A national audit of pollen immunotherapy for children in the United Kingdom: patient selection and programme safety.

BACKGROUND: Specific immunotherapy (SIT) is an effective treatment for grass and/or tree pollen-induced severe allergic rhinoconjunctivitis. However, there are limited detailed data on the use of immunotherapy in children in the United Kingdom. OBJECTIVES: We audited NHS paediatric practice against current national guidelines to evaluate patient selection, SIT modalities and adverse events (AEs). METHODS: Paediatricians offering pollen SIT were identified through the British Society of Allergy and Clinical Immunology Paediatric Allergy Group (BSACI-PAG) and the database of SIT providers compiled for the Royal College of Physicians and Royal College of Pathologists 2010 joint working group. Standardized proformas were returned by 12 of 20 centres (60%), including 12 of 14 centres offering subcutaneous immunotherapy (SCIT) (85%). RESULTS: Three hundred and twenty-three children, with mean age 11 years at initiation (69% boys), had undergone 528 SIT cycles (SCIT 31%) over 10 years. Fifty-five percent of all patients had asthma. Among SCIT programmes 24.5% patients had perennial (± seasonal) asthma; 75.6% of asthmatics undertaking SCIT had treatments at BTS/SIGN step 2 or above. AEs occurred frequently (50.4% of all SIT cycles) but were mild. In sublingual immunotherapy (SLIT) treatment, local intraoral immediate reactions were most common (44.9% SLIT cycles), as compared with delayed reactions around the injection site in SCIT (28.3% SCIT cycles). An asthma diagnosis had no impact on the number of cycles with AEs, or the severity reported. Few cycles (2.9%) were discontinued as a result of AE(s). CONCLUSIONS AND CLINICAL RELEVANCE: Pollen SIT is available across England, though small numbers of children are being treated. Current national guidelines to exclude asthmatic children in SIT programmes are not being adhered to by most specialist paediatric allergy centres. SCIT and SLIT has been well tolerated. Review of patient selection criteria is needed and may allow greater use of this therapeutic option in appropriate clinical settings.

Developmental outcome in newborn infants treated for acute respiratory failure with extracorporeal membrane oxygenation: present experience.

OBJECTIVE: To describe the later health status of newborn infants who received extracorporeal membrane oxygenation (ECMO) for acute respiratory failure in the era after the UK ECMO trial. DESIGN: Prospective follow up study of newborn infants who received ECMO at a single centre between January 1997 and January 2001. SETTING: Departments of ECMO and Paediatric Intensive Care, University Hospitals of Leicester. PATIENTS: All babies who received ECMO within 14 days of birth. INTERVENTIONS: Neurodevelopment screening using the schedule for growing skills-II (SGS-II) assessment tool. MAIN OUTCOME MEASURES: Survival at 12 months of age by disease and functional development at follow up. RESULTS: A total of 145 neonates received ECMO for treatment of respiratory failure. Of these, 108 (75%) were alive at 1 year of age. There were no deaths in children treated for respiratory failure secondary to meconium aspiration syndrome (73/145). Ninety three (86% of survivors) infants attended a follow up visit at 11-19 months postnatal age. Eighty two were classed as normal, seven as having "impairment", and four as having "severe disability". CONCLUSIONS: Most newborn infants with acute respiratory failure treated with ECMO will have a normal neurodevelopment screening assessment at 11-19 months of postnatal age. There is no evidence to suggest that changes in neonatal practice since the UK ECMO trial have led to changes in outcome of infants undergoing ECMO therapy.

Extracorporeal life support for children with meningococcal septicaemia.

