Inflammatory bowel disease and risk of idiopathic pulmonary fibrosis: A protocol for systematic review and meta-analysis.

INTRODUCTION: Inflammatory bowel disease is a relapsing chronic gastrointestinal inflammatory disease. Idiopathic pulmonary fibrosis is a rare but serious extraintestinal pulmonary manifestation of inflammatory bowel disease. However, the relationship between these two conditions is unclear. Therefore, this study aims to elucidate this relationship through a systematic review and meta-analysis, focusing on the risk of idiopathic pulmonary fibrosis in patients with inflammatory bowel disease.
METHODS: The systematic review will be outlined according to the Preferred Reporting Items for Systematic Review and Meta-Analyses Protocols and its extension statement for reporting systematic reviews incorporating network meta-analyses of healthcare interventions: checklist and explanations. Original articles published in any language will be searched in the following databases: PubMed, Web of Science, EMBASE, Google Scholar, and Ovid. Observational studies that reveal an association measure between idiopathic pulmonary fibrosis and inflammatory bowel disease will be included (cross sectional, cohort, and case-control trials). Two independent reviewers will be assigned to evaluate study quality using the Newcastle-Ottawa scale for assessing the quality of non-randomized studies in meta-analyses. Sensitivity analyses will be conducted based on the quality of included studies. All relevant studies will be assessed based on the study type, sample size, inflammatory bowel disease subtype, odds ratio, confidence interval, treatment strategy, and follow-up. The Grading of Recommendations Assessment, Development, and Evaluation approach will be used to rate the quality of the evidence. DISCUSSION: The results of this meta-analysis may show that patients with inflammatory bowel disease are at higher risk of developing idiopathic pulmonary fibrosis. This study will be the first meta-analysis to focus on the association between inflammatory bowel disease and idiopathic pulmonary fibrosis. Exploring the relationship between the two conditions may further enhance our understanding of the pathogenesis of inflammatory bowel disease and idiopathic pulmonary fibrosis and promote the development of related research fields.

Introduction

Inflammatory bowel disease (IBD) is a relapsing chronic inflammatory disease mediated by immune responses. There are two types—ulcerative colitis (UC) and Crohn’s disease (CD) [1]. The pathogenesis of IBD is not fully understood, but it is assumed to involve the intestinal flora, intestinal mucosal permeability, immune disorders, environment, and genetics [1, 2]. An increasing number of epidemiological studies have indicated that IBD is a health and economic burden for people worldwide [3]. Moreover, although the incidence of IBD has increased and then plateaued in the Western world during the past 100 years, its prevalence has risen rapidly in the East, with more patients presenting with complicated disease [4-6].

Extraintestinal manifestations of IBD in the lungs include interstitial lung disease, granulomatous lung disease, and eosinophilic pneumonia [7, 8]. In potentially related pulmonary diseases, idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fibrotic interstitial lung disease of unknown etiology that ultimately leads to death from respiratory failure. It tends to occur more commonly in older people and has a high mortality rate [9, 10]. Existing research data indicate that the prevalence and incidence of IPF have increased globally, particularly with age and especially in men compared to that in women [11, 12]. Recently, a large national epidemiological survey in South Korea has showed that the risk of developing IPF in patients with IBD is rising, and it is more obvious in patients with CD [13]. Although most small cohort studies have limited the depth of IPF research [14], more and more IBD lung manifestations have been reported, which deserve our attention [15-17].

According to existing literature, the risk and magnitude of IPF in patients with IBD are unclear. More research has been conducted; however, no systematic review has been conducted to elucidate this. Therefore, a systematic review and meta-analysis on this theme is necessary.

In recent decades, meta-analyses have been widely used to summarize literature, reach sound conclusions, and guide the establishment of clinical policies and guidelines. We propose this meta-analysis protocol as a feasible approach to explore the risk of IPF in patients with IBD. The results obtained will shed light on how these conditions relate to each other, aiding to identify the risk factors, prevention strategies, and treatments.

Methods

Study design and registration

This systematic review and meta-analysis aims to explore the risk of IPF in patients with IBD. The protocol has been developed according to the Preferred Reporting Items for Systematic Review and Meta-Analyses Protocols (PRISMA-P) [18] and the PRISMA extension statement for reporting systematic reviews incorporating network meta-analyses of healthcare interventions: checklist and explanations [19]. According to PRISMA-P, the study has been registered with the International Prospective Register of Systematic Reviews Network (PROSPERO, CRD 42020169014).

