Lower anti-echovirus antibody responses in children presenting to hospital with asthma exacerbations.

BACKGROUND: Rhinoviruses from the Enterovirus genus cause frequent infections and induce remarkably high titres of anticapsid antigen antibodies in asthmatics, while the prevalence of neutralising antibodies to the gut-trophic echoviruses from the same genus is diminished. OBJECTIVE: To assess the absolute and specific antibody titres to VP1 antigens of the gut-trophic enteroviruses, echovirus 30 and Sabin 1 poliovirus, in asthmatic and non-asthmatic children. METHODS: Recombinant polypeptides representing the VP1 capsid antigens of echovirus 30 and Sabin poliovirus 1 were produced. Their ability to bind IgG1 antibodies from the plasma of asthmatic (n = 45) and non-asthmatic (n = 29) children were quantitated by immunoassays that incorporated immunoabsorptions to remove cross-reactivity. RESULTS: The IgG1 antibody titres and prevalence of antibody binding to echovirus 30 were significantly lower for asthmatic children compared to controls (P < 0.05) and inversely correlated with total IgE levels for the whole study population (r = -0.262; P < 0.05). There was no difference in the prevalence and titre between groups to the VP1 antigen of Sabin poliovirus. Anti-tetanus toxoid titres measured for comparison did not correlate with anti-echovirus or poliovirus, but correlated with anti-rhinovirus titres in controls but not asthmatics, where the titres were higher for the asthmatic group. CONCLUSIONS AND CLINICAL RELEVANCE: The associations of lower antibody titres of asthmatic children to echovirus reported here and those of our previous findings of a heightened response to rhinovirus suggest a dichotomy where respiratory enterovirus infection/immunity increases the probability of developing asthma and enteric infections lower the risk. This provides further support for the concept of intestinal infection playing a key role in the development of allergic respiratory disease.

Controlling an outbreak of MRSA in the neonatal unit: a steep learning curve.

Meticillin resistant Staphylococcus aureus (MRSA) can cause serious infections in the newborn. While audit may show that a neonatal unit's main cause of infective morbidity is the coagulase negative staphylococcus, health authorities and politicians fear the implications of MRSA and its impact on the general public. MRSA causes mortality and morbidity in other areas of hospitals in the UK and in many other countries and there is an uneasy acceptance that this is now the established norm. However, MRSA in the neonatal unit carries sensitivities which have a huge impact on the reactions of health authorities, politicians and the press.

Beta2-Adrenoceptor polymorphisms and asthma phenotypes: interactions with passive smoking.

The aim of the present study was to assess the effects of possible interactions between beta(2)-adrenoceptor gene polymorphisms and passive smoking on forced expiratory volume in one second (FEV(1)), forced vital capacity (FVC) and exhaled nitric oxide (eNO) in children aged 11 yrs. A cross-sectional analysis of the longitudinal cohort was conducted for associations between beta(2)-adrenoceptor gene polymorphisms and lung function and eNO with regard to passive smoking. Among children exposed to tobacco smoke, those with Arg16 (at least one Arg allele) exhibited lower adjusted mean FEV(1) (2.19 versus 2.38 L) and FVC (2.43 versus 2.64 L) than Gly16 homozygotes. Those with Gln27 (at least one Gln allele) also exhibited a lower adjusted mean FEV(1) relative to Glu27 homozygotes (2.24 versus 2.39 L). Among children with no exposure to smoking, those with Arg16 or Gln27 showed lower adjusted geometric mean eNO levels compared with Gly16 homozygotes (15.4 versus 30.9 ppb) and Glu27 homozygotes (18.0 versus 49.7 ppb). In conclusion, passive smoking had a significant effect on associations between beta(2)-adrenoceptor gene polymorphisms and asthma-related phenotypes, enhancing the relationship between Arg16 and lung function and removing the relationship between Arg16 or Gln27 and exhaled nitric oxide levels.

CD14 C-159T and early infection with Pseudomonas aeruginosa in children with cystic fibrosis.

Early acquisition of Pseudomonas aeruginosa is associated with a poorer prognosis in patients with cystic fibrosis. We investigated whether polymorphisms in CD14, the lipopolysaccharide receptor, increase the risk of early infection. Forty-five children with cystic fibrosis were investigated with annual bronchoalveolar lavage (BAL) and plasma sCD14 levels. Plasma sCD14 levels were significantly lower in children from whom P.aeruginosa was subsequently isolated (492.75 microg/ml vs. 1339.43 microg/ml, p = 0.018). Those with the CD14 -159CC genotype had a significantly increased risk of early infection with P.aeruginosa suggesting that CD14 C-159T plays a role in determining the risk of early infection with P.aeruginosa.

