Efficacy of Budesonide vs Fluticasone for Initial Treatment of Eosinophilic Esophagitis in a Randomized Controlled Trial

Background and Aims: Topical steroid treatments for eosinophilic esophagitis (EoE) include swallowed fluticasone from a multi-dose inhaler (MDI) or oral viscous budesonide (OVB) slurry, but the 2 have never been compared. We assessed whether OVB was more effective than MDI for initial treatment of patients with EoE. Methods: In a double-blind, double-dummy trial, patients with a new diagnosis of EoE were randomly assigned to groups given 8 weeks of either OVB (1 mg/4 mL) twice daily plus a placebo inhaler (n = 56) or fluticasone MDI (880 μg) twice daily plus a placebo slurry (n = 55). Primary outcomes were post-treatment maximum eosinophil counts per high-power field (eos/hpf) and a validated dysphagia score (dysphagia symptom questionnaire [DSQ]) at week 8. Secondary outcomes included endoscopic severity (validated EoE endoscopic reference score), histologic response (<15 eos/hpf), and safety. Results: In a modified intention-to-treat analysis, the subjects had baseline peak eosinophil counts of 73 and 77 eos/hpf in the OVB and MDI groups, respectively, and DSQ scores of 11 and 8. Post-treatment eosinophil counts were 15 and 21 in the OVB and MDI groups, respectively (P =.31), with 71% and 64% achieving histologic response (P =.38). DSQ scores were 5 and 4 in the OVB and MDI groups (P =.70). Similar trends were noted for post-treatment total EoE endoscopic reference scores (2 vs 3; P =.06). Esophageal candidiasis developed in 12% of patients receiving OVB and 16% receiving MDI; oral thrush was observed in 3% and 2%, respectively. Conclusions: In a randomized clinical trial, initial treatment of EoE with either OVB or fluticasone MDI produced a significant decrease in esophageal eosinophil counts and improved dysphagia and endoscopic features. However, OVB was not superior to MDI, so either is an acceptable treatment for EoE. ClinicalTrials.gov ID NCT02019758

Paracetamol sales and atopic disease in children and adults: an ecological analysis

The authors recently observed that frequent paracetamol use was positively associated with asthma and rhinitis in young adults. Therefore, an ecological analysis was performed to measure international associations between paracetamol sales and atopic disease prevalences in children and adults. Published data from the International Study of Asthma and Allergies in Childhood (ISAAC) on the prevalence of four atopic symptoms in 13-14-yr-olds (112 centres) and 6-7-yr-olds (66 centres) in 1994/1995, and European Community Respiratory Health Survey (ECRHS) data on the prevalence of asthma symptoms, diagnosed asthma and rhinitis (44 centres), prevalence of atopy, mean bronchial responsiveness and mean total immunoglobulin E levels (34 centres) in young adults in 1991/1992, were used. Their associations with national 1994/1995 per capita paracetamol sales were measured using linear regression. Paracetamol sales were high in English-speaking countries, and were positively associated with asthma symptoms, eczema and allergic rhinoconjunctivitis in 13-14-yr-olds, and with wheeze, diagnosed asthma, rhinitis and bronchial responsiveness in adults. The prevalence of wheeze increased by 0.52% in 13-14-yr-olds and by 0.26% in adults (

Dietary intake of flavonoids and asthma in adults

Epidemiological studies have suggested that a high consumption of apples may protect against asthma and chronic obstructive pulmonary disease. This effect has been attributed to their high flavonoid content, but few studies have investigated the relationship between flavonoid intake and obstructive lung disease directly.In a population-based, case-control study of 1,471 adults aged 16–50 yrs in London (UK), the present study examined whether dietary intake of catechins, flavonols and flavones was negatively associated with asthma, asthma severity and chronic sputum production. Asthma was defined by positive responses to a standard screening questionnaire in 1996 and information about usual diet was obtained by a food frequency questionnaire in 1997.After controlling for potential confounders, dietary intake of these three flavonoid subclasses was not significantly associated with asthma, (odds ratio per quintile (95% confidence interval) = 0.94 (0.86–1.02); 1.00 (0.92–1.09); 0.98 (0.88 –1.08) for flavones, flavonols and total catechins, respectively) nor was it associated with asthma severity, or chronic sputum production.In conclusion, no evidence was found for a protective effect of three major subclasses of dietary flavonoids on asthma. It is possible that other flavonoids or polyphenols present in apples may explain the protective effect of apples on obstructive lung disease