Search strategy

Two independent researchers will search the PubMed, Web of Science, EMBASE, Google Scholar, and Ovid databases for original articles without language restrictions published as of January 10, 2022. The search terms will include inflammatory bowel disease, IBD, idiopathic pulmonary fibrosis, and IPF. The search strategy is IPF (or related terms, MeSH major topic) AND IBD (or related terms, MeSH major topic). The detailed search strategy for PubMed is presented in S1 Table. The search terms will be appropriately adjusted to fit the grammar rules of different databases. Additional resources including lists of references in all major research and review articles on the topic, erratum, and retraction rates of the included studies published in PubMed will be searched and the completion date of the above will be recorded in the review.

Inclusion criteria

Observational studies, including cross-sectional, cohort (retrospective or prospective), and case-control studies that reveal association measures between IBD and IPF and include adult participants (aged >18 years) with IPF (defined as pulmonary fibrosis without identifiable etiology) will be searched. Studies involving multiple lung lesions will be included, but only those with IPF data will be analyzed. IBD must have been diagnosed on a clinical basis or by colonoscopy. The exposure factor will be IBD. The control group will comprise either the general population or participants without IBD. The studies will not include restrictions in sample size, follow-up period, article language or publication status. The main outcome of our study will be to evaluate the risk of IPF in patients with IBD.

Exclusion criteria

Studies in any of the following categories will be excluded: experimental animal studies, review articles, case reports, studies without control group, studies with incomplete data, or editorials and conference abstracts. Additionally, in case of multiple studies of the same sample, the study with the largest sample size and the longest follow-up period will be analyzed.

Study selection

The data retrieved from each database will be imported into EndNote X9 software, and will be checked and deduplicated. Titles and abstracts of deduplicated articles will be read by two independent reviewers and initially screened based on inclusion criteria. If a study meets the inclusion criteria after the preliminary screening, the full text will be individually rechecked by two reviewers according to the predetermined criteria and finally included or excluded. Unverifiable literature and disagreements will be discussed between the two reviewers. If the two cannot reach a consensus, a third reviewer will step in. The author will be contacted if there is no full text or more details are needed. The process will follow the PRISMA flow diagram [20].

Data extraction

A table will be designed using Excel 2016 to extract information from the included studies. Data will be extracted separately by two independent reviewers. The data extraction table will include information on author name, contact information, journal name, year of publication, study characteristics (study design, sample size, study period, follow-up period, and country where study was conducted), demographic characteristics (age, sex, disease stage, and severity), study exposure, and outcome characteristics.

Subsequently, all relevant studies will be compared according to the study type, sample size, subtype of IBD, odds ratio (OR), 95% confidence interval (CI), treatment strategy, and follow-up. In case of a lack of any relevant data, the author(s) of the concerned study will be contacted directly.

Assessing risk of bias

The Newcastle–Ottawa scale will be used to assess the bias of non-randomized controlled trials in the meta-analysis [21]. The assessment of bias in the case-control study will include the selection of case and control groups, comparability, and exposure. The bias assessment in cohort studies will include cohort selection, comparability, and outcome. ‘Low’, ‘medium’ and ‘high’ quality studies will be represented with a score of 0–3, 4–6 and 7–9, respectively. Cross-sectional studies were evaluated according to the checklist advised by the Agency for Healthcare Research and Quality (https://www.ncbi.nlm.nih.gov/books/NBK35156/). The quality assessment is divided into three levels: ‘low’, ‘medium’ and ‘high’, and the scores correspond to 0–3, 4–7 , and 8–11 in turn. Bias assessments will be performed by two researchers; if the two hold different opinions, the issue will be settled by discussion until an agreement is reached.

Strategy for data synthesis

The currently available literature, including data on author name, year of publication, type of study, design, results of interest, sample size, author’s conclusions, and main findings will be reported. Qualitative evidence synthesis will be performed based on the available results. After describing the baseline characteristics of the studies, the outcome of interest will be summarized, that is, the association between IBD and the risk of IPF. Furthermore, the associations between CD and UC and the risk of IPF will be assessed separately.

