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Rosalind L Smyth

Publications and source records attributed to Rosalind L Smyth.

At least 19 recordsLinked to original sources
PubMed2007

Chemokine responses are increased in HIV-infected Malawian children with invasive pneumococcal disease.

BACKGROUND: Chemokines play an important role in the recruitment and regulation of leukocyte traffic during bacterial infection. The aims of this study were to investigate the chemokine response to invasive pneumococcal disease (IPD) and to examine the influence of HIV infection on the chemokine response, pneumococcal bacterial loads, and outcome. METHODS: We prospectively studied 95 children with IPD, and blood and cerebrospinal fluid (CSF) samples were taken at admission for the determination of chemokines, interferon-gamma (IFNgamma), and pneumococcal bacterial loads. RESULTS: Plasma CXCL8 and CCL2, CSF CXCL8 and CCL4, and IFNgamma were significantly higher in HIV-infected children than in HIV-uninfected children. Blood and CSF pneumococcal bacterial loads correlated with plasma and CSF chemokines, respectively, and were higher in HIV-infected children compared with HIV-uninfected children. Among HIV-infected children, plasma concentrations of CXCL8 and CCL2 were significantly higher in nonsurvivors than in survivors, but CCL5 was significantly lower. HIV-infected and HIV-uninfected children with IPD had higher concentrations of chemokines (except CCL5) than acutely ill HIV-infected and HIV-uninfected children with no detectable bacterial infection. Male gender and low plasma CCL2 concentrations were shown to be independently associated with survival. CONCLUSIONS: Chemokines, in particular CCL2, are associated with survival in IPD and correlate with pneumococcal bacterial loads, disease presentation, and outcome.

Adolescent↗
PubMed2006

Bronchiolitis.

Bronchiolitis is a distressing, potentially life-threatening respiratory condition that affects young babies. Around 2-3% of all infants younger than 1 year are admitted to hospital with bronchiolitis, usually during the seasonal epidemic. The majority of these infants are infected with respiratory syncytial virus and all have an intense inflammatory response in their airways. Although most infants recover, they have an increased risk of recurrent wheezing. Although bronchiolitis is common, little is known about what causes infants to be susceptible. Diagnostic interventions have little effect on clinical outcome, and apart from supportive measures, there is no specific treatment. Bronchiolitis therefore presents an intriguing clinical conundrum and a major challenge to researchers. High quality clinical studies are needed to clarify assessment of disease severity and criteria for hospital admission, particularly the use of pulse oximetry and chest radiography. Careful mapping of the inflammatory pathways in the pathogenesis of bronchiolitis should lead to development of new therapies to alleviate symptoms.

Antibodies, Monoclonal↗
PubMed2006

In a systematic review, infrared ear thermometry for fever diagnosis in children finds poor sensitivity.

BACKGROUND AND OBJECTIVES: To investigate sensitivity and specificity of infrared ear thermometry compared to rectal thermometry to detect fever in children. METHODS: Systematic review of studies comparing rectal and infrared ear temperatures in children. RESULTS: Sensitivity and specificity estimates were highly heterogeneous, and displayed an inverse relationship suggestive of a threshold effect, due in part to the different offsets used to obtain adjusted tympanic temperatures depending on the ear thermometer mode. To account for this threshold effect, results from each study were summarized as a diagnostic odds ratio (DOR). These varied extensively across studies, suggesting that heterogeneity between study estimates is not fully explained by the threshold effect. Pooled estimates of sensitivity and specificity from random effects models were 63.7% (95% CI 55.6%, 71.8%) and 95.2% (95% CI 93.5%, 96.9%), respectively. CONCLUSION: Pooled estimates of measures of diagnostic accuracy from these studies suggest that infrared ear thermometry would fail to diagnose fever in three or four out of every 10 febrile children (with fever defined by a rectal temperature of 38 degrees C or above). These findings support our previous concerns about the use of infrared ear thermometers in situations where a failure to detect fever has serious implications.

