Comparative Effect of Soft, Hard and Chlorinated Water on Atopic Skin and Clinical Benefits of a Dermocosmetic Routine

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Thank you for the invitation to review the manuscript entitled "Comparative Impact of Hard and Chlorinated Water on Biometrological Parameters of Atopic Skin and the Clinical Benefits of Dermocosmetic Routine Interventions." The presented work is a description of a small study referred to by the authors themselves as a clinical study. It concerns a group of patients with atopic dermatitis who underwent a series of interventions. The topic is important and interesting; however, the manuscript has several shortcomings that preclude its publication in a scientific journal.

First, I would like to address the appropriateness of the term “biometrological” in the manuscript title. Biometrological refers to biometrology, which is the science of measurement in biology and medicine, focusing on accuracy, method validation, and measurement uncertainty. This term does not describe the characteristics or function of the skin but rather the technical aspects of measurement. Therefore, the title itself is already inaccurate.

Secondly, the manuscript does not include information regarding review and approval by a Bioethics Committee for the conduct of this study. While testing cosmetics for marketing claims does not require such approval, studies intended for publication in a scientific journal do. In this specific case, this is particularly important because the study involved patients with a disease, rather than healthy volunteers, which requires careful consideration of any interventions (as evaluated by a Bioethics Committee). Clear inclusion and exclusion criteria are not reported, nor is it indicated whether all participants who enrolled in the study completed it. Furthermore, there is no information on whether participants were allowed to use other emollients or skincare products alongside the tested products. If they were not, this would make ethical approval even more crucial, since prohibiting the use of emollients is inconsistent with clinical knowledge and practice.

The manuscript also lacks a declaration of potential conflicts of interest. The authors’ affiliations suggest that they are employed by the manufacturer of the tested cosmetic products.

The manuscript contains minor errors, such as referencing tables and figures without providing their numbers. The captions of tables and figures do not meet the principle of self-explanatory labeling and do not provide sufficient information for interpreting the presented data. The citation style used in the text differs from that recommended by the journal. Lines 63-67, which appear in the Introduction, actually belong to the Methods section.

The authors have selected inappropriate statistical tests: it is not correct to compare three groups using a Student’s t-test. Using this test to analyze data on an ordinal scale is also a significant simplification. Statistical results are presented inconsistently: sometimes p-values are given to four decimal places, while in other instances it is only indicated whether they are greater or less than the significance threshold of 0.05.

The first sentence of section 2.2.4, claiming that a tool was used to obtain objective results, is incorrect.

In line 250 (Results section), there is a reference to literature. According to standard scientific practice, results should not be interpreted in this section. If the authors wish to introduce a method, it should be included in Materials and Methods; if they wish to discuss a result, it should be included in the Discussion.

The Discussion section requires substantial revision. It is currently insufficient, with the only interesting element being a reference to unpublished results. While referencing unpublished data is acceptable, it must be done with caution. It is advisable to provide a brief description of the method so that readers understand how the result was obtained.

Similarly, the Conclusions section requires a thorough overhaul. The most valuable element of this study is its protocol, which should be highlighted. The current conclusions largely contain truistic statements.

 

Author Response

Dear Editor,

We are pleased to submit the revised version of our manuscript and would like to thank you for the additional time allowed for revision. We are also sincerely grateful to the reviewers for their constructive comments.

In response to the reviewers’ comments, the dataset was entirely re-analysed using appropriate statistical methods. This resulted in substantial changes to the interpretation of the results and led to a complete rewriting of the manuscript. Although we provide a detailed point-by-point response to the reviewers, the submitted file is an entirely new version of the manuscript; for this reason, tracked changes have not been applied.

Sincerely,

Helena Polena

 

Reviewer 1

Thank you for the invitation to review the manuscript entitled "Comparative Impact of Hard and Chlorinated Water on Biometrological Parameters of Atopic Skin and the Clinical Benefits of Dermocosmetic Routine Interventions." The presented work is a description of a small study referred to by the authors themselves as a clinical study. It concerns a group of patients with atopic dermatitis who underwent a series of interventions. The topic is important and interesting; however, the manuscript has several shortcomings that preclude its publication in a scientific journal.

We are grateful to the reviewer for the thorough and constructive assessment of our manuscript. We fully acknowledge that, as the reviewer correctly identified, the original submission suffered from significant shortcomings.

Among these, the use of unsuitable statistical tests led to the presentation of results that did not accurately reflect the data and affected their interpretation. In light of this, we took the decision to re-analyse the entire dataset using appropriate statistical methods, as detailed in the revised Section 2.5. This re-analysis produced significantly different outcomes, necessitating a complete rewriting of the Results, Discussion, and Conclusions sections. The Materials and Methods were also substantially revised to address the additional methodological deficiencies identified by the reviewer.

The revised manuscript has been entirely rewritten and differs so fundamentally from the original submission that point-by-point references to specific line numbers would be uninformative. We trust that the reviewer will find the new version sufficiently reorganised and improved to allow straightforward cross-referencing with the individual comments addressed below. For the same reason, the revised manuscript is not presented with tracked changes, as the volume and nature of the modifications rendered this approach impractical. We hope the reviewer will accept this departure from standard practice in light of the circumstances.

First, I would like to address the appropriateness of the term “biometrological” in the manuscript title. Biometrological refers to biometrology, which is the science of measurement in biology and medicine, focusing on accuracy, method validation, and measurement uncertainty. This term does not describe the characteristics or function of the skin but rather the technical aspects of measurement. Therefore, the title itself is already inaccurate.

