Stefania Zanconato

Corticosteroids decrease exhaled nitric oxide in children with acute asthma

OBJECTIVES Nitric oxide (NO) produced in human airways seems to have both homeostatic and proinflammatory actions in the respiratory system. NO production has been shown to be higher in the exhaled air of asthmatic adults than in normal subjects. The aim of this study was to evaluate exhaled NO production during asthma exacerbation in children and the effect of a rescue course of oral steroid therapy. STUDY DESIGN We measured NO in the exhaled air of 16 children (8 girls and 8 boys, aged 6 to 13 years) with an acute asthmatic episode before and after 5 days of therapy with prednisone, and in 16 healthy children. To measure NO, children inhaled NO-free air and, breathing at tidal volume, exhaled in a circuit from which a chemiluminescence analyzer sampled continuously. To assess the effect of acute changes in bronchial caliber on exhaled NO levels, we measured NO before and after a positive bronchodilation test result with albuterol in seven children with asthma whose disease was stable. RESULTS In the group with acute asthma (forced expiratory volume in 1 second 62% +/- 4.4% predicted, mean +/- SEM), NO levels were significantly higher (31.3 +/- 4.2 parts per billion [ppb]) than in healthy children (5.4 +/- 0.4 ppb, p < 0.001). Administration of prednisone (1 mg/kg per day orally) for 5 days resulted in a mean decrease of 46% +/- 4% in exhaled NO concentrations (16.5 +/- 2.3 ppb, p < 0.001) compared with baseline, accompanied by a significant improvement in lung function (forced expiratory volume in 1 second 90.7% +/- 4.3% predicted). However, in patients with asthma exhaled NO levels remained significantly higher than in control children (p < 0.001) after steroid treatment. When exhaled NO was measured before and after a positive result after bronchodilator reversibility testing, we found no difference in exhaled NO levels (24 +/- 3.8 ppb vs 23.8 +/- 3 ppb; difference not significant). This demonstrates that inhaled albuterol and acute changes in bronchial caliber do not affect exhaled NO measurement. CONCLUSIONS These data show that children with asthma exacerbation have high levels of exhaled NO that rapidly decrease with oral steroid therapy. We suggest that measurement of exhaled NO may represent a noninvasive method of monitoring airway inflammation in children with asthma.

Cysteinyl leukotrienes and 8-isoprostane in exhaled breath condensate of children with asthma exacerbations

Background: Cysteinyl leukotrienes (Cys-LTs) and isoprostanes are inflammatory metabolites derived from arachidonic acid whose levels are increased in the airways of asthmatic patients. Isoprostanes are relatively stable and specific for lipid peroxidation, which makes them potentially reliable biomarkers for oxidative stress. A study was undertaken to evaluate the effect of a course of oral steroids on Cys-LT and 8-isoprostane levels in exhaled breath condensate of children with an asthma exacerbation. Methods: Exhaled breath condensate was collected and fractional exhaled nitric oxide (FENO) and spirometric parameters were measured before and after a 5 day course of oral prednisone (1 mg/kg/day) in 15 asthmatic children with an asthma exacerbation. Cys-LT and 8-isoprostane concentrations were measured using an enzyme immunoassay. FENO was measured using a chemiluminescence analyser. Exhaled breath condensate was also collected from 10 healthy children. Results: Before prednisone treatment both Cys-LT and 8-isoprostane concentrations were higher in asthmatic subjects (Cys-LTs, 12.7 pg/ml (IQR 5.4–15.6); 8-isoprostane, 12.0 pg/ml (9.4–29.5)) than in healthy children (Cys-LTs, 4.3 pg/ml (2.0–5.7), p=0.002; 8-isoprostane, 2.6 pg/ml (2.1–3.0), p<0.001). After prednisone treatment there was a significant decrease in both Cys-LT (5.2 pg/ml (3.9–8.8), p=0.005) and 8-isoprostane (8.4 pg/ml (5.4–11.6), p=0.04) concentrations, but 8-isoprostane levels remained higher than in controls (p<0.001). FENO levels, which fell significantly after prednisone treatment (p<0.001), did not correlate significantly with either Cys-LT or 8-isoprostane concentrations. Conclusion: After a 5 day course of oral prednisone there is a reduction in Cys-LT and 8-isoprostane levels in EBC of children with an asthma exacerbation, although 8-isoprostane levels remain higher than in controls. This finding suggests that corticosteroids may not be fully effective in reducing oxidative stress in children with an exacerbation of asthma.

Safety and success of exhaled breath condensate collection in asthma

Background: Exhaled breath condensate (EBC) is a rapidly expanding area of research to study airway inflammation through the detection of volatile and non-volatile substances in the airways. Aims: To determine the safety and feasibility of EBC procedure in a group of children with asthma of varying severity. Methods: In a cross sectional study of children aged 4–17 years, 18 healthy and 91 asthmatic children (69 in stable condition and 22 with asthma exacerbation) underwent the EBC procedure. Outcomes assessed included completion of the procedure, decrease in FEV1, change in fractional exhaled nitric oxide (FENO), and adverse effects. No pretreatment with β2 agonists was given. All children were able to successfully complete the EBC procedure. Results: Median fall in FEV1 after the procedure was −1% (IQR −3.5, 1.8) in asthmatics and was comparable to that observed in healthy children. In only one asthmatic child did the drop in FEV1 exceed 12%. No significant changes in FENO were observed after EBC. Conclusion: This study suggests that EBC is a simple and well tolerated method for evaluating biological samples from the lower airway. The procedure was safe in children with asthma exacerbation, and the success rate was 100% in children aged 4 years and above.