OBJECTIVE: To describe the short-term outcome of children with meningococcal sepsis treated with extracorporeal membrane oxygenation (ECMO) in a single centre. DESIGN: Retrospective analysis of case notes. SETTING: The Heartlink ECMO Centre, Glenfield Hospital, Leicester. PATIENTS: Eleven children (8 boys) out of a total caseload of 800 patients were treated for meningococcal sepsis with ECMO. INTERVENTIONS: Extracorporeal membrane oxygenation. RESULTS: All children with meningococcal sepsis treated with ECMO had a Glasgow Meningococcal Septicaemia Prognostic Score (GMSPS) > or = 12 (positive predictive risk of death of approximately 90%). Five children had adult respiratory distress syndrome (ARDS) and six had refractory shock with multi-organ dysfunction syndrome (MODS) at presentation for ECMO. All five children in the ARDS group survived, four of five receiving veno-venous (VV-) ECMO therapy. In contrast, only one of six children with refractory shock with MODS survived, all of whom required veno-arterial (VA-) ECMO therapy. CONCLUSIONS: Most children with meningococcal sepsis and severe ARDS can be successfully treated with VV-ECMO. In contrast, children with refractory shock and MODS die despite treatment with VA-ECMO. This report does not resolve whether ECMO therapy offers any advantage over conventional therapy in treating severe meningococcal sepsis.

Recurrent cough: natural history and significance in infancy and early childhood.

We investigated the outcome for a sample of children in whom recurrent cough was reported in the preschool years to determine 1) whether they shared the characteristics attributed to cough variant asthma, and 2) the proportion who developed classical wheezy asthma at follow-up during the early school years. A cohort of children identified as having recurrent cough in the preschool period was reassessed during the early school years. Previously identified asymptomatic preschool children who remained symptom-free provided a comparison group with respect to current respiratory symptoms, lung function, bronchial reactivity to inhaled methacholine, atopic status, peak flow variability, and recorded night cough. The response rate was modest, with 41% attending the follow-up study; information on current symptoms was available from a further 16%. Ascertainment of current symptoms showed that 70 of 125 (56.0% [95% CI 47.3-64.5%]) were symptom-free at follow-up, 46 (36.8% [28.7-45.5%]) continued to have recurrent cough in the absence of colds, and 9 (7.2% [3.6-12.8%]) reported recent attacks of wheeze. When comparing the 46 children whose recurrent cough persisted from the preschool period through to follow-up with subjects from the asymptomatic comparison group, the former had significantly more night cough (50.0% vs. 16.8%; P< 0.01), were more likely to be treated (10.9% vs. 1.7%; P=0.01), or were diagnosed (26.1% vs. 5.7%; P < 0.001) as asthmatic. They also showed greater bronchial reactivity than their asymptomatic counterparts (1.23 mg/ml vs. 3.35 mg/ml; P=0.002). Atopic status and other indices of lung function were similar between groups. We conclude that there are a group of children with long-term recurrent cough who display features consistent with a diagnosis of cough variant asthma, but at 2-4 years of follow-up, few progress to develop asthma characterized by wheeze.

Clinical presentation of chronic non-infectious rhinitis in children.

UNLABELLED: Chronic rhinitis is one of the commonest conditions affecting humans and there is evidence that its prevalence (and especially that of allergic rhinitis) is increasing. Although common, it is poorly recognised by doctors, parents and patients, particularly in children. AIMS: This study surveyed children with chronic non-infectious rhinitis to describe their presenting symptoms, differences in presentation between preschool and school-aged children and the prevalence of complications. SUBJECTS AND METHODS: We prospectively surveyed patients with a diagnosis of chronic rhinitis that was subsequently confirmed by response to therapy. Symptoms of rhinitis were assessed via an interview-conducted questionnaire. RESULTS: 567 children (357 boys), with a mean age (+/-SD) of 5.3 +/- 3.6 years, were studied over 14 months. Three hundred and fourteen were preschool children. Symptoms of a blocked or a runny nose were reported in 85% of patients, both symptoms occurring simultaneously in 59.9%. A blocked nose occurred more frequently in school-aged children, while a runny nose was commoner in preschool children. Sneeze and itch occurred less frequently in 56.1% and 33.6%, respectively. Complicating recurrent ear infections were reported in 46.9% of patients, more frequently in preschool children (P = 0.01); almost one-third (32.02%) had had grommets inserted. Learning problems, possibly secondary to somnolence as a result of poor sleep induced by sleep apnoea (snoring was reported in 58.4%), were reported in 24.1% of school-going children. CONCLUSION: As chronic rhinitis in South Africa commonly manifests with a blocked nose, patients display a high prevalence of associated complications. Doctors need to be aware of the presenting symptoms to diagnose and treat chronic non-infectious rhinitis earlier to prevent these complications.