We concur with the reviewer that the use of "biometrological" is inaccurate. We have removed all instances of this term (previously appearing three times, including in the title). The revised manuscript now employs standard terminology throughout the study.

Secondly, the manuscript does not include information regarding review and approval by a Bioethics Committee for the conduct of this study. While testing cosmetics for marketing claims does not require such approval, studies intended for publication in a scientific journal do.

In this specific case, this is particularly important because the study involved patients with a disease, rather than healthy volunteers, which requires careful consideration of any interventions (as evaluated by a Bioethics Committee).

We fully acknowledge that the original submission lacked an Ethics section and an IRB statement, and we agree that these are essential components of any manuscript intended for publication in a peer-reviewed journal, irrespective of the regulatory context. Both omissions have been corrected in the revised manuscript.

A dedicated Ethics section has been added to the Materials and Methods (Section 2.2), and an Institutional Review Board statement has been included in the back matter.

As detailed therein, both studies consisted in the non-invasive evaluation of dermocosmetic products and were conducted in Poland. Under the applicable legislative framework — Regulation (EC) No 1223/2009, Commission Regulation (EU) No 655/2013, and the Polish Order of the Minister of Health of 2 May 2012 (Dz.U. 2012, item 491) — such studies are explicitly exempted from mandatory ethics committee review. This exemption applied even though the participants had atopic dermatitis, given that the interventions involved no experimental drug, medical device, or invasive procedure. Both studies were conducted in full accordance with the principles of the Declaration of Helsinki and Good Clinical Practice. Written informed consent was obtained from all participants prior to enrolment, and adverse events were monitored throughout the studies.

Clear inclusion and exclusion criteria are not reported, nor is it indicated whether all participants who enrolled in the study completed it. Furthermore, there is no information on whether participants were allowed to use other emollients or skincare products alongside the tested products. If they were not, this would make ethical approval even more crucial, since prohibiting the use of emollients is inconsistent with clinical knowledge and practice.

All three points raised by the reviewer have been addressed in the revised manuscript.

Inclusion and exclusion criteria are now explicitly detailed in the Subjects subsections of both studies (Sections 2.3.1 and 2.4.1). For the controlled immersion study, inclusion required a physician-confirmed diagnosis of atopic dermatitis in the absence of active flares; exclusion criteria comprised active eczema flares, cutaneous lesions or excessive forearm hair, and receipt of topical or systemic treatments liable to interfere with the study within the preceding two weeks. The real-life study applied equivalent exclusion criteria, with inclusion additionally requiring fulfilment of the UK Working Party's diagnostic criteria for atopic dermatitis.

Study completion is now reported at the beginning of the Results section (Section 3.1): 65 of 66 enrolled subjects completed the controlled immersion study (one participant in the chlorinated water subgroup withdrew at the end of day 1 due to an adverse reaction to chlorinated water); all 66 participants enrolled in the real-life study completed the investigation.

Regarding concomitant skincare use, participants in both studies were explicitly asked to maintain their usual hygiene routine. They were also asked to refrain from applying hygiene or skincare products to the forearm test areas in the controlled study, and to avoid other hygiene or skincare products on the forearm test areas in the real-life study. This is now clearly stated in the Interventions subsections (Sections 2.3.2 and 2.4.2). The study design therefore remained consistent with established clinical practice and current atopic dermatitis management guidelines, which recommend the continued use of emollients as a cornerstone of maintenance therapy.

The manuscript also lacks a declaration of potential conflicts of interest. The authors’ affiliations suggest that they are employed by the manufacturer of the tested cosmetic products.

The reviewer is correct that the original submission lacked a conflict of interest declaration, and we fully acknowledge this omission. The revised manuscript now includes a complete set of back matter, comprising Author Contributions, Funding, Institutional Review Board Statement, Informed Consent Statement, Data Availability Statement, Acknowledgments, and a Conflicts of Interest statement.

The Conflicts of Interest statement explicitly discloses that all authors are full-time employees of NAOS (Bioderma), the manufacturer of the products evaluated in the study. The Funding section likewise identifies NAOS (Bioderma) as the study sponsor. The Acknowledgments section further clarifies the respective roles of the parties involved: the clinical evaluations were conducted independently by EUROFINS Dermscan/Pharmascan, who were responsible for subject recruitment, measurement acquisition, data collection, and quality control, whilst statistical analysis and scientific writing were performed by an independent consultant. This tripartite structure — industry sponsorship, independent clinical execution, and independent statistical analysis — is disclosed transparently and is consistent with standard practice for industry-sponsored dermocosmetic research.

The manuscript contains minor errors, such as referencing tables and figures without providing their numbers. The captions of tables and figures do not meet the principle of self-explanatory labeling and do not provide sufficient information for interpreting the presented data. The citation style used in the text differs from that recommended by the journal. Lines 63-67, which appear in the Introduction, actually belong to the Methods section.

We fully agree with the reviewer's assessment that the original manuscript contained numerous formal deficiencies. The revised manuscript has been comprehensively restructured and corrected in the following respects.

All figures and tables are now explicitly numbered and cross-referenced in the text. Figure and table captions have been entirely rewritten to meet the principle of self-explanatory labelling: each caption now provides a full description of the data presented, defines all abbreviations used, specifies the time points evaluated, and explains the statistical notation employed, such that each figure and table can be interpreted independently of the main text.

The citation style has been revised throughout to conform to the formatting requirements of Cosmetics (MDPI), using sequential numbered references in square brackets.

The text previously appearing at lines 63-67 of the Introduction, which described methodological elements, has been removed from the Introduction and integrated into the appropriate subsections of the Materials and Methods.