Copy-number variation genotyping of GSTT1 and GSTM1 gene deletions by real-time PCR

Background: Structural variation in the human genome is increasingly recognized as being highly prevalent and having relevance to common human diseases. Array-based comparative genome-hybridization technology can be used to determine copy-number variation (CNV) across entire genomes, and quantitative PCR (qPCR) can be used to validate de novo variation or assays of common CNV in disease-association studies. Analysis of large qPCR data sets can be complicated and time-consuming, however.Methods: We describe qPCR assays for GSTM1 (glutathione S-transferase mu 1) and GSTT1 (glutathione S-transferase theta 1) gene deletions that can genotype up to 192 samples in duplicate 5-µL reaction volumes in &lt;2 h on the ABI Prism 7900HT Sequence Detection System. To streamline data handling and analysis of these CNVs by qPCR, we developed a novel interactive, macro-driven Microsoft Excel® spreadsheet. As proof of principle, we used our software to analyze CNV data for 1478 DNA samples from a family-based cohort.Results: With only 8 ng of DNA template, we assigned CNV genotypes (i.e., 2, 1, or 0 copies) to either 96% (GSTM1) or 91% (GSTT1) of all DNA samples in a single round of PCR amplification. Genotyping accuracy, as ascertained by familial inheritance, was &gt;99.5%, and independent genotype assignments with replicate real-time PCR runs were 100% concordant.Conclusions: The genotyping assay for GSTM1 and GSTT1 gene deletion is suitable for large genetic epidemiologic studies and is a highly effective analysis system that is readily adaptable to analysis of other CNV

Umbilical cord and maternal blood red cell fatty acids and early childhood wheezing and eczema

Background: Few studies have explored whether fetal exposure to n-6 and n-3 fatty acids influences the inception of atopic disease.Objective: To assess prenatal fatty acid exposures as predictors of early childhood wheezing and eczema.Methods: In the Avon Longitudinal Study of Parents and Children, late pregnancy maternal blood samples and umbilical cord blood samples were assayed for n-6 and n-3 fatty acids (percentage of total red cell phospholipid), and mothers were asked about wheezing and eczema in their children. We measured associations of 11 n-6 and n-3 fatty acid exposures with wheezing at 30 to 42 months, with wheezing patterns defined by presence (+) or absence (?) of wheezing during 2 periods, 0 to 6 months and 30 to 42 months (transient infant, +/?; later-onset, ?/+; persistent, +/+; n = 1191 and n = 2764 for cord and maternal analyses, respectively), and with eczema at 18 to 30 months (n = 1238 and n = 2945 for cord and maternal analyses, respectively).Results: In cord blood red cells, the ratio of arachidonic:eicosapentaenoic acid was positively associated with eczema (adjusted odds ratio [OR] per doubling, 1.14; 95% CI, 1.00-1.31; P = .044), the ratio of linoleic acid:?-linolenic acid was positively associated with later-onset wheeze (OR, 1.30; CI, 1.04-1.61; P = .019), and the ratio of ?-linolenic acid:n-3 products was negatively associated with later-onset wheeze (OR, 0.86; CI, 0.75-0.99; P = .040). However, these associations were no longer significant after adjusting for multiple comparisons.Conclusions: It seems unlikely that fetal exposure to n-6 and n-3 fatty acids is an important determinant of early childhood wheezing and atopic disease

Maternal Nrf2 and gluthathione-S-transferase polymorphisms do not modify associations of prenatal tobacco smoke exposure with asthma and lung function in school-aged children

