Robert Ross-Russell

Lymphocyte apoptosis in acute respiratory syncytial virus bronchiolitis

Respiratory syncytial virus (RSV) infection may have an effect on the development of T cell memory responses. RSV bronchiolitis in infants is associated with a transient decline in circulating lymphocytes. We hypothesized that the mechanism underlying this lymphopenia is apoptosis. Blood was taken from 32 infants during primary RSV bronchiolitis and three months later. Using flow cytometry, we found that absolute numbers of both CD3+/CD4+ T‐helper lymphocytes (P = 0·029) and CD3+/CD8+ cytotoxic lymphocytes (CTL) (P = 0·043) were significantly reduced during acute infection. Up‐regulated expression both of Fas (P < 0·001) and tumour necrosis factor‐related apoptosis‐inducing ligand (TRAIL) receptor (P < 0·001) was found during acute illness on both CD3+/CD4+ and CD3+/CD8+ lymphocytes, when compared with convalescent samples. Expression of Fas on CD4+ lymphocytes was inversely related to CD4+ number (P = 0·03). Plasma levels of soluble Fas ligand (P = 0·028) and caspase‐1 (P = 0·037), determined by enzyme‐linked immunosorbent assay, were increased during bronchiolitis. Plasma interleukin‐18, a product of caspase‐1 activity, was not raised. Taken together, these data suggest that in acute RSV infection, CD4+ helper lymphocytes and CD8+ cytotoxic lymphocytes are primed to undergo apoptosis. This is a mechanism through which lymphopenia may occur and T cell memory may be altered.

Early severe neutropenia and thrombocytopenia identifies the highest risk cases of severe meningococcal disease.

Objective To determine the performance of established predictors of mortality in pediatric acute meningococcal disease (MD) in a contemporary population and to develop a simple predictive score that will not vary with observer. Design Prospective study for development set and mixed retrospective and prospective study for validation set. Setting and Patients A total of 227 patients with clinical meningococcal disease who were referred to three multidisciplinary pediatric intensive care units from 1993 to 1999. Early deaths before transfer to pediatric intensive care unit and deaths from cerebral herniation were included in the analysis. Measurements and Main Results The product of platelet and neutrophil counts at presentation (PN product) predicts mortality from meningococcal disease better than either count alone and at least as well as established severity scores. The Glasgow Meningococcal Septicaemia Prognostic Score and Malley scores performed poorly in these populations. The positive predictive value (PPV) for a Glasgow meningococcal septicemia prognostic score of ≥8/15 was 17.5% (16 of 91; 95% CI = 9%–25%), significantly lower than published estimates of 30%–74%, (p < .01). The PPV for death (or amputation) with a Malley score of 3/3 was 50% (12 of 24; 29%–71%), significantly lower than the published value of 100% (p < .001). The PN product appears to be a useful predictor. For a PN product of <40, PPV = 82% (9 of 11), specificity = 99% (195 of 197), and sensitivity = 73% (23 of 30). The performance of this score was greatest in younger children <5 yrs of age in whom clinical cerebral herniation was not seen as a cause of death (0 of 21 deaths at <5 yrs of age; 4 of 9 deaths at ≥5 yrs of age). Conclusion Established scores significantly overestimate the occurrence of adverse outcomes in meningococcal disease. This may reflect improved resuscitation and outcome or variability in the application of these scores. The PN product achieves similar prediction to the scores currently in use and is independent of the observer. Factors that reflect the extent of the inflammatory response rather than the care before presentation are becoming increasingly important.

The neuroendocrine stress response and severity of acute respiratory syncytial virus bronchiolitis in infancy.

Objective Neuroendocrine hormones have profound effects on the immune system. The immune response is a major factor in the pathogenesis of acute respiratory syncytial virus (RSV) infection. We hypothesised that there is a relationship between the neuroendocrine response in acute RSV infection, the severity of illness, and the degree of lymphopenia.Design Prospective, non-randomised cohort study of infants hospitalised for RSV infection requiring mechanical ventilation or managed conservatively. The study assessed the effect of age, gender, birth gestation, and severity of illness on stress hormone profile and its relationship to lymphocyte count.Setting Regional Paediatric Intensive Care Unit (PICU) and children’s wards.Patients Thirty-two consecutive infants with RSV infection were enrolled, of which thirteen were mechanically ventilated on PICU (study subjects) and nineteen treated on the ward (comparison group). Twenty-three children (72%) returned for follow-up.Measurements and main results A specific neuroendocrine profile was found in PICU patients compared to ward patients (Wilks Lambda = 0.36, F = 9.05, P =.03). PICU patients had significantly higher prolactin and growth hormone, and significantly lower leptin and IGF-1. Cortisol levels were the same. PICU patients were more lymphopenic compared to ward patients (P =.0001). On multiple regression analysis, prolactin and leptin levels accounted for 57% of the variation in lymphocyte count.Conclusions Whereas the effect of intensive care (mechanical ventilation and medication) could not be controlled for, our results suggest that there is an association between the neuroendocrine hormone response, severity of illness and degree of lymphopenia.

