Bronchial hyperreactivity is associated with enhanced grain dust-induced airflow obstruction

Abstract

Bronchial hyperreactivity (BHR) is associated with the presence of airway inflammation in asthma and is seen in individuals occupationally exposed to grain dust. To better understand the relationship between BHR and pulmonary inflammation after grain dust exposure, we carried out an inhalation challenge to corn dust extract (CDE) on seven subjects with BHR [a 20% or greater decrease in forced expiratory volume in 1 s (FEV(1)) compared with diluent FEV(1) with a cumulative dose of histamine </=47.3 breath units] and compared their physiological and inflammatory responses with those of seven matched control subjects. BHR subjects were exposed to nebulized CDE (target dose of 0.16 microg/kg endotoxin) as tolerated; matched controls received equal amounts of CDE. Subjects with BHR complained of chest tightness and dyspnea within the 2 h after inhalation of CDE significantly more frequently than controls. Similarly, subjects with BHR developed significantly greater percent declines in FEV(1) at time points up to 4 h after exposure to CDE. Significant increases in total cells, neutrophils, tumor necrosis factor-alpha, interleukin-6, and interleukin-8 were detected in bronchoalveolar lavage fluid 4 h after inhalation of CDE in all subjects, but no differences were detected between the control and BHR groups. These results suggest that, although subjects with BHR develop a more precipitous decline in FEV(1) after exposure to CDE, the inflammatory response to CDE is similar in subjects with and without BHR.

Respiratory Syncytial Virus Up-regulates TLR4 and Sensitizes Airway Epithelial Cells to Endotoxin

“…It is also a ubiquitous contaminant of environmental exposures such as grain dust, house dust, and air pollution particles (47)(48)(49)(50)(51). For this reason, the reactivity of airway epithelium, especially as it relates to LPS, can have a profound effect on lung inflammatory responses.…”

Retracted: The Role of the Extracellular Matrix Protein Mindin in AirwayResponse to Environmental Airways Injury

“…LPS is ubiquitous in the environment. Experimental data from both mice (Schwartz 1996; Schwartz et al 1994) and humans (Jagielo et al 1996; O’Grady et al 2001) show that LPS can cause airway obstruction that lasts as long as 48 hr immediately after a single exposure (Kline et al 2000). Tlr4 is the transmembrane surface receptor for bacterial LPS.…”

Toll-like receptor 4 antagonist (E5564) prevents the chronic airway response to inhaled lipopolysaccharide

“…ENVIRONMENTAL ENDOTOXIN IS closely associated with asthma exacerbation (5,21) and by itself can cause persistent lung disease in humans (17,18) and mice (7,12,26) that shares many features in common with allergic asthma. Among agricultural workers, the concentration of endotoxin in the bioaerosol is the most important occupational exposure associated with the development (24,29) and progression (27) of persistent environmental airway disease.…”