Study of inflammatory biomarkers in Chronic obstructive pulmonary disease (COPD) and their association with comorbidities

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This study investigates the relationships between inflammatory biomarkers in COPD and their associations with comorbidities. By focusing on specific biomarkers such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-ALFA), and fibrinogen, we seek to find the complex interplay between systemic inflammation, COPD severity, and the prevalence of comorbidities. This research is critical for advancing our understanding of the systemic manifestations of COPD and informing targeted interventions for improved patient management. Methods This cross-sectional observational study will be conducted at AVBRH, a tertiary care hospital in central India, over two years (August 2022 to August 2024). A sample size of 90 COPD patients will be randomly selected based on inclusion and exclusion criteria. Diagnostic tests will be performed, including pulmonary function tests, chest X-rays, and biomarker assessments. Statistical analyses, encompassing chi-square tests, Pearson’s correlation coefficient, and logistic regression, will explore associations between inflammatory biomarkers, COPD severity, and comorbidities. The study design ensures rigorous data collection and adherence to ethical standards, with SPSS 27.0 utilized for statistical analyses. Expected Outcome Anticipated outcomes include a comprehensive understanding of how inflammatory biomarkers correlate with the severity of COPD and their associations with comorbidities. We expect to identify specific biomarkers that may serve as indicators of increased risk for certain comorbid conditions. The findings will contribute valuable insights into the systemic nature of COPD and inform healthcare strategies tailored to mitigate comorbidity-related risks in COPD patients. This research has the potential to enhance clinical decision-making, guide personalized treatment plans, and ultimately improve the overall management of individuals living with COPD. " } { "@context": "http://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": "1", "item": { "@id": "https://f1000research.com/", "name": "Home" } }, { "@type": "ListItem", "position": "2", "item": { "@id": "https://f1000research.com/browse/articles", "name": "Browse" } }, { "@type": "ListItem", "position": "3", "item": { "@id": "https://f1000research.com/articles/13-334/v1", "name": "Study of inflammatory biomarkers in Chronic obstructive pulmonary..." } } ] } Home Browse Study of inflammatory biomarkers in Chronic obstructive pulmonary... ALL Metrics - Views Downloads Get PDF Get XML Cite How to cite this article KEDAR A and Jadhav U. Study of inflammatory biomarkers in Chronic obstructive pulmonary disease (COPD) and their association with comorbidities [version 1; peer review: 1 not approved] . F1000Research 2024, 13 :334 ( https://doi.org/10.12688/f1000research.146033.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Study Protocol Study of inflammatory biomarkers in Chronic obstructive pulmonary disease (COPD) and their association with comorbidities [version 1; peer review: 1 not approved] AISHWARYA KEDAR https://orcid.org/0009-0009-5013-9696 1 , Ulhas Jadhav 1 AISHWARYA KEDAR https://orcid.org/0009-0009-5013-9696 1 , Ulhas Jadhav 1 PUBLISHED 23 Apr 2024 Author details Author details 1 Respiratory Medicine, Datta Meghe Institute of Higher Education and Research, Wardha, Maharashtra, 442001, India AISHWARYA KEDAR Roles: Investigation, Methodology, Writing – Original Draft Preparation, Writing – Review & Editing Ulhas Jadhav Roles: Conceptualization, Investigation, Methodology, Supervision, Validation, Visualization OPEN PEER REVIEW DETAILS REVIEWER STATUS This article is included in the Datta Meghe Institute of Higher Education and Research collection. Abstract Background Chronic Obstructive Pulmonary Disease (COPD) is a prevalent respiratory condition associated with systemic inflammation and various comorbidities, significantly impacting patients’ health outcomes. This study investigates the relationships between inflammatory biomarkers in COPD and their associations with comorbidities. By focusing on specific biomarkers such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-ALFA), and fibrinogen, we seek to find the complex interplay between systemic inflammation, COPD severity, and the prevalence of comorbidities. This research is critical for advancing our understanding of the systemic manifestations of COPD and informing targeted interventions for improved patient management. Methods This cross-sectional observational study will be conducted at AVBRH, a tertiary care hospital in central India, over two years (August 2022 to August 