(CARE Network Trial - Treating Children to Prevent Exacerbations of Asthma (TREXA)

Asthma is a common, serious illness among children in the United States. It can be effectively controlled through the use of preventative medications and "rescue" medications, which are used to control symptoms. This study will evaluate the impact and severity of asthma exacerbations that occur in children with mild persistent asthma who are receiving various combinations of medications for daily and rescue use.

Almost 9 million children in the United States have asthma, and it is a leading cause of hospitalizations and school absenteeism. Common asthma symptoms include wheezing, shortness of breath, chest tightness, and coughing. While there is no cure for asthma, most children who receive proper treatment are able to control symptoms and lead a normal life. Asthma is commonly treated with two types of medications: long-term control medication, such as inhaled corticosteroids (ICS), which is taken on a regular schedule to prevent symptoms and keep asthma under control, and quick-relief, or "rescue" medication, such as albuterol, which is used on an as-needed-basis with the onset of symptoms or an asthma attack. The purpose of this study is to assess the impact and severity of asthma exacerbations that occur in children with mild persistent asthma who are receiving ICS on a daily basis plus ICS and albuterol as rescue medications. This study will begin with a 4-week screening period during which participants will be monitored while they use an inhaler with a low dose of ICS medication. Study visits will occur at study entry and Week 4. Participants will undergo a physical examination, lung function and airway pressure testing, and blood collection. At the Week 4 study visit, participants will be randomly assigned to one of the following four groups for 44 weeks of treatment: * Group 1 will take ICS twice a day and ICS plus albuterol as rescue medication * Group 2 will take ICS twice a day and placebo ICS plus albuterol as rescue medication * Group 3 will take placebo ICS twice a day and ICS plus albuterol as rescue medication * Group 4 will take placebo ICS twice a day and placebo ICS plus albuterol as rescue medication Each participant will receive three inhalers with their assigned medication. One inhaler will be used twice daily throughout the study. The other two inhalers will be used consecutively on an as-needed-basis as rescue medication. Study visits will occur at Weeks 8, 16, 24, 32, 40, and 48. A physical examination, blood collection, and lung function and airway pressure testing will occur at selected visits. Questionnaires to assess quality of life and asthma control will also be completed. A methacholine challenge test will be completed at some study visits. This test artificially triggers an asthma attack to determine the severity of an individual's asthma. Throughout the study, participants will record asthma symptoms and rescue medication usage in a daily diary.