Safety of budesonide inhalation suspension in infants aged six to twelve months with mild to moderate persistent asthma or recurrent wheeze

OBJECTIVE: To compare the safety of budesonide inhalation suspension (BIS) with placebo in infants 6 to 12 months of age with mild to moderate persistent asthma or recurrent wheeze. STUDY DESIGN: In this multicenter, randomized, double-blinded, parallel-group, placebo-controlled study, 141 patients received 0.5 mg BIS (n = 48), 1.0 mg BIS (n = 44), or placebo (n = 49) once daily for 12 weeks. The primary variable was adrenal function, based on cosyntropin-stimulated plasma cortisol levels. Spontaneous adverse events and clinical laboratory findings also were monitored. RESULTS: Overall, the types and frequencies of adverse events reported during the study were comparable across treatment groups. The response to cosyntropin stimulation was similar across treatment groups, with no significant difference between BIS treatment and placebo. CONCLUSIONS: The safety profile of BIS was similar to that of placebo, with no suppressive effect on adrenal function in patients 6 to 12 months of age with mild to moderate persistent asthma or recurrent wheeze.     

Efficacy and safety of fluticasone propionate hydrofluoroalkane inhalation aerosol in pre-school-age children with asthma: a randomized, double-blind, placebo-controlled study

OBJECTIVE: To evaluate the efficacy and tolerability of fluticasone propionate (FP) hydrofluoroalkane (HFA) in children age 1 to < 4 years with asthma. STUDY DESIGN: Children were assigned (2:1) to receive FP HFA 88 mug (n = 239) or placebo HFA (n = 120) twice daily through a metered-dose inhaler with a valved holding chamber and attached facemask for 12 weeks. The primary efficacy measure was mean percent change from baseline to endpoint in 24-hour daily (composite of daytime and nighttime) asthma symptom scores. RESULTS: The FP-treated children had significantly greater (P < or = .05) reductions in 24-hour daily asthma symptom scores (-53.9% vs -44.1%) and nighttime symptom scores over the entire treatment period compared with the placebo group. Daytime asthma symptom scores and albuterol use were slightly more decreased with FP than with placebo; however, the differences were not statistically significant. Increases in the percentage of symptom-free days were comparable. The percentage of patients who experienced at least 1 adverse event was similar in the 2 groups. Baseline median urinary cortisol excretion values were comparable between the groups, and there was little change from baseline at endpoint. FP plasma concentrations demonstrated that systemic exposure was low. CONCLUSIONS: FP HFA 88 mug twice daily was effective and well tolerated in pre-school-age children with asthma.     

Nebulized budesonide for the treatment of moderate to severe asthma in infants and toddlers*

Maintenance treatment with nebulized budesonide was studied in young children with asthma not controlled without steroids. In a blind parallel-group study for 18 weeks, 102 children, mean age 22 (5–47) months, were randomized for treatment starting with 0.25 or 1 mg b.i.d. The patients were reviewed every 3 weeks, and if symptom control had been achieved the dose was reduced, otherwise it was kept. The clinical effect was very good with both dose regimens. The median time to 7 consecutive days without any asthma symptoms was about 1 month with both, highlighting the importance of the duration of therapy rather than the benefits of a high starting dose. In 18 of 24 children who attained the placebo stage, symptoms had reappeared at the last visit. Although an overall minimal effective maintenance dose could not be demonstrated, 47% achieved symptom control on 0.25 mg b.i.d., i.e. fulfilled criteria for further dose reduction. No significant side effects were seen. On average, 25% of the nominal dose reached the patients.     