The authors have selected inappropriate statistical tests: it is not correct to compare three groups using a Student’s t-test. Using this test to analyze data on an ordinal scale is also a significant simplification. Statistical results are presented inconsistently: sometimes p-values are given to four decimal places, while in other instances it is only indicated whether they are greater or less than the significance threshold of 0.05.

We fully concur with the reviewer's critique. The entire dataset has been re-analysed using appropriate statistical methods, as detailed in the revised Section 2.5 (Statistical Analysis). Specifically: (i) comparisons between two conditions are now performed using paired t-tests for normally distributed continuous data and Wilcoxon signed-rank tests otherwise, following prior assessment of distributional normality using the Shapiro–Wilk test; (ii) multiple comparisons of continuous data are now performed using repeated-measures ANOVA followed by Tukey's HSD post-hoc tests for normally distributed data, and the Friedman test followed by pairwise Wilcoxon signed-rank tests for non-normally distributed data, with p-values adjusted using the Bonferroni correction in both cases; and (iii) all subjective discomfort outcomes, being ordered categorical data, are now analysed exclusively using Wilcoxon signed-rank tests, with Friedman tests applied prior to pairwise comparisons where multiple conditions are involved. These corrections have affected the results. Sections 3.1 and 3.2, as well as the relevant passages of the Discussion, have been entirely rewritten to reflect the revised analyses.

P-value reporting has also been standardised throughout: results are reported as Bonferroni-adjusted p-values where applicable, using consistent threshold notation (p<0.05, p<0.01, p<0.001) in all figures, tables, and text.

The first sentence of section 2.2.4, claiming that a tool was used to obtain objective results, is incorrect.

The reviewer is correct. The opening sentence of Section 2.2.4 in the original manuscript erroneously stated that both subjective and objective parameters were assessed in the real-life study. In fact, no instrumental measurements were performed in either real-life condition; all outcomes were based on subjective self-assessment (five-item discomfort scale and DLQI) and clinical tolerability evaluation. This inaccurate claim has been removed in the revised manuscript. Section 2.4.3 (Subjective and Tolerance Assessments) now accurately describes only the self-assessment methods employed, without any reference to objective measurements.

In line 250 (Results section), there is a reference to literature. According to standard scientific practice, results should not be interpreted in this section. If the authors wish to introduce a method, it should be included in Materials and Methods; if they wish to discuss a result, it should be included in the Discussion.

The literature reference appearing at line 250 of the original manuscript was misplaced in the Results section. It has been removed from the revised manuscript. No literature references now appear in the Results section.

The Discussion section requires substantial revision. It is currently insufficient, with the only interesting element being a reference to unpublished results. While referencing unpublished data is acceptable, it must be done with caution. It is advisable to provide a brief description of the method so that readers understand how the result was obtained.

Similarly, the Conclusions section requires a thorough overhaul. The most valuable element of this study is its protocol, which should be highlighted. The current conclusions largely contain truistic statements.

We fully concur that both sections were insufficient, and both have been entirely rewritten in the revised manuscript.

The new version of the Discussion reflects the results arising from the corrected statistical analyses, especially that repeated immersion in all three water types induced only limited and largely comparable effects on TEWL, hydration, and subjective discomfort in untreated forearms. This finding contrasts with the previously presented results and is now discussed in the context of the inherent constraints of short-term experimental models relative to the chronic cumulative exposure reflected in epidemiological data. The revised Discussion further addresses: the known kinetics of water–skin interaction and the disruption of the canonical inverse TEWL–hydration relationship in atopic skin; the transient anti-pruritic effect of controlled water exposure in untreated forearms; the comparable efficacy of the routine across all three water types, interpreted as reflecting its intrinsic barrier-supporting properties independently of water-type-specific stress; an ingredient-level mechanistic rationale for the observed effects; and the interpretation of the post-immersion pattern of results as partial restoration of physiological barrier coupling.

The Conclusions have likewise been entirely rewritten. The revised Conclusions foreground the study protocol – notably the controlled three-day immersion model designed to mimic two weeks of daily washing – as a methodological contribution. Conclusions are now grounded directly in the study findings and acknowledge the limitations of the experimental approach.

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

This study addresses the evaluation of hard, and chlorinated water on atopic skin and the efficacy of a daily dermocosmetic routine. This topic is of great interest, as immersion in chlorinated water has been observed to cause serious skin and respiratory problems.

The manuscript is clear and relevant to the skincare industry, as there is evidence that skin discomfort in atopic dermatitis can be reduced through cosmetic formulations aimed at repairing the skin barrier function, thus improving skin comfort and hydration. Despite the relatively small sample size, the results are conclusive. The experimental design is adequate for testing the hypothesis, as are the tables and graphs. The cited references are relevant, and the conclusions are consistent with the evidence and arguments presented.

Therefore, I propose to accept the manuscript in its present form.

Author Response

Dear Editor,

We are pleased to submit the revised version of our manuscript and would like to thank you for the additional time allowed for revision. We are also sincerely grateful to the reviewers for their constructive comments.

In response to the reviewers’ comments, the dataset was entirely re-analysed using appropriate statistical methods. This resulted in substantial changes to the interpretation of the results and led to a complete rewriting of the manuscript. Although we provide a detailed point-by-point response to the reviewers, the submitted file is an entirely new version of the manuscript; for this reason, tracked changes have not been applied.

Sincerely,

Helena Polena

 

Reviewer 2

This study addresses the evaluation of hard, and chlorinated water on atopic skin and the efficacy of a daily dermocosmetic routine. This topic is of great interest, as immersion in chlorinated water has been observed to cause serious skin and respiratory problems.

