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.

Assessing efficient patient care: should length of stay be calculated independently of local admission rates?

OBJECTIVE: To compare the length of hospitalisation for infants with bronchiolitis across the Eastern region and to assess the impact of the varying admission rates in each hospital. DESIGN: Data collection through the Hospital Episode Statistics (HES) using the ICD clinical coding for bronchiolitis across all hospitals in east of England for three winter seasons (October to March for the years 2009/10, 2010/11 and 2011/12). MAIN OUTCOME MEASURE: Length of hospital stay, corrected to adjust for local population. RESULTS: Seventeen hospitals across the east of England were included in this study. Overall admission rate (as a percentage of the population) for the region was 3.3% and consistent with national data, but rates within individual hospitals varied between 1.5% and 5.7% over the 3-year period. Bed days per 1000 population ('standardised bed days') per year varied almost fourfold, from 34.5 to 122.3 in different hospitals. Corrected length of stay showed high discordance when compared to average length of stay. CONCLUSIONS: The average length of stay is substantially affected by admission rates, with hospitals who admit a greater proportion of infants appearing to have a shorter uncorrected length of stay. We propose that a single corrected measure for length of stay should be used when assessing the efficiency of care because it is unaffected by variations in local admission rates and is adjusted for local population size.

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.

Lymphocyte apoptosis in acute respiratory syncytial virus bronchiolitis.

Respiratory syncytial virus (RSV) infection may have an effect on the development of T cell memory responses. RSV bronchiolitis in infants is associated with a transient decline in circulating lymphocytes. We hypothesized that the mechanism underlying this lymphopenia is apoptosis. Blood was taken from 32 infants during primary RSV bronchiolitis and three months later. Using flow cytometry, we found that absolute numbers of both CD3+/CD4+ T-helper lymphocytes (P = 0.029) and CD3+/CD8+ cytotoxic lymphocytes (CTL) (P = 0.043) were significantly reduced during acute infection. Up-regulated expression both of Fas (P < 0.001) and tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor (P < 0.001) was found during acute illness on both CD3+/CD4+ and CD3+/CD8+ lymphocytes, when compared with convalescent samples. Expression of Fas on CD4+ lymphocytes was inversely related to CD4+ number (P = 0.03). Plasma levels of soluble Fas ligand (P = 0.028) and caspase-1 (P = 0.037), determined by enzyme-linked immunosorbent assay, were increased during bronchiolitis. Plasma interleukin-18, a product of caspase-1 activity, was not raised. Taken together, these data suggest that in acute RSV infection, CD4+ helper lymphocytes and CD8+ cytotoxic lymphocytes are primed to undergo apoptosis. This is a mechanism through which lymphopenia may occur and T cell memory may be altered.

Bereavement support following sudden and unexpected death: guidelines for care.

Dealing with families who have suffered a sudden and unexpected death is a skill that may be needed by any paediatrician. Offering a bereavement follow up meeting to such families is part of accepted practice and is perceived to be of value in helping the family to come to terms with the loss. Unfortunately, there is very little guidance on the objectives for such a meeting, or the training required to help staff conduct such meetings. The nature of the work on a paediatric intensive care unit (PICU) means that staff have a greater experience of handling families in such a situation. We have reviewed our experience over the past five years following up the families of 51 children who have died suddenly and unexpectedly in our regional PICU. In doing this we have identified five key elements that we suggest are essential to a successful follow up meeting, and have supported this with case studies as illustration.

Normal values for phrenic nerve latency in children.

Data derived from detailed studies of normal phrenic nerve latency in a large group of children are presented. They highlight the major differences between the three previously published studies of normal children. Phrenic nerve latency shows a curvilinear relationship with age, averaging 6.0 ms at 0-6 months, falling to 4.8 ms between 1 and 2 years, then rising to 6.3 ms between 10 and 18 years of age. These data represent the largest published study on normal phrenic nerve latency in children.