Sustained-release terbutaline vs sustained-release theophylline in young patients with asthma

Twenty patients with asthma (mean age, 10.9 +/- 2 years) entered a six-week, randomized, double-blind, crossover comparison of sustained-release (S-R) terbutaline sulfate (Bricanyl Durules) vs S-R theophylline (Theo-Dur). In each two-week study period each patient received S-R theophylline twice daily in doses previously adjusted to give serum theophylline concentrations in the range of 10 to 20 mg/L (56 to 111 mumol/L); or S-R terbutaline sulfate, 5 mg twice daily; or S-R terbutaline sulfate, 7.5 mg twice daily. All treatment regimens produced significant improvement in one or more pulmonary function test values compared with prestudy values. The incidence of acute asthma episodes were similar during each treatment regimen. No clinically significant difference occurred between the regimens for daily symptom scores, peak expiratory flow rates, or use of a terbutaline metered-dose inhaler. At the end of the theophylline treatment period, the mean (+/- SD) theophylline level 12 to 14 hours after the last dose was 10.1 +/- 3.3 mg/L (56 +/- 18 mumol/L); at the end of the terbutaline treatment periods, the mean trough terbutaline levels were 2.22 micrograms/L (9.9 +/- 4.4 nmol/L) (S-R terbutaline sulfate, 5 mg twice daily) and 3.07 micrograms/L (13.7 +/- 5.4 nmol/L) (S-R terbutaline sulfate, 7.5 mg twice daily). Adverse effects, including tremor, occurred with similar frequency during all three drug regimens. Sustained-release formulations of theophylline and terbutaline, in the dosages studied, provided comparable control of asthma symptoms.     

Oral oseltamivir improves pulmonary function and reduces exacerbation frequency for influenza-infected children with asthma

BACKGROUND: Among asthmatic children, influenza is associated with increased hospitalizations. Although vaccination is safe and effective among asthmatic children, its protective efficacy varies and uptake rates can be low. In comparison, oseltamivir (Tamiflu) is effective against all influenza strains and can reduce the severity and duration of influenza among adults and children. This study determined the effects of oseltamivir among influenza-infected children with asthma. METHODS: Asthmatic children (6-12 years of age) were randomized to receive oseltamivir (2 mg/kg) or placebo twice daily, as a syrup. The primary efficacy endpoint was the time to freedom from illness. Secondary endpoints included the area under the symptom score-hour curve, the proportion of patients with asthma exacerbations and changes in forced expiratory volume at 1 second during the dosing period. Analysis was performed for both the intent-to-treat infected (n = 179) and per protocol (n = 162) populations. RESULTS: The primary endpoint for this study was not met. Oseltamivir tended to reduce the time to freedom from illness in the intent-to-treat infected population (10.4 hours, 8%; P = 0.5420), the per protocol population (24.3 hours, 17%; P = 0.1607) and patients who started treatment <24 hours after symptom onset (39.8 hours, 25%; P = 0.0780). However, an improvement in pulmonary function was observed. The improvement in forced expiratory volume at 1 second was significantly greater among oseltamivir-treated patients (10.8% versus 4.7%; P = 0.0148). Oseltamivir-treated patients also experienced fewer asthma exacerbations up to day 7 (68% versus 51%; P = 0.031). Oseltamivir was safe and well-tolerated. CONCLUSIONS: Oseltamivir is safe and well-tolerated among asthmatic children, may reduce symptom duration and helps improve lung function and reduce asthma exacerbations during influenza infection.     

Double blind, placebo controlled study of nedocromil sodium in asthma.

After a two week baseline, 209 asthmatic children (mean age 10 years, range 6-17) were randomly allocated to receive 4 mg nedocromil sodium (n = 110) or placebo (n = 99) four times daily for 12 weeks in addition to their current treatment. The children completed daily diary cards and visited the clinic at four week intervals. Statistically significant differences in favour of nedocromil sodium were seen for clinician assessment of asthma severity and diary card symptom scores, pulmonary function and inhaled beta 2 bronchodilator use. Total symptom score decreased by 50% from baseline in the nedocromil sodium group and by 9% in the placebo group during the final four weeks. Nedocromil sodium was considered very or moderately effective by 78% of children/parents (placebo 59%) and 73% of clinicians (placebo 50%). Nausea, headache and sleepiness, and dyspnoea led to withdrawal of one child from nedocromil sodium and placebo treatments, respectively. Reports of sore throat and headache were marginally greater with the nedocromil sodium treatment. It is concluded that nedocromil sodium was both effective and safe in the treatment of asthma in children.     