Gas exchange during exercise in obese children

Twenty-three obese children, aged 9 to 14 years, ranging in percentage overweight from 26% to 83% (median 51.6%±16.3%), and 37 normal-weight children, matched for sex, age and height, performed a maximal exercise test on a treadmill. Cardiorespiratory performance was assessed by determination of the ventilatory anaerobic threshold (VAT) expressed in ml O2/min per kg and as a percent of maximal oxygen uptake (% VO2max). VAT and VO2max related to body weight were significantly lower (P<0.01) in the obese than in the normal-weight children. VAT % VO2max was similar in the two groups. A significant correlation was found between VAT and VO2max both in the obese (r=0.85) and in the control groups (r=0.79). The habitual level of physical activity was lower in the obese subjects compared to the control subjects (P<0.001). In conclusion our study shows that physical fitness of overweight children is quantitatively lowered and that it can be assessed by VAT. VAT does not require a maximal test and is particularly useful in the ergometric study of subjects with exercise intolerance.

3-Nitrotyrosine, a marker of nitrosative stress, is increased in breath condensate of allergic asthmatic children.

Background:  Asthmatic patients have high exhaled nitric oxide (NO) levels. NO‐mediated inflammatory actions are mainly due to NO conversion into reactive nitrogen species, which can lead to nitrotyrosine formation. The aim of this study was to assess 3‐nitrotyrosine (3‐NT) levels in exhaled breath condensate (EBC) of asthmatic and healthy children and to investigate whether there is any relationship with exhaled NO (FENO) and lung function.

Benefits and risks of anemia correction with recombinant human erythropoietin in children maintained by hemodialysis

Ten children with renal failure (age range 2 years 6 months to 18 years 9 months; median 11 years 10 months), maintained by long-term hemodialysis, had successful correction of their anemia after intravenous administration of recombinant human erythropoietin in a dosage escalating every 2 weeks (75 to 150 to 300 to 450 IU/kg/wk). Mean hemoglobin concentration increased from 6.4 +/- 0.9 to 11.5 +/- 1.0 gm/dl. Blood cell counts used to evaluate the correction of anemia were done after dialysis; this was especially important for children less compliant with water restriction. The higher hemoglobin concentration resulted in improvement of the quality of life, a greater tolerance for physical effort (exercise tolerance doubled and the ventilatory anaerobic threshold increased significantly), correction of some subclinical central nervous system abnormalities detected by evoked potentials testing, and reduction of bleeding time. Few side effects were noted; severe hypertension developed in one patient when postdialysis hematocrit was only 28%, and there were two episodes of hypertransaminasemia with no other evidence of liver dysfunction. We conclude that in children with renal failure the use of recombinant human erythropoietin to correct anemia is safe and strongly advisable, because of the resolution of many of the symptoms correlated with anemia.

Effect of montelukast added to inhaled corticosteroids on fractional exhaled nitric oxide in asthmatic children.

The aim of this prospective, self-controlled, single-blind study was to assess the effect of montelukast added to maintenance therapy with inhaled corticosteroids (ICS) on fractional exhaled nitric oxide (FENO) in asthmatic children. Thirty-five children (age 11.2±0.4 yrs (mean±sem)) with mild-to-moderate persistent asthma treated with low to medium doses of ICS and FENO>20 parts per billion (ppb) were included. The patients were randomly assigned to two groups: 17 patients continued ICS (group C) and 18 had montelukast added to ICS for 3 weeks (group M). FENO measurements were performed in both groups at baseline (T1) and after 3 weeks (T2), and in group M also after 2 weeks of washout. FENO was measured by a chemiluminescence analyser using an on-line method (50 mL·s−1) with nitric oxide-free air. The overall mean daily dose of ICS was equivalent to 530±58 µg·day−1 of beclomethasone in group M and to 564±55 µg·day−1 of beclomethasone in group C. There were no significant differences in baseline FENO and forced expiratory volume in one second (FEV1) between the two groups. After 3 weeks there was a significant reduction of FENO values in patients of group M (T1 52.2±7.8 ppb, T2 36.1±4.6 ppb) but no significant changes in group C (T1 43.5±6.0 ppb, T2 47.8±9.4 ppb). In group M after 2 weeks of montelukast withdrawal, FENO rose to baseline values (55.6±8.7 ppb). In conclusion, after montelukast treatment there is a fractional exhaled nitric oxide reduction in asthmatic children receiving maintenance therapy with inhaled corticosteroids. This suggests an anti-inflammatory effect of montelukast additive to that of inhaled corticosteroids.