Adolescent↗
PubMed2006

Oral protein energy supplements for children with cystic fibrosis: CALICO multicentre randomised controlled trial.

OBJECTIVE: To determine whether oral protein energy supplements, used long term in children with cystic fibrosis who are moderately malnourished, improve nutritional and other outcomes. DESIGN: Multicentre randomised controlled trial. SETTING: Seven specialist paediatric cystic fibrosis centres and their associated shared care clinics and seven smaller paediatric cystic fibrosis clinics. PARTICIPANTS: 102 children with cystic fibrosis, aged between 2 and 15 years, who were moderately malnourished. INTERVENTIONS: Oral protein energy supplements in addition to usual dietary advice compared with dietary advice alone, for 12 months. MAIN OUTCOME MEASURE: Change in body mass index centile over one year. RESULTS: Use of supplements was not associated with a change in body mass index centile (mean difference 2.99 centile points, 95% confidence interval -2.70 to 8.68) or other nutritional and spirometric outcomes in this group of children. CONCLUSIONS: Long term use of oral protein energy supplements did not result in an improvement in nutritional status or other clinical outcomes in children with cystic fibrosis who were moderately malnourished. Oral protein energy supplements should not be regarded as an essential part of the management of this group of children. TRIAL REGISTRATION: ISRCTN: 95744468.

Administration, Oral↗
PubMed2005

Controlled clinical trials in cystic fibrosis--are we doing better?

We have previously reported the time trends, design and interventions in randomised controlled trials (RCTs) in cystic fibrosis (CF) from 1961 through 1997 [Cheng K, Smyth RL, Motley J, O'Hea U, Ashby D, Randomised controlled trials in cystic fibrosis (1966-1997) categorized by time, design, and intervention. Pediatr Pulmonol 2000, 29:1-7.]. We maintain an ongoing register of all RCTs and controlled clinical trials (CCTs) in CF and have noted that in the five years since 1997 there has been a 48% increase in published trials. We aimed to assess whether this increase has been associated with an improvement in design quality. All RCTs and CCTs from 1961-2002 were assessed. Two epochs were then compared, 1961-1997 and 1998-2002. For each trial we recorded the design, participant numbers and the intervention studied. 261 trials in 1998-2002 were compared with 544 trials in 1961-1997. Comparing the two epochs a similar proportion of trials were parallel, double-blind and placebo controlled; also the median number of participants was similar. In the later epoch 25% of trials were multicentre, compared with 11% previously. Whilst this recent increase in clinical trials in CF is welcome, this has not been associated with improvements in quality. The trend for an increasing proportion of trials to be multicentre is encouraging. There are however, still deficiencies in the design of clinical trials in CF.

Cystic Fibrosis↗
PubMed2005

High prevalence but low impact of data extraction and reporting errors were found in Cochrane systematic reviews.

BACKGROUND AND OBJECTIVE: Extracting data from primary articles is an essential component in conducting systematic reviews. Incorrect data extraction can lead to false conclusions. The objective of this study was to retrospectively repeat the data extraction in all systematic reviews conducted by the Cochrane Cystic Fibrosis and Genetic Disorders Group. STUDY DESIGN AND SETTING: For each review, data extraction was conducted, by an experienced statistician, for the same publications used by the reviewers. Results were compared with those obtained by the reviewers. RESULTS: Errors were found in 20 of 34 reviews, including incorrect calculations made when converting data in primary articles into data required for the review (2 reviews) and misinterpretation of data that were reported in the primary article (7 reviews). All data-handling errors led to changes in the summary results, but none of these affected the review conclusions. CONCLUSIONS: Important errors were identified in a high proportion of reviews. A variety of problems relating to the reporting of results within a review were identified, but these did not lead to substantial changes in any conclusion.

Cystic Fibrosis↗
PubMed2005

Production of chemokines in the lungs of infants with severe respiratory syncytial virus bronchiolitis.

