'Free' surfactant in gastric aspirates and bronchoalveolar lavage in children with and without reflux oesophagitis

Aim: Dipalmitoylphosphatidycholine (DPPC) is the characteristic and main constituent of surfactant. Adsorption of surfactant to epithelial surfaces may be important in the masking of receptors. The aims of the study were to (i) compare the quantity of free DPPC in the airways and gastric aspirates of children with gastroesophageal reflux disease (GORD) to those without and (ii) describe the association between free DPPC levels with airway cellular profile and capsaicin cough sensitivity. Methods: Children aged <14 years were defined as 'coughers' if a history of cough in association with their GORD symptoms was elicited before gastric aspirates and nonbronchoscopic bronchoalveolar lavage (BAL) were obtained during elective flexible upper gastrointestinal endoscopy. GORD was defined as histological presence of reflux oesophagitis. Spirometry and capsaicin cough-sensitivity test was carried out in children aged >6 years before the endoscopy. Results: Median age of the 68 children was 9 years (interquartile range (IQR) 7.2). Median DPPC level in BAL of children with cough (72.7 μg/mL) was similar to noncoughers (88.5). There was also no significant difference in DPPC levels in both BAL and gastric aspirates of children classified according to presence of GORD. There was no correlation between DPPC levels and cellular counts or capsaicin cough-sensitivity outcome measures. Conclusion: We conclude that free DPPC levels in the airways and gastric aspirate is not influenced by presence of cough or GORD defined by histological presence of reflux oesophagitis. Whether quantification of adsorbed surfactant differs in these groups remain unknown. Free DPPC is unlikely to have a role in masking of airway receptors. © 2006 Royal Australasian College of Physicians.

Airway cellularity, lipid laden macrophages and microbiology of gastric juice and airways in children with reflux oesophagitis

Background: Gastroesophageal reflux disease (GORD) can cause respiratory disease in children from recurrent aspiration of gastric contents. GORD can be defined in several ways and one of the most common method is presence of reflux oesophagitis. In children with GORD and respiratory disease, airway neutrophilia has been described. However, there are no prospective studies that have examined airway cellularity in children with GORD but without respiratory disease. The aims of the study were to compare (1) BAL cellularity and lipid laden macrophage index (LLMI) and, (2) microbiology of BAL and gastric juices of children with GORD (G+) to those without (G-). Methods: In 150 children aged <14-years, gastric aspirates and bronchoscopic airway lavage (BAL) were obtained during elective flexible upper endoscopy. GORD was defined as presence of reflux oesophagitis on distal oesophageal biopsies. Results: BAL neutrophil% in G- group (n = 63) was marginally but significantly higher than that in the G+ group (n = 77), (median of 7.5 and 5 respectively, p = 0.002). Lipid laden macrophage index (LLMI), BAL percentages of lymphocyte, eosinophil and macrophage were similar between groups. Viral studies were negative in all, bacterial cultures positive in 20.7% of BALs and in 5.3% of gastric aspirates. BAL cultures did not reflect gastric aspirate cultures in all but one child. Conclusion: In children without respiratory disease, GORD defined by presence of reflux oesophagitis, is not associated with BAL cellular profile or LLMI abnormality. Abnormal microbiology of the airways, when present, is not related to reflux oesophagitis and does not reflect that of gastric juices. © 2005 Chang et al; licensee BioMed Central Ltd.

Dichotomy of food and inhalant allergen sensitization in eosinophilic esophagitis

Background: Eosinophilic esophagitis (EE) is an emerging condition where patients commonly present with symptoms of gastroesophageal reflux disease and fail to respond adequately to anti-reflux therapy. Food allergy is currently recognized as the main immunological cause of EE; recent evidence suggests an etiological role for inhalant allergens. The presence of EE appears to be associated with other atopic illnesses. Objectives: To report the sensitization profile of both food and inhalant allergens in our EE patient cohort in relation to age, and to profile the prevalence of other allergic conditions in patients with EE. Method: The study prospectively analyzed allergen sensitization profiles using skin prick tests to common food allergens and inhalant allergens in 45 children with EE. Patch testing to common food allergens was performed on 33 patients in the same cohort. Comorbidity of atopic eczema, asthma, allergic rhinitis and anaphylaxis were obtained from patient history. Results: Younger patients with EE showed more IgE and patch sensitization to foods while older patients showed greater IgE sensitization to inhalant allergens. The prevalence of atopic eczema, allergic rhinitis and asthma was significantly increased in our EE cohort compared with the general Australian population. A total of 24% of our cohort of patients with EE had a history of anaphylaxis. Conclusion: In children with EE, the sensitization to inhalant allergens increases with age, particularly after 4 years. Also, specific enquiry about severe food reactions in patients presenting with EE is strongly recommended as it appears this patient group has a high incidence of anaphylaxis. © 2007 The Authors.