The Cochrane Review Manager software RevMan and the statistical software SPSS-25 will be used to assess the data. If quantitative research is not appropriate, qualitative research will be adopted to describe the included research. Forest plots will be created to intuitively evaluate the effect size and corresponding 95% CI. Weighted mean differences with 95% CI will be used for continuous outcomes; OR or RR with 95% CI will be used for dichotomous outcomes.

Heterogeneity will be assessed based on the results of the Chi2 test and the I2 statistic. Homogeneity will be defined if the Chi2 test of P-value was >0.1 and the I2 value is <50%, and the fixed effects model will be adopted; otherwise, the random effects model will be adopted to integrate the meta-analysis data.

Subgroup analysis

Subgroup analyses will be performed to analyse the causes of heterogeneity. Subgroup analysis should include but not be limited to study type, age, sex, country, ethnicity, sample size, and follow-up period. Additionally, a potential source of heterogeneity should be considered, which is the method to achieve a diagnosis of IBD and IPF (medical records/ICD criteria/prospective studies with histology/multidisciplinary evaluation). Furthermore, other subgroup analyses will be considered in the study, including tobacco exposure, a potential analysis by cofounder for IBD and IPF.

Sensitivity analysis

Sensitivity analyses will be proceeded based on the quality of the included studies to determine potential reasons of heterogeneity by omitting studies one by one and evaluating the resulting effect.

Assessment of publication bias

Publication bias will be assessed using funnel plots and Egger tests if >10 studies are included. If the funnel plot shows asymmetry, it will indicate publication bias. If publication bias exists, trim and fill analyses will be used to assess the impact of publication bias on the results. Any bias will be explained through the analyses and discussions.

Quality of evidence

The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach will be used to assess the quality of the evidence [22]. The GRADE includes five factors that can reduce the quality of the evidence—limitations in designing the study or its execution (risk of bias), inconsistent results, indirectness of evidence, lack of precision, and publication bias—and three factors that can increase the quality of the evidence—very obvious therapeutic effect, conclusive evidence for a dose-response relationship, or all reasonable biases reduce the true treatment effect. Two independent researchers will rate the quality of the evidence for each result as high, moderate, low, or very low according to GRADE.

Patient and public involvement

This research will be based solely on published research, so patients and the public will not be directly involved.

Ethics and dissemination

This study will not be related directly to any patients or raise ethical concerns and, therefore, does not require ethics committee approval. The results will be published and disseminated in a peer-reviewed journal article.

Discussion

This study aims to assess the risk of IPF in patients with IBD. The results of this meta-analysis may show an association between IBD and IPF and suggest that patients with IBD are at a higher risk of developing IPF.

In recent years, the incidence of IBD and IPF has increased worldwide. Previous studies have not clearly articulated the pathogenesis of these two factors or their correlation. However, with increasing research, evidence has shown that the two may be linked. Some factors that contribute to the extraintestinal manifestations of IBD may cause IPF [23, 24]. Both IBD and IPF are associated with abnormal coagulation and are prone to thromboembolic disease. With the development of the disease, both are prone to malignant transformation to form tumors. Some studies have found that excessive Toll-interacting protein expression may contribute to the deterioration of IPF, whereas decreased expression may be associated with the occurrence of IBD [25]. Interleukin-25 and CDKN2B-AS1 are associated with IPF and IBD [26, 27]. In terms of treatment, studies have found that drugs used to treat IPF, such as pirfenidone, may be useful for intestinal fibrosis, a complication of CD [28-31]. Furthermore, calemin, integrin, and G protein-coupled receptor 84 may be targets for the treatment of both [30, 32, 33]. Fat stem/stromal cell and stromal vascular fraction treatment can improve IBD and IBF by reducing inflammation and promoting tissue repair [34]. However, existing literature is insufficient to account for the relationship between the two. Therefore, further exploration of this relationship is necessary.

To our knowledge, this study will be the first systematic review and meta-analysis focusing on the association between IBD and IPF. Strict adherence to the PRISMA-P guidelines and the use of a combination of quantitative and qualitative analyses are strengths of this study. A limitation is that there is currently limited information describing a relationship between IPF in IBD, and therefore, the studies may not be sufficient to indicate whether there is a true association between the two. Regardless of the outcome, exploring the relationship between the two may further enhance our understanding of IBD pathogenesis. If our findings indicate an association, they may provide new strategies for the diagnosis, treatment, and prevention of IBD and may promote the development of related research fields. We will issue a statement regarding whether there are important amendments to this protocol in the future.

