Paediatrics in Barcelona: highlights from the 2010 ERS Annual Congress.

The aim of this update is to describe the paediatric highlights from the 2010 European Respiratory Society Annual Congress in Barcelona, Spain. Abstracts from the seven groups of the Paediatric Assembly (Respiratory physiology, Asthma and allergy, Cystic fibrosis, Respiratory infection and immunology, Neonatology and paediatric intensive care, Respiratory epidemiology and Bronchology) are presented in the context of the current literature.

Paediatrics in Vienna.

The aim of this article is to describe the paediatric highlights from the 2009 European Respiratory Society Annual Congress in Vienna, Austria. The best abstracts from the seven groups of the Paediatric Assembly (asthma and allergy, respiratory epidemiology, cystic fibrosis, respiratory physiology, respiratory infections and immunology, neonatology and paediatric intensive care, and bronchology) are presented alongside findings from the current literature.

Influence of pulmonary factors on pulse oximeter saturation in preterm infants.

AIM: To describe how the stability of oxygen saturation measured by pulse oximetry (SpO2%) varies within and between infants with bronchopulmonary dysplasia (BPD). METHODS: Clinically stable infants with BPD had SpO2 measured at different inspired oxygen concentrations (FIO2 expressed as %). A computer model of gas exchange, that is, ventilation/perfusion ratio (VA/Q) and shunt, plotted the curve of SpO2 versus FIO2 best fitting these data. The slope of this curve is the change in SpO2 per % change in FIO2, hence SpO2 stability, calculated at each SpO2 from 85% to 95%. RESULTS: Data from 16 infants with BPD previously described were analysed. The dominant gas exchange impairment was low VA/Q (median 0.35, IQR, 0.16-0.4, normal 0.86). Median shunt was 1% (IQR, 0-10.5; normal <2%). Slope varied markedly between infants, but above 95% SpO2 was always <1.5. In infants with least severe BPD (VA/Q ≈0.4, shunt ≤2%) median slope at 85% SpO2 was 5.1 (IQR, 3.7-5.5). With more severe BPD (VA/Q ≤0.3) slope was flatter throughout the SpO2 range. The highest FIO2 for 90% SpO2 was in infants with the lowest VA/Q values. CONCLUSIONS: In infants with BPD, there was large variation in the slope of the curve relating SpO2% to inspired oxygen fraction in the SpO2 range 85%-95%. Slopes were considerably steeper at lower than higher SpO2, especially in infants with least severe BPD, meaning that higher SpO2 target values are intrinsically much more stable. Steep slopes below 90% SpO2 may explain why some infants appear dependent on remarkably low oxygen flows.

Assessment of nutritional status and in vivo immune responses in alcoholic liver disease.

Nutritional status and in vivo immune responses were investigated in 30 patients with alcoholic liver disease who were drinking heavily up until emergency hospital admission. Investigations were performed on admission and after 2 wk abstention and adequate hospital diet. No relationship was found between the severity of liver disease revealed histologically and the recent quantity or total duration of alcohol intake, inadequacy of diet, or nutritional status. Skin anergy was more common in those patients with cirrhosis but did not relate to depletion in circulating T lymphocytes, poor nutritional status, or to the direct effect of alcohol toxicity. Acute alcohol toxicity did, however, produce extensive and rapidly reversible metabolic and cellular changes including reduction in serum potassium, magnesium and phosphate and depletion of all circulating lymphocyte subpopulations.

Gemfibrozil--the effect of biliary cholesterol saturation of a new lipid-lowering agent and its comparison with clofibrate.

Clofibrate is known to increase cholesterol saturation of bile and the prevalence of gallstones. We studied 10 healthy volunteer subjects to determine the effect of gemfibrozil (a new lipid-lowering agent) on biliary cholesterol saturation and to compare it with that of clofibrate. Biliary cholesterol saturation indices were calculated on fasting duodenal bile samples collected before and after administration of each drug for 4 weeks using a 4-week "washout" period between each preparation. There was a statistically significant rise in the cholesterol saturation index from a control value, taken as the mean of 2 samples, of 1.226 (0.785--1.526), median (range), to 1.547 (0.807--1.781) after clofibrate, P less than 0.05, but the rise to 1.352 (0.840--2.686) after gemfibrozil was not significant. However, direct comparison of the cholesterol saturation indices on clofibrate and gemfibrozil revealed no statistically significant difference. Only prospective clinical trials will establish definitively the risk of cholelithiasis on gemfibrozil but these results suggest that this drug is unlikely to have an advantage over clofibrate in this respect.

Protective effects of the prostaglandins on the gastric mucosa.

Prostaglandins are a group of 20-carbon, oxygenated fatty acids derived from arachidonic acid. They are present in most mammalian cells and tissues, and since their half-life is short, they are considered to exert their actions in the tissues where they are produced. The gastrointestinal mucosa contains relatively large amounts of prostaglandin. Prostacyclin is the most common prostaglandin formed by the gastric mucosa, and this compound and prostaglandin E2, which is also present in the gastric mucosa, may affect gastric mucosal blood flow and acid secretion. Prostaglandins have been shown to protect against gastric and duodenal mucosal damage in animals and humans. This protection can occur independently of acid inhibition and may be direct or adaptive.

Is an acid pH medium required for the protective effect of sucralfate against mucosal injury?

It has been suggested that an acidic medium is required for the action of sucralfate in providing mucosal protection. We have examined the effect of sucralfate (300 mg/kg) at an acidic pH of 1.5 and a near-neutral pH of 6.5 on the occurrence of mucosal damage induced in rats by aspirin alone and aspirin combined with bile acids. Fasting Sprague-Dawley rats received test solutions by oral intubation, and their stomachs were examined four hours later for the presence of hemorrhagic erosions. Sucralfate significantly reduced mucosal erosions induced by aspirin alone and aspirin combined with bile acids at pHs of both 1.5 and 6.5. These results indicate that the protective effect of sucralfate against mucosal injury induced by aspirin and bile acids is not dependent on an acidic medium.

Review article: dietary and nutritional management of Crohn's disease.

The value of dietary alteration and the nutritional management of Crohn's disease is assessed in this review. Lactose restriction, low-fat diets and low-residue diets may be of value in specifically indicated clinical situations. A fibre-rich, unrefined carbohydrate diet has not been shown to alter the course of the disease, and the value of 'exclusion diets' remains to be confirmed in controlled, prospective studies. Nutritional insufficiency of varying degrees is common in Crohn's disease and can be corrected by the efficient use of enteral diets (usually with polymeric preparations) or intravenous nutritional support. Growth retardation in adolescents with Crohn's disease can usually be improved by enteral nutrition. Nutritional support of various kinds may be of value in the management of local complications of Crohn's disease; sub-acute obstruction, anal, perianal and rectal lesions, fistulas and ileostomy complications, and the management of bile acid-induced diarrhoea. The use of nutrition as 'primary therapy; in Crohn's disease is considered. Theoretical reasons why nutritional support and bowel rest may possibly induce remission of the disease are discussed. The evidence to date suggests that intravenous nutrition and bowel rest may not be effective in inducing a primary remission of the disease, and the possible value of elemental diets and polymeric diets in this respect are assessed. Further prospective controlled studies of elemental diets as primary therapy in Crohn's disease are required.

Replacing the acetyl linkage in aspirin with choline and magnesium moieties reduces the occurrence of gastric mucosal injury.

The acetyl moiety in aspirin (acetyl salicylic acid: ASA) is considered to play a major part in the pathogenesis of ASA-induced mucosal injury. At equivalent salicylate doses and pH values, the induction of acute gastric mucosal haemorrhagic erosions in rats by ASA and choline magnesium trisalicylate (CMT), a new non-acetylated salicylate, with and without the potentiating damaging effect of taurodeoxycholic acid (TDCA) were compared. Test solutions were administered by per oral intubation to five groups of fasting Sprague-Dawley rats (n = 24). Gastric mucosa were examined after 4 hours and mucosal injury assessed by a lesion-scoring system. The incidence and severity (median lesion scores with quartiles) of the lesions were 83% and 13 (7:20) respectively for ASA (128 mg kg-1) compared with 17% and 0 (0:0) for CMT (128 mg kg-1) (P less than 0.001 and P less than 0.001). TDCA increased mucosal damage to 100% and 29 (20:34) for ASA compared with 30% and 0 (0:4) for CMT (P less than 0.001) and P less than 0.001). Serum salicylate levels (median values of 1.4 for ASA and 1.5 mmol litre-1 for CMT) were not significantly different. It is concluded that replacing the acetyl moiety in ASA with choline and magnesium moieties reduces the ASA-induced mucosal injury, without affecting blood salicylate concentrations.