Poor discriminatory performance of the Pediatric Risk of Mortality (PRISM) score in a South African intensive care unit.

OBJECTIVE: The use of the Pediatric Risk of Mortality (PRISM) score or other scoring systems in the intensive care unit (ICU) is of great importance for evaluating the efficacy and efficiency of a particular ICU. However, the PRISM score was developed and validated in the United States and subsequently validated in Europe, but has not been evaluated in a less affluent society. In general, scoring systems should be used only in populations similar to the reference population in which the prediction model was developed. We set out to determine the applicability of the PRISM score at Baragwanath Hospital, South Africa. DESIGN: Prospective, descriptive study. SETTING: Twenty-four-bed multidisciplinary ICU. PATIENTS: We analyzed 1,528 consecutive pediatric admissions from January 1989 to June 1994. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: PRISM scores, Therapeutic Intervention Scoring System scores, demographic, and clinical data collected prospectively were entered and stored by means of a commercial software package at the time of admission of each patient. The prediction of actual mortality by PRISM scoring was evaluated by the Hosmer and Lemeshow goodness-of-fit test (chi2[8 degrees of freedom]). Receiver operating characteristic curves were constructed and compared with those curves from pediatric ICU populations in the United States and Europe. Individual receiver operating characteristic curves were constructed for surgical and nonsurgical patients, age categories, and diagnostic categories. Compared with European and American ICU populations, our patients were younger, were mostly nonsurgical emergency admissions, stayed longer in the ICU, and were more severely ill with a higher admission PRISM score and overall mortality rate. Respiratory and septic diagnoses predominated, with very few surgical cases admitted. The Hosmer and Lemeshow goodness-of-fit test showed a significant failure of the PRISM scoring system to accurately predict mortality over a wide range of expected mortality rates (chi2[8 degrees of freedom] = 465, p = 0). Similarly, receiver operating characteristic analysis indicated a poor predictive power (Az = 0.73 +/- 0.01 [SEM]), with an area under the curve significantly less than that for the PRISM reference population (p = 0). PRISM showed equally poor discriminatory function at all age groups and diagnostic categories. CONCLUSIONS: The PRISM score needs to be recalibrated or recalculated for our patient population in view of the high discrepancy and poor discriminatory function shown. Part of the inaccuracy may derive from different demographic characteristics of our ICU population and a different pattern of diseases. It appears that PRISM is not population independent.

Confirmation of the safety of central venous catheterisation in critically ill infants and children--the Baragwanath experience.

OBJECTIVE: To evaluate, in critically ill children, the safety and effectiveness of routine central venous catheterisations (CVCs) performed by residents from all disciplines. DESIGN: Prospective audit of all CVCs over a 24-month period. SETTING: Multidisciplinary intensive care unit at Baragwanath Hospital, Soweto. PATIENTS: All critically ill patients 12 years of age or younger requiring CVC. All percutaneous sites (subclavian, internal jugular and femoral) were used; these were selected by the attending doctor and not influenced by the audit. RESULTS: There were 272 catheterisation attempts, of which 241 (88.6%) were successful. Patient age and size but not disease severity influenced incidences of both catheterisation failure and minor bleeding. The latter was the commonest early complication, occurring in 63 (23.2%) successful catheterisations. There were 7 major complications-3 pneumothoraces, 2 tachyarrhythmias and 2 major bleeds, all with subclavian vein catheterisation. Catheter-related infections (CRIs) occurred in 85 (51.2%) of 166 lines and catheter-related septicaemia (CRS) in 10 (5.7%) of 175 lines where there were sufficient data for evaluation. No patient or line factor, including duration of insertion, influenced CRI or CRS. In CRI, Staphylococcus epidermidis was the commonest organism. Other common CRI isolates were Enterococcus faecalis, Klebsiella spp. and Candida albicans. Six different organisms were implicated in CRS. CONCLUSIONS: CVC is a safe procedure with a high success rate. The femoral vein is the recommended percutaneous site of choice as it carries no great risk of sepsis and does not expose the patient to the hazard of intrathoracic complications.

