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Background More evidence is needed on which to base recommendations for treatment of mild-moderate persistent asthma in school-aged children. Objective The Pediatric Asthma Controller Trial (PACT) compared the effectiveness of 3 regimens in achieving asthma control. Methods A total of 285 children (ages 6-14 years) with mild-moderate persistent asthma on the basis of symptoms, and with FEV 1 ≥ 80% predicted and methacholine FEV 1 PC 20 ≤ 12.5 mg/mL, were randomized to 1 of 3 double-blind 48-week treatments: fluticasone 100 μg twice daily (fluticasone monotherapy), fluticasone 100 μg/salmeterol 50 μg in the morning and salmeterol 50 μg in the evening (PACT combination), and montelukast 5 mg in the evening. Outcomes included asthma control days (primary outcome), exacerbations, humanistic measurements, and pulmonary function measurements. Results Fluticasone monotherapy and PACT combination were comparable in many patient-measured outcomes, including percent of asthma control days, but fluticasone monotherapy was superior for clinic-measured FEV 1 /forced vital capacity ( P = .015), maximum bronchodilator response ( P = .009), exhaled nitric oxide ( P .001), and PC 20 ( P .001). Fluticasone monotherapy was superior to montelukast for asthma control days (64.2% vs 52.5%; P = .004) and for all other control outcomes. Growth over 48 weeks was not statistically different (fluticasone, 5.3 cm; PACT combination, 5.3 cm; montelukast, 5.7 cm). Conclusion Both fluticasone monotherapy and PACT combination achieved greater improvements in asthma control days than montelukast. However, fluticasone monotherapy was superior to PACT combination in achieving other dimensions of asthma control. Growth was similar in all groups. Clinical implications Therefore, of the regimens tested, the PACT study findings favor fluticasone monotherapy in treating children with mild-moderate persistent asthma with FEV 1 ≥ 80% predicted, confirming current guideline recommendations.

Background Few studies have characterized the atopic profile of toddler-aged children with recurrent wheezing at high risk of the development of persistent asthma. Objective We sought to determine the atopic profile of toddler-aged children with frequent wheeze at high risk for the development of persistent asthma who either had a parental history of asthma, a personal history of atopic dermatitis, or both. Methods Participants enrolled in the Prevention of Early Asthma in Kids study (n=285) on the basis of a modified Asthma Predictive Index were characterized on the basis of allergy and asthma questionnaire responses and allergy skin puncture test results. Results The majority of the children (60.7%, n=148) were sensitized to either food or aeroallergens. Male children were significantly more likely to be sensitized to aeroallergens ( P =.03) and to have a blood eosinophil level of 4% or greater ( P =.03) and a total serum IgE level of greater than 100 IU/mL ( P =.0004). Additionally, eosinophilia and total serum IgE level had the strongest correlation with aeroallergen sensitization. Conclusion The high prevalence of aeroallergen sensitization in this high-risk cohort suggests that aeroallergens might have an important role in the early development of asthma. As such, the Prevention of Early Asthma in Kids cohort appears to be an appropriate cohort in which to test whether early intervention with an inhaled corticosteroid can significantly attenuate, or perhaps even prevent, the allergic march from the initial stages of allergic sensitization to the subsequent development of asthma in toddlers with episodic wheezing.

