Ionic Components of Particulate Matter 2.5 May Influence Daily Prevalence of Skin Symptom Exacerbations in Allergy Sufferers

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This paper presents a scientific report on an epidemiological study examining the observed association between ambient particulate matter (PM) 2.5 and its ionic components and the prevalence of skin symptoms in patients with allergic diseases in Fukuoka, Japan. This study is innovative as few investigations have explored the health effects of ionic components of PM2.5 on a population level. While the paper is generally scientifically rigorous, certain improvements are required before publication. These areas for improvement include:

1.     The health outcome was assessed daily using the question, 'Did your skin get worse?' This approach aims to measure the daily incidence of changes in skin symptoms rather than the prevalence of skin disorders. Therefore, I recommend changing the outcome to 'incidence of skin disorder' instead of 'prevalence of skin disorder'. Given that you conducted a prospective cohort study, incidence is typically the outcome measurement for this study design.

2.     In the introduction section, the third sentence of the first paragraph states that 'few studies have evaluated the effects of air pollution on the prevalence of skin symptoms.' However, this may not be entirely accurate as there have been studies, such as the publication (Wang, H. L., Sun, J., Qian, Z. M., Gong, Y. Q., Zhong, J. B., Yang, R. D., . . . Lin, H. L. (2020). Association between Air Pollution and Atopic Dermatitis in Guangzhou, China: Modification by Age and Season. Br J Dermatol. doi:10.1111/bjd.19645.), that have explored the acute effects of air pollution on skin conditions. While you have discretion in selecting papers to cite, I recommend conducting a thorough literature review to include recent publications and cover recent findings. It may be prudent to acknowledge the reported association between ambient PM2.5 exposure and skin symptoms, while also noting the scarcity of studies on the health effects of ionic components of PM2.5 on skin conditions. You can state that this scarcity could introduce information bias, especially considering the variability in ionic components across different regions, potentially leading to different effect estimates on the health effects of PM2.5.

3.     Please acknowledge that your study may be subject to self-report bias since patients self-evaluate and report their symptoms.

4.     From lines 78 to 80, please provide scientific evidence supporting the assertion that air pollution from China is carried by the wind to Fukuoka. Additionally, expand on this explanation, as it currently lacks clarity and may cause confusion. Most people would think that the influence of regional pollution is considered to have a more direct impact on residents’ health. Furthermore, please address the apparent contradiction between the mention of China’s improved air pollution in major cities since 2013 and the high PM2.5 concentrations in Fukuoka during the same time (lines 86 to 88). These conflicting pieces of information undermine the focus and logical flow of this section. Please revise the paragraphs to align more closely with the specific purpose of the study and avoid presenting contradictory information.

5.     From lines 71 to 89, you mentioned that the air monitor is located on the rooftop of the hospital, which is situated in a corner of Ogi facing the sea. You also noted the direction of the prevailing wind, which blows from the ocean, through the city center, toward the mountains, and collects at their base. Therefore, it seems that the air measurements at the hospital may not fully capture the air quality across the entire city. Instead, an air monitor positioned at the base of the mountains would likely provide a more comprehensive assessment of air quality, considering that the air collects at this location. Therefore, this description is unnecessary and may diminish the quality of your study. Moreover, it's essential to acknowledge that monitoring stations, regardless of their location, may not accurately measure personal exposure to ambient PM2.5. Therefore, I recommend acknowledging the potential for misclassification bias in your study. Many studies that rely on monitoring stations to estimate personal exposure to air pollution are susceptible to this bias. However, it's crucial to emphasize that this acknowledgment does not diminish the significance of your study findings.

6.     If you decide to use incidence as the measurement of outcome, then you need to use survival analysis, such as Cox proportional hazards regression. Or, you can measure the health outcome as a prevalence of any skin symptoms, and stick to linear regression.

7.     Table 1 should be the characteristics of the study population at baseline because your study is a prospective cohort study. A Cohort Study Flow Chart is recommended for this type of study as well, to describe how study participants are included and excluded. The statistics of PM2.5 and its ionic components can be Table 2.