Night cough in a population-based sample of children: characteristics, relation to symptoms and associations with measures of asthma severity.

Nocturnal cough in asthma is a common but poorly understood phenomenon. The aims of this study were to determine the relationship between recorded night cough, reported night cough and current wheeze in a population-based sample of children previously identified as wheezy, and to examine the relationship of nocturnal cough to current symptoms, markers of asthma severity and environmental exposure. Children were reassessed in the early school years by measuring current symptoms, ventilatory function, bronchial reactivity, peak flow variability, respiratory symptom diaries and home monitoring of overnight cough, transcutaneous arterial oxygen saturation, room temperature and humidity. Night studies were performed on 59 asymptomatic children and 41 children with current wheeze. Cough occurred more frequently in current wheezers compared to asymptomatic children (16 out of 41 (39%) vs 11 out of 59 (19%)), and more cough episodes were recorded (median 3.5 vs 2.0). Night cough was not associated with bronchial reactivity, peak flow variability, degree of morning dip, mean overnight arterial oxygen saturation, ventilatory function, maternal smoking or treatment of asthma. However, it was associated with lower overnight air temperature. Although night cough is more common in current wheezers, there is poor agreement between recorded and reported night cough. Objective tests of asthma severity are of little use in predicting its presence in this age group. The sleeping environment deserves further study.

The natural history of respiratory symptoms in preschool children.

We studied the natural history of preschool respiratory symptoms in a population-based sample of children followed during the early school years. Current symptoms, ventilatory function, bronchial responsiveness to methacholine (BR), atopic status, and peak expiratory flow variability (PEFV) were assessed. Among those initially asymptomatic (210 subjects), 83.3% remained symptom-free, 6.7% started to wheeze, and 10% developed recurrent cough. Nearly half (46.9%) of the initial wheezing group (145 subjects) became symptom-free, 37.9% continued to wheeze, and 15.2% reported recurrent cough. Over half (56.0%) of the cough group (127 subjects) became symptom-free, 7.2% developed wheeze, and 36.8% reported continuing cough. Preschool wheezers showed the greatest BR (geometric mean 1.91 mg/ml) and the highest atopic prevalence (AP) (43.6%) when compared with the preschool asymptomatic group (BR: 3.39 mg/ml; AP: 23.8%) and the cough group (BR: 2.62 mg/ml; AP: 26.7%) (p = 0.0001 and p = 0.006 respectively). Children whose wheeze had persisted from the preschool period exhibited the poorest ventilatory function, the highest BR, a high AP, and high PEFV. The study shows that fewer than half of preschool wheezy children continued to wheeze in the early school years but those with persistent wheeze display many of the clinical characteristics consistent with a diagnosis of asthma.

Changes in vancomycin pharmacokinetics in critically ill infants.

We aimed to assess the pharmacokinetics of vancomycin in critically ill infants, and to evaluate the standard recommended dose of 10 mg/kg 6 hourly. All infants admitted to the Baragwanath Hospital ICU who had arterial lines in situ, and for whom vancomycin 10 mg/kg 6 hourly was prescribed for an infective insult and who had parental consent, were included in the study. Vancomycin was infused over 60 minutes. Serum samples were taken immediately before the dose and at 30, 60, 120 and 300 minutes after the end of the vancomycin infusion, on days 2 and 8 of therapy. Extrapolated peak concentration (Cmax), trough concentration (Cmin), apparent volume of distribution (Vd), elimination half-life (t1/2el) and clearance (CL) were determined for each patient. Day 2 values were compared with those of day 8. Day 2 serum concentrations were assayed on 20 patients and day 8 concentrations in 15. The mean vancomycin Vd on day 2 (0.81 l/kg) was significantly (P = 0.007) larger than that on day 8 (0.44 l/kg). The change in Vd resulted in a significant change in mean Cmax (29.1 vs 35.5 micrograms/ml) (P = 0.02) and mean t1/2el (5.3 vs 3.4h) (P = 0.01) over the treatment period. Critically ill infants displayed a large initial volume of distribution which probably resulted from aggressive fluid resuscitation. This also results in a large variation in other pharmacokinetic parameters, namely Cmax and t1/2el. Although the routine monitoring of vancomycin serum concentrations remain controversial, we feel that in view of these large pharmacokinetic variations, the critically ill infant is a specific group where monitoring of vancomycin serum levels is indicated.

