© 2003 American Thoracic Society
Environmental endotoxin and asthmaTo the Editor:Environmental endotoxin may have an atopy-protective effect according to several authors. Gehring and colleagues have shown that exposure to higher levels of house dust endotoxin is associated with lower prevalence of allergic sensitization in children. They could not correlate this observation with asthma due to lack of statistical significance (1). Recently, endotoxin levels in dust from children's mattresses were found to be inversely related to the occurrence of hay fever, atopic asthma and atopic sensitization (2). However, in both studies, the authors did not identify by culture or other methods the gram-negative bacteria producing the endotoxin. The endotoxin receptor CD14 and Toll-like receptor of immune cells play important roles in the induction of endotoxin tolerance and are affected differentially by diverse species of gram-negative bacteria (3). This fact underlines the need to identify the gram-negative bacteria involved. Enterobacteriaceae have often been isolated in dust. It would, therefore, be important to detect antibodies against Enterobacteriaceae in the children's sera to determine if their level or presence is also inversely related to allergic disease. Enterobacterial common antigen (ECA) would be an appropriate target for this investigation. ECA is a cell surface antigen shared by all members of Enterobacteriaceae, and the wec gene cluster is implicated in its synthesis. Antibodies against ECA are found in all adults, including pregnant women. They belong to the IgM class, and newborns do not have anti-ECA antibodies (4). It is a strong argument against the potential benefit of an in utero exposure to endotoxin, a hypothesis that has been raised in the literature (5). The study of environmental endotoxin, using a kinetic limulus assay, has been widely used. We also need more specific methods to identify the gram-negative bacteria producing the endotoxin with protective effects, found in house dust of children who have lived in the same home since birth (1) or in a farm environment in their first year. We have devised consensus primers, using wec gene templates for the specific PCR-based detection of Enterobacteriaceae DNA (6). The nature of bacterial DNA in dust could be ascertained with this molecular method or another one able to detect viable and nonviable microorganisms. Such a combined approach, in a large prospective control study with statistical power, would help to define the role of Enterobacteriaceae in asthma and to develop a specific strategy for primary prevention of the disease.
Centre Hospitalier de l'Université de Montréal Montreal, Quebec, Canada REFERENCES
From the Authors: We thank Dr. Bayardelle for his comments on our paper, which showed a protective effect of exposure to higher levels of house dust endotoxin on allergic sensitization in schoolchildren (1). Dr. Bayardelle correctly states that we did not distinguish different species of gram-negative bacteria as major sources of bacterial endotoxin. We agree with him that there is a need to identify the species of gram-negative bacteria that are responsible for the protective effect. The approach suggested by Dr. Bayardelle may give us further insight as to the species of bacteria involved if application to large epidemiological studies is feasible.
However, besides endotoxin there are other components of house dust with immunostimulatory properties, such as other bacterial components and ß(1
GSF—Institute of Epidemiology Neuherberg, Germany REFERENCES
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3)-glucans. Cell–wall components from atypical mycobacteria or gram-positive bacteria such as lipoteichoic acid, are known to affect immune responses similar to endotoxin (