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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.

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A patient with guanosine triphosphate cyclohydrolase I deficiency passed the newborn phenylketonuria screening program. The characteristic clinical phenotype developed in a 5-month-old patient; elevated plasma phenylalanine, undetectable urinary pterins, and absence of the enzyme activity in a liver biopsy were present. A point mutation that results in an amino acid substitution from methionine to isoleucine at position 211 was proposed to be the cause for this new phenotypic expression of guanosine triphosphate cyclohydrolase I deficiency.

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We describe four Italian male infants with a novel clinical phenotype characterized by orthostatic acrocyanosis, relapsing petechiae, chronic diarrhea, progressive pyramidal signs, mental retardation, and brain magnetic resonance imaging abnormalities. The first symptoms appeared after the termination of breast-feeding and introduction of formula feeding. Marked persistent 2-ethylmalonic aciduria was associated with abnormal excretion of C4-C5(n-butyryl-, isobutyryl-, isovaleryl-, and 2-methylbutyryl-)acylglycines and acylcarnitines and with intermittent lactic acidosis. Short- and branched-chain plasma acylcarnitine levels were also elevated. 2-Ethylmalonic aciduria is generally regarded as being indicative of a defect in fatty acid oxidation. Extensive studies of cultured fibroblasts failed to reveal such a defect. The observation of intermittent urinary excretion of 2-ethylhydracrylic acid pointed to involvement of the isoleucine R pathway in ethylmalonate biosynthesis. This hypothesis was tentatively corroborated by the biochemical responses to an oral isoleucine challenge in two patients. However, fibroblast studies showed normal oxidation rates of (14C)isoleucine (ul), indicating that this is not a defect of isoleucine oxidation expressed in skin fibroblasts. In one of two patients tested, cytochrome c oxidase activity was partially reduced (45%) in cultured fibroblasts. This unique clinical and biochemical phenotype identifies a new metabolic encephalopathy of yet undetermined cause.

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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.

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