Association Between the Lead I Electrocardiographic Sign and Chronic Obstructive Pulmonary Disease: A Case Control Study

Association Between the Lead I Electrocardiographic Sign and Chronic Obstructive Pulmonary Disease: A Case Control Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Association Between the Lead I Electrocardiographic Sign and Chronic Obstructive Pulmonary Disease: A Case Control Study Nitya Panyala, Bhavneet Singh, Ahmed Munir, J Matthew Neal, Simant Thapa This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8956144/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 15 You are reading this latest preprint version Abstract Background Chronic Obstructive Pulmonary Disease (COPD) affects millions worldwide, yet early diagnosis remains challenging due to limited availability of pulmonary function testing. The Lead I sign on electrocardiogram has been anecdotally observed in COPD patients. Objective To determine the association between the presence of Lead I sign on ECG and COPD diagnosis in patients aged 30–70 years. Methods This retrospective case-control study included 201 patients (96 with positive Lead I sign, 105 with negative Lead I sign). Lead I sign was defined as ≥ 2 criteria: isoelectric P wave, QRS amplitude < 1.5 mm, and T wave amplitude < 0.5 mm in lead I. COPD diagnosis was confirmed through pulmonary function testing and clinical documentation. Results Among patients with positive Lead I sign, 80 (83.3%) had COPD, while only 12 (11.4%) with negative Lead I sign had COPD (p < 0.001). The Lead I sign demonstrated sensitivity 87.0%, specificity 85.3%, positive predictive value 83.3%, and negative predictive value 88.6%. Conclusion The Lead I sign shows a strong association with COPD diagnosis with excellent diagnostic performance, suggesting potential utility as an accessible screening tool. Figures Figure 1 Figure 2 Figure 3 Introduction Chronic obstructive pulmonary disease (COPD) affects millions of individuals worldwide and represents a major cause of morbidity, mortality, and healthcare utilization. Early identification of COPD is critical for slowing disease progression, optimizing symptom control, and reducing long-term healthcare costs. However, conventional diagnostic strategies rely primarily on pulmonary function testing (PFT), which may be limited by availability, patient cooperation, or access in certain clinical settings. The electrocardiogram (ECG) is a widely available, low-cost diagnostic tool routinely obtained in outpatient and inpatient settings. Multiple ECG abnormalities have been described in patients with pulmonary disease, particularly in advanced COPD, where findings consistent with right heart strain are commonly observed. 1 Another finding, the Lead I sign, characterized by specific morphologic changes in lead I, has been reported in association with COPD. 2 This sign incorporates alterations in P-wave morphology, reduced QRS amplitude, and diminished T-wave amplitude, potentially reflecting cardiopulmonary interactions related to lung hyperinflation and cardiac displacement. 3 Given the widespread availability of ECGs and their potential role in disease detection, exploring the possible diagnostic benefit of simple markers such as the Lead I sign is warranted. This study aimed to evaluate the association between the Lead I sign and COPD diagnosis in adults aged 30–70 years seen in an internal medicine clinic. Methods This study was approved by the Indiana University Institutional Review Board. We conducted a retrospective case-control study using non-probability consecutive sampling at a Midwestern community hospital. The study included 201 adult patients evaluated in the internal medicine clinic during the study period. Consecutive patients meeting eligibility criteria were included to reduce selection bias. Patients were categorized into two groups based on electrocardiographic findings: those with a positive Lead I sign (n = 96) and those with a negative Lead I sign (n = 105). The Lead I sign was defined as the presence of at least two of the following three electrocardiographic criteria in lead I: (1) isoelectric P wave, (2) QRS amplitude < 1.5 mm, and (3) T-wave amplitude < 0.5 mm, consistent with previously published descriptions. 2 Inclusion criteria were age 30–70 years, availability of an interpretable ECG, and a diagnosis of COPD supported by pulmonary function testing or computed tomography imaging. Exclusion criteria included age 70 years, irregular or paced cardiac rhythms, uninterpretable ECGs, and COPD diagnoses lacking objective confirmation by PFT or imaging. COPD diagnosis was established through pulmonary function testing demonstrating an FEV₁/FVC ratio < 0.70, indicating persistent airflow limitation. In cases where spirometry was unavailable, supportive chest CT findings suggestive of obstructive lung disease, such as evidence of emphysematous change, were also considered in confirming the diagnosis. All pulmonary function tests and chest CT studies used for diagnostic confirmation were obtained within one year of the ECG from which lead I sign status was determined. Categorical variables were summarized using frequencies and percentages. The association between the Lead I sign and COPD diagnosis was assessed using Pearson’s chi-square test. Statistical analyses were performed using IBM SPSS Statistics version 30. A two-sided p value < 0.05 was considered statistically significant. Results A total of 201 patients met inclusion criteria and were included in the analysis. Of these, 96 patients (47.8%) demonstrated a positive Lead I sign, while 105 patients (52.2%) had a negative Lead I sign. The cohort included 97 males (48.3%) and 104 females (51.7%), with comparable sex distribution between the Lead I–positive and Lead I–negative groups. A strong association was observed between the presence of the Lead I sign and COPD diagnosis. Among patients with a positive Lead I sign, 80 of 96 individuals (83.3%) had confirmed COPD. In contrast, only 12 of 105 patients (11.4%) with a negative Lead I sign were diagnosed with COPD. Pearson’s chi-square analysis demonstrated a highly significant association between the Lead I sign and COPD (χ² = 104.462, p < 0.001). The Lead I sign demonstrated excellent diagnostic performance: sensitivity 87.0%, specificity 85.3%, positive predictive value 83.3%, and negative predictive value 88.6%. A similar association was observed between the presence of the Lead I sign and COPD diagnosis in males and females. Among male patients with a positive Lead I sign, 39 of 45 individuals (86.7%) had confirmed COPD. In contrast, only 6 of 52 male patients (11.5%) with a negative Lead I sign were diagnosed with COPD. These findings suggest that the Lead I sign demonstrates high sensitivity (86.7%) and specificity (88.5%) for detecting COPD in male patients. These findings were statistically significant as well with p < 0.001. Among female patients with a positive Lead I sign, 41 of 51 individuals (80.4%) had confirmed COPD. In contrast, only 6 of 53 female patients (11.3%) with a negative Lead I sign were diagnosed with COPD. These findings indicate that while the Lead I sign maintains high sensitivity (87.2%) in females, its specificity (82.5%) is comparatively lower than in males. These findings were also statistically significant with p < 0.001. Among the 105 patients with a negative Lead I sign, 12 patients (11.4%) were confirmed to have COPD. Of these 12 patients, 6 were diagnosed based on pulmonary function testing, with disease severity classified as mild to moderate (GOLD class 1–2). All 6 PFT-diagnosed patients were appropriately initiated on guideline-directed medical therapy. The remaining 6 patients were diagnosed based on computed tomography findings suggestive of COPD; however, none of these CT-diagnosed patients were started on guideline-directed medical therapy. Among the 96 patients with a positive Lead I sign, 80 (83.3%) were confirmed to have COPD. Of these, 39 patients (48.8%) received their diagnosis through pulmonary function testing. Their disease severity ranged from GOLD class 1 (n = 2), class 2 (n = 15), class 3 (n = 11), and class 4 (n = 11), showing that most patients fell within the moderate to very severe categories. The majority of PFT-confirmed patients—37 of 39 (94.8%)—were receiving guideline-directed medical therapy. The remaining 41 patients (51.25%) were diagnosed based on computed tomography findings suggestive of COPD. In contrast to the PFT-diagnosed group, only 3 of these 41 patients (7.3%) were initiated on guideline-directed medical therapy, while 38 patients (92.7%) remained untreated despite radiological evidence of disease. Sixteen of 96 Lead I positive patients (16.7%) were ultimately found to be COPD-absent. Table 1 Lead 1 negative 105 COPD present 12 Patients diagnosed with PFT 6 GOLD1 2 GOLD2 4 Started on guideline medical therapy 6 Patients with CT findings suggestive of COPD 6 Not started on guideline medical therapy 6 COPD absent 93 Lead 1 positive 96 COPD present 80 Patients diagnosed with PFT 39 GOLD1 2 GOLD2 15 GOLD3 11 GOLD4 11 Started on guideline medical therapy 37 Not started on guideline medical therapy 2 Patients with CT findings suggestive of COPD 41 Started on guideline medical therapy 3 Not started on guideline medical therapy 38 COPD absent 16 Discussion In this retrospective case-control study of adults aged 30–70 years, we observed a strong and statistically significant association between the presence of the Lead I electrocardiographic sign and confirmed COPD. Patients with a positive Lead I sign were substantially more likely to have COPD compared with those without the sign (83.3% vs. 11.4%, p < 0.001). The diagnostic characteristics of the Lead I sign demonstrated high sensitivity (87.0%), specificity (85.3%), positive predictive value (83.3%), and negative predictive value (88.6%). These findings suggest that this simple ECG-based composite marker may have potential utility as an adjunctive clinical tool for identifying individuals at increased likelihood of COPD. The association observed is biologically plausible. COPD, particularly in the presence of emphysema and lung hyperinflation, results in structural and electrical changes within the thorax. In emphysema-predominant COPD, chronic local and systemic inflammatory processes drive destruction of the alveolar walls and degradation of the extracellular matrix, leading to lung hyperinflation and air trapping. The resulting increase in intrathoracic air volume expands the physical separation between the myocardium and surface ECG electrodes, diminishing electrical signal transmission. As a result, low-voltage QRS complexes are commonly seen on both limb and precordial leads. 4 Studies have demonstrated that electrocardiographic changes in COPD are not solely markers of right ventricular hypertrophy or cor pulmonale, but may also result from geometric and conductive changes within the thorax. 3 Hyperinflated lungs increase intrathoracic air content, reduce electrical conductivity, and may vertically displace and rotate the heart. These changes can attenuate electrical forces recorded in limb leads, particularly lead I, which reflects leftward cardiac vectors. 2 The P wave is often isoelectric in lead I in patients with COPD due to a rightward and vertical shift of the mean frontal P wave axis, often approaching + 90° or greater. This verticalization results from lung hyperinflation, which flattens the diaphragm, displaces the heart into a more vertical orientation, and contributes to right atrial remodeling. These anatomical and electrical alterations reduce the amplitude of the P wave in Lead I and may produce the characteristic Lead I sign. 4,5 An isoelectric P wave, reduced QRS amplitude, and diminished T-wave amplitude in lead I may therefore reflect altered cardiac orientation and increased impedance related to hyperinflated lung tissue in COPD. Importantly, the Lead I sign performed well across both sexes. While minor differences in specificity were observed between males and females, the association between the sign and COPD remained strong and statistically significant in both groups. This suggests that the electrocardiographic pattern is not sex-restricted and may be broadly applicable within adult populations in this age range. We also observed that disease severity among patients diagnosed by pulmonary function testing was predominantly moderate to very severe, consistent with prior literature showing that ECG abnormalities become more prevalent with increasing COPD severity. One study reported that electrocardiographic abnormalities, particularly conduction disturbances, are more common in patients with COPD than in those without the disease, and that ECG abnormalities related to cardiac pathology increase in prevalence with greater severity of airflow obstruction. 6 Nearly all patients with spirometry-confirmed COPD were receiving guideline-directed medical therapy, whereas the majority of patients diagnosed based on CT findings alone were untreated. This disparity suggests that incidental radiographic detection of emphysema may not consistently translate into therapeutic intervention when airflow limitation is not formally documented. An additional observation from our study was that several patients with radiographic evidence of emphysematous changes on CT did not undergo formal pulmonary function testing and, in many cases, were not started on guideline directed therapy. In routine clinical practice, chest CT imaging is often obtained to evaluate acute symptoms such as dyspnea, chest pain, or suspected infection rather than for systematic assessment of chronic lung disease. As a result, incidental findings of emphysema may not consistently prompt longitudinal pulmonary evaluation. Our findings suggest that even when emphysematous changes are documented on imaging, structured follow-up with spirometry and clinical reassessment may not occur. Physicians should therefore remain vigilant in recognizing incidental CT evidence of obstructive lung disease and ensure appropriate confirmatory testing and