[HTML][HTML] Does inhalation of endotoxin cause asthma?

DA Schwartz - American journal of respiratory and critical care …, 2001 - atsjournals.org
American journal of respiratory and critical care medicine, 2001atsjournals.org
Asthma is a chronic inflammatory disorder of the airways that is characterized by reversible
airflow obstruction, airway hyperreactivity, and airway remodeling (1). Although the
prevalence, incidence, severity, and mortality rate of asthma are increasing in the United
States (1), we are only beginning to identify the environmental, genetic, and biological
factors that are responsible for this epidemic. The article by Park and coworkers (pp. 322–
328)(2) in this issue of the Journal raises the intriguing possibility that chronic inhalation of …
Asthma is a chronic inflammatory disorder of the airways that is characterized by reversible airflow obstruction, airway hyperreactivity, and airway remodeling (1). Although the prevalence, incidence, severity, and mortality rate of asthma are increasing in the United States (1), we are only beginning to identify the environmental, genetic, and biological factors that are responsible for this epidemic. The article by Park and coworkers (pp. 322–328)(2) in this issue of the Journal raises the intriguing possibility that chronic inhalation of endotoxin contributes to the development of this disorder. Endotoxin or lipopolysaccharide (LPS), a cell wall component of gram-negative bacteria, is ubiquitous in the environment, and is often present in high concentrations in organic dusts (3), as well as in air pollution (4) and household dusts (5). Given the potent inflammatory effects of endotoxin, it is logical to consider the role of this agent in the development and exacerbation of asthma.
Inhaled endotoxin can exacerbate airflow obstruction and airway inflammation in individuals with allergic asthma. Among those with allergic asthma who are sensitive to house dust mite allergen, the concentration of endotoxin in the home environment, but not the concentration of mite allergen (Der p1), was significantly associated with the severity of asthma (5). Experimentally, subjects with allergic asthma are more sensitive to the bronchoconstrictive effects of inhaled endotoxin (6). Moreover, among those with allergic asthma, prior allergen challenge significantly augments the inflammatory response to inhaled endotoxin (7). The enhanced response to inhaled endotoxin among individuals with allergic asthma may simply reflect the additive effect of preexisting airway inflammation but could also be caused by release of lipopolysaccharidebinding protein (LBP) when subjects with allergic asthma are challenged with allergen (8). In mice sensitized to ovalbumin, inhalation of LPS has been shown to exacerbate the inflammatory response to ovalbumin (9). In aggregate, these findings indicate that allergic airways can enhance the response to inhaled endotoxin, and that endotoxin can enhance the airway response to allergens.
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