Wade Watson

Treatment of allergic rhinitis with intranasal corticosteroids in patients with mild asthma: Effect on lower airway responsiveness

The effect of treatment of allergic rhinitis with intranasal corticosteroids on lower airway responsiveness was assessed in a randomized, double-blind, placebo-controlled, crossover study. Twenty-one young patients with perennial allergic rhinitis and asthma, with documented lower airway hyperresponsiveness (PC20 methacholine < 8 mg/ml), were treated with intranasal aqueous beclomethasone dipropionate and placebo, each given for 4 weeks. Patients recorded rhinitis and asthma symptom scores and monitored peak expiratory flow rates every morning and evening. Patients recorded global assessment of rhinitis and global asthma symptom scores at the beginning and end of each treatment. PC20 methacholine was performed at baseline and at the end of each treatment period. Intranasal beclomethasone dipropionate significantly reduced global rhinitis symptom scores (p = 0.05) after 4 weeks of treatment. Global asthma scores did not change significantly (p = 0.2). Geometric mean PC20 methacholine improved significantly after 4 weeks of intranasal beclomethasone, but not after placebo (p = 0.04). Daily morning and evening rhinitis symptom scores were lower in patients treated with intranasal corticosteroids over the first 4 weeks of treatment, but carryover effect of steroids precluded comparative analysis of the second 4-week block (morning p = 0.06, evening p = 0.03). Morning asthma scores tended to decrease (p = 0.07). Evening asthma scores were significantly decreased at weeks 2 and 3 (p = 0.001, p = 0.02, respectively). No change in peak expiratory flow rate was seen. This study confirms that treatment of inflammation in the upper airways indirectly improves asthma symptoms and decreases bronchial hyperreactivity. Ignoring inflammation in the upper airway may lead to suboptimal results in asthma treatment.

Pharmacokinetics and pharmacodynamics of terfenadine and chlorpheniramine in the elderly

In a double-blind, randomized, crossover study, the H1-receptor antagonists, terfenadine and chlorpheniramine, were investigated in eight healthy, fasting female subjects, aged 67.8 +/- SD 0.8 years, who ingested single doses of terfenadine, 1 mg/kg (mean dose, 69.6 +/- 11.2 mg), and chlorpheniramine, 0.12 mg/kg (mean dose, 8.4 +/- 1.3 mg). The mean serum-elimination half-life of terfenadine metabolite I was 8.7 +/- 3.7 hours. After terfenadine ingestion, significant wheal suppression occurred from 2 to 24 hours compared to predose wheal size, with maximum wheal suppression, 42 +/- 13% to 60 +/- 16% from 2 to 12 hours. Significant flare suppression occurred from 2 to 24 hours, with maximum flare suppression, 75 +/- 15% to 78 +/- 13% from 4 to 8 hours. The mean serum-elimination half-life of chlorpheniramine was 22.6 +/- 11.0 hours. After chlorpheniramine ingestion, significant wheal suppression occurred from 1 to 10 hours, inclusive, compared to predose wheal size, with maximum wheal suppression, 36 +/- 11% to 37 +/- 11% from 5 to 6 hours. Significant flare suppression occurred from 1 to 12 hours, with maximum flare suppression of 43 +/- 14% to 46 +/- 19% at 2, 5, and 6 hours (p less than 0.01). Adverse effects, chiefly sedation, occurred in five of eight patients after receiving terfenadine, and in all eight patients after receiving chlorpheniramine; but, since no placebo control was administered, these adverse effects could not be definitely attributed to H1-receptor-antagonist ingestion.

Genetic variants of the IL13 and IL4 genes and atopic diseases in at-risk children

We studied a cohort containing 368 children at high risk of developing atopy and atopic disorders and 540 parents of those children to investigate whether the IL13 Arg130Gln and C−1112 T polymorphisms were associated with these outcomes. We also investigated whether haplotypes consisting of any two polymorphisms of IL13 Arg130Gln, IL13 C−1112 T and IL4 C−589 T were associated with these phenotypes. In 288 white children, the IL13 130Gln allele was associated with atopy (RR=1.9, P=0.047), and with atopic dermatitis (RR=2.5, P=0.014). The associations were confirmed using a family-based test of association (P=0.027 and 0.030, respectively) in all subjects. In white subjects there were associations of haplotypes consisting of IL13 Arg130Gln and IL4 C−589 T with atopic dermatitis (P=0.006) and with atopy (P=0.009). Our data suggest that the IL13 Arg130Gln polymorphism and haplotypes consisting of IL13 Arg130Gln and IL4 C−589 T were associated with the development of atopy and atopic dermatitis at 24 months of age.

