Patient description: A 39-year-old man came to the clinic with cough and shortness of breath that was not relieved by his inhaler. He had these symptoms for 5 days during the past 2 weeks. He doubled his oral corticosteroids in the past week. He is a chef with a history of asthma for 3 years, suffering from frequent cough, wheezing, and shortness of breath and chest tightness. The symptoms become more bothersome within 1-2 hours of starting work every day and worsen throughout the work week. His symptoms improve within 1-2 hours outside the workplace. Spirometry was performed revealing a forced expiratory volume in the first second (FEV1) of 63% of the predicted. His past medical history is significant for seasonal allergic rhinitis in the summer. He doesn't smoke or use illicit drugs. His family history is significant for asthma in his father and sister. He currently uses inhaled corticosteroid (ICS) and fluticasone 500 mcg/salmeterol 50 mcg, one puff twice daily.

Clinical trial eligibility criteria: eligible ages (years): 6.0-17.0,  Asthma At Enrollment (V0) Age 6-17 years at time of enrollment. A goal of 33% minority and 40% female subjects will be incorporated in recruitment Weighs at least 25 kg Asthma diagnosed by a physician and present for at least one year prior to study entry Moderate to severe persistent asthma: 1. Patients will be identified in the following general categories. The general principle is that patients will be uncontrolled on a relatively low dose of ICS that can be stepped-up, or controlled on a moderate or high dose of ICS that can be stepped-down. i) On low dose ICS with or without salmeterol and uncontrolled. This patient will be treated with budesonide and salmeterol to determine criteria. If the addition of salmeterol results in control of symptoms, the patient would be excluded from MARS. If control was not established on low dose budesonide and salmeterol, the dose of budesonide would be increased and entry evaluated based on the algorithm in Figure 1. ii) On a dose of ICS equivalent to budesonide at 400 mcg per day with or without any other medication and uncontrolled. This patient will be treated with budesonide and salmeterol to determine criteria. iii) On a dose of ICS equivalent to budesonide at 800 mcg per day with or without any other medication and controlled. iv) On a dose of ICS equivalent to budesonide at 1600 mcg per day with or without any other medication and uncontrolled but not requiring prednisone acutely. These patients will be followed to see if they become well controlled with increased adherence or more careful monitoring of symptoms. 2. Examples are given for Advair as this drug is a commonly used form of ICS and LABA: i) Patients on Advair 100/50 bid and inadequately controlled ii) Patients on Advair 250/50 bid and inadequately controlled iii) Patients on Advair 250/50 bid and well controlled for greater than 3 months and being considered for stepping-down to Advair 100/50 iv) Patients well controlled on Advair 100/50 bid + either montelukast or theophylline for greater than 3 months and being considered for stepping-down to Advair 100/50 bid alone v) Patients on Advair 500/50 bid and well controlled for greater than 3 months and being considered for stepping-down to Advair 250/50 vi) Patients well controlled on Advair 250/50 bid + either montelukast or theophylline for greater than 3 months and being considered for stepping-down to Advair 250/50 bid alone 3. Patients on an equivalent of budesonide 400 mcg, 800 mcg, or 1600 mcg per day with no symptoms, but with an FEV1 less than 80% predicted, will be enrolled as uncontrolled and observed closely for symptoms or low peak flows for 2 weeks. The rationale for enrolling these patients and observing them as "uncontrolled" is that patients with an FEV1 below the range of normal may be having symptoms and/or low peak flows that will become apparent under close observation after appropriate education. Note that a percent predicted value for FEV1 will be used only at the enrollment visit, with for control and inadequate control during both run-in and during the double-blind portions of the study using the highest FEV1 value obtained during run-in for decisions prior to randomization and the FEV1 at randomization for decisions subsequent to that visit FEV1 at least 80% predicted if there is going to be step-down at enrollment or at least 50% predicted if already suboptimally controlled historically and to be observed for 2 weeks to define baseline symptoms. FEV1 measurements will be obtained pre-bronchodilator Demonstrate a bronchodilator response with an improvement in FEV1 of at least 12% or airway responsiveness to methacholine with a PC20 less than 12.5 mg/ml. 1. Bronchodilator responsiveness testing will be done at Visit 0 (Enrollment) in all patients using 4 puffs albuterol. 2. Methacholine challenge will be done at Visit 1 (Step-up) in patients who did not respond to bronchodilator at Visit 0. Patients with a FEV1 less than 70% predicted or an upper respiratory infection at the time of Visit 1 will have a second bronchodilator challenge rather than a methacholine Varicella immunization complete (unless the subject has already had clinical varicella). If the subject needs varicella vaccine, this will be arranged with the primary care physician and must be received prior randomization Willingness to provide informed consent by the child's parent or guardian Nonsmoker in the past year; in addition, no use of smokeless tobacco products in the year prior to study entry  At Enrollment (V0) More than four courses of systemic corticosteroids for asthma during the 12 months prior to study entry More than one hospitalization for wheezing illnesses within the 12 months prior to study entry Current treatment with antibiotics for diagnosed sinus disease History of severe sinusitis requiring sinus surgery within the past 12 months Use of maintenance oral or systemic antibiotics for treatment of an ongoing condition Use of macrolide antibiotics within the 6 weeks prior to study entry Requirement for prednisone therapy for concurrent illness, e.g., RA, SLE, IBD Asthma exacerbation requiring systemic corticosteroids within 4 weeks of study entry Contraindication for use of macrolide or LTRA