PRISMA-P checklist.

(DOCX)

Click here for additional data file.

Search strategy for PubMed.

(DOCX)

Click here for additional data file.

12 May 2022

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- https://www.worldgastroenterology.org/guidelines/inflammatory-bowel-disease-ibd/inflammatory-bowel-disease-ibd-english

- https://openres.ersjournals.com/content/6/4/00391-2020.full

- https://link.springer.com/article/10.1007/s11739-019-02195-0

- https://www.atsjournals.org/doi/full/10.1164/rccm.201807-1255ST

- https://journals.lww.com/md-journal/Fulltext/2020/08140/Association_between_hyperuricemia,_gout,_urate.50.as

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Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #1: Partly

Reviewer #2: Yes

Reviewer #3: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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Reviewer #2: Yes

Reviewer #3: Yes

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Reviewer #2: No

Reviewer #3: Yes

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(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The authors described a protocol for systematic review and meta-analysis for

IBD and the risk of idiopathic pulmonary fibrosis. I suggest, the authors consider the following points.

1) The introduction section (paragraphs two and three) has some grammatical problems. Language editing is required.

2) Trim and fill analysis would be helpful in case of existing publication bias.

Reviewer #2: Inflammatory bowel disease and risk of idiopathic pulmonary fibrosis, a protocol for

systematic review and meta-analysis

This article presents the study protocol of a systematic review and meta-analysis aims to find the association between inflammatory bowel disease (IBD) and idiopathic pulmonary fibrosis (IPF) risk.

The subject is novel and interesting, but the authors must correct and explain these points:

General comment

1. The manuscript text suffers from fragmentary sentences and poor cohesion. The quality of scientific writing needs attention. Please consider a major revision of the manuscript by a native English speaker with a demonstrated history of scientific writing.

Abstract

1. Introduction: The rationale of the study is not well presented. Please revise.

2. Methods: Please consider using passive voice when presenting methods.

3. Results: Need to be re-written.

Strengths and limitations of this study

1. Needs to be re-written.

Methods

1. Please include relevant references, where necessary.

Discussion

1. Please review the discussion, check its storyline, and improve its coherency. It is not easy to follow in its current form.

2. Please include relevant references, where necessary.

Reviewer #3: Thanks for sending me this interesting SRMA protocol. I think the quality of this paper is suitable for publication. Here are some suggestions:

• Abbreviations should be in complete form at their first appearance

• The English wording and the narrative synthesis should be improved.

• The flow of narrative, how the study was conducted, and the overall structure and sectioning of methods and other parts are acceptable.

• I have no more suggestions to disclose and would be happy to do re-reviewing of the modifications.

**********

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Reviewer #1: No

Reviewer #2: Yes: Mohsen Abbasi-Kangevari

Reviewer #3: Yes: Esmaeil Mohammadi

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1 Jun 2022

Dear editors:

Thank you for your comments concerning our manuscript. Those comments are all valuable and very helpful for revising and improving our paper, as well as the important guiding significance to our researches. We have done the full English language editing. Specific modifications can be quickly found based on the line number in new "Manuscript". For the full text of the revision changes, see the "Revised Manuscript with Track Changes" file. We hope that the revised new manuscript will be approved.

1.If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter.

Response: Funding information has not changed, so there is no need to update the statement in the cover letter.

2.Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

Response: The figure file was deleted. The PRISMA flow diagram takes the form of references.

3.Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

Response: The full text has been revised in accordance with the journal format requirements.

4.Your ethics statement should only appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please delete it from any other section.

Response: The ethical statement has been removed from sections besides the Methods.

5.Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information.

Response: The table "Search strategy of PubMed" in the original manuscript has been modified as supplementary information. According to the requirements of the journal, the table is named "S1_Table.docx". This manuscript is a protocol for systematic review and meta-analysis, and the PRISMA-P checklist should be used. We have added this checklist as supporting information as required. Because the PRISMA-P checklist requires authors contributions and fundings information, we add them before the references in manuscript. The PRISMA-P checklist is named "S2_File.docx", as requested. The title of Supporting Information files are appended to the end of the manuscript.