Inflammatory mediators have been implicated in the pathogenesis of human asthma and have been demonstrated to increase in bronchoalveolar lavage fluid during the time of the immediate asthmatic response (IAR) after allergen instillation in the lungs. However, the relationship of these mediators, measured early to the late asthmatic response (LAR), airway reactivity, and clinical asthma, is unknown. In the present study, we evaluated mediator levels in bronchoalveolar lavage fluid before and 5 minutes after allergen challenge from three subject groups: atopic subjects without asthma (N = 7), atopic subjects with asthma and without LAR [-) LAR) (N = 6), and atopic subjects with asthma and with LAR [+) LAR) (N = 6). Subjects with asthma were differentiated into subjects with and without LARs based on at least a 15% decrease in FEV1 between 3 to 8 hours postallergen inhalation. The mediators, prostaglandin D2 thromboxane B2 leukotriene C4 (LTC4), and histamine, were measured both before and after allergen instillation. Baseline prechallenge levels were similar, except in the case of LTC4. LTC4 was detectable at baseline significantly more frequently in the atopic subjects with asthma with and without LAR when these subjects were compared to the atopic subjects without asthma (nine of 12 detectable versus one of seven detectable). In all groups, significant increases in mediator levels were observed in the groups with asthma postallergen challenge, compared to the atopic subjects without asthma. Atopic subjects with asthma and without LAR had significantly higher levels of all four mediators after challenge than atopic subjects with asthma and with LAR and atopic subjects without asthma.(ABSTRACT TRUNCATED AT 250 WORDS)

Background Determination of the benefits and limitations of specific physiologic tests has not been well studied in long-term clinical pediatric trials. Objective We sought to determine the utility of impulse oscillometry in a long-term comparison of 3 controller regimens in children with persistent asthma. Methods Children 6 to 14 years of age with mild-to-moderate persistent asthma were characterized with oscillometry and spirometry before entry into a clinical trial and then serially during 48 weeks of therapy with either an inhaled corticosteroid, a combination inhaled corticosteroid with a long-acting β-agonist, or a leukotriene receptor antagonist. Results The FEV 1 /forced vital capacity ratio, as well as the forced expiratory flow from 25% to 75% of forced vital capacity in terms of spirometric parameters and the reactance area (XA) from impulse oscillometry, appeared to complement information provided by FEV 1 when comparing the tests and factors that appeared to predict a response to treatment. XA was unique in that it, as distinct from spirometric variables, reflected ongoing improvement during the latter part of the trial. In general, improvements in XA during the latter part of the study occurred independently of indices of atopy and the level of airway responsiveness. Conclusion Assessment of respiratory mechanics over time with oscillometry might offer additional insights into the response of asthmatic patients to therapy. In particular, the pattern of improvement seen in XA over the course of therapy suggests this test might detect alterations in airway mechanics not reflected by spirometry. The possibility that changes in XA reflect ongoing improvement in small airway function deserves additional study.

Background Acute wheezing illnesses in preschoolers require better management strategies to reduce morbidity. Objectives We sought to examine the effectiveness of episodic use of an inhaled corticosteroid and a leukotriene receptor antagonist in preschoolers with intermittent wheezing. Methods In a randomized, double-blind, placebo-controlled 12-month trial, 238 children aged 12 to 59 months with moderate-to-severe intermittent wheezing received 7 days of either budesonide inhalation suspension (1 mg twice daily), montelukast (4 mg daily), or placebo in addition to albuterol with each identified respiratory tract illness (RTI). Proportion of episode-free days (EFDs) during the 12-month trial was the primary outcome. Results The 3 treatment groups did not differ in proportions of EFDs, with adjusted mean EFDs of 76% (95% CI, 70% to 81%) for budesonide, 73% (95% CI, 66% to 79%) for montelukast, and 74% (95% CI, 65% to 81%) for conventional therapy (P = .66). The 3 groups did not differ in oral corticosteroid use, health care use, quality of life, or linear growth. However, during RTIs, budesonide and montelukast therapy led to modest reductions in trouble breathing (38% [P = .003] and 37% [P = .003], respectively) and interference with activity scores (32% [P = .01] and 40% [P = .001], respectively) that were most evident in those with positive asthma predictive indices. Conclusions In preschool children with moderate-to-severe intermittent wheezing, episodic use of either budesonide or montelukast early in RTIs, when added to albuterol, did not increase the proportion of EFDs or decrease oral corticosteroid use over a 12-month period. However, indicators of severity of acute illnesses were reduced, particularly in children with positive asthma predictive indices.