management. The identification of a Lead I sign on ECG may serve as an additional cue to reconsider underlying COPD and facilitate comprehensive follow-up, particularly in busy primary care or acute care settings where chronic disease management may otherwise be deferred. One article reports that COPD prevalence estimates vary substantially worldwide, with 10 to 95 percent underdiagnosis and 5 to 60 percent overdiagnosis, largely attributable to differences in diagnostic criteria and the limited availability of spirometry in rural regions of low and middle income countries where disease burden is often high. 7 In this context, ECG based approaches may have particular relevance in primary care and resource limited settings where pulmonary function testing is not readily accessible, while ECGs remain inexpensive, widely available, and frequently obtained for cardiovascular evaluation. Simple markers such as the Lead I sign could function as opportunistic markers that prompt further pulmonary assessment in high-risk individuals. Importantly, this strategy is not intended to replace spirometry, but rather to complement it by identifying patients who warrant further diagnostic evaluation. Emerging evidence further supports the concept of ECG-based detection of COPD. Recent artificial intelligence–enabled analyses of routine ECGs have demonstrated consistent discrimination of COPD across large and diverse populations, with correlations to spirometric impairment. 8 These findings reinforce the notion that subtle electrocardiographic signatures of obstructive lung disease exist and may be leveraged through both advanced computational methods and simpler morphological criteria such as the Lead I sign. Furthermore, one study also suggested that ECG findings may have value beyond diagnosis and may also provide prognostic information. This indicates that electrocardiographic patterns could contribute to risk assessment and ongoing clinical evaluation in patients with COPD. 9 These observations support the broader role of ECG as a useful and accessible clinical tool in the management of obstructive lung disease. Importantly, ECG should not replace established diagnostic methods such as spirometry or imaging, but rather serve as a complementary tool that may prompt further evaluation and help guide comprehensive patient care. The relatively high negative predictive value observed in this study suggests that absence of the Lead I sign reduces the likelihood of COPD in this enriched population. However, given the case-control design and the higher prevalence of COPD within the study sample, predictive values may differ in a general screening population. Therefore, the Lead I sign should not be interpreted as a standalone diagnostic test, particularly in symptomatic individuals. Several limitations should be considered. The retrospective case-control design limits causal inference and may overestimate diagnostic performance compared with population-based screening cohorts. The study was conducted at a single Midwestern community hospital, potentially limiting generalizability. Certain clinical variables, including body mass index, comorbid cardiovascular disease, and medication use, were not adjusted for and may influence ECG morphology. Some COPD diagnoses were based on CT findings without spirometric confirmation, introducing heterogeneity in disease classification. Interobserver variability in ECG interpretation was not formally assessed. Finally, because disease prevalence was enriched in this case-control framework, positive and negative predictive values may not directly translate to lower-prevalence primary care populations. Prospective, multicenter studies are warranted to validate these findings in broader and more diverse populations. Future investigations should assess the incremental value of the Lead I sign beyond established clinical risk factors and symptom-based screening tools. Evaluation of automated ECG analysis for standardized detection, as well as correlation with quantitative measures of hyperinflation and long-term outcomes, may further clarify clinical relevance. In summary, the Lead I electrocardiographic sign demonstrates a strong association with COPD and favorable diagnostic characteristics in this case-control study. Given the widespread availability and low cost of ECG, the Lead I sign may represent a practical adjunctive clinical marker to prompt further pulmonary evaluation, particularly in settings where access to spirometry is limited. Prospective validation is required before routine clinical implementation. Conclusion The Lead I electrocardiographic sign demonstrates a strong association with COPD and favorable diagnostic characteristics in this case-control study. Given the widespread availability and low cost of ECG, the Lead I sign may represent a practical adjunctive clinical marker to prompt further pulmonary evaluation, particularly in settings where access to spirometry is limited. Prospective validation is required before routine clinical implementation. Abbreviations Chronic Obstructive Pulmonary Disease (COPD); electrocardiogram (ECG); pulmonary function testing (PFT). Declarations This research did not receive funding. Ethics, Consent to Participate, and Consent to Publish declarations: not applicable. Ethics approval and consent to participate: This study was reviewed by the Indiana University Institutional Review Board and determined to be exempt under Category 4(iii). The study was conducted in accordance with the principles of the Declaration of Helsinki. As this study involved secondary analysis of existing data, the requirement for informed consent was waived. Consent for publication: Not applicable. Availability of data and materials: The datasets analyzed during the current study are included in the attached materials. Additional information may be available from the corresponding author upon reasonable request, in accordance with institutional policies. Competing Interests: The authors declare that they have no competing interests. Funding: No external funding was received for this study. Authors' contributions: All authors contributed to the conception and design of the study. Data collection and chart review were performed by the research team, and data analysis and interpretation were conducted collaboratively. The first draft of the manuscript was prepared by the primary author, and all authors contributed to manuscript revision. All authors read and approved the final manuscript. Acknowledgements: The authors thank the Indiana University clinical and administrative staff who assisted with institutional processes supporting this study. References Rodman DM, Lowenstein SR, Rodman T. The electrocardiogram in chronic obstructive pulmonary disease. J Emerg Med . 1990;8(5):607-615. doi:10.1016/0736-4679(90)90458-8 Gupta P, Jain H, Gill M, et al. Electrocardiographic changes in Emphysema. World J Cardiol . 2021;13(10):533-545. doi:10.4330/wjc.v13.i10.533 Larssen MS, Steine K, Hilde JM, et al. Mechanisms of ECG signs in chronic obstructive pulmonary disease. Open Heart . 