Safety and effectiveness of terbutaline in children with chronic asthma.

The bronchodilator and cardiovascular effects of orally administered tablets containing 2.5 mg of terbutaline and 25 mg of ephedrine were compared in a double-blind parallel manner in children (ages, 7 to 14 years) weighing 25 to 50 kg (44 to 110 lb). Both drugs produced bronchodilation within one-half hour, and this effect was maintained up to six hours, with a peak between two and three hours. Small increases in the pulse rate were measured within an hour following administration of both drugs. No significant variation was noted in blood pressure. No adverse effects (including tachyphylaxis and tremor) were observed for either drug during a three-month period. Both bronchodilator agents were shown to be equally effective in the dosages used. Terbutaline is a safe bronchodilator drug when administered orally in 2.5-mg doses for children with chronic asthma in this range of ages and weights, with minimal cardiovascular side effects and effective bronchodilation.     

Treatment of exercise-induced asthma with beclomethasone dipropionate in children with asthma.

A new hydrofluoroalkane-beclomethasone dipropionate (HFA-BDP) aerosol markedly increases drug delivery to the airways. Therefore, even low doses of HFA-BDP should be effective, and the present study assesses this. A randomised, double-blind, crossover study was used to compare the effect of placebo, HFA-BDP 50 microg or 100 microg given q.d. (QVAR(TM) Autohaler(TM); 3M Pharmaceuticals, St. Paul, MN, USA) on exercise-induced bronchoconstriction and exhaled nitric oxide (eNO). After a 14-day run-in, 25 children (5-14 yrs old) entered three 4-week treatment periods, separated by a 1-week washout. After each period, the fall in forced expiratory volume in one second (FEV1), after an exercise test, and eNO were measured. Significant treatment effects with no carry-over or period effects were seen for both eNO and maximum fall in FEV1 after exercise. Differences were seen between placebo (fall in FEV1=27.9%; eNO=14.4 parts per billion (ppb)) and either dose of HFA-BDP, but not between the two active doses (50 microg: fall in FEV1=20.8%, eNO=9.3 ppb; 100 microg: fall in FEV1=20.9%, eNO=8.9 ppb). In conclusion, low q.d. doses of hydrofluoroalkane-beclomethasone dipropionate reduced exhaled nitric oxide and exercise-induced bronchoconstriction. Further studies are needed to assess whether q.d. administration of beclomethasone dipropionate is as effective as b.i.d. administration.     

Effects of ipratropium bromide nebulizer solution with and without preservatives in the treatment of acute and stable asthma.

In a recent study, it was suggested that the preservatives in ipratropium bromide nebulizer solution may cause a paradoxic bronchoconstrictor response in 20 percent or more of patients with stable asthma. The frequency of this response in patients with acute asthma is unknown. The aim of this study was to examine the acute effects of the usual dose of nebulized ipratropium bromide (0.25 mg) in patients with either stable or acute asthma using formulations with and without added preservatives. Twenty-five patients with stable asthma and 25 patients with acute asthma were studied. Each subject was given preservative-containing ipratropium bromide, preservative-free ipratropium bromide, pH 7 preservative-free ipratropium bromide, and saline solution in random order using a double-blind crossover technique with at least 4 h between drug administrations. Very frequent measurements of FEV1 were made for 30 min after each drug administration and then 5 mg of albuterol was nebulized and the FEV1 was measured again after another 30 min. Changes in FEV1 were expressed as a percentage of the predicted FEV1. Paradoxic bronchoconstriction to ipratropium was detected in only one patient with acute asthma (12 percent fall in FEV1) but in none of the patients with stable asthma. A 6 percent fall in FEV1 change occurred with the saline solution in this subject suggesting that the response may have been a nonspecific one due to increased bronchial responsiveness. The mean response (+/- 1 SD) to albuterol plus either preservative-containing ipratropium, preservative-free ipratropium, or pH7 preservative-free ipratropium was significantly greater (p less than 0.05) than the response to albuterol alone both in the patients with acute asthma (25 +/- 12 percent, 27 +/- 15 percent, 26 +/- 15 percent, and 20 +/- 15 percent, respectively) and stable asthma (26 +/- 7 percent, 25 +/- 8 percent, 24 +/- 6 percent, and 22 +/- 9 percent) supporting the use of ipratropium bromide as an additional bronchodilator in patients with asthma who do not show a satisfactory response to nebulized beta-adrenergic agonist.     

