Grain Dust and Endotoxin Inhalation Challenges Produce Similar Inflammatory Responses in Normal Subjects

doi:10.1378/chest.110.1.263

Chest

Volume 110, Issue 1, July 1996, Pages 263-270

https://doi.org/10.1378/chest.110.1.263 Get rights and content

Study objective

To compare the physiologic and inflammatory response following inhalation of corn dust extract (CDE) and lipopolysaccharide (LPS) solutions in normal subjects.

Design

Randomized, double-blind crossover design.

Participants

Fourteen healthy, nonatopic, nonasthmatic, never-smoking volunteers.

Interventions

On separate visits, subjects underwent a series of four inhalation challenges to LPS or CDE, each containing either a high (6 pg/mL) or low (0.9 pg/mL) endotoxin concentration, and administered at equal volumes.

Results

Chest tightness, cough, dyspnea, and sputum production were experienced following both LPS and CDE exposures and with similar frequency at both high and low endotoxin concentrations. LPS and CDE inhalations caused acute declines in FEV₁, and the changes in FEV₁ from baseline following exposure to both inhalants were not significantly different at both high and low endotoxin concentrations. Following exposure to the high-endotoxin LPS and CDE, no consistent differences in total cell and cytokine (tumor necrosis factor-α [TNF-α], interleukin-1β [IL-1β], IL-6, IL-8) concentrations were seen between exposures, although the neutrophil concentration was greater following the LPS exposure (p=0.01). BAL cellularity and cytokine concentrations following the low-endotoxin LPS and CDE exposure revealed no differences, except for IL-1β, which was greater following LPS exposure (p=0.05). The high-endotoxin LPS and CDE exposures resulted in greater increases in BAL neutrophils and cytokines in comparison to its respective low-endotoxin exposure.

Conclusions

At equivalent exposure levels of endotoxin, LPS and CDE result in similar symptoms, changes in airflow, and increases in BAL inflammatory cells and mediators. Moreover, the physiologic and inflammatory response to LPS and CDE appears to be related to the exposure level of endotoxin.

Section snippets

MATERIALS AND METHODS

We used a double-blind, randomized, crossover design to compare the physiologic and inflammatory response to inhalation of CDE to LPS solution containing equivalent concentrations of endotoxin activity.

RESULTS

Fourteen subjects, 9 men and 5 women, participated in the study, with subjects' ages ranging from 20 to 48 years (mean age, 30 years). All subjects completed a paired (CDE-LPS) exposure at the high endotoxin concentration (6 μg/mL), and 12 subjects completed a second paired (CDE-LPS) exposure at the low endotoxin concentration (0.9 μg/mL). Two subjects did not wish further participation because of the time commitment.

Following inhalation exposure to both the high and low endotoxin CDE and LPS

DISCUSSION

Our results indicate that following inhalation of LPS and CDE, which contain equal concentrations of endotoxin activity, similar physiologic and biological changes occur in otherwise healthy subjects. In addition, a similar percentage of study subjects developed specific symptoms following exposure to LPS and CDE at both high and low endotoxin concentrations, respectively. Moreover, the presence of respiratory symptoms, declines in airflow, and inflammation in the lower respiratory tract were

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: This study was supported by grants from the National Institute of Occupational Safety and Health, the Centers for Disease Control (UO7CCU7061454 and OH00134-02), the National Institute of Environmental Health Sciences (ES00203 and ES06537), and the General Clinical Research Centers Program (RR00059).

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Chest

Occupational and Environmental Lung DiseaseGrain Dust and Endotoxin Inhalation Challenges Produce Similar Inflammatory Responses in Normal Subjects

Study objective

Design

Participants

Interventions

Results

Conclusions

Section snippets

MATERIALS AND METHODS

RESULTS

DISCUSSION

Chest

Chest

J Allergy Clin Immunol

Chest

Toxicol Appl Pharmacol

Environ Res

Respiratory abnormalities among grain handlers: a clinical, physiologic, and immunologic study

Am Rev Respir Dis

Epidemiologic health survey of grain elevator workers in British Columbia

Am Rev Respir Dis

Chronic bronchitis and decreased forced expiratory flow rates in lifetime nonsmoking grain workers

Am Rev Respir Dis

A follow-up study of the grain elevator workers in the port of Vancouver

Arch Environ Health

Acute effects of grain dust exposure during a work shift

Am Rev Respir Dis

Epidemiologic study of clinical and physiologic parameters in grain handlers of northern United States

Am Rev Respir Dis

Grain dust and lung function: dose-response relationships

Am Rev Respir Dis

Rapid decline in FEV1 in grain handlers

Am Rev Respir Dis

Grain dust-induced airflow obstruction and inflammation of the lower respiratoiy tract

Am J Respir Crit Care Med

Gram-negative bacterial endotoxins in grain elevator dusts

Am Ind Hyg Assoc J

Occupational and Environmental Lung Disease
Grain Dust and Endotoxin Inhalation Challenges Produce Similar Inflammatory Responses in Normal Subjects

Rapid decline in FEV₁ in grain handlers