Gail G. Shapiro

Montelukast once daily inhibits exercise-induced bronchoconstriction in 6- to 14-year-old children with asthma☆☆☆★★★

OBJECTIVE To determine whether montelukast, a leukotriene receptor antagonist, attenuates exercise-induced bronchoconstriction (EIB) in 6- to 14-year-old children with asthma. STUDY DESIGN Double-blind, multicenter, 2-period crossover study. Children (n = 27) with forced expiratory volume in 1 second (FEV1) > or =70% of the predicted value and a fall in FEV1 > or =20% after exercise on 2 occasions. Patients received montelukast (5-mg chewable tablet) or placebo once daily in the evening for 2 days in crossover fashion (at least 4 days between treatment periods). Standardized exercise challenges were performed 20 to 24 hours after the last dose in each period. End points included area above the postexercise percent fall in FEV1 versus time curve (AAC0-60 min), maximum percent fall in FEV1 from pre-exercise baseline, and time to recovery of FEV1 to within 5% of pre-exercise baseline. RESULTS Montelukast significantly reduced AAC0-60 min (265 vs 590% x min for montelukast and placebo, respectively, P < or = .05; approximately 59% protection relative to placebo) and the maximum percent fall (18% vs 26% for montelukast and placebo, respectively, P < or = .05). Montelukast treatment resulted in a shorter time to recovery (18 vs 28 minutes for montelukast and placebo, respectively, P = .079). CONCLUSIONS Montelukast attenuates EIB at the end of the dosing interval in 6- to 14-year-old children with asthma.

The relationships among environmental allergen sensitization, allergen exposure, pulmonary function, and bronchial hyperresponsiveness in the Childhood Asthma Management Program ☆ ☆☆ ★

BACKGROUND Sensitivity and exposure to indoor allergens constitutes a risk factor for the development and persistence of asthma in children. OBJECTIVE Our purpose was to evaluate the relationship between sensitivity and exposure to inhalant allergens and lung function and bronchial responsiveness in a group of children (n = 1041) aged 8.9 +/- 2.1 years with mild to moderate asthma enrolled in the Childhood Asthma Management Program (CAMP). METHODS With use of the extensive CAMP baseline cross-sectional data on spirometry, bronchial responsiveness, allergen sensitivities, and household allergen levels, the relationship of sensitization and exposure to allergens to lung function and methacholine sensitivity was evaluated. Children who enrolled in CAMP stopped all antiasthma medication except rescue use of albuterol and prednisone for exacerbations during the 5- to 16-week screening period. During the last 2 of these weeks they underwent spirometry and methacholine challenge. Indoor allergen exposures were determined from questionnaires completed by the parent. Household levels of indoor allergens (mite, cat, dog, cockroach, mold) were determined on house dust samples. Allergen sensitivity was determined by percutaneous skin testing with a standard battery of allergens plus locally important pollen and fungal spores. Lung function and bronchial hyperresponsiveness were compared for children sensitive and not sensitive to both indoor and outdoor allergens on skin testing and, if sensitive, for exposed and not exposed to the allergens to which they were positive on skin testing. RESULTS There was a strong direct correlation between increased sensitivity to inhaled methacholine and skin test sensitivity to tree, weed, Alternaria, cat, dog, and indoor molds. When the relationship was examined by stepwise regression, the skin test sensitivities showing the strongest associations with the concentration of methacholine that caused a 20% fall in FEV(1) were dog (P =.003), Alternaria (P =.01), and cat (P =.05). Children sensitive to any one of the aeroallergens tested were compared for the presence or absence of exposure to that allergen at the time that the methacholine challenge was performed. Those who were sensitive and exposed to weed and cat had greater methacholine sensitivity than those similarly sensitive but not exposed (P =.003 and P =.02, respectively). CONCLUSIONS Sensitivity to dog or cat dander or Alternaria by skin testing was associated with increased bronchial responsiveness but not decreased lung function in children with mild to moderate asthma. These findings support the important role that sensitization to certain allergens plays in modulating bronchial responsiveness.

Efficacy and safety of budesonide inhalation suspension (Pulmicort Respules) in young children with inhaled steroid–dependent, persistent asthma

