Trend in blood lead levels in Taiwanese adults 2005–2017

Chun-Wan Fang; Hsiao-Chen Ning; Ya-Ching Huang; Yu-Shao Chiang; Chun-Wei Chuang; I-Kuan Wang; Nai-Chia Fan; Cheng-Hao Weng; Wen-Hung Huang; Ching-Wei Hsu; Tzung-Hai Yen

doi:10.1371/journal.pone.0260744

Peer Review History

Original SubmissionJuly 29, 2021
17 Sep 2021 Decision Letter - Purvi Purohit, Editor PONE-D-21-24583 Trend in blood lead levels in Taiwanese adults 2005 - 2017 PLOS ONE Dear Dr. Tzung-Hai Yen, 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. Please give a point to point reply of the reviewer comments in your revised manuscript. Please submit your revised manuscript by 10 Sep. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. 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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: No Reviewer #2: No ****** 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: Yes 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 authors here present a trend in blood lead levels in Taiwanese adults. The objectives, methods, and summary of the results have been described succinctly with relevant statistics. However, minor revisions need to be incorporated. General: 1. There are syntax and punctuation issues throughout the document, which detracts the readability of the text. I have highlighted a few, but a thorough proofreading of the manuscript would be beneficial. Some of the longer sentences could also benefit from rephrasing. Further, a period should go after "et al" regardless of where it is mentioned in the sentence. 2. It would be helpful for the readers if the statistics/tests performed for the comparisons in the tables and figures are also mentioned in the table footnotes/figure legends. Abstract: The last sentence is a repetition of the findings already mentioned, and hence, can be removed. Introduction:,. Line 66: remove ‘because’ Results: Line 85: age Table 1 depicts the demographic and laboratory data. In the demographic data, the participants are further divided into 18-60 years of age and 60 years and older. (1) Both groups seem to have included the participants who are 60 years of age. Based on the data shown in Figure 2a and 2b, I presume the first group is 18-59 years and the second group would be 60 years and older. Kindly rectify. (2) In Table 1, the BLL should also be compared between these two age groups separately. (3) The BLL is reported as geometric mean and range in the tables 1 and 3 but as geometric mean and SD (this is geometric SD, I presume; kindly clarify) elsewhere in the text. The authors should address the reason for this or keep the reporting uniform throughout. Line 97: The authors mention a significant decreasing trend of BLL. Statistical details of how the differences between both the trends were analyzed can be included in the figure legend (Figure 1). Lines 98-99, 145-156: BLL rebounds are noted in Linkou branch in 2009 and 2016. However, Figure 1 seems to depict the same for Kaosiung branch. Kindly confirm or address. Line 135: Fix the citation. Discussion: Since eGFR was a significant predictor for blood lead levels, a brief section can be added discussing the relation between lead exposure and kidney function citing relevant literature. Lines 155, 157: same word with and without hyphen; make them uniform. Line 198: “by the fact..” Line 210: “by the lack of a standard sampling protocol..” Methods: In the statistics section, mention the tests used for checking the normality of distribution and equality of variance. Reviewer #2: Manuscript is technically sound, and the data supports the conclusions. The statistical analysis has been performed appropriately.The data points behind means, medians and variance measures should be made available. 1. In introduction section: Please elaborate on "BLL < 10 μg/dL showed higher cardiovascular mortality than those with BLLs >3.61 μg/dL and <10 μg/dL"... 2. In results section"Figure 1 Trend of blood lead levels (BLLs) in Taiwanese adult, 2005 -2017" should be rephrased to Figure 1 shows the trend of blood lead levels (BLLs) in Taiwanese adult, 2005 -2017.... and CI (confident interval): 5.682 – 8.929]"...its confidence interval 3. In discussion section the sentence " It is recommended that BLL should be < 10 µg/dL but < 5 µg/dL for children aged 1–5 years" should be elaborated. eGFR is the novelty of the paper and hence BLL and eGFR should be discussed in detail. 4. In methodology, inclusion exclusion criteria "Lead is concentrated in the kidney after body absorption and is then excreted in urine. Patients with chronic kidney disease might show elevated BLLs due to decreased urinary excretion"....this is a generalized statement and support the statement with adequate references. ****** 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 [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. 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Revision 1
