Sharon Christie

Respiratory viral infection in exacerbations of COPD

Summary Background Patients with COPD have frequent exacerbations. The role of respiratory viral infection is just emerging. We wished to determine prospectively the incidence of viral infection in exacerbated and stable COPD patients as well as smokers who do not have airways obstruction. Methods Stable and exacerbated COPD patients were recruited along with a group of patients who had smoked but who did not have any airways obstruction. Spirometry was performed and sputum specimens were tested for a range of 12 different respiratory viruses using PCR. Results One hundred and thirty-six patients with exacerbations of COPD, 68 stable COPD patients and 16 non-obstructed smokers were recruited. A respiratory virus was detected in 37% of exacerbations, 12% of stable COPD patients and 12% of non-obstructed smokers, p <0.0005. Rhinovirus was most frequently detected. The symptom of fever was associated with virus detection, p <0.05. Infection with more than one virus was only found in the exacerbated COPD patients. Conclusion Respiratory viral infection is associated with exacerbations of COPD. Rhinovirus was the most common infecting agent identified and in two cases human metapneumovirus was also detected. Dual infections were only seen amongst those patients admitted to hospital with acute exacerbations of COPD. Viruses were more commonly detected in those with more severe airways disease.

Children with stable asthma have reduced airway matrix metalloproteinase-9 and matrix metalloproteinase-9/tissue inhibitor of metalloproteinase-1 ratio.

Background Childhood asthma is characterized by inflammation of the airways. Structural changes of the airway wall may also be seen in some children early in the course of the disease. Matrix metalloproteinases (MMPs) are key mediators in the metabolism of the extracellular matrix (ECM).

High levels of Epstein–Barr virus in COPD

Latent viral infection has been implicated in the pathophysiology of chronic obstructive pulmonary disease (COPD). Epstein–Barr virus (EBV) is known to be important in pulmonary fibrosis. The current authors hypothesised that EBV is associated with the pathogenesis of COPD. Sputum samples were collected from patients both during exacerbations of COPD and when stable. A control group of smokers who did not have airways obstruction also had their sputum examined. The presence of EBV DNA was established and quantified using a real-time nucleic acid amplification assay. A total of 136 patients with COPD were recruited during an acute exacerbation and a total of 68 when stable. EBV was detected in 65 (48%) exacerbation cases and 31 (46%) stable patients. In the comparison group of 16 nonobstructed smokers, EBV was demonstrated in only one (6%) case. Risk of COPD in patients with EBV and who are smokers confers an odds ratio of 12.6. Epstein–Barr virus DNA is more frequently identified in the respiratory tract of chronic obstructive pulmonary disease patients in comparison with unaffected smokers. It is present both during exacerbation and when stable, suggesting that infection is persistent. Smokers who do not develop chronic obstructive pulmonary disease rarely have Epstein–Barr virus in their sputum. This finding may be of importance in the pathogenesis of chronic obstructive pulmonary disease.

Human Parechovirus Infection in Neonatal Intensive Care

Background: Approximately 5–6% of all infective episodes in neonatal intensive care unit (NICU) are of viral origin. Previous studies suggest that human parechovirus (HPeV) infection presents most commonly in term infants, as a sepsis-like syndrome in which meningoencephalitis is prominent. Our aim was to study the infection rate and associated features of HPeV. Methods: Blood samples were taken from NICU babies older than 48 hours, who were being investigated for late onset sepsis. Clinical and laboratory data were collected at the time of the suspected sepsis episode. Samples were tested using universal primers and probe directed at the 5′-untranslated region of the HPeV genome by reverse transcriptase polymerase chain reaction (RT-PCR). Results were confirmed by electrophoresis and DNA sequencing. Results: HPeV was detected in 11 of 84 samples (13%). These infants had a mean [interquartile range (IQR)] gestational age of 28.9 (26.9–30.6) weeks and mean birth weight of 1.26 (SD = 0.72) kg. The median day of presentation was 16 (IQR: 11–27). These characteristics were similar to the infants without positive viral detection. Six infants presented with respiratory signs. One infant presented with signs of meningitis. Six of the 11 episodes of HPeV infection occurred during the winter months (December to February). No HPeV positive infants had abnormal findings on their 28-day cranial ultrasound examination. Conclusions: We found an HPeV infection rate of 13% in infants being tested for late onset sepsis. HPeV should be considered as a possible cause of sepsis-like symptoms in preterm infants.