Association of alpha(1)-antichymotrypsin deficiency with milder lung disease in patients with cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is characterised by an excess of free proteinases that destroy lung tissue. Despite this, previous studies have shown that patients with CF with a mild deficiency variant of the proteinase inhibitor alpha(1)-antitrypsin have less, rather than more, severe pulmonary disease. Alpha(1)-antichymotrypsin is another important serine proteinase inhibitor that protects the lung against proteolytic attack, and point mutations in the alpha(1)-antichymotrypsin gene that result in plasma deficiency are associated with chronic obstructive pulmonary disease. METHODS: The effect of alpha(1)-antichymotrypsin deficiency and the -15 alpha(1)-antichymotrypsin signal peptide genotype on lung function was assessed in patients with CF. RESULTS: One hundred and fifty seven patients with CF were screened and 10 were identified with a plasma deficiency of alpha(1)-antichymotrypsin (plasma concentration <0.2 g/l). In a multivariate analysis these individuals had significantly less severe lung disease than those who had normal or raised levels of alpha(1)-antichymotrypsin: forced expiratory volume in one second (FEV(1)) 69.9% predicted versus 53. 2% predicted (p=0.04) and chest radiographic score of 7.2 versus 9.7 (p=0.03) for those with and without alpha(1)-antichymotrypsin deficiency, respectively. The -15 signal peptide genotype did not affect plasma levels, but the -15 Ala/Ala signal peptide genotype was over-represented in individuals with CF compared with healthy blood donor controls. CONCLUSION: These data indicate that deficiency of alpha(1)-antichymotrypsin is associated with less severe pulmonary disease in patients with CF, and support our previous observations that mild genetic deficiency of a proteinase inhibitor is associated with an improved outcome.

Non-steroidal anti-inflammatory drug toxicity in the upper gastrointestinal tract.

Non-steroidal anti-inflammatory drug (NSAID) toxicity in the upper gastrointestinal tract is the most common serious drug-induced toxicity reported to drug regulatory authorities. In the last two decades, the rediscovery of H. pylori, development of potent ulcer-healing drugs and specific Cox-II inhibitors have opened new horizons in the management of NSAID toxicity. A Working Party composed of gastroenterologists and rheumatologists in the Asia-Pacific region met in Cairns, Australia, in 1999 to review the literature and develop appropriate guidelines. Recommendations were made based on the latest existing evidence. The importance of clinical events as study endpoints was emphasized. While differences exist between NSAIDs and aspirin, most studies have shown that advanced age, history of peptic ulcer disease, serious concomitant illnesses and coprescription of NSAID/aspirin with anticoagulants and steroids are high risk factors. These patients should be considered for prophylactic anti-ulcer therapy. Helicobacter pylori infection may aggravate the toxicity of NSAIDs and, in selected cases, should be treated before NSAID/aspirin is prescribed. Proton pump inhibitors and misoprostol are the most promising agents in preventing gastric and duodenal ulcers. When NSAID/aspirin needs to be continued in patients who develop an NSAID-related ulcer, proton pump inhibitors offer the best healing effect. With the discovery of cyclo-oxygenase isoforms (Cox-I and Cox-II), preferential and specific Cox-II inhibitors have been developed. While early clinical data have suggested promising antiinflammatory effects and improved safety profile in the gastrointestinal tract, several key issues on long-term safety remain unresolved. The use of potent anti-ulcer therapy, treatment of H. pylori infection and the development of Cox-II inhibitor will change the scenario of NSAID/aspirin-related gastrointestinal toxicity in the next millennium.

Small-intestinal mucosal protein synthesis and whole-body protein turnover in alcoholic liver disease.

We used stable-isotope-labelled amino acids to measure the effects of alcoholic liver disease (ALD) on whole-body protein turnover and small-intestinal mucosal protein synthesis. Groups comprising eight patients with ALD and eight healthy control subjects were studied. They received primed, continuous intravenous infusions of L-[1-(13)C]leucine after an overnight fast; after 4 h, duodenal biopsies were obtained via endoscopy. Protein synthesis was calculated from protein labelling relative to intracellular leucine enrichment. Rates of duodenal mucosal protein synthesis were 2. 58+/-0.32%.h(-1) (mean+/-S.D.) in the normal subjects and 2.04+/-0. 18%.h(-1) in the ALD patients (P<0.003), despite the fact that the protein synthetic capacity (microgram of RNA/mg of protein) was higher in ALD patients (160+/-14 compared with 137+/-6 microgram/mg; P<0.003). The mucosal cell size (protein/DNA ratio) was lower in ALD patients (9.23+/-0.91 compared with 13+/-2.2 microgram/mg; P<0.002). Although the mean rates of whole-body protein turnover were not significantly different between the two groups (204+/-18 and 196+/-44 micromol leucine.h(-1).kg(-1) for ALD and control subjects respectively), there was, in the ALD patients, an inverse relationship between the rate of small-intestinal mucosal protein synthesis and the severity of ALD; furthermore, there was a direct relationship between the rate of whole-body protein turnover and the severity of ALD. Thus there was an inverse relationship between the rate of small-intestinal mucosal protein synthesis and the rate of whole-body protein turnover in ALD patients, which was not seen in the normal subjects.