Rural children with asthma: impact of a parent and child asthma education program.

The goal of this study was to determine the effectiveness of an asthma educational intervention in improving asthma knowledge, self-efficacy, and quality of life in rural families. Children 6 to 12 years of age (62% male, 56% white, and 22% Medicaid) with persistent asthma (61%) were recruited from rural elementary schools and randomized into the control standard asthma education (CON) group or an interactive educational intervention (INT) group geared toward rural families.Parent/caregiver and child asthma knowledge, self-efficacy, and quality of life were assessed at baseline and at 10 months post enrollment. Despite high frequency of symptom reports, only 18% children reported an emergency department visit in the prior 6 months. Significant improvement in asthma knowledge was noted for INT parents and young INT children at follow-up (Parent: CON = 16.3; INT = 17.5, p < 0.001; Young children: CON = 10.8, INT = 12.45, p < 0.001). Child self-efficacy significantly increased in the INT group at follow-up; however, there was no significant difference in parent self-efficacy or parent and child quality of life at follow-up. Asthma symptom reports were significantly lower for the INT group at follow-up. For young rural children, an interactive asthma education intervention was associated with increased asthma knowledge and self-efficacy, decreased symptom reports, but not increased quality of life.     

Clinical usefulness of inflammatory markers in asthma

Asthma is a significant and increasing health problem. Airway inflammation and hyperresponsiveness are key pathophysiological mechanisms underlying asthma. Currently, effective treatments target these two processes and can lead to clinically important improvements in disease control. At present, decisions to initiate or modify therapy are based on symptoms and measures of airway caliber, with no direct assessment of airway inflammation or hyperresponsiveness. It is now possible to measure airway inflammation using noninvasive markers such as exhaled gases, induced sputum and serum measurements. Exhaled nitric oxide (eNO) and induced sputum eosinophils show the greatest promise as clinically useful markers of airway inflammation in asthma. Induced sputum can now be applied to the diagnosis of airway diseases, based on its ability to detect eosinophilic bronchitis in cough, and to differentiate between eosinophilic and non-eosinophilic asthma. The place of induced sputum and eNO in the ongoing monitoring of patients with asthma are now being investigated in controlled trials.     

The development and establishment of a care map in children with asthma in Taiwan.

BACKGROUND: It is often difficult to predict the timing and frequency of asthma attacks. In addition to interrupting the daily life of both the affected child and his/her family, asthma can also pose sudden danger to a child. Based on clinical observations, many asthma-affected children and their parents must constantly adjust themselves to the uncertainty of the disease, which leads to increased stress on the family. The use of care maps has demonstrated increased efficiency and effectiveness in the care of asthma patients from a variety of settings. OBJECTIVE: We designed this study to construct and evaluate a care map for asthmatic children in Taiwan. Specific attention was placed on comparing the study and control subjects by parental knowledge of asthma, medication used for asthma, hospital readmission, and health care resource usage. SUBJECTS AND METHODS: The care map was constructed by in-depth interviews with eight sets of parents of children with asthma. Forty-four parents of 42 asthma children were randomized into two groups in the Allergic Clinic of the Chang Gung Children's Hospital. The experimental group of 22 parents received individual instruction and training sessions in addition to the regular care provided to the control group of 22 parents. RESULTS: Forty-two children with asthma were surveyed in this study. To examine the reliability and validity of a care map for children with asthma, a quantitative survey was conducted with 42 outpatient parents with asthmatic children. There was less emergency room attending rate in experimental group (6/month; p<0.05) The understanding of the disease was much improved in parents of experimental group (13.85+/-1.04 vs. 10.91+/-2.14; p<0.01). Furthermore, parents acquired a more positive attitude to asthma, and almost all of the control group had irregular follow-ups by a physician and had irregular use of medication. CONCLUSION: This study emphasizes that a care map in children with asthma (CACM) can be used to educate parents in how to provide the best treatment plan for their children. This study also shows how a CACM can help parents train their children in the best behaviors during asthma attacks. Empathetic assessment and elimination of cultural barriers, a well-designed educational program, and a mutually developed treatment plan could significantly improve the quality of life for families and specific asthma outcomes.     