31 Oct 2021 Author Response Reviewer #1: The authors here present a trend in blood lead levels in Taiwanese adults. The objectives, methods, and summary of the results have been described succinctly with relevant statistics. However, minor revisions need to be incorporated. General: 1. There are syntax and punctuation issues throughout the document, which detracts the readability of the text. I have highlighted a few, but a thorough proofreading of the manuscript would be beneficial. Some of the longer sentences could also benefit from rephrasing. Further, a period should go after "et al" regardless of where it is mentioned in the sentence. Response: Thank you for the comments. This manuscript has been sent to AJE for English grammar editing prior to first submission. Please advise us again if we miss out anything. 2. It would be helpful for the readers if the statistics/tests performed for the comparisons in the tables and figures are also mentioned in the table footnotes/figure legends. Response: Thank you for the comment. The information has been included in the table footnotes/figure legends. Abstract: The last sentence is a repetition of the findings already mentioned, and hence, can be removed. Response: Thank you for the comment. The sentence has been removed. Introduction:,. Line 66: remove ‘because’ Response: Thank you for the comment. The word has been removed. Results: Line 85: age Response: Thank you for the comment. The word has been included. Table 1 depicts the demographic and laboratory data. In the demographic data, the participants are further divided into 18-60 years of age and 60 years and older. (1) Both groups seem to have included the participants who are 60 years of age. Based on the data shown in Figure 2a and 2b, I presume the first group is 18-59 years and the second group would be 60 years and older. Kindly rectify. Response: Thank you for the comment. The paragraph has been revised. The participants are further divided into 18 - 60 years of age and 60 years and older. Nevertheless, there was no significant difference in BLL between participants with 18 - 60 years of age and 60 years and older (3.34 ± 3.15 versus 3.08 ± 2.22 µg/dL; P = 0.064). (2) In Table 1, the BLL should also be compared between these two age groups separately. Response: Thank you for the comment. The paragraph has been revised. The participants are further divided into 18-60 years of age and 60 years and older. Nevertheless, there was no significant difference in BLL between participants with 18 - 60 years of age and 60 years and older (3.34 ± 3.15 versus 3.08 ± 2.22 µg/dL; P = 0.064). (3) The BLL is reported as geometric mean and range in the tables 1 and 3 but as geometric mean and SD (this is geometric SD, I presume; kindly clarify) elsewhere in the text. The authors should address the reason for this or keep the reporting uniform throughout. Response: Thank you for the comment. The footnote of Table 1 and 3 have been revised. BLL was expressed as geometric mean (range). Other parametric variables were presented as the means ± standard deviation, and nonparametric variables were presented as n (%). The geometric mean of BLL was used in this study because it was less affected by extreme values than the arithmetic mean. Line 97: The authors mention a significant decreasing trend of BLL. Statistical details of how the differences between both the trends were analyzed can be included in the figure legend (Figure 1). Response: Thank you for the comment. The figure legend has been revised according to comments of both reviewers. Figure 1 Trend of blood lead levels (BLLs). The figure shows the trend of BLLs in Taiwanese adult, 2005 -2017. The differences between the means of BLLs in each year were examined by one-way analysis of variance test. A significant continuous decreasing trend (P < 0.001) was noted. Furthermore, the mean BLLs of the Kaohsiung branch were higher than those of the Linkou branch throughout the indicated periods [odds ratio (OR): 7.882; 95% CI (confident interval): 5.682 – 8.929]. Lines 98-99, 145-156: BLL rebounds are noted in Linkou branch in 2009 and 2016. However, Figure 1 seems to depict the same for Kaosiung branch. Kindly confirm or address. Response: Thank you for the comment. The sentences have been revised. A significant continuous decreasing trend in BLLs had been observed (P < 0.001, Figure 1). Moreover, there were rebounds of BLL noted at Kaoshiung branch of Chang Gung Memorial Hospital in 2009, 2013 and 2016. Rebounds of BLL were also noted at Linkou branch in 2009 and 2014. Line 135: Fix the citation. Response: Thank you for reminding us. The citation has been revised. Discussion: Since eGFR was a significant predictor for blood lead levels, a brief section can be added discussing the relation between lead exposure and kidney function citing relevant literature. Response: Thank you for the comment. A new paragraph has been added in Discussion section. Lead exposure, even at low-level, is associated with renal impairment and incident of chronic kidney disease. In a series of studies, it was demonstrated that environmental exposure to lead was related to progressive renal insufficiency in patients with [36] and without [37-39] diabetes, and chelation therapy may retard renal disease progression in these patients [40]. In a population-based study, researchers from Sweden found that low-level lead exposure was associated with reduced kidney function and incident chronic kidney disease [41]. In another cross-sectional study, researchers from United States [42] reported that low-level lead exposure was associated with lower intelligence quotient and more inattention in children with chronic kidney disease. In a recent systematic review and meta-analysis study [43], it was confirmed that lead exposure was associated with reduced estimated glomerular filtration rate and increased proteinuria risks. Lines 