8.     Please address confounding bias in your study by providing information on how you selected the potential confounders and covariates in your multivariate model. Most studies include at least the patient’s age, humidity, and temperature. For skin disorders, other important confounders need to be considered as well. However, only those that can change the effect estimate by 5-10% need to be included.

9.     In Table 2, please provide 95% confidence intervals instead of p-values, as they can offer more informative insights. Additionally, please retain either Table 2 or Figure 1, as duplicating the linear relationship between pollutants and skin symptoms is unnecessary. Instead, consider including the correlation results between pollutants. Please refer to Table 2 in my publication for guidance.

10.  Please provide the results of your collinearity analysis, including your criterion for determining highly correlated variables. Some studies use a Variance Inflation Factor (VIF) of 5 or below to indicate independent variables, while others use a VIF of 10 or below. When variables are highly correlated, it's important to retain at least one in the model or consider them as a group rather than separate variables. Alternatively, you can create multiple multivariate models, each including one of the correlated ionic components, and conduct a sensitivity analysis to assess the impact of adding correlated variables. Please refer to my publication for further guidance on this method.

11.  Have you assessed whether specific allergic diseases or socioeconomic status modify the association you are studying? Examining these factors could have significant public health implications, helping to identify vulnerable groups and allocate medical resources more efficiently.

Comments for author File: Comments.pdf

Author Response

This paper presents a scientific report on an epidemiological study examining the observed association between ambient particulate matter (PM) 2.5 and its ionic components and the prevalence of skin symptoms in patients with allergic diseases in Fukuoka, Japan. This study is innovative as few investigations have explored the health effects of ionic components of PM2.5 on a population level. While the paper is generally scientifically rigorous, certain improvements are required before publication. These areas for improvement include:

Response:

We thank you for your valuable time and comments on our paper. We have tried to revise it as follows.

I have also indicated in blue the parts that were deleted from the original manuscript and in red the parts that were added.

Comment 1:

The health outcome was assessed daily using the question, 'Did your skin get worse?' This approach aims to measure the daily incidence of changes in skin symptoms rather than the prevalence of skin disorders. Therefore, I recommend changing the outcome to 'incidence of skin disorder' instead of 'prevalence of skin disorder'. Given that you conducted a prospective cohort study, incidence is typically the outcome measurement for this study design.

 

Response 1:

Thank you for your comment. I agree with this comment. However, because the subjects were already symptomatic and symptoms improved and worsened, it was difficult to express the incidence rate. Therefore, we used the expression "prevalence of symptom exacerbation " and explained this point in the methodology. Again, we appreciate your comments.

We understand it as follows, and from this point of view, we have thought as above. Prevalence is an indicator that shows the proportion of people in a population who have a particular disease at a certain point in time, and includes not only new cases but also existing cases. Incidence is an indicator that shows the number of new cases of a disease in a certain period of time, and only counts new cases. Is this the correct way of thinking?

 

Comment 2.     In the introduction section, the third sentence of the first paragraph states that 'few studies have evaluated the effects of air pollution on the prevalence of skin symptoms.' However, this may not be entirely accurate as there have been studies, such as the publication, that have explored the acute effects of air pollution on skin conditions. While you have discretion in selecting papers to cite, I recommend conducting a thorough literature review to include recent publications and cover recent findings. It may be prudent to acknowledge the reported association between ambient PM2.5 exposure and skin symptoms, while also noting the scarcity of studies on the health effects of ionic components of PM2.5 on skin conditions. You can state that this scarcity could introduce information bias, especially considering the variability in ionic components across different regions, potentially leading to different effect estimates on the health effects of PM2.5.

 

Response ２:

Thank you for pointing that out. Due to my lack of awareness, I thought that my expression was inappropriate. I have made the corrections shown in red below.