The interaction between Helicobacter pylori culture filtrate and indomethacin: effects on the integrity of human gastric antral mucosa and its prostaglandin E2 production in vitro.

Histopathological methods and radioimmunoassay were used to assess the microstructure and prostaglandin E2 production by paired specimens of human gastric antral mucosa; the specimens were studied after 48 h of incubation in base-line tissue culture medium, Helicobacter pylori culture filtrate, H. pylori culture control fluid, indomethacin, and H. pylori culture filtrate plus indomethacin. When applied alone, the filtrate did not affect the structure of the mucosal tissue or its prostaglandin E2 synthesis. In the overall group (n = 21), specimens incubated with the mixture of H. pylori filtrate and indomethacin had a median histological grade of 1 and prostaglandin E2 of 29 pg/mg tissue, compared to 2 pg/mg (P = 0.04) and 60 pg/mg (P = 0.0007) respectively, in specimens incubated with indomethacin alone. These results indicate that an interaction may exist between indomethacin and a factor contained in H. pylori culture filtrate. Such interaction is damaging to the human gastric antral mucosa, and its understanding might have therapeutic implications.

Gastric and duodenal mucosal blood flow in patients receiving non-steroidal anti-inflammatory drugs--influence of age, smoking, ulceration and Helicobacter pylori.

Using laser Doppler flowmetry, we measured gastric and duodenal mucosal blood flow in 70 patients who had taken non-steroidal anti-inflammatory drugs (NSAIDs) for longer than 4 weeks, and studied the correlation with demographic factors, ulceration, and Helicobacter pylori. Blood flow was also measured in 17 other subjects not taking any drugs. Measurements were taken from healthy-looking mucosa in the gastric antrum and the first part of the duodenum. Both gastric and duodenal blood flow values were significantly lower in patients taking NSAID than in those who did not. In the NSAID group, the median duodenal mucosal blood flow was 150 perfusion units in smokers (n = 29) compared with 175 in non-smokers (P = 0.024), 123 units in patients with duodenal ulcers (n = 12) compared with 160 in those without duodenal ulcers (P = 0.020), 135 units in patients with H. pylori (n = 30) compared with 168 in patients without H. pylori (P = 0.033), and 118 in smokers infected with H. pylori compared with 175 units in non-smokers not infected with H. pylori (F = 13.4, P = 0.0005). There was no correlation with age. Gastric blood flow was not significantly influenced by any of the above variables. These results suggest that chronic NSAID intake is associated with reduced blood flow in both the stomach and duodenum. However, amongst NSAID patients, duodenal, but not gastric, mucosal blood flow is reduced in smokers, and in those with duodenal ulcers and H. pylori.(ABSTRACT TRUNCATED AT 250 WORDS)

Protection from gastrointestinal side-effects by azapropazone by its incorporation into a glucose-sodium acid citrate formulation.

Addition of glucose and sodium citrate to azapropazone, in proportions of 1:1:1 by weight reduced gastric mucosal damage in rats and there was a trend towards reduction in radiolabelled faecal red cell loss in human volunteers compared with that with azapropazone alone. The glucose and citrate did not affect the pharmacokinetics of azapropazone, or its therapeutic efficacy. While no difference was observed in endoscopic injury and in symptomatic gastrointestinal complaints in a multicentre comparison in rheumatic patients, a striking reduction in symptoms was observed in those patients with a history of severe gastrointestinal intolerance to non-steroidal anti-inflammatory drugs.

Inhibition of human gastric cyclic AMP production by Helicobacter pylori protein--possible involvement of mucosal prostaglandin E2.

