Inspection confirmed mold damage in schools and new use of drugs for airway obstruction: A cohort study

Juha Pekkanen; Martin Täubel; Lauri Lehtimäki; Tero Marttila; Anne M. Karvonen

doi:10.1371/journal.pone.0333486

Peer Review History

Original SubmissionMay 21, 2025
12 Jun 2025 Decision Letter - Thomas Behrens, Editor PONE-D-25-22528Inspection confirmed mold damage in schools and new use of drugs for airway obstruction: A cohort studyPLOS ONE Dear Dr. Pekkanen, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. In particular, both reviewers were concerned with the unspecificity of the outcome for mould exposure that shoukld be discussed in more detail. Also, to the correlation with maternal SES a few more statements should be dedicated in the discussion. Please ensure that your decision is justified on PLOS ONE’s publication criteria and not, for example, on novelty or perceived impact. 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If your ethics statement is written in any section besides the Methods, please move it to the Methods section and delete it from any other section. Please ensure that your ethics statement is included in your manuscript, as the ethics statement entered into the online submission form will not be published alongside your manuscript. Additional Editor Comments (if provided): [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: No Reviewer #2: Partly ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: N/A Reviewer #2: Yes ****** 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: No Reviewer #2: Yes ****** 5. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: The aim of this study was to examine whether the extent and severity of mould damage in school buildings increases the risk of newly initiated medication use due to airway obstruction among students, and whether a dose-response relationship can be established. Mould infestation in buildings can lead to various health impairments in sensitive and particularly predisposed individuals – ranging from unpleasant odours and irritations to allergies and asthmatic symptoms. However, asthmatic symptoms may have diverse causes and are not solely dependent on mould infestation in school buildings. A direct association between mould infestation and increased medication use is therefore not immediately evident, making the study’s finding – that there is no association between mould infestation and students’ medication use – is not surprising. While mould exposure was assessed in detail and various confounding factors were taken into account, no information was available on the students’ health complaints. It remains unclear why maternal socioeconomic status was correlated with mould exposure. Although the data from the registry study and the exposure assessment were extensive, the information is insufficient to answer the study’s research question. In particular, the students’ health status is not adequately documented. Data should be included on whether, among other factors, there is an early childhood atopic predisposition. Reviewer #2: My opinion is that the outcome variables (new asthma or new obstructive airway disease) are too nonspecific for mold exposure and a specific part of discussion should be dedicated to that part. Also we know from many studies that a low dose of allergen is allergenic and a high dose exposure induces tolerance. This should be also discussed in detail. This two points are important when interpreting the obtained results. ****** 6. PLOS authors have the option to publish the peer review history of their article (what does this mean? ). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy . Reviewer #1: No Reviewer #2: No ******** https://doi.org/10.1371/journal.pone.0333486.r001
Revision 1
1 Sep 2025 Author Response Plos One Dear editors, Please find below our responses to the reviewers comments. The editor commented: “In particular, both reviewers were concerned with the unspecificity of the outcome for mould exposure that should be discussed in more detail. Also, to the correlation with maternal SES a few more statements should be dedicated in the discussion.” We have now carefully addressed both of these concerns. In addition to the below changes requested by the reviewers, we have made following changes to the manuscript: 1. In previous analyses, we used mother’s nationality as a confounder, but this variable had a lot of missing values. As maternal SES is potentially an important confounder, we have now replaced mother’s nationality with mother’s language and rerun all analyses. This resulted, however, in only minor changes in the second decimal of the odds ratios. 2. While redoing the analyses, we noticed that there was a mistake in the footnotes of all tables except tables 1 and 4: model 1 is adjusted only for age and sex. This is now corrected. On behalf of all of the authors Helsinki 23.8.2025 Juha Pekkanen [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: No Reviewer #2: Partly ________________________________________ 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: N/A Reviewer #2: Yes ________________________________________ 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes ________________________________________ 4. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: No Reviewer #2: Yes ________________________________________ 5. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: The aim of this study was to examine whether the extent and severity of mould damage in school buildings increases the risk of newly initiated medication use due to airway obstruction among students, and whether a dose-response relationship can be established. Mould infestation in buildings can lead to various health impairments in sensitive and particularly predisposed individuals – ranging from unpleasant odours and irritations to allergies and asthmatic symptoms. However, asthmatic symptoms may have diverse causes and are not solely dependent on mould infestation in school buildings. A direct association between mould infestation and increased medication use is therefore not immediately evident, making the study’s finding – that there is no association between mould infestation and students’ medication use – is not surprising. Response 1: Thank you for this comment. It is true that asthma and asthmatic symptoms have many causes, like practically all medical problems. The challenge in epidemiological studies is to control those causes, which confound the association under study, and to avoid other biases. We discuss in length that the control for confounders and assessment of exposure was not perfect, but were pleased with the reviewer’s comment on that ‘mould exposure was assessed in detail and various confounding factors were taken into account’ (see next comment). It should also be noted that previous evidence on the association between mould damage and development of new asthmatic problems comes exactly from the same type of studies as the present one (see references 1-6). Therefore, we