Double blind, placebo controlled study of nedocromil sodium in asthma

After a two week baseline, 209 asthmatic children (mean age 10 years, range 6-17) were randomly allocated to receive 4 mg nedocromil sodium (n = 110) or placebo (n = 99) four times daily for 12 weeks in addition to their current treatment. The children completed daily diary cards and visited the clinic at four week intervals. Statistically significant differences in favour of nedocromil sodium were seen for clinician assessment of asthma severity and diary card symptom scores, pulmonary function and inhaled beta 2 bronchodilator use. Total symptom score decreased by 50% from baseline in the nedocromil sodium group and by 9% in the placebo group during the final four weeks. Nedocromil sodium was considered very or moderately effective by 78% of children/parents (placebo 59%) and 73% of clinicians (placebo 50%). Nausea, headache and sleepiness, and dyspnoea led to withdrawal of one child from nedocromil sodium and placebo treatments, respectively. Reports of sore throat and headache were marginally greater with the nedocromil sodium treatment. It is concluded that nedocromil sodium was both effective and safe in the treatment of asthma in children.     

Clinical response to 2 dosing regimens of lansoprazole in infants with gastroesophageal reflux

Proton pump inhibitors such as lansoprazole are used in the treatment of gastroesophageal reflux disease (GERD), but dosing guidelines for infants have not been determined. The objective of this study was to assess the clinical efficacy of 2 dosing regimens of lansoprazole in infants with GERD using the revised infant gastroesophageal reflux questionnaire scores (I-GERQ-R). Thirty consecutive infants (3-7 months) with GERD, whose conditions were diagnosed by I-GERQ-R scores of > or =16, were randomly assigned to receive 1 of 2 lansoprazole dosing regimens: 15 mg given once per day (group A) or approximately 7.5 mg given 2 times per day (group B). Matched infants in a control group were treated with an extensively hydrolyzed formula (group C). Daily I-GERQ-R scores were gathered, and the scores after 1 and 2 weeks of treatment were used for analysis. The mean pretreatment scores were similar in groups A, B, and C (26.6, 26.9, and 25.9, respectively). After treatment there was a similar drop in the mean scores in groups A and B (20.6 and 20.0, respectively), but not in group C (25.8). At the end of the first week of treatment, in group A, 5 of 15 infants (33%) had a significant reduction in their I-GERQ-R scores, whereas in group B, 10 of 15 infants (67%) had a significant reduction in their I-GERQ-R scores (P < 0.05). At the end of the second week of treatment, groups A and B had similar numbers of patients with significant improvement (60% and 67%), which was higher than in group C (3/15, 20%). Overall, there was no difference in the symptom response, as measured by I-GERQ-R scores, between 15 mg of lansoprazole given once per day and 7.5 mg given twice per day in infants with GERD, but the twice-daily regimen produced a faster symptom response. Both regimens were significantly better than treatment of infants with an extensively hydrolyzed formula.     

Efficacy of cromoglycate in persistently wheezing infants

A prospective study was undertaken to evaluate the efficacy of (sodium) cromoglycate in the treatment of persistent wheezing in 31 children between 4 and 12 months of age. The subjects were randomised to receive either 40 mg of cromoglycate (n = 16) or physiological saline as placebo (n = 15) three times a day by wet nebulisation in a double blind fashion for a period of six weeks. The patients were evaluated with daily symptom scores and respiratory function testing measuring maximal expiratory flow at functional residual capacity (VmaxFRC) before initiating treatment and upon completion. At baseline, mean (SD) symptom scores between the two groups were comparable (cromoglycate 99.5 (29.8), placebo 104.5 (29.7)) as were VmaxFRC expressed as per cent of predicted normals (cromoglycate 48 (28), placebo 46 (20)). Upon completion of the treatment protocol, no significant difference could be found between the two groups for either symptom score (cromoglycate 67.6 (40.2), placebo 58.6 (41.4)), or VmaxFRC (cromoglycate 52 (24), placebo 60 (32)). It is concluded, therefore, that 40 mg of cromoglycate three times a day administered via facemask and wet nebulisation was no more effective than placebo in the treatment of our sample of persistently wheezing infants under 1 year of age.     

