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G97 PARAPNEUMONIC EFFUSION AND EMPYEMA: THE EXPERIENCE OF 101 CASES IN ONE CENTRE

N. Barnes, J. Hull, A. Thomson. Department of Paediatrics, John Radcliffe Hospital, Oxford, UK

Introduction: Considerable heterogeneity exists in the management of parapneumonic effusion and empyema both within and between centres in the UK. Our unit first line management comprises intravenous antibiotic therapy with chest tube drainage and intra-pleural fibrinolysis, with surgery reserved for those children who subsequently fail to improve.

Methods: A retrospective database analysis of the management of all children with parapneumonic effusion and empyema admitted to the John Radcliffe Hospital over a 7 year period, 1996–2003.

Results: 101 children were admitted. 10 were excluded as they were part of a multicentre RCT and had received intra-pleural saline instead of urokinase. Of the remaining 91, 47 were female and 44 male. Median age on admission was 5.8 years (range 0.3–14.0). Symptoms pre-admission averaged 11 days, with February the commonest month for presentation. 79 underwent chest ultrasound, confirming an effusion in all, described as loculated/septated (58) or echogenic (9). In 12 cases no specific comment was made regarding the nature of the fluid seen on ultrasound. 87 had subsequent chest tube drainage and then received intra-pleural fibrinolysis with urokinase. An aetiological organism was identified in 20 cases (22%) (Streptococcus pneumoniae (9), group A streptococcus (5), Staphylococcus aureus (4), Haemophilus influenzae (1), coliform (1)). In a further eight cases (9%), Gram positive organisms were seen on pleural fluid microscopy but did not grow on culture. Two (2%) required surgery when medical management had failed. Median duration of admission was 7 days (range 2–21 days); median duration of stay from intervention was 5 days (range 2–19 days). At follow up all children were symptom free with minimal pleural thickening on chest x ray.

Conclusion: Antibiotic therapy with chest drain insertion and intra-pleural urokinase is effective in treating empyema and is associated with a good long term outcome.

G98 INTRAMUSCULAR TRIAMCINOLONE FOR DIFFICULT ASTHMA

J. R. Panickar, P. Kenia, J. Grigg. Leicester Royal Infirmary Children’s Hospital, UHL NHS Trust, Leicester

Background: Some children suffer from chronic severe asthma, despite maximal inhaled therapy. In 2002, we started to treat some of these children with three or more monthly injections of intramuscular triamcinolone acetonide. In 2003, we performed a retrospective review of these children. We were particularly interested in whether any beneficial effect persisted after 4 weeks, a period beyond the expected duration of effect of intramuscular steroid.

Methods and Results: Data were extracted from retrospective review of case notes. Severity variables of the 3 month preceding treatment were compared with the period during treatment (3–4 months) and 3 months post treatment. Eight children received three or more monthly doses of intramuscular triamcinolone from 1 January 2002 to 31 October 2003. The results are summarised in the table. Two children reported cushingoid appearance during treatment. No other adverse effects were reported.

Abstract G98 Variables are summarised as the mean (SD) events per patient per month, and compared to pre-treatment period by paired t test

Conclusion: In a severe group of asthmatic children, intramuscular triamcinolone significantly reduced the number of exacerbations, days and dose of oral steroids, number of hospital admissions, and inpatient days during treatment. There is evidence of persistent effect for at least 3 months after the pharmacological activity of the last intra muscular dose.

G99 PROSPECTIVE LONGITUDINAL STUDY OF LUNG FUNCTION IN CHILDREN WITH SICKLE CELL DISEASE

K. P. Sylvester1, R. A. Patey1, G. F. Rafferty1, M. Dick1, D. Rees2, S. L. Thein2, A. Greenough1. 1Departments of Child Health and 2Haematological Medicine, Guy’s, King’s & St Thomas’ School of Medicine, King’s College London, UK

Background: Lung function abnormalities are commoner in children with sickle cell disease (SCD) than ethnic matched controls and more severe in older compared with younger SCD children. Children who have suffered an acute chest syndrome (ACS) are particularly at risk of lung function abnormalities, but whether this influences the rate of deterioration in lung function in childhood remains untested.

