The relationship of aeroallergen sensitization phenotypes to asthma control in primarily Hispanic asthmatic children.

OBJECTIVE: The purpose of this study was to determine whether aeroallergen sensitization phenotypes could predict maintenance of well-controlled asthma. METHODS: Asthmatic children age 2-18 years who enrolled in the CHOC Children's Breathmobile™ program from April 2002 to December 2011 were included in this retrospective analysis if they had been skin tested to a panel of indoor and outdoor aeroallergens and had returned for follow-up care within 6 months of their baseline visit. The study observation period encompassed all year one visits. Asthma severity and control were defined by NHLBI EPR-3 Guidelines criteria. RESULTS: In the 1627 primarily Hispanic children evaluated, those with persistent asthma were more likely than those with intermittent disease to be sensitized to each aeroallergen tested and to have more total sensitizations. Children with intermittent, but not persistent, asthma at baseline who were sensitized to pollen2 (trees or weeds) were less likely to maintain well-controlled asthma at follow-up visits. Whereas, sensitization to dander (cat, dog or feather) showed a protective effect to maintenance of well-controlled asthma in patients with persistent, but not intermittent, baseline disease severity. CONCLUSIONS: Our data suggest that both indoor and outdoor aeroallergens should be assessed regardless of baseline asthma severity, including those with intermittent asthma.

Clinical prescribing of allergic rhinitis medication in the preschool and young school-age child: what are the options?

Allergic rhinitis (AR) is the most common chronic condition in children and is estimated to affect up to 40% of all children. It is usually diagnosed by the age of 6 years. The major impact in children is due to co-morbidity of sinusitis, otitis media with effusion, and bronchial asthma. AR also has profound effects on school absenteeism, performance and quality of life. Pharmacotherapy for AR should be based on the severity and duration of signs and symptoms. For mild, intermittent symptoms lasting a few hours to a few days, an oral second-generation antihistamine should be used on an as-needed basis. This is preferable to a less expensive first-generation antihistamine because of the effect of the latter on sedation and cognition. Four second-generation antihistamines are currently available for children under 12 years of age: cetirizine, loratadine, fexofenadine and azelastine nasal spray; each has been found to be well tolerated and effective. There are no clearcut advantages to distinguish these antihistamines, although for children under 5 years of age, only cetirizine and loratadine are approved. Other agents include pseudoephedrine, an oral vasoconstrictor, for nasal congestion, and the anticholinergic nasal spray ipratropium bromide for rhinorrhoea. Sodium cromoglycate, a mast cell stabiliser nasal spray, may also be useful in this population. For patients with more persistent, severe symptoms, intranasal corticosteroids are indicated, although one might consider azelastine nasal spray, which has anti- inflammatory activity in addition to its antihistamine effect. With the exception of fluticasone propionate for children aged 4 years and older, and mometasone furoate for those aged 3 years and older, the other intranasal corticosteroids including beclomethasone dipropionate, triamcinolone, flunisolide and budesonide are approved for children aged 6 years and older. All are effective, so a major consideration would be cost and safety. For short term therapy of 1 to 2 months, the first-generation intranasal corticosteroids (beclomethasone dipropionate, triamcinolone, budesonide and flunisolide) could be used, and mometasone furoate and fluticasone propionate could be considered for longer-term treatment. Although somewhat more costly, these second-generation drugs have lower bioavailability and thus would have a better safety profile. In patients not responding to the above programme or who require continuous medication, identification of specific triggers by an allergist can allow for specific avoidance measures and/or immunotherapy to decrease the allergic component and increase the effectiveness of the pharmacological regimen.

Safety of budesonide inhalation suspension (Pulmicort Respules) after up to 52 weeks of treatment in infants and young children with persistent asthma.

Three open-label extension trials evaluated the safety of budesonide inhalation suspension (BIS; Pulmicort Respules) in 670 children (8 months-9 years of age) with mild-to-severe persistent asthma. Patients were randomized to receive either BIS or conventional asthma therapy (CAT) for 52 weeks. The percentage of patients who discontinued because of clinical adverse events was low and similar among the CAT (0.4%) and BIS (0.7%) groups. After adjusting for length of time in the studies, there were no clinically relevant differences between the BIS and CAT groups in the type, incidence, or intensity of adverse events; vital signs or physical examination outcomes; or changes in clinical laboratory evaluations or oral fungal cultures.

