Hypersensitivity pneumonitis (HP) is a difficult disease to identify the causative agent. There have been over 300 antigens, including animal proteins, bacteria, fungi, and low molecular weight chemicals identified as agent(s) important in the etiology of HP. Symptomatic treatment generally involves the use of corticosteroids. The most effective treatment is for patients to avoid exposure to the causal antigen, which has the potential to stabilize and reverse the patient?s disease, and in one study significantly reduced mortality. Mortality due to HP has been shown to be increasing in the United States. Central to the four published guidelines for diagnosis is the identification of the antigen involved in the etiology of a patient?s HP. Just as important as the accurate identification of the causal antigen is the determination of the circumstances in which the patient is being exposed so as to be able to recommend exposure avoidance. At present, clinicians do not have an effective strategy to identify antigen related to a patient?s HP. Current practice to identify the exposure involves a clinical history, and ordering commercially available tests measuring antibody response to a limited set of antigens. It is difficult to identify the source of relevant exposures through interview alone, and results of commercial HP panels are difficult to interpret as positive antibody response may simply be a measure of exposure and unrelated to a patient?s disease, or difficult to identify the source in the patient?s environment where the patient is being exposed. This proposal builds on a successful pilot study in which we were able to isolate antigen from a patient?s environment resulting in a positive antibody response. We included lymphoproliferation testing for candidate antigens to demonstrate a strong antigen specific immune response to the causative agent. We hypothesize that personalized antigen testing combined with demonstration of a strong antigen specific immune response (i.e. lymphoproliferation) rather than the use of a generic antigen panel is a more effective strategy for identifying the causative antigen(s) in patients diagnosed with HP. With the support of the pulmonary community in Michigan (letters of support from the President of the Michigan Thoracic Society and pulmonologists at four major health-systems) we will recruit 155 patients diagnosed with HP and control subjects matched by exposure. For each patient (case) we will determine and isolate antigen(s) from their home/workplace environment resulting in a positive antibody response, utilize antigen-driven lymphoproliferation and cytokine expression to distinguish between antigens to which each case exhibits a positive antibody response as a biomarker of exposure versus an immunological response that contributes to the disease process, create exposure avoidance plans for each case, and follow them for 1 year to determine clinical status. Statistical modeling procedures will be used to determine whether this ?patient-centered' approach is more useful than results of office-based 'exposure' interviews and/or results of standardized antigen panel testing in determining causative antigen and improving respiratory function in patients with HP.