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ARTICLE: Wanda Phipatanakul, Juan C. Celedón, Benjamin A. Raby, Augusto A. Litonjua, Donald K. Milton, Diane Sredl, Scott T. Weiss, and Diane R. Gold Endotoxin Exposure and Eczema in the First Year of Life Pediatrics 2004; 114: 13-18 [Abstract] [Full text] [PDF]

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Residual Detergent May Confound the Protector Effect of Endotoxin

Yo-Shen Chen   (21 October 2004)

Author's Response to "Residual Detergent May Confound the Protective Effect of Endotoxin"

Wanda Phipatanakul, MD, MS, Donald K. Milton, MD, DrPH, Juan C. Celedon, MD, DrPH, Diane R. Gold, MD, MPH   (27 October 2004)

Residual Detergent May Confound the Protector Effect of Endotoxin 21 October 2004
Yo-Shen Chen, Assistant Professor (Food Microbiology) Dept. of Food Science, Nutrition & Health Promotion, Mississippi State University Send letter to journal: Re: Residual Detergent May Confound the Protector Effect of Endotoxin yoshen{at}foodscience.msstate.edu Yo-Shen Chen	The authors found that "exposure to high levels of endotoxin in house dust in the first 2 to 3 months of life is associated with a decreased risk of eczema in the first year of life" (p. 17).  They interpreted this finding as to show "a potentially important protective effect of exposure to endotoxin in early life against the development of eczema in the first year of life" (p. 15).  I disagree with the interpretation that exposure to endotoxin yields any protective effect.  There is no direct bacteriological or biochemical theories that suggest endotoxin may be associated with lower level of allergic reactions.  In fact, existing evidence suggests that endotoxin may increase allergic reactions (Int J Occ Env Health 1997; 4(suppl 1):S26-31; Am Rev Respir Dis 1992; 146:352-7; Thorax 1998; 53(12):1047-52).  I argue that the residual cleaning detergents, presumably negatively associated with the level of endotoxin and trigger of immunal responses, may confound the protector effect reported in this study.  I suggest that the authors measure, and statistically control for, the level of residual detergenets in the home environment in their next study.
Author's Response to "Residual Detergent May Confound the Protective Effect of Endotoxin" 27 October 2004
Wanda Phipatanakul, MD, MS, Pediatric Allergist and Immunologist Children's Hospital, Boston, Donald K. Milton, MD, DrPH, Juan C. Celedon, MD, DrPH, Diane R. Gold, MD, MPH Send letter to journal: Re: Author's Response to "Residual Detergent May Confound the Protective Effect of Endotoxin" wanda.phipatanakul{at}childrens.harvard.edu Wanda Phipatanakul, MD, MS, et al.	Author’s Response: There are strong biological theories and evidence to support the hypothesis that endotoxin may modulate development of the immune system early in life(1, 2). Endotoxin may direct the immune system toward an effective Th1 phenotype, or at least a more balanced Th1/Th2 phenotype. There is also significant evidence that endotoxin can induce airways inflammation and may enhance Th2 responses later on in life. All of the references cited by the author of this letter concern responses to high doses of endotoxin in adulthood and are less relevant to potential effects of endotoxin exposure on the development of immune responses during infancy. Endotoxin effects are well known to depend very sensitively on target, timing of exposure, dose, and dose rate. (3) The issue of irritant effects of cleaning detergents is an interesting one. There is some data to suggest that certain cleaning compounds, and especially quaternary ammonium compounds, may act as adjuvants as well as direct irritants and are a risk factor for asthma. (4) Several recent reports have suggested that exposure to cleaning compounds in homes and work environments are associated with asthma. (5) Whether use of cleaning compounds in the home is associated with endotoxin exposure is not known. One study suggested that steam cleaning carpets was associated with increased endotoxin. (6) Studies designed to reduce endotoxin exposures in homes are limited in number. In summary, while the writer's suggestion that there is no biological basis for the observed association with endotoxin is unfounded, a study of residual disinfectants such as ammonium compounds would be interesting. Wanda Phipatanakul, MD, MS Donald K. Milton, MD, DrPH Juan C. Celedón, MD, DrPH Diane R. Gold, MD, MPH REFERENCES 1. Tulic MK, Wale JL, Holt PG, Sly PD. Modification of the inflammatory response to allergen challenge after exposure to bacterial lipopolysaccharide. Am J Respir Cell Mol Biol 2000;22(5):604-12. 2. Vercelli D, Baldini M, Stern D, Lohman IC, Halonen M, Martinez F. CD14: a bridge between innate immunity and adaptive IgE responses. J Endotoxin Res 2001;7(1):45-8. 3. Eisenbarth SC, Piggott DA, Huleatt JW, Visintin I, Herrick CA, Bottomly K. Lipopolysaccharide-enhanced, Toll-like Receptor 4-dependent T Helper Cell Type 2 Responses to Inhaled Antigen. J. Exp. Med. 2002;196(12):1645-1651. 4. Preller L, Doekes G, Heederik D, Vermeulen R, Vogelzang PF, Boleij JS. Disinfectant use as a risk factor for atopic sensitization and symptoms consistent with asthma: an epidemiological study. Eur Respir J 1996;9(7):1407-13. 5. Zock JP, Kogevinas M, Sunyer J, Almar E, Muniozguren N, Payo F, et al. Asthma risk, cleaning activities and use of specific cleaning products among Spanish indoor cleaners. Scand J Work Environ Health 2001;27(1):76- 81. 6. Wickens K, Douwes J, Siebers R, Fitzharris P, Wouters I, Doekes G, et al. Determinants of endotoxin levels in carpets in New Zealand homes. Indoor Air 2003;13(2):128-35.