A dose-ranging study of mometasone furoate aqueous nasal spray in children with seasonal allergic rhinitis.

BACKGROUND: The efficacy and safety of mometasone furoate aqueous nasal spray (MFNS; Nasonex) 200 microg once daily for the treatment and prophylaxis of seasonal allergic rhinitis (SAR) and treatment of perennial rhinitis have been demonstrated in adults. However, the dose response of MFNS in pediatric patients has not yet been characterized. OBJECTIVE: This study was conducted to determine the dose-response relationship of 3 different doses of MFNS in a pediatric population. METHODS: This was a multicenter, double-blind, active- and placebo-controlled study of 679 children 6 to 11 years of age with histories of SAR and documented positive skin test responses. Patients were randomized to one of the following treatment groups for 4 weeks: MFNS 25 microgram once daily, MFNS 100 microgram once daily, MFNS 200 microgram once daily, beclomethasone dipropionate 84 microgram twice daily (168 microgram/day), or placebo. Physician evaluations were performed at days 4, 8, 15, and 29, and patient evaluations were analyzed for days 1 to 15 and 16 to 29. RESULTS: The mean reduction from baseline in physician-evaluated total nasal symptom scores at day 8 (the primary efficacy variable) was significantly greater in the MFNS and beclomethasone dipropionate groups than in the placebo group (P

Validation of an asthma symptom diary for interventional studies.

OBJECTIVE: The Pediatric Asthma Diary was developed and validated to assess efficacy of interventions in children with asthma. DESIGN, PATIENTS, AND SETTING: Diary validation was performed in a three week, prospective study of 106 children aged 6-14 years with asthma. Children were classified at baseline as either stable (requiring no additional asthma treatment) or new onset/worse (requiring either addition of or increase in anti-inflammatory treatment). RESULTS: A daytime symptom scale and "day without asthma" were defined from diary questions. Both measures demonstrated significant validity and responsiveness to anti-inflammatory treatment. The stable group experienced a higher percentage of days without asthma during week 1 compared with the new onset/worse group (39.6% v 11.6%, respectively). The new onset/worse patients experienced significant improvement in days without asthma (24.5%) compared with stable patients (6.4%). CONCLUSIONS: The Pediatric Asthma Diary daytime symptom scale and day without asthma are acceptable measures for use in asthma intervention studies of children aged 6-14 years.

Diskus and diskhaler: efficacy and safety of fluticasone propionate via two dry powder inhalers in subjects with mild-to-moderate persistent asthma.

BACKGROUND: Fluticasone propionate is a topically active glucocorticoid with potent antiinflammatory activity in the treatment of asthma. OBJECTIVE: This study evaluated the safety and efficacy of fluticasone propionate administered via the Diskus and Diskhaler powder delivery devices in subjects with mild-to-moderate asthma. METHODS: Fluticasone propionate (500 microg twice daily) or placebo was administered via the Diskus and Diskhaler to 213 adolescent and adult asthma subjects in a randomized, double-blind, double-dummy, parallel-group study for 12 weeks. Subjects were stratified according to baseline therapy of inhaled corticosteroids or beta2-agonists alone. Subjects were dropped from the study if they met predefined criteria for lack of efficacy. RESULTS: Fluticasone propionate improved pulmonary function both in subjects previously treated with inhaled corticosteroids or beta2-agonists alone. At endpoint, fluticasone propionate significantly improved forced expiratory volume in 1 second (P < .001), morning and evening peak expiratory flow (P < .001), and asthma symptom scores (P < or = .016), and significantly reduced nighttime awakenings (P = .016; Diskhaler group only) and rescue albuterol use (P < .001). Overall, efficacy measurements for the Diskus and Diskhaler were similar. More placebo-treated subjects (34%) withdrew from the study due to lack of efficacy than subjects in the Diskus (5%) or Diskhaler (5%) groups. The incidence and severity of adverse events were similar across groups. Measurement of plasma fluticasone propionate and cortisol concentrations showed no apparent influence of device on systemic exposure. CONCLUSION: Fluticasone propionate powder, administered via the Diskus or Diskhaler inhalation devices, was well tolerated and effective in the treatment of mild-to-moderate persistent asthma.

