Anne Thomson

Association of respiratory syncytial virus bronchiolitis with the interleukin 8 gene region in UK families

BACKGROUND Respiratory syncytial virus (RSV) infects nearly all children by the end of their second winter. Why some develop bronchiolitis is poorly understood; it is not known whether there is a genetic component. The pathological features include neutrophil infiltration and high levels of interleukin 8 (IL-8), a potent neutrophil chemoattractant. METHODS Common genetic variants of the promoter region of the IL-8gene were identified by sequencing DNA from 36 healthy individuals. Genetic correlates of IL-8 production were assessed using whole blood from 50 healthy subjects. To investigate genetic correlates of disease severity 117 nuclear families were recruited in which a child had required hospital admission for RSV bronchiolitis. RESULTS A common single nucleotide polymorphism (allele frequency 0.44) was identified 251u2009bp upstream of the IL-8 transcription start site. The IL8–251A allele tended to be associated with increased IL-8 production by lipopolysaccharide stimulated whole blood (p=0.07). Using the transmission disequilibrium test, the frequency of this allele was significantly increased in infants with bronchiolitis (transmission = 62% (95% confidence interval (CI) 53 to 71), p=0.014) and particularly in those without known risk factors (transmission = 78% (95% CI 62 to 93), p=0.004). CONCLUSION Disease severity following RSV infection appears to be determined by a genetic factor close to the IL-8 gene. Further analysis of this effect may elucidate causal processes in the pathogenesis of RSV bronchiolitis.

British Thoracic Society guidelines for the management of community acquired pneumonia in children: update 2011

The British Thoracic Society first published management guidelines for community acquired pneumonia in children in 2002 and covered available evidence to early 2000. These updated guidelines represent a review of new evidence since then and consensus clinical opinion where evidence was not found. This document incorporates material from the 2002 guidelines and supersedes the previous guideline document.

BTS guidelines for the management of pleural infection in children

“It seems probable that this study covers the period of practical extinction of empyema as an important disease.” Lionakis B et al , J Pediatr 1958. nn### 1.1 Structure of the guidelinennThe format follows that used for the BTS guidelines on the management of pleural disease in adults.1 At the start there is a summary table of the abstracted bullet points from each section. Following that is an algorithm summarising the management of pleural infection in children (fig 1). Each section starts with bulleted points of key recommendations using the revised SIGN grading system (table 1) available on http://www.sign.ac.uk/guidelines/fulltext/50/section6.html. Beneath each set of bullet points is a short paragraph detailing the referenced literature and the rationale behind the recommendations. The primary source literature has been individually graded for its methodology and the grading is given alongside each reference using the revised SIGN levels of evidence (table 2).nnView this table:nn Table 1 nu2003Revised SIGN grading system: grades of recommendationnnnnView this table:nn Table 2 nu2003Revised SIGN grading system: levels of evidencennnnnn Figure 1 nu2003Algorithm for the management of pleural infection in children.nnnn### 1.2 Methodology for generation of the guidelinesnnThe initial literature search was carried out by the Library of the National Heart Lung Institute, Imperial College London. Further searches were then carried out by members of the working group who concentrated on their own topics. Details of the search strategy are given in Appendix 1.nnEach section of the guideline was researched and drafted by a subgroup of the Paediatric Pleural Diseases Subcommittee (itself a subcommittee of the BTS Standards of Care Committee). Publications were rated according to the SIGN criteria for the calibre of the methodology of the research to give levels of evidence (table 2). Tables of evidence were then produced before writing the guideline sections using the SIGN grades of recommendations (table 1). Once all parts were merged into one document, the whole group then met to discuss …

Increase in emergency admissions to hospital for children aged under 15 in England, 1999–2010: national database analysis

Objective To investigate a reported rise in the emergency hospital admission of children in England for conditions usually managed in the community. Setting and design Population-based study of hospital admission rates for children aged under 15, based on analysis of Hospital Episode Statistics and population estimates for England, 1999–2010. Main outcome Trends in rates of emergency admission to hospital. Results The emergency admission rate for children aged under 15 in England has increased by 28% in the past decade, from 63 per 1000 population in 1999 to 81 per 1000 in 2010. A persistent year-on-year increase is apparent from 2003 onwards. A small decline in the rates of admissions lasting 1u2005day or more has been offset by a twofold increase in short-term admissions of <1u2005day. Considering the specific conditions where high emergency admission rates are thought to be inversely related to primary care quality, admission rates for upper respiratory tract infections rose by 22%, lower respiratory tract infections by 40%, urinary tract infections by 43% and gastroenteritis by 31%, while admission rates for chronic conditions fell by 5.6%. Conclusions The continuing increase in very-short-term admission of children with common infections suggests a systematic failure, both in primary care (by general practice, out-of-hours care and National Health Service Direct) and in hospital (by emergency departments and paediatricians), in the assessment of children with acute illness that could be managed in the community. Solving the problem is likely to require restructuring of the way acute paediatric care is delivered.