Rates of small intestinal mucosal protein synthesis in human jejunum and ileum.

We investigated possible differences in the rates of mucosal protein synthesis between the proximal and distal regions of the small intestine. We took advantage of access to the gut mucosa available in otherwise healthy patients with ileostomy in whom the terminal ileum was histologically normal. All subjects received primed, continuous intravenous infusions of L-[1-(13)C]leucine after an overnight fast. After 4 h of tracer infusion, jejunal biopsies were obtained using a Crosby-Kugler capsule introduced orally; ileal biopsies were obtained via endoscopy via the ileostomy. Protein synthesis was calculated from protein labeling relative to intracellular leucine enrichment obtained by appropriate mass spectrometric measurements. Rates of jejunal and ileal mucosal protein synthesis were significantly different (P < 0.001) at 2.14 +/- 0.2 and 1.2 +/- 0.2 %/h (means +/- SD). These are lower than rates in normal healthy duodenum (2.53 +/- 0.25 %/h), suggesting a gradation of rates of synthesis along the bowel. Together with other data, these results suggest that mucosae of the bowel contribute not more than 10% to whole body protein turnover.

Anti-neutrophil cytoplasmic antibodies (ANCA) against bactericidal/permeability-increasing protein (BPI) and cystic fibrosis lung disease.

Persistent infection with Pseudomonas aeruginosa and inflammatory mechanisms play an important role in cystic fibrosis (CF) lung disease. ANCA against BPI, a potent host defence protein with anti-bacterial and anti-endotoxin properties, have been described in CF. We have assessed the relationship of anti-BPI antibodies to pulmonary disease severity in 148 CF subjects. IgA and IgG anti-BPI antibodies were found in 55.4% and 70.3% of CF patients, respectively, and higher levels were strongly associated with colonization with P. aeruginosa (P = 0.001 and 0.039 for IgA and IgG antibodies, respectively). IgA and IgG anti-BPI antibodies were independently associated with more severe lung disease as assessed by chest radiograph score (P = 0.023) and a significantly lower forced expiratory volume in 1 s (FEV1)% (P = 0.01). The pathophysiological relevance of the autoantibodies was investigated further by determining their epitope specificity and their effect on bacterial phagocytosis in vitro. Both isotypes of anti-BPI antibodies were specific for the C-terminus of BPI shown recently to be important for BPI-mediated opsonization, and in vitro affinity-purified anti-BPI antibodies significantly reduced BPI-induced phagocytosis of Escherichia coli compared with controls. These data indicate that anti-BPI autoantibodies are associated with colonization with P. aeruginosa and worse lung disease in CF. The inhibition of bacterial phagocytosis suggests that these autoantibodies may contribute to the persistence of P. aeruginosa in the CF lung and so play a role in perpetuating CF lung damage.

Defining patients at risk of non-steroidal anti-inflammatory drug gastropathy.

Non-steroidal anti-inflammatory drugs have long been known to cause gastro-duodenal damage. However, all parts of the gastrointestinal tract may be affected, including the small intestine, colon and oesophagus. Non-steroidal anti-inflammatory drugs can cause dyspeptic symptoms, erosions, ulceration, which may lead to haemorrhage or perforation, and a requirement for surgery. The purpose of this report is to assess risk factors which may lead to gastrointestinal damage and, thus, to identify those patients at greatest risk of non-steroidal anti-inflammatory drug damage. Possible risk factors include age, sex, previous ulcer history, the presence of Helicobacter pylori, the type and severity of arthritis, individual non-steroidal anti-inflammatory drugs (dose, duration of treatment, route of administration), other debilitating diseases, smoking, alcohol, and the use of concomitant drugs. Risk of non-steroidal anti-inflammatory drug damage is higher in older patients (RR > 60 5.52; < 60 1.65), but there is no convincing sex difference. There is increased risk in patients with a previous history of peptic ulceration (RR first gastrointestinal event 2.39; subsequent gastrointestinal event 4.76), and in the first three months of treatment. Debate continues about the relevance of Helicobacter pylori, and this will be discussed in a later report. There is no strong evidence that patients with rheumatoid arthritis are more likely to have more trouble than those with osteoarthritis, but the former are more likely to require higher doses of non-steroidal anti-inflammatory drugs. Highest risk non-steroidal anti-inflammatory drugs include azapropazone, ketoprofen and piroxicam, and those with least risk include ibuprofen, diclofenac and etodolac. There is an increased risk of gastrointestinal complications with relatively small-dose prophylactic aspirin. Other factors increasing the risk are smoking and the presence of chronic underlying respiratory and cardiovascular disease. Risk of gastrointestinal problems is increased with concomitant drugs, especially corticosteroids (RR 14.6 if given with non-steroidal anti-inflammatory drugs), but also with anticoagulants and some other drugs. The clinical importance of identifying possible risk factors lies in being aware of likely problem patients and in the use of safer non-steroidal anti-inflammatory drugs or combination therapy with protective drugs in these patients.