Zafirlukast improves asthma symptoms and quality of life in patients with moderate reversible airflow obstruction.

BACKGROUND: Previous trials demonstrated the effectiveness of the leukotriene receptor antagonist zafirlukast in patients with mild-to-moderate asthma. OBJECTIVES: We sought to assess the efficacy and safety of zafirlukast and its effect on patients' quality of life (QOL) during a 13-week, double-blind, placebo-controlled, multicenter trial in adults and adolescents with moderate reversible airflow obstruction. METHODS: Patients (age range, 12 to 68 years) with total daytime asthma symptoms scores of 10 or greater over 7 consecutive days (maximum, 21/wk), FEV1 45% or greater but less than or equal to 80% of predicted value (>/=6 hours after beta2 -agonist), and reversible airway disease were randomized to 20 mg zafirlukast twice daily (nZ = 231) or placebo twice daily (nP = 223). Efficacy was assessed from changes in daytime and nocturnal symptoms, beta2 -agonist use, nasal congestion score, and pulmonary function. QOL was evaluated with a disease-specific Asthma Quality of Life Questionnaire. Safety was determined from adverse event information and clinical laboratory test results. RESULTS: Zafirlukast was significantly (P <.001) more effective than placebo, with reductions from baseline in the daytime asthma symptoms score (-23%), nighttime awakenings with asthma (-19%), and beta2 -agonist use (-24%) and improvements from baseline in morning (+25 L/min) and evening (+18 L/min) peak expiratory flow rates. Compared with placebo, zafirlukast significantly (P /=0.5-unit change from baseline; P

Fluticasone propionate compared with theophylline for mild-to-moderate asthma.

BACKGROUND: The inhaled corticosteroid, fluticasone propionate, was compared with the oral bronchodilator theophylline in the maintenance treatment of asthma. OBJECTIVE: The objective of the present study was to compare the efficacy and safety of twice-daily inhaled fluticasone propionate, 50 micrograms, and fluticasone propionate, 100 micrograms, with that of theophylline in the maintenance treatment of mild-to-moderate asthma. METHODS: In this randomized, double-blind, placebo-controlled, parallel-group study, 353 adult and adolescent patients with asthma inadequately controlled with inhaled beta-agonist therapy alone received fluticasone propionate, 50 micrograms, or fluticasone propionate, 100 micrograms, by metered-dose inhaler; theophylline capsules; or placebo twice daily for 12 weeks. Only inhaled albuterol was permitted as needed for acute symptoms. RESULTS: Both fluticasone propionate groups had a significantly greater probability of remaining in the study (ie, meeting asthma stability criteria) than did either the theophylline or placebo group (P < or = .008); 39% and 51% in the theophylline and placebo groups, respectively, were withdrawn due to lack of treatment efficacy compared with 14% and 21% in the fluticasone propionate, 50 micrograms, and fluticasone propionate, 100 micrograms, groups. Both fluticasone propionate groups experienced significantly greater improvement in FEV1 and PEF compared with patients in the theophylline or placebo group (P < or = .004). The incidence of potentially drug-related adverse events was significantly greater in the theophylline group (25%) than in the placebo group (11%) (P = .031), while there were no differences between placebo and fluticasone propionate, 50 micrograms, (18%) or fluticasone propionate 100 micrograms, (22%). CONCLUSION: Twice daily treatment with inhaled fluticasone propionate 50 micrograms or 100 micrograms was significantly more effective than theophylline in the treatment of mild-to-moderate asthma.

Growth and the nutritional status of nonsteroid-dependent asthmatic children.

Nonsteroid dependent children were evaluated to determine the effect of asthma on growth and nutritional status. No significant differences were observed for the growth of asthmatics and control groups. In addition, dietary records indicated asthmatics met or exceeded the recommended daily allowance for total calories and nutrients.