155, 157: same word with and without hyphen; make them uniform. Response: Thank you for the comment. The word has been revised. Line 198: “by the fact..” Response: Thank you for the comment. The sentence has been revised. Line 210: “by the lack of a standard sampling protocol..” Response: Thank you for the comment. The sentence has been revised. Methods: In the statistics section, mention the tests used for checking the normality of distribution and equality of variance. Response: Thank you for the comment. The analytical method has been provided. The Quantile-quantile plot and Kolmogorov-Smirnov test were used to check the normality of distribution. The Levene test was used to check the equality of variance. Reviewer #2: Manuscript is technically sound, and the data supports the conclusions. The statistical analysis has been performed appropriately. The data points behind means, medians and variance measures should be made available. 1. In introduction section: Please elaborate on "BLL < 10 μg/dL showed higher cardiovascular mortality than those with BLLs >3.61 μg/dL and <10 μg/dL"... Response: Thank you for the comment. The study has been elaborated. In 2006, Menke et al [5] investigated U.S. adult participants with a BLL < 10 μg/dL and reported that the hazard ratios for comparisons of participants in the highest tertile of BLL (≥ 3.62 μg/dL) with those in the lowest tertile (< 1.94 μg/dL) were 1.25 for all-cause mortality and 1.55 for cardiovascular mortality. The BLL was strongly correlated with myocardial infarction and stroke mortality, and the correlation was apparent at levels of ≥ 2 μg/dL. 2. In results section "Figure 1 Trend of blood lead levels (BLLs) in Taiwanese adult, 2005 -2017" should be rephrased to Figure 1 shows the trend of blood lead levels (BLLs) in Taiwanese adult, 2005 -2017.... and CI (confident interval): 5.682 – 8.929]"...its confidence interval Response: Thank you for the comment. The figure legend has been revised according to comments of both reviewers. Figure 1 Trend of blood lead levels (BLLs). The figure shows the trend of BLLs in Taiwanese adult, 2005 -2017. The differences between the means of BLLs in each year were examined by one-way analysis of variance test. A significant continuous decreasing trend (P < 0.001) was noted. Furthermore, the mean BLLs of the Kaohsiung branch were higher than those of the Linkou branch throughout the indicated periods [odds ratio (OR): 7.882; 95% CI (confident interval): 5.682 – 8.929]. 3. In discussion section the sentence " It is recommended that BLL should be < 10 µg/dL but < 5 µg/dL for children aged 1–5 years" should be elaborated. eGFR is the novelty of the paper and hence BLL and eGFR should be discussed in detail. Response: Thank you for the comment. A new paragraph has been added in Discussion section. Lead exposure, even at low-level, is associated with renal impairment and incident of chronic kidney disease. In a series of studies, it was demonstrated that environmental exposure to lead was related to progressive renal insufficiency in patients with [36] and without [37-39] diabetes, and chelation therapy may retard renal disease progression in these patients [40]. In a population-based study, researchers from Sweden found that low-level lead exposure was associated with reduced kidney function and incident chronic kidney disease [41]. In another cross-sectional study, researchers from United States [42] reported that low-level lead exposure was associated with lower intelligence quotient and more inattention in children with chronic kidney disease. In a recent systematic review and meta-analysis study [43], it was confirmed that lead exposure was associated with reduced estimated glomerular filtration rate and increased proteinuria risks. 4. In methodology, inclusion exclusion criteria "Lead is concentrated in the kidney after body absorption and is then excreted in urine. Patients with chronic kidney disease might show elevated BLLs due to decreased urinary excretion"....this is a generalized statement and support the statement with adequate references. Response: Thank you for the comment. The statement has been referenced. Attachments Attachment Submitted filename: Response to reviewers.doc https://doi.org/10.1371/journal.pone.0260744.r002
17 Nov 2021 Decision Letter - Purvi Purohit, Editor Trend in blood lead levels in Taiwanese adults 2005 - 2017 PONE-D-21-24583R1 Dear Dr. Tzung-Hai Yen 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 for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org. 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, Purvi Purohit Academic Editor PLOS ONE Additional Editor Comments (optional): The authors have responded appropriately to all the queries raised by the reviewers. The manuscript has been revised and the manuscript is now acceptable for publication. https://doi.org/10.1371/journal.pone.0260744.r003
Formally Accepted
22 Nov 2021 Acceptance Letter - Purvi Purohit, Editor PONE-D-21-24583R1 Trend in blood lead levels in Taiwanese adults 2005 - 2017 Dear Dr. Yen: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. 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. If we can help with anything else, please email us at plosone@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Purvi Purohit Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0260744.r004

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