Low‐dose budesonide improves exercise‐induced bronchospasm in schoolchildren

The aim of this study was to compare the clinical efficacy of low‐dose inhaled budesonide (once or twice daily) and placebo, administered via Turbuhaler^®, on exercise‐induced bronchoconstriction (EIB) in children with mild asthma. Fifty‐seven steroid‐naive children (7–16 years old; 41 boys, 16 girls) with EIB participated in this sub‐population study according to the following inclusion criterion: a maximum fall in forced expiratory volume in 1 s ( FEV ₁) ≥ 10% after a standardized treadmill test. Mean baseline FEV ₁ was 100.3% of predicted, and mean maximum fall in FEV ₁ after the standardized exercise test was 22%. The study was a double‐blind, randomized, parallel‐group design. After 2 weeks of run‐in, the children received inhaled budesonide 100 µg or 200 µg once daily in the morning, 100 µg twice daily, or placebo, for 12 weeks. After 12 weeks of treatment, the fall in FEV ₁ after the exercise test was significantly less in all three budesonide groups (7.2–7.8%) vs. placebo (16.7%). Daytime symptom scores were significantly lower in all three budesonide groups compared with placebo (p < 0.02). The three budesonide groups did not differ significantly, and no significant change in lung function was found in any group. Therefore children with mild asthma, but with significant EIB, improved their exercise tolerance and symptom control after 3 months of treatment with a low dose of inhaled budesonide given once or twice daily.     

Inhaled budesonide for chronic wheezing under 18 months of age.

The role of budesonide in controlling chest symptoms in infants was assessed. It was administered from a metered dose inhaler into a large volume spacer (Nebuhaler) with attached Laerdal mask. Twenty nine infants were recruited into a double blind crossover trial. Five defaulted. The remaining 24 (mean age 11 months) were assessed for the tolerance of the device, adverse effects, treatment failures, parental opinion, and daily symptom and treatment records. Twenty tolerated the modified Nebuhaler. One developed meningitis on placebo. Two experienced exacerbations on placebo. Eleven of 18 parents whose children completed the maximum treatment preferred budesonide to placebo and one preferred placebo. Mean symptom scores on budesonide were better than on placebo for the 15 children with complete symptom records. Fewer bronchodilator doses were used while taking budesonide. Our findings indicate that budesonide given in this way is an effective treatment for infants who may need prophylaxis for their wheezing.     

Effect of formoterol on clinical parameters and lung functions in patients with bronchial asthma: a randomised controlled trial.

AIMS: To determine the role of formoterol in the treatment of children with bronchial asthma who are symptomatic despite regular use of inhaled corticosteroids. METHODS: A randomised, double blind, parallel group, placebo controlled study to investigate the effects of inhaled formoterol (12 microg twice a day) in 32 children with moderate to severe bronchial asthma. The study consisted of two week run in periods and six week treatment periods, during both of which the patients continued their regular anti-inflammatory drugs. The efficacy parameters were symptom scores, bronchodilator use, daily peak expiratory flow rates (PEFR), methacholine hyper-reactivity, forced expiratory volume in one second (FEV1), lung volumes, and airway conductance. RESULTS: Formoterol treatment for six weeks decreased symptom scores, PEFR variability, and the number of rescue salbutamol doses, and increased morning and evening PEFR significantly. No adverse reactions were seen. CONCLUSION: These findings suggest that inhaled formoterol is effective in controlling chronic asthma symptoms in children who are symptomatic despite regular use of inhaled corticosteroids.     