Modulations in breathing patterns during intermittent feeding in term infants and preterm infants with bronchopulmonary dysplasia.

As infants with bronchopulmonary dysplasia (BPD) have difficulty maintaining adequate levels of oxygenation during rest, it was decided to investigate how the additional respiratory demands associated with nutritive feeding disrupt their breathing rates. The sucking and breathing patterns of six (three male, three female) preterm infants (between 23 and 29 weeks gestational age at birth), classified as having BPD were individually compared with the patterns observed in 12 (six male, six female) healthy term (control) infants (> or = 38 weeks gestational age at birth) with no known respiratory ailments. All infants were recruited from the neonatal unit at Simpson's Maternity Pavilion, Edinburgh, Scotland. In general, the breathing patterns recorded for the infants with BPD during the pause periods of intermittent feeding lacked the striking regularity observed in the term infants. It was found that the severity of the BPD affected breathing rates by significantly reducing the duration and the regularity of a breath (P<0.05) while sucking during the intermittent phase of feeding.

A polymorphism of the CC16 gene is associated with an increased risk of asthma.

Several quantitative traits associated with the asthma phenotype have been linked to markers on chromosome 11q13, although the gene responsible has yet to be well established. The gene for Clara cell secretory protein (CC16) is an ideal candidate for involvement in an inherited predisposition to asthma because of its chromosomal location, the role of the CC16 protein in controlling airway inflammation, and differences in levels of the protein between asthmatics and healthy controls. All three CC16 exons were screened in an unselected population of 266 subjects from 76 families and a cohort of 52 severely asthmatic children. A combination of single strand conformational polymorphism (SSCP) analysis, heteroduplex analysis, DNA sequencing, and restriction digestion was used. Mutation detection methods identified an adenine to guanine substitution in the CC16 gene at position 38 (A38G) downstream from the transcription initiation site within the non-coding region of exon 1. In the unselected population, 43.6% were homozygous for the polymorphic sequence (38GG) and 46.2% were heterozygous (38AG). All the asthmatic and unaffected children from both populations were selected for an unmatched case control analysis consisting of 67 asthmatic and 46 unaffected subjects. Those homozygous for the published sequence (38AA) had a 6.9-fold increased risk of developing asthma (p=0.049) and heterozygotes (38AG) a 4.2-fold increased risk (p=0.028). Modelling of genotype as a continuous covariate indicated evidence of a significant linear trend across the three genotypes (odds ratio=2.84 per unit increase in genotype code, p=0.018). These associations were independent of age, gender, and tobacco smoke exposure. These data and the known anti-inflammatory role of CC16 in the respiratory tract suggest that alteration to the gene at position 38 may contribute to asthma.

Association of polymorphisms within the tumour necrosis factor (TNF) genes and childhood asthma.

BACKGROUND: Tumour necrosis factor alpha (TNFalpha) is a potent modulator of immune and inflammatory responses, and has been implicated in a variety of autoimmune diseases, including asthma. Increased levels of TNFalpha have been detected in both sputa and bronchoalveolar lavage fluid of asthmatic subjects during acute attacks. Interindividual variation in TNFalpha levels may be genetically determined and polymorphisms within the TNF genes and nearby HLA Class II region have been associated with differences in TNFalpha production. OBJECTIVE: To investigate the association of differences in asthma-related phenotypes with two biallelic polymorphisms: a G to A substitution at position - 308 of the TNFalpha gene promoter (TNF1 and TNF2 alleles) and an NcoI polymorphism in the first intron of the lymphotoxin alpha gene (LT-alpha*1 and LT-alpha*2 alleles). METHODS: The regions of interest were amplified from genomic DNA using specific primers and PCR. Dot blot analysis was used for genotyping individuals for the TNFalpha - 308 polymorphism, while restriction enzyme digestion was used for genotyping individuals for the LT-alpha gene NcoI polymorphism. A case-control analysis was then performed on 74 asthmatic and 50 non-asthmatic unrelated children for each polymorphism. RESULTS: The TNFalpha - 308 TNF1 allele was present at a significantly higher frequency in cases than controls (OR= 2.4, P=0.003), and homozygosity for the TNF1 allele was associated with a fivefold increased risk of physician diagnosed asthma relative to the other genotypes (OR = 5.23, P = 0.004). The LT-alpha*2 allele showed similar associations, including an approximately fivefold higher risk of physician diagnosed asthma for LT-alpha*2 homozygotes (OR = 4.89, P = 0.019). Evidence of a significant linear trend in asthma risk across the three genotypes was found for both polymorphisms. CONCLUSION: These results suggest an important role for the TNFalpha gene or a linked locus in an inherited asthma diathesis.