The effect of Helicobacter pylori protein on cAMP and prostaglandin (PGE2) production was studied in incubates of human gastric fundic mucosa. At 24 hours, specimens incubated in the control fluid had a median cAMP value of 81 pmol/mg protein, compared to 28 pmol/mg (P less than 0.05) when incubated in H. pylori protein, 155 pmol/kg (P less than 0.006) in histamine, and 23 pmol/kg (P less than 0.05) in histamine plus H. pylori protein. A similar trend was observed at 48 hours. Although H. pylori protein had no direct effect on mucosal PGE2, it intensified the inhibitory effect of indomethacin and prevented the stimulatory effect of histamine on both PGE2 and cAMP production. Given the role of cAMP in various physiological responses, these results suggest that H. pylori protein might alter those functional aspects of the human gastric mucosa which rely on cAMP as a second messenger. Assuming that PGE2 is involved in mediating such effect, its role would appear to be either partial or indirect.

Bedside assessment of phrenic nerve function in infants and children.

Phrenic nerve damage is widely recognized after cardiac operations and is associated with an increased morbidity and mortality. Retrospective studies in children have estimated a prevalence of phrenic damage of between 0.5% and 2.2%, but all these studies have limited their investigations to patients who have clinical problems postoperatively, and they have all used clinical or radiologic methods to diagnose the damage. These methods are indirect and hard to evaluate, making the accurate early diagnosis of phrenic nerve damage very difficult. Measurement of phrenic nerve conduction time (phrenic latency) allows direct evaluation of phrenic function and integrity, making it potentially much more specific than indirect methods. Using a simplified method of direct phrenic nerve stimulation, we have developed a method of measuring phrenic latency at the bedside in infants and children. A 1 Hz electrical stimulus is applied over the phrenic nerve in the neck and a diaphragmatic electromyogram from the seventh and eighth intercostal spaces is displayed on a storage oscilloscope. Phrenic latency can be measured directly from the screen. Using these methods we have now studied 37 children (aged 2 days to 15 years) before and after cardiac operations. Mean phrenic latency was 5.4 +/- 1.0 msec on the right and 5.4 +/- 1.0 msec on the left. Prolongation of phrenic latency by more than 2 msec was found in seven of 66 postoperative measurements (10.6%). These patients had a substantially worse postoperative course. We believe this technique to be an important contribution to the diagnosis of postoperative phrenic nerve damage, and one that can help in clinical practice to elucidate an important cause of postoperative morbidity and mortality.

Importance of cryptolytic lesions and pericryptal granulomas in inflammatory bowel disease.

AIMS: To explore the diagnostic importance of pericryptal granulomas associated with epithelial lysis in colorectal biopsy specimens (cryptolytic colitis). METHODS: A series of patients with suspected inflammatory bowel disease and colorectal biopsy specimens showing either isolated pericryptal granulomas (14 cases) or non-granulomatous pericryptal inflammation (eight cases) were followed. A diagnosis of Crohn's disease was established if subsequent biopsy specimens or intestinal resections showed unequivocal non-crypt related granulomas, or if there was evidence of significant small bowel disease. RESULTS: Of the 14 patients with pericryptal granulomas and biopsy specimens, 10 were subsequently found to have Crohn's disease; of the eight patients with pericryptal inflammation only, one developed Crohn's disease. The former group also had a much higher instance of morbidity and required surgical intervention more often. CONCLUSIONS: The presence of cryptolytic granulomas in a colorectal biopsy specimen otherwise showing only non-specific inflammatory changes should always raise suspicion of Crohn's disease, especially if surgery or ileo-anal pouch formation is contemplated.

Oesophageal histology in long term users of non-steroidal anti-inflammatory drugs.

AIMS: To study the oesophageal histological changes in long term users of non-steroidal anti-inflammatory drugs (NSAIDs) compared with patients not receiving these drugs. METHODS: Ninety eight patients were studied, 53 of whom had taken NSAIDs for three years; 45 had not. Oesophageal biopsy specimens were taken from healthy-looking mucosa in the lower third of oesophagus. The papillary length, the thickness of the basal cell layer, and the intensity of cells infiltrating the epithelium were all assessed blind. RESULTS: The NSAID group included four (7%) cases of papillary elongation and two (4%) cases of basal cell hyperplasia, compared with 13 (29%; p < 0.01) and eight (18%; p < 0.02), respectively, in patients not taking NSAIDs. The total histological scores were also lower in patients treated with NSAIDs. CONCLUSION: Long term NSAID users have fewer oesophageal histological abnormalities than patients not receiving NSAIDs. Macroscopic damage related to NSAID use is, therefore, unlikely to require pre-existing histological oesophagitis for its development.