Ding Chuan Tang, a Chinese herb decoction, could improve airway hyper-responsiveness in stabilized asthmatic children: a randomized, double-blind clinical trial.

Traditional Chinese medicine has a long history of application in the treatment of bronchial asthma. Solid scientific evidence, however, is not available despite its widespread use among patients worldwide and in Taiwan. To assess the effect of Ding Chuan Tang (DCT) in airway hyper-responsiveness (AHR) on asthmatic children via randomized, double blind, placebo-controlled clinical trial. This study enrolled children who were aged 8-15 and diagnosed as mild to moderate persistent asthma patients. They were randomly allocated to receive 6.0 g DCT or placebo daily for 12 wk. Self-recorded daily symptom scores, medication scores, and morning and evening peak expiratory flow rates were returned at the monthly clinic. Pulmonary function test, methacholine challenge test, and serum inflammatory mediators were measured before and at the end of the trial. Fifty-two asthmatic children completed the clinical study. Twenty-eight patients were assigned to the treatment group and 24 to the placebo group. At the end of the treatment period, AHR determined by log PC(20) was significantly improved in the DCT group (0.51 +/- 1.05 mg/ml vs. 0.26 +/- 0.84 mg/ml, p = 0.034). The total clinical and medication reduced parameters showed improvement in the DCT group (p = 0.004). The AHR, symptom and medication scores in children with persistent asthma were significantly improved with DCT treat for 12 wk. The results suggested more stable airways achieved with such an add-on complementary therapy.     

Zanamivir for treatment of symptomatic influenza A and B infection in children five to twelve years of age: a randomized controlled trial

BACKGROUND: Influenza infection rates are higher in children than in other age groups. This study evaluated the efficacy, safety and tolerability of a 5-day course of twice daily inhaled zanamivir, 10 mg, compared with placebo in the treatment of symptomatic influenza A and B viral infections among children 5 to 12 years of age. METHODS: This double blind, randomized, placebo-controlled, parallel group, multicenter study conducted in the Northern Hemisphere during the 1998 and 1999 influenza season enrolled 471 patients with influenza-like symptoms for < or = 36 h. Patients were randomly assigned to zanamivir (n = 224) or placebo (n = 247). Symptoms were recorded on diary cards twice daily during treatment, for 9 days after treatment and for 14 additional days (if still reporting moderate/severe cough and/or taking relief medication). FINDINGS: A total of 346 (73%) patients were influenza-positive by culture, serology or polymerase chain reaction (65% influenza A, 35% influenza B). Zanamivir reduced the median time to symptom alleviation by 1.25 days compared with placebo among patients with confirmed influenza infection (P < 0.001). Zanamivir-treated patients returned to normal activities significantly faster and took significantly fewer relief medications than placebo-treated patients. Zanamivir was well-tolerated, demonstrating adverse event profiles similar to those of placebo and no clinically significant changes in laboratory findings. Viral susceptibility testing revealed no zanamivir-resistant strains of influenza A or B. CONCLUSIONS: Zanamivir was effective in shortening the duration and severity of influenza symptoms and was well-tolerated among children 5 to 12 years of age.     

The effect of beclomethasone dipropionate in ultrafine particles on bronchial hyper-reactivity in young children

Aim: Bronchial hyper‐reactivity (BHR) provides a tool for asthma diagnosis, assessment of severity and response to treatment. The effect of beclomethasone dipropionate in ultrafine particles (BDP‐HFA) on BHR as measured by the adenosine challenge test in young children has not yet been determined. Our aim was to determine the effect of BDP‐HFA (100 μg twice daily) on BHR as evaluated by a reduction of 20% from baseline FEV1 (PC20‐FEV1) values in young asthmatic children. Methods: Twenty‐one young children (13 males), mean age 4.95 ± 1.05 years, with partially controlled or controlled asthma completed a double‐blind randomized, placebo‐controlled, cross‐over study. Each child received 4 weeks of treatment with either 100 μg BDP‐HFA twice daily or placebo, and after a 2‐week washout period the other way around. Primary outcomes were PC20‐FEV1 concentration, and the stage number at which FEV1 values dropped by 20%. Results: Following 4 weeks of treatment, median PC20‐FEV1 was 81.28 mg/mL while on BDP‐HFA, compared with 9.64 mg/mL on placebo (p < 0.001). The median increase in stages required to achieve PC20 on BDP‐HFA compared with placebo was three (95% CI 2.28–4.86). Conclusion: Four weeks of treatment with BDP‐HFA resulted in significantly decreased BHR in young children.     