Using Measurements of Shunt and Ventilation-to-Perfusion Ratio to Quantify the Severity of Bronchopulmonary Dysplasia

Background: Classifying the severity of bronchopulmonary dysplasia (BPD) by continuous numerical variables would facilitate follow-up of disease progression and quantified analysis of disease determinants. Objectives: To non-invasively measure oxygenation impairment in BPD by the degree of right-to-left shunt, right shift of the oxyhaemoglobin dissociation curve and ventilation/perfusion (VA/Q) inequality and to explore their relation with clinical parameters. Methods: Prospective cohort study of 24 infants with a median (interquartile range, IQR) gestation of 25 weeks (24-27) and a birth weight of 0.70 kg (0.63-0.93), studied at 36 days (30-66), at a postmenstrual age (PMA) of 33 weeks (29-36). Inspired oxygen (FIO2) was varied to obtain three to five transcutaneous oxygen saturation (SpO2) values between 85 and 96%. Values of shunt, shift and VA/Q were obtained by plotting the paired data of SpO2 against FIO2 for each infant using a unique program. Right-to-left shunt, right shift of the oxyhaemoglobin dissociation curve and VA/Q were measured in infants born <32 weeks PMA receiving oxygen at 28 days. Results: The median (IQR) shunt was 8% (0.3-16.5), shift 14.5 kPa (10.9-19.4) and VA/Q 0.40 (0.30-0.48). Shunt, shift and VA/Q were significantly related to gestational age (GA) at birth, PMA at study, weight at study and weight gain per week. Conclusions: Severity of pulmonary oxygenation impairment in BPD can be quantified at the cot-side by non-invasive measurement of shunt, shift and VA/Q. Low GA at birth, low weight at birth and at the time of study and impaired weight gain are significantly associated with the severity of oxygen-exchange impairment in infants with BPD.

Paediatrics in Vienna

The aim of this article is to describe the paediatric highlights from the 2009 European Respiratory Society Annual Congress in Vienna, Austria. The best abstracts from the seven groups of the Paediatric Assembly (asthma and allergy, respiratory epidemiology, cystic fibrosis, respiratory physiology, respiratory infections and immunology, neonatology and paediatric intensive care, and bronchology) are presented alongside findings from the current literature.

Correlation of radiographic thoracic area and oxygenation impairment in bronchopulmonary dysplasia

We hypothesized that radiographically-assessed hyperinflation in bronchopulmonary dysplasia (BPD) is related to the degree of oxygenation impairment. Our objective was to explore the relation of chest radiographic thoracic area (CRTA) with right-to-left shunt, right shift of the oxyhemoglobin dissociation curve and ventilation/perfusion ratio (VA/Q) in infants with BPD. Twenty-two infants born at median (IQR) gestation of 26 (24-28) weeks with BPD were prospectively studied at 39 (30-69) days. Inspired oxygen (FiO2) was varied to obtain transcutaneous oxygen saturation (SpO2) values between 85 and 96%. Shunt, shift and VA/Q were derived by plotting and analysing pairs of SpO2 and FiO2. CRTA was measured by free hand-tracing the perimeter of the thoracic area in anterio-posterior chest radiographs. Median (IQR) shunt was 8 (1-14)%, shift was 13 (11-19)kPa and VA/Q 0.42 (0.30-0.48). Median (IQR) CRTA/kg was 2495 (1962-2838)mm(2) and was significantly related to shift (r=0.674, p<0.001), VA/Q (r=-0.633, p<0.001), weight at study (r=-0.457, p=0.003) and day of life (r=-0.406, p=0.009), but not to shunt. CRTA in BPD is significantly related to oxygenation impairment as quantified by shift and VA/Q. CRTA can be used as a simple radiographic test to quantify BPD severity.