Spatial variation in the risk of hospitalization with childhood pneumonia and empyema in the North of England.

The aim of this study was to investigate spatial variation in risk of hospitalization in childhood pneumonia and empyema in the North of England and associated risk factors. Data on childhood (0-14 years) hospital admissions with a diagnosis pneumonia or empyema were linked to postcode districts. Bayesian conditional autoregressive models were used to evaluate spatial variation and the relevance of specific spatial covariates in an area-based study using postcode as the areal unit. There was a sixfold variation in the risk of hospitalization due to pneumonia across the study region. Variation in risk was associated with material deprivation, Child Well-being Index (CWI) health domain score, number of children requiring local authority support, and distance to hospital. No significant spatial variation in risk for empyema was found.

The efficacy of cough plates in the identification of bacterial pathogens in children with cystic fibrosis.

BACKGROUND: Identification of bacterial pathogens is paramount for prompt and effective treatment of respiratory exacerbations in children with cystic fibrosis (CF). This can be a challenge in non-expectorating patients as reliability of cough swabs (CS) is poor. More recently, cough plates (CP) have been reported to give high yields in some series. The aim of the study was to ascertain their effectiveness compared to CS and to assess the impact of cough strength on efficacy of CP. METHOD: Non-expectorating children with CF aged 3-16 years were recruited. Baseline data was recorded and peak cough flow measured. Specimens were obtained with CP and a cough swab in a randomised order and repeated at up to four clinic visits to obtain multiple measurements. Subjects completed a short questionnaire. RESULTS: Number of subjects was 95, mean age 8.8±4.1 years, 45 males. Mean baseline % predicted FEV1 was 90.8±18. In total, 324 sets of specimens were collected. Pathogens were isolated in 18.2% of CS and 8% of CP. Agreement between the two specimens occurred in only 5.5% of cases. CP isolated pathogens on six occasions when the CS was negative while 40 CS were positive with a corresponding negative CP. Cough strength increased with age, and there was a trend towards older children isolating more pathogens on CP. However, this was not statistically significant. The majority of subjects preferred the CP. CONCLUSIONS: CP are less effective than CS in identifying respiratory pathogens in children with CF.

Impact of the 7-valent pneumococcal conjugate vaccine on the incidence of childhood pneumonia.

In September 2006, the 7-valent pneumococcal conjugate vaccine (PCV7) was added to the UK immunization programme. We aimed to evaluate the impact of PCV7 on the incidence of all-cause community-acquired pneumonia (CAP) in children. A prospective survey was undertaken in 2008-2009 at 11 hospitals in North East England of children aged 0-16 years with radiologically confirmed pneumonia. Data were compared to those from a similar survey undertaken in the same hospitals in 2001-2002. A total of 542 children were enrolled, of which 74% were aged <5 years. PCV7 uptake was 90∙7%. The incidence of pneumonia was 11∙8/10,000 [95% confidence interval (CI) 10∙9-12∙9], and the hospitalization rate was 9∙9/10,000 (95% CI 9∙0-10∙9). Compared to 2001, there was a 19% (95% CI 8-29) reduction in the rate of CAP in those aged <5 years, and in those <2 years a 33∙1% (95% CI 20-45) reduction in the incidence of CAP and 38∙1% (95% CI 24-50) reduction in hospitalization rates. However, for those unvaccinated aged ≥5 years, there was no difference in the incidence of CAP and hospitalization rate between both surveys. Since 2001, the overall reduction in incidence was 17∙7% (95% CI 8-26) and for hospitalization 18∙5% (95% CI 8-28). For the <5 years age group there was a lower incidence of CAP in PCV7-vaccinated children (25∙2/10,000, 95% CI 22∙6-28∙2) than in those that were not vaccinated (37∙4/10,000, 95% CI 29∙2-47∙1). In conclusion, PCV7 has reduced both incidence and rate of hospitalization of pneumonia in children, particularly in the <2 years age group.

A follow-up study of children hospitalised with community-acquired pneumonia.