2017;4(1):e000552. doi:10.1136/openhrt-2016-000552 Valente D, Segreti A, Celeski M, et al. Electrocardiographic alterations in chronic obstructive pulmonary disease. J Electrocardiol . 2024;85:58-65. doi:10.1016/j.jelectrocard.2024.05.083 Kazibwe R, Ahmad MI, Luqman-Arafat TK, Chen H, Yeboah J, Soliman EZ. Relationship between abnormal P-wave axis, chronic obstructive pulmonary disease and mortality in the general population. J Electrocardiol . 2023;79:100-107. doi:10.1016/j.jelectrocard.2023.03.085 Warnier MJ, Rutten FH, Numans ME, et al. Electrocardiographic Characteristics of Patients with Chronic Obstructive Pulmonary Disease. COPD J Chronic Obstr Pulm Dis . 2013;10(1):62-71. doi:10.3109/15412555.2012.727918 Ho T, Cusack RP, Chaudhary N, Satia I, Kurmi OP. Under- and over-diagnosis of COPD: a global perspective. Breathe Sheff Engl . 2019;15(1):24-35. doi:10.1183/20734735.0346-2018 Vaid A, Sharma J, Jiang J, et al. Automated diagnosis of chronic obstructive pulmonary disease using deep learning applied to electrocardiograms. EBioMedicine . 2026;123:106066. doi:10.1016/j.ebiom.2025.106066 Kulirova M, Solar M, Kopecky M, et al. A normal electrocardiogram indicates a better prognosis in patients with moderate to very severe chronic obstructive pulmonary disease. Sci Rep . 2025;15(1):4427. doi:10.1038/s41598-025-89013-0 Additional Declarations No competing interests reported. Supplementary Files BMCdata.xlsx Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 02 May, 2026 Reviews received at journal 19 Apr, 2026 Reviewers agreed at journal 18 Apr, 2026 Reviews received at journal 15 Apr, 2026 Reviews received at journal 13 Apr, 2026 Reviewers agreed at journal 12 Apr, 2026 Reviews received at journal 12 Apr, 2026 Reviewers agreed at journal 11 Apr, 2026 Reviewers agreed at journal 09 Apr, 2026 Reviewers agreed at journal 09 Apr, 2026 Reviewers invited by journal 02 Apr, 2026 Editor assigned by journal 31 Mar, 2026 Editor invited by journal 10 Mar, 2026 Submission checks completed at journal 10 Mar, 2026 First submitted to journal 10 Mar, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8956144","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":617645372,"identity":"1c265238-b520-4858-9ebd-9c8b268b5768","order_by":0,"name":"Nitya Panyala","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAuElEQVRIiWNgGAWjYPACCwZ+ZhDNRrwWCQbJZpK1GBwgVou5dPOzxzw1EvLGx3kMGD6UHSasxXLOMXNjnmMShtsO8xgwzjhHhBaDGwlm0jxsEowgLcy8bURpSf8mzfNPwn5zM1DLX+K05JhJ87ZJJG5gBmphJErLnTNlknP7JJJnHGYrONhzLp0ILbfbt0m8+WZj299/eOODH2XWhLUAY4SBiQfKPkCEeogWxh/EKR0Fo2AUjIKRCgDAWTWcJDucKwAAAABJRU5ErkJggg==","orcid":"","institution":"Indiana University","correspondingAuthor":true,"prefix":"","firstName":"Nitya","middleName":"","lastName":"Panyala","suffix":""},{"id":617645373,"identity":"9a978bf8-243a-40e7-bcae-4cdd3309115f","order_by":1,"name":"Bhavneet Singh","email":"","orcid":"","institution":"Indiana University","correspondingAuthor":false,"prefix":"","firstName":"Bhavneet","middleName":"","lastName":"Singh","suffix":""},{"id":617645374,"identity":"08d4a27a-5e99-4e75-9fbe-d87c80d87c5c","order_by":2,"name":"Ahmed Munir","email":"","orcid":"","institution":"Ball Memorial Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ahmed","middleName":"","lastName":"Munir","suffix":""},{"id":617645375,"identity":"843afa6f-34d3-43cd-911f-86ff56782913","order_by":3,"name":"J Matthew Neal","email":"","orcid":"","institution":"Ball Memorial Hospital","correspondingAuthor":false,"prefix":"","firstName":"J","middleName":"Matthew","lastName":"Neal","suffix":""},{"id":617645376,"identity":"3b59d519-f1d7-4b4d-9cb4-a355bbecd9a4","order_by":4,"name":"Simant Thapa","email":"","orcid":"","institution":"Ball Memorial Hospital","correspondingAuthor":false,"prefix":"","firstName":"Simant","middleName":"","lastName":"Thapa","suffix":""}],"badges":[],"createdAt":"2026-02-24 10:26:52","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8956144/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8956144/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":106725950,"identity":"5f9b4ab0-b72c-4051-a15a-18e2d51b9671","added_by":"auto","created_at":"2026-04-12 18:34:37","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":72209,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eLead 1 Crosstabulation\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8956144/v1/f1ecadd129c0cb3e109ae521.png"},{"id":106543478,"identity":"384a6bf5-a4bc-4463-8eef-2c41156532e3","added_by":"auto","created_at":"2026-04-09 16:37:28","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":67551,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMale Lead 1 Crosstabulation\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8956144/v1/7bab441924428d392009912b.png"},{"id":106726694,"identity":"bf2cc860-56e5-47b2-a3c1-80f4978912fb","added_by":"auto","created_at":"2026-04-12 18:37:04","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":64472,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFemale Lead 1 Crosstabulation\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-8956144/v1/c19c3660bb7465a67d3361ea.png"},{"id":106993987,"identity":"dbf31401-7627-49e2-bf2e-fe0bf7df0fd6","added_by":"auto","created_at":"2026-04-15 15:01:38","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":645099,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8956144/v1/d4c057d7-bbc8-4e45-8685-3c987d85c4d2.pdf"},{"id":106726683,"identity":"ffd4dcf2-8c13-4fde-a29d-c0962c8d4eb2","added_by":"auto","created_at":"2026-04-12 18:37:03","extension":"xlsx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":11181,"visible":true,"origin":"","legend":"","description":"","filename":"BMCdata.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-8956144/v1/c8cb6ac67099644af2405a28.xlsx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Association Between the Lead I Electrocardiographic Sign and Chronic Obstructive Pulmonary Disease: A Case Control Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eChronic obstructive pulmonary disease (COPD) affects millions of individuals worldwide and represents a major cause of morbidity, mortality, and healthcare utilization. Early identification of COPD is critical for slowing disease progression, optimizing symptom control, and reducing long-term healthcare costs. However, conventional diagnostic strategies rely primarily on pulmonary function testing (PFT), which may be limited by availability, patient cooperation, or access in certain clinical settings.\u003c/p\u003e \u003cp\u003eThe electrocardiogram (ECG) is a widely available, low-cost diagnostic tool routinely obtained in outpatient and inpatient settings. Multiple ECG abnormalities have been described in patients with pulmonary disease, particularly in advanced COPD, where findings consistent with right heart strain are commonly observed.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e Another finding, the Lead I sign, characterized by specific morphologic changes in lead I, has been reported in association with COPD.