2024). A sample size of 90 COPD patients will be randomly selected based on inclusion and exclusion criteria. Diagnostic tests will be performed, including pulmonary function tests, chest X-rays, and biomarker assessments. Statistical analyses, encompassing chi-square tests, Pearson’s correlation coefficient, and logistic regression, will explore associations between inflammatory biomarkers, COPD severity, and comorbidities. The study design ensures rigorous data collection and adherence to ethical standards, with SPSS 27.0 utilized for statistical analyses. Expected Outcome Anticipated outcomes include a comprehensive understanding of how inflammatory biomarkers correlate with the severity of COPD and their associations with comorbidities. We expect to identify specific biomarkers that may serve as indicators of increased risk for certain comorbid conditions. The findings will contribute valuable insights into the systemic nature of COPD and inform healthcare strategies tailored to mitigate comorbidity-related risks in COPD patients. This research has the potential to enhance clinical decision-making, guide personalized treatment plans, and ultimately improve the overall management of individuals living with COPD. READ ALL READ LESS Keywords Chronic Obstructive Pulmonary Disease (COPD), Inflammatory Biomarkers, Comorbidities, Systemic Inflammation, Respiratory Medicine, Cross-sectional Study Corresponding Author(s) AISHWARYA KEDAR ( [email protected] ) Close Corresponding author: AISHWARYA KEDAR Competing interests: No competing interests were disclosed. Grant information: The author(s) declared that no grants were involved in supporting this work. Copyright: © 2024 KEDAR A and Jadhav U. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: KEDAR A and Jadhav U. Study of inflammatory biomarkers in Chronic obstructive pulmonary disease (COPD) and their association with comorbidities [version 1; peer review: 1 not approved] . F1000Research 2024, 13 :334 ( https://doi.org/10.12688/f1000research.146033.1 ) First published: 23 Apr 2024, 13 :334 ( https://doi.org/10.12688/f1000research.146033.1 ) Latest published: 23 Apr 2024, 13 :334 ( https://doi.org/10.12688/f1000research.146033.1 ) Introduction Chronic Obstructive Pulmonary Disease (COPD) represents a significant global health challenge characterized by persistent respiratory symptoms and airflow limitation. 1 Beyond its pulmonary manifestations, COPD is increasingly recognized as a systemic inflammatory disorder with a propensity for various comorbidities, including cardiovascular diseases, diabetes, and renal dysfunction. 2 , 3 Identifying and characterizing inflammatory biomarkers associated with COPD may provide valuable insights into the complex interplay between pulmonary and systemic manifestations of the disease. Previous studies have implicated biomarkers such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-ALFA), and fibrinogen in systemic inflammation and their potential roles as indicators of disease severity and comorbidity risk in COPD. 4 – 6 However, a comprehensive understanding of the relationships between these biomarkers, COPD severity, and comorbidities remains an area of ongoing investigation. This study protocol outlines a cross-sectional and observational investigation to assess inflammatory biomarkers in COPD patients and their associations with comorbidities. The study aims to contribute to the existing knowledge base, informing future research and enhancing clinical strategies for the holistic management of COPD patients. By employing rigorous methodologies and statistical analyses, we anticipate elucidating key relationships that may guide targeted interventions and improve patient outcomes. Aim The primary aim of this study is to investigate inflammatory biomarkers in Chronic Obstructive Pulmonary Disease (COPD) and explore their associations with comorbidities. Objectives 1. To Study Inflammatory Biomarkers in COPD: Measure levels of inflammatory biomarkers, including CRP (C-reactive protein), IL-6, TNF-ALFA, and fibrinogen, in patients diagnosed with COPD. 2. To Investigate the Association with Comorbidities: Explore the prevalence of comorbidities such as heart diseases, anemia, chronic renal failure, and diabetes in COPD patients. 3. To Correlate Biomarker Levels with COPD Severity: Examine the correlation between the levels of inflammatory biomarkers and the severity of COPD, assessed through pulmonary function tests and chest imaging. 