Dose-response relationship of inhaled metaproterenol sulfate in preschool children with mild asthma.

The dose-response relationship of single doses of nebulized metaproterenol sulfate 5% inhalant solution was evaluated by placebo-controlled, parallel-group study of 30 children, aged 3 to 6 years old, with stable asthma. Total respiratory resistance, the primary variable used to assess response, was measured by the forced oscillation method for a period of 6 hours from the start of inhalation. When comparisons were made between metaproterenol sulfate and saline, only 0.01 and 0.02 mL/kg showed significant bronchodilation (P less than .05) in percent change from baseline and area under the curve. However, no significant differences were seen between these doses. Moreover, the effect was sustained for 3 hours with both higher doses. Minimal side effects were observed. Metaproterenol sulfate 5% inhalant solution at a dose of 0.01 mL/kg seems to be optimal to elicit significant and sustained bronchodilatory response in preschool children with mild asthma.

Treatment of asthma. New and time-tested strategies.

Early, aggressive therapy in conjunction with good communication with a knowledgeable, caring physician may reverse the trends of increasing morbidity and mortality from asthma. Allergen avoidance and immunotherapy are helpful in some patients. For those who need medication, bronchodilation with a beta 2-adrenergic drug, often in conjunction with an anticholinergic and theophylline, is the current treatment of choice for acute symptoms. For prophylaxis of chronic symptoms, sustained-release theophylline is still an excellent drug. However, an anti-inflammatory agent (eg, cromolyn sodium [Intal]) or, in some cases, an inhaled corticosteroid, may be an effective alternative. Whatever treatment is used, its success depends on effective self-management, which begins with education of the patient and family.

Allergy shots for hay fever.

Although allergy shots have been used for many years, immunotherapy for symptoms of allergic rhinitis has only recently been clearly shown to be effective. Standardization of allergens will provide even better results in the diagnosis and treatment of allergic rhinitis in the future. Success in an individual patient depends on appropriate application. Immunotherapy should be reserved for patients who have allergy to airborne allergens, have significant symptoms after exposure to them, have sensitivity that has been proven by a skin or in vitro test, and cannot avoid the allergen or control symptoms with drugs. Thus, allergy shots are generally not used for allergy to pet dander or food. Immunotherapy is begun with a very dilute concentration of allergen, which is gradually increased to the maximum dose that is safely tolerated. The interval between shots is then increased gradually to once a month. Duration of treatment is usually 3 years in children and longer in adults. Treatment usually fails if the patient cannot free the environment of large amounts of known allergens, if the allergen was not correctly determined during initial evaluation, or if the allergen dose is inadequate. The patient must have realistic expectations: Allergy shots often do not totally eliminate symptoms, and improvement takes time.

Association of lipid-laden alveolar macrophages and gastroesophageal reflux in children.

The association of lipid-laden alveolar macrophages (LLAM) and gastroesophageal reflux (GER) was investigated prospectively in 115 patients in two groups. Group 1 included 74 children with chronic respiratory tract disorders and documented GER by prolonged esophageal pH monitoring, barium esophagram, and esophagoscopy; group 2 included 41 children with chronic respiratory tract disorders without GER. LLAM were present in 63 (85%) and eight (19%) children from groups 1 and 2, respectively (P less than 0.0001). Thus a strong association between the presence of LLAM and GER in children with chronic respiratory tract disorders was established. We suggest that LLAM from bronchial lavage may be a useful marker for tracheal aspiration in children with GER in whom chronic lung disease may subsequently develop.

Aeroallergen exposure in the elementary school setting.

Ten elementary schools in southern California were surveyed to identify and quantitate allergens present in the school environment. The Anderson sampler was used to quantitate viable molds. Pollens and non-viable molds were determined by roto rod techniques. Statistically significant differences existed between indoor and outdoor mean counts for molds and pollens identified by roto rod techniques. Viable mean mold spore counts inside schools compared favorably to local homes. House dust mites were found in considerably lower concentrations in the schools than in homes in the same area. Results indicate that the school interior is a protective environment for individuals sensitive to mold, pollens, and house dust mites.