Randomized, prospective double-blind trial of metoclopramide and placebo for gastroesophageal reflux in infants

The effect of metoclopramide on gastroesophageal reflux was studied in 30 infants less than 1 year of age. Gastroesophageal reflux was documented in all infants by extended pH monitoring before enrollment in the study. Patients were randomly assigned to receive metoclopramide 0.1 mg/kg or placebo four times a day, 1/2 hour before feeding for 1 week, followed by the alternate regimen for 1 week. The infants were reevaluated with extended pH monitoring and scintigraphy after 4 to 7 days of each treatment. A symptom score was derived by determining the average number of occurrences of all symptoms recorded daily by parents on a symptom checklist during pretreatment, placebo, and metoclopramide treatment periods. There was a difference between pretreatment evaluation and placebo periods with respect to daily symptom scores (p less than 0.005), reflecting a significant placebo response. However, no difference in scintigraphic study was found between placebo and metoclopramide periods. A significant difference between placebo and metoclopramide periods was noted in the percentage of time esophageal pH was less than 4.0 (p less than 0.001). However, although metoclopramide decreased the proportion of time esophageal pH was less than 4.0, pH remained less than 4.0 for more than 5% of the time in most patients. Substratification of the total group into infants younger and older than 3 months revealed that older infants had greater average daily weight gain during the metoclopramide treatment period (34.3 gm/day) than in the placebo treatment period (6.6 gm/day, p = 0.05). We conclude that metoclopramide in the dosage 0.1 mg/kg four times daily reduces reflux in infants and may be useful for infants with poor weight gain and other serious complications of gastroesophageal reflux.     

Slow-release terbutaline and theophylline for the long-term therapy of children with asthma: a Latin square and factorial study of drug effects and interactions

To evaluate the long-term effects of slow-release formulations of theophylline and terbutaline on pulmonary function, clinical symptoms, and side effects, 24 children with stable and moderately severe perennial asthma participated in a prospective double-blind cross-over study. The patients and the treatments were randomized according to the Latin square design to eliminate all possible period/climate biases throughout the protracted study period. The treatments consisted of terbutaline, 5 mg, theophylline, 200 mg, the combination, and placebo, given twice daily orally and crossing over every 28 days. The two drugs, administered alone or in combination, improved lung function and symptoms when compared with placebo. The interaction of theophylline and terbutaline was quantitatively shown by 2 x 2 factorial statistical design to be essentially additive rather than synergistic in the control of asthma. No increase in side effects was noted when the combined therapy was used. These findings suggest therapeutic advantages to combining submaximal oral doses of sustained-release theophylline and terbutaline for the long-term treatment of children with asthma.     

Effects of nebulized corticosteroids therapy on hypothalamic–pituitary–adrenal axis in young children with recurrent or persistent wheeze