4. To Identify Other Observations: Investigate any additional observations or patterns that may emerge during the study, contributing to a comprehensive understanding of the relationship between COPD, inflammatory biomarkers, and comorbidities. Methods Study design This study will employ a cross-sectional and observational design to investigate the relationship between inflammatory biomarkers and COPD and their association with comorbidities. The cross-sectional design allows data collection at a single point, providing a snapshot of the relationship between variables. Study population The study population will consist of patients diagnosed with Chronic Obstructive Pulmonary Disease (COPD) who meet the inclusion criteria. Patients will be selected from the Respiratory Medicine department at AVBRH. Inclusion criteria encompass individuals diagnosed with COPD and those aged above 40 years. Exclusion criteria include patients unwilling to provide consent, non-cooperative patients, and those with connective tissue disorders such as rheumatoid arthritis or COPD asthma overlap. Place of study The study will be conducted at AVBRH, a tertiary care hospital attached to Jawaharlal Nehru Medical College. AVBRH is situated in the rural area of Sawangi, Meghe, Wardha, in central India. This location provides a diverse and representative sample of patients with COPD in a real-world clinical setting. The choice of a rural area enhances the study’s external validity, capturing a population that may have different characteristics compared to urban populations. Inclusion criteria 1. Diagnosis of COPD: Patients must have a confirmed diagnosis of Chronic Obstructive Pulmonary Disease (COPD) based on established criteria, including clinical symptoms, pulmonary function tests (spirometry), and chest X-rays. 2. Age criteria: Participants must be aged 40 years or above. This age threshold is chosen to focus on the population commonly affected by COPD and its associated comorbidities. Exclusion criteria 1. Consent and cooperation: Patients unwilling or unable to provide informed consent for participation in the study will be excluded. Additionally, individuals who exhibit non-cooperative behavior during the study procedures may be excluded to ensure data reliability. 2. Connective tissue disorders: Patients with known connective tissue disorders, such as rheumatoid arthritis, will be excluded. These conditions may introduce confounding variables that could affect the interpretation of inflammatory biomarkers. 3. COPD asthma overlap: Patients diagnosed with COPD asthma overlap will be excluded. This exclusion aims to maintain a homogeneous study population and focus specifically on COPD without the potential influence of overlapping conditions. Bias 1. Selection bias: • Potential issue: If the inclusion criteria are not strictly followed or certain groups of COPD patients are systematically excluded, it may introduce selection bias. • Mitigation: Ensuring rigorous adherence to inclusion and exclusion criteria during participant selection can minimize this bias. Random selection of patients can also help in reducing selection bias. 2. Information bias: • Potential issue: Inaccuracies in data collection or measurement of biomarkers, comorbidities, or COPD severity may lead to information bias. • Mitigation: Standardizing data collection methods, employing validated measurement tools, and providing appropriate training to personnel can minimize information bias. 3. Confounding bias: • Potential issue: Factors not considered in the study that may influence the relationship between inflammatory biomarkers and comorbidities, leading to confounding bias. • Mitigation: Controlling for potential confounding variables through study design, statistical methods, or matching can help minimize confounding bias. 4. Observer bias: • Potential issue: The knowledge of the study hypothesis or the involvement of biased observers in data collection may introduce observer bias. • Mitigation: Blinding participants and researchers to the study hypothesis, especially during the outcomes assessment, can reduce observer bias. Data collection process The data collection process for this study on inflammatory biomarkers in Chronic Obstructive Pulmonary Disease (COPD) and their association with comorbidities will be conducted with meticulous attention to detail and adherence to standardized procedures. Participant recruitment will involve identifying eligible individuals from the Respiratory Medicine department at AVBRH based on stringent inclusion and exclusion criteria. Informed consent will be sought from each participant, ensuring they fully understand the study’s purpose, procedures, and potential implications. Upon obtaining consent, a baseline assessment will be conducted to gather demographic information and confirm the diagnosis of COPD through pulmonary function tests and chest X-rays. Diagnostic tests, including spirometry for lung function, chest X-rays for initial assessment, and HRCT of the thorax in cases of severe derangement, will