Chemical gastritis and Helicobacter pylori related gastritis in patients receiving non-steroidal anti-inflammatory drugs: comparison and correlation with peptic ulceration.

AIMS: To evaluate the prevalence and significance of chemical gastritis, in comparison with gastritis related to Helicobacter pylori in patients receiving non-steroidal anti inflammatory drugs (NSAIDs). METHODS: Two hundred and eighteen patients were studied, 174 of whom were taking NSAIDs. Chemical gastritis was defined as the presence of foveolar hyperplasia, muscle fibres in the lamina propria, oedema and vasodilation, in the absence of a chronic inflammatory cell infiltrate. RESULTS: Chemical gastritis was found in 46 (26%) patients taking NSAIDs, and three (7%) in subjects not taking these drugs (p less than 0.01). H pylori was detected in 56 (32%) subjects taking NSAIDs compared with 22 (50%) not taking these agents (p less than 0.02). Ulcers were found in 16 out of 72 patients (22%) taking NSAIDs and without H pylori infection or chemical gastritis compared with 27 out of 56 (48%) with H pylori related gastritis (p less than 0.01), and 25 out of 46 (54%) with chemical gastritis (p less than 0.01). CONCLUSIONS: Peptic ulcers associated with the use of NSAIDs seem to occur more commonly in patients with chemical gastritis or H pylori infection. Patients taking NSAIDs also seem to have a greater prevalence of chemical gastritis but a lower prevalence of H pylori than those not taking these drugs.

Functional and structural changes of the human proximal small intestine after cytotoxic therapy.

The effects of cytotoxic therapy on the structure and function of the proximal jejunum were studied in six patients receiving intravenous cyclophosphamide (300 mg/m2), methotrexate (40 mg/m2), and 5-fluorouracil (600 mg/m2) as adjuvant therapy for breast cancer. Using a steady state, triple lumen tube perfusion system the absorption of water and electrolytes was measured before and 48 h after administration of the cytotoxic agents. Jejunal biopsies were obtained at each perfusion. Median (range) water absorption fell from 126 (40-142) to 84 (46-142) ml/h/30 cm, with parallel changes for electrolytes; none of the changes was significant. Brush border disaccharidases did not change at 48 h after chemotherapy, while mature enterocytes appeared normal by both light and electron microscopy. Crypt cells and immature enterocytes, however, showed focal vacuolation by light microscopy, corresponding to the occurrence of large residual bodies (secondary lysosomes) containing partially degraded fragments of damaged crypt cells. The confinement of ultrastructural changes to the immature cell population may explain the failure of this study to show a consistent change in the absorptive function of the jejunum 48 h after chemotherapy.

Diagnostic tests for Helicobacter pylori: comparison and influence of non-steroidal anti-inflammatory drugs.

AIMS: To evaluate the efficacy of culture, histology, CLO-test, Helico-G and Pyloriset tests in diagnosing Helicobacter pylori in the presence or absence of non-steroidal anti-inflammatory drugs (NSAIDs). METHODS: Of 134 patients studied, 75 had taken NSAIDs. At endoscopy, biopsy specimens were taken for culture, histology, and CLO-test. Blood was also taken for enzyme linked immunosorbent assay (ELISA) (Helico-G) and latex agglutination (Pyloriset) tests. RESULTS: The sensitivity, specificity, and predictive values of histology and CLO-test, compared with culture, ranged from 90% to 97%, regardless of NSAID intake. In the 59 patients not taking NSAIDs Helico-G had a sensitivity of 75% (p < 0.05) and a specificity of 61%; Pyloriset's sensitivity and specificity were, respectively, 63% (p < 0.05) and 67%. In the 75 patients taking NSAIDs the sensitivity of Helico-G was 81% and its specificity 45% (p < 0.05); Pyloriset had a sensitivity of 61% (p < 0.05) and a specificity of 50% (p < 0.05). CONCLUSION: These findings suggest that H pylori is more reliably diagnosed by culture, histology, and CLO-test than by the serological tests used in this study, especially in patients treated with NSAIDs.