Inhaled corticosteroids (ICS) are preferred drugs for the long-term treatment of all severities of asthma in children. However, data about the safety of ICS in infants is lacking. So, it is essential to do further clinical studies to examine the safety and efficacy of ICS in this population. In this study, the effects of nebulized budesonide and nebulized fluticasone propionate suspensions on hypothalamic–pituitary–adrenal axis is examined in infants with recurrent or persistent wheeze. Thirty-one children aged 6–24 months admitted to our hospital between January and December 2005 with symptoms of recurrent or persistent wheeze were included in the study. The patients were randomly allocated to receive 0.25 mg BUD or 0.25 mg fluticasone propionate twice daily for 6 wk and half dose for another 6 wk with a jet nebulizer at home. Blood samples for basal cortisol concentration, adrenocarticotropic hormone, glucose, HbA1c and electrolytes were obtained at the beginning and at the end of the study. Adrenal function assessment was based on changes in cosyntropin-stimulated plasma cortisol levels. The study was completed with 31 patients, 16 of whom received BUD and 15 FP. All patients except one had plasma cortisol concentrations above 500 nmol/l (18 μg/dl) or had an incremental rise in cortisol of >200 nmol/l after stimulation. Although nebulized steroids seem to be safe in infancy, we recommend that adrenal functions should be tested periodically during long-term treatment with nebulized steroids.     

A placebo-controlled trial of cetirizine in seasonal allergic rhino-conjunctivitis in children aged 6 to 12 years

A total of 124 children of both sexes aged between 6 and 12 years with pollen-associated rhino-conjunctivitis were included in a multicentre double-blind study of parallel group design to compare the effects of cetirizine 10 mg daily, given as 5 mg morning and evening for 2 weeks, with those of placebo of identical appearance. Rhinorrhea, sneezing, nasal obstruction and nasal and ocular pruritus were evaluated using symptom scores by patients on daily self-evaluation cards and by investigators who, in addition, made a global evaluation at the end of treatment. Appropriate wash-out periods for previous medicines were observed. Unchanged treatment of asthma was allowed and inhaled corticosteroids were continued in 3 placebo patients. Compliance was checked and found to be less than 80% of the prescribed dosage in 2 cetirizine patients. The mean percentage of study days when symptoms were absent or at the most mild (i.e. present but not disturbing), as reported daily by the patients, was significantly greater with cetirizine (56.2%) than placebo (29.7%). This 26.5% difference was considered clinically significant. The value of this method of expressing treatment effects in allergic rhinitis is discussed. Improvement in maximum symptom scores (severest symptoms) assessed by investigators was better for cetirizine than placebo after treatment for 1 week and 2 weeks. Improvement in individual daily symptoms was greater for cetirizine than placebo after a few days. Global evaluations of response by investigators at the end of the study showed improvement in both groups that was significantly greater with cetirizine, providing a response that was considered excellent or good in 79% of patients on cetirizine compared with 50% of patients on placebo. Tolerance was good. Somnolence that was generally mild and transient was reported in 6 patients of the cetirizine group and in 2 patients of the placebo group.     

Multicenter study with ketotifen (Zaditen) oral drop solution in the treatment of wheezy children aged 6 months to 3 years

One hundred and seven chronically wheezing infants, aged 6 months to 3 years, completed a double-blind placebo controlled multicenter study. Alter a two-week baseline period the patients were randomized into two groups receiving twice daily either ketotifen or placebo for a period of 12 weeks. The ketotifen dosage was 0. 5 mg for children younger than one year and 1 mg for the older. During the 12-week treatment period the patients from the two groups demonstrated gradual improvement of the disease severity parameters, as compared with the baseline period. The amelioration was more marked in the ketotifen treated patients and during the 0-4, and 4-8 weeks of treatment a significant decrease was achieved in the percentage of days with a cough (p < 0.04) and in the number of wheezing episodes (p = 0.02). Moreover, a 50% reduction of the days and nights with cough and in the number of wheezing episodes occurred earlier in the ketotifen than in the placebo treated patients, i. e. after 1. 2 vs 4. 6; 4. 4 vs 8. 6 and 5. 2 vs 7. 2 weeks, respectively. It should be stressed that the ameloration of the asthmatic morbidity in the ketotifen group was achieved with a significantly reduced need for the concomitant use of bronchodilators. The principal side effects observed were weight gain and transient sedation. It is concluded that ketotifen may be effective in the amelioration of asthma associated symptomatology and acceleration in the natural tendency for improvement in chronic wheezing infants.