be carried out to evaluate the respiratory status of participants comprehensively. The biomarker testing phase will involve a series of laboratory tests. Blood samples will be collected for C-reactive protein (CRP) testing and the Westergren Katz tube test to measure Erythrocyte Sedimentation Rate (ESR). A complete blood count (CBC) will also be performed to assess leukocyte count and hemoglobin levels. Participants will undergo HbA1c testing to rule out diabetes. Cardiac evaluations, including echocardiogram and ECG, will be conducted to assess heart function. Furthermore, kidney function tests and measurements of inflammatory biomarkers such as Interleukin-6 (IL-6), Tumor Necrosis Factor-Alpha (TNF-ALFA), and fibrinogen will be performed. Data management will be a critical aspect of the process, involving the design of a secure and structured database to store and manage collected data. Regular checks and validation procedures will ensure data integrity throughout the study. Statistical analysis will be conducted using the SPSS 27.0 version, employing appropriate methods such as chi-square tests and Pearson’s correlation coefficient to analyze the relationships between biomarkers, COPD severity, and comorbidities. Sample size n = Z 2 ∗ P ∗ 1 − P d 2 Where; Z is the level of significance at 5%, i.e., 95% confidence interval = 1.96 P = Prevalence of COPD = 7.4% (Reference study 7 ) 80% of COPD patients had comorbidity: 7.4 ∗ 80 100 = 5.92 % d = Desired error of margin = 5% = 0.05 n = 1.96 2 ∗ 0.0592 ∗ 1 − 0.0592 0.05 2 = 85.58 n = 90 COPD patients needed in the study. Statistical method The study on inflammatory biomarkers in Chronic Obstructive Pulmonary Disease (COPD) and their association with comorbidities will rigorously utilize various statistical methods to analyze the relationships among key variables. The initial phase involves descriptive statistics, which will summarize the study population’s demographic details, COPD severity, and prevalence of comorbidities. Measures such as mean, median, standard deviation, and percentages will provide an overview of the characteristics of the participants. Chi-square tests will be employed to analyze categorical variables, particularly assessing the presence or absence of comorbidities across different COPD severity groups. This statistical method aids in understanding the associations between inflammatory biomarkers and the occurrence of specific comorbidities. Pearson’s correlation coefficient will be used to explore the linear relationship between continuous variables, such as the levels of inflammatory biomarkers and the severity of COPD. The strength and direction of these correlations will be assessed, providing valuable insights into potential associations. Multivariate analysis, including multiple regression analysis, may be considered to simultaneously examine the independent contributions of various factors to the observed associations. This approach provides a more comprehensive understanding of the interplay between inflammatory biomarkers, COPD severity, and comorbidities. Comparative analysis will involve statistical tests, such as t-tests or analysis of variance (ANOVA) for continuous variables and chi-square tests for categorical variables, to compare biomarker levels between different groups, such as varying COPD severity categories or the presence/absence of specific comorbidities. Furthermore, logistic regression will be employed to model the likelihood of comorbidities based on factors such as inflammatory biomarker levels and COPD severity. This statistical method aids in identifying potential predictors of comorbidities within the study population. Subgroup analysis will be conducted to explore variations in relationships across different subgroups, such as age groups or gender, providing insights into potential effect modifiers. Survival analysis techniques like Kaplan-Meier curves and Cox proportional hazards models may be considered in cases involving longitudinal data and time-to-event outcomes. These methods can provide valuable information on the occurrence of specific comorbidities over time. Sensitivity analysis will be conducted to assess the robustness of results, testing the impact of variations in key parameters or assumptions. The statistical software chosen for these analyses is SPSS version 27.0 statistical tools, 8 ensuring the accuracy and reliability of the results. Through the thoughtful application of these statistical methods, the study aims to unveil meaningful associations, correlations, and predictors related to inflammatory biomarkers, COPD severity, and comorbidities, contributing to a nuanced understanding of the intricate relationships within this complex medical landscape. Ethical considerations The