did expect to see at least a weak direct association between mould in schools and development of new asthma, which however was not the case, despite a very large study population. While mould exposure was assessed in detail and various confounding factors were taken into account, no information was available on the students’ health complaints. Response 2: This comment refers to two possible points, which are also raised in other comments: first, that better information on students’ health complaints at baseline could help to identify a susceptible subgroup of students (see response 2.1); and second, that better information on students’ health complaints at follow-up would be needed to answer the research question of the present study (see response 2.2) Response 2.1: It is true that predisposing factors are important for some adverse effects of mould, but only very few studies have observed predisposing factors for new asthma associated with mould damage (reference 2). One study has shown stronger associations between mould and new asthma among those with previous atopic sensitization (see reference 24) and one with previous rhinosinusitis (see new reference 41). A new paragraph has been added on this on lines 392-399. As we now point out in the discussion (line 395), we did not have information of students’ atopic sensitization or past atopic eczema or rhinosinusitis, which could potentially be used to identity sensitive subjects. We also did not have data on self-reported symptoms, but we have now done additional analyses on a subgroup of 2881 students with previous respiratory complaints (based on medication use), but who had not yet developed asthma before the start of the follow-up. The results are very similar to those among all the students. The result has been added as new table 5 and to the Abstract, Methods (lines 160-161) and Discussion (lines 278 and 397-399) Response 2.2: It is true that better information of students’ health complaints at follow-up would be needed to study many potential outcomes related to mould damage, like atopic sensitization. However, the present study’s research question was, if mould damage in schools increases the risk of new asthma or asthmatic problems. This research question was chosen, as new asthma is considered the most important possible long-term consequence of indoor dampness and mold (see references 1-3). As we now point out in the Discussion, the definitions used in the present study are taken from previous studies on asthma (line 340, reference 20 and the new reference 36). It has also been earlier shown that data on medication use obtained from registries is a valid indicator of asthma (line 342-343, new reference 38). We now point out in the Discussion as a weakness that we did not have data to separate different phenotypes of asthma, like allergic asthma (343-344). As previously, we point out the specificity of the used definition for asthma and the results for another, less specific definition of obstructive airway problems (lines 338-351). It remains unclear why maternal socioeconomic status was correlated with mould exposure. Response 3: It is unclear, why such a correlation exists in our data, but it may be related to the fact that families living in the new neighborhoods built in Helsinki in the 1990’s were more often of lower social class and also were more often from foreign background (see new reference 39). This has now been pointed out in the Discussion (lines 359-361). Although the data from the registry study and the exposure assessment were extensive, the information is insufficient to answer the study’s research question. In particular, the students’ health status is not adequately documented. Data should be included on whether, among other factors, there is an early childhood atopic predisposition. Response 4: Thank you for the comments. This is discussed in response 2.1 above. Reviewer #2: My opinion is that the outcome variables (new asthma or new obstructive airway disease) are too nonspecific for mold exposure and a specific part of discussion should be dedicated to that part. Response 5: We appreciate this comment and have discussed this issue in response 2.2 Also we know from many studies that a low dose of allergen is allergenic and a high dose exposure induces tolerance. This should be also discussed in detail. This two points are important when interpreting the obtained results. Response 6: The present study’s research question was, if mould damage in schools increases the risk of new asthma or asthmatic problems. Mold exposure is only weakly associated with allergic sensitization (reference 2) and it is hypothesized that the pathogenetic mechanism between mold damage and development of asthma is related to enhancement of inflammatory reactions in the airways, rather that development of sensitization (reference 2). Also, we are not aware of previous evidence suggesting that high dose exposure to moisture damage and indoor mould could induce tolerance, while low dose would cause increased risk of asthma and sensitization. We now point out in the Discussion as a weakness that we did not have data to separate different phenotypes of asthma, like allergic asthma (line 343-344), however, we propose not to discuss in more detail the mechanisms of allergic sensitization and tolerance. Attachments Attachment Submitted filename: Response to reviewers.docx https://doi.org/10.1371/journal.pone.0333486.r002
15 Sep 2025 Decision Letter - Thomas Behrens, Editor Inspection confirmed mold damage in schools and new use of drugs for airway obstruction: A cohort study PONE-D-25-22528R1 Dear Dr. Pekkanen, We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements. Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. For questions related to billing, please contact billing support . If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Thomas Behrens Academic Editor PLOS ONE Comments to the Author 1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation. Reviewer #1: All comments have been addressed Reviewer #2: All comments have been addressed ******** 2. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Partly Reviewer #2: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: N/A Reviewer #2: Yes ****** 4. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes ****** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: Thank you for the addition of further detailed information. Some issues are now more clear and enhanced the quality of the manuscript Reviewer #2: The authors have answered all raised questions by reviewers in a proper and understandable way. The changes are visible in the text in the part with track changes. ****** 7. PLOS authors have the option to publish the peer review history of their article (what does this mean? ). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy . Reviewer #1: No Reviewer #2: No ******** https://doi.org/10.1371/journal.pone.0333486.r003
Formally Accepted
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