Performance of a Novel Molecular Method in the Diagnosis of Late-Onset Sepsis in Very Low Birth Weight Infants

Objective To compare the use of a generic molecular assay to ‘standard’ investigations used to assist the diagnosis of late onset bacterial sepsis in very low birth weight infants (VLBW, <1500g). Methods VLBW infants, greater than 48 hours of age, who were clinically suspected to have sepsis were investigated using standard tests (full blood count, C-reactive protein (at presentation) and blood culture), in addition, blood was taken for a universal molecular assay (16S rRNA reverse transcriptase PCR) for comparison. Clinical data were recorded during the suspected infection episode. A validated sepsis score (NEO-KISS) was used to retrospectively determine the presence of sepsis (independent of blood culture). The performance of each of the tests were compared by sensitivity, specificity, positive/negative likihood ratios (+/-LR) and postive/negative predictive values (PPV/NPV). Results Sixty-five babies with suspected clinical sepsis were prospectively included. The performance indicators are presented with 95% confidence limits. For the detection of bacteria, blood culture had sensitivity of 0.57 (0.34–0.78), specificity of 0.45 (0.30–0.61); +LR of 1.05 (0.66–1.66) and—LR of 0.94 (0.52–1.7); PPV of 33.3 (18.56–50.97) and NPV of 68.97 (49.17–87.72). Serum CRP had sensitivity of 0.92 (0.64–1) and specificity of 0.36 (0.17–0.59); +LR of 1.45 (1–2.1) and-LR of 0.21 (0.03–1.5); PPV of 44.46 (26.6–66.6) and NPV of 88.9 (51.8–99.7). The universal molecular assay had sensitivity of 0.76 (0.53–0.92), specificity of 0.95 (0.85–0.99); +LR of 16.8 (4.2–66.3) and-LR of 0.25 (0.1–0.5); PPV of 88.9 (65.3–98.6) and NPV of 89.4 (76.9–96.5). Conclusions In VLBW infants this universal molecular assay performed better in the diagnosis of late onset sepsis (LOS) than blood culture and CRP. Further development is required to explore and improve the performance of the assay in real-time diagnosis.

An interesting case of ptosis in an infant

A 6-week-old infant presented to accident and emergency with apnoeic episodes. On arrival, the infant was pale and floppy, requiring fluid resuscitation and intubation prior to transfer to the paediatric …

Answers to Epilogue

1. This is left oculomotor nerve palsy. The oculomotor nerve innervates the levator palpebrae superioris, ciliary/iris sphincter muscles and all extra-ocular muscles except the lateral rectus (cranial nerve VI innervation) and superior oblique (cranial nerve IV innervation). Therefore, paralysis prevents elevation of the eyelid (ptosis), pupillary dilatation and results in deficient eye adduction, supraduction and infraduction. The unopposed lateral rectus and superior oblique muscle action cause the affected eye to look downward and outward at rest. 2. Oculomotor nerve palsy is rare in children and is most commonly congenital or developmental in origin. Damage to the Edinger-Westphal/motor nuclei supplying the nerve …

Comparison of generic bacterial molecular detection (16S rRNA) with C-reactive protein and blood culture in the diagnosis of late-onset sepsis preterm infants: Abstract G177 Table 1

Background Preterm infants are at great risk of bloodstream infection while receiving intensive care. The incidence of late-onset bloodstream infection varies between 10–60%. Diagnosis is currently made with a combination of clinical signs and laboratory investigations. The use of new molecular methods to improve diagnosis in a range of infections has been reported in other age groups. Objective To compare a molecular 16S rRNA assay to conventional laboratory methods (C-reactive protein (CRP) and blood culture) in the diagnosis of late-onset sepsis in preterm babies. Methods A single-centre, prospective observational study was conducted. All babies with suspicion of late-onset sepsis were included. Blood for the 16S rRNA assay was taken along with routine investigations for sepsis (blood culture, CRP). The decision to label a baby as being “septic” was based on clinical data and the assessment by a national nosocomial infection scoring system. Sepsis status was then compared to results of blood culture, CRP and the 16S rRNA assay. Diagnostic odds ratio, sensitivity, specificity, positive likelihood and negative likelihood ratios were calculated. Abstract G177 Table 1 Diagnostic odds ratio (95% CI) Sensitivity Specificity + Likelihood ratio − Likelihood ratio 16s rRNA 228 (75 to 2074) 0.79 0.98 57.5 0.21 Blood culture 0.93 (0.3 to 2.4) 0.50 0.48 0.97 1.03 C-reactive protein 1.41 (0.46 to 4.3) 0.52 0.55 1.47 0.65 Results Conclusion This assay, which enables generic detection of bacteria without reliance on culture, has superior sensitivity and specificity in the diagnosis of late-onset infection than conventional laboratory methods. These results indicate that molecular methods should have a place in the diagnosis of late-onset sepsis in preterm babies. Further study is required to determine the extent to which these methods could be utilised.