Severe and difficult to treat asthma patients represent a small percentage of all asthmatics, yet they account for much of the morbidity, mortality, and cost of the disease. The factors that make this group of asthmatics difficult to manage are poorly understood. OBJECTIVE: To establish a cohort of severe or difficult to treat asthmatics to examine the relationships between features of asthma, treatments and health outcomes using the Internet. METHODS: This study, "An Observational Study of The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regiments (TENOR)," is designed to follow at least 5000 subjects for 3 years. Subjects 6 years or older with a diagnosis of asthma and considered by their physician to have severe or difficult to treat asthma are eligible for enrollment. Physicians and coordinators will conduct biannual visits to collect data including: healthcare utilization, days of work or school missed, the asthma therapy assessment questionnaire (ATAQ), asthma-related quality of life (AQLQ), medications, IgE level, and lung function. Data will be entered onto a secure website. RESULTS: Subjects are being enrolled into the cohort from over 300 U.S. pulmonologists and allergists in managed care organizations, community practices, and academic centers. All study sites have Internet access. The TENOR website was built using WebCollectSM services and PhaseForward's InFormTM application. Built-in edit checks and an automatic electronic audit trail ensure data accuracy and completeness. This technology eliminates the need for paper case report forms and improves data cleaning efficiency. CONCLUSIONS: TENOR provides a unique opportunity to examine factors related to poor health outcomes in this understudied patient population. The Internet allows real time access to data and facilitates dissemination of data to investigators and the asthma community. TENOR may serve as a model for future large epidemiologic or clinical studies using web-based technology.