Institutional Ethics Committee of Datta Meghe Institute of Higher Education and Research (DU) has granted its approval to the study protocol (Reference number: DMIHER (DU)/IEC/2022/119. Date: 21-07-2022). Before commencing the study, we will obtain written informed consent from all participants, providing them with a comprehensive explanation of the study’s objectives. Limitations Despite the careful planning and execution of the study on inflammatory biomarkers in Chronic Obstructive Pulmonary Disease (COPD) and their association with comorbidities, several limitations must be considered. While efficient for snapshot assessments, the cross-sectional design cannot establish causal relationships, warranting the need for longitudinal studies to explore temporal dynamics. Sampling bias is inherent due to the study’s reliance on a specific tertiary care hospital in a rural area, potentially limiting the generalizability of findings to diverse populations. The exclusion of individuals with connective tissue disorders and COPD asthma overlap might introduce selection bias, impacting the representation of specific subgroups within the COPD population. Additionally, self-reported data may introduce recall and social desirability biases, affecting the accuracy of information provided by participants. The focus on specific inflammatory biomarkers may limit the study’s comprehensiveness, as other relevant biomarkers may exist. Unmeasured confounders, external factors, and ethnic and cultural influences could further impact the study’s generalizability. Acknowledging these limitations is essential for a proper interpretation of results and highlight the need for cautious application to broader populations. Dissemination After the completion of the study, we will publish it in an indexed journal or conference. Study status The study has yet to start. After the publication of the protocol, we will start recruitment in the study. Discussion The observed correlations between inflammatory biomarkers, COPD severity, and comorbidities in this proposed study underscore the systemic nature of COPD, aligning with previous findings that have highlighted the intricate interplay between pulmonary and extra-pulmonary manifestations. 1 , 2 The association of COPD with systemic inflammation has been consistently reported in the literature, with elevated levels of biomarkers such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-ALFA), and fibrinogen linked to disease progression and severity. 4 – 6 By examining these specific biomarkers, our study aims to provide a more nuanced understanding of the underlying inflammatory processes in COPD. Identifying these biomarkers as potential indicators of comorbidity risk in COPD patients is consistent with existing evidence. 4 Studies have reported a higher prevalence of comorbidities, including cardiovascular diseases, diabetes, and renal dysfunction, in individuals with COPD. 9 By investigating the correlation between biomarker levels and the presence of comorbidities, our study seeks to contribute valuable insights into the pathophysiological mechanisms linking systemic inflammation and associated health complications in COPD patients. However, it is essential to acknowledge the limitations of this proposed study. The cross-sectional design restricts our ability to establish causation, and the selected sample, drawn from a specific tertiary care hospital in central India, may limit the generalizability of our findings to broader populations. The exclusion criteria, mainly the exclusion of individuals with connective tissue disorders and COPD asthma overlap, might introduce selection bias, influencing the representation of specific COPD subgroups. Data availability No data are associated with this article. References 1. Global Initiative for Chronic Obstructive Lung Disease: Global Initiative for Chronic Obstructive Lung Disease - GOLD. Accessed: December 5, 2023. Reference Source 2. Agustí A, Edwards LD, Rennard SI, et al. : Persistent systemic inflammation is associated with poor clinical outcomes in COPD: a novel phenotype. PLoS One. 2012; 7 : e37483. PubMed Abstract | Publisher Full Text | Free Full Text 3. Sin DD, Anthonisen NR, Soriano JB, et al. : Mortality in COPD: Role of comorbidities. Eur. Respir. J. 2006; 28 : 1245–1257. Publisher Full Text 4. Donaldson GC, Hurst JR, Smith CJ, et al. : Increased risk of myocardial infarction and stroke following exacerbation of COPD. Chest. 2010; 137 : 1091–1097. PubMed Abstract | Publisher Full Text 5. Gan WQ, Man SFP, Senthilselvan A, et al. : Association between chronic obstructive pulmonary disease and systemic inflammation: a systematic review and a meta-analysis. Thorax. 