Background: Maternal smoking during pregnancy has detrimental effects on the respiratory health of infants and children. Polymorphisms of antioxidant genes including glutathione-S-transferases (GSTs) have been proposed as candidates for asthma and reduced lung function in children. Methods: Women enrolled in the Avon Longitudinal Study of Parents and Children reported smoking habits during pregnancy. Asthma status in their children was established at age 7.5 years from parental reports and lung function was measured by spirometry at age 8.5 years. Maternal and child DNA were genotyped for deletions of GSTM1 and GSTT1 and functional polymorphisms of GSTP1 and Nrf2 genes. Associations of prenatal tobacco smoke exposure with asthma and lung function in children were stratified by maternal genotype. Results: In 6606 children, maternal smoking during pregnancy was negatively associated with maximal mid expiratory flow (FEF25-75) (?0.05 SD units, 95% CI ?0.07 to ?0.03, p&lt;0.001). There was little evidence for interactions between maternal smoking and any maternal genotype considered on children's asthma or lung function. Maternal smoking was associated with reduced childhood FEF25-75 only in mother-child pairs (n=1227) with both copies of GSTM1 deleted (?0.08 SD units, 95% CI ?0.14 to ?0.02, p=0.01) or (n=2313) at least one copy of GSTT1 present (?0.05 SD units, 95% CI ?0.09 to 0, p=0.03). Conclusion: This study confirms a detrimental effect of intrauterine tobacco smoke exposure on childhood lung function but no strong evidence of modification by maternal genotype for important antioxidant genes. Adverse effects of fetal exposure to tobacco smoke on the respiratory health of children may be mediated by pathways other than oxidative stress. <br/

The relation of dietary patterns to adult lung function and chronic obstructive pulmonary disease

Previous studies of diet and lung function have focused on associations with individual nutrients and foods, and not dietary patterns.The relationships between dietary patterns and lung function and spirometrically defined chronic obstructive pulmonary disease (COPD) were investigated in 1,551 males and 1,391 females in Hertfordshire, UK. Dietary information was obtained by food frequency questionnaire and dietary patterns were identified using principal components analysis.Using regression analysis, after controlling for confounders, a "prudent" pattern (high consumption of fruit, vegetables, oily fish and wholemeal cereals) was positively associated with Forced Expiratory Volume in one second (FEV1) (P trend &lt;0.001 in men, 0.008 in females) (difference in FEV1 between top and bottom quintiles of pattern score, 0.18 litres (95% CI: 0.08 to 0.28) in men, 0.08 litres (-0.00 to 0.16) in females). This pattern was also positively associated with Forced Vital Capacity (FVC) in both sexes. Males with a higher "prudent" pattern score had a higher FEV1/FVC (P trend 0.002) and a lower prevalence of COPD (odds ratio comparing top versus bottom quintile, 0.46 (0.26 to 0.81), P trend 0.012). Associations in males were stronger in smokers than non-smokers (P interaction for FEV1/FVC 0.002).A "prudent" dietary pattern may protect against impaired lung function and COPD, especially in male smoker

Umbilical cord trace elements and minerals and risk of early childhood wheezing and eczema

It has been suggested that foetal nutrition might influence the inception of wheezing and atopic disorders in childhood but specific nutrients have not been implicated.&lt;p&gt;&lt;/p&gt; In the Avon Longitudinal Study of Parents and Children umbilical cord samples were assayed for trace elements and minerals, and mothers were asked about wheezing and eczema in their children. Associations of cord concentrations of selenium, zinc, copper, manganese, magnesium, iron, lead and mercury with wheezing at 30–42 months, with wheezing patterns defined by the presence or absence of transient infant, later onset or persistent wheezing at 0–6 months and 30–42 months, respectively (n=2,044), and with eczema at 18–30 months (n=2,173), were analysed.&lt;p&gt;&lt;/p&gt; Cord selenium was negatively associated with persistent wheeze (adjusted odds ratio (OR) per doubling concentration: 0.67). Cord iron was negatively associated with later onset wheeze (OR: 0.86) and with eczema (OR: 0.90). Children with high cord concentrations of selenium and iron were less likely than those with low concentrations to wheeze transiently in infancy.&lt;p&gt;&lt;/p&gt; The level of foetal exposure to selenium and iron may possibly influence the risk of wheezing and eczema in early childhood although, in view of the multiple analyses carried out, it is possible that the main findings occurred by chance.&lt;p&gt;&lt;/p&gt