The manuscript is clear and relevant to the skincare industry, as there is evidence that skin discomfort in atopic dermatitis can be reduced through cosmetic formulations aimed at repairing the skin barrier function, thus improving skin comfort and hydration. Despite the relatively small sample size, the results are conclusive. The experimental design is adequate for testing the hypothesis, as are the tables and graphs. The cited references are relevant, and the conclusions are consistent with the evidence and arguments presented.

Therefore, I propose to accept the manuscript in its present form.

We thank the reviewer for her/his positive assessment.

We must, however, note that the two other reviewers raised serious and justified concerns regarding the statistical methodology, the completeness of the Methods section, and the quality of the Discussion and Conclusions. These concerns led us to re-analyse the entire dataset using appropriate statistical tests, which had an impact on result interpretations, and resulted in a complete manuscript rewriting.

The revised version therefore differs substantially from the original submission. Given the volume and nature of the modifications, it was not possible to present the revised manuscript with tracked changes, and we hope the reviewer will accept this departure from standard practice.

Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

The present manuscript explores the impact of water quality (hard, chlorinated, and soft water) on skin barrier function and discomfort in subjects with atopic skin, combining a controlled experimental exposure model with two real-life observational studies. The subject matter is pertinent to the fields of cosmetic science and dermatology, especially in light of the mounting evidence for the role of environmental factors in the development of atopic dermatitis (AD), and the significance of complementary dermocosmetic interventions.
The manuscript demonstrates a generally robust structure, with a foundation that is supported by pertinent epidemiological literature. Furthermore, the manuscript integrates objective biometrological measurements (TEWL, hydration index) with patient-reported outcomes and quality-of-life assessments (DLQI). This translational approach is a significant strength of the work.
However, it is imperative to address several significant issues related to transparency, methodological limitations, statistical interpretation, and the exaggeration of conclusions before the manuscript can be considered for publication.

Major Comments

Conflict of Interest and Funding Transparency
It is evident that all authors are affiliated with NAOS Ecobiology Company, and the tested products are commercial NAOS dermocosmetics. Whilst the practice of industry-sponsored cosmetic research is prevalent, the manuscript does not adequately clarify the following points: Funding sources, the role of the sponsor in study design, data analysis, interpretation, and manuscript preparation: these are all aspects of the research process that are of paramount importance in ensuring that the standards of the MDPI are met.

It is imperative that clear sections on funding and conflicts of interest be included, explicitly describing sponsor involvement and any measures taken to minimise bias.

Study Design and Control Limitations
The experimental study is open-label and intra-individual, without blinding. The two real-life studies are characterised by an absence of a control or comparator group, a factor which complicates the exclusion of placebo effects, regression to the mean, and spontaneous symptom improvement.
Although the Discussion section acknowledges certain limitations, the manuscript does, at times, employ causal language that may give an unduly positive impression of the strength of the evidence.

It is recommended that causal interpretations be employed with caution throughout the Results, Discussion and Conclusion sections. It is imperative to explicitly state that the real-life studies are uncontrolled observational studies.

Characterisation of Water Exposure
The characterisation of water quality is incomplete. The definition of hard water is provided using semi-quantitative test strips; however, the mineral composition of the water is not detailed. Furthermore, the chlorine concentration in chlorinated water is not specified. The composition of soft water is not described, and variability in real-life water exposure is not quantified.

Where possible, greater detail should be provided on the composition of the water, and these limitations must be discussed explicitly.

Statistical Considerations
Multiple comparisons are conducted across a range of parameters and time points. There is no indication that corrections for multiple testing were applied, which increases the risk of type I error. Furthermore, the relatively modest sample sizes (n = 22 per experimental group) may compromise the statistical power to detect meaningful between-group differences.

It is imperative to elucidate whether multiple comparison adjustments were taken into consideration. Furthermore, the discourse on statistical power limitations must be expanded.

Interpretation of Soft Water Findings
Soft water is characterised as being neutral with respect to skin barrier function. However, dermocosmetic treatment resulted in similar improvements across all water types, including soft water. This prompts the question of whether the observed benefits are independent of water-induced stress.

It is imperative to ascertain whether enhancements in product efficacy are attributable to factors other than water exposure, and to refine the interpretation in accordance with this determination.

Minor comments

The term "biometrological" is uncommon; therefore, either "biophysical" should be used or justification should be provided.

Numerous figures and tables are cited without numbering, for example, "Figure " or "Table".

Minor typographical and encoding issues are present.

It is imperative that ethical approval is explicitly stated, inclusive of the name of the ethics committee and the approval number.

It is imperative that the relevance and accuracy of Reference 14 be verified in relation to the MoistureMap methodology.

Author Response

Dear Editor,

We are pleased to submit the revised version of our manuscript and would like to thank you for the additional time allowed for revision. We are also sincerely grateful to the reviewers for their constructive comments.

In response to the reviewers’ comments, the dataset was entirely re-analysed using appropriate statistical methods. This resulted in substantial changes to the interpretation of the results and led to a complete rewriting of the manuscript. Although we provide a detailed point-by-point response to the reviewers, the submitted file is an entirely new version of the manuscript; for this reason, tracked changes have not been applied.

Sincerely,

Helena Polena

 

Reviewer 3

The present manuscript explores the impact of water quality (hard, chlorinated, and soft water) on skin barrier function and discomfort in subjects with atopic skin, combining a controlled experimental exposure model with two real-life observational studies. The subject matter is pertinent to the fields of cosmetic science and dermatology, especially in light of the mounting evidence for the role of environmental factors in the development of atopic dermatitis (AD), and the significance of complementary dermocosmetic interventions.