OBJECTIVE: To investigate the outcome for children hospitalised with radiologically confirmed community-acquired pneumonia (CAP) DESIGN: Controlled follow-up study. SETTING: Community based in Newcastle upon Tyne, North Tyneside and Northumberland schools. PATIENTS: 103 cases of radiologically confirmed CAP a median of 5.6 years (range 4.4-7.4) after admission to Newcastle General Hospital, matched for sex and school class to a mean of two controls (n = 248). INTERVENTIONS: A respiratory questionnaire, clinical examination and spirometry measurements. MAIN OUTCOME MEASURES: Multiple regression was used to describe associations between explanatory variables, including CAP, and outcome variables: forced expiratory volume in 1 s percent predicted (FEV(1) %), forced vital capacity percent predicted (FVC %), persistent cough, doctor diagnosis of asthma and abnormal chest shape. RESULTS: Cases were 2.9 times more likely (95% CI 1.45 to 5.71, p = 0.020) than controls to have persistent cough and 5.5 times more likely to have an abnormal chest shape (95% CI 1.65 to 18.28, p = 0.005). Cases of an atopic parent had a 7.0% deficit in FEV(1) % predicted (95% CI -10.5 to -3.2, p<0.001) and a 4.4% deficit in FVC % predicted (95% CI -8.0 to -0.78, p = 0.017), but were not at increased risk of subsequent asthma. Cases of a non-atopic parent were at increased risk of subsequent asthma (OR 4.8, 95% CI 1.43 to 16.34, p = 0.011) but not of deficit in lung function. CONCLUSIONS: CAP requiring admission to hospital is associated with deficits in lung function and persistent respiratory symptoms. This has implications for follow-up for which recommendations are currently lacking. Parental atopy may be a determinant of outcome.

Hypomagnesaemia in cystic fibrosis patients referred for lung transplant assessment.

BACKGROUND: Hypomagnesaemia in patients with cystic fibrosis (CF) is under-recognized although the true incidence is unknown. Many patients are asymptomatic, although severe deficiency may be associated with muscle weakness, cramps and tetany. Hypomagnesaemia may be a risk factor for post-transplant complications including convulsions, which may be exacerbated by the use of calcineurin inhibitors. The aims of the present study were to describe serum magnesium levels and to investigate the relationship between magnesium levels and age, and renal function measurements in patients with CF referred to a transplant centre for lung transplant assessment. METHODS: We reviewed the data of all 106 CF patients referred for transplant assessment from January 1995 to December 2003. Demographic and biochemical data were recorded and the explanatory variables were subjected to univariate analysis and linear regression analysis. RESULTS: Mean serum magnesium level was 0.75 mmol/L (range 0.46-1.03, normal range 0.74-1.1). 57% of patients had hypomagnesaemia. Serum magnesium levels were not associated with age, serum creatinine or GFR. CONCLUSIONS: Hypomagnesaemia is a common finding in patients with CF referred for lung transplant assessment. Serum magnesium levels should be monitored in all CF patients being referred for lung transplant irrespective of the results of other renal function tests.

Postmortem diagnosis of chronic granulomatous disease: how worthwhile is it?

A previously healthy 11 year old boy died unexpectedly after a rapid course of progressive pneumonia. Postmortem microbiology and histopathology suggested an underlying diagnosis of chronic granulomatous disease. This was confirmed by neutrophil oxidative burst and gene mutation analysis of other family members, one of whom benefited from early bone marrow transplantation.

The effects of intravenous tobramycin on renal tubular function in children with cystic fibrosis.

BACKGROUND: Tobramycin, used to treat respiratory exacerbations in cystic fibrosis (CF), is also a renal tubular toxin. Tubular dysfunction leads to increased urinary levels of the proximal tubular lysosomal enzyme, N-acetyl-beta-D-glucosaminidase (NAG) and the proximal tubular protein, retinol-binding protein (RBP). Hypermagnesuria and resulting hypomagnesaemia are indicative of more severe tubular damage, occasionally seen following repeated courses of intravenous tobramycin. Using these biochemical markers we studied the effect of a 2-week course of this agent on tubular function. METHODS: Twenty-two children (11 boys) with CF were studied. Median age = 10.9 years, range 3.1-16.4 years. All had a normal predicted glomerular filtration rate (pGFR). They received tobramycin 3 mg/kg/dose tds. Urinary NAG, RBP, creatinine and plasma magnesium and creatinine were assayed: a) immediately before commencing tobramycin, b) immediately following the course, c) 4 weeks after the end of the course. RESULTS: Mean log UrNAG and UrRBP rose significantly between time points a) and b) before falling to almost pre-treatment levels by time c). Using two way ANOVA analysis the results for UrNAG and UrRBP were both highly statistically significant (p<0.0001). Paired t-tests on the logged values revealed highly significant differences between all time points for UrNAG and in the case of UrRBP for all other than a) compared to c). In all patients plasma magnesium and pGFR remained within normal limits. CONCLUSIONS: Intravenous tobramycin produces acute tubular injury, which showed evidence of almost complete recovery after 4 weeks. The insult to the tubules was not sufficient to produce hypomagnesaemia in our study group. To assess cumulative tubular damage in more detail it would be necessary to repeat this study after further courses of tobramycin. We recommend monitoring plasma magnesium during courses of intravenous tobramycin.