2004; 59 : 574–580. PubMed Abstract | Publisher Full Text | Free Full Text 6. Pinto-Plata VM, Müllerova H, Toso JF, et al. : C-reactive protein in patients with COPD, control smokers and non-smokers. Thorax. 2006; 61 : 23–28. PubMed Abstract | Publisher Full Text | Free Full Text 7. Daniel RA, Aggarwal P, Kalaivani M, et al. : Prevalence of chronic obstructive pulmonary disease in India: A systematic review and meta-analysis. Lung India. 2021; 38 : 506–513. PubMed Abstract | Publisher Full Text | Free Full Text 8. IBM SPSS Statistics: Accessed: February 21, 2024. Reference Source 9. Mannino DM, Thorn D, Swensen A, et al. : Prevalence and outcomes of diabetes, hypertension and cardiovascular disease in COPD. Eur. Respir. J. 2008; 32 : 962–969. Publisher Full Text Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 23 Apr 2024 ADD YOUR COMMENT Comment Author details Author details 1 Respiratory Medicine, Datta Meghe Institute of Higher Education and Research, Wardha, Maharashtra, 442001, India AISHWARYA KEDAR Roles: Investigation, Methodology, Writing – Original Draft Preparation, Writing – Review & Editing Ulhas Jadhav Roles: Conceptualization, Investigation, Methodology, Supervision, Validation, Visualization Competing interests No competing interests were disclosed. Grant information The author(s) declared that no grants were involved in supporting this work. Article Versions (1) version 1 Published: 23 Apr 2024, 13:334 https://doi.org/10.12688/f1000research.146033.1 Copyright © 2024 KEDAR A and Jadhav U. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article KEDAR A and Jadhav U. Study of inflammatory biomarkers in Chronic obstructive pulmonary disease (COPD) and their association with comorbidities [version 1; peer review: 1 not approved] . F1000Research 2024, 13 :334 ( https://doi.org/10.12688/f1000research.146033.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 1 VERSION 1 PUBLISHED 23 Apr 2024 Views 0 Cite How to cite this report: Stockley PR. Reviewer Report For: Study of inflammatory biomarkers in Chronic obstructive pulmonary disease (COPD) and their association with comorbidities [version 1; peer review: 1 not approved] . F1000Research 2024, 13 :334 ( https://doi.org/10.5256/f1000research.160065.r308276 ) The direct URL for this report is: https://f1000research.com/articles/13-334/v1#referee-response-308276 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 14 Aug 2024 Prof RA Stockley , Lung Investigation Unit, Medicine, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, Edgbaston, UK Not Approved VIEWS 0 https://doi.org/10.5256/f1000research.160065.r308276 The association and causation of comorbidities in COPD is both intriguing and complex. COPD is accepted as an inflammatory disease with a presumed neutrophilic background. CV disease,Type 2 diabetes,osteoporosis,gingivitis are all present with greater prevalence in COPD but the reason/s ... Continue reading READ ALL The association and causation of comorbidities in COPD is both intriguing and complex. COPD is accepted as an inflammatory disease with a presumed neutrophilic background. CV disease,Type 2 diabetes,osteoporosis,gingivitis are all present with greater prevalence in COPD but the reason/s are difficult to dissect. All are features of aging . COPD CVD Osteoporosis and gingivitis are all associated with smoking and all have a presumed inflammatory Pathophysiology although with different putative specific cytokine profiles. This leads to the concepts that one leads to systemic overspill influencing the prevalence of the others or that they all have the same inflammatory background (features that are difficult to dissect! COPD alone has clinical and pathological features that vary including bronchitis, emphysema, small airways dysfunction, bronchiectasis with and without chronic airways colonisation apart from “severity” as defined by airflow obstruction. These features have variable outcomes and variable local and systemic inflammation. The inflammatory markers chosen also reflect obesity and are largely non specific. It seems unclear why the power calculations indicate such a low data set. With all these variables and the confounding factors and low prevalence a much larger data set is required. If the outcome is to identify common pathophysiological processes a clearer selection of putative markers is needed. If the plan is to use biomarkers to determine the likelihood of co morbidity that is already a recognised clinical approach to COPD. Characterisation of the presence of comorbidities requires much clearer and detailed assessment. For instance CVD requires Q risk scores and vascular stiffness. Perhaps the first step is to define a Local COPD cohort in detail and define the prevalence of comorbidities in detail as well as putative confounders. Thereafter define the comorbidities with