Safety of a cyclooxygenase-2 inhibitor in patients with aspirin-sensitive asthma

BACKGROUND: In 5 to 10% of adult patients with asthma, aspirin (acetylsalicylic acid [ASA]) and most other nonsteroidal anti-inflammatory drugs (NSAIDs) precipitate acute asthmatic attacks. Therefore, choosing an alternative anti-inflammatory agent for patients with adverse reactions to an NSAID is a common problem in clinical practice. The discoveries that cyclooxygenase (COX)-2 is an inducible form of COX that is involved in inflammation and that COX-1 is the major isoform responsible for the production of prostaglandins have provided a reasonable basis for the development of specific COX-2 inhibitors as a new class of anti-inflammatory agents. OBJECTIVE: The purpose of this study was to demonstrate that rofecoxib, a specific inhibitor of COX-2, does not cause asthmatic attacks in patients with ASA and/or other NSAID-induced asthma. METHODS: We studied 40 patients, all of whom had experienced asthma induced by at least two different NSAIDs. The patients were challenged in a single-blind manner with different doses of rofecoxib on 3 different days, until either the therapeutic dose of 25 mg or intolerance was reached. Each patient was rechallenged with 25 mg of rofecoxib 7 days later if no evidence of intolerance had been observed previously. RESULTS: Rofecoxib, 25 mg, was proven to be well tolerated in all 40 patients with ASA-induced and NSAID-induced asthma. CONCLUSION: Our study appears to demonstrate that rofecoxib is a suitable NSAID for treatment of patients with ASA and/or other NSAID-induced asthma.     

Poor perception of airway obstruction in children with asthma.

The aims of this study were to evaluate children's perception of asthma symptoms and to determine a clinically useful method for identifying poor patient perception of airway obstruction. Three methods were used to analyze the relationships among indices of lung function and perception of breathlessness in 35 children. Approximately half the children in our sample did not perceive either airway obstruction or bronchodilation. We propose that <20% improvement in visual analog scale scores post-bronchodilation may provide a simple index for identifying patients with poor perception of airway obstruction, who may be at risk for fatal or near-fatal asthma.     

Poor perception of dyspnoea in children with undiagnosed asthma.

The aim of the present study was to establish the differences in dyspnoea perception between children with undiagnosed and diagnosed asthma. A cross-sectional community-based study was performed, which included a parental questionnaire on the child's respiratory health and testing of airway reversibility and bronchial hyperresponsiveness (BHR). "Diagnosed asthma" was defined by a physician's diagnosis of asthma. "Undiagnosed asthma" was defined by the presence of asthma symptoms combined with either airway reversibility or BHR without a physician's diagnosis of asthma. Only children with a positive BHR test were selected for further analysis. Perception of dyspnoea was assessed using the Borg scale and the visual analogue scale (VAS), plotted against the percentage fall in forced expiratory volume in one second and expressed as the slope of the regression line. Of the initial 1,758 participating children, 70 had undiagnosed asthma and 38 had diagnosed asthma. The Borg and VAS slopes in children with undiagnosed asthma were less steep than those of children with diagnosed asthma (Borg: 0.07 and 0.14, respectively; VAS: 0.06 and 0.11, respectively). Among children with bronchial hyperresponsiveness, those without a parent's report of physician's diagnosis of asthma had a worse perception of dyspnoea than children with diagnosed asthma.     

Paternal history of asthma and airway responsiveness in children with asthma

RATIONALE: Little is known regarding the relationship between parental history of asthma and subsequent airway hyperresponsiveness (AHR) in children with asthma. OBJECTIVES: We evaluated this relationship in 1,041 children with asthma participating in a randomized trial of antiinflammatory medications (the Childhood Asthma Management Program [CAMP]). METHODS: Methacholine challenge testing was performed before treatment randomization and once per year over an average of 4.5 years postrandomization. Cross-sectional and longitudinal repeated measures analyses were performed to model the relationship between PC20 (the methacholine concentration causing a 20% fall in FEV1) with maternal, paternal, and joint parental histories of asthma. Models were adjusted for potential confounders. MEASUREMENTS AND MAIN RESULTS: At baseline, AHR was strongly associated with a paternal history of asthma. Children with a paternal history of asthma demonstrated significantly greater AHR than those without such history (median log(e)PC20, 0.84 vs. 1.13; p = 0.006). Although maternal history of asthma was not associated with AHR, children with two parents with asthma had greater AHR than those with no parents with asthma (median log(e)PC20, 0.52 vs. 1.17; p = 0.0008). Longitudinal multivariate analysis of the relation between paternal history of asthma and AHR using repeated PC20 measurements over 44 months postrandomization confirmed a significant association between paternal history of asthma and AHR among children in CAMP. CONCLUSIONS: Our findings suggest that the genetic contribution of the father is associated with AHR, an important determinant of disease severity among children with asthma.     

