Chronic allergic airway disease in the sheep model: Functional and lung-lavage features

Abstract

We developed an animal model of chronic allergic airway disease by repeatedly exposing nine sheep to tracheal instillation of ascaris antigen until stable increase in lung resistance at three times control in six reactive sheep (group C) was obtained. They were then compared to the three nonreactive sheep (group B) and a control group of eight sheep exposed to saline only (group A) in terms of pulmonary function tests and bronchoalveolar lavage (BAL) analyses. Lung resistance was 1.5 ± 0.3 cm H 2O/L/sec in group A, 1.8 ± 0.3 in group B, and 5.9 ± 1.3 in group C. Trapping volume (functional residual capacity by plethysmography and by helium rebreathing technique) was 0 ± 0.1 L in group A, 0.05 ± 0.1 in group B, and 0.51 ± 0.17 in group C. Upstream resistance at peak flow did not differ between any two groups, but upstream resistance near residual volume was 1.8 ± 0.3 cm H 2O/L/sec in A, 6.2 ± 1.0 in B, and 28 ± 6 in C. In BAL, total cells were 25 ± 5 × 10 4/ml in A, 35 ± 8 in B, and 31 ± 6 in C. Macrophages in BAL were 16 ± 2 in A, 27 ± 9 in B, and 24 ± 4 in C. Neutrophils were 0.5 ± 0.2 in A, 3.4 ± 2.5 in B, 2.8 ± 1.5 in C. Eosinophils were 0.1 ± 0.1 in A, 0.5 ± 0.2 in B, and 0.9 ± 0.3 in C (p < 0.05 group C versus group A). Total proteins, albumin, alkaline phosphatase, and fibronectin did not differ between groups. Histamine levels were 0.7 ± 0.2 ng/ml in A, 0.7 ± 1 in B, and 1.3 ± 0.2 in C; cAMP levels were 9.9 ± 1.8 pM/ml in A, 6.8 ± 1.8 in B, and 4.7 ± 0.9 in C. Thus, the small airway disease in the ascaris-reactive sheep is characterized, on BAL, by elevated eosinophils and histamine but depressed cAMP. These observations further support a sympathoadrenergic imbalance and an inflammatory component in chronic allergic airway disease.