The manuscript demonstrates a generally robust structure, with a foundation that is supported by pertinent epidemiological literature. Furthermore, the manuscript integrates objective biometrological measurements (TEWL, hydration index) with patient-reported outcomes and quality-of-life assessments (DLQI). This translational approach is a significant strength of the work.

However, it is imperative to address several significant issues related to transparency, methodological limitations, statistical interpretation, and the exaggeration of conclusions before the manuscript can be considered for publication.

We appreciate the reviewer’s recognition of the relevance of the topic, the epidemiological grounding, and the strength of combining instrumental skin measurements with patient-reported outcomes and quality-of-life assessments. We also acknowledge that, as the reviewer correctly points out, the original version suffered from shortcomings in terms of transparency, methodological reporting, statistical analysis, and the strength of the discussion and the conclusion.

In light of these justified concerns (convergent with those of Reviewers 1), we have undertaken a comprehensive revision of the work. The entire dataset has been re-analysed using appropriate statistical methods, which impacted results and their interpretation. The Methods (including Ethics, water characterisation, inclusion/exclusion criteria, and statistical analysis), Results, Discussion, and Conclusions sections have been entirely rewritten to reflect the corrected analyses, provides a deeper discussion of results and to better align the conclusions with the actual strength of the evidence.

We have also substantially reinforced transparency regarding funding, sponsor involvement, and conflicts of interest by adding dedicated Funding and Conflicts of Interest sections, and by clarifying the respective roles of the sponsor, the independent CRO, and the independent statistician/medical writer in the Acknowledgments and back matter.

Because of the extent of these changes, the revised manuscript differs fundamentally from the original submission and is not presented with tracked changes, as the volume and nature of the modifications rendered this approach impractical. We hope the reviewer will accept this departure from standard practice in light of the circumstances.

Major Comments

Conflict of Interest and Funding Transparency

It is evident that all authors are affiliated with NAOS Ecobiology Company, and the tested products are commercial NAOS dermocosmetics. Whilst the practice of industry-sponsored cosmetic research is prevalent, the manuscript does not adequately clarify the following points: Funding sources, the role of the sponsor in study design, data analysis, interpretation, and manuscript preparation: these are all aspects of the research process that are of paramount importance in ensuring that the standards of the MDPI are met.

It is imperative that clear sections on funding and conflicts of interest be included, explicitly describing sponsor involvement and any measures taken to minimise bias.

We agree that the original submission did not provide any information regarding funding, sponsor involvement, and potential conflicts of interest, as well as back matter sections in line with MDPI standards.

The revised manuscript now includes dedicated Funding and Conflicts of Interest sections in the back matter. Specifically, the Funding section now states that the study was funded by NAOS (Bioderma). The Conflicts of Interest section explicitly discloses that all authors are employees of NAOS, the manufacturer of the investigated dermocosmetic products. The Acknowledgments further detail the respective roles of the different parties: the clinical evaluations were conducted by the clinical team from an independent contract research organisation (EUROFINS Dermscan/Pharmascan), which was responsible for subject recruitment, conduct of the study procedures, and raw data collection; statistical analysis and scientific writing were performed by an independent medical writer/consultant; and NAOS provided the test products and financial support but did not have access to individually identifiable participant data.

These additions and clarifications are intended to make the sponsor’s involvement fully transparent and to document the measures taken to minimise bias, in accordance with MDPI’s requirements for industry-sponsored research.

Study Design and Control Limitations

The experimental study is open-label and intra-individual, without blinding. The two real-life studies are characterised by an absence of a control or comparator group, a factor which complicates the exclusion of placebo effects, regression to the mean, and spontaneous symptom improvement.

Although the Discussion section acknowledges certain limitations, the manuscript does, at times, employ causal language that may give an unduly positive impression of the strength of the evidence.

It is recommended that causal interpretations be employed with caution throughout the Results, Discussion and Conclusion sections. It is imperative to explicitly state that the real-life studies are uncontrolled observational studies.

We agree with the reviewer that the open-label, intra-individual design of the controlled study and the uncontrolled nature of the two real-life studies limit causal inference and do not exclude placebo effects, regression to the mean, or spontaneous improvement.

In the revised manuscript, these aspects are now explicitly stated in the Methods and Discussion. The controlled study is described as an “open-label, intra-individual controlled study” (Section 2.3), and the real-life investigations are now clearly labelled as “open-label, observational studies” (Section 2.4). The Limitations paragraph of the Discussion has been expanded to underline that the real-life studies are uncontrolled observational studies and that, as a result, placebo effects and spontaneous symptom changes cannot be ruled out, particularly for subjective endpoints.

In addition, we have systematically reviewed the Results, Discussion, and Conclusions to temper causal language and avoid overstatement of the strength of the evidence. Descriptions of the findings now use associational wording (e.g., “was associated with reductions in discomfort” or “provided improvements in TEWL and hydration”) and the Conclusions have been rephrased to state that the findings “support the role” of dermocosmetic routines as adjuncts to long-term management, rather than implying definitive causality.

Characterisation of Water Exposure

The characterisation of water quality is incomplete. The definition of hard water is provided using semi-quantitative test strips; however, the mineral composition of the water is not detailed. Furthermore, the chlorine concentration in chlorinated water is not specified. The composition of soft water is not described, and variability in real-life water exposure is not quantified.

Where possible, greater detail should be provided on the composition of the water, and these limitations must be discussed explicitly.