BACKGROUND Inhaled glucocorticosteroids are indicated for the treatment of persistent asthma; however, many young children are unable to effectively use currently available inhalers. OBJECTIVE We sought to evaluate the efficacy and safety of 3 different twice daily doses of budesonide inhalation suspension (Pulmicort Respules) in inhaled steroid-dependent asthmatic children. METHODS This was a 12-week, randomized, double-blind, placebo-controlled, parallel-group study involving 178 children (age range, 4 to 8 years) at 17 centers in the United States. Budesonide inhalation suspension doses of 0.25 mg, 0.50 mg, or 1.0 mg twice daily were administered by means of a jet nebulizer and air compressor system. Efficacy was assessed by recording at home nighttime and daytime asthma symptom scores, use of rescue medication, pulmonary function tests, and treatment discontinuation because of worsening symptoms. Safety was assessed by reported adverse events and changes in baseline and adrenocorticotrophic hormone-stimulated plasma cortisol levels in a subset of patients. RESULTS Baseline demographics, symptom scores, and pulmonary function data were similar across treatment groups. All doses of budesonide inhalation suspension were superior to placebo in improving nighttime and daytime asthma symptom scores (P </=.026), reducing use of breakthrough medication (P </=.032), and improving morning peak expiratory flow (P </=.030). The number of dropouts because of worsening asthma was also significantly fewer in the budesonide groups (P </=.015). There were no differences between doses of budesonide. Adverse events and basal and adrenocorticotrophic hormone-stimulated cortisol responses were not different between budesonide and placebo groups. CONCLUSION Budesonide inhalation suspension, 0.25 mg, 0.50 mg, and 1.0 mg twice daily, is an effective and safe treatment for young children with inhaled steroid-dependent, persistent asthma.

Effects of ambient air pollution on symptom severity and medication use in children with asthma

BACKGROUND Exposure to air pollutants has been investigated as a possible cause of asthma attacks in children. OBJECTIVE To investigate the short-term effects of air pollutants on a panel of 133 children with asthma who enrolled in the Childhood Asthma Management Program. METHODS During screening, the children completed daily diary cards for an average of 58 days to indicate their medication use and asthma severity. We used ordinal logistic regression to compare the odds of a more serious relative to a less serious asthma attack, and we used a Poisson model to analyze medication use. In both analyses we accommodate dependence in the data and different periods of observation for study subjects. RESULTS Our results indicate that a 10-microg/m3 increase in particulate matter less than or equal to 2.5 microm (PM2.5) lagged 1 day was associated with a 1.20 times increased odds of having a more serious asthma attack [95% confidence interval (CI), 1.05 to 1.37] and a 1.08-fold increase in medication use (95% CI, 1.01 to 1.15). A 10-microg/m3 increase in particulate matter less than or equal to 10 microm (PM10) increased the odds of a more serious asthma attack (odds ratio = 1.12; 95% CI, 1.04 to 1.22) and also increased medication use (relative risk = 1.05; 95% CI, 1.00 to 1.09). CONCLUSIONS Increases in PM2.5 and PM10 are significantly associated with an increased risk of more severe asthma attacks and medication use in Seattle area children with asthma. We also found associations with carbon monoxide, but we believe that carbon monoxide is a marker for exposure to combustion byproducts.

Dose-related efficacy of budesonide administered via a dry powder inhaler in the treatment of children with moderate to severe persistent asthma.

OBJECTIVE To determine the efficacy and safety of budesonide delivered by an inhalation-driven dry powder inhaler (Turbuhaler) in children with moderate to severe persistent asthma. STUDY DESIGN In our randomized, double-blind, placebo-controlled, parallel-group, multicenter study, a total of 404 children with asthma, who were aged 6 to 18 years and who had been receiving inhaled glucocorticosteroid therapy, were randomly assigned to receive either 100, 200, or 400 micrograms of budesonide or placebo twice daily for 12 weeks. At baseline, mean forced expiratory volume in 1 second (FEV1) was 74.6% (range, 30.7% to 123.3%) of the predicted normal value. RESULTS Patients in each of the three budesonide treatment groups showed significant dose-related improvements in lung function (morning peak expiratory flow and FEV1), in asthma symptoms, and with a significant decrease in inhaled beta 2-agonist use in comparison with placebo. Improvements were evident within 2 weeks and were maintained throughout the 12 weeks. Budesonide treatment had no significant effect on hypothalamic-pituitary-adrenal axis function, and the incidence of reported adverse events was similar in all treatment groups. CONCLUSION Budesonide administered via a dry powder inhaler provided dose-related improvements in lung function and clinical status and was well tolerated by children (6 to 18 years of age) with moderate to severe persistent asthma.

Cromolyn Sodium: A Review

Cromolyn is a white crystalline powder which is poorly absorbed from the gastrointestinal tract. Its therapeutic value lies in its functions as an inhaled or topically applied agent.