Respiratory infections for which general practitioners consider prescribing an antibiotic: a prospective study

Objective: To determine the viral aetiology of respiratory infections in children presenting to primary care with “more than a simple cold”. Design: Observational study in 18 Oxfordshire general practices over four winters (2000–01 to 2003–04). Patients: 425 children aged 6 months to 12 years with cough and fever for whom general practitioners considered prescribing an antibiotic. Methods: Nasopharyngeal aspirate obtained from 408 (96%) children was subjected to PCR for respiratory viruses. Parents completed an illness diary for the duration of illness. Results: A viral cause of infection was detected in most (77%) children. Clinical symptoms correctly identified the infecting virus in 45% of cases. The duration of illness was short and the time course was very similar for all infecting viruses. One third of children were prescribed an antibiotic (34%), but this made no difference to the rate of parent-assessed recovery (Kruskal-Wallis, pu200a=u200a0.67). About one in five children with influenza who did not receive an antibiotic had persistent fever on day 7 compared to no children receiving antibiotics (pu200a=u200a0.02); this difference remained after adjustment for severity and other factors and was not seen with other viruses. Conclusions: Most children receiving antibiotics for respiratory symptoms in general practice have an identifiable viral illness. In routine clinical practice, neither the specific infecting virus nor the use of antibiotics has a significant effect on the time course of illness. Antibiotics may reduce the duration of fever in children with influenza which could reflect an increased risk of secondary bacterial infection for such children.

Gastro-oesophageal reflux and childhood asthma: the acid test.

The presence of gastro-oesophageal reflux was investigated in 18 children with moderate to severe asthma by overnight oesophageal pH monitoring. Appreciable reflux was found during sleep in eight; its relevance to nocturnal asthma was not clear. On another occasion the same children were challenged in a double blind fashion with a drink of dilute hydrochloric acid (0.001 N) and the response of the airways was monitored by peak flow measurements and by histamine challenge tests. There was a significant increase in mean histamine sensitivity (p = 0.001) 90 minutes after the acid drink without any associated change in baseline peak flow rate. Eight children had a significant response to the acid drink, and a further three reacted to a more concentrated solution (0.01 N). In those asthmatic children in whom reflux is associated with a positive response to an acid drink (five out of 18 in the present study) it seems likely that reflux exacerbates nocturnal symptoms.

Genetic predisposition to wheeze following respiratory syncytial virus bronchiolitis.

Background The nature of the association between severe respiratory syncytial virus (RSV) bronchiolitis and subsequent wheezing remains unknown. In a previous study, we showed that genetic variation in the IL‐8‐promoter region is associated with susceptibility to severe bronchiolitis.

Clinical symptoms and signs for the diagnosis of Mycoplasma pneumoniae in children and adolescents with community‐acquired pneumonia

BACKGROUNDnMycoplasma pneumoniae (M. pneumoniae) is a significant cause of community-acquired pneumonia in children and adolescents.xa0Treatment with macrolide antibiotics is recommended.xa0However, M. pneumoniae is difficult to diagnose based on clinical symptoms and signs.xa0Diagnostic uncertainty can lead to inappropriate antibiotic prescribing, which may worsen clinical prognosis and increase antibiotic resistance.nnnOBJECTIVESnThe objectives of this review are (i) to assess the diagnostic accuracy of symptoms and signs in the clinical recognition of M. pneumoniae in children and adolescents with community-acquired pneumonia; and (ii) to assess the influence of potential sources of heterogeneity on the diagnostic accuracy of symptoms and signs in the clinical recognition of M. pneumoniae.nnnSEARCH METHODSnWe searched MEDLINE (January 1950 to 26 June 2012) and EMBASE (January 1980 to 26 June 2012).xa0We identified additional references by handsearching the reference lists of included articles and snowballing.xa0We searched the reference lists of relevant systematic reviews identified by searching the Medion database, Database of Reviews of Effects 2012, Issue 6 (25 June 2012) and the Cochrane Register of Diagnostic Test Accuracy studies (2 July 2012). Experts in the field reviewed our list of included studies for any obvious omissions.nnnSELECTION CRITERIAnWe included peer-reviewed published studies which prospectively and consecutively recruited children with community-acquired pneumonia from any healthcare setting, confirmed the presence of M. pneumoniae using serology with or without other laboratory methods and reported data on clinical symptoms and signs in sufficient detail to construct 2 x 2 tables.nnnDATA COLLECTION AND ANALYSISnOne review author scanned titles to exclude obviously irrelevant articles. Two review authors independently scanned the remaining titles and abstracts, reviewed full-text versions of potentially relevant articles, assessed the quality of included articles and extracted data on study characteristics and the following clinical features: cough, wheeze, coryza, crepitations, fever, rhonchi, shortness of breath, chest pain, diarrhea, myalgia and headache.We calculated study-specific values for sensitivity, specificity and positive and negative likelihood ratios with 95% confidence intervals (CIs). We estimated the post-test probability of M. pneumoniae based on the absence or presence of symptoms and signs.We calculated pooled sensitivities, specificities, positive and negative likelihood ratios with 95% CIs for symptoms and signs where data were reported by at least four included studies by fitting a bivariate normal model for the logit transforms of sensitivity and specificity. We explored potential sources of heterogeneity by fitting bivariate models with covariates using multi-level mixed-effects logistic regression. We performed sensitivity analyses excluding data from studies for which we were concerned about the representativeness of the study population and/or the acceptability of the reference standard.nnnMAIN RESULTSnOur search identified 8299 articles (excluding duplicates).xa0We examined the titles and abstracts of 1125 articles and the full-text versions of 97 articles.xa0We included seven studies in our review, which reported data from 1491 children;xa0all were conducted in hospital settings.xa0Overall, study quality was moderate.xa0In two studies the presence of chest pain more than doubled the probability of M. pneumoniae. Wheeze was 12% more likely to be absent in children with M. pneumoniae (pooled positive likelihood ratio (LR+) 0.76, 95% CI 0.60 to 0.97; pooled negative likelihood ratio (LR-) 1.12, 95% CI 1.02 to 1.23).xa0Our sensitivity analysis showed that the presence of crepitations was associated with M. pneumoniae, but this finding was of borderline statistical significance (pooled LR+ 1.10, 95% CI 0.99 to 1.23; pooled LR- 0.66, 95% CI 0.46 to 0.96).nnnAUTHORS CONCLUSIONSnM. pneumoniae cannot be reliably diagnosed in children and adolescents with community-acquired pneumonia based on clinical symptoms and signs. Although the absence of wheeze is a statistically significant diagnostic indicator, it does not have sufficient diagnostic value to guide empirical macrolide treatment. Data from two studies suggest that the presence of chest pain more than doubles the probability of M. pneumoniae. However, further research is needed to substantiate this finding. More high quality large-scale studies in primary care settings are needed to help develop prediction rules based on epidemiological data as well as clinical and baseline patient characteristics.