From hemp seed and porcupine quill to HRCT: advances in the diagnosis and epidemiology of bronchiectasis.

Over the last decade there has been a significant improvement in our ability to recognise non-cystic fibrosis (CF) bronchiectasis in children. The precise incidence is uncertain, and it varies greatly depending on the populations studied and the methods used to make the diagnosis. It is unlikely that many of the underlying causes of non-CF bronchiectasis will be eradicated in the near future, and so it must be expected that with ever improving technology this diagnosis will be made with increasing frequency. This emphasises the need to improve our understanding of the aetiology, pathophysiology, epidemiology, and management options for children with this group of conditions.

Clinical features, aetiology and outcome of empyema in children in the north east of England.

BACKGROUND: The incidence of empyema in children in the UK is increasing. The reason for this is unclear. A prospective study was undertaken to investigate the clinical features, aetiology, and outcome of cases of empyema and parapneumonic effusion presenting to a tertiary paediatric respiratory centre between February 1997 and August 2001. METHOD: Routine bacterial culture of blood and pleural fluid was performed for 47 cases. Forty three pleural fluid specimens, culture negative for pneumococcus, were analysed for pneumococccal DNA by real time polymerase chain reaction (PCR). Penicillin susceptibility was determined for DNA positive specimens using complementary PCR assay. Capsular serotype specific antigen detection was by enzyme immunoassay (EIA) using monoclonal antibodies to serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F. Clinical data were obtained from patient notes, supplemented by a postal questionnaire. RESULTS: The median (range) age of the patients was 5.6 (0.6-16.9) years and 70% were male. The median (range) duration of illness before referral to hospital was 5 (0-25) days. Forty five (96%) had received antibiotics before referral; 32 (68%) required decortication and eight (21%) thoracocentesis. Median postoperative stay was 4 days (2-8). Thirty two (75%) pneumococcal culture negative specimens were pneumococcal DNA positive; 17 (53%) of these were serotype 1. All were penicillin sensitive. CONCLUSIONS: Pneumococcus is the major pathogen in childhood empyema and serotype 1 is the prevalent serotype. This has implications for vaccine development and immunisation strategy as the current 7-valent pneumococcal conjugate vaccine does not protect against serotype 1.

The need to redefine non-cystic fibrosis bronchiectasis in childhood.

BACKGROUND: Non-cystic fibrosis (CF) bronchiectasis has previously been reported to be rare and progressive in children living in western societies. METHOD: A clinical and radiological review was undertaken of 93 children with non-CF bronchiectasis defined by high resolution computed tomographic (HRCT) scanning presenting to a tertiary paediatric respiratory centre since 1996. RESULTS: Cases constituted 9.6% of all new referrals. Male to female ratio was 2:1. Median age at symptom onset was 1.1 years (range 0-16) and of HRCT diagnosis was 7.2 years (1.6-18.8). The most common referral diagnosis of asthma was refuted in 39 of 45 cases. Associations were previous pneumonic illness (30%), immunocompromise (21%), obliterative bronchiolitis (9%), congenital lung abnormality (5%), chronic aspiration (3%), eosinophilic oesophagitis (2%), familial syndrome (2%), primary ciliary dyskinesia (1%), and right middle lobe syndrome (1%). 8% had two associated diagnoses and 18% were idiopathic. There was agreement between the chest radiograph and HRCT scan for diagnosis and lobe affected in only five cases (5%). A repeat HRCT scan in 18 cases at a minimum interval of 18 months showed total resolution of the changes in six, improvement in one, progression in five, and was unchanged in six. CONCLUSIONS: Radiologically defined non-CF bronchiectasis in children is not uncommon. Diagnostic delay is a problem. The most common association is a previous pneumonia. Chest radiography is of little diagnostic value, but resolution is possible on HRCT scanning. Bronchiectasis is currently defined as a condition which is both permanent and progressive. This term is not necessarily appropriate for all paediatric patients for whom we suggest an alternative nomenclature.