Aim: To test the hypothesis that children who had had an ACS episode would have a greater change in lung function over time than SCD children who had had no ACS episodes.

Methods: Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), FEV1/FVC, and peak expiratory flow (PEF) were assessed by spirometry in 45 SCD children. The children had a median age of 10 (range 4–16) years. Their lung function was assessed on two occasions a median of 9 (range 2–27) months apart.

Results: Thirteen of the 45 SCD children, who were of similar age to the rest of the cohort, had been hospitalised for an ACS episode (ACS children). At baseline, the ACS children, compared with age matched SCD children, had lower FEV1/FVC (p 0.03) and a greater percent change in FVC (p 0.04) post bronchodilator. The children with ACS episodes had a greater change in FEV1 between the two sets of measurements (p 0.05) than the rest of the cohort.

Conclusion: These results suggest SCD patients who have ACS episodes are at risk of a greater speed of deterioration in lung function even in childhood.

G100 RISK FACTORS FOR RESPIRATORY MORBIDITY AT 6 AND 12 MONTHS OF AGE IN VERY PREMATURELY BORN INFANTS

A. Greenough1, E. Limb2, L. Marston2, N. Marlow4, S. Calvert3, J. Peacock2. 1Department of Child Health, Guy’s, King’s, and St Thomas’ Medical School; 2Department of Public Health Sciences, St George’s Hospital Medical School; 3Department of Paediatrics, St George’s Hospital, London; 4University Hospital, Nottingham, UK

Background: Recurrent cough and/or wheeze requiring treatment are frequently reported at follow up of very prematurely born infants.

Aim: To identify risk factors for this chronic respiratory morbidity.

Methods: Structured questionnaires were completed by local paediatricians when 395 infants of less than 29 weeks of gestational age, who had been entered into the UKOS trial, were seen in outpatients at 6 and 12 months of age corrected for prematurity. Relationships of respiratory morbidity with possible risk factors, including mode of ventilation, were investigated using unifactorial and multifactorial analyses.

Results: At 6 and 12 months of corrected age 21% and 17%, respectively, of infants had frequent (more than once a week) cough and 18% and 21%, respectively, had frequent wheeze. Logistic regression analysis demonstrated that the only risk factors for frequent cough at 6 and 12 months were male sex (odds ratio (OR) 2.62, 95% CI 1.07 to 6.42) and having older siblings less than 5 years of age (OR 4.52, 95% CI 1.92 to 10.64), and for frequent wheeze at 6 and 12 months were male sex (OR 13.56, 95% CI 1.76 to 104.71). The prevalence of symptoms was unrelated to mode of ventilation. At 6 and 12 months 45% and 52% of infants, respectively, had taken bronchodilators and/or inhaled/systemic steroids; risk factors were male sex (OR 2.45, 95% CI 1.32 to 4.54), oxygen dependency at 36 weeks (OR 2.36, 95% CI 1.13 to 4.93), and being discharged home on oxygen (OR 2.08, 95% CI 1.04 and 4.14).

Conclusion: Both genetic and environmental factors are important in determining chronic respiratory morbidity in infants born very prematurely.

G101 TH1 LYMPHOCYTES ARE DEPLETED DURING ACUTE RESPIRATORY SYNCYTIAL VIRUS INFECTION

M. F. E. Roe1, D. M. Bloxham2, D. K. White1, R. I. Ross-Russell1, R. C. Tasker1, D. R. O’Donnell1. 1Department of Paediatric, University of Cambridge, Cambridge; 2Department of Haematology, Addenbrooke’s Hospital, Cambridge

Aims: Lymphopenia is a feature of acute respiratory syncytial virus infection. We hypothesised that chemokine receptors could be used to show changes in T helper (Th) 1, Th2, and suppressor lymphocyte numbers during acute RSV infection.