We agree that the characterisation of water in the controlled forearm‑immersion study was incomplete, and we acknowledge that we underestimated the importance of a more detailed characterisation of water composition at the design stage.

We have now added the information we have to Section 2.3.2. All three water types (soft, hard, chlorinated) originated from the same local hard tap water supply. Hard water is described as unmodified local tap water within the Polish “hard water” range (350-550 mg CaCO₃/l, 19.6-30.8°dH), with hardness verified before each session using Aquadur^® 4-21 semi‑quantitative strips (CaCO₃ >400 mg/l). Soft water is defined as the output of a domestic ion‑exchange softener (Claro 25L USTM) fed with this same hard water, with an expected residual hardness <17 mg CaCO₃/l. The chlorinated water is now described as softened water supplemented with sodium hypochlorite to a calculated free chlorine concentration of 28.6 mg Cl₂/l, which is substantially exceeding Polish swimming pool regulation (0.3-1.4 mg Cl₂/l).

In the Discussion, we explicitly state that, despite these additions, water characterisation remains insufficient and is clearly acknowledged as a limitation of the study. We acknowledge that unmeasured compositional differences between hard and soft/chlorinated water may have influenced the results and that the high chlorine concentration in the chlorinated water condition further limits the extrapolation of these findings to real‑life swimming pool exposure.

Statistical Considerations

Multiple comparisons are conducted across a range of parameters and time points. There is no indication that corrections for multiple testing were applied, which increases the risk of type I error. Furthermore, the relatively modest sample sizes (n = 22 per experimental group) may compromise the statistical power to detect meaningful between-group differences.

It is imperative to elucidate whether multiple comparison adjustments were taken into consideration. Furthermore, the discourse on statistical power limitations must be expanded.

We fully concur with the reviewer's critique. The statistical analyses in the original manuscript contained significant methodological shortcomings, especially, the lack of appropriate statistical test use and multiple-comparison adjustment.

The entire dataset has been re-analysed using appropriate statistics, as detailed in the revised Section 2.5 (Statistical Analysis). Specifically: (i) comparisons between two conditions are now performed using paired t-tests for normally distributed continuous data and Wilcoxon signed-rank tests otherwise, following prior assessment of distributional normality using the Shapiro–Wilk test; (ii) multiple comparisons of continuous data are now performed using repeated-measures ANOVA followed by Tukey's HSD post-hoc tests for normally distributed data, and the Friedman test followed by pairwise Wilcoxon signed-rank tests for non-normally distributed data, with p-values adjusted using the Bonferroni correction in both cases; and (iii) all subjective discomfort outcomes, being ordered categorical data, are now analysed exclusively using Wilcoxon signed-rank tests, with Friedman tests applied prior to pairwise comparisons where multiple conditions are involved. These corrections have affected the results. Sections 3.1 and 3.2, as well as the relevant passages of the Discussion, have been entirely rewritten to reflect the revised analyses.

Interpretation of Soft Water Findings

Soft water is characterised as being neutral with respect to skin barrier function. However, dermocosmetic treatment resulted in similar improvements across all water types, including soft water. This prompts the question of whether the observed benefits are independent of water-induced stress.

It is imperative to ascertain whether enhancements in product efficacy are attributable to factors other than water exposure, and to refine the interpretation in accordance with this determination.

We agree with the reviewer that the original version did not address the fact that the dermocosmetic routine produced similar improvements across all three water types, including soft water, and that this has important implications for how the results are interpreted.

In the revised Discussion, we now explicitly state that, because the controlled immersion study showed only limited and largely comparable effects of soft, hard, and chlorinated water on untreated forearms, and because the dermocosmetic routine yielded improvements of similar magnitude across all three conditions (including soft water), the observed benefits are best interpreted as being primarily product‑related rather than as evidence of selective protection against water‑induced stress. We further clarify that, under the present design, it is not possible to disentangle a potential interaction between water type and product efficacy, but the pattern of results does not support a strong water‑specific effect; instead, it is more consistent with intrinsic moisturising and barrier‑supporting properties of the routine that are expressed irrespective of water composition.

Minor comments

The term "biometrological" is uncommon; therefore, either "biophysical" should be used or justification should be provided.

We agree that the term “biometrological” is uncommon. In our case, it is also improper, as it refers to the science of measurement methodologies and metrological accuracy. Therefore, we have removed all instances of this term (previously appearing three times, including in the title). The revised manuscript now employs standard terminology throughout.

Numerous figures and tables are cited without numbering, for example, "Figure " or "Table".

We fully agree with the reviewer that the original manuscript contained several deficiencies. The revised manuscript has been comprehensively restructured and corrected in the following respects.

All figures and tables are now explicitly numbered and cross-referenced in the text. Figure and table captions have been entirely rewritten to meet the principle of self-explanatory labelling: each caption now provides a full description of the data presented, defines all abbreviations used, specifies the time points evaluated, and explains the statistical notation employed, such that each figure and table can be interpreted independently of the main text.

Minor typographical and encoding issues are present.

With the entire rewriting of the manuscript, we hope that these errors were corrected.

It is imperative that ethical approval is explicitly stated, inclusive of the name of the ethics committee and the approval number.

We fully acknowledge that the original submission lacked an Ethics section and an IRB statement, and we agree that these are essential components of any manuscript intended for publication in a peer-reviewed journal, irrespective of the regulatory context. Both omissions have been corrected in the revised manuscript.

A dedicated Ethics section has been added to the Materials and Methods (Section 2.2), and an Institutional Review Board statement has been included in the back matter.

