Weaning of epoprostenol in a small infant receiving concomitant bosentan for severe pulmonary arterial hypertension secondary to bronchopulmonary dysplasia.

Endothelin receptor antagonism is an important therapeutic tool of pulmonary arterial hypertension (PAH). Bosentan was the first orally active, dual antagonist of endothelin receptors in human adults, and has been recently considered for children as well. However, little is known about bosentan treatment in children weighing less than 10 kg. We describe the use of bosentan concomitantly to epoprostenol in an infant weighing 3.5 kg and affected with severe bronchopulmonary dysplasia (BPD) and PAH. At 5 months old, when she presented subsystemic PAH secondary to severe BPD, she was treated with oxygen, digoxin and diuretics. At 8 months old, due to severe PAH not responsive to 100% oxygen, high frequency oscillatory ventilation (HFOV) and nitric oxide (NO), we started epoprostenol and bosentan. Bosentan dose was doubled at 9 months old, when HFOV and NO were slowly discontinued due to improved oxygenation index. Regular echocardiographic measurements of systolic right ventricular pressure were recorded by the method of tricuspidal atrio-ventricular gradient. A four-month combined epoprostenol and bosentan treatment decreased systolic right ventricular pressure from 68% to 40% of the systemic level, till its normalization at 11 months old. Later, when bosentan and epoprostenol were discontinued and sildenafil was started, severe PAH was reported again. Our patient died due to septic shock and refractory hypoxia at 14 months old.

Artificial feeding: progresses and problems.

The introduction of infant formulas represents an important result in the field of the newborn and infant artificial feeding, reducing the gap with maternal feeding. In the last decade technological evolution allowed to obtain milk formulas which became more and more similar to human milk starting from cow's milk, thus obtaining a composition adequate to the digestive and nutritional requirements of the newborn and of the infant, starting from the model of the breast feeding (infant formulas). The major differences between human and cow's milk have been corrected by dilution, skimming, addition of carbohydrates, acidification. From an allergenic viewpoint, in a recent study, we observed that no significant differences can be observed in the development of atopic symptoms for children supplemented with different substances in the first 5 days of life or receiving cow's milk infant formulas in the first three months of life, compared to those breast fed. In the case of the development of intolerance or allergy to cow's milk proteins, the substitution of the cow's milk based formula with hydrolysed or soy formulas is required. Maternal feeding represents the best choice for the nutrition of the newborn; however, when it is not possible, milk formulas despite they still show marked differences with human milk, concerning both nutrients and defensive factors, allow to reach satisfactory results about both nutrition and health.

Nedocromil sodium vs. sodium cromoglycate pressurized aerosol in the prevention of bronchoconstriction induced by ultrasonic nebulized distilled water in asthmatic children.

To compare the effectiveness of nedocromil sodium (NS) and sodium cromoglycate (SCG), administered by metered dose inhaler (MDI) with a 700 mL holding chamber (Fisonair Fisons UK) in preventing bronchoconstriction induced by inhalation of ultrasonically nebulized distilled water (UNDW), 12 asthmatic children were studied in a randomized, double-blind, placebo-controlled, intrapatient study. Following a baseline challenge with UNDW, the protective effect of NS, SCG, or placebo was evaluated in each subject. Cumulative doses of delivered nebulized water producing a 20% fall in forced expiratory volume in 1 sec (PD20 UNDW) was measured. Mean (+/- SD) PD20 UNDW was 4.83 (+/- 4.84), 10.16 (+/- 7.05), 1.58 (+/- 0.5), and 15.93 (+/- 0.23) respectively, for baseline, and placebo, SCG, and NS-treated groups. A significant (P < 0.05) protection from UNDW induced bronchoconstriction by NS was observed in comparison with placebo, while no such effect was evident when the children were treated with SCG.

Comparison of the effects of loratadine and astemizole in the treatment of children with seasonal allergic rhinoconjunctivitis.

The efficacy and safety of a once-daily dose of loratadine 10 mg (5 mg in patients whose body weight was less than or equal to 30 kg) and astemizole 2 mg/10 kg body weight o.d. were compared in a 14-day third-party blind study. Forty-one children (30 boys and 11 girls, aged 6-14 years) with seasonal allergic rhinoconjunctivitis entered the study. The pollen count was monitored throughout the study. A significant improvement (p less than 0.01) in allergy symptoms was observed from the third day for both drugs; there was no significant difference between drugs, although loratadine led to a greater reduction in symptoms. In the astemizole group, the apparently rapid onset of drug action might by explained by reduced pollen exposure. Therapeutic response was excellent/good in 83.3% and 58.8% of the loratadine and astemizole groups, respectively. The results reported by the patients/parents were similar. Nine of the children on astemizole and four children on loratadine complained of side effects; three patients in the astemizole group were withdrawn from treatment because of adverse effects. No abnormal changes in lab values were observed in either group.

Efficacy and duration of action of oral procaterol in asthmatic children after single administration of different dosages.

A double-blind crossover study was performed to evaluate the bronchodilating effect of different single doses of procaterol (less than 0.5 micrograms/kg, 1.5 micrograms/kg, and placebo) orally administered. Sixteen asthmatic children, age 6-12 years, participated in the trial. Pulmonary function, heart rate, blood pressure, and tremor were evaluated at 30, 60, 90, and 120 min and then hourly for 8 hours after administration. All three doses were therapeutically effective. The 1.5 micrograms/kg dose produced a more sustained bronchodilatation effect, but was also associated with an increase in the incidence of tremors. The 0.5 micrograms/kg dosage may, however, be a good starting dose because it assures a reasonable risk/benefit ratio.

Efficacy and safety of loratadine suspension in the treatment of children with allergic rhinitis.

The safety and efficacy of loratadine was compared with that of dexchlorpheniramine in children with allergic rhinitis. Twenty-one children received loratadine 0.11-0.24 mg/kg ideal body weight once daily and 19 dexchlorpheniramine 0.10-0.23 mg/kg every 8 h (0.30-0.69 mg/24 h) for 14 consecutive days. Both loratadine and dexchlorpheniramine were effective in reducing nasal and ocular symptoms in allergic children. Substantial improvement in allergy symptoms was observed at the first evaluation (day 3 of treatment) and was maintained for the study duration. No significant trend of abnormality in laboratory parameters was observed. Drowsiness was present only in the dexchlorpheniramine-treated group. Loratadine appears to be a simple, effective and safe therapy for seasonal allergic rhinitis.

Skin and serum reactivity to some storage mites in children sensitive to Dermatophagoides pteronyssinus.

The incidence of skin test and RAST positivity for Dermatophagoides farinae and storage mites (Glycyphagus privatus, Lepidoglyphus destructor, Tyrophagus putrescentiae, Acarus siro, and Gohieria fusca) have been evaluated in children with bronchial asthma and positive prick test to Dermatophagoides pteronyssinus. The storage mite with highest incidence of skin and RAST positivity was Gohieria fusca, which caused a positive response in more than 50% of the children evaluated. This antigen appears to possess allergenic determinants not present in Dermatophagoides pteronyssinus. The sensitivity to this antigen might be considered in house dust mite-allergic children who do not improve after specific immunotherapy with Dermatophagoides pteronyssinus extracts.

Spinhaler specific bronchoprovocation challenges: short interval administration of micronized freeze-dried allergen in children with bronchial asthma. III.

Two different methods of antigen bronchial challenge, with micronized freeze-dried extract of D. pteronyssinus administered as a powder by a spinhaler, were evaluated in 15 asthmatic children, who were skin test positive and RAST positive for house dust mite D. pteronyssinus. In one method, daily increasing dose method (DIDM), a single antigen challenge was performed every day successively. In the other method, cumulative dose method (CDM), the antigen doses were administered successively with 7-minute intervals. The tests were considered positive when there was a fall of FEV1 greater than or equal to 20% of the baseline value. The DIDM showed a greater incidence of isolated late bronchoconstrictions. The CDM revealed a great incidence of biphasic reactions (early and late) and of laryngeal spasm. Two patients showed discordant results (positive with one method and negative with the other) suggesting problems related to intrasubject reproducibility.

Comparison of the protective effect and duration of action of orally administered clenbuterol and salbutamol on exercise-induced asthma in children.

Clenbuterol (C), a long-acting beta 2-selective bronchodilator was compared with salbutamol (S) in exercise-induced asthma (EIA) at two premedication time levels. Sixteen asthmatic children with EIA living at an altitude of 1,750 m were treated with C (0.001 mg/kg) and S (0.12 mg/kg), administered randomly in a double-blind cross-over study 90 and 300 minutes before exercise tests of running on a treadmill for 6 minutes. Pulmonary functions were evaluated prior to the administration of the drugs and immediately before, at the end of, and 2, 5, 10, 15, 20, and 25 minutes after exercise tests. In the preliminary screening exercise test the mean fall of FEV1 was 41.1%, but it was 21.0% and 27.1% after S and 21.9% and 19.9% after C administered 90 and 300 min prior to the test, respectively. Salbutamol administered 300 minutes before the test was statistically less effective than the same drug administered 90 minutes before the test or C administered 300 minutes before the test. Therefore, we can conclude that clenbuterol provides a more lasting protection than salbutamol in EIA.

The efficacy of ketotifen in a controlled double-blind food challenge study in patients with food allergy.

The effectiveness of oral ketotifen was compared with that of placebo in 26 patients with food allergy in a randomized, double-blind parallel study. Patients were selected on the basis of food allergy as established by history, clinical improvement after an exclusion diet, and reappearance of the symptoms after a challenge with the food. Thirteen patients were given ketotifen and 13, placebo. Ketotifen or placebo were administered twice daily for 1 month after the first oral provocation test and the last dose was given 12 hours before the second oral provocation test. Ketotifen protected patients (7/13) significantly more than placebo (2/13; P less than .05). The results of this study suggest that ketotifen may be useful for some patients with food allergy.

Hypothalamic-pituitary-adrenal function in children with atopic dermatitis treated with clobetasone butyrate and its clinical evaluation.

Twenty-nine patients with symmetrical eczematous lesions were treated with 0.05% clobetasone butyrate cream. Clinical conditions and cortisol and ACTH concentrations were evaluated at the beginning and after 1 week in 12 children and after 2 weeks of treatment in 17 patients respectively. The lesions and symptoms improved steadily and no significant change in cortisol and ACTH plasma levels was observed throughout the study in all children. This steroid offers clinically effective topical antiinflammatory activity with a wide margin of safety.

Adrenocortical function during prolonged treatment with clobetasone butyrate in children with chronic atopic dermatitis and elevated IgE levels.

Twelve children with chronic atopic dermatitis and elevated IgE levels (age range: 2-13 years; mean age = 8.2 +/- 3.5 years) were selected for the study and treated with clobetasone butyrate (0.05% cream) thrice daily during the first week, then twice daily for three weeks. Adrenocortical function was evaluated at the beginning and the end of treatment period. The results show that there was no statistically significant change in adrenal function during the study period (tetracosactrin test). The results of the immunological studies, namely total IgE using the paper disc radioimmunoassay technique, specific IgE using the radioallergosorbent test and immunoglobulin levels are given.