Management of community-acquired pneumonia in children.

Community-acquired pneumonia (CAP) is a significant cause of childhood morbidity and mortality worldwide. Viral etiology is most common in young children and decreases with age. Streptococcus pneumoniae is the single most common bacterial cause across all age groups. Atypical organisms present similarly across all age groups and may be more common than previously recognized.A bacterial pneumonia should be considered in children presenting with fever >38.5°C, tachypnea, and chest recession. Oxygen therapy is life saving and should be given when oxygen saturation is <92%. For non-severe pneumonia, oral amoxicillin is the antibacterial of choice with low failure rates reported. Severely ill children are traditionally treated with parenteral antibacterials. Penicillin non-susceptible S. pneumoniae prevalence rates are increasing and have been linked to community antibacterial prescribing. Most pneumococci remain sensitive to high-dose penicillin-based antibacterials but macrolide resistance is also a problem in some communities. However, primary combination treatment with macrolides is indicated in areas where there is a high prevalence of atypical organisms. The most common complications in CAP are parapneumonic effusions and empyema. The use of ultrasonography combined with intercostal drainage augmented with the use of fibrinolytic therapy has significantly reduced the morbidity associated with these complications. There is increasing evidence that a preventative strategy with the 7-valent pneumococcal conjugate vaccine (PCV-7) results in a significant fall in CAP in early childhood.

The role of negative pressure ventilation

In the 3rd century bc Erasistratus of Chios recognised that breathing depended on muscular action. By 1555 Vesalius had described assisted positive pressure ventilation and in 1667 Hooke used a pair of bellows to keep a dog alive in his demonstration to the Royal Society. By the mid-1800s it was recognised that air would be drawn into the lungs through the mouth and nose if a subatmospheric pressure could be developed around the thorax and abdomen, and the first body enclosing negative pressure ventilators developed. These experimental devices were gradually refined and the first negative pressure ventilator to be of clinical value was described by Drinker in 1928.1 This tank ventilator or ‘iron lung’ in its many modifications was widely used in the polio epidemics from 1930 to 1960 and saved many lives.nnThe iron lung has many disadvantages. It is bulky, cumbersome, and limits access to the patients. Simpler non-tank negative pressure ventilators were developed in the 1950s and 1960s, with cuirasses, negative pressure jackets, or wraps, all of which fitted over the trunk and abdomen.2 In all of these designs inspiration was controlled, but expiration relied on passive recoil of the lung and so this was a rather inefficient form of ventilation. By the 1950s the greater efficiency of positive pressure ventilation delivered through a tracheostomy or endotracheal tube had been demonstrated and negative pressure ventilation fell out of favour, with its use largely restricted to chronic ventilatory support in neuromuscular disorders. Over the past 10 years, however, the development of newer forms of negative pressure ventilators which overcome in large measure the drawbacks of their predecessors has seen a resurgence of interest in this mode of ventilation for children.nnThe principle of negative pressure ventilation is that inspiration is initiated by an intermittent negative pressure …