As detailed therein, both studies consisted in the non-invasive evaluation of dermocosmetic products and were conducted in Poland. Under the applicable legislative framework — specifically European Directive 2001/20/EC and the Order of the Minister of Health of 2 May 2012 on Good Clinical Practice (Dz.U. 2012, item 491) — such studies are explicitly exempted from mandatory ethics committee review, even though the participants had atopic dermatitis.

Both studies were nonetheless conducted in full accordance with the principles of the Declaration of Helsinki and Good Clinical Practice. Written informed consent was obtained from all participants prior to enrolment, and adverse events were monitored throughout.

It is imperative that the relevance and accuracy of Reference 14 be verified in relation to the MoistureMap methodology.

There was indeed a problem with reference #14, which is now reference #16. The appropriate work is now cited: Gayraud F, Sayag M, Jourdan E. Efficacy and tolerance assessment of a new type of dermocosmetic in infants and children with moderate atopic dermatitis. J Cosmet Dermatol. 2015, 14, 107-12.

 

Author Response File: Author Response.pdf

Reviewer 4 Report

Comments and Suggestions for Authors

Comparative Impact of Hard and Chlorinated Water on Biometrological Parameters of Atopic Skin and the Clinical Benefits of Dermocosmetic Routine Interventions – review

 

The goal of the work was to objectify the detrimental effects of hard and chlorinated water on atopic skin, both under controlled experimental conditions and in real-life settings. The studies assessed the efficacy of a daily dermocosmetic routine (comprising a cleanser and moisturizer adapted for atopy-prone skin) for reducing water-induced discomfort and improving the quality of life. Article is interesting, however, I have a lot of comments.

General comments:

1. What are the measurement ranges of the measuring instruments used (tewameter, MoistureMap)? Without this information, the reader will have no idea whether the data obtained is high/low and what ranges are desirable.
2. The description of the results does not refer to specific tables and figures included in the text. It is unclear which ones to look at in order to read the data. This creates chaos and disorder.
3. In my opinion, the results are written in very general terms. This also applies to section 4. Discussion. There are no references to the research results (specific data) obtained by other researchers.
4. The drawings are very small and have poor resolution. This makes it difficult to read the results easily. The data is basically invisible.

 

Detailed comments:

1. Did all participants in the experiment use the same cosmetics and follow the same daily skincare routines? If yes/no, this should be described in section 2.
2. Pages 2-4, section2: in my opinion, the measurement methodology should be described in more detail. If the authors provide a specific example/reference to the literature, then this part can be generalized.
3. Page 2 line 52: the names of raw materials in cosmetics should be given in accordance with INCI in capital letters, so the name „sodium lauryl sulfate” should be written in capitals.
4. Page 4 Section 3: Table 1 should be moved to section 2 because it does not present the results obtained, but only data concerning the subjects.
5. Page 5 line 165: No reference to a specific table number. This creates confusion.
6. Page 5 Figure 1: very poor image quality. The Y axis starts at 9.0 and ends at 12.0. The scales for all TEWL images should be standardized.
7. Page 6 lines 202, 208: No reference to a specific table/figure number.
8. Page 6 Figure 3: Very poor quality drawings. The beginning and end of the Y axis should be standardized—the same ranges for each drawing!!!
9. Page 6 Figure 3: see above!
10. Page 8 line 230 and 242: No reference to a specific table number.
11. Page 9 section 4, lines: 260-261: Authors wrote: „Yet, few instrumental studies have directly assessed the effects of repeated water exposure on atopic skin” – please give the references.

Author Response

Dear Editor,

We are pleased to submit the revised version of our manuscript and would like to thank you for the additional time allowed for revision. We are also sincerely grateful to the reviewers for their constructive comments.

In response to the reviewers’ comments, the dataset was entirely re-analysed using appropriate statistical methods. This resulted in substantial changes to the interpretation of the results and led to a complete rewriting of the manuscript. Although we provide a detailed point-by-point response to the reviewers, the submitted file is an entirely new version of the manuscript; for this reason, tracked changes have not been applied.

Sincerely,

Helena Polena

 

Reviewer 4

The goal of the work was to objectify the detrimental effects of hard and chlorinated water on atopic skin, both under controlled experimental conditions and in real-life settings. The studies assessed the efficacy of a daily dermocosmetic routine (comprising a cleanser and moisturizer adapted for atopy-prone skin) for reducing water-induced discomfort and improving the quality of life. Article is interesting, however, I have a lot of comments.

We thank the reviewer for the positive assessment of the study and for the detailed and constructive comments. We fully concur that the original version required substantial improvement in several respects, including the methodological description, the clarity of results presentation, the quality of the figures, the referencing of tables and figures in the text, and the depth of the discussion.

In response to the comments raised by two reviewers regarding statistical methodology and manuscript quality, the entire dataset has been re-analysed using appropriate statistical methods, which materially changed the interpretation of the results. Consequently, the manuscript has been comprehensively rewritten, paying attention that the new version also addresses the specific points raised by the present reviewer, as detailed below.

Because of the extent of these changes, the revised version differs substantially from the original submission. Although we provide this response to the reviewer's comments, it was not practicable to identify every change by line number in the original manuscript, and tracked changes were therefore not used.

General comments:

What are the measurement ranges of the measuring instruments used (tewameter, MoistureMap)? Without this information, the reader will have no idea whether the data obtained is high/low and what ranges are desirable.

TEWL and the hydration index are both reported together with their units in the revised manuscript (g/m²/h and arbitrary units, respectively). Reference values for TEWL in atopic skin are now contextualised in the Discussion with reference to published normative data. The MoistureMap MM100 has been removed from the revised manuscript as data were not included in the analysis; the hydration index reported in the revised manuscript is based solely on corneometry (Tewameter TM 300 system).