" Research reports on air pollution and skin have been gradually increased in recent years [3]. However, there are currently few reports on the relationship between PM2.5 components, especially ionic components. By researching ionic components and other components of PM2.5, it may be possible to consider the causes and effects of PM2.5, even if it is the same PM2.5, as well as regional differences, and it may be possible to consider the health effects in more depth.（L43～L48）．

 

Comment 3.     Please acknowledge that your study may be subject to self-report bias since patients self-evaluate and report their symptoms.　

 

Response 3:

Thank you so much. We agree. We added following;

“One of the limitations of this study is that our data may be subject to self-reporting bias because participants reported their own symptoms, and for this reason, data were reviewed by an allergy nurse during outpatient visits”（L252-254）.

 

Comment 4.     From lines 78 to 80, please provide scientific evidence supporting the assertion that air pollution from China is carried by the wind to Fukuoka. Additionally, expand on this explanation, as it currently lacks clarity and may cause confusion. Most people would think that the influence of regional pollution is considered to have a more direct impact on residents’ health. Furthermore, please address the apparent contradiction between the mention of China’s improved air pollution in major cities since 2013 and the high PM2.5 concentrations in Fukuoka during the same time (lines 86 to 88). These conflicting pieces of information undermine the focus and logical flow of this section. Please revise the paragraphs to align more closely with the specific purpose of the study and avoid presenting contradictory information.

Response 4:

 agree with your point. I also thought that this part was unnecessary from the perspective of the overall flow, so I deleted it.

 

Comment 5.     From lines 71 to 89, you mentioned that the air monitor is located on the rooftop of the hospital, which is situated in a corner of Ogi facing the sea. You also noted the direction of the prevailing wind, which blows from the ocean, through the city center, toward the mountains, and collects at their base. Therefore, it seems that the air measurements at the hospital may not fully capture the air quality across the entire city. Instead, an air monitor positioned at the base of the mountains would likely provide a more comprehensive assessment of air quality, considering that the air collects at this location. Therefore, this description is unnecessary and may diminish the quality of your study. Moreover, it's essential to acknowledge that monitoring stations, regardless of their location, may not accurately measure personal exposure to ambient PM2.5. Therefore, I recommend acknowledging the potential for misclassification bias in your study. Many studies that rely on monitoring stations to estimate personal exposure to air pollution are susceptible to this bias. However, it's crucial to emphasize that this acknowledgment does not diminish the significance of your study findings.

 

Response 5:

That is indeed correct. I have deleted the part you pointed out. I have also made the following corrections

“Measuring pollutant concentrations for use in investigating the health effects of air pollutants ideally requires each individual subject to carry a measuring device and be monitored. However, carrying out such monitoring in actual clinical cases poses many difficulties. The pollutant concentration measurements in this study were carried out on the roof of Fukuoka Hospital. Measurements were carried out daily by experienced laboratory technicians. The idea was to verify predictions to a certain extent using this method, and to conduct more detailed investigations if necessary. At this stage, a certain tendency has been identified between the ionic components of pollutants and skin symptoms, so the results are reported here” (L87-L95).

 

Comment 6.     If you decide to use incidence as the measurement of outcome, then you need to use survival analysis, such as Cox proportional hazards regression. Or, you can measure the health outcome as a prevalence of any skin symptoms, and stick to linear regression.

 

Response 6:

Thank you. Here, I will consider the prevalence rate rather than the incidence rate. Thank you.

 

Comment 7.     Table 1 should be the characteristics of the study population at baseline because your study is a prospective cohort study. A Cohort Study Flow Chart is recommended for this type of study as well, to describe how study participants are included and excluded. The statistics of PM2.5 and its ionic components can be Table 2.

 

Response 7:

Thank you for pointing that out. I think you're right. I'll create Table 1 and move the old Table 1 up to Table 2.

 

Comment 8.     Please address confounding bias in your study by providing information on how you selected the potential confounders and covariates in your multivariate model. Most studies include at least the patient’s age, humidity, and temperature. For skin disorders, other important confounders need to be considered as well. However, only those that can change the effect estimate by 5-10% need to be included.