An objective study of acid reflux and cough in children using an ambulatory pHmetry-cough logger

Objective There are no objective ambulatory studies on the temporal relationship between reflux and cough in children. Commercial pHmetry loggers have slow capture rates (0.25 Hz) that limit objective quantification of reflux and cough. The authors aimed to evaluate if there is a temporal association between cough and acid pH in ambulatory children with chronic cough. setting and patients The authors studied children (aged <14 years) with chronic cough, suspected of acid reflux and considered for pHmetry using a specifically built ambulatory pHmetry–cough logger that enabled the simultaneous ambulatory recording of cough and pH with a fast (10 Hz) capture rate. Main outcome measures Coughs within (before and after) 10, 30, 60 and 120 s of a reflux episode (pH<4 for >0.5 s). Results Analysis of 5628 coughs in 20 children. Most coughs (83.9%) were independent of a reflux event. Cough–reflux (median 19, IQR 3–45) and reflux–cough (24.5, 13–51) sequences were equally likely to occur within 120 s. Within the 10 and 30 s time frame, reflux–cough (10 s=median 2.5, IQR 0–7.25; 30 s=6.5, 1.25–22.25) sequences were significantly less frequent than reflux–no cough (10 s=27, IQR 15–65; 30 s=24.5, 14.5–55.5) sequences, (p=0.0001 and p=0.001, respectively). No differences were found for 60 and 120 s time frame. Cough–reflux sequence (median 1.0, IQR 0–8) within 10 s was significantly less (p=0.0001) than no cough–reflux sequences (median 29.5, 15–67), within 30 s (p=0.006) and 60 s (p=0.048) but not within 120 s (p=0.47). Conclusions In children with chronic cough and suspected of having gastro-oesophageal reflux disease, the temporal relationship between acid reflux and cough is unlikely causal.

Cough and reflux esophagitis in children: their co-existence and airway cellularity

Background There are no prospective studies that have examined for chronic cough in children without lung disease but with gastroesophageal reflux (GER). In otherwise healthy children undergoing flexible upper gastrointestinal endoscopy (esophago-gastroscopy), the aims of the study were to (1) define the frequency of cough in relation to symptoms of GER, (2) examine if children with cough and reflux esophagitis (RE) have different airway cellularity and microbiology in bronchoalveolar lavage (BAL) when compared to those without. Methods Data specific for chronic cough (>4-weeks), symptoms of GER and cough severity were collected. Children aged <16-years (n = 150) were defined as 'coughers' (C+) if a history of cough in association with their GER symptoms was elicited before BAL were obtained during elective esophago-gastroscopy. Presence of esophagitis on esophageal biopsies was considered reflux esophagitis positive (E+). Results C+ (n = 69) were just as likely as C- (n = 81) to have esophagitis, odds ratio 0.87 (95%CI 0.46, 1.7). Median neutrophil percentage in BAL was significantly different between groups; highest in C+E- (7, IQR 28) and lowest in C-E+ (5, IQR 6). BAL positive bacterial culture occurred in 20.7% and were more likely present in current coughers (OR 3.37, 95%CI 1.39, 8.08). Airway neutrophilia (median 20%, IQR 34) was significantly higher in those with BAL positive bacterial cultures than those without (5%, 4; p = 0.0001). Conclusion In children without lung disease, the common co-existence of cough with symptoms of GER is independent of the occurrence of esophagitis. Airway neutrophilia when present in these children is more likely to be related to airway bacterial infection and not to esophagitis.

The sleep patterns of infants and young children with gastro-oesophageal reflux

Objective: Sleep disturbance in gastro-oesophageal reflux disease (GORD) in infants and young children has not been systematically studied nor has this manifestation been compared with population norms. Methods: Sleep patterns of 102 infants and children aged 1 to 36 months with and without GORD, defined by pH monitoring, were analysed using the same questionnaire as in recent studies of normal sleep behaviour in this age range. Main outcome measures included time taken to settle at night, the number of night time wakenings requiring parental intervention, day time sleep patterns and parents problems with their childs' sleep behaviour. Results: Compared with the population norms (n=3102), those with GORD (n=76) had greater prevalence of night time waking >3/night (50% vs 13% aged 3-12 months; 60% vs 10% aged 12-24 months, P<0.001), requirement of parental intervention (82% vs 55% aged 3-12 months, P < 0.05; 92% vs 55% aged 12-24 months, P < 0.001), significantly delayed onset of sleeping through the night, and greater prevalence of daytime sleep beyond 24 months. Similar but less striking differences were seen comparing those with (n = 76) and without GORD (n = 26). Conclusions: Sleep interruption occurs more frequently in infants and children with GORD than population norms. Objective evaluation of infants and children with sleep disturbance after the age of 3 months may avoid unnecessary over or under diagnosis of GORD. Systematic investigation of the contribution of GORD to sleep disturbance in infants and young children is warranted