The description of the results does not refer to specific tables and figures included in the text. It is unclear which ones to look at in order to read the data. This creates chaos and disorder.

All tables and figures are now explicitly numbered and cross-referenced throughout the Results section. This deficiency has been fully corrected.

In my opinion, the results are written in very general terms. This also applies to section 4. Discussion. There are no references to the research results (specific data) obtained by other researchers.

The Result and Discussion sections have been entirely rewritten. The Discussion now includes references to published quantitative findings on water–skin interactions, the TEWL–hydration relationship in atopic skin, the transient anti-pruritic effect of water exposure, and the mechanistic basis of the barrier-supporting ingredients.

The drawings are very small and have poor resolution. This makes it difficult to read the results easily. The data is basically invisible.

All figures have been redrawn. Axis scales are now standardised within each parameter (TEWL and hydration index) across subpanels.

Detailed comments:

Did all participants in the experiment use the same cosmetics and follow the same daily skincare routines? If yes/no, this should be described in section 2.

The Materials and Methods section has been rewritten, providing greater details on each study.

Pages 2-4, section2: in my opinion, the measurement methodology should be described in more detail. If the authors provide a specific example/reference to the literature, then this part can be generalized.

Please, see our reply above.

Page 2 line 52: the names of raw materials in cosmetics should be given in accordance with INCI in capital letters, so the name „sodium lauryl sulfate” should be written in capitals.

In the revised manuscript, this substance appears in the Introduction as part of a descriptive sentence citing published literature (Danby et al., 2018). The INCI convention (capital letters) applies to ingredient labelling in product formulations, not to the generic use of chemical names in running text. The usage in the revised manuscript is therefore appropriate as written.

Page 4 Section 3: Table 1 should be moved to section 2 because it does not present the results obtained, but only data concerning the subjects.

Page 5 line 165: No reference to a specific table number. This creates confusion.

Page 5 Figure 1: very poor image quality. The Y axis starts at 9.0 and ends at 12.0. The scales for all TEWL images should be standardized.

Page 6 lines 202, 208: No reference to a specific table/figure number.

Page 6 Figure 3: Very poor quality drawings. The beginning and end of the Y axis should be standardized—the same ranges for each drawing!!!

Page 6 Figure 3: see above!

Page 8 line 230 and 242: No reference to a specific table number.

As stated in our reply to the General Comments, all figures have been redrawn. All tables and figures are now explicitly numbered and cross-referenced throughout the Results section. This deficiency has been fully corrected.

Page 9 section 4, lines: 260-261: Authors wrote: „Yet, few instrumental studies have directly assessed the effects of repeated water exposure on atopic skin” – please give the references.

This sentence has been revised in the Discussion of the new version of the manuscript, which now includes specific references to the published instrumental studies on water exposure and skin barrier function.

Author Response File: Author Response.pdf

Round 2

Reviewer 3 Report

Comments and Suggestions for Authors

This manuscript examines how different water types (soft, hard, and chlorinated) affect atopic skin and assesses the effectiveness of a dermocosmetic cleansing and moisturizing routine in both controlled and real-life settings. The topic is clinically relevant and fits well within the scope of Cosmetics, particularly given the increasing interest in environmental triggers of atopic dermatitis (AD) and supportive skincare approaches.

The manuscript is well written, scientifically sound, and supported by a solid literature review. Its combination of a controlled immersion model and a real-life observational study enhances the translational value of the findings. Overall, the results indicate that water type has limited short-term differential effects on atopic skin, whereas the dermocosmetic routine consistently improves skin barrier-related measures and subjective comfort.

The study design, statistical analysis, and discussion are generally appropriate. However, several points require clarification or refinement before the manuscript can be accepted.

Clinical Severity of Participants

The manuscript states that participants had “atopic skin” or physician-diagnosed AD, but baseline disease severity is not described clearly enough. Please specify whether validated severity measures such as SCORAD, EASI, or IGA were assessed. If these measures were not collected, this should be stated explicitly as a limitation.

Potential Bias from the Open-Label Design

Although this issue is acknowledged in the discussion, the implications of the open-label design should be addressed more critically, especially for subjective outcomes such as discomfort scores and DLQI. Because all participants received active products and no comparator formulations were included, placebo and expectancy effects cannot be ruled out.

Real-Life Study Design

The observational study does not include a control arm. Although the reported improvements are substantial, the lack of a comparator limits causal interpretation. The authors should therefore moderate some of the efficacy claims and clarify that the real-life findings are exploratory and supportive rather than confirmatory.

Chlorinated Water Concentration

The chlorinated water concentration used in the controlled immersion study (28.6 mg Cl₂/L) appears considerably higher than typical swimming pool levels. Although this is mentioned in the limitations section, the Methods section should provide a clearer justification for selecting such a high concentration.

Minor Comments

The manuscript uses both “atopic skin” and “atopic dermatitis.” Please standardize the terminology where possible for clarity.

The manuscript is generally well written, but some Discussion sentences are too long and should be simplified for readability.

Table 1 is detailed and informative, but clearer formatting or ingredient grouping could improve readability.

Please use consistent p-value formatting throughout the manuscript.

The figure legends are comprehensive, but Figures 3 and 4 would be easier to read with larger axis labels and higher annotation contrast.

Although the exemption rationale is explained, it would be helpful to state whether independent ethics consultation or institutional confirmation of exemption was obtained.

Reviewer 4 Report

Comments and Suggestions for Authors

I accept the manuscript in present form.

 

Regards