled trial.

CONTEXT: Epidemiologic data demonstrate that moderate alcohol intake is associated with improved insulin sensitivity in nondiabetic individuals. No controlled-diet studies have addressed the effects of daily moderate alcohol consumption on fasting insulin and glucose concentrations and insulin sensitivity. OBJECTIVE: To determine whether daily consumption of low to moderate amounts of alcohol influences fasting insulin and glucose concentrations and insulin sensitivity in nondiabetic postmenopausal women. DESIGN, SETTING, AND PARTICIPANTS: Randomized controlled crossover trial of 63 healthy postmenopausal women, conducted at a clinical research center in Maryland between 1998 and 1999. INTERVENTIONS: Participants were randomly assigned to consume 0, 15, or 30 g/d of alcohol for 8 weeks each as part of a controlled diet. All foods and beverages were provided during the intervention. An isocaloric beverage was provided in the 0-g/d arm. Energy intake was adjusted to maintain constant body weight. MAIN OUTCOME MEASURES: Fasting insulin, triglyceride, and glucose concentrations, measured at the end of each dietary period; insulin sensitivity, estimated with a published index of glucose disposal rate corrected for fat-free mass based on fasting insulin and fasting triglyceride concentrations, compared among treatments with a mixed-model analysis of variance. RESULTS: A complete set of plasma samples was collected and analyzed for 51 women who completed all diet treatments. Consumption of 30 g/d of alcohol compared with 0 g/d reduced fasting insulin concentration by 19.2% (P =.004) and triglyceride concentration by 10.3% (P =.001), and increased insulin sensitivity by 7.2% (P =.002). Normal-weight, overweight, and obese individuals responded similarly. Only fasting triglyceride concentration was significantly reduced when comparing 0 and 15 g/d of alcohol (7.8%; P =.03), and no difference was found between consumption of 15 and 30 g/d of alcohol; however, there was a significant linear trend (P =.001). Fasting glucose concentrations were not different across treatments. CONCLUSIONS: Consumption of 30 g/d of alcohol (2 drinks per day) has beneficial effects on insulin and triglyceride concentrations and insulin sensitivity in nondiabetic postmenopausal women.

Moderate alcohol consumption lowers risk factors for cardiovascular disease in postmenopausal women fed a controlled diet.

BACKGROUND: Moderate alcohol consumption (1-2 drinks/d) may decrease cardiovascular disease risk in postmenopausal women by improving lipid profiles. OBJECTIVE: We measured the effect of moderate alcohol consumption on lipids and lipoproteins in postmenopausal women. DESIGN: Postmenopausal women (n = 51) consumed 0 (control), 15 (1 drink), and 30 (2 drinks) g alcohol (ethanol)/d for 8 wk each as part of a controlled diet in a randomized crossover design. The control diet provided approximately 15%, 53%, and 32% of energy from protein, carbohydrate, and fat, respectively. The energy provided from alcohol in the 15- and 30-g alcohol diets was replaced with energy from carbohydrate. RESULTS: Compared with concentrations after the control diet, plasma LDL cholesterol decreased from 3.45 to 3.34 mmol/L (P = 0.04) and triacylglycerol from 1.43 to 1.34 mmol/L (P = 0.05) after 15 g alcohol/d. There were no additional significant decreases in either lipid after an increase in alcohol intake from 15 to 30 g/d. Compared with concentrations after the control diet, plasma HDL cholesterol increased nonsignificantly from 1.40 to 1.43 mmol/L after 15 g alcohol/d but increased to 1.48 mmol/L after 30 g alcohol/d (P = 0.02). Apolipoprotein A-I increased significantly and apolipoprotein B decreased significantly after 30 g alcohol/d relative to the concentration after the control diet. CONCLUSIONS: Consumption of 15-30 g alcohol/d by postmenopausal women apparently decreases cardiovascular disease risk by improving lipid profiles. Plasma LDL-cholesterol and triacylglycerol concentrations improve after 15 g alcohol/d; plasma HDL cholesterol improves only after 30 g alcohol/d.