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Authors’ response
  1. M J Blaser,
  2. Y Chen,
  3. J Reibman
  1. New York University, School of Medicine, New York, USA
  1. Dr M J Blaser, New York University, School of Medicine, 550 First Avenue, New York, NY 10016, USA; martin.blaser{at}med.nyu.edu

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Dr Wjst addresses a number of important issues. First, he raises the point that “the stomach is not the first immunological line of defence”. We are not certain what the definition of the “first line” might be, but the literature contains ample evidence that the stomach has immunological function,1 2 and that the presence of Helicobacter pylori affects the nature of the response.35 For example, Mattson and colleagues provided evidence that H pylori-positive subjects had stronger gastric, intestinal and systemic responses to an orally administered cholera vaccine than did H pylori-negative subjects;3 in addition to providing evidence of measurable immunological functions, their study also provides a biological explanation for how H pylori may have provided a symbiotic function in the era when lethal intestinal infections selected human populations (and their indigenous microbes).6

Secondly, he is concerned that H pylori is acquired after the earliest time of life, which is a critical period for the development of asthma, and thus its presence or absence is irrelevant. This is a very reasonable consideration. One possibility is that whereas H pylori may not be detected until after the first year of life, it may actually be acquired earlier but remain at relatively low levels, below the level of detection. There is increasing evidence that the phenomenon of a low-level colonisation, below the level of conventional detection, may exist in general in some adults,7 8 but this has not been examined in children. The strong relationship of maternal colonisation,9 and specifically maternal genotypes,10 to the H pylori colonisation of children provides support for such a concept. However, this hypothesis has not been directly tested in children.

Thirdly, Wjst questions whether the inverse association of H pylori and asthma (and related allergic disorders) merely reflects confounding due to antibiotic use. Although this is a reasonable concern, two observations point against it—the specificity of the inverse association with cagA+ H pylori, and with childhood rather than adult asthma. The partial confounding effect of antibiotics should equally affect the relationship of asthma with both cagA+ and cagA strains, and might even be more notable for adult asthma with a greater cumulative exposure to antibiotics than for childhood asthma, but these were not observed. In our analyses of National Health and Nutrition Examination Survey (NHANES) data, we observed strong inverse associations between cagA+ H pylori strains and asthma,11 and between H pylori+ strains and early-life onset asthma.12 There was no association between H pylori positivity and time since asthma onset among participants who ever had asthma.12

Finally, Wjst faults us for stating that there is “no evidence of plausible competing theories or rival hypotheses”. Although, as he points out, there are many rival hypotheses, the issue of plausibility is a more complex issue. The wonderful characteristic of science, unlike religion, dogma and faith, is that hypotheses can be tested. Prospective studies are needed to understand causal relationships and to help ascertain intermediate mechanisms. We are continuing to test the hypothesis that H pylori protects against childhood asthma and related allergic disorders.

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