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.

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.

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.

Alpha1-antitrypsin deficiency alleles and the Taq-I G-->A allele in cystic fibrosis lung disease.

Cystic fibrosis (CF) is characterized by progressive and ultimately fatal pulmonary disease although there are notable variations in clinical features. This heterogeneity is thought to lie outside the cystic fibrosis transmembrane regulator (CFTR) gene locus and may stem from deficiencies in the antiproteinase screen that protects the lung from proteolytic attack. One hundred and fifty seven patients were recruited from two UK CF centres. The serum concentrations of alpha1-antitrypsin, alpha1-antichymotrypsin and C-reactive protein (CRP) were determined and patients were screened for the common S and Z deficiency alleles of alpha1-antitrypsin and the G-->A mutation in the 3' noncoding region of the alpha1-antitrypsin gene (Taq-I G-->A allele). Alpha1-antitrypsin deficiency phenotypes were detected in 20 (16 MS, 1 S and 3 MZ) out of 147 unrelated tested CF patients and were, surprisingly, associated with significantly better lung function (adjusted mean forced expiratory volume in one second (FEV1) 62.5% of predicted for deficient group and 51.1% pred for normal alleles; p=0.043). The Taq-I G-->A allele was found in 21 out of 150 unrelated patients and had no significant effect on CF lung disease or on levels of alpha1-antitrypsin during the inflammatory response. We show here that, contrary to current thinking, common mutations of alpha1-antitrypsin that are associated with mild to moderate deficiency of the protein predict a subgroup of cystic fibrosis patients with less severe pulmonary disease. Moreover, the Taq-I G-->A allele has no effect on serum levels of alpha1-antitrypsin in the inflammatory response, which suggests that the previously reported association of the Taq-I G-->A allele with chronic obstructive pulmonary disease is not mediated by its effect on the serum level of alpha1-antitrypsin.

Phrenic nerve damage via a right thoracotomy in older children with secundum ASD.

Phrenic nerve damage (PND) in children after cardiac operations is now recognized as being more frequent than previously thought. In a prospective study on 400 children, we previously demonstrated electrophysiologic evidence of postoperative PND in approximately 16% of patients, with one third of cases occurring in children under 18 months. In the past 18 months, 30 children have had atrial septal defect (ASD) repairs as their only operative procedure. Fourteen children had ASD repairs via a midline incision, and 16 ASD repairs were via a right thoracotomy. No PND (assessed by phrenic nerve latency) was found after a midline approach. In the right thoracotomy group, 5 children had evidence of PND (31%; p = 0.05). Four of these 5 patients were female and more than 14 years of age. The incidence of damage in this pubescent group was 80% (p < 0.05). In the older age group the duration of ventilation was not prolonged, but affected patients had symptoms of fatigue and breathlessness postoperatively. These data suggest a strong association between right thoracotomies for ASD repairs and PND, especially in the female pubescent group when a low submammary skin incision (seventh to eighth space) is used with a fifth to sixth space entry into the thoracic cavity. In conclusion, the right thoracotomy approach for ASD repair appears to be a significant risk factor for PND in older children.

Fetal anaemia and its relation with increased concentrations of adenosine.

Adenosine concentrations were measured in umbilical venous blood obtained by cordocentesis from 14 fetuses of 19-34 weeks' gestation. The concentration did not change significantly with gestational age, but anaemic fetuses showed significantly increased concentrations of adenosine and there was a positive association with blood oxygen tension. These findings suggest that the fetus responds to tissue hypoxia by increasing blood adenosine concentrations from at least 19 weeks' gestation.

Comparative accuracy of pulse oximetry and transcutaneous oxygen in assessing arterial saturation in pediatric intensive care.

Recent improvements in the noninvasive measurement of oxygen saturation by pulse oximetry (SapO2) have resulted in the development of easily used bedside monitors. We compared the performance of the Biox 3700 and Nellcor N100E models against arterial saturation (SaO2) measured on a Radiometer OSM2 hemoximeter and against transcutaneous SO2 (StcO2) derived from transcutaneous oxygen tensions (PtcO2) (632, Roche Kontron). Twenty-four hemodynamically stable patients were studied, all with indwelling arterial lines, aged between 1 month and 13 yr. Mean differences +/- SD between SapO2 and SaO2 were -0.77 +/- 3.23 for the Nellcor and -2.90 +/- 2.19 for the Biox. The Biox machine generally read lower than the Nellcor with a mean difference of -1.63 +/- 2.65. SaO2 derived from PtcO2 (StcO2) did not differ significantly (-0.27 +/- 2.12) from SaO2. In hemodynamically stable infants and children, StcO2 and SapO2 have similar accuracy limits when compared with each other and with SaO2.