Marked increase in proton pump inhibitors use in Australia

Objectives: To examine the trends in the prescribing of subsidised proton pump inhibitors (PPIs) and histamine receptor antagonists (H2RAs), in the Australian population from 1995 to 2006 to encourage discussion regarding appropriate clinical use. PPIs and H2RAs are the second highest drug cost to the publicly subsidised Pharmaceutical Benefits Scheme (PBS). Design: Government data on numbers of subsidised scripts, quantity and doses for PPIs and H2RAs were analysed by gender and age, dose and indication. Main outcome measure: Drug utilisation as DDD [defined daily dose]/1000 population/day. Results: The use of combined PPIs increased by 1318%. Utilisation increased substantially after the relaxation of the subsidised indications for PPIs in 2001. Omeprazole had the largest market share but was substituted by its S-enantiomer esomeprazole after its introduction in 2002. There was considerable use in the elderly with the peak use being in those aged 80 years and over. The utilisation of H2RAs declined 72% over 12 years. Conclusions: PPI use has increased substantially, not only due to substitution of H2RAs but to expansion in the overall market. Utilisation does not appear to be commensurate with prevalence of gastro-oesophageal reflux disease (GORD) nor with prescribing guidelines for PPIs, with significant financial costs to patients and PBS. This study encourages clinical discussion regarding quality use of these medicines. © 2010 John Wiley & Sons, Ltd.

HER2 positive gastric and gastroesophageal adenocarcinoma; An Irish tertiary center experience

Background: Trastuzumab has been approved for patients with human epidermal growth factor receptor 2 (HER2) over expression and gene amplification metastatic gastric cancer. Here we present the prevalence of HER2 positive gastric cancer in an Irish population, the use of Trastuzumab in first line and beyond progression. Methods: The study was conducted in St James's Hospital, Dublin. A retrospective analysis of the date of patients with HER2 positive gastric cancer over a period of 3 years was carried out. Her2 positive was defined as immunohistochemistry (IHC) score of +3, of IHC score of +2 and increased gene copy number by fluorescence in situ hybridization (FISH). Overall survival was calculated from the day of initiation of treatment with Trastuzumab until death. Results: During the study period 140 patients with gastric and gastro-esophageal junction adenocarcinoma were treated. Out of those, 30 (21.4%) had HER2 positive disease. Among HER2 positive disease patients 18 (12.8%) were treated with first line Trastuzumab containing regimen with a median overall survival of 13 months. Nine (50%) developed progressive disease while on Trastuzumab and of those, 4 (22.2%) patients continued on Trastuzumab beyond progression, two (11.1%) of whom achieved stable disease and a prolonged survival. Conclusion: HER2 positivity rate in an Irish population with advanced gastric and gastro-esophageal junction adenocarcinoma is 21.4%. Treatment with Trastuzumab in the first line in combination with chemotherapy is a reasonable approach. Continuation of Trastuzumab beyond progression is a feasible strategy that requires further exploration.

Weather variability, tides, and Barmah Forest Virus Disease in the Gladstone region, Australia

In this study we examined the impact of weather variability and tides on the transmission of Barmah Forest virus (BFV) disease and developed a weather-based forecasting model for BFV disease in the Gladstone region, Australia. We used seasonal autoregressive integrated moving-average (SARIMA) models to determine the contribution of weather variables to BFV transmission after the time-series data of response and explanatory variables were made stationary through seasonal differencing. We obtained data on the monthly counts of BFV cases, weather variables (e.g., mean minimum and maximum temperature, total rainfall, and mean relative humidity), high and low tides, and the population size in the Gladstone region between January 1992 and December 2001 from the Queensland Department of Health, Australian Bureau of Meteorology, Queensland Department of Transport, and Australian Bureau of Statistics, respectively. The SARIMA model shows that the 5-month moving average of minimum temperature (β = 0.15, p-value < 0.001) was statistically significantly and positively associated with BFV disease, whereas high tide in the current month (β = −1.03, p-value = 0.04) was statistically significantly and inversely associated with it. However, no significant association was found for other variables. These results may be applied to forecast the occurrence of BFV disease and to use public health resources in BFV control and prevention.