© 2006 American Thoracic Society
Endotoxin and AsthmaFrom the Authors:We appreciate Dr. Rylander's interest in our recent article (1). We wish to point out that we did not conclude "that the symptomatology reflects an inflammatory response" as stated in Dr. Rylander's letter. Rather, we reported associations of self-reported health outcomes (diagnosed asthma, asthma symptoms, wheezing, and asthma medication use) with endotoxin exposure while adjusting for exposure to other environmental agents such as common household allergens (Der p, Der f, Can f, Fel d) and environmental tobacco smoke. We concluded that household endotoxin exposure is a significant risk factor for increased asthma prevalence and speculated that the lack of impact of endotoxin exposure on allergy status suggests that inflammation was the most important effect of the endotoxin exposure. We did not assess environmental concentrations of other microbial inflammatory agents and made no statements regarding causality. As with any observational study, it is possible that confounding may have masked the true agent responsible for the relationship of endotoxin to the assessed health outcomes. It is recognized that various components of microorganisms have immunomodulatory or inflammatory potency, although human and animal exposure studies point to endotoxin as especially potent. Recent work has shown that as few as 100 molecules of endotoxin are capable of initiating signal transduction via TLR4 mobilization and activation (2). Since each gram-negative bacterium contains about 1 million endotoxin molecules, a single bacterium can activate 103 to104 host cells (3). Other microbial agents are either less potent or their potency has not been established. While the potential for confounding cannot be dismissed, we can consider the role of endotoxin by evaluating the degree to which it satisfies criteria for causality (4). The so-called Iowa Postulates evaluate data from epidemiological studies, human challenges, case reports, animal studies, and in vitro studies and apply a weighting of the evidence in seven categories to assess causality: (1) assessment of exposure to specific agents, (2) control or consideration of confounders, (3) evidence of a dose–response relationship, (4) consistent results from different studies, (5) objective clinical data, (6) endpoints related to human disease (from animal studies), and (7) appropriate subjects or models. If we consider the evidence in each of these categories for household bacterial or fungal components as agents of inflammatory lung disease leading to asthma exacerbation, the evidence is clear and convincing only for endotoxin. However, our cross-sectional study did not allow us to address the issue of causality directly.
University of Iowa, Iowa City, Iowa
National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina REFERENCES
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