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.