Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Reply to “Acid inhibitors and allergy: comorbidity, causation and confusion”

The Original Article was published on 07 August 2020

Replying to Kewin Tien Ho Siah Nature Communications (2020).

We cordially thank Dr. Siah for their comments on our publication1, giving us the opportunity to clarify some points and to discuss limitations inherent in observational studies in general and analysis of claims data in particular.

Our publication “Country-wide medical records infer increased allergy risk of gastric acid inhibition”2 confirmed smaller previous studies in adults and children3,4,5. The relationship between anti-acid drug prescriptions followed by anti-allergy medication prescriptions was specific and not observed after prescriptions of other commonly prescribed drugs. With this in mind, we agree that the sequence of prescriptions is important and was among the first things we checked in our data base. However, it has to be considered that prescription rates of anti-acid drugs are around three times higher than anti-allergy medication prescriptions. It follows, that without any influence of an anti-allergy medication prescription on subsequent anti-acid drug prescriptions, this sequence must occur more frequently than the opposite one. However, our analyses of the country-wide and regional data sets showed that prescription of anti-allergy substances did not result in any elevated risk for subsequent anti-acid drug prescriptions. Contrarily, the hazard ratio for prescription of gastric acid-inhibiting drugs after anti-allergy drugs was below 1 (0.82 [95% confidence interval 0.80–0.84]; p < 0.001) when compared with other commonly prescribed drug classes used as controls, clearly implying an asymmetric relationship.

Considering the unidirectional phenomenon of an increased risk of anti-allergy medications after an anti-acid drug prescription, we agree that future research might reveal relationships linking dyspepsia and allergic diseases. Dr. Siah stressed correctly that observational studies and especially analyses of claims data, provide on their own no firm basis for cause-and-effect statements. Therefore, we referred the reader to the consistency of our findings with experimental data. Although we also agree that randomized controlled studies (RCTs) could, in principle, clarify whether or not the observed association is causal, we doubt that such RCTs will ever be conducted owing to a lack of commercial interest and because of the ethical issues.

As medical doctors, we regard gastric acid-inhibiting drugs as invaluable therapeutic options in a variety of dyspeptic diseases, if indication and reasonable prescription duration are considered. Also as MDs, we are trained to handle patients’ many anxieties, and must take the responsibility to explain, prescribe, and discontinue the anti-acid treatments in a controlled manner. We further stress that guidelines, pointing to a discontinuation of acid-inhibiting drug prescriptions as soon as there is no further indication, should be adhered to.

Data availability

The data that support the findings of this study were made available to the authors of this study by all major Austrian compulsory health insurance companies under the ethics vote ECS 1134/2014. General Data Protection Regulations Restrictions apply to the availability of these data, which were used under license for this study. However, any researcher can access the data by obtaining an ethical approval from the regional ethical review board and thereafter addressing requests for data to DI Berthold Reichardt, representative for the involved Austrian compulsory health insurance companies.

Code availability

Most analyses were conducted using standard procedures without special code development. For data extraction and calculation of prevalences, code can be obtained upon request to the corresponding author.


  1. Siah, K. T. H. Acid inhibitors and allergy: comorbidity, causation and confusion. Nat. Commun. (2020). 

  2. Jordakieva, G. et al. Country-wide medical records infer increased allergy risk of gastric acid inhibition. Nat. Commun.10, 3298 (2019).

    ADS  Article  Google Scholar 

  3. Untersmayr, E. et al. Anti-ulcer drugs promote IgE formation toward dietary antigens in adult patients. FASEB J.19, 656–658 (2005).

    CAS  Article  Google Scholar 

  4. Devine, R. E., McCleary, N., Sheikh, A. & Nwaru, B. I. Acid-suppressive medications during pregnancy and risk of asthma and allergy in children: a systematic review and meta-analysis. J. Allergy Clin. Immunol.139, 1985–1988.e12 (2017).

    CAS  Article  Google Scholar 

  5. Dehlink, E., Yen, E., Leichtner, A. M., Hait, E. J. & Fiebiger, E. First evidence of a possible association between gastric acid suppression during pregnancy and childhood asthma: a population-based register study. Clin. Exp. Allergy39, 246–53 (2009).

    CAS  Article  Google Scholar 

Download references

Author information

Authors and Affiliations



G.J. wrote the manuscript draft, contributed to data collection, and performed the data analysis. M.K. performed the analysis, contributed analysis tools, contributed to conceiving and designing the analysis, and to writing of the manuscript. E.U. and I.P.S. contributed to data analysis and writing of the manuscript. B.R. collected the data and contributed to the analysis design. G.J., I.P.S., and E.J.J. designed Figure 1. E.J.J. conceived and designed the analysis, contributed to collection of the data, data analysis, writing of the paper, and critical revision of the manuscript.

Corresponding author

Correspondence to Erika Jensen-Jarolim.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Peer review informationNature Communications thanks Marino Venerito and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Jensen-Jarolim, E., Kundi, M., Untersmayr, E. et al. Reply to “Acid inhibitors and allergy: comorbidity, causation and confusion”. Nat Commun 11, 3949 (2020).

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI:


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing