Severe asthma in children

Most children with asthma have their disease easily controlled if low‐dose inhaled corticosteroids (ICSs) are regularly and correctly administered. If a child presents with asthma which is apparently resistant to therapy with high‐dose ICS and other controllers, then they have problematic severe asthma. However, in light of the UK National Review of Asthma Deaths, definitions of severe asthma based solely on the levels of prescribed treatment are too narrow. A detailed assessment of all such children should be performed. First, the diagnosis of asthma should be confirmed, then co‐morbidities assessed. Next, a nurse‐led assessment further characterizes the problem, conventionally categorizing the child as either having difficult asthma or severe therapy‐resistant asthma. Here, we reassess in particular the interactions between, and management of, these two categories, highlighting that this dichotomous classification may need reconsideration. We use bronchoscopy and an intramuscular steroid injection to determine if the child has steroid‐resistant asthma, using a novel, multidomain approach because the adult definition does not apply to around half the children we see. Finally, we highlight some mechanistic data which have emerged from this protocol such as the absence of T‐helper 2 (TH2) cytokines even in eosinophilic severe asthma and the potential role of the innate epithelial cytokine IL‐33, novel data on lineage negative innate lymphoid cells, which we can measure in induced sputum, and demonstrating that intraepithelial neutrophils are associated with better, not worse asthma outcomes. Severe paediatric asthma is very different from severe asthma in adults, and approaches must not be uncritically extrapolated from adult disease to children.     

Hydrogen peroxide contrast echocardiography

Several agents are used as echocardiographic contrast agents, but their unreliability discourages routine clinical use. Studies from the early 1960s suggest that dilute hydrogen peroxide (H₂O₂) is a safe intravascular agent. Its use was evaluated in contrast echocardiography. To obtain dense opacification reliably, H₂O₂ (3%) was passed through a sterile 0.2 μ Millipore filter and diluted with heparinized saline solution to make a 0.1 to 0.2% solution. A drop of blood was withdrawn from an indwelling peripheral venous needle into a syringe containing 0.5 to 2.0 ml of the dilute H₂O₂ and the contents injected. Studies in dogs, normal adults and 36 patients with noncyanotic congenital and acquired cardiac disorders produced dense opacification with no complications. In vitro mixture of H₂O₂ (0.3%) with leukocyte-poor blood or plasma produced only a few microbubbles, while addition to whole blood or buffy coat produced many, suggesting a role for leukocyte peroxidase. H₂O₂ contrast echocardiography is simple, inexpensive, and reliably provides dense, sustained opacification. This study and previous studies suggest that intravenous injection of 0.2% H₂O₂ can be done safely. Great caution should be exercised in patients with severe pulmonary hypertension or large right-to-left shunts because little clinical experience with H₂O₂ is available.     

A randomized,double-blind,placebo-controlled trial of dexamethasone in severe respiratory syncytial virus (RSV) infection: effects on RSV quantity and clinical outcome

Forty-one previously healthy children <2 years of age who required mechanical ventilation for respiratory syncytial virus (RSV) infection were randomized to receive dexamethasone (0.5 mg/kg; n=22) or saline placebo (n=19) intravenously every 12 h for 4 days. RSV quantity was measured by quantitative plaque assay in fresh tracheal and nasal aspirates obtained at intervals of 24+/-3 h on days 0, 1, 2, 5, and 7 following entry. Analysis by linear mixed-effects modeling demonstrated a significantly greater decline in mean tracheal RSV quantity in the placebo group than in the dexamethasone group from day 0 to day 1 (0.82 vs. 0.21 log pfu/mL; P=.01) and from day 0 to day 2 (1.45 vs. 0.53 log pfu/mL; P=.03). No differences were found between groups in nasal RSV quantity, white blood cell counts in tracheal or nasal aspirates, serum neutralizing antibody titers during convalescence, or duration of mechanical ventilation, intensive care unit stay, or hospital stay.     

A comparison between a conventional and a fiberoptic flow-directed thermal dilution pulmonary artery catheter in critically ill patients

Invasive hemodynamic monitoring is frequently required in the management of patients in intensive care units. A fiberoptic flow-directed thermal dilution pulmonary artery catheter capable of continuously monitoring the mixed venous saturation, while more expensive than a conventional pulmonary artery catheter, theoretically could result in better patient care, and might be cost-effective if it resulted either in fewer blood tests being ordered or in less time in the intensive care unit. To test this hypothesis, we designed a randomized trial in our Medical Intensive Care Unit to compare a standard pulmonary artery catheter with a fiberoptic catheter. Twenty-six patients received a standard catheter and 25 patients received the fiberoptic catheter. There were no statistical differences between the groups in age, time in the intensive care unit, number of tests ordered, hours of mechanical ventilator therapy, hours of vasoactive drug therapy, or mortality rate. The only statistically significant differences between the groups were that (1) the fiberoptic catheter required a longer insertion time and (2) there were more technical problems in consistently obtaining the wedge pressure in the patients with the fiberoptic catheters. We conclude that routine substitution of a fiberoptic catheter for the standard pulmonary artery catheter is not indicated.