The elimination half-life of urinary cotinine in children of tobacco-smoking mothers.

Exposure to environmental tobacco smoke (ETS) is strongly associated with childhood morbidity. Cotinine, the major metabolite of nicotine, is a useful marker of tobacco smoke exposure. Cotinine levels in infants are higher than in older children or adults exposed to the same reported quantity of ETS. One hypothesis to explain this difference is that the urinary elimination half-life of cotinine is different between infants and older children. Urine was collected at admission, 12, 24 and 48 h, cotinine levels were subsequently measured and then standardized by correcting for creatinine excretion. Urinary elimination half-life of cotinine was calculated in 31 infants and 23 older children. The median half-life was 28.3 h (range 6.3-258.5 h) in infants, and 27.14 h (range 9.7-99.42 h) in older children. A Mann-Whitney U test showed no significant difference in the median half-life of cotinine between the two age groups (P = 0.18). Multivariate linear regression analysis demonstrated no significant relationship between half-life of cotinine and corrected cotinine level (P = 0.24). Our results support the hypothesis that higher cotinine levels in infants is due to greater exposure, rather than slower metabolism of cotinine.

Effect of absent end diastolic flow velocity in the fetal umbilical artery on subsequent outcome.

Sixty babies, delivered over a six and a half year period, who had absent end diastolic frequency (AEDF) in the umbilical artery, were studied. Individually matched control pregnancies for gestational age, birth-weight, maternal clinical condition and date of delivery, in whom umbilical artery recordings showed end diastolic frequency, were also studied. Matching was achieved in 36 cases. Neonates from case pregnancies showed no increase in necrotising enterocolitis, intraventricular haemorrhage, pneumothorax, neonatal death or bronchopulmonary dysplasia. However, they were significantly less likely to require ventilation for respiratory distress syndrome (P = 0.02). Although AEDF indicates a fetus under vascular stress, this finding alone will include a spectrum of response in the baby, from the well compensated to the irreversibly damaged. Delivery at different points in the deteriorating fetal environment may explain discrepant study results. This intrauterine stress, by increasing fetal corticosteroid and thyroid hormones, may account for enhanced lung maturity. Predictions of neonatal course need to be based on more comprehensive awareness of fetal status.

An audit of the 1995 Royal College of Ophthalmologists guidelines for screening for retinopathy of prematurity applied retrospectively in one regional neonatal intensive care unit.

To test the effectiveness of the 1995 Royal College of Ophthalmologists (RCO) guidelines for screening for retinopathy of prematurity (ROP) in one regional neonatal intensive care unit, an analysis was carried out of screening examination results over a 4 year period, retrospectively applying the rules of the 1995 RCO guidelines. Four hundred and forty-eight examinations would have been performed in 258 infants, significantly fewer than the 764 examinations which had been performed using our existing screening protocol. Threshold ROP developed in 36 infants, and would have been detected promptly in every case. No case of threshold ROP developed in infants of birth weight greater than 1250 g. The 1995 RCO guidelines for ROP screening provide an effective and efficient means of detecting treatable ROP. The need to include infants of birth weight > 1250 g should be reviewed at a future date, following a period of further national data collection.

Young diabetics: memories, current lifestyles and attitudes.

Eighty-six subjects aged 22.3 +/- 2.3 years (mean +/- S.D.), who attended one clinic as diabetic children, filled in a questionnaire designed to evaluate their present health and lifestyles, as well as discover their childhood memories. About two-thirds (66.3%) had unhappy recollections particularly of such irritating routines as urine testing, injections, and special food programmes. Only 6% complained that future complications were not discussed with the child at the appropriate time, but with the exception of blindness, childhood knowledge of diabetic complications was poor. Around two-thirds (66.4%) left school with some examination result; 44.2% went into further education, while 19.8% entered into a trade. These attainments were comparable to those of local school leavers. As young diabetic adults, 62.8% were employed; 22.1% were students or housewives with no other occupations.

Percutaneous transhepatic occlusion for bleeding oesophageal varices in polycystic disease.

A 7-year-old boy with congenital polycystic disease of the kidneys and liver developed portal hypertension and gastro-oesophageal varices. After two episodes of upper gastrointestinal bleeding, percutaneous transhepatic occlusion of varices and of the left gastric vein was carried out. During the next year there was no evidence of further haemorrhage.