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e This sign incorporates alterations in P-wave morphology, reduced QRS amplitude, and diminished T-wave amplitude, potentially reflecting cardiopulmonary interactions related to lung hyperinflation and cardiac displacement.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eGiven the widespread availability of ECGs and their potential role in disease detection, exploring the possible diagnostic benefit of simple markers such as the Lead I sign is warranted. This study aimed to evaluate the association between the Lead I sign and COPD diagnosis in adults aged 30\u0026ndash;70 years seen in an internal medicine clinic.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e This study was approved by the Indiana University Institutional Review Board.\u003c/p\u003e \u003cp\u003eWe conducted a retrospective case-control study using non-probability consecutive sampling at a Midwestern community hospital. The study included 201 adult patients evaluated in the internal medicine clinic during the study period. Consecutive patients meeting eligibility criteria were included to reduce selection bias.\u003c/p\u003e \u003cp\u003ePatients were categorized into two groups based on electrocardiographic findings: those with a positive Lead I sign (n\u0026thinsp;=\u0026thinsp;96) and those with a negative Lead I sign (n\u0026thinsp;=\u0026thinsp;105). The Lead I sign was defined as the presence of at least two of the following three electrocardiographic criteria in lead I: (1) isoelectric P wave, (2) QRS amplitude\u0026thinsp;\u0026lt;\u0026thinsp;1.5 mm, and (3) T-wave amplitude\u0026thinsp;\u0026lt;\u0026thinsp;0.5 mm, consistent with previously published descriptions. \u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eInclusion criteria were age 30\u0026ndash;70 years, availability of an interpretable ECG, and a diagnosis of COPD supported by pulmonary function testing or computed tomography imaging. Exclusion criteria included age\u0026thinsp;\u0026lt;\u0026thinsp;30 or \u0026gt;\u0026thinsp;70 years, irregular or paced cardiac rhythms, uninterpretable ECGs, and COPD diagnoses lacking objective confirmation by PFT or imaging.\u003c/p\u003e \u003cp\u003eCOPD diagnosis was established through pulmonary function testing demonstrating an FEV₁/FVC ratio\u0026thinsp;\u0026lt;\u0026thinsp;0.70, indicating persistent airflow limitation. In cases where spirometry was unavailable, supportive chest CT findings suggestive of obstructive lung disease, such as evidence of emphysematous change, were also considered in confirming the diagnosis. All pulmonary function tests and chest CT studies used for diagnostic confirmation were obtained within one year of the ECG from which lead I sign status was determined.\u003c/p\u003e \u003cp\u003eCategorical variables were summarized using frequencies and percentages. The association between the Lead I sign and COPD diagnosis was assessed using Pearson\u0026rsquo;s chi-square test. Statistical analyses were performed using IBM SPSS Statistics version 30. A two-sided p value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 201 patients met inclusion criteria and were included in the analysis. Of these, 96 patients (47.8%) demonstrated a positive Lead I sign, while 105 patients (52.2%) had a negative Lead I sign. The cohort included 97 males (48.3%) and 104 females (51.7%), with comparable sex distribution between the Lead I\u0026ndash;positive and Lead I\u0026ndash;negative groups.\u003c/p\u003e \u003cp\u003eA strong association was observed between the presence of the Lead I sign and COPD diagnosis. Among patients with a positive Lead I sign, 80 of 96 individuals (83.3%) had confirmed COPD. In contrast, only 12 of 105 patients (11.4%) with a negative Lead I sign were diagnosed with COPD. Pearson\u0026rsquo;s chi-square analysis demonstrated a highly significant association between the Lead I sign and COPD (χ\u0026sup2; = 104.462, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The Lead I sign demonstrated excellent diagnostic performance: sensitivity 87.0%, specificity 85.3%, positive predictive value 83.3%, and negative predictive value 88.6%. A similar association was observed between the presence of the Lead I sign and COPD diagnosis in males and females.\u003c/p\u003e \u003cp\u003eAmong male patients with a positive Lead I sign, 39 of 45 individuals (86.7%) had confirmed COPD. In contrast, only 6 of 52 male patients (11.5%) with a negative Lead I sign were diagnosed with COPD. These findings suggest that the Lead I sign demonstrates high sensitivity (86.7%) and specificity (88.5%) for detecting COPD in male patients. These findings were statistically significant as well with p\u0026thinsp;\u0026lt;\u0026thinsp;0.001.\u003c/p\u003e \u003cp\u003eAmong female patients with a positive Lead I sign, 41 of 51 individuals (80.4%) had confirmed COPD. In contrast, only 6 of 53 female patients (11.3%) with a negative Lead I sign were diagnosed with COPD. These findings indicate that while the Lead I sign maintains high sensitivity (87.2%) in females, its specificity (82.5%) is comparatively lower than in males. These findings were also statistically significant with p\u0026thinsp;\u0026lt;\u0026thinsp;0.001.\u003c/p\u003e \u003cp\u003eAmong the 105 patients with a negative Lead I sign, 12 patients (11.4%) were confirmed to have COPD. Of these 12 patients, 6 were diagnosed based on pulmonary function testing, with disease severity classified as mild to moderate (GOLD class 1\u0026ndash;2). All 6 PFT-diagnosed patients were appropriately initiated on guideline-directed medical therapy. The remaining 6 patients were diagnosed based on computed tomography findings suggestive of COPD; however, none of these CT-diagnosed patients were started on guideline-directed medical therapy.\u003c/p\u003e \u003cp\u003eAmong the 96 patients with a positive Lead I sign, 80 (83.3%) were confirmed to have COPD. Of these, 39 patients (48.8%) received their diagnosis through pulmonary function testing. Their disease severity ranged from GOLD class 1 (n\u0026thinsp;=\u0026thinsp;2), class 2 (n\u0026thinsp;=\u0026thinsp;15), class 3 (n\u0026thinsp;=\u0026thinsp;11), and class 4 (n\u0026thinsp;=\u0026thinsp;11), showing that most patients fell within the moderate to very severe categories. The majority of PFT-confirmed patients\u0026mdash;37 of 39 (94.8%)\u0026mdash;were receiving guideline-directed medical therapy. The remaining 41 patients (51.25%) were diagnosed based on computed tomography findings suggestive of COPD. In contrast to the PFT-diagnosed group, only 3 of these 41 patients (7.3%) were initiated on guideline-directed medical therapy, while 38 patients (92.7%) remained untreated despite radiological evidence of disease. Sixteen of 96 Lead I positive patients (16.7%) were ultimately found to be COPD-absent.