Methods: Specific chemokine receptors are expressed on activated Th lymphocytes and may be used to identify phenotype. In particular, CXCR3 is found exclusively on Th1 lymphocytes while CCR4 is a marker of Th2 cells. Suppressor activity may also be important in the overall T lymphocyte function and these cells will express CD25+. Blood was taken from 20 infants with acute RSV infection and after recovery. Cell surface expression of CXCR3, CCR4, and CD25 on CD3+/CD4+lymphocytes was determined by flow cytometry. Absolute lymphocyte counts were determined by haematological blood count.

Results: We found that absolute numbers of CXCR3+Th1 cells were significantly depleted in acute RSV infection when compared with convalescent samples (p<0.01). In contrast, numbers of CCR4 Th2 were unchanged in acute RSV infection. The Th1:Th2 ratio was significantly different between acute and convalescent samples. There was no difference in numbers of CD25+cells between acute and convalescent samples.

Conclusions: Our findings may have implications for the long term memory response to acute RSV infection. In particular, a lymphocyte response that is weighted towards Th2 predominance may promote the development of asthma and atopy.

Funded by 2002 HC Roscoe Fellowship, British Medical Association.

G102 AIRWAY INFLAMMATION AND REMODELLING IN CHILDREN WITH CYSTIC FIBROSIS (CF)

T. N. Hilliard1,2, N. Madden2, A. G. Nicholson2, J. Shute3, E. W. F. W. Alton1, J. C. Davies1,2, A. Bush2. 1Department of Gene Therapy, Imperial College, 2Royal Brompton Hospital, London; 3Department of Pharmacology, University of Portsmouth

Introduction: The airway inflammatory response is exaggerated in CF, but there is little information on the relationship between inflammation and structural airway changes in early stage disease. We aimed to compare this relationship between CF and other inflammatory lung diseases.

Methods: Flexible bronchoscopy was performed for clinical reasons in three groups of children: 1) CF, 2) Primary ciliary dyskinesia (PCD), and 3) recurrent respiratory tract infections (RTI). Broncholaveolar lavage (BAL) and endobronchial biopsy were performed under standardised conditions.

Results: 53 children underwent bronchoscopy (27 CF, 6 PCD, 20 RTI). 49 biopsies were available, of which 33 were of sufficient quality for measurement of reticular basement membrane (RBM) thickness (67%; 16 CF, 5 PCD, 12 RTI). Both CF and PCD groups had raised neutrophil and interleukin 8 (IL 8) concentrations compared with the RTI group (see table). RBM was thickened in the CF group but this was not predicted by age, bacterial count, or cell counts.

Abstract G102 Data are expressed as median (range)

Conclusions: This study provides evidence of remodelling within the airways of children with cystic fibrosis. With similar levels of inflammatory markers in BAL between CF and PCD, RBM thickening may therefore not be directly related to inflammation occurring within the airway lumen.

G103 LONGITUDINAL ASSESSMENT OF LUNG FUNCTION IN INFANTS AND PRE-SCHOOL CHILDREN WITH CYSTIC FIBROSIS (CF)

W. J. Kozlowska, P. Aurora, S. Lum, C. Saunders, S. Ranganathan, R. Castle, J. Stocks, the LondonC. F. Collaboration (LCFC). Portex Respiratory Unit, Institute of Child Health, London, WC1N 1EH

Background: Following recent advances in full forced expiratory manoeuvres in infants and pre-school children, longitudinal assessments are now feasible. We have reported significant reductions in FEV0.5 (raised volume technique) in infants newly diagnosed with CF when compared to healthy controls.1

Aim: To follow this cohort up to school age, with spirometric parameters expressed as z scores (z scores <−2 being below the normal range).

Methods: Healthy infants and those with CF, recruited as part of the LCFC, were invited to return at age 3.5 years for incentive spirometry.

Results: 22 CF and 10 healthy controls have been retested to date. Infants with CF (mean age 0.66 years) had a mean (SD) z score for FVC and FEV0.5 of −2.3 (1.5) and −2.5 (2.2), respectively, with FEV0.5 being abnormally low in 12 subjects. When retested at a mean age of 3.9 years, mean (SD) z scores were −1.27 (1.85) for FVC and −0.55 (0.85) for FEV0.5, with only one child with CF still having an abnormal FEV0.5.