Introduction and definition of sinusitis

We entered the world of clinical research and clinical practice at the same time but in two different locations. Within a short time we became intrigued by patients who had chronic respiratory symptoms that did not fall into the limited diagnostic pigeonhole diagnoses of the early 1970s. Soon we were reporting our experiences and agreeing that patients who were referred for evaluation of allergies commonly had sinus disease. Over the years our interest in sinusitis has grown as has the number of scientists and practitioners who share our desire to understand and better manage this complex problem. This symposium was an opportunity to assemble many of the most knowledgeable researchers and clinicians devoting time to the study of sinus disease today. We expect their contributions to form a body of knowledge that will appeal to the sophisticated clinician whose expertise surpasses what one finds in a textbook. The topics addressed include anatomy of the paranasal sinuses, physiologic defense mechanisms, diagnostic measures, medical management, surgical management, and the relationship between sinusitis and asthma and sinusitis and cystic fibrosis. We hope that these symposium proceedings will serve multiple purposes: to provide a knowledge base for the interested reader, to allow cross-fertilization of ideas among contributors, and to plant the seeds for further research endeavors.

House dust mite avoidance for children with asthma in homes of low-income families

BACKGROUND Home exposure to high levels of house dust mite allergen has been shown to aggravate airways reactivity and asthma. OBJECTIVE The purpose of this study was to determine whether specific house dust mite control measures could reduce exposure levels and asthma severity. METHODS This double-blinded, randomized trial compared asthma progression over 1 year in children whose homes received standard environmental control intervention with those whose homes received aggressive intervention for dust mite elimination. The primary end point was doubling in PD20 methacholine. RESULTS Symptom scores and quality-of-life scores were similar for the standard and aggressive intervention groups. PD20 methacholine doubling occurred in 9 members of the aggressive intervention group vs 4 control patients (P <.05). Dust mite levels decreased in the aggressive intervention homes compared with the standard intervention homes (P <.05). CONCLUSION Aggressive dust mite intervention decreased dust mite levels and improved bronchial hyperresponsiveness.

The effects of perennial allergic rhinitis on dental and skeletal development: A comparison of sibling pairs

This study analyzed the effect of perennial allergic rhinitis on dental and facial skeletal characteristics. Twenty-five allergic children who were apparent mouth breathers, their 25 siblings who did not have the disease and were apparent nose breathers, and 14 nasal breathing control subjects were examined medically, dentally, and cephalometrically. Compared with their siblings, the allergic subjects had more nasal mucosal edema, a higher proportion of eosinophils in their nasal secretions, and greater nasal power. The allergic subjects were characterized by deeper palatal height, retroclined mandibular incisors, increased total anterior facial height and lower facial height, a larger gonial angle, and greater SN, palatal, and occlusal planes to mandibular plane angles. All of these measures except gonial angle were also significantly different between the allergic children and the nonconsanguineous controls. Also, the allergic subjects compared with controls had smaller SNB and SN-pogonion angles and an increased overjet. Both allergic and nonallergic sibling groups showed larger mean adenoid size on radiographs than controls. For most variables the nonallergic siblings fell between the allergic children and the control subjects. Overall, the allergic children had longer, more retrusive faces than controls. This retrusive characteristic was present in nonallergic siblings and cannot be ascribed to the apparent breathing mode at the time of the study. These results confirm earlier reports that allergic rhinitis may be associated with altered facial growth. Controlled longitudinal studies to analyze a possible cause-and-effect relationship and the effects of medical and surgical treatments should be undertaken.

Fluticasone propionate aqueous nasal spray compared with terfenadine tablets in the treatment of seasonal allergic rhinitis

BACKGROUND Comparative studies with topical corticosteroids and antihistamines for treatment of allergic rhinitis have not always demonstrated clear distinctions between the two on the basis of therapeutic efficacy. OBJECTIVE This study was designed to compare the efficacy and tolerability of fluticasone propionate aqueous nasal spray with those of terfenadine in the treatment of seasonal allergic rhinitis. METHODS Three hundred forty-eight patients with allergic rhinitis were given fluticasone propionate aqueous nasal spray (200 micrograms once daily), terfenadine tablets (60 mg twice daily), or placebo for 4 weeks in a multicenter, randomized, double-blind, double-dummy, parallel-group study. RESULTS Clinician-rated total nasal symptom scores after 1, 2, 3, and 4 weeks of therapy and patient-rated total nasal symptom scores throughout treatment were significantly (p <0.05) lower in the fluticasone propionate group compared with the terfenadine group or the placebo group. Terfenadine was not statistically different from placebo on the basis of clinician-related nasal symptom scores, except for sneezing. Total nasal airflow, measured by rhinomanometry, significantly (p <0.05) improved in the fluticasone propionate group compared with the terfenadine group or the placebo group. More fluticasone propionate-treated patients compared with placebo-treated patients had reduced nasal mucosal eosinophil counts after 4 weeks of therapy (p <0.05). No serious or unusual drug-related adverse events were reported. Morning plasma cortisol concentrations after 4 weeks of therapy did not differ among groups. CONCLUSION Fluticasone propionate aqueous nasal spray is more effective than terfenadine tablets for treatment of seasonal allergic rhinitis.