Canadian Pediatric Asthma Consensus Guidelines, 2003 (updated to December 2004): Introduction

Background: Although guidelines for the diagnosis and management of asthma have been published over the last 15 years, there has been little focus on issues relating to asthma in childhood. Since the last revision of the 1999 Canadian asthma consensus report, important new studies, particularly in children, have highlighted the need to incorporate this new information into asthma guidelines. Objectives: To review the literature on asthma published between January 2000 and June 2003 and to evaluate the influence of new evidence on the recommendations made in the Canadian Asthma Consensus Report, 1999 and its 2001 update with a major focus on pediatric issues. Methods: Diagnosis of asthma in young children, prevention strategies, pharmacotherapy, inhalation devices, immunotherapy and asthma education were selected for review by small expert resource groups. In June 2003, the reviews were discussed at a meeting under the auspices of the Canadian Network For Asthma Care and the Canadian Thoracic Society. Data published up to December 2004 were subsequently reviewed by the individual expert resource groups. Results: This report evaluates early life prevention strategies and focuses on treatment of asthma in children. Emphasis is placed on the importance of an early diagnosis and prevention therapy, the benefits of additional therapy and the essential role of asthma education. Conclusion: We generally support previous recommendations and focus on new issues, particularly those relevant to children and their families. This guide for asthma management is based on the best available published data and the opinion of health care professionals including asthma experts and educators.

Diphenhydramine: Pharmacokinetics and Pharmacodynamics in Elderly Adults, Young Adults, and Children

The pharmacokinetics and pharmacodynamics of the H1‐receptor antagonist diphenhydramine were studied in 21 fasting subjects divided into three age groups: elderly, (mean age 69.4 ± 4.3 years), young adults, (mean age 31.5 ± 10.4 years), and children, (mean age 8.9 ± 1.7 years). All subjects ingested a single dose of diphenhydramine syrup 1.25 mg/kg, in mean doses of 86.0 ± 7.3 mg, 87.9 ± 12.4 mg, and 39.5 ± 8.4 mg, respectively. Blood samples were collected hourly for 6 hours, every 2 hours until 12 hours, at 24 hours, and, in the adults, up to 72 hours after diphenhydramine administration. At these times, histamine skin tests were performed and wheal and flare areas were computed. The mean serum elimination half‐life values for diphenhydramine differed significantly in elderly adults, young adults, and children, with values of 13.5 ± 4.2 hours, 9.2 ± 2.5 hours, and 5.4 ±1.8 hours being found respectively in each age group. Clearance rates for diphenhydramine also differed significantly with age, being 11.7 ± 3.1 mL/min/kg in elderly adults, 23.3 ± 9.4 mL/min/kg in young adults and 49.2 ± 22.8 mL/min/kg in children. Diphenhydramine produced a maximum wheal suppression of 39.6 ± 22.5% and a maximum flare suppression of 46.5 ± 32.1% at 5 and 6 hours respectively in the elderly, a maximum wheal suppression of 45.5 ± 25.0% and a maximum flare suppression of 53.4 ± 16.9% at 6 and 4 hours respectively in young adults; and a maximum wheal suppression of 68.4 ± 10.2% and a maximum flare suppression of 87.2 ± 4.2% at 2 hours in children.