Clinical characteristics of black asthmatic children.

A prospective study of 455 black asthmatic children (277 boys) attending the Baragwanath Hospital asthma clinic was undertaken. A history was obtained by means of a standardised questionnaire and skin tests were performed. Cough was the commonest presenting symptom and upper respiratory tract infections, exercise and cold weather the commonest symptom precipitants. The relative incidences of the other precipitants reflected the environment of the study population. Associated atopic conditions were present in 75.5% of patients and a family background in 22.2%. Other respiratory diagnoses were commonly made, particularly tuberculosis, which was diagnosed in 7.4%. Fewer than one-third had no positive skin reaction. The commonest allergens were grasses, pollen and house-dust mites. The high proportion of house-dust mite sensitivity (44.2%) contradicts beliefs that they are rare at higher altitudes.

Wheeze in preschool children: who is followed-up, who is treated and who is hospitalized?

This study determined the proportions of children < or = 5 yrs of age with reported wheeze who were undergoing medical follow-up, receiving anti-asthma medication, or admitted to hospital; and investigated factors important in determining which children would receive these treatments. The symptomatic children represented a wheeze prevalence of 16% of the study sample of 1,422 children. The cumulative incidence of treatment and hospitalization and point prevalence of current medical follow-up were determined using a parent-answered postal questionnaire study of a population-based random sample of 222 children. Odds ratios (OR) were calculated for wheeze severity, environmental, social, familial and demographic factors found to affect the likelihood of these treatment end-points. Among 222 children with wheeze, 99 (35%) were under current medical review, 165 (75%) had received medication, and 48 (22%) reported being hospitalized. Current follow-up was more likely in girls (OR 2.22; 95% confidence interval (95% CI) 1.12-4.38), with more than three attacks of wheeze in the last year (OR 17.44; 95% CI 5.22-58.3), or with a household pet (cat or dog) where inhalants were wheeze precipitants (OR 13.65; 95% CI 3.16-58.94). Treatment became more likely in older children (OR 3.91; 95% CI 1.10-12.71), with inhalants as wheeze precipitants (OR 4.66; 95% CI 1.08-20.14) or with a household pet (OR 2.28; 95% CI 1.04-5.03). Hospitalization was less likely with frequent wheeze (OR 0.30; 95% CI 0.12-0.77), but more likely if shortness of breath occurred with wheeze. Medical follow-up and treatment are related to wheeze severity and exposure to inhaled precipitants, whereas hospital admission occurred in children with attacks causing shortness of breath, and with decreasing frequency of attacks per year.

Comparison of central venous pressure measurements in the intrathoracic and the intra-abdominal vena cava in critically ill children.

A prospective study was conducted to compare simultaneous intrathoracic and intra-abdominal central venous pressures in 10 critically ill, ventilated paediatric intensive care patients. Central venous pressures were measured using the water column technique over a 6 h study period. There was excellent correlation between intrathoracic and intra-abdominal vena caval pressure measurements (r = 0.974, p < 0.001). The difference between paired measurements did not exceed the limits of agreement (+/- 2SD, -2.36 to 4.42 cm H2O). The mean (SD) difference between readings was small (1.03 +/- 1.69 cmH2O) and was within clinically tolerable limits. These data suggest a clinically useful, close relationship between intra-abdominal and conventional intrathoracic central venous pressure measurement in this group of patients.

Wheeze in preschool children and its relation with doctor diagnosed asthma.