and without COPD and both generalised and specific biomarkers. This alone requires a major effort and cohort size. Is the rationale for, and objectives of, the study clearly described? Partly Is the study design appropriate for the research question? No Are sufficient details of the methods provided to allow replication by others? Partly Are the datasets clearly presented in a useable and accessible format? Partly Competing Interests: No competing interests were disclosed. Reviewer Expertise: Pathophysiology of COPD,inflammation, comorbidities and biomarkers I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Stockley PR. Reviewer Report For: Study of inflammatory biomarkers in Chronic obstructive pulmonary disease (COPD) and their association with comorbidities [version 1; peer review: 1 not approved] . F1000Research 2024, 13 :334 ( https://doi.org/10.5256/f1000research.160065.r308276 ) The direct URL for this report is: https://f1000research.com/articles/13-334/v1#referee-response-308276 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 23 Apr 2024 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 Version 1 23 Apr 24 read Prof RA Stockley , University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, Edgbaston, UK Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2024 Stockley P. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 14 Aug 2024 | for Version 1 Prof RA Stockley , Lung Investigation Unit, Medicine, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, Edgbaston, UK 0 Views copyright © 2024 Stockley P. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Not Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions The association and causation of comorbidities in COPD is both intriguing and complex. COPD is accepted as an inflammatory disease with a presumed neutrophilic background. CV disease,Type 2 diabetes,osteoporosis,gingivitis are all present with greater prevalence in COPD but the reason/s are difficult to dissect. All are features of aging . COPD CVD Osteoporosis and gingivitis are all associated with smoking and all have a presumed inflammatory Pathophysiology although with different putative specific cytokine profiles. This leads to the concepts that one leads to systemic overspill influencing the prevalence of the others or that they all have the same inflammatory background (features that are difficult to dissect! COPD alone has clinical and pathological features that vary including bronchitis, emphysema, small airways dysfunction, bronchiectasis with and without chronic airways colonisation apart from “severity” as defined by airflow obstruction. These features have variable outcomes and variable local and systemic inflammation. The inflammatory markers chosen also reflect obesity and are largely non specific. It seems unclear why the power calculations indicate such a low data set. With all these variables and the confounding factors and low prevalence a much larger data set is required. If the outcome is to identify common pathophysiological processes a clearer selection of putative markers is needed. If the plan is to use biomarkers to determine the likelihood of co morbidity that is already a recognised clinical approach to COPD. Characterisation of the presence of comorbidities requires much clearer and detailed assessment. For instance CVD requires Q risk scores and vascular stiffness. Perhaps the first step is to define a Local COPD cohort in detail and define the prevalence of comorbidities in detail as well as putative confounders. Thereafter define the comorbidities with and without COPD and both generalised and specific biomarkers. This alone requires a major effort and cohort size. Is the rationale for, and objectives of, the study clearly described? Partly Is the study design appropriate for the research question? No Are sufficient details of the methods provided to allow replication by others? Partly Are the datasets clearly presented in a useable and accessible format? Partly Competing Interests No competing interests were disclosed. Reviewer Expertise Pathophysiology of COPD,inflammation, comorbidities and biomarkers I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. reply Respond to this report Responses (0) Stockley PR. Peer Review Report For: Study of inflammatory biomarkers in Chronic obstructive pulmonary disease (COPD) and their association with comorbidities [version 1; peer review: 1 not approved] . F1000Research 2024, 13 :334 ( https://doi.org/10.5256/f1000research.160065.r308276) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/13-334/v1#referee-response-308276 Alongside their report, reviewers assign a status to the article: Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. 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