Conclusions: These initial results suggest either that there is a relative improvement in lung function during the pre-school years in children diagnosed with CF during infancy, or that spirometric measurements are less sensitive in detecting changes in airway function during the pre-school years than in infancy. Testing continues.

Supported by the CF Trust and Portex Ltd.


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Abstract G103

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G104 INERT GAS MULTIPLE BREATH WASHOUT IS MORE SENSITIVE THAN PLETHYSMOGRAPHY OR SPIROMETRY FOR DETECTING LUNG DISEASE IN PRE-SCHOOL CHILDREN WITH CYSTIC FIBROSIS (CF)

P. Aurora1, A. Bush2, C. Oliver1, P. Gustafsson3, J. Stocks1, the LCFC. 1Institute of Child Health, London; 2Royal Brompton Hospital, London; 3Sahlgrenska University Hospital, Goteborg, Sweden

Rationale: The current emphasis on early detection and treatment of CF has created an urgent need for sensitive measures of lung function applicable to very young subjects.

Methods: 40 children with CF aged 2–5 years and 37 matched healthy controls performed multiple breath washout (MBW), plethysmography, and spirometry. Outcome measures were lung clearance index (LCI) from MBW; sRaw from plethysmography; and FEV0.5 and FEF25–75 from spirometry. z sores were calculated from published reference data. Comparisons were by t test; by cross tabulation of normal v abnormal results, using mean 2 SD as limits of normality; and by calculation of the area under the receiver operator characteristic curve (AUCROC).

Results: Success rate at first visit was between 75% and 80% for all tests. 30 children with CF and 31 healthy children completed all three measurements. LCI in healthy children was independent of age and height.

Conclusion: Most pre-school children can perform MBW, plethysmography, and spirometry at first attempt. The majority of children with CF have abnormal LCI, including those with normal sRaw and normal spirometry. MBW has potential for early detection of CF lung disease in pre-school children.

Funding: Dunhill Medical Trust, BLF, CF Trust.

Abstract G104

G105 LUNG FUNCTION IN ASIANS WITH CYSTIC FIBROSIS (CF) IS WORSE THAN CAUCASIAN HOMOZYGOUS ΔF508 CONTROLS

J. McCormick, E. J. Sims, A. Mehta. UK CF Database, Tayside Institute of Child Health, Ninewells Hospital, Dundee, Scotland UK DD1 9SY

Introduction: Using the UK CF Database, we tested the hypothesis that the CF phenotype in Asian patients is as severe as matched homozygous ΔF508 Caucasian controls.

Methods: Asian patients were matched with up to five controls and analysed for mean height, weight, BMI z scores, FEV1, and FVC% predicted data and the use of inhaled corticosteroids (ICS) and pancreatic enzymes. Controls were Caucasian homozygous ΔF508 patients matched for sex, age (+/−12 months), location (by CF centre or clinic), and chronic Pseudomonas aeruginosa status. CF related diabetes patients were excluded. Anthropometric measures were analysed +/− adjustment for ethnicity, and FEV1% predicted was calculated using three different formulae to adjust for ethnicity and malnourishment.

Results: 51 Asian CF patients (30 male) were matched with 145 controls (93 male). Asian patients had significantly lower weight (males p<0.01, females p<0.05) and BMI (p<0.01 males, females p<0.01) z scores compared with matched controls. Differences were not significant with ethnicity adjustments though the trend towards lower values persisted. Asian patients had significantly poorer FEV1 and FVC% predicted compared with controls, irrespective of corrective factors. There were no differences in ICS use or pancreatic enzyme dosage between groups.

Conclusions: CF is increasingly recognised in the non-Caucasian population and these data suggest that the Asian CF phenotype is more severe for lung function than the Caucasian homozygous ΔF508 phenotype, and as severe for anthropometric measures. Sociocultural factors and rare CF genotypes may be contributing to this severity. This vulnerable group should be candidates for further study to prevent earlier morbidity and mortality.