OBJECTIVE: To describe the characteristics of wheeze and its relation with doctor diagnosed asthma in children aged 5 years and under. DESIGN: Questionnaire survey of population based random sample of children registered on Leicestershire Health Authority's child health index for immunisation; questionnaire completed by parents. SUBJECTS: 1650 white children born in 1985 to 1989 who were surveyed in 1990. MAIN OUTCOME MEASURES: Age distribution, severity, precipitants, seasonal characteristics, and diurnal variation of wheeze, family history of asthma/atopy, and their association(s) with doctor diagnosed asthma. RESULTS: There were 1422 replies (86.2%). Two hundred and twenty two (15.6%) were reported to have wheezed and of these 121 (8.6%) had formally been diagnosed as having asthma. More than 80% of the former had recurrences of wheeze and 40% (72) had three or more episodes in the preceding 12 months. Age, number of episodes per year, the severity of shortness of breath with attacks, and precipitants other than colds were the major factors determining the probability that a wheezy child will be diagnosed as having asthma. The data also suggest that despite the strong association of symptom based criteria with the label asthma, asthma was not diagnosed by these same severity criteria in one quarter of cases. CONCLUSIONS: Clinical and physiological follow up studies of children identified as asthmatic by the above criteria during the preschool years should validate or refute the predictive value of these measures of wheeze severity.

Paediatric acute renal failure. A report on 2 cases successfully managed with continuous venovenous haemodiafiltration.

In critically ill patients continuous venovenous haemodiafiltration (CVVHD) is a method of renal replacement therapy gaining popularity. The advantage of CVVHD over intermittent haemodialysis and peritoneal dialysis lies in the accurate control of ultrafiltration and of solute clearance. Two paediatric patients with acute renal failure treated successfully with CVVHD are described. The role of CVVHD in renal supportive therapy in South African paediatric intensive care units is discussed.

Epidemiological study of wheeze, doctor diagnosed asthma, and cough in preschool children in Leicestershire.

OBJECTIVE: To determine the cumulative prevalences of wheeze and doctor diagnosed asthma and the point prevalences of recurrent cough and wheeze in children aged 5 years and under. DESIGN: Questionnaire survey of population based random sample of children registered on regional authority's child health index for immunisation; questionnaire completed by parents. SETTING: Leicestershire. SUBJECTS: 1650 white children born in 1985-9 who were surveyed in 1990. MAIN OUTCOME MEASURES: Cumulative prevalences of wheeze and doctor diagnosed asthma and point prevalences of recurrent cough and wheeze by age and sex. RESULTS: There were 1422 replies (86.2%; 726 for boys, 696 for girls). Overall, 11.0% (95% confidence interval 9.4% to 12.6%) of children had formally been diagnosed as having asthma, the cumulative prevalence in boys (12.7%) being somewhat higher than in girls (9.2%) (age adjusted odds ratio 1.47, p = 0.03). As expected, the cumulative prevalence of asthma increased significantly with age (7.5% (13/173) in children under 1 year, 15.9% (61/383) in children of 4 years and over; p < 0.001). The cumulative prevalence of wheeze overall was 15.6% (13.7% to 17.5%), being higher in boys (17.6%) than in girls (13.5%) (odds ratio 1.38, p = 0.03). The overall prevalence of recurrent cough without colds was 21.8% (19.6% to 23.9%), with a non-significant excess in boys (23.1% v 20.4%). The overall prevalence of wheezing attacks during the previous 12 months was 13.0% (11.3% to 14.8%) with a non-significant excess in boys (14.5% v 11.5%). CONCLUSIONS: These findings are baseline results and emphasise the importance of studying the age group of interest rather than relying on the recall of parents of school age children.

Thalassemia: lung function with reference to iron studies and reactive oxidant status.

Pulmonary function tests were performed in 15 thalassemic patients (age 5 years 8 months to 18 years 6 months), receiving both regular transfusions and desferrioxamine, to determine the presence and nature of any abnormalities in lung function. Reactive oxidant production from neutrophils was measured simultaneously to ascertain if a causal relationship existed between free radical production and tissue damage in the lungs. Mean total lung capacity, mean residual volume, and mean forced vital capacity were significantly reduced, indicating a restrictive pattern of lung function abnormality. In addition, the carbon monoxide diffusion was low, and hypoxemia was present in 6 of 13 patients tested. These pulmonary function abnormalities did not correlate with age, cumulative volume of transfusion, or serum ferritin levels. In addition, neutrophil reactive oxidant status did not correlate with these or with pulmonary function parameters. These results indicate that neutrophil-derived oxygen free radicals do not appear to be a major cause of lung function abnormalities in thalassemics.