 

Response 8:

Thank you for your comment.
Table 4 on multicollinearity has been added. Also, this time, temperature and humidity are not included in the consideration items. It is estimated that there are many other leisure factors besides these. For example, with regard to temperature and humidity, along with the recent global warming, many homes use air conditioners. This influence must be taken into account, but this consideration is not easy, so this time we will first investigate the relationship with the ionic components of air pollutants, and if a possible relationship is found, we would like to proceed further in future studies.

 

Comment 9.     In Table 2, please provide 95% confidence intervals instead of p-values, as they can offer more informative insights. Additionally, please retain either Table 2 or Figure 1, as duplicating the linear relationship between pollutants and skin symptoms is unnecessary. Instead, consider including the correlation results between pollutants. Please refer to Table 2 in my publication for guidance.

 

Response ９：

I wanted to refer to the literature and comment on it from Referee 1, but the identity of the referee is confidential. Therefore, I was not able to get it. In any case, I showed the correlation between the pollutants and modified Table 2.

 

Comment 10.  Please provide the results of your collinearity analysis, including your criterion for determining highly correlated variables. Some studies use a Variance Inflation Factor (VIF) of 5 or below to indicate independent variables, while others use a VIF of 10 or below. When variables are highly correlated, it's important to retain at least one in the model or consider them as a group rather than separate variables. Alternatively, you can create multiple multivariate models, each including one of the correlated ionic components, and conduct a sensitivity analysis to assess the impact of adding correlated variables. Please refer to my publication for further guidance on this method.

 

Response 10:

As mentioned above, I do not know who Referee 1 is. Unfortunately, I cannot study the document, but I would like to study it again.

 

Comment 11.  Have you assessed whether specific allergic diseases or socioeconomic status modify the association you are studying? Examining these factors could have significant public health implications, helping to identify vulnerable groups and allocate medical resources more efficiently.

 

Response 1Ⅰ:　

I have never evaluated something in detail before, but I am interested in such perspectives and would like to study them further.

I really appreciate your detailed evaluation, thank you very much.

Reviewer 2 Report

Comments and Suggestions for Authors

To the authors and editors:

The manuscript has looked into the correlation between the iron components in the pm2.5 and the skin symptoms in patients with allergies. The samples were observed from patients in the hospitals.

The research object is promising. However, there are certain flaws in the current manuscript to address. The most obvious one is the manuscript's logic, which reads more like a technical report than a scientific journal paper.

Insufficient background and reasons for this study in the introduction. Lack of details on study design, data process and statistical analysis. Poor presentations of the results such as unaligned numbers, and quite raw data figures. I would recommend giving subtitles in the discussion.

 

I would suggest a major revision to the manuscript. 

Comments on the Quality of English Language

Moderate editing of English language required

Author Response

Comment　The manuscript has looked into the correlation between the iron components in the pm2.5 and the skin symptoms in patients with allergies. The samples were observed from patients in the hospitals.

 

Response

Thank you for taking the time to read this article. This time, we investigated the relationship between ionic components of PM2.5 and skin symptoms. We have made some minor revisions based on various comments from Reference Person 1, so please take a look.

 

Comment1 The research object is promising. However, there are certain flaws in the current manuscript to address. The most obvious one is the manuscript's logic, which reads more like a technical report than a scientific journal paper.

 

Response 1.　I have tried to make corrections, but if they are not satisfactory, I would like to make major corrections at another opportunity.

 

Comment２：Insufficient background and reasons for this study in the introduction. Lack of details on study design, data process and statistical analysis. Poor presentations of the results such as unaligned numbers, and quite raw data figures. I would recommend giving subtitles in the discussion.

 

Response 2: Thank you. I've organized it and given it a title.

 

Comment 3：I would suggest a major revision to the manuscript.

Comments on the Quality of English Language

 

Response３；

Moderate editing of English language required

Thank you for your time and effort on my paper. I will rewrite it and resubmit it.

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

Good job! Thank you very much for the revision.