Relationship between mucosal levels of Helicobacter pylori-specific IgA, interleukin-8 and gastric inflammation.

Mucosal IgA is important in local immune defence. Helicobacter pylori induces a specific IgA response in antral mucosa, but its immunopathology is unknown. Interleukin-8 (IL-8) has been suggested to be important in H. pylori-induced inflammation. Current information on the relationship between H. pylori-induced IgA and mucosal inflammation is limited. To investigate possible associations between mucosal-specific IgA, the toxinogenicity of H. pylori, mucosal levels of IL-8 and gastric inflammation, 52 endoscoped patients were studied. These comprised 28 patients with peptic ulcer and 24 with non-ulcer dyspepsia. Of these patients, 38 had H. pylori infection: 28 with peptic ulcer and 10 with non-ulcer dyspepsia. Antral biopsies were taken for histology, H. pylori culture and measurement of mucosal levels of IL-8 (pg/mg) and specific IgA (A450x1000) by ELISA. Mucosal H. pylori IgA was detectable in 35 out of 38 patients with H. pylori infection, with a median (interquartile) level of 220 (147, 531) units. There was no significant difference in mucosal levels of the IgA antibodies between patients infected with cytotoxin-positive or cagA-positive strains of H. pylori and those with toxin-negative or cagA-negative strains. The IgA levels in those patients with severe neutrophil infiltration were lower than in those with mild or moderate infiltration (P<0.05). There was a weak inverse correlation between antral mucosal IgA and IL-8 in infected patients (r=-0.36; P=0.04). H. pylori infection induced a significant local mucosal IgA response in most infected patients. The level of IgA antibodies does not appear to be correlated with the toxinogenicity of H. pylori. However, patients with severe active inflammation appear to have decreased levels of IgA. An inverse correlation between mucosal IL-8 and IgA may suggest that IL-8-induced inflammation compromises the mucosal IgA defence and renders the mucosa susceptible to further damage.

Neutrophils, Helicobacter pylori, and nonsteroidal anti-inflammatory drug ulcers.

BACKGROUND & AIMS: Gastric injury by nonsteroidal anti-inflammatory drugs (NSAIDs) is minimal in neutropenic animals. This study examined peptic ulcer development in the presence or absence of gastric neutrophils in patients requiring long-term use of NSAIDs. METHODS: Gastric histology, neutrophils, and Helicobacter pylori were assessed in 120 patients randomized to receive placebo or 20 or 40 mg famotidine twice daily as prophylaxis against NSAID-related ulcers and who underwent endoscopy at 0, 4, 12, and 24 weeks. RESULTS: In 43 patients without gastric neutrophils, ulcers developed in 1 of 14 (7.7%) taking placebo, 2 of 16 (12.5%) taking 20 mg famotidine, and none of 13 taking 40 mg famotidine. However, in 77 patients with neutrophils, ulcers developed in 13 of 28 (47. 4%) taking placebo (P < 0.001), 3 of 26 (12.6%) taking 20 mg famotidine, and 3 of 23 (13%) taking 40 mg famotidine. Eight of 46 patients (17%) without H. pylori had neutrophils compared with 69 of 74 (93%) with both H. pylori and neutrophils (P < 0.001). CONCLUSIONS: Gastric neutrophils increase the incidence of ulceration in long-term NSAID users. Because neutrophils exist with H. pylori, eradicating this infection might prevent NSAID-related peptic ulcers.