Pulmonary malacoplakia in an immunocompetent girl: a case report.

Malacoplakia is an unusual inflammatory condition with distinctive histologic features. Involvement of the lung is quite uncommon and is rarely described in paediatrics. We report on a case of pulmonary malacoplakia in a teenage girl.

Comparison of lung deposition of colomycin using the HaloLite and the Pari LC Plus nebulisers in patients with cystic fibrosis.

AIM: To examine the effectiveness of delivery of nebulised colistin by the HaloLite nebuliser compared to the Pari LC Plus in patients with cystic fibrosis. METHODS: Randomised crossover trial of 15 patients aged >6 years. Inhalation of one mega unit of colistin in 3 ml diluent, labelled with technetium-99m DTPA, was used to assess lung deposition. The Pari was nebulised to dryness and one button press of the HaloLite was completed. Following a seven day washout period, patients inhaled colistin twice daily for seven days through the first device. Sputum specimens were analysed for colistin levels and pseudomonas load. This procedure was repeated with the alternative device. RESULTS: Lung uptake of radiolabelled colistin was significantly higher with the Pari. However, lung uptake calculated as a percentage of the amount of drug used was significantly higher for the HaloLite. Time to nebulise was significantly shorter with the HaloLite. Sputum levels of colistin were higher following use of the Pari; this was close to significance. CONCLUSION: The manufacturer's recommended dosages for nebulising antibiotics with a HaloLite result in a lower delivery than patients receive when using a Pari nebuliser. The concept of adaptive aerosol delivery has several theoretical advantages but the recommended doses for the HaloLite need to be modified in order to improve effectiveness.

Aminoglycoside-associated hypomagnesaemia in children with cystic fibrosis.

Hypomagnesaemia in children with cystic fibrosis (CF) is under-recognized. We report a child with CF who developed significant hypomagnesaemia following intravenous (i.v.) treatment with aminoglycosides for exacerbations of Pseudomonas aeruginosa infection. Three additional cases have also been observed. Investigations in two patients have revealed excessive renal loss of magnesium. It is postulated that renal tubular damage secondary to the cumulative effects of repeated courses of aminoglycosides resulted in hypomagnesaemia, and we suggest screening for this problem by monitoring serum magnesium regularly in all patients with CF receiving multiple courses of aminoglycosides.

Empyema thoracis: a role for open thoracotomy and decortication.

BACKGROUND: Thoracentesis and antibiotics remain the cornerstones of treatment in stage I empyema. The management of disease progression or late presentation is controversial. Open thoracotomy and decortication is perceived to be synonymous with protracted recovery and prolonged hospitalisation. Advocates of thoracoscopic adhesiolysis cite earlier chest drain removal and hospital discharge. This paper challenges traditional prejudice towards open surgery. METHODS: A five year audit of empyema cases referred to a regional cardiothoracic surgical unit analysing previous clinical course, surgical management, and outcome. RESULTS: Between February 1992 and February 1997, the number of referrals to this centre increased dramatically. Twenty-two children were referred for surgery (15 boys, seven girls; age range, 0.5-16 years). Before referral, patients had been unwell for 6-50 days (median, 15), had been treated with several antibiotics, and had undergone chest ultrasound (15 patients), computed tomography (five patients), pleural aspiration attempts (13 patients), and intercostal drainage (seven patients). The organism responsible was identified in only two cases (Streptococcus pneumoniae). Three patients had intraparenchymal abscess formation. Eighteen patients underwent open thoracotomy and decortication. Drain removal was performed on the first or second day. Fever resolved within 48 hours. Median hospital stay was four days. All patients had complete clinical and radiological resolution. CONCLUSIONS: Treatment must be tailored to the disease stage. In stage II and III diseases, open decortication followed by early drain removal results in rapid symptomatic recovery, early hospital discharge, and complete resolution. In the early fibrinopurulent phase, alternative strategies should be considered. However, even in ideal cases, neither fibrinolysis nor thoracoscopic adhesiolysis can achieve more rapid resolution at lower risk.