6.Thank you for submitting the above manuscript to PLOS ONE. During our internal evaluation of the manuscript, we found significant text overlap between your submission and the following previously published works.

-https://www.worldgastroenterology.org/guidelines/inflammatory-bowel-disease-ibd/inflammatory-bowel-disease-ibd-english

- https://openres.ersjournals.com/content/6/4/00391-2020.full

- https://link.springer.com/article/10.1007/s11739-019-02195-0

- https://www.atsjournals.org/doi/full/10.1164/rccm.201807-1255ST

-https://journals.lww.com/md-journal/Fulltext/2020/08140/Association_between_hyperuricemia,_gout,_urate.50.as

We would like to make you aware that copying extracts from previous publications, especially outside the methods section, word-for-word is unacceptable. In addition, the reproduction of text from published reports has implications for the copyright that may apply to the publications.

Please revise the manuscript to rephrase the duplicated text, cite your sources, and provide details as to how the current manuscript advances on previous work. Please note that further consideration is dependent on the submission of a manuscript that addresses these concerns about the overlap in text with published work.

We will carefully review your manuscript upon resubmission, so please ensure that your revision is thorough.

Response: We reviewed 5 linked sources, revised duplicate text, and supplemented and updated references. Here we need to explain the following. Regarding the issue of text overlap with published articles, we have done our best to reword the repeated text in the full text, and also tried our best to resolve the text overlap including but not limited to the Methods section to avoid the possibility of plagiarism, and marked the source of citation . However, because the systematic reviews and meta-analyses are based on the PRISMA series of standards, it is inevitable that there will be duplications in the manuscript. Finally, we very much hope that through our efforts to pass this review.

Special thanks to you for your good comments. We tried our best to improve the manuscript and made some changes in the manuscript. These changes will not influence the content and framework of the paper.

We appreciate for warm work of editors and reviewers earnestly, and hope that the correction will meet with approval. Once again, thank you very much for your comments and suggestions.

Dear Reviewer 1:

Thank you for your comments concerning our manuscript. Those comments are all valuable and very helpful for revising and improving our paper, as well as the important guiding significance to our researches. We have done the full english language editing. Specific modifications can be quickly found based on the line number in new "Manuscript". For the full text of the revision changes, see the "Revised Manuscript with Track Changes" file. We hope that the revised new manuscript will be approved.

The authors described a protocol for systematic review and meta-analysis for

IBD and the risk of idiopathic pulmonary fibrosis. I suggest, the authors consider the following points.

1) The introduction section (paragraphs two and three) has some grammatical problems. Language editing is required.

Response: The whole text has been significantly revised by a native English-speaking language editor with a scientific writing certificate, and the english wording, grammar problems, language articulation and other issues have been solved.

2) Trim and fill analysis would be helpful in case of existing publication bias.

Response: We are sorry for our negligence of it, and this suggestion has been adopted and supplemented in the manuscript (line 189-190).

Special thanks to you for your good comments. We tried our best to improve the manuscript and made some changes in the manuscript. These changes will not influence the content and framework of the paper.

We appreciate for warm work of editors and reviewers earnestly, and hope that the correction will meet with approval. Once again, thank you very much for your comments and suggestions.

Dear Reviewer 2:

Thank you for your comments concerning our manuscript. Those comments are all valuable and very helpful for revising and improving our paper, as well as the important guiding significance to our researches. We have done the full english language editing. Specific modifications can be quickly found based on the line number in new "Manuscript". For the full text of the revision changes, see the "Revised Manuscript with Track Changes" file. We hope that the revised new manuscript will be approved.

Inflammatory bowel disease and risk of idiopathic pulmonary fibrosis, a protocol for systematic review and meta-analysis

This article presents the study protocol of a systematic review and meta-analysis aims to find the association between inflammatory bowel disease (IBD) and idiopathic pulmonary fibrosis (IPF) risk.

The subject is novel and interesting, but the authors must correct and explain these points:

General comment

1. The manuscript text suffers from fragmentary sentences and poor cohesion. The quality of scientific writing needs attention. Please consider a major revision of the manuscript by a native English speaker with a demonstrated history of scientific writing.

Response: The whole text has been significantly revised by a native English-speaking language editor with a scientific writing certificate, and the english wording, grammar problems, language articulation and other issues have already been solved.