Cetirizine: A pharmacokinetic and pharmacodynamic evaluation in children with seasonal allergic rhinitis

In a double-blind, randomized, parallel-group 5-week study, cetirizine, 5 mg or 10 mg daily, was ingested by 10 and nine children, respectively. Cetirizine was rapidly absorbed with mean peak cetirizine concentrations of 427.6 +/- SD, 144.2 ng/ml, 1.4 +/- 1.1 hours after the 5 mg dose, and 978.4 +/- 340.6 ng/ml, 0.8 +/- 0.4 hours after the 10 mg dose. The dose-independent serum-elimination half-life of cetirizine was 7.1 +/- 1.6 hours after cetirizine, 5 mg, and 6.9 +/- 1.6 hours after cetirizine, 10 mg. Urinary excretion of unchanged cetirizine during 24 hours after the initial dose of cetirizine, 5 mg, was 40 +/- 15%, and after cetirizine, 10 mg, it was 39 +/- 14%. The mean histamine-induced wheal-and-flare areas were significantly suppressed from 1 to 24 hours after the first dose of cetirizine, 5 mg, and from 1/2 to 24 hours after the first dose of cetirizine, 10 mg, compared to the mean predose wheal-and-flare areas (p less than 0.01). During daily dosing with cetirizine, 5 mg or 10 mg at bedtime for 35 days, serum cetirizine concentrations and suppression of histamine-induced wheals and flares were monitored every 7 days, 12 hours after the cetirizine dose. The mean serum cetirizine concentrations remained relatively stable during this time, and the mean wheal-and-flare areas remained significantly suppressed (p less than 0.01) compared to baseline wheal-and-flare areas measured before the first dose of cetirizine. The symptoms and signs of allergic rhinitis were suppressed throughout the study by cetirizine, 5 mg and 10 mg.(ABSTRACT TRUNCATED AT 250 WORDS)

Cord blood IgE: its determinants and prediction of development of asthma and other allergic disorders at 12 months

BACKGROUND The value of cord blood IgE in predicting the development of asthma and other IgE-mediated allergic diseases is unclear. OBJECTIVE The purpose of this study is twofold: (1) to determine factors affecting cord blood IgE level and (2) to determine whether cord blood IgE predicts the development of asthma and other IgE-mediated allergic diseases in high risk (defined as those with at least one first degree relative with asthma or 2 first degree relatives with other IgE-mediated allergic diseases) infants at 12 months. METHODS The study utilized cord blood obtained from a group of high risk infants who took part in a randomized controlled trial to assess the effectiveness of an intervention program in the primary prevention of asthma and other IgE-mediated allergic diseases. Total IgE and cotinine in the cord blood were measured. Assessment of the infants was done at 12 months for these diseases. RESULTS Sixty-four (17.8%) infants had detectable total IgE in cord blood >0.5 kU/L. The proportion of infants with elevated cord blood IgE was significantly higher among nonwhites, birth during winter months, and those with a maternal history of asthma. There was no correlation between cord blood IgE and cord blood cotinine level. Cord blood IgE was found to be a significant predictor for the development of urticaria due to food allergy but not for other outcomes. CONCLUSION Both genetic and environmental risk factors play a role in determining the level of IgE in cord blood. Cord blood IgE was a significant risk factor for the development of urticaria due to food allergy at 12 months of life. As urticaria due to food allergy is a prodrome for anaphylaxis, measurement of IgE in cord blood may be indicated in infants at high risk for developing allergic diseases so that preventive measures can be applied.

Comparison of ipratropium solution, fenoterol solution, and their combination administered by nebulizer and face mask to children with acute asthma

In a randomized, double-blind, parallel-group trial, 47 children with acute asthma received a combination of ipratropium bromide solution (250 micrograms) and fenoterol hydrobromide solution (625 micrograms), fenoterol solution (625 micrograms) alone, or ipratropium solution (250 micrograms) alone, administered by face mask and nebulizer, with the dose repeated 60 minutes later. The groups did not differ significantly with regard to age, pulmonary function at baseline, or any other variable. They were monitored at 30, 60, 90, and 120 minutes by use of a clinical score, oxygen saturation, and pulmonary function tests. At the end of the study, albuterol was administered to assess residual bronchoconstriction. Clinical scores improved significantly after treatment in all groups at all times compared with baseline. The greatest improvement in FEV1 was seen in the patients treated with ipratropium/fenoterol, whether considered as absolute change, change in percent predicted, or percent change from baseline. Ipratropium/fenoterol was significantly better than fenoterol alone only when considered as percent change from baseline. Improvement in flow at mid and low lung volumes was significantly greater for the ipratropium/fenoterol combination than for ipratropium alone; no significant differences were noted between ipratropium/fenoterol and fenoterol for flow at mid and low lung volumes. Treatment with albuterol did not significantly improve pulmonary function in the groups receiving ipratropium/fenoterol or fenoterol alone, but it did increase flow at all lung volumes in the group receiving ipratropium alone. No patient complained spontaneously of any adverse reactions, and no clinically significant changes in heart rate or systolic or diastolic blood pressures occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchodilator and bronchoprotective effects of salmeterol in young patients with asthma.