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e\u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eLead 1 negative\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e105\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCOPD present\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePatients diagnosed with PFT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGOLD1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGOLD2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eStarted on guideline medical therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePatients with CT findings suggestive of COPD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNot started on guideline medical therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCOPD absent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e93\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLead 1 positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e96\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCOPD present\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e80\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePatients diagnosed with PFT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGOLD1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGOLD2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGOLD3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGOLD4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eStarted on guideline medical therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNot started on guideline medical therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePatients with CT findings suggestive of COPD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eStarted on guideline medical therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNot started on guideline medical therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCOPD absent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this retrospective case-control study of adults aged 30\u0026ndash;70 years, we observed a strong and statistically significant association between the presence of the Lead I electrocardiographic sign and confirmed COPD. Patients with a positive Lead I sign were substantially more likely to have COPD compared with those without the sign (83.3% vs. 11.4%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The diagnostic characteristics of the Lead I sign demonstrated high sensitivity (87.0%), specificity (85.3%), positive predictive value (83.3%), and negative predictive value (88.6%). These findings suggest that this simple ECG-based composite marker may have potential utility as an adjunctive clinical tool for identifying individuals at increased likelihood of COPD.\u003c/p\u003e \u003cp\u003eThe association observed is biologically plausible. COPD, particularly in the presence of emphysema and lung hyperinflation, results in structural and electrical changes within the thorax.\u003c/p\u003e \u003cp\u003eIn emphysema-predominant COPD, chronic local and systemic inflammatory processes drive destruction of the alveolar walls and degradation of the extracellular matrix, leading to lung hyperinflation and air trapping. The resulting increase in intrathoracic air volume expands the physical separation between the myocardium and surface ECG electrodes, diminishing electrical signal transmission. As a result, low-voltage QRS complexes are commonly seen on both limb and precordial leads. \u003csup\u003e4\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eStudies have demonstrated that electrocardiographic changes in COPD are not solely markers of right ventricular hypertrophy or cor pulmonale, but may also result from geometric and conductive changes within the thorax.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eHyperinflated lungs increase intrathoracic air content, reduce electrical conductivity, and may vertically displace and rotate the heart. These changes can attenuate electrical forces recorded in limb leads, particularly lead I, which reflects leftward cardiac vectors. \u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe P wave is often isoelectric in lead I in patients with COPD due to a rightward and vertical shift of the mean frontal P wave axis, often approaching\u0026thinsp;+\u0026thinsp;90\u0026deg; or greater. This verticalization results from lung hyperinflation, which flattens the diaphragm, displaces the heart into a more vertical orientation, and contributes to right atrial remodeling. These anatomical and electrical alterations reduce the amplitude of the P wave in Lead I and may produce the characteristic Lead I sign. \u003csup\u003e4,5\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eAn isoelectric P wave, reduced QRS amplitude, and diminished T-wave amplitude in lead I may therefore reflect altered cardiac orientation and increased impedance related to hyperinflated lung tissue in COPD.\u003c/p\u003e \u003cp\u003eImportantly, the Lead I sign performed well across both sexes. While minor differences in specificity were observed between males and females, the association between the sign and COPD remained strong and statistically significant in both groups. This suggests that the electrocardiographic pattern is not sex-restricted and may be broadly applicable within adult populations in this age range.\u003c/p\u003e \u003cp\u003eWe also observed that disease severity among patients diagnosed by pulmonary function testing was predominantly moderate to very severe, consistent with prior literature showing that ECG abnormalities become more prevalent with increasing COPD severity. One study reported that electrocardiographic abnormalities, particularly conduction disturbances, are more common in patients with COPD than in those without the disease, and that ECG abnormalities related to cardiac pathology increase in prevalence with greater severity of airflow obstruction. \u003csup\u003e6\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e Nearly all patients with spirometry-confirmed COPD were receiving guideline-directed medical therapy, whereas the majority of patients diagnosed based on CT findings alone were untreated. This disparity suggests that incidental radiographic detection of emphysema may not consistently translate into therapeutic intervention when airflow limitation is not formally documented.\u003c/p\u003e \u003cp\u003e An additional observation from our study was that several patients with radiographic evidence of emphysematous changes on CT did not undergo formal pulmonary function testing and, in many cases, were not started on guideline directed therapy. In routine clinical practice, chest CT imaging is often obtained to evaluate acute symptoms such as dyspnea, chest pain, or suspected infection rather than for systematic assessment of chronic lung disease. As a result, incidental findings of emphysema may not consistently prompt longitudinal pulmonary evaluation. Our findings suggest that even when emphysematous changes are documented on imaging, structured follow-up with spirometry and clinical reassessment may not occur. Physicians should therefore remain vigilant in recognizing incidental CT evidence of obstructive lung disease and ensure appropriate confirmatory testing and management. The identification of a Lead I sign on ECG may serve as an additional cue to reconsider underlying COPD and facilitate comprehensive follow-up, particularly in busy primary care or acute care settings where chronic disease management may otherwise be deferred.