Abstract

1. Introduction: The rationale of the study is not well presented. Please revise.

Response: The theoretical basis of the introduction has been re-elaborated (line 21-27).

2. Methods: Please consider using passive voice when presenting methods (line 28-43).

Response: The passive voice is already used in the method.

3. Results: Need to be re-written.

Response: The results have been revised. After reviewing the journal format requirements and historical documents that have been published in the journal, we revised the expected results and moved them to the discussion (line 210-212).

Strengths and limitations of this study

1. Needs to be re-written.

Response: The strengths and limitations of this study have been revised. After reviewing the journal format requirements and the historical documents that have been published in the journal, we revised the advantages and limitations and moved them to the discussion (line 230-235).

Methods

1. Please include relevant references, where necessary.

Response: Because this Agreement was developed primarily in accordance with PRISMA-P, the method part was also produced in accordance with PRISMA-P, so the main reference is PRISMA-P, in addition to The PRISMA 2020 statement. Therefore, the necessary reference materials for the method part have been attached to the text and have been updated with some updates (line 88,90,130,145,151).

Discussion

1. Please review the discussion, check its storyline, and improve its coherency. It is not easy to follow in its current form.

Response: The discussion has been reviewed and the storyline has been revised to improve coherence to some extent (line 209-240).

2. Please include relevant references, where necessary.

Response: References have been supplemented and updated in the discussion (line 216-226).

Special thanks to you for your good comments. We tried our best to improve the manuscript and made some changes in the manuscript. These changes will not influence the content and framework of the paper.

We appreciate for warm work of editors and reviewers earnestly, and hope that the correction will meet with approval. Once again, thank you very much for your comments and suggestions.

Dear Reviewer 3:

Thank you for your comments concerning our manuscript. Those comments are all valuable and very helpful for revising and improving our paper, as well as the important guiding significance to our researches. We have done the full english language editing. Specific modifications can be quickly found based on the line number in new "Manuscript". For the full text of the revision changes, see the "Revised Manuscript with Track Changes" file. We hope that the revised new manuscript will be approved.

Thanks for sending me this interesting SRMA protocol. I think the quality of this paper is suitable for publication. Here are some suggestions:

1. Abbreviations should be in complete form at their first appearance.

Response: Abbreviations have been added to the full name at first occurrence.

2. The English wording and the narrative synthesis should be improved.

Response: The whole text has been significantly revised by a native English-speaking language editor with a scientific writing certificate, and the english wording, grammar problems, language articulation and other issues have been solved. The comprehensive narrative during the discussion has been revised.

Special thanks to you for your good comments. We tried our best to improve the manuscript and made some changes in the manuscript. These changes will not influence the content and framework of the paper.

We appreciate for warm work of editors and reviewers earnestly, and hope that the correction will meet with approval. Once again, thank you very much for your comments and suggestions.

Submitted filename: Response to Reviewers.docx

Click here for additional data file.

8 Jun 2022

Inflammatory bowel disease and risk of idiopathic pulmonary fibrosis: a protocol for systematic review and meta-analysis

PONE-D-22-02613R1

Dear Dr. Li,

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,

Negar Rezaei, M.D., Ph.D.,

Academic Editor

PLOS ONE

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #2: Yes

Reviewer #3: Yes

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2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory.

Reviewer #2: Yes

Reviewer #3: Yes

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3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible.

Reviewer #2: Yes

Reviewer #3: Yes

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4. Have the authors described where all data underlying the findings will be made available when the study is complete?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. 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 #2: No

Reviewer #3: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

Reviewer #3: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: I would like to thank the author for the extensive revision of the manuscript. I think the quality of the manuscript has dramatically improved.

Reviewer #3: thanks again for sending me this revision paper. I read this again with great interest and believe that all my comments are addressed pretty well and have no further concerns.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

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Reviewer #2: Yes: Mohsen Abbasi-Kangevari

Reviewer #3: Yes: Esmaeil Mohammad, MD MPH

**********

17 Jun 2022

PONE-D-22-02613R1

Inflammatory bowel disease and risk of idiopathic pulmonary fibrosis: a protocol for systematic review and meta-analysis

Dear Dr. Li:

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. Negar Rezaei

Academic Editor

PLOS ONE