To determine whether patients with fixed airflow obstruction have distinct pathologic and functional characteristics depending on a history of either asthma or chronic obstructive pulmonary disease (COPD), we characterized 46 consecutive outpatients presenting with fixed airflow obstruction by clinical history, pulmonary function tests, exhaled nitric oxide, sputum analysis, bronchoalveolar lavage, bronchial biopsy, and high-resolution computed tomography chest scans. Subjects with a history of COPD (n = 27) and subjects with a history of asthma (n = 19) had a similar degree of fixed airflow obstruction (FEV1: 56 +/- 2 versus 56 +/- 3% predicted) and airway hyperresponsiveness (PC20FEV1: 2.81 [3.1] versus 1.17 [3.3]). Subjects with a history of asthma had significantly more eosinophils in peripheral blood, sputum, bronchoalveolar lavage, and airway mucosa; fewer neutrophils in sputum and bronchoalveolar lavage fluid; a higher CD4+/CD8+ ratio of T cells infiltrating the airway mucosa; and a thicker reticular layer of the epithelial basement membrane. They also had significantly lower residual volume, higher diffusing capacity, higher exhaled nitric oxide, lower high-resolution computed tomography scan emphysema score, and greater reversibility to bronchodilator and steroids. In conclusion, despite similar fixed airflow obstruction, subjects with a history of asthma have distinct characteristics compared with subjects with a history of COPD and should be properly identified and treated.