\u003c/p\u003e \u003cp\u003eOne article reports that COPD prevalence estimates vary substantially worldwide, with 10 to 95 percent underdiagnosis and 5 to 60 percent overdiagnosis, largely attributable to differences in diagnostic criteria and the limited availability of spirometry in rural regions of low and middle income countries where disease burden is often high.\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eIn this context, ECG based approaches may have particular relevance in primary care and resource limited settings where pulmonary function testing is not readily accessible, while ECGs remain inexpensive, widely available, and frequently obtained for cardiovascular evaluation. Simple markers such as the Lead I sign could function as opportunistic markers that prompt further pulmonary assessment in high-risk individuals. Importantly, this strategy is not intended to replace spirometry, but rather to complement it by identifying patients who warrant further diagnostic evaluation.\u003c/p\u003e \u003cp\u003eEmerging evidence further supports the concept of ECG-based detection of COPD. Recent artificial intelligence\u0026ndash;enabled analyses of routine ECGs have demonstrated consistent discrimination of COPD across large and diverse populations, with correlations to spirometric impairment.\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e These findings reinforce the notion that subtle electrocardiographic signatures of obstructive lung disease exist and may be leveraged through both advanced computational methods and simpler morphological criteria such as the Lead I sign.\u003c/p\u003e \u003cp\u003eFurthermore, one study also suggested that ECG findings may have value beyond diagnosis and may also provide prognostic information. This indicates that electrocardiographic patterns could contribute to risk assessment and ongoing clinical evaluation in patients with COPD.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e These observations support the broader role of ECG as a useful and accessible clinical tool in the management of obstructive lung disease. Importantly, ECG should not replace established diagnostic methods such as spirometry or imaging, but rather serve as a complementary tool that may prompt further evaluation and help guide comprehensive patient care.\u003c/p\u003e \u003cp\u003eThe relatively high negative predictive value observed in this study suggests that absence of the Lead I sign reduces the likelihood of COPD in this enriched population. However, given the case-control design and the higher prevalence of COPD within the study sample, predictive values may differ in a general screening population. Therefore, the Lead I sign should not be interpreted as a standalone diagnostic test, particularly in symptomatic individuals.\u003c/p\u003e \u003cp\u003eSeveral limitations should be considered. The retrospective case-control design limits causal inference and may overestimate diagnostic performance compared with population-based screening cohorts. The study was conducted at a single Midwestern community hospital, potentially limiting generalizability. Certain clinical variables, including body mass index, comorbid cardiovascular disease, and medication use, were not adjusted for and may influence ECG morphology. Some COPD diagnoses were based on CT findings without spirometric confirmation, introducing heterogeneity in disease classification. Interobserver variability in ECG interpretation was not formally assessed. Finally, because disease prevalence was enriched in this case-control framework, positive and negative predictive values may not directly translate to lower-prevalence primary care populations.\u003c/p\u003e \u003cp\u003eProspective, multicenter studies are warranted to validate these findings in broader and more diverse populations. Future investigations should assess the incremental value of the Lead I sign beyond established clinical risk factors and symptom-based screening tools. Evaluation of automated ECG analysis for standardized detection, as well as correlation with quantitative measures of hyperinflation and long-term outcomes, may further clarify clinical relevance.\u003c/p\u003e \u003cp\u003eIn summary, the Lead I electrocardiographic sign demonstrates a strong association with COPD and favorable diagnostic characteristics in this case-control study. Given the widespread availability and low cost of ECG, the Lead I sign may represent a practical adjunctive clinical marker to prompt further pulmonary evaluation, particularly in settings where access to spirometry is limited. Prospective validation is required before routine clinical implementation.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe Lead I electrocardiographic sign demonstrates a strong association with COPD and favorable diagnostic characteristics in this case-control study. Given the widespread availability and low cost of ECG, the Lead I sign may represent a practical adjunctive clinical marker to prompt further pulmonary evaluation, particularly in settings where access to spirometry is limited. Prospective validation is required before routine clinical implementation.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eChronic Obstructive Pulmonary Disease (COPD); electrocardiogram (ECG); pulmonary function testing (PFT).\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eThis research did not receive funding.\u003c/p\u003e\n\u003cp\u003eEthics, Consent to Participate, and Consent to Publish declarations: not applicable.\u003c/p\u003e\n\u003cp\u003eEthics approval and consent to participate:\u003cbr\u003e This study was reviewed by the Indiana University Institutional Review Board and determined to be exempt under Category 4(iii). The study was conducted in accordance with the principles of the Declaration of Helsinki. As this study involved secondary analysis of existing data, the requirement for informed consent was waived.\u003c/p\u003e\n\u003cp\u003eConsent for publication:\u003cbr\u003e Not applicable.\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials:\u003cbr\u003e The datasets analyzed during the current study are included in the attached materials. Additional information may be available from the corresponding author upon reasonable request, in accordance with institutional policies.\u003c/p\u003e\n\u003cp\u003eCompeting Interests:\u003cbr\u003e The authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003eFunding:\u003cbr\u003e No external funding was received for this study.\u003c/p\u003e\n\u003cp\u003eAuthors\u0026apos; contributions:\u003cbr\u003e All authors contributed to the conception and design of the study. Data collection and chart review were performed by the research team, and data analysis and interpretation were conducted collaboratively. The first draft of the manuscript was prepared by the primary author, and all authors contributed to manuscript revision. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003eAcknowledgements:\u003cbr\u003e The authors thank the Indiana University clinical and administrative staff who assisted with institutional processes supporting this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eRodman DM, Lowenstein SR, Rodman T. The electrocardiogram in chronic obstructive pulmonary disease. \u003cem\u003eJ Emerg Med\u003c/em\u003e. 1990;8(5):607-615. doi:10.1016/0736-4679(90)90458-8\u003c/li\u003e\n\u003cli\u003eGupta P, Jain H, Gill M, et al. Electrocardiographic changes in Emphysema. \u003cem\u003eWorld J Cardiol\u003c/em\u003e. 2021;13(10):533-545. doi:10.4330/wjc.v13.i10.533\u003c/li\u003e\n\u003cli\u003eLarssen MS, Steine K, Hilde JM, et al. Mechanisms of ECG signs in chronic obstructive pulmonary disease. \u003cem\u003eOpen Heart\u003c/em\u003e. 2017;4(1):e000552. doi:10.1136/openhrt-2016-000552\u003c/li\u003e\n\u003cli\u003eValente D, Segreti A, Celeski M, et al. Electrocardiographic alterations in chronic obstructive pulmonary disease. \u003cem\u003eJ Electrocardiol\u003c/em\u003e. 2024;85:58-65. doi:10.1016/j.jelectrocard.2024.05.083\u003c/li\u003e\n\u003cli\u003eKazibwe R, Ahmad MI, Luqman-Arafat TK, Chen H, Yeboah J, Soliman EZ. Relationship between abnormal P-wave axis, chronic obstructive pulmonary disease and mortality in the general population. \u003cem\u003eJ Electrocardiol\u003c/em\u003e. 2023;79:100-107. doi:10.1016/j.jelectrocard.2023.03.085\u003c/li\u003e\n\u003cli\u003eWarnier MJ, Rutten FH, Numans ME, et al. Electrocardiographic Characteristics of Patients with Chronic Obstructive Pulmonary Disease. \u003cem\u003eCOPD J Chronic Obstr Pulm Dis\u003c/em\u003e. 2013;10(1):62-71. doi:10.3109/15412555.2012.727918\u003c/li\u003e\n\u003cli\u003eHo T, Cusack RP, Chaudhary N, Satia I, Kurmi OP. Under- and over-diagnosis of COPD: a global perspective. \u003cem\u003eBreathe Sheff Engl\u003c/em\u003e. 2019;15(1):24-35. doi:10.1183/20734735.0346-2018\u003c/li\u003e\n\u003cli\u003eVaid A, Sharma J, Jiang J, et al. Automated diagnosis of chronic obstructive pulmonary disease using deep learning applied to electrocardiograms. \u003cem\u003eEBioMedicine\u003c/em\u003e. 2026;123:106066. doi:10.1016/j.ebiom.2025.106066\u003c/li\u003e\n\u003cli\u003eKulirova M, Solar M, Kopecky M, et al. A normal electrocardiogram indicates a better prognosis in patients with moderate to very severe chronic obstructive pulmonary disease. \u003cem\u003eSci Rep\u003c/em\u003e. 2025;15(1):4427. doi:10.1038/s41598-025-89013-0\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pulmonary-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pulm","sideBox":"Learn more about [BMC Pulmonary Medicine](http://bmcpulmmed.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/pulm/default.aspx","title":"BMC Pulmonary Medicine","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-8956144/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8956144/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eChronic Obstructive Pulmonary Disease (COPD) affects millions worldwide, yet early diagnosis remains challenging due to limited availability of pulmonary function testing. The Lead I sign on electrocardiogram has been anecdotally observed in COPD patients.\u003c/p\u003e\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eTo determine the association between the presence of Lead I sign on ECG and COPD diagnosis in patients aged 30\u0026ndash;70 years.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis retrospective case-control study included 201 patients (96 with positive Lead I sign, 105 with negative Lead I sign). Lead I sign was defined as \u0026ge;\u0026thinsp;2 criteria: isoelectric P wave, QRS amplitude\u0026thinsp;\u0026lt;\u0026thinsp;1.5 mm, and T wave amplitude\u0026thinsp;\u0026lt;\u0026thinsp;0.5 mm in lead I. COPD diagnosis was confirmed through pulmonary function testing and clinical documentation.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAmong patients with positive Lead I sign, 80 (83.3%) had COPD, while only 12 (11.4%) with negative Lead I sign had COPD (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The Lead I sign demonstrated sensitivity 87.0%, specificity 85.3%, positive predictive value 83.3%, and negative predictive value 88.6%.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThe Lead I sign shows a strong association with COPD diagnosis with excellent diagnostic performance, suggesting potential utility as an accessible screening tool.\u003c/p\u003e","manuscriptTitle":"Association Between the Lead I Electrocardiographic Sign and Chronic Obstructive Pulmonary Disease: A Case Control Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-09 16:37:24","doi":"10.21203/rs.3.rs-8956144/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-05-02T06:53:42+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-19T16:39:37+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"37198821361470767509843146390184223758","date":"2026-04-18T12:52:41+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-15T10:49:19+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-13T21:34:22+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"288870192361304072979339653428426077319","date":"2026-04-12T13:10:09+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-12T08:02:52+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"334207651862073275848100201428540474017","date":"2026-04-11T20:34:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"58106267977657885762730508049669122405","date":"2026-04-09T10:15:42+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"222854401094993911079793065555792071163","date":"2026-04-09T09:48:21+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-02T11:17:27+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-31T12:20:03+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-03-10T20:15:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-10T20:07:10+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pulmonary Medicine","date":"2026-03-10T14:05:02+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pulmonary-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pulm","sideBox":"Learn more about [BMC Pulmonary Medicine](http://bmcpulmmed.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/pulm/default.aspx","title":"BMC Pulmonary Medicine","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e14f2f76-b8ad-403c-b325-01bd1b127af7","owner":[],"postedDate":"April 9th, 2026","published":true,"recentEditorialEvents":[{"type":"editorInvitedReview","content":"","date":"2026-05-02T06:53:42+00:00","index":77,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-09T16:37:24+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-09 16:37:24","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8956144","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8956144","identity":"rs-8956144","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}