BACKGROUND: Respiratory syncytial virus (RSV) bronchiolitis in infants is characterized by a massive neutrophilic infiltrate into the airways. Chemokines direct migration of leukocytes and contribute to the pathogenesis of RSV disease. However, little is known about pulmonary chemokine responses to RSV in humans. Our aim was to characterize the production of chemokines in the lungs of infants with RSV bronchiolitis and how this production changes over time. METHODS: Chemokine mRNA and the concentration of chemokines were measured in nonbronchoscopic bronchoalveolar lavage (BAL) samples from infants with RSV bronchiolitis and from control infants. In infants with RSV bronchiolitis, changes in the concentrations of chemokines during the 7 days after intubation and between the days of intubation and extubation were examined. RESULTS: The production of chemokines within the lower respiratory tract was shown in all patients with RSV bronchiolitis. CXC chemokines (particularly CXCL10/interferon-inducible protein 10 and CXCL8/interleukin-8) were found to be the most abundant, but CC chemokines (CCL2/monocyte chemotactic protein 1 and CCL3/macrophage inflammatory protein-1 alpha) were also present. Concentrations of some of these chemokines remained elevated over the course of the illness, whereas others decreased steadily. No differences in the concentrations were found between the days of intubation and extubation. CONCLUSIONS: CXC chemokines predominate within the RSV-infected lung. Much of this response comes from inflammatory cells within the lower respiratory tract. Chemokine response patterns vary over time, possibly indicating different cellular sources for individual chemokines in the RSV-infected lung.

Bronchiolitis↗
PubMed2005

Interleukin-9 as a possible therapeutic target in both asthma and chronic obstructive airways disease.

Asthma and chronic obstructive pulmonary disease (COPD) are important causes of morbidity and mortality worldwide. Both asthma and COPD are characterized by airflow limitation but distinct differences occur in the pulmonary inflammatory responses in the two conditions. Treatment options for asthma and COPD are limited (especially so for COPD), and both are in need of novel therapeutic interventions. Interleukin-9 (IL-9) is a potential target for such a therapy. This Th2-type cytokine, is secreted by a number of different cell types, and has multiple effects on a wide range of cells within the lung. In this review we will summarize current knowledge about the immunobiology of IL-9 and discuss the role played by IL-9 in inflammation in both asthma and COPD, and its potential as a therapeutic target.

Animals↗
PubMed2004

Dual infection of infants by human metapneumovirus and human respiratory syncytial virus is strongly associated with severe bronchiolitis.

The association between severe bronchiolitis and dual infection by human metapneumovirus (hMPV) and human respiratory syncytial virus (hRSV) was investigated in <2-year-old infants with bronchiolitis who were admitted to the hospital during the 2001-2002 winter season. hMPV in nasopharyngeal aspirate and/or cells and fluid collected by nonbronchoscopic bronchoalveolar lavage was detected by reverse transcriptase-polymerase chain reaction (RT-PCR). hRSV was detected in nasopharyngeal aspirate and/or cells and fluid collected by nonbronchoscopic bronchoalveolar lavage by enzyme immunoassay, tissue culture, and RT-PCR. Dual infection with hMPV and hRSV confers a 10-fold increase in relative risk (RR) of admission to a pediatric intensive-care unit for mechanical ventilation (RR, 10.99 [95% confidence interval, 5.0-24.12]; P<.001, by Fisher exact test). Dual infection by hMPV and hRSV is associated with severe bronchiolitis.

Bronchiolitis, Viral↗
PubMed2004

Interleukin 9 production in the lungs of infants with severe respiratory syncytial virus bronchiolitis.

