All reviews of published articles are made public. This includes manuscript files, peer review comments, author rebuttals and revised materials. Note: This was optional for articles submitted before 13 February 2023.
Peer reviewers are encouraged (but not required) to provide their names to the authors when submitting their peer review. If they agree to provide their name, then their personal profile page will reflect a public acknowledgment that they performed a review (even if the article is rejected). If the article is accepted, then reviewers who provided their name will be associated with the article itself.
The authors have attended to the reviewers' and my concerns.
Please attend to the reviewer 1 comments, particularly those related to the discussion section.
While the study's improved articulation highlights the significant correlation between KL-6 levels and respiratory function test severity, it is important to note that the clinical utility of requesting KL-6 levels for all patients may be limited. Implementing KL-6 testing universally could be impractical due to cost constraints and the availability of resources. Additionally, the variability in individual patient cases might necessitate a more selective approach, where KL-6 testing is reserved for patients with specific clinical indications or those at higher risk of severe lung disease. This limitation underscores the need for a balanced approach in clinical practice, where the benefits of such testing are weighed against practical considerations. Despite these limitations, the study provides valuable insights into the potential role of KL-6 as a biomarker in respiratory medicine, emphasizing the importance of targeted and judicious use of this test in clinical settings.
The improved study design, which organizes patients by connective tissue diseases and treatment status, significantly enhances the clarity and relevance of the findings. By categorizing patients into treated and untreated groups, the study allows for a more precise analysis of KL-6 levels and their correlation with respiratory function. This stratification helps to account for the variability in disease progression and treatment effects, providing a more nuanced understanding of how KL-6 can serve as a biomarker. Consequently, the study's refined design not only strengthens the validity of the results but also improves its applicability to clinical practice.
The conclusions are strong, but it would be beneficial to include in the discussion the work titled "Serum KL-6 levels reflect the severity of interstitial lung disease associated with connective tissue disease," which is referenced but not discussed. Integrating this study into the discussion could provide additional context and support for the findings, highlighting how KL-6 levels correlate with disease severity. Including this reference would not only enhance the depth of the discussion but also align the study's findings with existing research, thereby strengthening the overall argument and providing a more comprehensive view of the clinical implications of KL-6 as a biomarker.
I agree with the structure and text provided
Methods are now better described
findings have validity although an limited support of results
none
no comment
no comment
no comment
no comment
The reviewers found several issues to be attended to before considering a final response.
Please review each comment and re-submit an updated version with the track changes tool (or highlight the changes). Also, include a response letter for each reviewer/comments.
**PeerJ Staff Note:** Please ensure that all review and editorial comments are addressed in a response letter and that any edits or clarifications mentioned in the letter are also inserted into the revised manuscript where appropriate.
**Language Note:** The review process has identified that the English language must be improved. PeerJ can provide language editing services - please contact us at [email protected] for pricing (be sure to provide your manuscript number and title). Alternatively, you should make your own arrangements to improve the language quality and provide details in your response letter. – PeerJ Staff
Perelas et al (Lancet, 2020, page 3) have shown that the phrase you use in lines 46-63 is not the most accurate. It is important to mention the role of antibodies in mediating the inflammatory and fibrotic processes; it is such an interesting observation because there is evidence to support the idea that not all interstitial lung diseases have the same behavior. For example, systemic sclerosis is by far considered to have more fibrotic evolution than inflammatory myopathies. Your introduction needs to explore in more detail the physiopathology of each type of autoimmune connective tissue disease.
KL6 has already been explored and there is large evidence of its role as a marker of lung injury, you could provide more information about its differences for each disease, and you should expand the knowledge about it.
On the other hand, I couldn’t find references that denote the importance of inflammatory biomarkers in interstitial lung disease, the information extrapolated from other diseases (lines 86-96) is not enough to support its use as biomarkers. You have to consider that not all patients will course with elevated inflammatory biomarkers for example Khanna et al (Lancet, 2023) in their study to evaluate effectiveness and security for tocilizumab only recruited 30% of patients with IL-6 >10 pg/ml.
I suggest including an analysis using stratification by type of connective tissue disease or antibody, and to explore if there is any difference related to KL6 or inflammatory biomarkers.
I suggest including within the demographic description basal FVC and DLCO and the type of tomographic pattern because it is difficult to infer if the analysis belongs to patients with fibrotic or inflammatory behavior.
The conclusion is not enough strong concerning inflammatory biomarkers and they do not highly contribute to the knowledge of autoimmune connective tissue diseases-interstitial lung disease.
No comment
Thanks for inviting me to review the manuscript entitled "The clinical values of KL-6, NLR, SII. MLR, PLR, and RDW for predicting the occurrence and severity of connective tissue disease-associated interstitial lung disease". The results of the manuscript are interesting. However, the following points need attention:
1) Is it necessary for the authors to specify when they say patients are untreated? The definition that uses “lines 107-110” is unclear. What medication? Is the therapeutic scheme for interstitial lung disease or each CTD?
2) It is necessary to consider the symptoms' onset or evolution time for CTD (weeks, months, years) because the authors consider interstitial lung disease as a comorbidity. This information should be included.
3) In this study, it is reported that the elevated RDW-SD in CTD-ILD patients was unrelated to medication. At the same time, the SII, MLR, and RDW-CV were influenced by medication treatment. However, the potential mechanism needs to be discussed.
4) In this study, it is reported that the correlations of SII or PLR with pulmonary function parameters were no longer evident in CTD-ILD patients after medication (lines 263-265); then, were the study participants followed up post-treatment?
5) Explain the adjusted regression model; what variables were included?
6) Why did the authors not include the variables of forced vital capacity, forced expired volume in one second, and diffusing capacity of the lungs for carbon monoxide in the descriptive table 1 or 2, or according to “treatment group,” Table 3? what is the behavior of these clinical variables in both study groups?
I believe the authors can redirect the title of this manuscript to the principal conclusion.
no comment
no comment
no comment
CTD-ILD group includes several autoimmune entities and different forms of ILD associated. Where the type of interstitial pattern have an influence ton he behavior of CTD-ILD
The authors did not separate the groups according to the type of ILD present to compere the differents biomarkers
none
none
biomarkers analysis should not only be carried out between CTD and CTD-ILD, with or without treatment, but should focus on the type of ILD present in each entity.
All text and materials provided via this peer-review history page are made available under a Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.