Data supplied by the Directors of UK CF Centres.

G106 THE CLINICAL VALUE OF OBTAINING SPUTUM AND COUGH SWAB SAMPLES FOLLOWING INHALED HYPERTONIC SALINE IN CHILDREN WITH CYSTIC FIBROSIS (CF)

S. A. Ho, R. Ball, L. J. Morrison, K. G. Brownlee, S. P. Conway. Leeds Regional Paediatric Cystic Fibrosis Unit, St James’s University Hospital, Leeds, UK

Aims: Prompt detection and treatment of lower respiratory tract infection is essential in the management of patients with CF who often have signs or symptoms of respiratory infection without any pathogens being isolated from sputum or cough swab specimens. The aims of this study were to assess the efficacy and clinical value of obtaining sputum and oropharyngeal cough swab samples following induction with hypertonic saline (HS) in this group of patients.

Methods: Patients attending the regional CF unit in Leeds for routine outpatient appointments were invited to enter the study. Nebulised salbutamol was administered followed by 6% HS. Sputum was preferentially obtained before and after HS induction if possible. If the patient was not able to expectorate oropharyngeal cough swabs were taken instead. Statistics was performed using χ2test.

Results: Forty three outpatients with CF, mean age 7.2 years (range 1.8–12.9 years) were recruited over a 2 year period. The procedure was tolerated in 41 of 43 patients. Four patients were able to expectorate sputum before and 19 after HS induction. Samples obtained following inhaled HS were more likely to grow respiratory pathogens than pre-induced specimens (p 0.006). Pathogens were isolated from 13 patients’ HS induced samples but not from their corresponding pre-induced specimens, and four patients’ pre-induced specimens cultured organisms that were not identified from their HS induced samples. Significant changes were made in the management of 13 (30.2%) patients directly resulting from the positive culture of pathogens only from HS induced samples.

Conclusions: Cultures from oropharyngeal cough swab or expectorated sputum specimens following inhalation of HS provide additional microbiological information which is of clinical value and may lead to changes in patient management.

G107 DRUG RESISTANCE HAS NOT EMERGED DESPITE INCREASED USE OF ANTIBIOTIC THERAPY FOR NEW ACQUISITIONS OF PSEUDOMONAS AERUGINOSA IN CHILDREN WITH CYSTIC FIBROSIS (CF)

S. A. Ho, M. Denton, K. G. Brownlee. MMedSci in Child Health, University of Leeds

Aims: This study examined the antibiotic sensitivity profile (ASP) of children with CF who had new acquisitions of P aeruginosa to 1) investigate if drug resistance was increasing since the introduction of more aggressive antibiotic treatment; and 2) elucidate the source of infection for this organism.

Methods: A retrospective study was completed on all patients attending the Leeds regional CF unit from January 1990 to December 2000. ASP scores for each patient were devised based on the drug resistance of their P aeruginosa isolates from sputum and cough swab cultures. Statistical analyses included Spearman’s correlation and Wilcoxon signed ranks test.

Results: 288 isolates of P aeruginosa were grown from 242 patients (87 first acquisitions and 155 with previous colonisation but free of infection for preceding 12 months or longer). The median age was 8.3 years (range 3 months to 18.3 years). Overall antibiotic sensitivity rates were high (⩾86.5%) to six common front line antibiotics for all newly acquired P aeruginosa strains, and resistance rates were lower than those of chronically infected patients with CF. No statistically significant linear trend was observed in the antibiotic sensitivity of new acquisitions for P aeruginosa. The ASP scores of patients on subsequent growths of P aeruginosa, when compared with scores of their initial isolates, did not show increasing drug resistance.

Conclusions: These data suggested that the main source of infection for new acquisitions of P aeruginosa existed in the community. Subsequent new growths of P aeruginosa did not show emerging drug resistance despite aggressive antibiotic treatment of earlier infection, which supported the current practice of eradicating new acquisitions for this bacterium with antimicrobial agents.

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