BACKGROUND: Respiratory syncytial virus (RSV) bronchiolitis is the most prevalent acute wheezing disorder in infants and is associated with recurrent wheeze and asthma in childhood. Interleukin 9, a type 2 cytokine has been proposed as a key cytokine in susceptibility to asthma. We aimed to investigate whether interleukin 9 was produced in the lungs of infants with severe RSV disease and if found, from which cells it originated. METHODS: We did 150 non-bronchoscopic bronchoalveolar lavages during the course of ventilation in 24 term infants and 21 preterm infants ventilated for RSV bronchiolitis. We also did 10 bronchoalveolar lavages on the day of intubation in 10 control infants ventilated for non-respiratory causes. We measured pulmonary interleukin 9 mRNA and protein in samples from all groups. We used immunostaining to identify the cells that produce interleukin 9. FINDINGS: Interleukin 9 mRNA expression, which persisted over the course of ventilation, was noted in all infants with bronchiolitis. Three of the control group also showed interleukin 9 mRNA expression. Median interleukin 9 protein concentration on day 1 (1.9 microg/L [range 0.1-36.2]) was significantly greater in term infants with bronchiolitis than either preterm infants (0.4 microg/L [0.1-2.9]; p<0.05) or the control group (0.7 microg/L [0.4-2.5]; p<0.05). There was a trend for interleukin 9 protein concentrations in term, but not preterm infants to decrease over time. Immunostained cell smears showed that most interleukin 9 expression in bronchoalveolar lavage was by neutrophils. INTERPRETATION: In term infants with RSV bronchiolitis, we noted large amounts of interleukin 9 mRNA and interleukin 9 protein. Neutrophils seem to be the main source of this type 2 cytokine. Interleukin 9 production by neutrophils may contribute to the pathogenesis of RSV disease. These findings may be relevant to other disease processes in the lung where neutrophils are the predominant inflammatory cell type.

Acute Disease↗
PubMed2003

Update on Cochrane data on paediatric respiratory diseases.

INTRODUCTION: Systematic reviews seek to describe and summarise the best evidence for a given intervention by pooling data from relevant quality clinical trials. The Cochrane Collaboration has fostered the development and dissemination of systematic reviews throughout the world. We have identified and summarised The Cochrane systematic reviews of relevance to the paediatric pulmonologist. METHODS: We performed an expert search of the Cochrane Database of Systematic Reviews using a combination of medical subject headings and free text terms relating to paediatric respiratory disease. RESULTS: The search identified 120 systematic reviews with interventions specific to children with some relevance to pulmonary disease, and 327 reviews with interventions relating to pulmonary disease in adults and children. After pragmatic exclusions, 81 reviews were sorted by disease and 59 of these are discussed in detail. CONCLUSIONS: There are now many systematic reviews that make a positive contribution to paediatric pulmonology. The majority of reviews (69%) found evidence that either confirmed or refuted an accepted practice. The remaining reviews concluded that the evidence for an accepted practice is poor and sometimes wholly absent. Clinicians must be aware that lack of evidence of effect is not the same as evidence of lack of effect. Caution must be exercised before applying the conclusions of systematic reviews based upon adult data to childhood disease.

Adolescent↗
PubMed2003

Oral protein-energy supplements for children with chronic disease: systematic review.

Growth failure and poor nutritional status are features of children with chronic disease. Oral protein-energy supplements are one of a number of interventions provided with the aim of improving nutritional status in these children. The present paper describes a Cochrane systematic review assessing the efficacy of these products in children with chronic disease. The objective was to examine the evidence that in children with chronic disease oral protein-energy supplements alter nutrient intake, nutritional indices, survival and quality of life. All randomised controlled trials of the use of oral protein-energy supplements in children with chronic disease were identified through searching electronic databases and hand searching the abstract books of nutrition conferences. Studies identified were independently assessed for eligibility and methodological quality, and data on outcomes of interest were combined in a meta-analysis where possible. Two trials were eligible for inclusion in the review, both of which were undertaken with children with cystic fibrosis. No statistical differences could be found between treatment and control groups when data from both studies were combined. Oral protein-energy supplements are widely used to improve the nutritional status of children with chronic disease. No conclusions can be drawn on the efficacy of these products based on the limited data available. Further randomised controlled trials are required to investigate the use of these products in children with chronic disease. Until further data are available, these products should be used with caution.

Adolescent↗