Abstract: Treatment and diagnostic methods are provided for pulmonary disease, including chronic obstructive pulmonary disease. Various pro-inflammatory mediators are elevated in a model of COPD that can be used predict the presence of COPD and/or subtypes of COPD in human patients. Profiles of these mediators can also predict the responsiveness of some patients to certain therapies, including thromboxane receptor antagonist treatment. Methods are provided for diagnosing a subject as a pulmonary disease candidate that include determining leukocyte expression in the subject of at least one pro-inflammatory mediator and identifying the subject as a pulmonary disease candidate when leukocyte expression in the subject of the pro-inflammatory mediator is increased compared to leukocyte expression of the pro-inflammatory mediator in a healthy individual. The pulmonary disease candidate can also be treated by administering a therapeutically effective amount of a thromboxane receptor antagonist.

Abstract: Treatment and diagnostic methods are provided for pulmonary disease, including chronic obstructive pulmonary disease, Arhgef1, a leukocyte signaling molecule, functions normally to suppress integrin-mediated MMP production by alveolar macrophages. MMP9 production by fibronectin-stimulated monocytes and macrophages depends on autocrine thromboxane receptor signaling and this signaling pathway is attenuated by Arhgef1. Expression of ARHGEF1 by human peripheral blood monocytes varies between individuals and inversely correlates with fibronectin-mediated MMP9 production. Arhgef1 levels can function as a predictor for a pulmonary disease candidate and a thromboxane receptor antagonist can treat a pulmonary disease condition resulting from low Arhgef1 levels.

Abstract: Treatment and diagnostic methods are provided for pulmonary disease, including chronic obstructive pulmonary disease. Various pro-inflammatory mediators are elevated in a model of COPD that can be used predict the presence of COPD and/or subtypes of COPD in human patients. Profiles of these mediators can also predict the responsiveness of some patients to certain therapies, including thromboxane receptor antagonist treatment. Methods are provided for diagnosing a subject as a pulmonary disease candidate that include determining leukocyte expression in the subject of at least one pro-inflammatory mediator and identifying the subject as a pulmonary disease candidate when leukocyte expression in the subject of the pro-inflammatory mediator is increased compared to leukocyte expression of the pro-inflammatory mediator in a healthy individual. The pulmonary disease candidate can also be treated by administering a therapeutically effective amount of a thromboxane receptor antagonist.

Abstract: Treatment and diagnostic methods are provided for pulmonary disease, including chronic obstructive pulmonary disease, Arhgef1, a leukocyte signaling molecule, functions normally to suppress integrin-mediated MMP production by alveolar macrophages. MMP9 production by fibronectin-stimulated monocytes and macrophages depends on autocrine thromboxane receptor signaling and this signaling pathway is attenuated by Arhgef1. Expression of ARHGEF1 by human peripheral blood monocytes varies between individuals and inversely correlates with fibronectin-mediated MMP9 production. Arhgef1 levels can function as a predictor for a pulmonary disease candidate and a thromboxane receptor antagonist can treat a pulmonary disease condition resulting from low Arhgef1 levels.