I-CLIC Projects

UIOWA UIHC

ENDOCT -- High Resolution CT-based Evaluation Of Airway Responses To Endotoxin Inhalation

Asthma, a disorder of airway inflammation, airflow obstruction, and hyperresponsiveness, has been increasing in prevalence and severity over the past several decades. An important subset of asthma is that seen in the workplace, especially in agricultural settings. Following inhalation of organic dusts, asthmatics (and many non-asthmatics) develop airflow obstruction. Endotoxin is an important dust component that leads to airway inflammation and airflow obstruction. Importantly, currently available asthma therapies have little effect on endotoxin-induced lung disease 1, leading to few options for asthmatics who wish to continue working on the farm. Inhaled corticosteroids, the ”gold standard“ treatment, have been optimized for delivery to relatively large airways; responses to endotoxin may occur in smaller, more distal bronchi, thus reducing the benefit of these agents. To better understand endotoxin-induced airways disease, we propose the hypothesis that inhaled endotoxin induces a specific and characteristic pattern of inflammation and bronchospasm among individuals with hyperreactive airways, which we will study in the following Specific Aims:

1. Evaluate, using high-resolution computed tomography scanning, the heterogeneity and spatial pattern of endotoxin-induced bronchospasm in normal subjects.
2. Compare these effects of endotoxin inhalation between normal and mild asthmatic subjects.
3. Compare the effects of inhaled endotoxin and inhaled methacholine on patterns of bronchospasm in mild asthmatic subjects.

This study will improve our understanding of the natural history of asthma as well as that of airway inflammation from inhaled organic dusts. In addition, it may lead to novel therapeutic approaches to the treatment of asthma and airway responses in farmers.