Thresholds of resistive load detection in children with asthma.

Threshold detection of added resistive loads was studied in asthmatic children and compared to data previously obtained in a group of healthy children. The relationships between possible psychological predictors of perceptual ability, the perceptual threshold, and functional morbidity variables were also investigated. Our subjects were 103 children (mean age, 10.9 years) with asthma who completed two laboratory protocols in which they were asked to distinguish breaths with varying degrees of added resistance from unloaded breaths. Using two different computer-driven protocols, resistances were presented as percentages of each child's intrinsic respiratory system resistance (R(rs)). Cognitive ability was assessed through subtests of the Wechsler Intelligence Scale for Children, 3rd edition (WISC-III), and functional morbidity was quantified through a combination of school absences, emergency medical visits, and days hospitalized. Detection thresholds for both protocols were highly correlated with intrinsic resistance (r = 0.49 and 0.66; P < 0.001). Weber fraction thresholds were significantly lower for asthmatic children than healthy controls. Thresholds were not significantly related to either intelligence or pulmonary functional abnormalities due to asthma. Methodologic limitations require cautious interpretation of the results, but we conclude that psychophysical approaches may be useful in the study of symptom perception in pediatric asthma.     

Patient compliance in a clinical trial with inhaled budesonide in children with mild asthma.

Children's use of inhalation devices can give valuable information about their adherence to asthma therapy. The aim of this study was to examine treatment adherence of low dose inhaled budesonide or placebo administered via Turbuhaler twice daily in children with mild asthma participating in an asthma trial, by comparing diary registration with the number of doses remaining in the inhaler. A total of 163 children (age 7-16 yrs, 56 females, 107 males) with mild asthma (mean baseline forced expiratory volume in one second (FEV1) was 103% of predicted), were included into a double blind, randomized study. After a two-week run-in period, the children received inhaled budesonide, either 100 microg or 200 microg daily, and/or placebo for 12 weeks. All patients used daily diary cards throughout the study. Results from 161 patients were analysed. Mean compliance according to the diary was 93%, whereas estimated mean compliance when counting remaining doses in the Turbuhaler was 77%. Overuse of medication was found in 7% of the children. There was no significant difference in compliance between sex in the study group, whereas children aged < or =9 yrs had significantly better drug adherence than older children. No significant relationship was found between symptom score and compliance. In conclusion, even with optimal patient follow-up in a clinical trial, adherence to prophylactic asthma treatment is considerably lower than the patients own reports from the use of daily diary cards.     

Delivery of albuterol and ipratropium bromide from two nebulizer systems in chronic stable asthma. Efficacy and pulmonary deposition

Bronchodilator responses to both nebulized albuterol (salbutamol) and ipratropium bromide and aerosol delivery to the tracheobronchial tree have been assessed in eight patients with chronic stable asthma (mean baseline FEV1, 50 percent; reversibility greater than 20 percent). Two commercially available nebulizer systems were used, namely, a Turret nebulizer operated at a compressed gas flow rate of 12 L/min (droplet MMD, 3.3 mu) and an Inspiron nebulizer driven at 6 L/min (MMD, 7.7 mu). Albuterol was given as doses of 250 micrograms, 250 micrograms, 500 micrograms, and 1,000 micrograms (cumulative dose, 2 mg) and ipratropium bromide as doses of 50 micrograms, 50 micrograms, 100 micrograms, and 200 micrograms (cumulative dose, 400 micrograms) at intervals of 35 minutes. For albuterol, bronchodilatation was significantly (p less than 0.05) greater at all dosage levels with the Turret. For ipratropium, bronchodilatation was similar for both nebulizers. Measurements of aerosol deposition using 99mTc-labelled pentetic acid (diethylenetriamine pentaacetic acid; DTPA) showed that 9.1 +/- 1.1 percent and 2.7 +/- 0.2 percent of the dose reached the lungs during nebulization to dryness for Turret and Inspiron, respectively (p less than 0.01); distribution within the lungs was similar for the two aerosols. Selection of nebulizer apparatus can influence delivery of aerosol and subsequent bronchodilator response to albuterol in patients with chronic stable asthma but is less important for aerosol delivery of ipratropium bromide in these patients.