BACKGROUND In adults with asthma, the selective beta 2-adrenergic agonist salmeterol has a prolonged bronchodilator and bronchoprotective effect. To date, there are few published studies of salmeterol in children. METHODS We compared the bronchodilator and bronchoprotective effects of salmeterol, 25 and 50 micrograms, with salbutamol, 200 micrograms, and with placebo, administered via metered-dose inhaler, in a randomized, double-blind, within-patient, four-way crossover, single-dose study in 20 children. RESULTS Mean baseline forced expiratory volume in 1 second (FEV1) and PC20 methacholine were not significantly different (p > 0.05) on the 4 study days, and did not change significantly after placebo. FEV1 increased significantly from 5 to 30 minutes after salbutamol, and from 5 minutes to 12 hours after 25 micrograms or 50 micrograms salmeterol, compared with placebo. After 25 micrograms or 50 micrograms salmeterol, FEV1 was significantly lower than after salbutamol at 5 and 10 minutes, did not differ from salbutamol at 30 minutes, and was significantly greater than after salbutamol from 3 to 12 hours. No significant difference occurred between the effect of 25 micrograms salmeterol and the effect of 50 micrograms salmeterol on FEV1. After salbutamol, there was a significant increase in PC20 only at 30 minutes. After 25 micrograms or 50 micrograms salmeterol, PC20 increased significantly from 30 minutes to 12 hours. Salmeterol, 25 micrograms and 50 micrograms provided significantly greater bronchoprotection than salbutamol from 3 to 12 hours and from 30 minutes to 12 hours, respectively. Salmeterol, 50 micrograms, provided significantly better bronchoprotection than 25 micrograms salmeterol from 30 minutes to 12 hours. The amount of change in PC20 accounted for by change in FEV1 varied from 14% to 28%, indicating that protection against bronchoconstriction was not entirely dependent on bronchodilation. CONCLUSIONS Salmeterol is a potent, long-acting bronchodilator, with a slower onset of bronchodilation than salbutamol. It provides significantly greater and longer-lasting protection against bronchoconstriction than salbutamol.

Small-group, interactive education and the effect on asthma control by children and their families

Background: Effective approaches to education about asthma need to be identified. We evaluated the impact on asthma control by children and their caregivers of an intervention involving small-group, interactive education about asthma. Methods: We randomly assigned children who visited an emergency department for an exacerbation of asthma (n = 398) to either of 2 groups. Children assigned to the control group followed the usual care recommended by their primary care physician. Those assigned to the intervention group participated in a small-group, interactive program of education about asthma. We examined changes in the number of visits to the emergency department during the year after the intervention. Results: During the year after enrolment, children in the intervention group made significantly fewer visits to the emergency department (0.45 visits per child) compared with those in the control group (0.75 visits per child) (p = 0.004). The likelihood of a child in the intervention group requiring emergency care was reduced by 38% (relative risk [RR] 0.62, 95% confidence interval CI 0.48–0.81, p = 0.004). Fewer courses of oral corticosteroids (0.63 per child) were required by children in the intervention group than by those in the control group (0.85 per child) (p = 0.006). We observed significant improvements in the symptom domain of the questionnaire on pediatric asthma quality-of-life (p = 0.03) and the activity domain of the questionnaire on caregivers’ quality of life (p = 0.05). Parents of children in the intervention group missed less work because of their child’s asthma after participating in the educational program (p = 0.04). No impact on hospital admissions was observed. Interpretation: Education about asthma, especially in a small-group, interactive format, improved clinically important outcomes and overall care of children with asthma.