Heart rate recovery from 1 minute of exercise in children and adults

ABSTRACT: Previous studies demonstrated that the time required for oxygen uptake, CO2 production, and minute ventilation to return to baseline levels after 1-min bursts of exercise is different in children compared with adults. To test the hypothesis that the heart rate (HR) recovery time after exercise is also different in children compared with adults, we examined HR in 10 children (range 7–11 y old) and 12 adults (26–42 y old) for 10 min after 1 min of cycle ergometer exercise. Each subject exercised at work rates corresponding to 80% of the lactate or anaerobic threshold (AT), 50% of the difference between AT and maximal O2 uptake (Δ), 100% of maximal uptake, and 125% of maximal uptake. Gas exchange was measured breath by breath. In adults, the HR recovery time increased significantly with work intensity as judged by the time constant of a single exponential curve fit to postburst-exercise HR [23 ± 8 (SD) s at 80% AT, 55 ± 16 at 50%Δ, 74 ± 13 at 100% of maximal uptake, and 83 ± 20 at 125% of maximal uptake]. HR recovery time tended to increase with work intensity in children (16 ± 7, 20 ± 4, 23 ± 7, and 27 ± 9; for 80%AT, 50%Δ, 100% of maximal uptake, and 125% of maximal uptake respectively), but to a much smaller extent, and the HR recovery time was significantly smaller in children in the high-intensity (above AT) range of exercise (p < 0.001). Despite the markedly faster recoveries in children, the time course of the O2, pulse (Vo2/HR) was indistinguishable between children and adults. These data suggest that the regulation of HR after high-intensity exercise is different in children compared with adults, and that the pulsatile delivery of O2 to the tissues is controlled during the growth period.

Implementation of Adapted PECARN Decision Rule for Children With Minor Head Injury in the Pediatric Emergency Department

OBJECTIVES Of the currently published clinical decision rules for the management of minor head injury (MHI) in children, the Pediatric Emergency Care Applied Research Network (PECARN) rule, derived and validated in a large multicenter prospective study cohort, with high methodologic standards, appears to be the best clinical decision rule to accurately identify children at very low risk of clinically important traumatic brain injuries (ciTBI) in the pediatric emergency department (PED). This study describes the implementation of an adapted version of the PECARN rule in a tertiary care academic PED in Italy and evaluates implementation success, in terms of medical staff adherence and satisfaction, as well as its effects on clinical practice. METHODS The adapted PECARN decision rule algorithms for children (one for those younger than 2 years and one for those older than 2 years) were actively implemented in the PED of Padova, Italy, for a 6-month testing period. Adherence and satisfaction of medical staff to the new rule were calculated. Data from 356 visits for MHI during PECARN rule implementation and those of 288 patients attending the PED for MHI in the previous 6 months were compared for changes in computed tomography (CT) scan rate, ciTBI rate (defined as death, neurosurgery, intubation for longer than 24 hours, or hospital admission at least for two nights associated with TBI) and return visits for symptoms or signs potentially related to MHI. The safety and efficacy of the adapted PECARN rule in clinical practice were also calculated. RESULTS Adherence to the adapted PECARN rule was 93.5%. The percentage of medical staff satisfied with the new rule, in terms of usefulness and ease of use for rapid decision-making, was significantly higher (96% vs. 51%, p<0.0001) compared to the previous, more complex, internal guideline. CT scan was performed in 30 patients (8.4%, 95% confidence interval [CI]=6% to 11.8%) in the implementation period versus 21 patients (7.3%, 95% CI=4.8% to 10.9%) before implementation. A ciTBI occurred in three children (0.8%, 95% CI=0.3 to 2.5) during the implementation period and in two children (0.7%, 95% CI=0.2 to 2.5) in the prior 6 months. There were five return visits (1.4%) postimplementation and seven (2.4%) before implementation (p=0.506). The safety of use of the adapted PECARN rule in clinical practice was 100% (95% CI=36.8 to 100; three of three patients with ciTBI who received CT scan at first evaluation), while efficacy was 92.3% (95% CI=89 to 95; 326 of 353 patients without ciTBI who did not receive a CT scan). CONCLUSIONS The adapted PECARN rule was successfully implemented in an Italian tertiary care academic PED, achieving high adherence and satisfaction of medical staff. Its use determined a low CT scan rate that was unchanged compared to previous clinical practice and showed an optimal safety and high efficacy profile. Strict monitoring is mandatory to evaluate the long-lasting benefit in patient care and/or resource utilization.

A Case of Infant Botulism due to Neurotoxigenic Clostridium butyricum Type E Associated with Clostridium difficile Colitis

Abstract.Reported here is the sixth case of intestinal toxemia botulism caused by Clostridium butyricum type E in Italy since 1984. In this case, the patient was concomitantly affected with colitis due to Clostridium difficile toxin. A review of previously reported cases revealed that some of these patients may also have had intestinal toxemia botulism associated with Clostridium difficile colitis, based on the reported symptoms. Given that this association has been shown to exist not only in Italy but also in the USA, it is recommended that individuals with intestinal botulism and symptoms of colitis undergo testing for Clostridium difficile and its toxins in fecal samples.